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  • 1970-1974  (63)
  • 1965-1969  (72)
  • 1955-1959
  • 1920-1924
  • 1890-1899
  • Insulin
  • Psychopharmacology
  • 1
    ISSN: 1432-0428
    Keywords: Insulin ; epinephrine ; lipolysis ; glucose metabolism ; fat cell ; adipose tissue ; plasma NEFA ; KK ; yellow KK ; C57BL ; diabetes ; genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adipose tissue of KK mice was less sensitive to insulin in its stimulatory action on glucose oxidation or its inhibitory action on lipolysis, and to epinephrine in its stimulatory action on lipolysis as compared to that of C57BL mice. A lack of appreciable increase in plasma NEFA in response to fasting of the KK mice might be caused by the impaired response of lipolysis to the hormones. — Adipose tissue of KK mice was also less sensitive to insulin-like action of concanavalin A, ouabaine or omission of K+ in the medium on glucose oxidation or lipolysis. Lipolysis in response to theophylline and/or DcAMP was less marked in the tissue of KK mice. The mean diameter of the adipocytes was larger in KK than in C57BL mice. In the experiments using adipocytes with the same diameter, however, the cells of KK mice were less sensitive to the hormones than those of C57BL. — With respect to tissue sensitivity to the hormones, the mean diameter of adipocytes and the response of plasma NEFA to fasting, the F1-hybrid mice of KK and C57BL showed values between those of the parental strains. Yellow hybrid (genetically obese F1-hybrid) mice showed higher sensitivity to insulin in the adipose tissue, more remarkable response of plasma NEFA to fasting as compared with KK mice, although hypertrophy of adipocytes was more pronounced in the yellow hybrid mice. — These findings suggest that insulin insensitivity is associated with epinephrine insensitivity in adipocytes of KK mice; both appear to be subjected to genetic factor(s)per se rather than hypertrophy of the adipocytes. Furthermore, insensitivity to both hormones in the KK mice appears to be caused by a common defect in cellular process other than the hormone receptor systems. These genetically determined abnormalities of adipocytes may result in fat-storage metabolism through hyperinsulinemia; this is very similar to the metabolic profile due to thrifty genotype in human diabetes as proposed by Neel.
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  • 2
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Flupenthixol ; Flupenthixol-Decanoate ; Mice ; Methylphenidate ; Apomorphine ; Compulsive Behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract α-Flupenthixol and α-flupenthixol decanoate were tested in mice against methylphenidate-induced stereotyped gnaw-compulsions. The effect of both α-flupenthixol, and α-flupenthixol decanoate disappeared 2 days after administration. In addition, the influence of α-flupenthixol and α-flupenthixol decanoate on the apomorphine-induced behaviour in mice was followed over a period of 12 days. Under these conditions apomorphine-induced compulsive gnawing was seen on the days on which the methylphenidate antagonistic effect had subsided. The apomorphine-induced compulsive gnawing seen in α-flupenthixol and α-flupenthixol decanoate pretreated animals could be antagonized by additional small doses of α-flupenthixol given 2 h before apomorphine. The interference of the neuroleptic drugs with dopaminergic receptors is discussed.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 35 (1974), S. 371-379 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Sleep ; Insomnia ; Flunitrazepam ; Benzodiazepine ; Hypnotic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of flunitrazepam (Ro 5-4200), a benzodiazepine derivative, was assessed on the sleep cycle of insomniac patients by means of all-night reeordings. Baseline placebo nights were compared with the drug (2–8 mg p.o.) and with the placebo post-drug nights. Flunitrazepam induced a shift to faster frequencies of the EEG and a disappearance of sleep stages 3 and 4 while stage 2 was increased. In 10 out of 12 studied insomniacs the compound was effective in inducing and maintaining sleep (decrease in NREM sleep latency, wake time and number of wakes) throughout the drug administration period. Both NREM and REM sleep were increased, the latter most likely in relation to a blockade of processes precluding NREM emergence. The hypnotic action of flunitrazepam was still present during the first withdrawal night, pointing out to a carry over effect.
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  • 4
    ISSN: 1432-2072
    Keywords: Pigs ; Conflict Behaviour ; Non-Reinforcement ; Chlordiazepoxide ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two groups of four pigs were subjected to a punishment discrimination (conflict) or to a non-reinforcement procedure. Conflict behaviour was evidenced by the suppression of operant responding and the occurrence of a marked decrease in heart rate during the presentation of the conditioned stimulus. Pigs in the non-reinforcement procedure showed no consistent changes in heart rate although an important decrease occurred in response rate. Chlordiazepoxide was administered in order to establish whether it would attenuate the response suppression in either procedure. The drug produced a weak attenuation of conflict in terms of the operant and heart rate responses at the maximum dose used (20 mg/kg) and a small disinhibiting effect on the non-reinforced responding at 10 mg/kg. Such effects were less clear-cut than usually reported in other species.
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  • 5
    ISSN: 1432-2013
    Keywords: Active Sodium Transport ; Insulin ; Aldosterone ; Vasopressin ; Ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Exposure of either the isolated urinary bladder or abdominal skin ofBufo marinus to the cardiac glycoside ouabain was regularly followed by reversible decreases of electrical potential difference and short-circuit current. Residual sodium-transporting activity, stable after 1–2h, was a function of the concentration of the glycoside. 2. Ouabain-inhibited preparations still reacted to vasopressin: the hormonal effect was decreased in amplitude only, and this in proportion to decrease in baseline activity; a similar observation was made when aldosterone was responsible for hormonal stimulation. 3. On the other hand, the insulin-induced increment in sodium transport was quite sensitive to ouabain inhibition so that this hormonal effect could be eliminated at moderate concentrations of the glycoside; the same held true when sodium transport was stimulated by addition of glucose to substrate-depleted preparations, especially when they were under the influence of aldosterone. 4. The persistence of residual hormonal effects in the presence of ouabain is interpreted as a type of response due to the stimuli (vasopressin, aldosterone in the absence of exogenous substrate) influencing a step distinct from, and probably proximal to, the ouabain-sensitive sodium “pump” mechanism proper. As for the increased ouabain effect noted on preparations stimulated by insulin or by glucose repletion, it suggests another type of response, possibly characterized by a facilitated interaction between ouabain and specific cell membrane ATP-ase set in operation as a consequence of these treatments.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 348 (1974), S. 333-342 
    ISSN: 1432-2013
    Keywords: Mouse Pancreas ; Amylase ; Glucose ; Insulin ; Glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucose inhibited amylase release from batch-incubated and perifused pieces of mouse pancreas. Insulin (100μg/ml) reduced the amylase secretion. These effects, however, seemed to be independent of each other, since diazoxide, a potent inhibitor of glucose-induced insulin release, did not abolish the effect of glucose on amylase secretion. Glucagon (10–100 μg/ml) had no effect on the release of amylase from incubated pancreas. Glucagon has previously been shown to inhibit exocrine secretionin vivo. The present results suggest that the inhibitory action of glucagon may be mediated via an increased level of serum glucose and the subsequent release of insulin.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 117 (1974), S. 63-72 
    ISSN: 1432-1076
    Keywords: Growth hormone ; Newborn ; Glucose load ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous glucose tests (0.5 g/kg body weight) were performed in 13 newborn infants during their first 3 days of life. The variations in blood glucose, insulin and GH values were studied. In all patients there was a rise in plasma insulin. The correlation between initial insulin rise and glucose assimilation constant was 0.503 which is almost significant. The glucose load provoked a very variable response in plasma GH concentration, some infants showed a rise, others a fall. If the newborns were grouped according to this reaction it appeared that the GH response could be explained using Wilder's law of initial value. This hypothesis, however, did not stand up to a thorough statistical analysis including a discussion of a less well-known statistical error. In contrast to insulin secretion, GH apparently plays no major role in the short term regulation of the blood sugar in the newborn.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of applied physiology 33 (1974), S. 215-226 
    ISSN: 1439-6327
    Keywords: Exercise ; Training ; FFA ; Ketones ; Insulin ; Growth Hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight young men underwent a programme of training by running for 30 min at moderate speed three times a week for 4 weeks. Metabolic and hormonal changes in blood were studied during and after a run of 60 min at comparable speeds before and at the end of the training programme. Increases in lactate, pyruvate and plasma FFA during exercise were less after training. Increases in glucose were greater. There was a smaller increase in the post-exercise concentration of blood ketone-bodies after training. Plasma levels of insulin and human growth hormone (HGH) were lower after training. The fall in insulin and the rise in HGH during exercise were also smaller. There is a dissociation of the normal relationship between blood glucose and insulin during exercise. Insulin appears to be more important in the control of fat metabolism, in which its role may be altered by physical training. The changes observed in the longitudinal study of training imply that differences observed in cross-sectional studies of athletes and untrained subjects are not the result of an innate difference but do depend upon metabolic changes related to athletic training.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 12 (1973), S. 8-15 
    ISSN: 1432-0827
    Keywords: Insulin ; Bone ; Calcium ; Resorption ; Orthophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé L'administration d'insuline cristallisée à des rats thyroparathyroidectomisés provoque une augmentation de la calcémie et de la phosphorémie. Le calcium plasmatique s'élève de façon linéaire entre 31 et 250 m Unités d'insuline/100 g de poids corporel. La courbe obtenue n'est guère différente de celle obtenue par extrait parathyroidien. L'administration simultanée d'insuline et d'extrait parathyroidien à des rats thyro-parathyroidectomisés agit sur la calcémie et la phosphorémie par un effet additif. Lorsque des os frontaux d'embryons de poulet sont cultivésin vitro en présence d'insuline cristallisée, le taux de résorption augmente. L'insuline augmente le taux de consommation en glucose des explants et induit une accumulation de citrate dans le milieu de culture. L'insuline stimule donc la résorption osseuse.
    Abstract: Zusammenfassung Der Plasmagehalt an Calcium und Phosphor bei thyroparathyreoidektomierten Ratten wurde durch die Verabreichung von kristallinem Insulin erhöht. Das Plasmacalcium verhielt sich zwischen 31 und 250 m Einheiten Insulin pro 100 g Körpergewicht linear. Die Steigung der erhaltenen Kurve ist nicht signifikant verschieden von derjenigen, die nach Parathyreoidea-Extrakt erhalten wird. Die gleichzeitige Verabreichung von Insulin und Parathyreoidea-Extrakt von thyroparathyreoidektomierten Ratten hatte eine kumulative Wirkung auf den Gehalt von Calcium und Phosphor im Plasma. Wenn Stirnbeine von Kükenembryos mit kristallinem Insulinin vitro kultiviert wurden, erhöhte sich die Resorptionsrate. Das Insulin steigerte den Glucoseverbrauch der Explantate und verursachte eine Anreicherung von Citrat im Kulturmedium. Die Ergebnisse deuten auf eine Stimulation der Knochenresorption durch Insulin.
    Notes: Abstract the administration of crystalline insulin to thyroparathyroidectomized rats raised their calcium and phosphorus plasma levels. The plasma calcium gave a linear response between 31 and 250 mU of insulin/100 g body weight. The slope obtained is not significantly different from that obtained with parathyroid extract. The simultaneous administration of insulin and parathyroid extract to thyroparathyroidectomized rats affected the calcium and phosphorus plasma levels in an additive fashion. When chick embryo frontal bones were cultivatedin vitro with crystalline insulin the rate of resorption increased. Insulin increased the rate of glucose consumption by the explants and induced the accumulation of citrate in the culture medium. It is concluded that insulin stimulates bone resorption.
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  • 10
    ISSN: 1433-8580
    Keywords: Insulin ; Intestinal hormones ; Atropine ; Vagus ; Insulin ; Intestinale Hormone ; Atropin ; Vagus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung und Schluβfolgerung Bei 35 stoffwechselgesunden freiwilligen Probanden wurde vor sowie nach Atropingabe die Wirkung der intestinalen Hormone Sekretin und Cholecystokinin-Pankreozymin (CCK-PZ) auf die endokrine und exokrine Pankreasfunktion untersucht. Außerdem wurde die Wirkung von intravenös und oral bzw. intraduodenal verabreichter Glucose und Aminosäuren auf die Insulinsekretion, den Blutzucker und die freien Fettsäuren ebenfalls vor und nach Atropinmedikation geprüft. Intravenös verabreichtes Sekretin konnte weder in seiner exokrinen noch endokrinen Pankreasfunktion durch Atropin beeinflußt werden. Intravenös injiziertes CCK-PZ konnte mittels Atropin sowohl in seiner ekbolischen wie auch endokrinen Pankreasfunktion gehemmt werden. Die Wirkung von CCK-PZ ist somit an ein cholinerges System gebunden, so daß es erlaubt erscheint, bezüglich der Pankreozyminwirkung von einem synergistisch bzw. additiv wirksam werdenden „neurohormonalen“ Mechanismus zu sprechen. Die durch parenteral verabreichte Glucose oder Aminosäuren induzierte Insulinsekretion wurde durch Atropin nicht beeinflußt; hingegen hemmte Atropin dieβ-cytotrope Wirkung von oral bzw. intraduodenal verabreichter Glucose oder Aminosäuren. Dies läßt auf eine Abhängigkeit von einem cholinergen oder parasympathischen System in der Freisetzung dieser intestinalen Hormone schließen.
    Notes: Summary and Conclusions In 35 metabolically normal subjects the effect of i.v. secretin and cholecystokinin-pancreozymin (CCK/PZ) on the endocrine and exocrine pancreatic function was investigated, before and after atropine. In addition, the effect of oral, intravenous and intraduodenal administration of glucose and amino acids on blood sugar and free fatty acids before and after the injection of atropine was studied. The secretin stimulated endocrine and exocrine pancreas was not affected by atropine. However, atropine inhibited the ecbolic and endocrine pancreatic function after stimulation with CCK/PZ. Therefore, the effect of i.v. CCK/PZ seems to be mediated by the cholinergic system, or even a “neuro-hormonal” system which acts synergically or additively. No influence of atropine on the insulin secretion induced by i.v. glucose or amino acids was observed. On the other hand, atropine inhibited the beta-cytotropic effect of glucose and amino acids after oral or intraduodenal administration. These findings indicate that the release of these intestinal hormones is dependent on the cholinergic or parasympathetic system.
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  • 11
    ISSN: 1433-8580
    Keywords: Small intestine ; Absorption ; Insulin ; Man ; Dünndarm ; Resorption ; Insulin ; Mensch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Einfluß von Insulin auf die Resorption von Glucose, Wasser, Natrium und Kalium wurde mittels der segmentalen Dünndarmperfusion mit einer dreilumigen Sonde untersucht. Nach Messung der Resorption über zwei 30 min-Perioden wurden den Probanden 1,0 g Tolbutamid (Rastinon®) bzw. 20 IE Insulin (Actrapid®) intravenös injiziert und danach die Resorption über vier 15 min-Perioden bestimmt. Ergebnisse 1. Stoffwechselgesunde zeigten sowohl nach Injektion von Tolbutamid und dadurch induzierter Erhöhung des Seruminsulinspiegels als auch nach Insulininjektion eine signifikante Minderung der Resorption. 2. Diese Resorptionsminderung war auch nachweisbar, wenn Glucose zur Verhinderung des Blutzuckerabfalls unmittelbar nach der Insulininjektion infundiert wurde. 3. Insulinbedürftige Diabetiker lassen nach der Injektion von Tolbutamid — offenbar infolge fehlender Insulinsekretion — keine Resorptionsänderungen erkennen, zeigen aber eine Transportminderung nach Insulininjektion. Diese Befunde belegen, daß die Glucose-, Wasser-, Natrium- und Kaliumresorption im menschlichen Dünndarm durch Insulin reduziert wird.
    Notes: Summary The influence of insulin on the intestinal absorption of glucose, water, sodium and potassium was investigated in man using a triple lumen tube technique. After an absorption period of 60 min 1 g of tolbutamide was injected in order to stimulate endogenous insulin secretion. Alternatively 20 units of regular insulin were applied intravenously. Thereafter absorption was studied over 4 periods of 15 min duration. Results: 1. In healthy subjects the absorption of glucose water, sodium and potassium was decreased after the injection of tolbutamide as well as after the injection of insulin. 2. The decrease in absorption was also demonstrable when the insulin induced reduction of blood sugar levels was abolished by intravenous glucose infusion. 3. In insulin dependent diabetics there was no decrease in absorption after injection of tolbutamide. This was due to the unability to secrete insulin. On the other hand a decrease in absorption occurred if insulin was applied in insulin dependent diabetics. These results demonstrate that the absorption of glucose, water, sodium and potassium from the human intestine is reduced by insulin.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 447-452 
    ISSN: 1432-0428
    Keywords: Insulin ; obese mice ; pancreas ; glucose ; amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pancreatic insulin content and insulin secretion, from the pancreas of obese mice fed ad lib (ob/ob), obese mice maintained on a restricted diet (ob/ob RD) and lean mice has been studied using incubated pieces of pancreas in vitro and in a perifusion system. The ob/ob mice pancreas contained approximately twice as much insulin as the lean mice pancreas, whereas the ob/ob RD mice had a normal insulin content. Increasing the glucose concentration had a marked and prolonged stimulating effect on insulin secretion in the pancreas of the ob/ob and ob/ob RD mouse, but not in the lean mouse. Leucine stimulated insulin secretion in all three groups of animals both in the absence and presence of glucose in a biphasic manner; in the presence of glucose the insulin secreted from the pancreas of the ob/ob and ob/ob RD mice was abnormally high. Arginine stimulated insulin secretion from the lean mouse pancreas in the absence of glucose, whereas in the obese mouse pancreas stimulation was observed only in the presence of glucose, and the effect increased with increasing glucose concentration. The large amounts of insulin which can be secreted by the pancreas of the ob/ob and ob/ob RD mice under stimulation suggest that an abnormal response of the pancreas to biological stimuli of insulin secretion could be a primary defect in these animals.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 174-177 
    ISSN: 1432-0428
    Keywords: Insulin ; clearance ; perfusion ; radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hepatic insulin clearance was studied in normal male and female Wistar rats using the isolated liver perfusion technique and the dextran coated charcoal radioimmunoassay for insulin. The following results were obtained: — 1. In male rats there was a progressive increase in clearance with increasing body weight, liver weight and age. — 2. In adult female rats clearance was significantly greater than in comparable males, but no relationship between liver weight and clearance was observed. — 3. With each increase in insulin concentration there was an apparent decrease in clearance.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 28 (1973), S. 87-94 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Intragastric ; Self-Administration ; Benzodiazepines ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A technique for intragastric self-administration in rats is presented. Intravenous self-administration of morphine was compared with intragstric self-administration during 6 consecutive days. There was no difference between the two routes in the total rate of injections. Medazepam was given for intragastric self-administration at three different doses (2.5, 5.0 and 10.0 mg/kg/injection respectively) and compared with saline. There was an increased response rate at the dose 10 mg/kg/injection. Medazepam placebo solution (solvent alone) was also compared with medazepam 10 mg/kg/injection. Among the seven experimental rats, six responded higher on medazepam than on the solvent.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 33 (1973), S. 349-354 
    ISSN: 1432-2072
    Keywords: Cannabis Experience ; Drugs ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 705 Wuppertal School children were requested to give information upon their drug experience by using a standardized questionnaire. 46 school children reported to have taken cannabis. The information given by these children upon their first cannabis experience, cannabis experience after repeated use, their behaviour after taking cannabis, changes in mood and personality due to cannabis use, and the effect of cannabis use on sexuality, showed extreme individual variations, e.g. extremely positive and negative experiences. The results show that individually extremely varying effects of cannabis can also be observed in such a small homogeneous group of subjects as Wuppertal school children. In general, the cannabis effects experienced by the Wuppertal school children were similar to those experienced by the young people in Berlin. However, some differences were observed: The “strong feeling of hunger” and “thirst” which were reported by the young people in Berlin as typical cannabis effects, were absent in the Wuppertal school children.
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  • 16
    ISSN: 1432-2013
    Keywords: RQ ; Insulin ; Glucose ; Lactate ; Pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary RQ, plasma insulin, blood glucose, lactate and pyruvate were measured in six fit, normal subjects during a series of exercise and rest experiments with and without sucrose ingestion. Subjects exercised on a bicycle ergometer for 50 min of every hour for 6 h at about 47% of the group's average maximal aerobic capacity. In the resting experiments, the subjects sat for 6 h in an armchair. A solution containing 100 g of sucrose was ingested at the beginning of the fourth hour during the sucrose experiments. Ingestion of sucrose caused a significant increase in RQ, plasma insulin, blood glucose, lactate and pyruvate in both exercise and rest experiments. Insulin, lactate and pyruvate concentrations rose higher during rest after sucrose ingestion than during exercise. The time courses of the changes in RQ, insulin, glucose, lactate and pyruvate after sucrose ingestion, suggest that glucose entering the cell during rest is immediately oxidized, while during work there is some delay in the oxidation of glucose.
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  • 17
    ISSN: 1432-2013
    Keywords: Insulin ; Muscle Metabolism ; Carbohydrate Metabolism ; “Bis-Phosphoenolpyruvate”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course of the insulin effect on 1,2-bis-phosphoenolpyruvate (bis-PEP), a glucose metabolite, has been investigated. Within 30 sec insulin causes an increase of 60% in the amount of bis-PEP accumulated in incubation media of rat diaphragms.
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  • 18
    ISSN: 1432-1440
    Keywords: long acting glucagon ; glucose ; free fatty acids ; insulin ; left ventricular contractility ; Depot-Glucagon ; Glucosestoffwechsel ; freie Fettsäuren ; Insulin ; linksventriculäre Kontraktilität
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Zink-Protamin-Glucagon zeigt bei s.c.-Injektion in einer Dosis von 5 mg einen deutlichen, aber protrahierten Anstieg des Blutzuckers um rund 40% innerhalb 1 Std und behält dieses erhöhte Niveau durch mehrere Stunden bei. Die Lipase-Aktivitätssteigerung nach Glucagon ist beim Menschen nur kurzfristig und unbedeutend [rund 7% ige Zunahme der freien Fettsäuren (FFS) 10 min p. inj.], sie wird von einem insulininduzierten Abfall der FFS um rund 50% im Laufe von 6 Std gefolgt. Die Zunahme der Insulinspiegel im Serum ist zwar statistisch signifikant, erreicht aber nicht das Ausmaß der von der intravenösen Verabreichung bekannten Veränderungen. Die hämodynamischen Effekte einer Einzeldosis von 5 mg Zink-Protamin-Glucagon sind nicht eindeutig und lassen lediglich eine nicht signifikante Zunahme von LVdp/dt max um 16,7% nach 15 min erkennen, während alle anderen Parameter im wesentlichen unverändert bleiben. Die mögliche klinische Bedeutung dieser Glucagoneffekte wird diskutiert.
    Notes: Summary The subcutaneous injection of 5 mg of zincprotamine-glucagon results in a 40% increase of blood glucose within 1 hour; this elevated level is maintained for several hours. The activation of lipase after the administration of glucagon in patients is insignificant and of short duration (only 7% rise of plasma FFA 10 minutes after injection) and is followed by an insulin-induced fall of plasma FFA by 50% within 6 hours. There is a concomitant, statistically significant rise in serum insulin. Haemodynamic measurements following a single dose of 5 mg of zinc-protamine-glucagon revealed only a statistically non significant 16.7% rise in LVdp/dt max, after 15 minutes, the other parameters remaining essentially unchanged. The possible elinical significance of these glucagon effects is discussed.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 51 (1973), S. 63-67 
    ISSN: 1432-1440
    Keywords: Insulin ; glycaemia ; diabetes ; radioimmunoassay ; Insulin ; Glycaemia ; Diabetes ; Radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Bestimmung des immunoreaktiven Insulins im Plasma hat in der Diagnostik insulinsezernierender Tumoren allgemein Anwendung gefunden. Beim Diabetes mellitus ist diese Untersuchung von großer Bedeutung zur Unterscheidung der metabolischen und pankreatischen Faktoren dieser Krankheit. Sie erleichtert sowohl die Entscheidung in der Wahl der Therapie als auch die weitere Verlaufskontrolle.
    Notes: Summary The use of the measurement of plasma immunoreactive insulin levels is generally accepted for the diagnosis of insulin-secreting tumours. In diabetes, this determination is of major importance for the differentiation between the metabolic and pancreatic factors involved in the disease and it is helpful both for initiating therapy and following up cases over the years.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 51 (1973), S. 1010-1015 
    ISSN: 1432-1440
    Keywords: Hemodialysis ; glucose tolerance ; insulin ; Hämodialyse ; Glucosetoleranz ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 39 Dialysepatienten wurden i.v. Glucosetoleranzteste (i.v. GTT) durchgeführt und anhand des AssimilationskoeffizientenK beurteilt. Bei 25 Patienten wurde während des Testes das immunologisch meßbare Insulin (IMI) bestimmt. Bei 5 Patienten und 4 Kontrollpersonen wurden außerdem Insulintoleranzteste (i.v. ITT) durchgeführt. 56% der Patienten wiesen pathologischeK-Werte unter1,2 auf. Eine negative Korrelation zwischenK-Wert und Serumosmolarität konnte nachgewiesen werden. Bei allen Patienten waren die 5- und 10-min Blutzucker-(BZ-)Werte im i.v. GTT in Abhängigkeit des Hämatokrits vermindert. Ebenso waren die Insulinspiegel während des i.v. ITT bei den Patienten vermindert. Aufgrund dieser beiden Befunde ist ein Vergleich der Höhe der Insulinspiegel von Dialysepatienten und Stoffwechselgesunden nicht möglich. Allerdings konnte beobachtet werden, daß bei Patienten mitK〈1,2 die Insulinausschüttung verzögert erfolgte. Beim i.v. ITT fand sich ein verzögerter BZ-Abfall nach der Insulingabe, außerdem war die Halbwertszeit des i.v. applizierten Insulins verlängert. Demnach resultiert die Glucosestoffwechselstörung bei Dialysepatienten aus der Kombination von verlangsamter Insulinausschüttung aus dem Pankreas und verzögerter Insulinwirkung in der Peripherie.
    Notes: Summary In 39 patients undergoing regular hemodialysis treatment (RDT), intravenous glucose tolerance tests (IVGTT) were performed. They were evaluated on the basis of the assimilation coefficient (K-rate). During the tests, immunologically measurable insulin (IMI) was investigated in 25 cases. Intravenous insulin tolerance tests (IVITT) were performed in 5 patients and 4 controls. 56% of the patients showed abnormalK-values (K〈1.2). A negative correlation betweenK-rate and osmolarity could be demonstrated. Depending on the hematocrit, low blood glucose levels were found in all patients 5 and 10 minutes after beginning the IVGTT. Low insulin concentrations during IVITT were also observed. Because of these two findings, a comparison of insulin levels between dialysed patients and normal subjects is not possible. However, the release of insulin was delayed in patients withK-rates lower than 1.2. During IVITT patients on RDT showed a delayed decrease of blood glucose compared to controls, moreover, half-life of i.v. administered insulin was prolonged. It is concluded that the abnormal glucose metabolism in patients on RDT can result from a combination of delayed insulin secretion of the pancreas and delayed peripheral insulin activity.
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    Psychopharmacology 32 (1973), S. 343-349 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Sleep ; Flunitrazepam ; Benzodiazepines ; Insomnia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The action of flunitrazepam (Ro 5-4200) a benzodiazepine derivative was assessed on the sleep cycle of normal volunteers by means of all-night recordings. Baseline placebo nights were compared with the drug (2 mg p.o.) and with the placebo postdrug nights. Flunitrazepam induced a shift to faster frequencies of the EEG and increased non-rapid eye movement sleep. REM sleep was decreased at the expense of a smaller number of REM periods and shifted to the last two thirds of the night. During drug administration an adaptation was seen to the depressive action on REM sleep. Following withdrawal, an REM rebound was observed only during the first thirds of the night.
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  • 22
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    European journal of applied physiology 31 (1973), S. 163-172 
    ISSN: 1439-6327
    Keywords: Muscle Glycogen ; Exercise ; Insulin ; Testosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anin vitro preparation of electrically stimulated sartorius muscle of the frog was used as a model to investigate the effects of insulin and testosterone on the increased glycogen content of frog skeletal muscle that was observedin vivo 48 h after an exhaustive bout of treadmill exercise. Thein vitro preparation could effectively extract glucose from the bathing medium and continue glycogen synthesis for incubation periods up to 60 h, and the electrical stimulation depleted glycogen by 68%. Electrical stimulation enhanced rates of glucose uptake and glycogen synthesis when these variables were measured after prolonged periods of poststimulation incubation but did not cause an overshoot of glycogen storage similar to that observedin vivo. Stimulation did not produce increments in glycogen synthesis that were additive to those of insulin or testosterone. The absence of glycogen overshoot in thein vitro system may have resulted from the absence of neural factors.
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  • 23
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    Research in experimental medicine 158 (1972), S. 75-84 
    ISSN: 1433-8580
    Keywords: Renal Potassium Excretion ; Insulin ; Glucose ; Osmotic Diureses ; Kalium (renale Ausscheidung) ; Insulin ; Glucose ; Osmotische Diurese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Mannit in hypertonischer Lösung ruft bekanntlich eine osmotische Diurese mit erhöhter Natrium- und Kaliumausscheidung hervor. Hypertonische Glucoseinfusionen (Blutzuckerwerte 280–380 mg%) dagegen führen bei nieren- und stoffwechselgesunden Probanden trotz Entwicklung einer osmotischen Diurese zu einer verminderten Kaliumausscheidung bei nur gering gesteigerter Natriurese. Zusätzlich verabfolgtes Insulin verstärkt den kaliumretinierenden Effekt in Abhängigkeit von seiner Dosierung. Die Ergebnisse lassen eine direkte Insulinwirkung auf die renale Kaliumausscheidung annehmen. Unter den genannten Versuchsbedingungen wird ein Quotient für U/PKalium 〈 1 und gleichzeitig eine verminderte Natriumausscheidung bestimmt. Bei Patienten mit stärker eingeschränktem Glomerulumfiltrat (chronische Pyelonephritis) wird die bereits bestehende endogene osmotische Diurese durch intravenöse Glucosezufuhr (Blutzucker um 400 mg%) verstärkt und führt zu erheblicher Kalium- und Natriummehrausscheidung bei signifikant sinkenden Plasmaspiegeln dieser Elektrolyte.
    Notes: Summary In contrast to the increased excretion of sodium and potassium in mannitol-diuresis in healthy men, hypertonic glucose-infusion (bloodsugar 280 to 380 mg%) causes in spite of osmotic diuresis a decrease of potassium excretion and only a small loss of sodium. Insulin applied in addition raises this effect according to its dosage. It is suggested, that insulin modifies renal potassium excretion either by increasing reabsorption and/or decreasing secretion. Under these conditions the ratio U/Ppotassium was found 〈 1. In patients with markedly reduced glomerular filtration rate by chronic pyelonephritis endogenous osmotic diuresis is enhanced by glucose-infusion (bloodsugar 400 mg%). Now an increasing excretion both of potassium and sodium was found, while plasma levels of these ions decreased significantly.
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  • 24
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    Diabetologia 8 (1972), S. 260-266 
    ISSN: 1432-0428
    Keywords: Insulin ; radioimmunoassay ; total IRI in insulin-treated diabetics ; acid ethanol extraction of insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On décrit une méthode de routine pour le dosage de l'IRI (insuline immunoréactive) totale chez les diabétiques traités par l'insuline. La méthode comprend une extraction à l'acide-éthanol, très simple, pendant laquelle l'IRI liée aux anticorps est dissociée et séparée ainsi que l'IRI »libre« des protéines sériques, anticorps compris. La récupération de l'IRI par cette méthode est aux environs de 80%. Après la séparation, l'IRI totale isolée est mesurée par un dosage immunologique qui se sert de l'éthanol afin de séparer l'I125-insuline libre de celle liée aux anticorps. Chez 169 malades diabétiques traités par l'insuline à des doses allant de 6 à 120 unités par jour, l'IRI totale sérique à jeun était de 6 à 4374 μU/ml, avec une moyenne de 392 μU/ml. Pendant le traitement par l'insuline le taux de l'IRI totale est passé des niveaux normaux, enregistrés pendant les deux premiers mois, à des niveaux plus éleévs qui se stabilisent 5 mois environ apres le début du traitement. L'augmentation de l'IRI coïncide avec la formation d'anticorps. Les malades insulino-résistants présentent des valeurs très hautes d'IRI.
    Abstract: Zusammenfassung Für die Bestimmung des Gesamt-IRI (immunoreaktiven Insulins) bei Diabetikern, die mit Insulin behandelt wurden, wird eine Routinemethode beschrieben. Die Methode schließt eine einfache SäureÄthanol-Extraktion ein, wobei das antikörpergebundene IRI dissoziiert und zusammen mit dem „freien“ IRI von den Serumproteinen, einschließlich den Antikörpern, getrennt wird. Bei diesem Verfahren werden etwa 80% des IRI wiedergefunden. Nach der Trennung wird das isolierte Gesamt-IRI immunologisch gemessen. Für die Trennung des freien von dem an Antikörper gebundenen125I-Insulin wird Äthanol verwendet. Bei 169 Diabetikern, die mit 6 bis 120 E Insulin/Tag behandelt wurden, lag das Nuchternserum-Gesamt-IRI zwischen 6 und 4374 μE/ml (Mittelwert 392 μE/ml). Im Laufe der Insulinbehandlung stieg das Gesamt-IRI von Normalwerten, die während der ersten 2 Monate registriert wurden, auf ein höheres Niveau an, das sich nach etwa 5 Monaten Behandlungsdauer stabilisierte. Der Anstieg des IRI erfolgte gleichzeitig mit der Bildung von Antikörpern. Bei insulinresistenten Patienten ergaben sich sehr hohe IRI-Konzentrationen.
    Notes: Summary A routine method is described for the determination of total IRI (imraunoreactive insulin) in insulintreated diabetics. The method involves an easy acid ethanol extraction, whereby antibody-bound IRI is dissociated and separated, together with the “free” IRI from the serum proteins and the antibodies. The recovery of IRI in this procedure is about 80%. After the separation, the isolated total IRI is measured in an immunoassay, using ethanol for the separation of free and antibody bound125I-insulin. In 169 diabetic patients treated with insulin in doses of from 6 to 120 units/day, the fasting serum total IRI was between 6 and 4374 μU/ml, with a mean of 392 μU/ml. During treatment with insulin, the level of total IRI increased from normal values, registered during the first two months, to a higher level which became stable after about 5 months of treatment. The increase in IRI occurred simultaneously with the formation of antibodies. Insulin-resistant patients showed very high IRI levels.
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    Psychopharmacology 26 (1972), S. 62-72 
    ISSN: 1432-2072
    Keywords: Delta-9-Tetrahydrocannabinol ; Marihuana ; Timing ; Audition ; Monkeys ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In two experiments, macaques were trained to respond differentially to either the duration of a visual stimulus or to the frequency of an auditory clicker. In the duration discrimination experiment, delta-9-tetrahydrocannabinol (delta-9-THC) was administered acutely in doses from 1 to 16 mg/kg, producing dose-related decrements in accuracy of the discrimination performance, and a reduction in the rate at which the animals initiated discrimination trials. In both the duration and auditory discrimination experiments, chronic daily administrations of 2 to 16 mg/kg of delta-9-THC produced an initial decrement in accuracy and rate of trial initiation. Both measures showed some development of tolerance, tending to return to baseline levels, however, the time course of tolerance was different for the measures, with the rate of trial initiation recovering more quickly than accuracy. No differences in response to the drug were attributable to the different modalities used in these two experiments.
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    Psychopharmacology 27 (1972), S. 163-169 
    ISSN: 1432-2072
    Keywords: Marihuana (Cannabis) ; (−)δ 9-trans-Tetrahydrocannabinol (δ 9-THC) ; Psychopharmacology ; Operant Behavior ; Schedule of Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Four rats were trained to barpress for water reinforcement under a variable interval 60 sec schedule. Nine acute administrations of (−)δ 9-trans-tetrahydrocannabinol, in amounts ranging from 0.25 to 16.0 mg/kg, produced dose-related effects on responding; overall response rate increased at lower doses, while higher doses produced ataxia and a complete suppression of responding. Increased response rates reflected changes both in response spacing and in the lengths of post-reinforcement pauses. It was concluded that marihuana has a biphasic effect on variable interval water-reinforced behavior in rats.
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  • 27
    ISSN: 1432-2072
    Keywords: Marihuana (Cannabis) ; (−)δ 9-trans-tetrahydrocannabinol (δ 9-THC) ; Psychopharmacology ; Operant Behavior ; Schedule of Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Eight chimpanzees emitted panel push responses under a procedure in which three operant schedules of positive reinforcement, each associated with a different stimulus, were presented successively. The fixed ratio (FR) schedule required the emission of 40 responses for reinforcement. Reinforcement under the differential reinforcement of low rate (DRL) schedule was delivered only for a response that followed the immediately preceding response by 10 or more sec. No responses were reinforced under the extinction or time out from reinforcement (TO) schedule. The behavioral effects produced by a marihuana extract distillate containing a known amount of (−)δ 9-trans-tetrahydrocannabinol (δ 9-THC) were compared with those produced by a totally synthesized δ 9-THC. On four separate drug days each chimpanzee was orally administered one of the two compounds 2.5 h prior to experimentation in amounts yielding 1.0 mg/kg δ 9-THC. Only the DRL schedule performance was significantly affected by either drug compound. Both the marihuana extract and the synthetic δ 9-THC produced a statistically significant decrease in the percentage of correct DRL responses. However, no statistically significant differences between the drug effects produced by the two δ 9-THC dose forms were obtained.
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  • 28
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    Pflügers Archiv 334 (1972), S. 279-292 
    ISSN: 1432-2013
    Keywords: Insulin ; Iodoacetate ; Glycolysis ; Muscle Metabolism ; Carbohydrate Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1,2-Bisphosphoenolpyruvate (bis-PEP), a new intermediate of carbohydrate metabolism, accumulates in the incubation medium of rat diaphragms. The metabolic properties of this intermediate have been studied. Bis-PEP is determined after isolation, by its radioactivity and the total phosphorus content. The production is stimulated by insulin. The addition of adrenalin and monoiodoacetate to media containing insulin causes a further increase in concentration of bis-PEP in the medium. When incubating with glucose labeled in the first or the sixth carbon atom, the dilution of the isotope incorporated into bis-PEP is different. The use of 1-14C-glucose gives rise to the production of bis-PEP with low specific activity; this dilution is counteracted by the addition of monoiodoacetate to the medium. The addition of non-radioactivedl-glyceraldehyde to the medium causes a doubling of the total amount accumulated and an approximately equal increase in isotope dilution. The addition of inert hydroxypyruvate decreases the dilution factor without increasing the total amount. When glycogen in the diaphragms is labeled by preliminary incubation with14C-glucose, labeled bis-PEP can be isolated from a second, non-radioactive medium. Anaerobiosis does not inhibit production. Assuming that in the intact diaphragm as in isolated systems the effect of monoiodoacetate is first and foremost on glyceraldehydedehyrogenase, it is suggested that the synthesis of bis-PEP takes place at a point above the formation of 1,3-diphosphoglycerate.
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    Acta diabetologica 9 (1972), S. 540-561 
    ISSN: 1432-5233
    Keywords: Carbohydrates ; Cholesterol ; Fats ; Insulin ; Lipoprotein lipase ; Lipoproteins ; NEFA ; Nicotinic acid ; Pre-β-lipoproteins ; Serum lipids ; Triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a étudé 84 sujets diabétiques a fin de mettre en évidence la frequence et le type des complications hyperlipidémiques au cours de la maladie diabétique. Pour déterminer quelques aspects de la pathogénèse, des patients ont reçu une diète hyperglucidique (CHO 75–80%), des autres ont reçu un surplus diététique de beurre (30% des calories totales), des autres enfin ont été tratés par acide nicotinique (2 g/die pendant 8 jours). Les résultats ont mis en évidence que une hyperlipémie est très fréquente au cours de diabète mais elle jamais atteint à des niveaux élevés; le type II est rare tandis que prédomine le type IV; il y a même la présence de un type «mélangé» (II+IV) e de «sinking pre-β». L'hyperlipémie, caractérisée par une légère réduction de la lipoprotéine-lipase, n'est pas modifiable ni par des diètes hyperglucidiques ni avec le surplus de gras saturés; au contraire l'action de l'acide nicotinique a réduit l'hyperglycémie et la bande pre-β. La légère hyperlipémie habituelle des diabétiques semble causée par une aumentation de l'afflux de NEFA au foie et par un déficit de la rémotion plasmatique de VLDL. Excéptionnellement une «grosse» hyperlipemie complique le diabète de la maturité ou le diabète en acido-cétose; en ces cas il s'agirait plus de une association de plusieurs gènes morbides que de une interdèpendence pathogénétique.
    Abstract: Resumen Los autores han estudiados una serie de 84 diabéticos, al objeto de determinar la frecuencia con que la diabetes se complica con una hiperlipemia y el tipo de esta última. Para determinar algunos aspectos de la patogenesis, una parte de los pacientes se sometió a dieta hiperglucídica (carbohidratos 75–80 %), otra recibió un suplemento dietético de mantequilla (equivalente al 30% de la totalidad de calorías) y, finalmente, otra fue sometida a un tratamiento con ácido nicotínico (2 gramos diarios durante 8 días). Los datos obtenidos han demostrado que la hiperlipemia se da muy frecuentemente durante la diabetes pero que habitualmente no alcanza grados elevados; el tipo II se da con escasa frecuencia; predomina el tipo IV de hiperlipoproteinemia; y también se da la presencia de un tipo «mixto» y en un cierto porcentaje figuran también las «sinking pre-β». La hiperlipemia, caracterizada preferentemente por una leve reducción de la lipoproteinlipasa, no ha resultado susceptible de modificaciones ni con la dieta hiperglucídica ni con el suplemento de grasas saturadas; en cambio, tanto la hiperglicemia como lafaja pre-β se ha atenuado bajo el tratamiento con ácido nicotínico. La leve hiperlipemia habitual del diabético parece pues que se vincule a una hiperafluencia de NEFA al hígado y a un déficit de la eliminación plasmática de VLDL. En casos excepcionales una «gran» hiperlipemia complica la diabetes de la madurez o la diabetes quetonúrica; en tales casos más que una interdependencia patogenética parece que lo que está en juego es una asociación de genes morbosos plúrimos.
    Notes: Riassunto Gli AA. hanno studiato una serie di 84 diabetici, al fine di accertare la frequenza con cui il diabete si complica con una iperlipemia, nonché il tipo di questa. Per determinare alcuni aspetti della patogenesi, parte dei pazienti sono stati sottoposti a dieta iperglicidica (carboidrati 75–80 %), parte hanno ricevuto un supplemento dietetico di burro (pari al 30 % delle calorie totali), mentre altri sono stati sottoposti a trattamento con acido nicotinico (2 g/die per 8 giorni). I dati ottenuti hanno consentito di accertare come una iperlipemia sia molto frequente in corso di diabete, ma come essa non raggiunga abitualmente gradi elevati; il tipo II è scarsamente frequente, mentre predomina il tipo IV di iperlipoproteinemia; vi è presenza anche di un tipo «misto», mentre in una certa aliquota figurano anche le «sinking pre-β». L'iperlipemia, per lo più caratterizzata da una lieve riduzione della lipoprotein-lipasi, non è risultata modificabile né con la dieta iperglicidica né con il supplemento di grassi saturi; sia l'iperlipemia che la banda pre-β si sono invece attenuate sotto trattamento con acido nicotinico. La lieve iperlipemia abituale del diabetico sembra quindi legata a un iperafflusso di NEFA al fegato e a un deficit della rimozione plasmatica di VLDL. In casi eccezionali, una «grossa» iperlipemia complica il diabete della maturità o il diabete chetonurico; in questi casi, più che una interdipendenza patogenetica sembra in gioco l'associazione di geni morbosi plurimi.
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    Acta diabetologica 9 (1972), S. 900-923 
    ISSN: 1432-5233
    Keywords: Fat cells ; Glucose uptake ; Insulin ; Kinetic constants ; Rat epididymal tissue ; Second order kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Après avoir mesuré le captage de glucose par les adipocytes de rat, on calcule les valeurs de K (constante de semi-saturation) et de V (captage maximum à des concentrations de glucose saturantes). L'insuline accroît le captage de glucose, tandis que le mannose et le 3-O-méthylglucose l'interdisent. Plusieurs préparations cellulaires donnent des valeurs différentes en ce qui concerne K, V et la sensibilité à l'insuline. On prend en considération l'effet possible de la teneur en triglycérides des adipocytes sur ces différents paramètres. Cependant, le caractère non-linéaire de certains diagrammes où les deux variables sont transformées dans leurs valéurs réciproques et certaines corrélations entre les divers paramètres cinétiques laissent penser à deux systèmes de captage de glucose dans les adipocytes de rat.
    Abstract: Resumen Se calculan los valores de K (constante de semisaturación) y de V (captación máxima y concentraciones de glucosa saturantes), por medio de mediciones de la captación de glucosa por parte de adipocitos de rata. La insulina aumenta la captación de glucosa, mientras que la manosa y el 3-O-metilglucosa la inhiben. Preparados celulares diversos facilitan diferentes valores por lo que se refiere a K, V y la sensibilidad a la insulina. Se considera el posible efecto del contenido de triglicéridos de los adipocitos según esos diversos parámetros. Sin embargo, la falta de linealidad de algunos diagrams en los que las variables se han transformado en sus recíprocos y ciertas correlaciones entre los varios parámetros cinéticos dan lugar a que se pueda suponer que en los adipocitos de rata puedan existir dos sistemas de captación de la glucosa.
    Notes: Riassunto Da misurazioni della captazione di glucosio da parte di adipociti di ratto vengono calcolati i valori di K (costante di semi-saturazione) e di V (captazione massima a concentrazioni di glucosio saturanti). L'insulina aumenta la captazione di glucosio, mentre il mannosio ed il 3-O-metilglucosio la inibiscono. Preparati cellulari diversi forniscono differenti valori per quanto riguarda K, V e la sensibilità all'insulina. Viene considerato il possibile effetto del contenuto in trigliceridi degli adipociti su questi diversi parametri. Tuttavia, la non linearità di alcuni diagrammi in cui entrambe le variabili sono trasformate nei loro reciproci e certe correlazioni tra i varî parametri cinetici fanno pensare che negli adipociti di ratto possano esserci due sistemi di captazione del glucosio.
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    Acta diabetologica 9 (1972), S. 865-899 
    ISSN: 1432-5233
    Keywords: cAMP ; Chlorpropamide ; Diabetes ; Glibenclamide ; Glibornuride ; Glucagon ; Insulin ; Methylxanthines ; Sulphonylureas ; Tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A présent, il est certain que les sulfanilurées exerçent essentiellement leur action au niveau du pancréas, stimulant la sécrétion insulinique et interdisant la sécrétion du glucagone. Dès la découverte des substances hypoglycemisantes par la voie orale, le développement de nouvelles sulfanilurées encore plus fortes a fait l'objet d'un très vif intérêt. Tout récemment, par la synthèse d'un nouveau composé plus puissant appartenant au groupe des sulfanilurées — la glibenclamide (HB 419, Daonil®) —, des progrès encourageants ont été réalisés, notamment en ce qui concerne le traitment du diabète chez les individus d'un âge mûr. Nombre de patients dépendant de l'insuline atteints de cette forme de diabète peuvent être traités en effet avec de la glibenclamide. Parfois, il se peut que des hypoglycemies masquées se manifestent, ce qui témoigne de l'activité intense de cette substance. La glibenclamide se diversifie des autres sulfanilurées du fait des différentes modalités qui provoquent la sécrétion d'insuline. Cette substance agit également synergiquement avec le glucose stimulant cette sécrétion. Aucun autre médicament hypoglycemisant ne permet, chez l'animal aussi bien que chez l'homme, d'accroître dans une mesure autant considérable la tolérance des glycides. La glibenclamide semble exercer son influence au niveau de la cellule B sur le même récepteur ou avec le même mécanisme agissant avec le glucose.
    Abstract: Resumen Actualmente se considera como un hecho cierto que las sulfanilureas actúan principalmente a nivel del áncreas estimulando la secreción insulínica e inhibendo la de glucagón. Desde la época en que fueron descubiertas las substancias hipoglicémicas orales, ha sido objeto de vivo interés el desarrollo de sulfanilureas nuevas y más potentes. Recientemente, a través de la síntesis de un compuesto muy potente perteneciente al grupo de las sulfanilureas — la glibenclamida (HB 419, Daonil®) —, se han realizado progresos alentadores sobre todo en el tratamiento de la diabetes de la edad madura. En efecto, muchos enfermos insulinodependientes afectos de dicho tipo de diabetes pueden pasar a la glibenclamida. A veces se pueden virificar hipoglicemias disfrazadas, que prueban la intensa actividad de esta substancia. La glibenclamida se diferencia de las demás sulfanilureas por las diversas modalidades con que provoca la secreción de insulina. Además, actúa sinérgicamente con la glucosa en el stímulo de dicha secreción. Ningún otro producto hipoglicémico es capaz, tanto en el hombre como en el animal, de aumentar en medida tan notable la tolerancia glucídica. La glibenclamida parace actuar a nivel de la célula B en el mismo receptor o con el mismo mecanismo con que actúa la glucosa.
    Notes: Riassunto Attualmente, è considerato un fatto certo che le sulfaniluree agiscano principalmente a livello del pancreas, stimolando la secrezione insulinica ed inibendo quella del glucagone. Sin dall'epoca della scoperta degli ipoglicemizzanti orali, lo sviluppo di nuove e più efficaci sulfaniluree è stato oggetto di vivo interesse. Recentemente, attraverso la sintesi di un nuovo ed assai efficace composto appartenente al gruppo delle sulfaniluree — la glibenclamide (HB 419, Daonil®) —, incoraggianti progressi sono stati compiuti, soprattutto nel trattamento del diabete dell'età matura. Molti pazienti insulino-dipendenti affetti da tale tipo di diabete possono essere infatti passati alla glibenclamide. Talvolta possono verificarsi ipoglicemie mascherate, a dimostrazione dell'intensa attività di questa sostanza. La glibenclamide si differenzia dalle altre sulfaniluree per le diverse modalità con cui provoca la secrezione di insulina. Essa agisce inoltre sinergicamente con il glucosio nello stimolare tale secrezione. Nessun altro farmaco ipoglicemizzante è capace, sia nell'animale che nell'uomo, di aumentare in misura altrettanto notevole la tolleranza glicidica. La glibenclamide sembra agire a livello della cellula B sullo stesso recettore o con il medesimo meccanismo con cui agisce il glucosio.
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  • 32
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    Acta diabetologica 9 (1972), S. 299-304 
    ISSN: 1432-5233
    Keywords: Complex formation ; Cysteine ; Cystine ; Insulin ; Tryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Par la méthode chromatographique de la gel-filtration sous les mêmes conditions réalisées pour l'isolement du complexe insuline tryptophane, aucune formation de complexes avec cysteine et cystine n'a été vérifiée.
    Abstract: Resumen Empleando el método cromatográfico da la gel-filtración, en las mismas condiciones actuadas para el aislamiento del complejo insulina-triptófano, no se ha observado formación de complejos con la cisteina y la cistina.
    Notes: Riassunto Impiegando il metodo cromatografico della gel-filtrazione, nelle medesime condizioni attuate per l'isolamento del complesso insulina-triptofano, non è stata osservata formazione di complessi con la cisteina e la cistina.
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  • 33
    ISSN: 1432-5233
    Keywords: Adipose tissue ; Antilipolytic effect ; Glycerol release ; Insulin ; Isolated fat cells ; Norepinephrine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les Auteurs ont étudié l'effet antilypolytique de l'insuline sur la lypolyse induite par la noradrénaline. Après avoir choisi une dose minime d'hormone capable d'exercer sûrement une action antilypolytique, les Auteurs ont comparé des insulines de type différent, y compris l'insuline humaine, afin de déterminer l'existence éventuelle d'une efficacité différente.
    Abstract: Resumen Los autores han estudiato el efecto antilipolítico de la insulina sobre la lipolisis inducida por la noradrenalina. Tras haber elegido una dosis mínima de hormón capaz de desarrollar una acción antilipolítica segura, los autores han comparado entre ellas insulinas de diferentes especies, incluso de la humana, con la finalidad de determinar la posible existencia de una diversa eficacia.
    Notes: Riassunto Gli AA. hanno studiato l'effetto antilipolitico dell'insulina sulla lipolisi indotta dalla noradrenalina. Dopo aver scelto una dose minima di ormone capace di esercitare una sicura azione antilipolitica, gli AA. hanno confrontato tra loro insuline di specie differente, compresa quella umana, allo scopo di determinare l'eventuale esistenza di una diversa efficacia.
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  • 34
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    Acta diabetologica 9 (1972), S. 15-45 
    ISSN: 1432-5233
    Keywords: Biological activity ; Connecting-peptide (C-peptide) ; Diabetes ; Functioning islet cell tumor ; Immunological activity ; Insulin ; Obesity ; Proinsulin ; Serum C-peptide ; Serum proinsulinlike material
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La molécule de la proinsuline, precurseur à chaîne unique de l'insuline, commence par la chaîne B de l'insuline, continue à travers un peptide contenant quelque 30–35 acides aminés, par rapport à l'espèce, et se termine par la chaîne A de l'insuline. De nombreuses enquêtes expérimentalesin vitro ont révélé que la transformation de la proinsuline en insuline est liée à la formation des granules de sécrétion et que le C-peptide n'est pas métabolisé à l'intérieur des cellules B. Il a été démontré que la proinsuline et le C-peptide sont présents dans le sérum de sujets normaux, obèses et diabétiques. A jeun, la concentration de la proinsuline sérique représente environ 40 % de celle de l'insuline (c'est-à-dire 25 % de l'IRI sérique totale). Après une administration de 100 grammes de glucose, on a observé une diminution du rapport proinsuline/insuline. Dans quelques sujets ayant une tumeur fonctionnante des îlots de Langerhans, les valeurs de la proinsuline peuvent être extrêmement élevées, jusqu'à représenter environ 80–90 % de l'IRI sérique. La détermination du C-peptide dans le sérum a été effectuée par une méthode radioimmunologique spécifique. Après glucose, on a observé une augmentation des valeurs sériques du C-peptide. Dans des sujets normaux, obès et diabétiques et dans des sujets avec insulinome, les valeurs sériques du C-peptide et de l'insuline étaient essentiellement équivalents, si elles étaient évaluées sur base molaire. La présence de la proinsuline et du C-peptide dans la circulation a suscité un interêt considérable pour un effet éventuel biologique de ces substances. En dépit des résultats contrastants concernant l'activité biologique de la proinsuline, probablement à cause des techniques différentes utilisées, les effets métaboliques de la proinsuline dans les différents tissus sont très semblables à ceux de l'insuline. Par contre, le C-peptide ne semble pas posséder d'activité biologique. Il n'est pas encore certain si la proinsuline et le C-peptide présents dans la circulation exercent quelque action spécifique au niveau des tissus périphériques ou bien s'ils représentent simplement une conséquence passive du mécanisme de sécrétion de l'insuline.
    Abstract: Resumen La molécula de la proinsulina, precursora en cadena única de la insulina, inicia con la cadena B de la insulina, continua a través de un péptido compuesto de unos 30–35 aminoácidos, en relación con la especie y termina con la cadena A de la insulina. Numerosas investigaciones experimentalesin vitro sugieren que la transformación de la proinsulina en insulina se vincula a la formación de los gránulos de secreción y que el C-péptido no se metaboliza dentro de las células B. Se ha demostrado que la proinsulina y el C-péptido se hallan presentes en el suero de individuos normales, obesos y diabéticos. En ayunas, la concentración de la proinsulina serosa alcanza el 40 % aproximadamente de la correspondiente a la insulina (es decir, el 25 % del IRI sérico total). Tras suministro de 100 gramos de glucosa se ha observado una disminución de la relación proinsulina/insulina. En algunos individuos con tumor activo en las islas de Langerhans, los valores de la proinsulinemia pueden llegar a ser muy elevados, hasta alcanzar casi el 80–90 % del IRI suerosa. La determinación del C-péptido en el suero se ha efectuado por medio de un método radioinmunológico específico. Tras glucosa se ha observado un aumento de los valores suerosos del C-péptido. En individuos normales, obesos y diabéticos y en individuos con insulinoma los valores suerosos del C-péptido en circulación ha suscitado notable interés bajo el aspecto de un posible efecto biológico de esas substancias. A pesar de que con respecto a la actividad biológica de la proinsulina los resultados se presentan más bien en contraste, probablemente en función de las diversas técnicas seguidas, los efectos metabólicos de la proinsulina en los varios tejidos son muy parecidos a los de la insulina. Por el contrario, el C-péptido no parece tener actividad biológica alguna. Todavía no se conoce con seguridad si la proinsulina y el C-péptido presentes en la circulación desarrollan alguna función espécifica a nivel de los tejidos periféricos o si simplemente son una consecuencia pasiva del mecanismo de secreción de la insulina.
    Notes: Riassunto La molecola della proinsulina, precursore a catena unica dell'insulina, inizia con la catena B dell'insulina, prosegue attraverso un peptide composto di circa 30–35 aminoacidi, in rapporto alla specie e termina con la catena A dell'insulina. Numerose indagini sperimentaliin vitro suggeriscono che la trasformazione della proinsulina in insulina sia legata alla formazione dei granuli di secrezione e che il C-peptide non venga metabolizzato all'interno delle cellule B. É stato dimostrato che la proinsulina e il C-peptide sono presenti nel siero di soggetti normali, obesi e diabetici. A digiuno, la concentrazione della proinsulina sierica rappresenta circa il 40 % di quella dell'insulina (ovvero circa il 25 % dell'IRI sierica totale). Dopo somministrazione di 100 g di glucosio, è stata osservata una diminuzione del rapporto proinsulina/insulina. In alcuni soggetti con tumore funzionante delle isole di Langerhans, i valori della proinsulinemia possono essere molto elevati, fino a rappresentare circa l'80–90 % dell'IRI sierica. La determinazione del C-peptide nel siero è stata eseguita per mezzo di un metodo radioimmunologico specifico. Dopo glucosio, è stato osservato un aumento dei valori sierici del C-peptide. In soggetti normali, obesi e diabetici e in soggetti con insulinoma i valori sierici del C-peptide e dell'insulina erano essenzialmente equivalenti se valutati su base molare. La presenza della proinsulina e del C-peptide in circolo ha suscitato notevole interesse nei riguardi di un eventuale effetto biologico di queste sostanze. Nonostante che nei riguardi dell'attività biologica della proinsulina i risultati siano piuttosto contrastanti, probabilmente in rapporto alle diverse tecniche impiegate, gli effetti metabolici della proinsulina nei varî tessuti sono molto simili a quelli dell'insulina. Al contrario, il C-peptide non sembra possedere alcuna attività biologica. Non è ancora certo se la proinsulina e il C-peptide presenti in circolo svolgano qualche funzione specifica a livello dei tessuti periferici oppure se essi rappresentino semplicemente una conseguenza passiva del meccanismo di secrezione dell'insulina.
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  • 35
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    Naunyn-Schmiedeberg's archives of pharmacology 271 (1971), S. 361-373 
    ISSN: 1432-1912
    Keywords: Saponine ; Insulin ; Cell Membrane ; Glucose Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The glucose uptake by isolated adipose tissue of rat and by Yoshida sarcoma ascites tumour cells was determined in vitro in tbe presence of aescin,α-aescin, andβ-aescin. 2. With adipose tissue small concentrations of aescin (about 6 × 10−6 M) decreased glucose in the outside medium and increased14CO2-production from [1-14C]-glucose. Higher concentrations (about 3 × 10−5M) inhibited glucose permeation. The behaviour ofβ-aescin was similar, but more pronounced andα-aescin had similar effects at higher concentrations. 3. From the kinetic analysis of the overall process, the resulting impairment of stimulation by 3-O-methylglucose and the ineffectiveness of SH-containing substances it is concluded, that aescin (like insulin, proteases, and phospholipases) stimulates membrane carrier. Higher concentrations of aescin inhibit glucose permeation probably by interference with membrane structure. 4. No stimulation of glucose transport is seen after the addition of aescin to ascites tumour cells. Concentrations of 3 × 10−5 M, however, impeded glucose transport by 90%. This difference underlines the distinct but not specific pecularities of certain tissue membranes which can be stimulated by insulin and other stimulants.
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  • 36
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    Psychopharmacology 21 (1971), S. 294-301 
    ISSN: 1432-2072
    Keywords: Amphetamines ; Antagonism ; Anticholinergic ; Tetrahydrocannabinols ; Cholinergic ; Chlorpromazine ; Glycolate ; Hallucinogens ; Mice ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mice were intraperitoneally dosed with trans(−)-Δ 8 tetrahydrocannabinol, various anticholinergic agents, hallucinogenics, or other behaviourally active drugs immediately prior to a habituating experience. The anticholinergic agents and trans(−)-Δ 8 tetrahydrocannabinol inhibited the subsequent influence of the habituating experience relative to the other drugs and to solvent treated subjects. The habituation modifying effects of these drugs were antagonized by tacrine, but not by d-amphetamine. The results suggest that the behavioural effects of tetrahydrocannabinols might involve an anticholinergic mechanism.
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  • 37
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    Pflügers Archiv 323 (1971), S. 11-20 
    ISSN: 1432-2013
    Keywords: Insulin ; Sodium Excretion ; Potassium Excretion ; Water Excretion ; Isolated Kidney ; Insulin ; Natriumexkretion ; Kaliumexkretion ; Wasser-exkretion ; Isolierte Niere
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin has been shown to decrease sodium, potassium and water excretion by direct action on the kidney. Reduction of sodium excretion is due to enhanced tubular reabsorption as a probable consequence of stimulated active sodium transport. The renal effect of insulin is demonstrated with plasma hormone concentration observable in pathophysiological conditions; it offers therefore a possible explanation for some clinical findings such as the changes in sodium, potassium and water excretion occurring in man after fasting and subsequent glucose feeding.
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  • 38
    ISSN: 1432-1440
    Keywords: Glucagon ; potassium ; glucose ; insulin ; Glucagon ; Kalium ; Glucose ; Insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach Applikation von 3 mg Glucagon i.v. wurden an 6 Patienten im Blut von Lebervene und Aorta und an 2 Patienten im coronarvenösen Blut simultan die Kalium-und Glucosekonzentrationen bestimmt. Unmittelbar nach Glucagongabe kam cs zu einem Anstieg der Kaliumkonzentration, welche in der Lebervene frühzeitiger und in größerem Ausmaß nachweisbar war als in der Aorta. Nach 3 min nahm die Kaliumkonzentration in der Aorta wie in der Lebervene kontinuierlich ab. Zeitlich abgesetzt von der initialen Hyperkaliämie kam es unter Glucagon zu einer Hyperglykämie, welche ebenfalls in der Lebervene ausgeprägter und frühzeitiger erfolgte als in der Aorta. Die Befunde sprechen dafür, daß Glucagon beim Menschen zu einem Nettokaliumefflux aus der Leber mit konsekutiver Hyperkaliämie führt. Die sekundäre, anhaltende Hypokaliämie nach Glucagongabe wird auf eine Stimulation der endogenen Insulinsekretion bezogen.
    Notes: Summary Potassium and glucose were measured simultaneously after i.v. injection of 3 mg glucagon in the hepatic vein and the aorta of six patients. In two patients, the measurements were performed in the coronary sinus. Immediately thereafter an increase of the potassium concentration was observed. In the hepatic vein the potassium level rose earlier and attained higher values than in the aorta. Three minutes later, the potassium concentration decreased in the aorta as well as in the hepatic vein.—The hyperglycemia due to glucagon occurred later than the hyperkalemia and was also higher and earlier in the hepatic vein than in the aorta. Our findings indicate that glucagon causes a netpotassium-efflux from the liver in man.—The secondary persistent hypokalemia after glucagon may be regarded as the consequence of a stimulated insulin secretion.
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  • 39
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    Psychopharmacology 20 (1971), S. 242-252 
    ISSN: 1432-2072
    Keywords: Evoked Potential ; Psychopharmacology ; Thiothixene ; Treatment of Schizophrenia ; Quantitative EEG Analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of thiothixene, a thioxanthene derivate, on the somatosensory evoked response was studied in a group of 9 chronic schizophrenic patients. It was found that the drug induces significant changes in the latency and amplitude of the SEP, predominantly in the later peaks. The latency of several peaks increased markedly in the first three weeks of treatment (during the low dosage period), whereas a further latency increase in the high dosage treatment period was only slight. After the discontinuation of drug administration a decrease in latency was observed. The amplitude revealed itself to be a sensitive indicator of the drug effect on the central nervous system, as the decrease in amplitude which occurred during the low dosage drug period ceased during high dosage treatment, indicating an adaptation effect on the patient population. In the post-treatment placebo period the amplitude increased, suggesting a rebound phenomenon. Schizophrenics who exhibited a marked latency increase in evoked response with thiothixene treatment, also experienced an improvement in psychopathology, whereas patients showing only a small latency increase, or even a decrease, revealed themselves as psychopathologically therapy resistant. It was found that thiothixene also produced significant EEG changes, determined by analog power spectrum and period analysis. During the drug treatment periods an increase in theta and alpha activity and a decrease in beta activity was observed. As in the SEP, eight weeks after discontinuation of the drug a rebound phenomenon was seen.
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  • 40
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    Psychopharmacology 20 (1971), S. 280-287 
    ISSN: 1432-2072
    Keywords: Sleep ; Chlorpromazine ; Electroencephalography ; Psychopharmacology ; Tranquilizers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to examine human physiological sleep profiles, including the amount and distribution of electroenoephalographic (EEG) stages of sleep, variations in specific frequency bands in the EEG spectrum and certain phasic phenomena such as movement arousals, sigma spindles and rapid eye movements, following oral administration of a moderate dose (150 mg) of chlorpromazine (CPZ) to 12 young male volunteers. At this dose level the drug had few systematic effects on sleep, although it did reduce the latency of onset of stage REM and the number of movement arousals, while increasing the amount of slow-wave (SW) sleep. These effects persisted during the post-medication recovery night, but at no time was there any systematic change in the total amount or percent of REM sleep, the duration of the REM-to-REM cycle, the average length of REM episodes or the density of rapid eye movements during stage REM. Frequency analysis of EEG revealed that CPZ produced a trend toward increased fast (beta) activity recorded from pre-central placements during stage REM, and reduced density of sigma spindles in stage 2 sleep. Thus, for the most part, a single moderate dose of CPZ left the tonic, phasic and sequential properties of the sleep cycle unaltered. These results confirm previous investigations showing that for small to moderate clinical doses, CPZ invariably enhances SW sleep and reduces the frequency of movement arousals. On the other hand, the effect of the drug on stage REM apparently depends on dose. Small doses potentiate REM sleep or accelerate its onset, whereas larger doses either reduce stage REM or leave it unaffected. Several authors have pointed out that most hypnotic agents cause substantial alterations of the sleep profile, and that their withdrawal can cause profound disruption of sleep and marked clinical disturbance. It also has been suggested that there exists a relation between drug dependency and the degree of initial REM suppression caused by a drug. The finding confirmed by the present study that clinical doses of CPZ cause mild sedation, and enhanced SW sleep without any significant modification of REM, sleep, indicates that CPZ has features which may recommend it as a standard hypnotic.
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  • 41
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    Psychopharmacology 19 (1971), S. 134-147 
    ISSN: 1432-2072
    Keywords: Electroencephalography ; Psychopharmacology ; Reserpine ; Serotonin ; Sleep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies of the effects of reserpine on human sleep have reported increased rapid eye movement (REM) sleep, and decreased slow-wave (SW) sleep. These results are relevant to theories linking serotonin and the catecholamines to the control of different stages of sleep. However, since reserpine causes release and subsequent depletion of both monoamines, it is difficult to relate changes in sleep profiles to specific alterations in one or the other amine system. The results to be reported here, when compared to those obtained with other treatments which affect the biogenic amines, encourage the view that level and turnover of serotonin are the primary mediators for reserpine-induced modifications of sleep. In two separate experiments, EEG sleep patterns from 20 male Ss were examined following single and repeated oral doses (1 mg) of reserpine. In the single-dose study, reserpine caused increased REM, and decreased SW sleep, effects which became statistically significant on the post-medication (P-M) recovery session. These changes were accompanied by reduced frequency per minute of sigma spindles (stage 2) decreased eye-movement density (stage REM) and a tendency toward increased brief arousals, especially during stage REM. Examination of parameters of the REM cycle revealed that the potentiation of REM sleep was due to its reduced latency of onset, and more frequent cyclic occurrence, not to increased duration of REM episodes. The results of the repeated-dose study replicated and amplified those of the first experiment, showing that medication caused a progressive increase in the amount of stage REM, accompanied by a simultaneous loss of SW sleep. The increase in REM was again due to acceleration of its cycle rather than lengthening of its episodes. During medication, epochs of stage REM were increasingly interrupted by brief arousals, with a simulteneous decline in the density of rapid eye movements. Most of these reserpine effects persisted into the P-M recovery session. The acceleration of the REM cycle, loss of SW sleep, decrease in sigma spindles and increase in brief arousals indicate that the acute effects of reserpine on human sleep are in the direction of activation, and the persistence of most of these alterations into the P-M session implies that they are due to depletion of one or both monoamines. However, comparison of reserpine effects on sleep with those induced by precursors and blockers of serotonin, and by monoamine oxidase inhibitors suggests that the loss of SW sleep may have resulted from depletion of serotonin, whereas acceleration of the REM cycle may have been caused by a compensatory increase in its rate of synthesis.
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  • 42
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    Psychopharmacology 21 (1971), S. 131-138 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Psychopharmacology ; Conditioning and Drug Abuse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methedrine was chronically administered twice a day to a group of cats over a period of eleven days. The stereotyped behavior elicited after injection became increasingly constricted over the eleven days. After Day 1 when the cats were placed in the observation cages just prior to injection, the stereotyped behavior would most often be initiated even before the injection, indicating a conditioning process. The behavior induced, as well as the parameters of reward, appears to fit well the accidental contingencies conditioning paradigm.
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  • 43
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    Psychopharmacology 22 (1971), S. 333-351 
    ISSN: 1432-2072
    Keywords: Marihuana (Cannabis) ; (−)-Δ 9-trans-Tetrahydrocannabniol (Δ 9-THC) ; Operant Behavior ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Six chimpanzees were trained to panel push under a food reinforcement baseline in which three operant schedules, each associated with a different stimulus, were presented successively. The fixed ratio (FR) reinforcement schedule required the emission of 40 responses for reinforcement. Reinforcement under the differential reinforcement of low rate (DRL) schedule was delivered only when successive responses were spaced by at least 10 sec. During the extinction or time out from positive reinforcement schedule (TO), no responses were reinforced. In Experiment 1, amounts of marihuana extract containing from 0.2 to 4.0 mg/kg (−)-Δ 9-trans-tetrahydrocannabinol (Δ 9-THC) were orally administered 1 h prior to experimentation. In Experiment 2, 1.0 mg/kg Δ 9-THC was orally administered between 1 and 23 h prior to experimental sessions. No disruption of stimulus control or drug effects during TO were observed. Both DRL and FR response suppression occurred at the highest drug dose. Lower Δ 9-THC doses produced facilitation of DRL responding up to 12 h following drug administration. Although FR responding was less sensitive, Δ 9-THC stimulated FR behavior from 2 to 5 h following drug administration. It was concluded that marihuana has a biphasic effect on food reinforcement schedule controlled operant behavior.
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  • 44
    ISSN: 1432-5233
    Keywords: Arginine infusion ; Diet ; Fasting ; Glucose loading ; Growth hormone ; Insulin ; Intravenous insulin tolerance test ; Low-calorie diet ; NEFA ; Obesity ; Oral glucose tolerance test ; Plasma insulin ; Plasma NEFA ; Simple obesity ; Starvation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez 12 sujets atteints d'obésité essentielle on a étudié le comportement de la glycémie, des acides gras libres plasmatiques, de l'hormone de croissance et de l'insuline en conditions basales et au cours d'épreuves dynamiques (charge orale de glucose, charge d'insuline, infusion d'arginine). Cette observation a été répétée après une période de 30 jours de jeûne absolu et après une même période de régime hypocalorique (500 Cal). Les facteurs qui contribuent à déterminer les modifications observées au cours du jeûne absolu et du régime hypocalorique sont vraisemblablement de deux ordres: d'une part on souligne le rôle des acides gras libres en tant que facteurs capables de favoriser le dérèglement glucidique que l'on observe au cours du jeûne absolu, d'autre part on met en valeur l'importance de l'hypothalamus pour les modifications métaboliques que l'on trouve dans l'obésité. Les résultats obtenus démontrent de façon évidente que l'hyposécrétion de l'hormone de croissance joue un rôle d'importance considérable dans la physiopathologie de l'obésité.
    Abstract: Resumen En 12 individuos afectos de obesidad esencial se ha estudiado el comportamiento de la glicemia, de los NEFA plasmáticos, del HGH y de la insulina en condiciones de base y a lo largo de pruebas dinámicas (carga oral de glucosa, prueba de carga insulínica, infusión de arginina). Esta observación se ha repetido durante un periodo de 30 días de ayuno absoluto y después de un periodo de 30 días de dieta hipocalórica con 500 calorías. En el determinismo de las modificaciones observadas a lo largo del ayuno absoluto y de la dieta hipocalórica, intervienen verosimilmente dos órdenes de factores: por un lado se subraya la importancia de los NEFA como factores aptos para favorecer el desarreglo glucídico presente durante el ayuno absoluto y por el otro se reitera la importancia del hipotálamo al condicionar las modificaciones metabólicas que se observan en la obesidad. Del examen de los resultados se deduce con evidencia que la hipoincreción de HGH juega un papel de relieve en el cuadro fisiopatológico de la obesidad.
    Notes: Riassunto In 12 soggetti affetti da obesità essenziale è stato studiato il comportamento della glicemia, dei NEFA plasmatici, dell'HGH e dell'insulina in condizioni di base ed in corso di prove dinamiche (carico orale di glucosio, prova di carico insulinico, infusione di arginina). Questa osservazione è stata ripetuta dopo un periodo di 30 giorni di digiuno assoluto e dopo un periodo di 30 giorni di dieta ipocalorica (500 Cal). Nel determinismo delle modificazioni osservate in corso di digiuno assoluto e di dieta ipocalorica intervengono verosimilmente due ordini di fattori: da un lato si sottolinea l'importanza dei NEFA come fattori idonei a favorire la disregolazione glicidica presente in corso di digiuno assoluto, dall'altro si ribadisce l'importanza dell'ipotalamo nel condizionare le modificazioni metaboliche riscontrabili nell'obesità. Dall'esame dei risultati risulta evidente come l'ipoincrezione di HGH abbia un ruolo non trascurabile nel quadro fisiopatologico dell'obesità.
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  • 45
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    Acta diabetologica 8 (1971), S. 288-294 
    ISSN: 1432-5233
    Keywords: Antagonism ; India ; Insulin ; Rat diaphragm ; Synalbumin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'albumine extraite du plasma de 20 diabétiques indiens sur 21, essayée à la concentration de 1,25 %, s'est révélée antagoniste de l'insuline. Le même antagonisme a été relevé, à cette même concentration, pour l'albumine plasmatique de 5 sujets volontaires sains sur 29 (17,2 %). Les résultats de ces recherches, conduites dans l'Inde du nord, ne diffèrent pas de ceux qui ont été signalés auparavant dans l'émisphère occidental.
    Abstract: Resumen La albúmina extraída del plasma de 20 de entre 21 diabéticos indios, ha resultado ser antagonista de la insulina al efectuar la comprobación a 1,2 % de concentración; a esa misma concentración la albúmina plasmática de 5 sobre 29 (17,2%) voluntarios sanos acusaba también un antagonismo a la insulina. Los resultados de estas investigaciones efectuadas en la India septentrional no se diferencian de los referidos precedentemente referentes al hemisfero occidental.
    Notes: Riassunto L'albumina estratta dal plasma di 20 su 21 diabetici indiani è risultata antagonista all'insulina, quando veniva saggiata alla concentrazione dell'1,25 %; a questa stessa concentrazione, l'albumina plasmatica di 5 su 29 (17,2 %) volontarî sani mostrava anch'essa un antagonismo all'insulina. I risultati di queste ricerche effettuate nell'India settentrionale non differiscono da quelli precedentemente riferiti per quanto riguarda l'emisfero occidentale.
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  • 46
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    Naunyn-Schmiedeberg's archives of pharmacology 265 (1970), S. 372-382 
    ISSN: 1432-1912
    Keywords: Diabetes ; Glucuronates ; Insulin ; Liver ; Uridine-Diphosphateglucuronic acid ; Diabetes ; Glucuronide ; Insulin ; Leber ; Uridindiphosphat-Glucuronsäure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The synthesisin vitro of o-aminophenol-glucuronide by liver tissue has been investigated in diabetic rats. Insulin deficiency was induced by withdrawal of insulin in alloxan treated, insulin substituted rats or by injection of anti-insulinserum. The hepatic formation of o-aminophenol-glucuronide was strongly reduced under these conditions. This result could not be explained by differences in the activity of the UDP-glucuronyl-transferase. However, the concentration of UDP-glucuronic acid in liver tissue of the diabetic rats was also decreased to 50% of control values whereas the amount of UDPG was augmented. These findings are consistent with the observation that the activity of UDPG-dehydrogenase, the enzyme catalyzing the formation of UDP-glucuronic acid from UDPG, is reduced in the liver of diabetic or fasting rats. The activity of the UDPGA-pyrophosphatase which is responsible for inactivation of the nucleotide, has been found to be unchanged in the diabetic animals.
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  • 47
    ISSN: 1432-2072
    Keywords: 5-Substituted N,N-Dimethyltryptamines, α-Methyltryptamine, and Gramines ; Monoamine Oxidase Inhibitors ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three series of derivatives of N,N-dimethyltryptamine, α-methyltryptamine and gramine bearing substituents of varying electronic nature on the C-5 position were tested for acute toxicity, effect on barbiturate sleeping time, antireserpine effect, swim maze, variable interval conditioned behavior, and inhibition of monoamine oxidase. No correlation could be made between the electronic effects and their pharmacological activities. It was thus suggested that there exist different pharmacological receptors for the tryptamines and gramines.
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  • 48
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    Psychopharmacology 17 (1970), S. 14-33 
    ISSN: 1432-2072
    Keywords: Serotonin ; Hydroxytryptamine ; Psychopharmacology ; Psychology, physiological
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Comparison of rats given single or multiple injections of p-chlorophenylalanine (PCA) was used to assess non-serotonergic actions of the drug as well as providing information on the behavioral effects of serotonin (5-HT) depletion. In Experiment I all groups acquired an active avoidance response in accordance with decreased levels of 5-HT in the CNS and independently of probable PCA or phenylalanine levels. In Experiment II 5-HT depletion facilitated passive avoidance; again, independently of PCA levels. In Experiment III rats were run in an open field for 15 min with or without periods of extra stimulation by intense light or sound. Serotonin-deficient animals were more active than controls under conditions of extra stimulation but slightly less active without extra stimulation. Experiment IV showed that PCA in doses that do not reduce ad libitum drinking can depress quinine intake. It is suggested that 5-HT depletion makes rats more “reactive” to external stimulation.
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  • 49
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    Psychopharmacology 17 (1970), S. 34-48 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Narcotic Analgesics ; Codeine-Pethidine-Methadone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the concurrent food-reinforced and avoidance schedules, codeine, pethidine and methadone reduced the rate of response on avoidance and foodreinforced levers, reduced the number of avoided shocks at the highest dosages only, and caused variable modifications of the delay. At low doses methadone increased the rate of response. In the “carried extinction” test, codeine and pethidine reduced the rate of response in all the experimental situations; in certain cases methadone had the opposite effect. In the conditions of operant inhibition, the inhibitory action of shock was increased by codeine; it was reduced, over a narrow range of doses, by methadone and, less regularly, also by pethidine. The relative analgesic potency of the compounds studied does not correspond to their relative behavioral potency.
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  • 50
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Diphenylhydantoin ; Anxiety ; Hostility ; Psychiatric Status Rating Scales
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a six-week double-blind cross-over study, DPH, 100 mg, t.i.d., was found to be markedly more effective than DPH, 5 mg, t.i.d., used as a placebo, in reducing symptoms relating to anger, irritability, impatience, and anxiety. The psychoactive properties of DPH were demonstrated by both self-ratings and physician ratings of change. Improvement when changing from 5 mg to 100 mg was matched by worsening when changing from 100 mg to 5 mg. Patients in the controlled study were selected on the basis of the presence of symptoms of anger, irritability, and anxiety, a social class more typical of private patients than clinic patients, and a Barron Ego Strength score of 40 or above. No undesirable side effects were encountered.
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  • 51
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Short-Term Memory ; Memory Decay ; Memory Consolidation ; Passive Avoidance ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chlorpromazine in doses of 0.5 mg/kg was administered to mice 0.5, 2, or 10 min after a one-trial passive avoidance learning experience. The drug produced effects on the magnitude and rate of extinction of the learned response dependent upon the injection, time, confirming results contained in an earlier report. In a second experiment with doses of 2.0 mg/kg, the effects of further injecion times were investigated. The drug had no effect when given 240 min before learning, but produced maximal blocking of response acquisition when given 120 and 8 min before learning. Drug injections 6 and 3 min before learning were suggested as having actions on post-learning memory traces. A distinction was noted between the effects of drug injections 1 and 1.5 min after learning and this was related to an effect on a rapidly decaying short-term memory trace. Chlorpromazine had no effect when given 20 min after learning.
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  • 52
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    Psychopharmacology 18 (1970), S. 108-117 
    ISSN: 1432-2072
    Keywords: Cannabis (Marijuana) ; Alcohol ; Psychopharmacology ; Placebos ; Drug Abuse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Regular users of marijuana (cannabis sativa) were given smoked and orally administered marijuana, a placebo, or alcohol. They were unable to distinguish between smoked marijuana and the tetrahydrocannabinol-free placebo. The oral administration of tincture of cannabis produced primarily dysphoric symptoms and was similar to alcohol in this respect. The smoked marijuana altered pulse rate, time estimation, and EEG, but had no effect on a measure of field dependence or on a digit symbol substitution task. Both drugs appeared to be mild intoxicants in a laboratory setting. Consideration of the dose, prior experience with drugs, setting, and possible cross tolerance of marijuana and alcohol are important in evaluating the significance of the clinical effects.
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  • 53
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    Psychopharmacology 17 (1970), S. 391-398 
    ISSN: 1432-2072
    Keywords: Conflict Behavior ; Anti-Anxiety ; Chlordiazepoxide ; Pentobarbital ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A punishment discrimination (“conflict”) was conditioned in rats by simultaneously rewarding with food (sweetened, condensed milk) and punishing with shock all lever responses made in the presence of an auditory stimulus. Chlordiazepoxide and pentobarbital were administered in order to compare degrees of attenuation of conflict behavior relative to the production of behavioral debilitation. Chlordiazepoxide produced the maximum attenuation at doses that produced only minimum debilitation. In general, conflict attenuation (“anti-anxiety”) was greater under chlordiazepoxide while general debilitation (behavioral toxicity) was greater for pentobarbital.
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  • 54
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    Psychopharmacology 18 (1970), S. 366-377 
    ISSN: 1432-2072
    Keywords: Cyclazocine ; Nalorphine ; Opiate Antagonists ; Subjective Report ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The subjective effects of two doses of cyclazocine (0.6 mg and 1.2 mg/70 kg), nalorphine (16 and 32 mg/70 kg), no-drug and placebo were compared with 32 opiate addicts using drug sensitive scales of the Addiction Research Center Inventory (ARCI) items. The effects of these narcotic antagonists were highly similar on ARCI scales and items. Both drugs produced a general drug effect, difficulty in focusing eyes, physical weakness, tiredness, poor motivation, moodiness, misery, anxiety, tension, hallucinations, changes in sensation and perception, and inefficiency of physical, cognitive and social functions. Cyclazocine was 15–26 times more potent than nalorphine. The effects of cyclazocine and nalorphine were differentiated from the effects of other drugs such as morphine, pentobarbital and LSD when the overall pattern of effect was considered.
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  • 55
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    Pflügers Archiv 321 (1970), S. 1-14 
    ISSN: 1432-2013
    Keywords: CNS ; Hypoglycemia ; Insulin ; Metabolism ; Phospholipids ; Hypoglykämie ; Insulin ; Phospholipide ; Stoffwechsel ; ZNS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An Kaninchen in Pernocton®-Narkose wurde die Wirkung hoher Insulingaben auf Gesamtphospholipide und verschiedene Phospholipidkomponenten von Großhirn, Großhirnrinde, Kleinhirn und Medulla oblongata in zeitlicher Beziehung zur abnehmenden Blutglucosekonzentration und der elektrischen Hirnfunktion untersucht. 1. Statistisch signifikante Verminderungen im Gehalt der Phospholipide traten in Großhirn, Großhirnrinde und Kleinhirn erst mit Unterschreiten einer bestimmten, regional unterschiedlichen, kritischen Blutglucosekonzentration auf. In der Medulla oblongata war keine signifikante Abnahme der Phospholipidgehalte nachweisbar. 2. Es erfolgte keine Veränderung der Phospholipidgehalte einzelner Hirnanteile, wenn durch gleichzeitige Insulin- und Glucoseverabreichung die Blutglucosekonzentration erheblich erhöht wurde. 3. Die Verminderung endogener Phospholipide des Gehirns während Insulinhypoglykämie wird mit einem der Energiebildung dienenden Abbau sowie einer verzögerten Neubildung erklärt.
    Notes: Summary The effects of insulin in massive doses on total phospholipids and individual phospholipid fractions of cerebrum, cerebral cortex, cerebellum and medulla oblongata was studied on rabbits in Pernocton® anaesthesia. The experiments were performed in order to correlate the time course of the decrease in blood glucose with phospholipid changes and concomitant electrographic patterns of the CNS. 1. Statistically significant decreases in phospholipid content of cerebrum, cerebral cortex and cerebellum did not take place until blood sugar levels were lowered to a critical concentration. This concentration was found to be different in various parts of the brain. In the medulla oblongata no significant decrease of phospholipid content was detected. 2. No effect on regional phospholipids was observed when blood sugar levels were highly increased above normal levels by simultaneous administration of insulin and glucose. 3. The decrease in brain lipid phosphorus during insulin hypoglycemia is explained by a diminished rate of synthesis as well as a breakdown of phospholipids vielding energy supply.
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  • 56
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    Archives of toxicology 26 (1970), S. 1-7 
    ISSN: 1432-0738
    Keywords: Insulin ; Suicide ; Determination of Insulin in Autopsy Material ; Insulin ; Suicid ; Insulinnachweis an Leichenmaterial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird über einen 50jährigen Diabetiker berichtet, welcher sich in suicidaler Absicht insgesamt 1080 E Insulin Novo lente s.c. injiziert hatte und innert 26 Std verstorben war. Post mortem war der Nachweis des exogenen Hyperinsulinismus durch quantitative Bestimmung des freien Insulins im Serum und an den Injektionsstellen gelungen.
    Notes: Summary A case is described in which a 50 yr. old diabetic with suicidal intention injected a total of 1,080 units of lente insulin (Novo) s.c. and died within 26 hrs. It was possible to demonstrate the exogenous hyperinsulinism post mortem by quantitative determination of free insulin in the serum and at the injection site.
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  • 57
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    Psychopharmacology 18 (1970), S. 94-98 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Reserpine Antagonism ; Electroconvulsions ; Antidepressant Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The adynamic, ptotic, hypothermic and conditioned avoidance response blocking effects of reserpine were studied in normal rats and in rats subjected to electroconvulsions for 5 days. Prior exposure to electroconvulsions blocked only the hypothermic response of reserpine. The relevance of this observation to the screening of antidepressant drugs by studying the reserpine antagonism is discussed.
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  • 58
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Dose-response ; Psychopharmacology ; Behavioral Response ; Fixed Dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fixed daily doses of chlorpromazine (CPZ), in the amounts of 150, 300, and 600 mg were administered orally to chronic schizophrenic inpatients for 24 weeks while psychiatric and ward behavioral responses were monitored at regular intervals. It was found that within the dose range used response could be shown to be dose related, particularly early in the course of treatment (4–12 weeks). CPZ in the amount of 150 nig/day was found to be an effective dose relative to placebo, but was generally less effective than 300 or 600 mg/day. Little difference in clinical response was demonstrable between the 300 and 600 mg doses of CPZ except in the frequency of side effects and possible speed of onset or therapeutic effects, both being greater in the 600 mg group.
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  • 59
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    Psychopharmacology 18 (1970), S. 333-345 
    ISSN: 1432-2072
    Keywords: Chlorpromazine ; Passive Avoidance ; Dissociation of Learning ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mice given one-trial passive avoidance training were examined 24 hours later for retention of the acquired response. Testing was carried out with subjects given either chlorpromazine or saline injections before the test session. Three chlorpromazine doses (0.5, 2.0, and 3.5 mg/kg) were used, and three injection times (10, 90, or 180 min before testing). Chlorpromazine was found to impair the expression of the acquired response, both by depressing its initial elicitation and also by apparently facilitating extinction. A second experiment confirmed that extinction rate was indeed increased. A clear dosage effect was observed but injection time was not important in determining the drug's effect. Further experiments were undertaken to clarify the interpretation of the drug's action; in particular, the possibility that the effects might have been caused by a dissociation of learning between the training and test situations was examined. It is suggested that the elevated extinction rates observed during testing when subjects were given chlorpromazine represents a temporary effect resulting from the reduced stimulus control of behaviour. Permanent effects of pre-test drug administration were noted on the initial expression of the learned response.
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  • 60
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    Acta diabetologica 7 (1970), S. 211-219 
    ISSN: 1432-5233
    Keywords: Abnormal insulin ; Heredity of diabetes ; Insulin ; Insulinase ; Pathogenesis of diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Sur la base de la résistance à l'action de l'insulinase non purifiée de rat et à l'index d'incorporation du glucose14C administré par voie intrapéritoneale dans le glycogène du diaphragme de rat, on a démontré l'existence de différences entre l'insuline purifiée immunologiquement et extraite par le plasma de diabétiques jeunes et par le pancréas de certaines sujets affectés de diabète de la maturité d'une côté et insuline normale de l'autre. La différence semble être héritée ainsi que facteur mendelien simple.
    Abstract: Resumen Basándose en la resistencia a la acción de la insulina sin purificar procedente de ratón y al índice de incorporación del glucosio14C suministrado por vía intraperitoneal en el glicógeno del diafragma de ratón, se ha demostrado la existencia de diferencias entre la insulina purificada inmunologicamente y extraída del plasma de diabéticos jóvenes y del páncreas de algunos pacientes enfermos de diabetes maduro por una parte y la insulina normal por la otra. La diferencia parece ser heredada como factor mendeliano simple.
    Notes: Riassunto Sulla base della resistenza all'azione di insulinasi grezza di topo e all'indice di incorporazione del glucosio14C somministrato per via intraperitoneale nel glicogeno del diaframma di topo, è stata dimostrata l'esistenza di differenze fra insulina purificata immunologicamente ed estratta dal plasma di diabetici giovani e dal pancreas di alcuni soggetti affetti da diabete maturo da una parte e insulina normale dall'altra. La differenza sembra essere ereditata come fattore mendeliano semplice.
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  • 61
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    Acta diabetologica 7 (1970), S. 1004-1021 
    ISSN: 1432-5233
    Keywords: Computer ; Glucagon ; Glucose ; Glucose utilization ; Insulin ; Mathematical model ; Oral glucose tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les Auteurs ont élaboré un modèle analogique pour la simulation des courbes glycémiques et insulinémiques qu'on obtient après surcharge orale de glucose chez l'homme. Le modèle analogique simule avec bonne approximation les courbes obtenues expérimentalement chez un groupe de sujets normaux. Les caractéristiques, les limites et les éventuels advantages du modèle proposé sont discutés.
    Abstract: Resumen Los Autores han elaborado un modelo analógico para la simulación de las curvas glicémicas e insulinémicas que se obtienen después de carga oral de glucosa en el hombre. El modelo analógico simula con una buena aproximación la marcha de las curvas obtenidas experimentalmente en un grupo de individuos normales. Se exponen las características, los límites y las posibles ventajas del modelo propuesto.
    Notes: Riassunto Gli AA. hanno elaborato un modello analogico per la simulazione delle curve glicemiche ed insulinemiche che si ottengono dopo carico orale di glucosio nell'uomo. Il modello analogico simula con buona approssimazione l'andamento delle curve ottenute sperimentalmente in un gruppo di soggetti normali. Vengono discussi le caratteristiche, i limiti ed i possibili vantaggi del modello proposto.
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  • 62
    ISSN: 1432-5233
    Keywords: Glucose ; Human adipose tissue ; Insulin ; Isolated fat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume L'insuline agit de stimulus pour l'incorporation de l'114C du glucose dans le CO2 produit par les cellules adipeuses humaines isoléesin vitro. Cet effet est mis en évidence seulement par des concentrations assez élevées de l'hormone, dans les conditions expérimentales décrites dans ce travail. En même temps on peut aussi mettre en évidence l'effet antilypolitique de l'insuline, en faible quantité, seulement avec des concentrations assez élevées de l'hormone dans le médium d'incubation. La présence de glucose dans le médium d'incubation provoque une libération augmentée du glycérol et une libération diminuée des acides gras.
    Abstract: Resumen La insulina estimula la incorporación del 114C de la glucosa en el CO2 producido por células adiposas humanas aisladasin vitro. Dicho efecto parece ser evidente sólo con concentraciones bastante elevadas del hormón y en las condiciones experimentales descritas en el presente estudio. De manera análoga el efecto antilipolítico de la insulina se puede evidenciar, aunque limitadamente, sólo con concentraciones relativamente elevadas del hormón en el medio de incubación. La presencia de glucosa en el medio de incubación provoca una liberación mayor de glicerol y una liberación menor de los ácidos grasos.
    Notes: Riassunto L'insulina stimola l'incorporazione dell' 114C del glucosio nel CO2 prodotto da cellule adipose umane isolatein vitro. Tale effetto sembra essere evidente solo con concentrazioni abbastanza elevate dell'ormone, nelle condizioni sperimentali descritte nel presente lavoro. Analogamente, anche l'effetto antilipolitico dell'insulina è evidenziabile, in modesta entità, solo con concentrazioni relativamente elevate dell'ormone nelmedium di incubazione. La presenza di glucosio nelmedium di incubazione provoca aumentata liberazione di glicerolo e diminuita liberazione degli acidi grassi.
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  • 63
    ISSN: 1591-9528
    Keywords: Galactose infusion ; Glucose ; Insulin ; Blood ; Excretion ; Men ; Galaktoseinfusion ; Glucose ; Insulin ; Blut ; Ausscheidung ; Mensch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Gesunden Personen wurde Galaktose über einen Zeitraum von 6 Std infundiert, die konstanten Zufuhrraten betrugen 0,3, 0,5 und 0,75 g/kg/Std. Zwei Versuchspersonen erhielten Galaktose und Glucose gleichzeitig, je 0,5 g/kg/Std. Galaktose und Glucose im Blut und Urin wurden enzymatisch bestimmt, Insulin wurde radioimmunologisch nachgewiesen. 2. Galaktosezufuhrraten von 0,5 und 0,75 g/kg/Std führen während der ganzen Infusionszeit zu einem kontinuierlichen Anstieg der Galaktose im Blut, die Ausscheidung im Urin verläuft dazu parallel. Ein „steady state“ ergibt sich nur bei einer Zufuhr von 0,3 g/kg/Std. 3. Zu Beginn der Galaktoseinfusion zeigt sich ein geringer Anstieg der Glucose im Blut, spätestens nach 75 min ist der Ausgangswert wieder erreicht; von da ab verändern sich die Glucosespiegel nicht mehr. 4. Galaktoseinfusionen führen zu Glucoseverlusten im Urin. Die Gesamtausscheidung der Glucose innerhalb einer sechseinhalbstündigen Sammelperiode liegt zwischen 1 und 4 g. 5. Wenn gleichzeitig mit der Galaktose Glucose infundiert wird, ist der Galaktoseanstieg im Blut deutlich geringer, dafür steigt die Glucose bis auf Werte über 200 mg% an, nach 150 min ist aber ein konstanter Glucosespiegel erreicht. Die Galaktosurie ist geringer, die Glucosurie größer. 6. Die Plasmainsulinspiegel steigen nur während einer Galaktosezufuhr von 0,75 g/kg/Std um 11 μE/ml (p 〈 0,025) durchschnittlich an; niedrigere Zufuhrraten zeigen keine signifikanten Änderungen des Plasmainsulins. 7. Alle Galaktosezufuhrraten bewirken einen Abfall der freien Fettsäuren im Plasma, gegen Ende der Infusionen steigen diese aber wieder an. 8. Die Verwertung von Galaktose nimmt mit steigender Zufuhrrate zu; unter einer Zufuhr von 0,75 g/kg/Std werden durchschnittlich 42 g Galaktose/Std verwertet. 9. Als Nebenwirkungen hoher Galaktosezufuhrraten beobachteten wir gelegentlich Kopfschmerzen, Übelkeit und abdominale Beschwerden.
    Notes: Summary 1. 14 healthy volunteers received galactose infusions over a 6 h period intravenously by means of an infusion pump. Administration rates used were 0.3, 0.5 and 0.75 g/kg/h. In addition, two further individuals received a mixed galactoseglucose infusion of 0.5 g/kg/h of each hexose. Galactose and glucose in blood and urine were determined enzymatically at regular 1/2 h periods, insulin was assayed radioimmunologically. 2. 0.5–0.75 g/kg/h galactose cause a continuous rise of galactose blood level, the urinary galactose excretion paralleles the blood level, a steady state, however, is found only using an administration rate of 0.3 g/kg/h. 3. Glucose in blood during galactose infusion shows a short initial rise with subsequent fall to preinfusion level without further gross change. In addition to a rising galactosuria there is a small but definite increase of glucosuria. The overall glucosuria within a 6 1/2 h collecting time ranges, depending on the infusion rate used, between 1–4 g. 4. If at the same time glucose is administered together with galactose, there is a significantly smaller rise of galactose in blood. Glucose rises up to 200 mg% and reaches a constant blood level after 150 min. Galactosuria decreases, glucosuria increases. 5. Insulin in plasma rises only 11 μU/ml using an infusion rate of 0.75 g/kg/h, other administration rates do not cause a significant change of plasma insulin level. 6. Free fatty acids drop during the first hours of the infusion, rising, however, towards the end of the infusion. 7. Galactose retention increases with elevation of the administration rate. Using an infusion rate of 0.75 g/kg/h, 42 g galactose/h are retained. 8. Eventually galactose infusions may cause headache, nausea and abdominal discomfort.
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  • 64
    ISSN: 1432-1912
    Keywords: Amiloride ; Insulin ; Glucose Transport ; Leucine Incorporation ; Isolated Adipose Tissue ; Amilorid ; Insulin ; Glucosetransport ; Leucineinbau ; isoliertes Fettgewebe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Aufnahme von Glucose ins isolierte epididymale Fettgewebe und die Bildung von 14CO2 aus [1-14C]-Glucose wurde als Maß von Transportvorgängen, die Incorporation von [1-14C]-Leucin ins Fettgewebsprotein als Maß der Proteinsynthese vor und nach Zusatz von Amilorid in vitro verwendet. 2. Amilorid setzt den Transport durch die Membran sowohl ohne als auch mit Stimulierung durch Insulin halbmaximal in 10−4 M-Konzentration herab. Aus der Kinetik des Transportes kann geschlossen werden, daß Amilorid die maximale Geschwindigkeit des gesamten Vorganges verlangsamt, ohne die Transportkonstante zu verändern. 3. Der Einbau von Leucin ins Fettgewebsprotein wird durch Amilorid in 3 · 10−4 M-Konzentration auf ein Zehntel herabgesetzt. Das Verhalten von [1-14C]-α-Aminoisobuttersäure läßt den Schluß zu, daß der Aminosäuretransport durch die Membran des Fettgewebes nicht beeinflußt wird. 4. Die Wirkungen des Amilorids am Fettgewebe entsprechen im Prinzip denjenigen des Triamterens und des 6-Aminonicotinsäureamids. Ebenso ist allen gemeinsam, daß sie den renalen Natrium- und Kaliumtransport im distalen Abschnitt des Nephrons hemmen. 5. Es ist möglich, daß ein Zusammenhang zwischen den hemmenden Wirkungen dieser Pharmaka auf den Leucin-Einbau in das Fettgewebsprotein und der Störung von Transportvorgängen durch biologische Membranen besteht.
    Notes: Summary 1. The uptake of glucose and the formation of 14CO2 from [1-14C]-glucose were used as a measure of transport processes, and the incorporation of [1-14C]-leucine into the protein of adipose tissue served as a measure of protein synthesis before and after the addition of amiloride to the isolated epididymal adipose tissue of the rat in vitro. 2. In a concentration of 10−4 M, amiloride decreases the glucose transport through tissue membranes by 50% with and without stimulation by insulin. It can be deduced from the kinetics of the transport that amiloride slows down the maximal velocity of the complete process without influencing the transport constant. 3. The incorporation of leucine into adipose tissue protein was diminished to 10% by amiloride in a concentration of 3 × 10−4 M. Experiments with [1-14C]-α-aminoisobutyric acid allow the conclusion that the amino acid transport through the membrane of the adipose tissue remains uninfluenced. 4. The effects of amiloride on the adipose tissue are similar to those of triamterene and of 6-aminonicotinamide. In addition, they all inhibit renal sodium and potassium transport in the distal part of the nephron. 5. It is possible, that there is a connection between the inhibiting effects of these drugs on the incorporation of leucine into the protein of adipose tissue and the disturbance of transport processes through biological membranes.
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  • 65
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    Diabetologia 5 (1969), S. 195-197 
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; adipose tissue ; lipolysis ; FFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A des concentrations proches de celles qui sont rencontrées dans le plasma humain, le glucagon stimule fortement la lipolyse au niveau de la graisse épididymaire du rat, étudiéein vitro. Les effets de telles concentrations de glucagon sont réduits, voire abolis par l'insuline aux concentrations de 25 et 100μU/ml. Rapprochées de l'effet insulinogénique puissant du glucagon, ces observations peuvent fournir une explication quant au caractère retardé de l'élévation du taux sanguin des acides gras libres observée après injection de glucagonin vivo.
    Abstract: Zusammenfassung Glucagon stimuliert in Konzentrationen, wie sie auch im menschlichen Plasma vorkommen, die Lipolyse im Ratten-Nebenhodenfettgewebein vitro stark. Die Effekte derartiger Glucagonkonzentrationen werden durch Insulin (25–100μE/ml) verringert bis aufgehoben. Unter Berücksichtigung der ausgeprägten Wirkung von Glucagon auf die Insulinfreisetzung können diese Beobachtungen eine Erklärung für die Verzögerung des Anstiegs der freien Fettsäuren im Serum liefern, die man nach Glucagoninjektionenin vivo beobachtet.
    Notes: Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these “physiological” concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100μU/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.
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  • 66
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    Diabetologia 5 (1969), S. 61-66 
    ISSN: 1432-0428
    Keywords: Insulin ; islets of Langerhans ; mouse ; collagenase ; glucose ; mannoheptulose ; glucagon ; adrenaline ; phentolamine ; theophylline ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La libération de l'insuline pendant l'incubation des îlots de Langerhans de la souris, isolés après digestion du pancréas par la collagénase, a été étudiée, et l'influence de divers facteurs sur la vitesse de libération a été recherchée. Le glucose à 3.0 mg/ml (glucose élevé) stimulait la libération d'insuline, mais n'avait pas d'effet à 0.6 mg/ml (taux bas). Le mannoheptulose bloquait la stimulation provoquée par du glucose élevé, comme le faisait l'adrénaline. L'effet de l'adrénaline était aboli par la phentolamine, un agent bloquant alpha adrénergique. Le glucagon seul, ainsi qu'en pre'sence d'un taux de glucose bas, stimulait la libération d'insuline, mais non de façon constante avec un taux de glucose élevé. L'adrénaline abolissait la stimulation provoquée par le glucagon. La théophylline stimulait la libération lorsque le glucose était bas, mais beaucoup moins lorsque le glucose était élevé et pas du tout avec le glucagon, quelle que soit la concentration de glucose. Le tolbutamide stimulait la libération d'insuline avec une faible concentration de glucose et cet effet n'était pas inhibé par l'adrénaline. La convenance de cette préparation pour des études sur le métabolisme des cellules insulaires et sa relation avec la sécrét ion d'insuline est discutée.
    Abstract: Zusammenfassung Es wurde die Insulinausschüttung aus Langerhans'schen Inseln von Mäusen, die durch Kollagenase-Behandlung des Pankreas gewonnen worden waren, untersucht und der Einfluß verschiedener Faktoren auf die Freisetzungsgeschwindigkeit überprüft. Eine hohe Glucose-Konzentration von 3.0 mg/ml förderte die Insulin-Ausschüttung, während die niedrige Konzentration von 0.6 mg/ml keine Wirkung ergab. Mannoheptulose und Adrenalin blockierten die Stimulation durch die hohe Glucosekonzentration. Der AdrenalinEffekt konnte durch Phentolamin, eine alpha-Rezeptoren blockierende Substanz, wieder aufgehoben werden. Glucagon führte allein und in Gegenwart der niedrigen Glucosekonzentration zu einer verstärkten Insulininkretion: dies war jedoch bei Kombination mit der hohen Glucosekonzentration nicht konstant der Fall. Adrenalin hob die Stimulierung durch Glucagon auf. Theophyllin führte bei Gegenwart der niedrigen Glucosekonzentration zu einer gesteigerten Ausschüttung, dieser Effekt trat unter der höheren Glucosekonzentration in wesentlich geringerem Umfang und bei Zusatz von Glucagon und einer der beiden verwandten Glucosekonzentrationen überhaupt nicht auf. Bei niedriger Glucosekonzentration stimulierte Tolbutamid die Insulinfreisetzung; dieser Effekt ließ sich durch Adrenalin nicht aufheben. Die Aussagefähigkeit dieses Präparates für Untersuchungen des Inselzell-Stoffwechsels und seiner Beziehungen zur Insulininkretion wird diskutiert.
    Notes: Summary The release of insulin during incubation of mouse islets of Langerhans, isolated after digestion of the pancreas with collagenase, has been studied, and the influence of various factors on the rate of release investigated. Glucose at 3.0 mg/ml (high glucose) stimulated insulin release, but had no effect at 0.6 mg/ml (low glucose). Mannoheptulose blocked the stimulation by high glucose, as did adrenaline. The adrenaline effect was abolished by phentolamine, an alpha-adrenergic blocking agent. Glucagon alone, stimulated insulin release, and also with low glucose, but not consistently with high glucose. Adrenaline abolished the stimulation by glucagon. Theophylline stimulated release with low glucose, much less so with high glucose and not at all with glucagon at either glucose concentration. Tolbutamide stimulated release with low glucose, and this effect was not inhibited by adrenaline. The suitability of this preparation for studies of islet cell metabolism and its relationship to secretion of insulin is discussed.
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  • 67
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    Diabetologia 5 (1969), S. 304-308 
    ISSN: 1432-0428
    Keywords: Insulin ; bile ; rabbit ; 125I-insulin ; glucose ; galactose ; fructose ; tolbutamide ; phenformin ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On trouve de l'insuline immunoréactive dans la bile hépatique de lapins normaux. Moins de 1% d'une dose injectée d'insuline bovine atteint la bile. Quand de l'insuline bovine 125I, seule ou liée à l'anticorps, est administrée par voie intraveineuse, seulement 40% de la radioactivité retrouvée dans la bile est précipitable avec l'acide trichloracétique et moins de 10% réagit avec le sérum anti-insuline de cobaye. Le glucose, le fructose le galactose, le tolbutamide et la phenformine provoquent tous une élévation de l'insuline dans la bile, qui atteint son maximum 40 à 50 min après l'injection. L'alloxane atténue ou abolie ces réponses.
    Abstract: Zusammenfassung Immunoreaktives Insulin wird in der Leber-Galle normaler Kaninchen gefunden. Weniger als 1% einer injizierten Dosis von Rinder-Insulin erreicht die Galle. Wenn man reines oder an Antikörper gebundenes 125I-Rinderinsulin intravenös verabreicht, lassen sich mit Hilfe von Trichloressigsäure nur 40% der Radioaktivität ausfällen, die in der Galle gefunden wird, und weniger als 10% reagieren mit Meerschweinchen-Anti-Insulinserum. Glucose, Fructose, Galaktose, Tolbutamide und Phenformin verursachen ein Ansteigen von Insulin in der Galle, welches ein Maximum innerhalb von 40 bis 50 Min. nach der Injektion erreicht. Alloxan vermindert oder hebt diese Effekte auf.
    Notes: Summary Immuno-reactive insulin is found in the hepatic bile of normal rabbits. Less than 1% of an injected dose of bovine insulin reached the bile. When 125I-bovine insulin alone or complexed with antibody was given intravenously, only 40% of the radioactivity recovered in the bile was precipitable with trichloracetic acid, and less than 10% reacted with guinea pig anti-insulin serum. Glucose, fructose, galactose, tolbutamide and phenformin all caused an elevation in bile insulin, which reached a maximum 40 to 50 min after the injection. Alloxan attenuated or abolished these responses.
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  • 68
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    Diabetologia 5 (1969), S. 325-330 
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; blood sugar ; mice ; rats ; pancreatectomy ; nephrectomy ; hepatectomy (partial) alloxan diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez les rats et les souris le taux du sucre sanguin est abaissé par une proinsuline obtenue à partir de l'insuline bovine (Schmidt et Arens [6]). Chez les rats alimentés et les souris à jeun, le rapport d'activité proinsuline: insuline est de 1∶4, chez les rats à jeun de 1∶2, dans le cas de dose équimolaire et en mesurant l'abaissement maximum du sucre sanguin. L'abaissement du sucre sanguin évolue de façon plus lente après proinsuline qu'après insuline. La proinsuline, incubée in vitro avec la trypsine, agit quantitativement et au point de vue temps, comme l'insuline. Chez les rats pancréatectomisés, chez les rats néphrectomisés ainsi que chez ceux hépatectomisés aux deux tiers, l'action de la proinsuline est la même que chez les animaux normaux. Les souris rendues diabétiques par l'alloxane répondent également à la proinsuline comme les souris intactes. L'action hypoglycémiante de la proinsuline se manifeste de façon retardée probablement parce que l'insuline active doit tout d'abord se former par un processus protéolytique dépendant du facteur temps. Ceci pourrait être aussi la raison pour laquelle, Rubenstein et coll. [5] signalent l'absence d'effet de la proinsuline dans le test de convulsion chez la souris.
    Abstract: Zusammenfassung An Ratten und Mäusen wird der Blutzucker durch ein aus Rinderinsulin gewonnenes Proinsulin (Schmidt und Arens [6]) gesenkt. Bei gefütterten Ratten und nüchternen Mäusen ist das WirkungsVerhältnis Proinsulin: Insulin = 1∶4, bei nüchternen Ratten 1∶2, wenn äquiznolar dosiert und das Maximum der Blutzuckersenkung gewertet wird. Die Blutzuckersenkung verläuft nach Proinsulin protrahierter als nach Insulin. Proinsulin, welches in vitro mit Trypsin inkubiert wurde, wirkt quantitativ und zeitlich wie Insulin. Bei pankreatektomierten, bei nephrektomierten und bei zweidrittelhepatektomierten Ratten wirkt Proinsulin ebenso wie an Normaltieren. Auch alloxandidbetische Mäuse sprechen auf Proinsulin wie intakte Mäuse an. Die hypoglykämische Wirkung des Proinsulins tritt wahrscheinlich deshalb verzögert ein, weil das aktive Insulin in einem zeitabhängigen proteolytischen Prozeß erst entstehen muß. Dies könnte auch die Ursache für eine von Rubenstein et al. [5] zitierte, fehlende Wirkung von Proinsulin im Mäusekrampftest sein.
    Notes: Summary Proinsulin obtained from bovine insulin (Schmidt and Arens [6]) lowered the blood sugar level of rats and mice. The activity ratio proinsulin: insulin was 1∶4 in fed rats and fasted mice, and 1∶2 in fasted rats, based on an equimolar dosage and measuring the effect in terms of maximum lowering of the blood sugar value. After proinsulin the decrease of the blood sugar was more protracted than after insulin. Proinsulin which was incubated with trypsin in vitro, resembled insulin in degree and onset of action. In pancreatectomized, nephrectomized and two-thirds hepatectomized rats proinsulin acted as in normal animals. Alloxan-diabetic mice responded to proinsulin like intact mice. The reason why the onset of the hypoglycaemic action of proinsulin was delayed is probably due to the fact that the active insulin must first be produced by a time-dependent proteolytic process. This may also be the cause of the ineffectiveness of proinsulin in the mouse convulsion test which was quoted by Rubenstein et al. [5].
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  • 69
    ISSN: 1432-0428
    Keywords: Insulin ; mouse tissues ; kidney fluorescence microscopy ; microscopy ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La localisation d'insuline marquée avec I125 ou avec de l'isothiocyanate de fluorescéine a été étudiée au moyen d'autohistoradiographie au microscope optique, au microscope électronique et au moyen de microscopie à fluorescence dans les tissus de souris à jeun et de souris alimentées normalement. L'hormone fluorescente a été trouvée dans les cellules des tubules proximaux du rein de souris à jeun seulement, tandis que l'hormone radioactive a été repérée aussi dans le rein de souris alimentées, bien qu'en quantité inférieure à celle trouvée chez les souris à jeun. Au microscope électronique la radioactivité est présente dans le rein dans la bordure en brosse, les vacuoles et les mitochondries apicales et le noyau, mais pas dans l'appareil de Golgi ou dans les lysosomes. —L'hormone radioactive est aussi présente dans les autres tissus mais sans différence quantitative entre les souris à jeun et les souris alimentées. Les auteurs concluent que le procédé de ré-absorption de l'insuline par les cellules des tubules proximaux du rein est spécifique: l'hormone n'est pas dégradée de la même façon que les autres protéines mais probablement stockée afin de contrôler les processus métaboliques relevant des organelles subcellulaires dans lesquelles elle se trouve.
    Abstract: Zusammenfassung Gefütterte und fastende Mäuse erhielten fluoreszierendes oder mit125J markiertes Insulin i.v. Die Lokalisation des Insulins in den Geweben wurde untersucht. Nur bei Tieren im Hungerzustand fand sich das fluoreszierende Hormon in den Nieren, während sich das radioaktive Insulin bei gefütterten und fastenden Tieren in den proximalen Tubulusschlingen der Nieren nachweisen ließ. Die fastenden Tiere schienen dabei mehr Radioaktivität aufzuweisen. Wurden die Nieren unter Verwendung von Techniken mit hohem Auflösungsvermögen untersucht, so fand sich die Radioaktivität im Bürstensaum, in den apikalen Vakuolen und Mitochondrien und dem Kern, jedoch nicht im Golgi-Apparat oder den Lysosomen. Alle anderen Gewebe enthielten Hormon-Radioaktivität, aber weder ihre Menge noch ihre Lokalisation unterschieden sich bei gefütterten und fastenden Tieren. Es wird gefolgert, daß der Prozeß der Insulinabsorption durch die Zellen der proximalen Tubulusschlingen spezifisch ist und daß das Hormon nicht in ähnlicher Weise wie andere Eiweißkörper abgebaut wird. Wahrscheinlich kommt es über eine Speicherung zu einer Steuerung der entsprechenden Stoffwechselprozesse in den subzellulären Organellen, in denen das Hormon sich befindet.
    Notes: Summary Starved and fed mice were injected intravenously with either fluorescent or125I-insulin and the localization of the hormone was investigated in various tissues. The fluorescent hormone was found in the kidney of starved animals only, whereas the radioactive hormone was found in the proximal convoluted tubule cells of the kidney of both fed and fasted animals, although the latter group appeared to contain more radioactivity than the first. With high resolution techniques the radioactivity in the kidney was found in the brush border, the apical vacuoles, the apical mitochondria and the nucleus, and never in the Golgi apparatus or the lysosomes. All other tissues contained radioactivity due to the hormone, but no difference in either the amount or the localization was found between fed an starved animals. It is concluded that the process of absorption of insulin by the cells of the proximal convoluted tubules is specific and that the hormone is not degraded in a way similar to other proteins, but is likely to be stored and to control cellular metabolic processes from its sites of localization.
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  • 70
    ISSN: 1432-0428
    Keywords: Insulin ; 32P incorporation ; adenine nucleotides ; guanine nucleotides ; Na+K+ ATP-ase ; ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le but de ces investigations a été de contribuer à la compréhension du mécanisme d'action de l'insuline, en provoquant un turn-over accru du phosphate inorganique marqué au32P, en ATP et autres mononucléotides, dans le diaphragme du rat. Pendant l'incubation du diaphragme intact de rat dans un milieu bicarbonaté de Krebs Ringer, sans addition de substrat, on n'a pas observé d'effet de l'insuline sur le contenu en adénine-nucléotides, en guanine-nucléotides, y compris le 3′5′ AMP cyclique et le 3′5′ GMP cyclique. Quand du phosphate inorganique radioactif marqué au32P était présent dans le milieu, l'insuline augmentait l'activité spécifique du phosphate inorganique intracellulaire et provoquait une incorporation accrue du32P dans l'ATP et le GTP. L'effet sur l'ADP était moins prononcé. Il a été montré que ces effets de l'insuline dépendent de la composition ionique du milieu et du transport membranaire des ions. L'augmentation due à l'insuline de l'activité spécifique du phosphate inorganique intracellulaire et du marquage accru au32P de l'ATP (et du GTP) était en grande partie inhibée par l'ouabaïne. Pendant l'incubation dans les milieux où le chlorure de sodium a été remplacé isoosmotiquement par le chlorure de potassium ou de choline, les effets de l'insuline décrits ci-dessus étaient abolis. Les résultats indiquent que le marquage accru de l'ATP (et du GTP) provoqué par l'insuline, peut être en premier lieu attribué à des phénomènes survenant au niveau de la membrane cellulaire. L'augmentation de l'activité spécifique du phosphate inorganique intracellulaire en présence d'insuline, peut s'expliquer par une captation accrue du phosphate inorganique marqué au32P, à partir du milieu. Apparemment le marquage accru au32P de l'ATP (et du GTP) est une conséquence secondaire. On suggère que cet effet de l'insuline est d'abord en rapport avec un effet sur les enzymes de la membrane, en particulier sur l'ATP-ase activée par Na+, K+ et Mg2+.
    Abstract: Zusammenfassung Ziel dieser Untersuchungen war es, zu einem besseren Verständnis der stimulierenden Wirkung von Insulin auf den Einbau von anorganischem32P Phosphat in ATP und andere Mononucleotide im Rattenzwerchfell beizutragen. Während der Inkubation intakter Rattenzwerchfelle in Krebs-Ringer-Bicarbonat Puffer ohne Substratzusatz konnte kein Insulineffekt auf den Gehalt an Adenonucleotiden und Guaninnucleotiden, sowie von cyclischem 3′,5′ AMP und cyclischem 3′,5′ GMP beobachtet werden. In Gegenwart von anorganischem32P Phosphat steigerte Insulin die spezifische Aktivität von intrazellulärem anorganischen Phosphat und bewirkte einen verstärkten Einbau von32P in ATP und GTP. Die Wirkung auf ADP war weniger ausgeprägt. Es konnte gezeigt werden, daß diese Insulineffekte von dem IonenGehalt des Mediums und dem Membrantransport der Ionen abhängen. Die Steigerung der spezifischen Aktivität des anorganischen Phosphates und der Markierung von ATP (und GTP) mit32P ließ sich weitgehend durch Ouabain wieder aufheben. Bei Inkubation in Pufferlösungen, die statt NaCl isoosmolare Mengen von KCl oder Cholinchlorid enthielten, waren die oben erwähnten Insulineffekte nicht mehr nachweisbar. Die Resultate sprechen dafür, daß die verstärkte Markierung von ATP (und GTP) unter Insulin in erster Linie auf Vorgängen an der Zellmembran beruht. Die erhöhte spezifische Aktivität des intrazellulären anorganischen Phosphates in Gegenwart von Insulin läßt sich durch einen verstärkten Einstrom von32P Phosphat aus dem Medium erklären. Augenscheinlich kommt es dadurch sekundär zu einer gesteigerten32P Markierung von ATP (und GTP). Wir möchten annehmen, daß dieser Insulineffekt vorwiegend über die Membranenzyme erfolgt und sich vor allem auf die Na+, K+ und Mg++ aktivierbare ATPase erstreckt.
    Notes: Summary The aim of these investigations has been to contribute to an understanding of the mechanism of action of insulin in promoting increased turn over of32P inorganic phosphate into ATP and other mononucleotides in the rat diaphragm. During incubation of the intact rat diaphragm in Krebs Ringer bicarbonate medium without addition of substrate, no effect of insulin on the content of adenine nucleotides and guanine nucleotides including cyclic 3′,5′ AMP and cyclic 3′,5′ GMP has been observed. When32P radioactive inorganic phosphate was present in the medium, insulin increased the specific activity of intracellular inorganic phosphate and promoted an increased incorporation of32P into ATP and GTP. The effect on ADP was less pronounced. It has been shown that these effects of insulin depend upon the ionic composition of the medium and on ion membrane-transport. The insulin-promoted increase of specific activity of intracellular inorganic phosphate and of increased32P labelling of ATP (and GTP) was to a great extent inhibited by ouabain. During incubation in media where sodium chloride had been iso-osmotically replaced by potassium chloride or choline chloride, the above mentioned effects by insulin were abolished. The results indicate that the increased labelling of ATP (and GTP) promoted by insulin can be primarily attributed to events occuring at the cell membrane. The increased specific activity of intracellular inorganic phosphate in the presence of insulin can be explained by increased uptake of32P inorganic phosphate from the medium. Apparently the increased32P labelling of ATP (and GTP) occur as a secondary consequence. It is suggested that this insulin effect is primarily concerned with an effect on membrane enzymes, particularly the Na+, K+, Mg2+ activated ATP-ase.
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    Diabetologia 5 (1969), S. 143-145 
    ISSN: 1432-0428
    Keywords: Insulin ; galactose ; galactokinase ; deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez deux adultes souffrant d'une déficience en galactokinase la charge orale de galactose a été suivie d'une hypergalactosémie prolongée sans aucune élevation de l'insuline immunoréactive plasmatique.
    Abstract: Zusammenfassung Orale Belastung mit Galactose führte bei zwei Erwachsenen mit Galactokinasemangel zu einer prolongierten Hypergalactosämie, aber nicht zu einem Anstieg des immunoreaktiven Insulins im Plasma.
    Notes: Summary Oral galactose loading in two galactokinase-deficient adults produced the expected high and prolonged rise of galactose in peripheral blood, but no rise of circulating immunoreactive insulin.
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    Psychopharmacology 14 (1969), S. 18-22 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behaviour ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice were stained with pulverized charcoal and the resulting grooming behaviour observed. From 119 controls, the typical patterns indicated a late cleaning of the tail, the sacrum and the region between the ears. The following substances were tested: Imipramine, Desipramine, Trimeprimine, Amitriptyline, Nortriptyline, Chlordiazepoxide, Iproniazide, d-Amphetamine, Chlorpromazine, Haloperidol, Acetylsalicylic acid, Metronidazole. Of these Amitriptyline, Chlorpromazine, Haloperidol and Metronidazole were effective in doses less than 1/10 of LD 5.
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  • 73
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    Psychopharmacology 14 (1969), S. 62-73 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Hallucinogens ; Drug Addiction ; Psychopharmacology ; Phenylethylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The amphetamine analog, 2,5-dimethoxy-4-methylamphetamine (DOM), was studied in 18 volunteer subjects given single doses ranging from 2 to 14 mg. The former was a threshold dose, with definite psychotomimetic effects being evident from doses over 5 mg. The clinical syndrome greatly resembled that of the LSD-mescaline-psilocybin series of drugs, including its time-course. Somewhat more sedation was produced by DOM than would have been expected from the others, despite concomitant evidence of peripheral sympathetic stimulation. Just as with the other drugs, DOM increased plasma free fatty acids, decreased phosphorus and creatinine clearance, decreased circulating eosinophils and had little effect on catecholamine excretion. Performance of psychometric tests was impaired. Chlorpromazine treatment concurrently was found to attenuate the reaction. Tolerance rapidly developed when the drug was used chronically by patients.
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  • 74
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    Psychopharmacology 14 (1969), S. 200-210 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Hashish ; Cannabinoids ; Monkeys Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The psychopharmacological activity of Δ 1-tetrahydrocannabinol, (I); Δ 1(6)-tetrahydrocannabinol (4′ hexyl), (II); Δ 1(6)-tetrahydrocannabinol, (III); 1-ethoxyhexahydrocannabinol, (IV); 8-ethoxy-iso-hexahydrocannabinol, (V); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer I, (VI); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer II, (VII); cannabigerol, (VIII); Δ 1(6)-tetrahydrocannabinol (3′ hexyl), (IX); cannabichromene, (X); has been examined in a variety of animal species. 2. Compounds (I) and (III) caused severe motor disturbances and a stuporous state in dogs and ptosis, “tameness” and peculiar postural changes in monkeys. In the latter animal, compound (II) elicited similar effects. 3. Compounds (I) and (III) after intraperitoneal but not subcutaneous administration, suppressed the gerbil digging activity; reduced the rat conditioned avoidance response and induced a cataleptoid reaction in mice, rats and gerbils. In addition, compound (I) reduced the performance of mice on the rotating-rod. Both compounds, administered subcutaneously, induced a measurable ataxic gait in rats. 4. Amphetamine reversed the behavioural changes elicited by compounds (I) and (III) in monkeys, as well as the cataleptoid reaction in rats. 5. None of the other compounds provoked observable changes in any of the species studied. 6. It is suggested that Rhesus monkeys might serve as a suitable model for assessing the psychopharmacological activity of active cannabinoids.
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    Psychopharmacology 14 (1969), S. 394-403 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Morphine ; Skin Conductance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin conductance changes during periods of stress induced by hypercapnia were studied during a cycle of addiction to morphine. Conductance changes were found to be dose dependent in both tolerant and non-tolerant states. The effects of morphine on skin conductance changes induced by hypercapnia were similar to those effects previously observed on changes induced by electric shock.
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  • 76
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    Psychopharmacology 15 (1969), S. 196-206 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behavior ; Alcohol ; Atropine ; Discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two operant procedures were used for training albino rats to make differential responses on the basis of their drug or nondrug condition. In the Conflict procedure, every fifth lever press was rewarded by a food pellet in one condition (drug for half the animals, saline for the other half) and was punished by electric shock in the other condition. For 6 animals the drug condition was ethyl alcohol (1200 mg/kg of a 10% v/v solution in isotonic saline, injected i.p. 5 min before the start of the session); for 4 animals the drug condition was atropine sulfate (10 mg/kg in 1 ml/kg saline injected i.p. 30 min before the start of the session). In the Choice procedure, food reward was obtained by the first press on one of two levers at a variable time interval, averaging one minute, after the prior food reward. The rewarded lever depended on the animal's drug or saline condition (alcohol for 7 animals, atropine for 5 animals, administered as in the Conflict procedure); the same right-hand or left left-hand lever was rewarded in the drug condition for half the animals and in the saline condition for the other half. The response associated with 1200 mg/kg alcohol was generally elicited in tests with sufficiently high doses of pentobarbital sodium (10–20 mg/kg), chlordiazepoxide hydrochloride (10–15 mg/kg) and chloral hydrate (90–120 mg/kg, administered orally). Lower doses of these compounds, and of alcohol, were perceived as less similar to the alcohol and therefore more similar to the saline condition. Substantial doses of chlorpromazine hydrochloride (2 mg/kg) and d-amphetamine sulfate (1 mg/kg) also were perceived as similar to the saline condition. The response associated with a centrally acting anticholinergic (10 mg/kg atropine) was generally elicited in tests with several doses of scopolamine hydrobromide (0.06 to 1.0 mg/kg) and of atropine (2.5–5.0 mg/kg). The saline response was elicited by a lower dose of scopolamine (0.03 mg/kg) and by a peripherally-acting anticholinergic, atropine methyl bromide, at a dose (5 mg/kg) equimolar with 10 mg/kg atropine sulfate. The same results, including closely similar ED50 doses, were generally found with the Conflict and Choice procedures, despite the differences between them in the motivational basis for the differential drug and nondrug responses. The similarities and dissimilarities among these compounds in perceived stimulus characteristics also correspond closely with those reported by Overton (1966) with a locomotor shock-escape procedure in tests which were generally limited to a single high dose of each drug.
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    Psychopharmacology 15 (1969), S. 245-254 
    ISSN: 1432-2072
    Keywords: Aggression ; Lithium ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of lithium on aggressive behavior was studied in Siamese fighting fish, mice and golden hamsters. The fish stopped fighting when exposed to concentrations of 10 to 30 meq/l LiCl in the surrounding water. Also in mice and hamsters which ingested LiCl with the drinking fluid lithium abolished intraspecific aggression. Measurements of plasma and brain lithium levels revealed astonishing individual differences in the concentrations which were necessary for the antiaggressive effect. In all species normal aggressive behavior reappeared after lithium treatment was discontinued.
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  • 78
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Antidepressants ; Reserpine Emesis ; Apomorphine Pecking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seven psychic energizers have been quantitatively evaluated for their antidepressant and tranquillizing activity using antagonism of reserpine induced emesis and apomorphine induced pecking in pigeons as test procedures for the two activities respectively. Pheniprazine and deanol possess anti-reserpine activity only whereas imipramine, desmethylimipramine, amitriptyline, opipramol and orphenadrine possess both anti-reserpine as well as anti-apomorphine activity. It is suggested that the two tests form a simple and reliable combination for evaluating potential antidepressants.
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    Psychopharmacology 15 (1969), S. 425-429 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Methysergide ; Mania ; Lithium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six manic patients were studied in an open sequential drug trial of placebo and the serotonin antagonist methysergide; lithium was then substituted double-blind. No dramatic change occurred in individual manic item scores or in mean daily mania ratings after 48 hours or seven days of methysergide, although several of the patients showed slight trends toward improvement. However, after a mean duration of 10.3 days of lithium treatment, all manic item scores improved dramatically and significantly, so that complete clinical remission was evident in all patients. In view of the discrepancy between these essentially negative findings and several recent positive reports on the efficacy of methysergide in the treatment of mania, the authors feel that the indolealkylamine hypothesis of affective disorders should be further investigated.
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    Psychopharmacology 15 (1969), S. 109-115 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Hallucinogens ; Drug Effects ; Behavior Exploratory ; Monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of Psilocybin on the behavior of the baboon Papiopapio has been studied. Animal watchfulness, as estimated from the E.E.G., is enhanced within the first five minutes after injection and then is not further modified. Psilocybin induces a decrease of spontaneous motility. Conversely, the frequency of eye movements is considerably increased. This pattern might be explained by alterations of visual perception.
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    Psychopharmacology 15 (1969), S. 134-143 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Anti-Anxiety ; Controlled Trial ; Doxepin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six patients with persistent anxiety symptoms were used in a preliminary assessment of a new anti-anxiety compound-Doxepin (Sinequan) with placebo. The factorial design is discussed as a potentially useful way of conducting a first-stage test of anti-anxiety compounds. Analysis of the results showed that Doxepin at 25 mg t.d.s. and 50 mg t.d.s. was associated with improvement in the patient's self ratings of anxiety symptoms.
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    Psychopharmacology 14 (1969), S. 142-149 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Amphetamine ; Cholinergics ; Drug Interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amphetamine was administered to a group of rats trained on a nondiscriminated avoidance procedure. An intraperitoneal dose of 2.0 mg/kg caused about a 75% increase in response rate for the three-hour session. Doses of atropine, Tremorine, eserine, and 4-(1-naphthylvinyl)-pyridine (NVP), an inhibitor of the enzyme choline acetylase, which were ineffective in themselves, markedly affected the increase in rate observed after amphetamine. The quarternary amine of NVP was without effect on the amphetamine response. Those agents that decreased cholinergic function, either by blocking the effect of acetylcholine or by preventing its synthesis, augmented the stimulating effect of amphetamine. Cholinergic stimulants, on the other hand, significantly antagonized the behavioral effects of amphetamine.
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    Psychopharmacology 14 (1969), S. 417-425 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Psychoses ; Reflex, Abnormal ; Chlorpromazine ; Trifluopromazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary According to our results in 117 subjects, recently taken medications, age and sex must be considered when duration of the Achilles-tendon reflex is used as a clinical test to assess thyroid status. Males have a shorter ATR than females. In older subjects the ATR lasts longer than in those below age 27. Fifty-two psychiatric patients before medication did not differ in ATR duration from 65 controls. However, after 28 patients took chlorpromazine and 24 received trifluoperazine, ATR was prolonged in the chlorpromazine group and shortened in the trifluoperazine group. Neither chlorpromazine concentrate, 1,800 mg, nor trifluoperazine concentrate, 180 mg, given during the first six days, affected ATR, but an additional 6,000 mg of chlorpromazine, or an additional 420 mg of trifluoperazine over the next six days, did significantly alter ATR-duration.
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  • 84
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Doxepin ; Diazepam ; Anti-Anxiety ; Antidepressant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Doxepin and diazepam were evaluated for therapeutic effectiveness in a double blind study carried out with 69 primarily anxious neurotic outpatients attending either a municipal hospital clinic or a general practitioner's office. Doxepin produced more clinical improvement than diazepam in several questionnaire clusters measuring depressive symptomatology, but not in clusters measuring anxious symptomatology. According to several outcome criteria, doxepin tended to produce more clinical improvement in general practice than in clinic patients, while diazepam produced either equal improvement in both populations or slightly more improvement in the clinic. Possibly contributing to the present results are low daily dosage of diazepam, differential pharmacological drug effects, population differences in levels of anxiety and depression, and differences in population characteristics, primarily as related to social class.
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  • 85
    ISSN: 1432-2072
    Keywords: Nicotine ; Antimuscarinic Drugs ; Ganglion-Blocking Drugs ; Operant Conditioning ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of nicotine on bar-pressing behaviour in the rat are blocked by mecamylamine. The depressant phase of the effect is blocked by atropine, supporting the conclusion that this depression is mediated by released acetylcholine. The quaternary compounds chlorisondamine and atropine methylnitrate also antagonise the behavioural effects of nicotine but the doses required for this are far in excess of those which are effective peripherally, suggesting that the sites of interaction are central.
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    Psychopharmacology 15 (1969), S. 351-360 
    ISSN: 1432-2072
    Keywords: Nicotine ; Conditioned Stimulus ; Discrimination Learning ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to respond for water rewards on different bars in a Skinner box depending on whether they had previously been injected with nicotine or with saline. No other drug tested could consistently elicit responses on the “nicotine correct” bar. Pre-treatment with mecamylamine abolished the rats' ability to distinguish between nicotine and saline but pretreatment with chlorisondamine did not.
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  • 87
    ISSN: 1432-2013
    Keywords: Toad Bladder ; Sodium Transport Pool ; Aldosterone ; Insulin ; Vasopressin ; Krötenblase ; Natrium-Transport-Pool ; Aldosteron ; Insulin ; Vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The size of toad bladder sodium transport pool, defined as that amount of sodium of apical origin and recovered in tissue at equilibrium, was compared with sodium transport rate, derived from short-circuit current read immediately before tissue analysis. Provided certain precautions be taken, the relationship between both variables can be described by a curve starting at the intersect ofX (pool, in μEq) andY (transport, in μEq/hr) axes, with a tendency forX to increase faster thanY. Assuming sodium transport pool forms one compartment, its calculated half-life averages 2–3 min. sodium transport pool measurements are thought to shed light on mechanism of sodium transport by toad bladder because pool size was large with respect to transport rate when tissue was exposed to several inhibitors of sodium transport. Conversely, upon stimulation of activity of (substrate — depleted) preparations by glucose, a relative reduction of pool size was observed. Aldosterone, vasopressin (and adenosine 3′,5′-phosphate) increased sodium pool size and transport rate, proportionately; insulin stimulated sodium transport more than it increased pool size. Thus, insulin presumably exerts its effect at the sodium “pump” while such a site of action need not be postulated for aldosterone and vasopressin: these 2 hormones would instead induce, permeability changes faciliting sodium movement at the apical border of toad bladder epithelial cells.
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  • 88
    ISSN: 1432-2072
    Keywords: Lysergic Acid Diethylamide or LSD ; Methylphenidate or Ritalin ; Chlordiazepoxide or Librium ; Psychopharmacology ; Alcoholism and Drug Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Through the retrospective use of the 156 item DWM Card Sort, the experiences from a single intravenous dose of 200 mcg of LSD, 75 mg of methylphenidate (Ritalin) and 75 mg of chlordiazepoxide (Librium) were compared in a population of 99 chronic male alcoholics treated in an “LSD setting” in a double-blind study. Surprisingly, 96 of the 156 items proved significantly different among the 3 groups. LSD was unique in producing Sensory and Perceptual Distortions (including Hallucinations or Illusions), and Mystical, Religious or Paranormal Sensations. However, contrary to expectation, LSD did not uniquely produce the traditional “therapeutic” experience, but appeared to be surpassed in that area by methylphenidate. Both drugs also produced some anxiety, while chlordiazepoxide produced relaxation, and enhanced music appreciation.
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    Psychopharmacology 14 (1969), S. 248-254 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Appetite Depressants ; Psychopharmacology ; Sympathomimetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method is described with which it is possible to measure locomotor activity and food intake simultaneously in the same rat or other small animal. From a study of a number of psychomotorstimulant drugs and anorectic agents it may be concluded that locomotorstimulation and appetite-suppression are two different effects that may or may not characterize the same drug. Methamphetamine and phenmetrazine are stimulants in doses that do not inhibit food intake. Amphepramon reduced food intake in low doses but acts as a stimulant in higher doses. Chlorphemternine and phenfluramine are anorectic agents that are not stimulants, even in high doses.
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    Psychopharmacology 15 (1969), S. 1-8 
    ISSN: 1432-2072
    Keywords: Cannabis (Marihuana) ; Lysergic Acid Diethylamide ; Hallucinogens (Psychopharmacology) ; Visual Perception ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four pigeons were trained on a visual discrimination task which required conditional responding along the independent dimensions of form and color. High doses of Cannabis sativa (marihuana) extract and lysergic acid diethylamide (LSD), which were equated on the basis of their effectiveness in suppressing responding, increased responding on a color dimension but not on a form dimension. High doses of LSD produced a decrement in discrimination performance while comparable doses of Cannabis did not effect accuracy. Treatment with Bromolysergic acid diethylamide, saline, and pentobarbital did not produce significant changes in performance. Results are discussed in terms of a break-down in stimulus control and central hallucinogenic activity.
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    Psychopharmacology 15 (1969), S. 19-27 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behavior ; Nicotine-Physical Performance ; Motivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In sessions of ten runs each, swimming time of rats through a 4 m long water alley was measured. Four doses of nicotine (0.05; 0.1; 0.2; 0.4 mg/kg given intraperitoneally 30 minutes before testing) were tested in sessions with a braking load on the tails of the animals either in all 10 runs of a session, or in every second run, or in none of the 10 runs. Regardless of the swimming condition, nicotine produced a considerable, and at doses of 0.1 mg/kg and over, significant decrease of performance in the first two runs. From the third to the 10th run, the changes caused by nicotine were smaller and differed depending on the swimming conditions. A dose of 0.1 mg nicotine/kg improved performance in the “without-load-sessions” and the “without-load-runs” of the alternating sessions, while both 0.1 and 0.2 mg/kg improved performance of the “with-load-runs” of the alternating sessions. Performance in the “without-load-sessions” and the “without-load-runs” was depressed by 0.4 mg/kg and that in the “with-load-sessions” by 0.2 and 0.4 mg/kg.
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    Psychopharmacology 15 (1969), S. 28-38 
    ISSN: 1432-2072
    Keywords: Drugs ; Sleep ; Electroencephalography ; Psychophysiology ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sleep physiological patterns were examined following a single oral dose (500 mg) of the hypnotic drug alpha chloralose. The drug increased SW sleep and decreased REM sleep without affecting total sleep time or the amount of stage 2. These changes were accompanied by a shift to slower frequencies and greater EEG synchrony, as well as a decrease in the number of spontaneous arousals in all stages of sleep, and throughout the night of medication. Except for a slight decrease in eye movement density, the drug had no systematic effects on phasic phenomena such as electrodermal or cardio-respiratory fluctuations, nor was there a systematic change in basal heart and breathing rates. On the night following medication a “rebound” increase in percent stage REM was associated with a sharp decrease in SW sleep, and increases in spontaneous arousals and waking time. Such findings suggest that sleep stages are controlled by homeostatic mechanisms whose function is to maintain equilibrium. A comparison of the effects of alpha chloralose with those of the barbiturate secobarbital revealed some striking differences. Although both alpha chloralose and the barbiturate reduced the amount of stage REM and the frequency of brief arousals, the latter compound enhanced EEG fast activity and desynchrony, and suppressed such phasic phenomena as rapid eye movements during stage REM, sigma spindles in stage 2, nonspecific electrodermal responses during SW sleep and cardio-respiratory variability in all sleep stages. For secobarbital, the decrease in percent stage REM was compensated by an increase in stage 2 rather than SW sleep. Several studies in the cat suggest that in subanesthetic doses, alpha chloralose acts primarily on cortical inhibitory processes, causing release of the reticular activating system from inhibitory influences. The results of this study show that moderate doses in man probably act on both cortical and subcortical systems involved in the mediation of SW sleep, REM sleep and arousal.
    Type of Medium: Electronic Resource
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  • 93
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    Psychopharmacology 15 (1969), S. 64-72 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Dextro Amphetamine ; Psychopharmacology ; Conditioning, Operant ; Pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bar pressing was maintained by food reinforcement of each fiftieth response (FR50 schedule). Rats were tested at 3 levels of food deprivation (60, 80 and 100% of ad libitum body weight) under three drug conditions (0, 0.2 and 0.4 mg of D-amphetamine per rat). Overall response rate was reduced by increasing doses of drug, but not significantly by deprivation, within the range studied. The components of response rate were analysed separately into the starting speed (latency of the first response of each ratio run of 50 responses) and running rate. Drug level affected running rate and first latency of the session, whereas body weight affected only first latency of the session. Only the first latency of the session showed an interaction of drug level and body weight. The lack of interaction raises the question, whether amphetamine is more properly administered as total dose per rat, rather than proportional to body weight.
    Type of Medium: Electronic Resource
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  • 94
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    Psychopharmacology 15 (1969), S. 144-152 
    ISSN: 1432-2072
    Keywords: Niacin ; Nicotinamide Adenine Dinucleotide ; Schizophrenia ; Phenothiazines ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two grams of NAD were administered orally to ten chronic schizophrenic patients for twenty-one days. Five of the patients were also receiving thioridazine. There was no gross clinical improvement noted in any of the patients despite the fact that related experiments suggested that the NAD was absorbed. In those patients who were not also receiving phenothiazines there was a distinct tendency towards increased hostility, aggressiveness and irritability beginning one week after the initiation of NAD treatment and lasting for nearly two weeks after the NAD was discontinued.
    Type of Medium: Electronic Resource
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  • 95
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    Psychopharmacology 14 (1969), S. 221-232 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behaviour ; Nicotine ; Punishment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of nicotine, amphetamine, chlordiazepoxide and caffeine were studied in rats trained on a VI 2 crf schedule of water reward with all rewards accompanied by electric shock. Responding, partially suppressed by the shock, was restored by chlordiazepoxide and further suppressed by amphetamine. Nicotine resembled amphetamine in its effects on most rats but occasionally increased responding. Caffeine also increased responding in some rats indicating that this property is not always confined to tranquillising drugs.
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  • 96
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    Acta diabetologica 6 (1969), S. 371-388 
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Insulin assay ; Laboratory technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 97
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    Acta diabetologica 6 (1969), S. 197-205 
    ISSN: 1432-5233
    Keywords: Diurnal variations ; Food intake ; Glucose load ; Insulin ; Tolbutamide test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume On a étudié l'effet de la lumière et de la période d'ingestion des aliments sur l'élimination d'insuline par les urines. On peut démontrer l'existence d'un rythme circadien et la présence de deux facteurs de régulation pour cette élimination. On présente quelques hypothèses concernant ces phénomènes.
    Abstract: Resumen Se estudió el efecto que sobre la eliminación de insulina urinaria ejercen los períodos de luzoscuridad y el horario de administración del alimento. Se demuestra la existencia de un ritmo circadiano de eliminación de dicha hormona, describiéndose dos reguladores del mismo. Se hacen especulaciones fisiopatológicas acerca de su significado.
    Notes: Riassunto E' stato studiato l'effetto della luce e del periodo di ingestione del cibo sull'eliminazione di insulina nelle urine. Si può dimostrare l'esistenza di un ritmo circadiano e la presenza di due fattori di regolazione per questa eliminazione. Vengono presentate alcune ipotesi concernenti questi fenomeni.
    Type of Medium: Electronic Resource
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  • 98
    ISSN: 1432-5233
    Keywords: Glybenclamide ; Insulin ; Insulin secretion ; Sulfonylureas ; Tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les effets métaboliques de la glybenclamide et de la tolbutamide ont été étudiés chez deux groupes de sujets normaux traités avec des doses comparables des deux sulphanylurées. En rapport aussi à la dose de 1:400, la glybenclamide a démontré une activité insuline-sécrétive bien majeure de celle de la tolbutamide. La réponse insulinique a été suivie par une rapide et prolongée diminution des NEFA sériques et par un moins persistant effet hypoglycémique. Les effets métaboliques de l'HB 419 sont encore évidents 10–12 heures après l'administration du médicament, tandis que l'activité de la tolbutamide est terminée géneralement entre 4–6 heures. Quand l'administration des médicaments a été pratiquée en concomitance avec une charge veineuse de glucose, le coéfficient de Conard était élevé d'une façon significative par toutes les deux sulphanylurées.
    Abstract: Resumen Los efectos metabólicos de la glibenclamida y de la tolbutamida han sido investigados en dos grupos de sujetos normales tratados con dosis comparables de las dos sulfanilúreas. Inclusive en una relación de dosificación de 1:400, la glibenclamida ha demostrado una actividad insulinosecretora mucho mayor de la tolbutamida. La respuesta insulínica ha sido seguida de una disminución pronta y prolongada de los NEFA séricos y de un efecto hipoglucemiante menos persistente. Los efectos metabólicos del HB 419 son aún evidentes a las 10–12 horas después de la administración del medicamento, mientras la actividad de la tolbutamida es anulada por lo general dentro de 4–6 horas. Cuando la suministración de los medicamentos ha sido practicada en coincidencia con una carga venosa de glucosa, el coeficiente de Conard apareció significativamente elevado por ambas sulfanilúreas.
    Notes: Riassunto Gli effetti metabolici della glibenclamide e della tolbutamide sono stati indagati in 2 gruppi di soggetti normali trattati con dosi comparabili delle due sulfaniluree. Anche in un rapporto di dosaggio di 1:400, la glibenclamide ha mostrato un'attività insulino-secretiva assai maggiore di quella della tolbutamide. La risposta insulinica è stata seguita da una pronta e prolungata diminuzione dei NEFA serici e da un meno persistente effetto ipoglicemico. Gli effetti metabolici del-l'HB 419 sono ancora evidenti 10–12 h dopo la somministrazione del farmaco mentre l'attività della tolbutamide si annulla generalmente entro 4–6 h. Quando la somministrazione dei farmaci è stata praticata in coincidenza con un carico venoso di glucosio, il coefficiente di Conard è apparso significativamente innalzato da entrambe le sulfaniluree.
    Type of Medium: Electronic Resource
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  • 99
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Islets of Langerhans ; Placenta ; Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Ce travail est la continuation des communications préliminaires sur la résistance insulinique des nouveaux-nés de mères insuline-résistantes. Les recherches ont été conduites sur cobayes et sur sujets humains. Les AA. ont démontré que les anticorps anti-insuline passent dans la circulation fœtale et provoquent l'apparition d'une insuline-résistance passive qui va disparaître dans les premières semaines de la vie. Les anticorps contre l'insuline bovine lient en partie l'insuline endogène des cobayes, ce qui est mis en evidence par l'hyperglycémie élevée des cobayes jeunes nées de mères insuline-résistantes. Les anticorps anti-insuline n'ont aucun effet important sur la structure du pancréas des cobayes dans la période périnatale.
    Abstract: Resumen Este trabajo representa la continuación de las comunicaciones preliminares sobre la resistencia insulínica que presentan las personas nacidas de madres insulino-resistentes. Las investigaciones han sido efectuadas en cobayas y hombres. Se ha demostrado que los anticuerpos anti-insulina pasan al círculo fetal, provocando la aparición de insulino-resistencia pasiva, que desaparece durante las primeras semanas de vida. Los anticuerpos contra la insulina bovina ligan en parte la insulina endógena de cobayas, como lo demuestra la hiperglucemia elevada de las cobayas jóvenes nacidas de madres insulino-resistentes. Los anticuerpos anti-insulina no ejercen ningún efecto apreciable sobre la estructura del páncreas de las cobayas durante el período peri-natal.
    Notes: Riassunto Questo lavoro rappresenta la continuazione delle comunicazioni preliminari sulla resistenza insulinica dei nati di madri insulino-resistenti. Le ricerche sono state condotte su cavie e su uomini. E' stato dimostrato che gli anticorpi anti-insulina passano nel circolo fetale inducendovi la comparsa di una insulino-resistenza passiva che scompare nelle prime settimane di vita. Gli anticorpi contro l'insulina bovina legano in parte l'insulina endogena di cavie, come è evidenziato dall'elevata iperglicemia delle cavie giovani nate da madri insulino-resistenti. Gli anticorpi anti-insulina non esercitano alcun effetto di rilievo sulla struttura del pancreas delle cavie nel periodo perinatale.
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  • 100
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    Acta diabetologica 6 (1969), S. 796-808 
    ISSN: 1432-5233
    Keywords: Desensitization ; Immunoglobulins ; Insensitivity ; Insulin ; Insulin allergy ; Insulin antibodies ; Macroglobulins ; Porcine insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Cinq patients atteints d'allergie à l'insuline ont été désensibilisés par de l'insuline de porc selon la méthode d'Urbach et Gotlieb. Le diagnostic d'allergie à l'insuline a été posé sur la base des manifestations cliniques, de la positivité des réactions cutanées et, dans 2 cas, des réactions de Prausnitz-Küstner (P.K.). On a obtenu dans 3 cas une désensibilisation. La présence d'anticorps anti-insuline a été révélée par la méthode immunoautoradiographique en employant de l'insuline131J. Avant la désensibilisation la présence d'anticorps IgG a été enregistrée chez 3 patients tandis que chez 2 on a démontré également des anticorps IgA. Une réaction de P.K. positive a été observée chez des patients dont les sérums contenaient des anticorps IgA. Pendant la désensibilisation on a observé une apparition transitoire de macroglobulines capables de lier l'insuline131J. Après la désensibilisation on a constaté la persistance de la positivité aux réactions cutanées immédiates à l'insuline de porc et de boeuf. En même temps les réactions retardées et la réaction de P.K. à l'insuline de porc étaient interverties, bien que les mêmes réactions à l'insuline bovine restaient positives.
    Abstract: Resumen Cinco pacientes que padecían de alergia a la insulina han sido desensibilizados con insulina porcina según el método de Urbach y Gotlieb. El diagnóstico de alergia a la insulina ha sido puesto teniendo en cuenta las manifestaciones clínicas, el positivismo de las reacciones cutáneas, y, en 2 casos, las reacciones de Prausnitz-Küstner (P.K.). En 3 casos se ha obtenido desensibilización. La presencia de anticuerpos anti-insulina ha sido puesta en evidencia con el método inmunoautoradiográfico, empleando insulina131J. Antes de la desensibilización, la presencia de anticuerpos IgG ha sido hallada en 3 pacientes, mientras que en 2 han sido demostrados también anticuerpos IgA. Una reacción de P.K. positiva ha sido observada en pacientes cuyos sueros contenían anticuerpos IgA. Durante la desensibilización se ha observado aparición transitoria de macroglobulinas capaces de ligar la insulina131J. Al cabo de la desensibilización se ha notado la persistencia del positivismo a las respuestas cutáneas inmediatas a la insulina porcina y bovina. Al mismo tiempo, las respuestas retardadas y la reacción de P.K. a la insulina porcina cstaban invertidas, no obstante que las mismas reacciones a la insulina bovina hubieran quedado positivas.
    Notes: Riassunto Cinque pazienti con allergia all'insulina sono stati desensibilizzati con insulina suina secondo il metodo di Urbach e Gotlieb. La diagnosi di allergia all'insulina è stata posta sulla base delle manifestazioni cliniche, della positività delle reazioni cutanee e, in 2 casi, delle reazioni di Prausnitz-Küstner (P.K.). In 3 casi si è ottenuta una desensibilizzazione. La presenza di anticorpi anti-insulina è stata rivelata con il metodo immunoautoradiografico impiegando insulina131J. Prima della desensibilizzazione la presenza di anticorpi IgG è stata riscontrata in 3 pazienti mentre in 2 sono stati dimostrati anche anticorpi IgA. Una reazione di P.K. positiva è stata osservata in pazienti i cui sieri contenevano anticorpi IgA. Durante la desensibilizzazione si è osservata una comparsa transitoria di macroglobuline capaci di legare l'insulina131J. Dopo la desensibilizzazione si è riscontrata la persistenza della positività delle risposte cutanee immediate all'insulina suina e bovina. Al tempo stesso le risposte ritardate e la reazione di P.K. all'insulina suina erano invertite, sebbene le stesse reazioni all'insulina bovina rimanessero positive.
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