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  • Chemistry  (5,694)
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  • 2000-2004
  • 1980-1984
  • 1975-1979  (5,772)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 343 (1976), S. 307-311 
    ISSN: 1435-2451
    Keywords: Ulcerative colitis ; Carrageenan ; 1,2-Dimethylhydrazine ; Adenocarcinoma ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Tierversuch wurde die Frage geprüft, ob der Dickdarm bei bestehender Colitis zur malignen Entartung disponiert ist. Männliche Wistarratten erhielten nach Induktion einer Colitis ulcerosa (durch Verabreichung von 4%igem Carrageenan im Trinkwasser) das dickdarmspezifische Karzinogen 1,2-Dimethylhydrazin (DMH; Gesamtdosis 132 mg/kg Körpergewicht subcutan während 7 Wochen). 17 von 18 Tieren entwickelten 15 Wochen nach der letzten Injektion des Karzinogens multiple Adenocarcinome im distalen Colon; dieser Dickdarmabschnitt war auch der bevorzugte Ort der Carrageenan-induzierten Colitis. In einem Kollektiv von Kontrolltieren (n = 18), welche nur DMH erhalten halten, erkrankten im gleichen Zeitraum lediglich 3 Ratten an einem Coloncarcinom. Der Unterschied ist statistisch signifikant (P 〉 0,01). Carrageenan allein wirkte nicht als Karzinogen. Die Ergebnisse unserer Untersuchungen zeigen, daß die Colitis ulcerosa auch im Tierversuch als Krebsrisikokrankheit aufzufassen ist.
    Notes: Summary Animal experiments were performed to answer the question whether ulcerative colitis is predisposed to malignant degeneration.-Male Wistar rats were given aqueous solutions of degraded Carrageenan (4%; w/v). After induction of ulcerative colitis, 1,2-Dimethylhydrazine (DMH; 132 mg/kg body weight) was applicated during a period of 7 weeks. 17 of 18 rats developed multiple adenocarcinomas in the distal colon 15 weeks after the last injection of DMH. The Carrageenan induced colitis was localized predominantly in the distal part of the large bowel. Only 3 rats of a control group of 18 animals exposed to DMH only showed carcinomas of the colon. The difference is proven significant (P 〈 0.01). Carrageenan for itself caused no malignancy.-The results of the experiments demonstrate that, during ulcerative colitis, the colon of the rat is more susceptible to induction of cancer than the intact one.
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  • 2
    ISSN: 1433-8580
    Keywords: Rat ; liver damage ; thoracic duct ; thermocoagulation ; lymphedema ; 3H-thymidine ; autoradiography ; electron microscopy ; Ductus-thoracicus-Blockade ; Rattenleber ; 3H-Thymidin ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 90 männlichen und weiblichen, weißen Sprague Dawley Ratten wurden autoradiographische Untersuchungen mit3H-Thymidin nach experimenteller Blockade des Ductus thoracicus unternommen. Dabei zeigte sich im akuten Versuch kein nennenswerter Einfluß der intrahepatischen Lymphstase auf den DNS-Einbau in die Kerne der Hepatozyten bzw. Sternzellen. Bei den Langzeittieren (20–360 Tage) lagen die Markierungsindices der Hepatozyten geringfügig über denjenigen gleich alter, gesunder Kontrolltiere. Bei 14 männlichen und weiblichen, weißen Sprague Dawley Ratten führten wir zusätzlich elektronenmikroskopische Untersuchungen in der Leber durch. Dabei fanden sich im akuten Versuch ein intra- und extra-zelluläres Ödem sowie Schädigungen läppchenperipherer Hepatozyten. Nach 12–15 Tagen haben sich diese Veränderungen weitgehend zurückgebildet. Somit scheint eine intrahepatische Lymphstase keinen nachhaltigen Einfluß auf das Regenerationsverhalten der Leberzellen auszuüben.
    Notes: Summary Autoradiographic studies with3H-thymidine were done in 90 male and female white Sprague Dawley rats following thermocoagulation of the thoracic duct at the base of the neck. In the acute stages of these experiments we were unable to find any significant influence of a lymphedema on the hepatocytes and Kupffer cells. In the longterm experiments the labelling indices of the hepatocytes were slightly above those of healthy controls of the same age. In another 14 male and female white Sprague Dawley rats we did electron microscopical investigations of the liver. In the acute phase of the experiment we found an intra- and extrahepatic edema as well as damages of the hepatocytes at the periphery of the liver acini. After 12–15 days these findings have regressed. It seems therefore that an intrahepatic lymphedema does not influence the regenerative capacity of the liver to a marked extend.
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  • 3
    ISSN: 1432-1106
    Keywords: Rat ; Hypoglossal nucleus ; Inhibited regeneration ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron micrographs of the left hypoglossal nucleus were quantitatively analyzed in adult rats 52 to 98 days after transection of the left hypoglossal nerve and implantation of the proximal stump into the already innervated ipsilateral sternomastoid muscle, a procedure which prevented the transected nerve from regenerating. Many presynaptic boutons with clear spherical synaptic vesicles and symmetrical synapses were lost from the injured perikarya and dendrites. Some perikarya and dendrites (and, rarely, boutons) became electron dense, and astrocyte or microglial sheaths partly surrounded them. Numbers of dendrite profiles in the neuropil decreased. These statistically significant effects persisted throughout the postoperative period, whereas after axotomy with unimpeded nerve regeneration, these features would have returned to normal by 84 days postoperatively. It was therefore suggested that their recovery depended upon successful regeneration and reconnection of the hypoglossal nerve with the tongue. Subsurface cisterns, and profiles containing unusual inclusions, were numerically normal 52 to 98 days postoperatively, so it was suggested that their early response and recovery after simple axotomy might be entirely dependent on nerve disconnection and not on nerve reconnection.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 26 (1976), S. 193-202 
    ISSN: 1432-1106
    Keywords: Inferior olive ; Trigeminal nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular recordings were obtained from inferior olivary neurones of the rat. The responses of fifty neurones evoked by electrical stimulation of a branch of the trigeminal nerve were recorded. Maxillary nerve stimulation was most effective. The response was characterized by an early discharge (single spike and wave, typically with latencies between 16 and 30 msec) and a weak late discharge which followed a period of inhibition of about 100 msec. Half of the neurones responded to one branch of the trigeminal nerve only whereas the other neurones displayed a varying degree of convergence, including sometimes a convergence from limb nerves. Forty-nine olivary neurones were tested for cutaneous receptive fields. Ten out of these had small receptive fields (〈20% of the contralateral face) and a low threshold to mechanical stimuli. Twenty neurones which had larger receptive fields responded also to low-threshold or to medium-threshold (i.e. non-nociceptive) mechanical stimuli. None of the neurones displayed receptive fields more extensive than half of the contralateral face and some of the larger fields had a small, low-threshold focus. Olivary neurones responding to electrical stimulation of trigeminal nerves or mechanical stimulation of the face were located in the medial segment of the olivary complex (dorsal accessory and principal olive). A few cells only were located in the lateral segment. It is concluded that neurones of the inferior olive receive a substantial input from trigeminal afferents and are capable of transmitting precise somatotopical information to the cerebellum.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 372 (1976), S. 97-108 
    ISSN: 1432-2307
    Keywords: Scanning electron microscopy ; Cirrhosis ; Liver ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The surface features of single cells and of multicellular tissue units in cirrhotic rat livers have been studied by scanning electron microscopy (SEM). Cirrhosis of the liver was produced in rats by simultaneously treating them with carbon tetrachloride and sodium phenobarbital. Connective tissue septa consisted of a loose mesh-work of fibers in which fibroblasts were embedded. The arrangement and surface features of hepatocytes in cirrhotic nodules differed from those found in parenchyma of normal livers. Hepatocytes in cirrhotic nodules universally formed plates two cells thick. The portion of the hepatocyte surface covered by microvilli was greatly increased in cells from cirrhotic livers, and this was reflected in a corresponding reduction in the area occupied by the smooth-surfaced narrow intercellular space. Canaliculi between hepatocytes in cirrhotic livers were reduplicated and frequently branched. Hepatocyte surfaces covered by microplicae and flattened microvilli, typical of connective tissue-facing surfaces in normal livers, were greatly increased in cirrhotic livers corresponding to the increase in connective tissue. Where hepatocytes directly contacted fibroblasts (and not fibers), their surfaces were entirely smooth. Sinusoidal endothelial cells in cirrhotic livers contained only isolated, relatively sparse pores, and they lacked both sieve plates (pore complexes) and large fenestrations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0568
    Keywords: CRF-granules ; Sodium chloride ; Adrenalectomy ; Rat ; Histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bilaterally adrenalectomized female SPF Wistar rats were given tap water containing various concentrations of sodium chloride to drink ad lib. After a survival period of 14 days the animals were killed by perfusion-fixation. Their brains were removed, fixed in pieric acid formalin solution and embedded in Paraplast. Serial sections of median eminence and hypophysial posterior lobe were cut and stained with crotonaldehyde-fuchsine. In the stained sections the amount of CRF-granules visible in the external zone of the median eminence, and the amount of “classical” neurosecretory material (NSM) occuring in the internal zone of the median eminence and in the posterior lobe of the hypophysis were estimated. After administration of drinking solutions to which 0%–1% sodium chloride were added, the amount of CRF-granules increased with increasing NaCl uptake, whereas the amount of “classical” NSM was not changed. Application of tap water containing 2% NaCl led to a marked decrease in the amount of “classical” NSM but did only slightly impair the amount of CRF-granules. From the findings it is concluded that 1. following bilateral adrenalectomy administration of sodium chloride inhibits the secretion of CRF-granules; 2. CRF-granules and “classical” NSM, although histochemical identical, have different functional significances; 3. the mechanisms regulating the secretion of CRF-granules are different from those controlling the release of “classical” NSM.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0568
    Keywords: Pineal organ ; Perivascular contact ; HIOMT ; Median eminence ; Adrenal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the pineal organ of the female rat, proportional changes in the area of contact of pinealocyte processes and glial processes with the perivascular space were found after bilateral adrenalectomy. The contact area was evaluated by measuring the length of pinealocyte and glial cell membranes directly abutting on the basal lamina. In the normal female rat, 40% of the contact area is occupied by pinealocyte and 60% by glial cell processes. Fourteen days after bilateral adrenalectomy, this proportion is reversed. In addition, cell counts demonstrate that more pinealocytes gain access to the pericapillary space due to the experimental conditions. In order to prove whether or not these results indicate an increase of pineal endocrine activity, the melatonin-forming enzyme hydroxyindole-O-methyltransferase (HIOMT, E.C. 2.1.1.4) was assayed. After bilateral adrenalectomy the HIOMT activity was found to significantly increase.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 149 (1976), S. 155-171 
    ISSN: 1432-0568
    Keywords: Large intestinal epithelium ; Postnatal development ; Rat ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The principal cells of the surface of the cecum, the ascending colon, and the descending colon in postnatal developing rats were investigated using both light and electron microscopy. In rats 1 to 14 days old the ultrastructure of the surface principal cells in the cecum and ascending colon were characterized by apical tubulo-vacuolar systems and large supranuclear vacuoles similar to those in the absorbing cells of the neo-natal ileum as reported by Clark, 1959, and others. After about the 16th day, the special membrane system disappears from the principal cells of the proximal large intestine. On the other hand, in the descending colon, this special membrane system was absent from the cytoplasmic matrix of the epithelium. It is thought that the proximal portion of the large intestine together with the distal part of the small intestine actively participate in the absorption of protein molecules at least during the early postnatal period.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 294 (1976), S. 109-113 
    ISSN: 1432-1912
    Keywords: 14C-Heteronium bromide ; Drug distribution ; Rat ; Anticholinergic agent
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tissue distribution of radioactivity after oral administration to rats of 14C-heteronium bromide is measured by liquid scintillation counting and the results expressed as specific activity and percentage of administered radioactivity. From the data obtained in blood, liver, kidney, stomach, duodenum, cecum, large intestine and stool some conclusions can be drawn. Heteronium bromide undergoes a rapid systemic absorption, the radioactivity being present as early as 15 min from the administration, in all the tested organs. The blood levels show two peaks: one at 120 min and a second at 360 min. This diphasic behaviour can be explained either by the presence of an active enterohepatic circulation, as indirectly indicated by the data from liver and duodenum, or by a transient shift of the molecule from blood to other tissues, rich in polysulfuronic acids. The principal route of excretion is represented by the kidney, where consistent levels are reached at 120 min, while the intestinal route becomes evident at 240 min and reaches its maximum at 720 min. The complete metabolic cycle of the compound is long lasting, since in all the tested tissues, marked radioactivity levels are still present after 720 min. The pharmacokinetic profile obtained, suggesting a long persistence of the drug and/or of its metabolites in the organism, is in agreement with previous pharmacodynamic data showing a long lasting action for heteronium bromide.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 295 (1976), S. 165-169 
    ISSN: 1432-1912
    Keywords: Digoxin ; Bile flow ; Biliary excretion ; Acetylcholine ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of acetylcholine (ACh), physostigmine, and atropine on bile flow and biliary elimination of digoxin were investigated using isolated rat liver perfusion. 1. ACh in the presence of physostigmine caused a temporary reduction in the bile secretion, while physostigmine alone had no effect on the bile flow. 2. The biliary concentration of radioactivity derived from 3H-digoxin was slightly decreased after an addition of physostigmine alone. This effect of physostigmine was not potentiated by ACh. 3. The addition of ACh decreased transiently the biliary elimination of digoxin, as a result of the reduced bile flow. 4. Atropine in the concentration range of 10−6–10−5 M in the perfusion medium did not affect bile flow or biliary excretion of digoxin; repeated addition of atropine (2×2×10−4 M) caused a choleresis lasting over the perfusion period. 5. This choleresis induced by atropine was associated with decreased concentration of tritium in the bile but slightly increased biliary elimination of total radioactivity. 6. The results allow us to draw the conclusion that ACh in the presence of physostigmine has an inhibitory action on bile flow and biliary elimination of digoxin in the isolated perfused rat liver.
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  • 11
    ISSN: 1432-2072
    Keywords: Chlordiazepoxide ; Rat ; Simultaneous discrimination ; Successive discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chlordiazepoxide (CDP) at a dose of 20 mg/kg, i.p. was found to exert a marked disruptive effect on black-white successive discrimination learning in rats, while this effect failed to be obtained on black-gray simultaneous discrimination. Since trials to the learning criterion were found almost equal for saline rats on both successive and simultaneous discrimination tasks, the differential inhibitory effects of CDP could not be accounted for in terms of differences in difficulties of the two tasks. It is suggested that present results might be interpreted in terms of the hypotheses (a) that CDP produces a deficit in the integration of relevant stimulus cues when they were presented across trials or (b) that CDP has a dis-inhibitory effect in that inhibition of dominant response (positional preference) patterns is weakened by the drug, in a manner similar to effects observed in hippocampectomized animals.
    Type of Medium: Electronic Resource
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 50 (1976), S. 281-283 
    ISSN: 1432-2072
    Keywords: Motor incoordination ; Runway test ; Diazepam ; Phenobarbital ; Chlorpromazine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A runway apparatus for rats has been developed for measuring motor incoordination and running time. Animals were trained to run along an elevated narrow pathway. Frequency and severity of slipping off and running time were automatically counted. Rats were given diazepam, phenobarbital or chlorpromazine orally and tested 1 h later. Diazepam, 8–64 mg/kg p.o., caused slipping off in a dose-dependent manner. Phenobarbital had a similar effect with 64 mg/kg p.o. Chloropromazine, 32 and 64 mg/kg p.o., caused other signs of motor deficit.
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  • 13
    ISSN: 1432-2072
    Keywords: Intracranial self-stimulation ; Caudateputamen ; Hypothalamus ; Serotonin ; Dopamine ; Para-chlorophenylalanine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were prepared with chronic bipolar electrodes aimed at either the caudate-putamen or lateral hypothalamus and those displaying consistent self-stimulation were given additional training at half-maximal current intensities. All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established. Responding in both brain areas was suppressed 24 h after drug treatment. The next day, self-stimulation rates in the hypothalamus increased to 115% of pre-drug levels reaching a level of 180% by the third day of post-drug testing. In contrast, self-stimulation of sites in the neostriatum continued to decline, with minimal levels reaching 48% of control on the fourth post-drug day. Self-stimulation rates in both groups had returned to control levels by post-drug day 6. These data indicate that the role of serotonergic mechanisms in brain stimulation is locus specific, and that the specific nature of this role may be determined by interaction with other neurochemical systems. The possible interaction between dopaminergic and serotinergic mechanisms in the neostriatum is discussed as a model of self-stimulation in this region of the brain.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 50 (1976), S. 89-94 
    ISSN: 1432-2072
    Keywords: Prostaglandins A1, E1, E2, F1α, F2α ; Intraventricular administration ; Rat ; Behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of prostaglandins (PGs) A1, E1, E2, F1α, and F2α administered intraventricularly at doses of 0.02–4.0 μg/rat were studied in some behavioral, antinociceptive and anticonvulsant tests in rats. Exploratory and locomotor activity were decreased by all PGs except A1 and F2α which had no effect on locomotor activity. All PGs studied, except A1, induced hyperthermia and afforded protection in the ‘hot-plate’ analgesic test and against maximal electroshock seizures.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 50 (1976), S. 103-105 
    ISSN: 1432-2072
    Keywords: Intravenous ; Intragastric ; Self-Administration ; Unit dose ; Route of administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were implanted with intravenous or intragastric cannulas and allowed to self-administer morphine sulfate in doses of 0 (saline), 0.03, 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg/infusion. For the intravenous route the number of infusions decreased with increasing unit dose, while the amount self-administered was directly related to unit dose. However, for the intragastric route the number of infusions first increased and then decreased as unit dose was elevated, while the amount self-administered again increased with unit dose. Comparisons between routes showed that for intragastric subjects the number of infusions and amount self-administered both were lower at the two lowest doses but higher for all other doses. These results support the expectation that intravenous injection should produce more potent reinforcing effects than intragastric administration.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1432-2013
    Keywords: Plasma volume ; Protein ; Electrolytes ; Dehydration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.
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  • 17
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Adipose innervation ; Rat ; Nonshivering heat production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two aspects of the coupling of neural information to brown fat thermogenesis were examined—namely, the thermal responses to increasing neural stimulation and the anatomical nature of the brown fat innervation. Upon stimulation of the nerves to the interscapular brown fat pad, there ensued a biphasic response. This response was manifested by an initial, but transient temperature decrease, followed by a rise in brown fat temperature. The magnitude of both components of this response increased with increasing stimulus strength, thereby demonstrating the ability of the tissue to respond in a graded manner—a feature which may underlie the controlled thermogenic response of brown fat observed in the cold-exposed intact animal. No anatomically unique fiber types appeared to be specifically associated with innervation to the brown adipocytes or to the vessels within the fat pad. On the other hand, the nerves entering the interscapular fat pad were morphologically dissimilar, a finding consonent with their functional dissimilarity (i.e., innervation of adipocytes, innervation of blood vessels in the fat pad, and innervation of areas in the overlying skin).
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 365 (1976), S. 183-189 
    ISSN: 1432-2013
    Keywords: Temperature regulation ; Circadian rhythms ; Ambiant temperature ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'enregistrement chronique des températures cérébelleuses et sous-cutanées par thermistance a été réalisé chez le rat soumis à différentes températures ambiantes et à une alternance lumière-obscurité de 12 h (lumière de 7 à 19 h). La période du rythme des températures cérébelleuses et sous-cutanées est de 24 h avec acrophase nocturne (1 h) et amplitude de 0,75° C. L'amplitude et l'acrophase ne sont pas modifiées au cours des expositions à différentes températures ambiantes (20-25-30-34-35° C). Chaque augmentation d'ambiance se traduit par une élévation du niveau moyen de la température interne. Cette augmentation, peu perceptible entre 25 et 30° C, atteint 0,5° C entre 20 et 25° C et 1° C entre 30 et 34° C. Elle se maintient tout au long des 10 jours d'observation. Ces résultats soulèvent au moins 3 questions: le degré de liaison entre les rythmes d'activité (éveil) et de température, la labilité de la température interne qui varie avec l'ambiance alors que l'amplitude du rythme circadien reste constante, l'absence de diminution de la température interne après plusieurs jours en ambiance chaude alors qu'activité et métabolisme sont diminués dès le 2ème jour d'exposition.
    Notes: Summary Chronic recording of cerebellar and subcutaneous temperatures were carried out in rats maintained at different ambient temperatures in a 12 h light-dark cycle (light from 7 to 19 h). Cerebellar and subcutaneous temperatures followed a rhythm with a period of 24 h with acrophase at 1 h and an amplitude of 0.75° C. The amplitude and acrophase were not altered by modification of the ambient temperature (20-25-30-34 or 35° C), but each elevation of ambient temperature produced a rise in the mean internal temperature of the rat. This rise, hardly perceptible at ambient temperatures, of 25 and 30° C, reaches 0.5° C between 20 and 25° C and 1° C between 30 and 34° C. This elevation of temperature was maintained for the duration of the 10 days of observation. These results pose at least three questions: the degree of liaison between the rhythms of activity (waking) and temperature; the lability of the mean internal temperature, which alter with ambient temperature while the amplitude of the circadian rhythm is unaltered and the absence of reduction of mean internal temperature several days exposure to a raised ambient temperature, even when activity and metabolism are reduced by the second day of exposure.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1976), S. 327-332 
    ISSN: 1432-1041
    Keywords: Antipyrine ; pharmacokinetics ; half-life ; blood ; plasma ; saliva ; individual variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). The levels in blood and saliva were comparable to those in plasma at every time studied. The half life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n=5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva and capillary blood.
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  • 20
    ISSN: 1432-1041
    Keywords: Chlorthalidone ; diuretics ; drug plasma concentration ; protein binding ; red blood-cell concentration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorthalidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n=10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those predicted from the single oral dose studies in healthy volunteers.
    Type of Medium: Electronic Resource
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1976), S. 367-372 
    ISSN: 1432-1041
    Keywords: Sotalol ; β-adrenoceptor blocking drugs ; exercise tachycardia ; efficacy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of sotalol after oral administration were measured on the tachycardia induced by strenuous exercise in normal subjects. Plasma sotalol levels were also determined. The oral administration of sotalol (50, 100, 200 and 400 mg) to 6 subjects produced a progressive reduction in the tachycardia induced by severe exercise. This was similar to the effects of 25, 50, 100, 200, 400 and 800 mg given to different subjects. Each increase in sotalol dose produced a successively greater reduction in exercise tachycardia. This did not appear to be maximum even with 800 mg. Oral sotalol was rapidly absorbed and produced peak blood levels in 2 – 3 hours. The plasma levels of sotalol measured 2 hours after the oral administration of 25 to 800 mg showed never more than a six-fold variation between different subjects. The half-life of sotalol in plasma was 12.7 ± SE 1.6 hours. There was a significant correlation between the logarithm of the plasma sotalol concentration and the percentage reduction of exercise heart rate. It is concluded that the oral administration of sotalol either once or twice daily (depending on dose level) will provide satisfactory 24-hour blockade of β-adrenoceptors.
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  • 22
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    European journal of clinical pharmacology 9 (1976), S. 443-450 
    ISSN: 1432-1041
    Keywords: Cyclobarbital calcium ; pharmacokinetics ; plasma concentration ; relative bioavailability ; oral administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and relative bioavailability of cyclobarbital calcium have been studied after oral administration of Phanodorm, of tablets according to the Formularium Nederlandse Apothekers (1968; FNA), and an aqueous solution. Six healthy volunteers participated in the investigation on three occasions and each received the three preparations. The dose administered was 300 mg cyclobarbital calcium. Plasma concentrations of cyclobarbital were determined at regular intervals. Absorption from the three preparations was rapid and was faster from the solution. Peak concentrations were usually attained within 1 h. The elimination of cyclobarbital could be described by a single first-order process with an average half-life of 11.6 h (range 8 – 17 h). There was little intra-subject variation of the half-life. Relative bioavailability for each volunteer was estimated by comparing the areas under the plasma concentration curves. The FNA-tablets and Phanodorm exhibited similar bioavailability, whereas the average bioavailability of the solution was 78% of that of FNA-tablets; the reason for this unexpected finding is unknown. It was concluded that cyclobarbital cannot be regarded as a uniformly suitable drug for the treatment of insomnia. The long half-life that was apparent in some of the volunteers (15 – 17 h) creates a substantial risk of residual effects on the following morning. In principle, however, the calcium salt of cyclobarbital may be used for induction of sleep, because of its rapid absorption.
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  • 23
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    European journal of clinical pharmacology 10 (1976), S. 251-256 
    ISSN: 1432-1041
    Keywords: Sisomicin ; pharmacokinetics ; bioavailability ; two-compartment analysis ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sisomicin, a new single component aminoglycoside antibiotic related to gentamicin c1a, were determined in four healthy volunteers after intravenous and intramuscular administration of a 1 mg/kg dose. The elimination profile of this antibiotic follows two-compartment model kinetics after I.V. administration. The fast (α) and slow (β) disposition rate constants averaged 0.072 and 0.004 min−1, respectively. The volume of distribution at the steady-state averaged 0.185 liters/kg which approximately corresponds to the volume of extracellular space. The physiological availability of an intramuscular dose appeared to be complete. A method of administration adapted to the kinetic properties of the drug is proposed.
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  • 24
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    European journal of clinical pharmacology 10 (1976), S. 311-317 
    ISSN: 1432-1041
    Keywords: Hydralazine ; instability of impaired renal function ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following a single 50 mg dose of hydralazine (Apresoline®) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=−0.69; p〈0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml·min−1, as compared to a T1/2 of 1.7–3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (C SS min : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml·min−1 (r=−0.63; p〈0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng·ml−1 in urine could be recovered after storage of the samples at room temperature for 24 h.
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  • 25
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    European journal of clinical pharmacology 10 (1976), S. 325-330 
    ISSN: 1432-1041
    Keywords: Flutiorex ; pharmacokinetics ; sex ; anorectic agent ; sympathetic stimulation ; CNS stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of flutiorex, a new anorectic agent, and of a placebo on food intake and the activity of the sympathetic and central nervous systems have been compared in a double blind trial in two groups of healthy volunteers, one of five males and the other of five females. Flutiorex 20 mg orally had a significant anorectic effect both in males and females, the observed reduction in food intake being 34.0 and 27.5%, respectively. It caused α-adrenergic stimulation (blood pressure and pupil diameter) and central nervous system excitation (critical flicker frequency), both of which were more marked in males than in females. Flutiorex was better tolerated by women than by men. Measurement of the blood level of flutiorex and its de-ethylated metabolite, norflutiorex, showed that both compounds were detectable in four of the five male subjects, but in only one of the five females. Sex-linked differences in the pharmacokinetics of flutiorex may explain the greater intensity of its effects in males.
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  • 26
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    European journal of clinical pharmacology 10 (1976), S. 343-347 
    ISSN: 1432-1041
    Keywords: Methaqualone ; hypnotic ; pharmacokinetics ; combination formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Concentrations of methaqualone have been measured in the serum of five male human subjects receiving five consecutive evening doses of a combination formulation containing methaqualone (250 mg), carbromal (300 mg) and benactyzine (0.33 mg) in each tablet. After administration of the first dose, mean peak serum concentrations of methaqualone (1.2 µg/ml) occurred at 3 h. After obtaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h and there-after more slowly during the next 18 h. After administration of the last (fifth) dose, mean peak serum concentrations of methaqualone (1.9 µg/ml; 1.5 µg/ml above the predose level) occurred at 2 h. After attaining peak levels, mean concentrations of methaqualone declined rapidly during the next 6 h, and thereafter more slowly, with a half-life of approximately 10 h. Mean concentrations of methaqualone in serum samples 24 h after the second, third, fourth or fifth doses were not significantly different (0.3 µg/ml – 0.6 µg/ml) during this period of dosing. This suggests that significant accumulation of methaqualone in the serum did not occur during a period of five consecutive evening doses of the combination formulation.
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  • 27
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    European journal of clinical pharmacology 10 (1976), S. 257-262 
    ISSN: 1432-1041
    Keywords: Anti-inflammatory and analgesic drug ; indoprofen ; pharmacokinetics ; bioavailability ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In a pharmacokinetic study of the new analgesic and anti-inflammatory drug indoprofen, plasma levels and urinary excretion were determined in four healthy volunteers after 100 mg and 200 mg iv, and after 100 mg (capsules) and 200 mg (tablets) oral doses. After iv administration, the mean biological half-life (t1/2 β) was about 2 h (range 1.4 to 3.2 h). The apparent volume of distribution Vdβ ranged between 11 to 17 % of body weight, indicating its limited extravascular distribution. Most of the drug was excreted in urine as glucuronide and a smaller proportion as unchanged indoprofen: the 24 h urinary excretion of these compounds accounted for 67 to 95 % of an iv dose. Peak plasma levels occurred between 30 and 120 minutes after oral administration of 100 mg as capsules or 200 mg as tablets. The mean biological half-life was about 2 h, as after iv administration. The bioavailability of oral doses was assessed using both plasma levels and urinary excretion data. The absorption of capsules and tablets was practically complete, that of the former being faster.
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  • 28
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    European journal of clinical pharmacology 10 (1976), S. 25-29 
    ISSN: 1432-1041
    Keywords: Digoxin ; exchange transfusion ; pharmacokinetics ; neonates ; 86Rb assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary By means of an86Rb-uptake inhibition assay, changes in the plasma concentration of digoxin and the amount of the glycoside removed during exchange transfusion have been studied in two newborns. For comparison, the exchange procedure was simulated by a computer on the basis of a two-compartment open model and available pharmacokinetic constants. A rapid decrease in plasma digoxin concentration during exchange transfusion was found when the glycoside was administered intravenously or intramuscularly within 60 min before the procedure. The amount of digoxin removed by the exchange was less than 6 per cent of the given dose. Computer simulation of the procedure also showed removal of only a minor amount of digoxin. It is concluded that the decrease in plasma concentration and the removal of only a small amount of glycoside by the exchange transfusion can be attributed mainly to extensive tissue distribution of digoxin. The results imply that replacement of digoxin after an exchange transfusion seems unnecessary.
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  • 29
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    European journal of clinical pharmacology 10 (1976), S. 121-126 
    ISSN: 1432-1041
    Keywords: Diazepam ; pharmacokinetics ; subchronic dosage in man ; desmethyldiazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n=5, age 29 – 35 years) the elimination half-life, T1/2 (β), of D was 33.9±10.6 h (mean±S.D.) after the single dose. The control study gave an almost identical result (35.7±12.1). After subchronic dosage in all patients T1/2 (β) showed a modest but significant prolongation (paired t-test p〈0.01) to 52.9±17.4 h. It was caused by a significant decrease (p=0.016) in total plasma clearance ( $$\overline {\user1{Cl}} $$ ), from 26.0±10.8 ml/min to 18.2±7.0 ml/min. Older patients (age 43–60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3–0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T1/2 (β) from 2.7 h to 5.2 h, with a corresponding decrease of $$\overline {\user1{Cl}} $$ from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.
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  • 30
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    Archives of toxicology 36 (1976), S. 305-316 
    ISSN: 1432-0738
    Keywords: Circadian rhythm ; Renin ; Aldosterone ; Corticosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der 24 Std-Verlauf der Plasma-Renin-Aktivität (PRA), der Plasma-Aldosteron-Konzentration (PAC), der Plasma-Corticosteron-Konzentration (PCC) sowie der Urinexkretion von Natrium, Kalium und Aldosteron wurde an männlichen Sprague-Dawley-Ratten unter verschiedenen experimentellen Bedingungen untersucht. Die Ergebnisse lassen sich wie folgt zusammenfassen: 1. Das Renin-Angiotensin-Aldosteron-System (RAAS) der Ratte weist einen zirkadianen Rhythmus auf, der dem gut bekannten Rhythmus des Hypophysen Nebennierenrinden-Systems parallel läuft. Dieser Rhythmus läßt sich durch Messung der PRA, der PAC und der Exkretionsrate von Aldosteron im Urin nachweisen. Der Rhythmus der Elektrolytausscheidung im Urin scheint nicht durch den Rhythmus der Aldosteronsekretion bedingt zu sein. 2. Der Licht-Dunkel-Zyklus ist der Zeitgeber für diese Rhythmen: Eine Umkehr des Licht-Dunkel-Zyklus für 5 Wochen bewirkt eine komplette Umkehr der Rhythmen aller genannten Parameter. 3. Unter Natrium-Restriktion oder Dexamethason-Behandlung wird eine Dissoziation des Rhythmus der PRA von dem der PAC beobachtet, während der Rhythmus der PAC unter allen Versuchsbedingungen mit dem der PCC parallel geht. Diese Beobachtung legt den Schluß nahe, daß das ACTH an der Steuerung des Rhythmus der Aldosteronsekretion beteiligt ist. 4. Der Grad der Stimulierbarkeit bzw. Supprimierbarkeit des RAAS unterliegt tageszeitlichen Schwankungen. 5. Es wird daher empfohlen, bei Untersuchungen über das RAAS der Ratte die Experimente nicht nur während der Inaktivitätsperiode (Lichtphase), sondern auch während der Aktivitätsperiode (Dunkelphase) dieser Tiere durchzuführen. Dies läßt sich durch Benutzung eines Tierstalls mit umgekehrtem Licht-DunkelZyklus vereinfachen.
    Notes: Abstract The 24 h-course of plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma corticosterone concentration (PCC) and of the urinary excretion of sodium, potassium and aldosterone was investigated in male Sprague-Dawley rats under different experimental conditions. The data obtained can be summarized as follows: 1. The renin-angiotensin-aldosterone system (RAAS) of the rat is subject to a circadian rhythm which is largely in phase with the well-known rhythm of the pituitary-adrenal axis. This rhythm can be demonstrated in PRA as well as in plasma concentrations and urinary excretion rates of aldosterone. The rhythm of urinary excretion of electrolytes is unlikely to be due to the rhythm of aldosterone secretion. 2. The light-dark cycle is the main synchronizer for these rhythms: inverting the light-dark cycle for 5 weeks entirely inverts the rhythms of all the parameters cited. 3. A dissociation of the rhythms of PRA and PAC can be observed following sodium restriction or dexamethasone treatment. A role of ACTH in regulating the rhythmic pattern of aldosterone secretion is suggested by the finding that PAC and PCC follow the same pattern of circadian variations under every experimental condition tested. 4. The responsiveness of the RAAS to stimulation or suppression varies with the time of day. 5. It is suggested that experiments ought to be performed not only during the inactive (light hours) but also during the active (dark hours) phase when investigating the RAAS in the rat. This can conveniently be achieved by the use of an animal room with a reversed lighting regime.
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  • 31
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    Archives of toxicology 35 (1976), S. 15-24 
    ISSN: 1432-0738
    Keywords: Inorganic mercury ; Chelating agents ; Excretion ; Distribution ; Rat ; Anorganisches Quecksilber ; Chelatbildner ; Ausscheidung ; Verteilung ; Ratte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Unter 15 untersuchten Chelatbildnern wurden die Ausscheidung und Organ-verteilung von Hg nur durch Natrium-2,3-Dimercaptopropan-1-sulfonat (DMPS), 2,3-Dimercaptopropanol (BAL), Natrium-Mercaptoäthyliminodiacetat (MEIDA) und D-Penicillamin (PA) beeinflußt. Das Ausscheidungsmuster ist jedoch bei diesen Substanzen unterschiedlich, und einen praktisch günstigen Effekt zeigt nur DMPS, das die renale Ausscheidungsrate erhöht und die Hg-Konzentration in allen Organen senkt.
    Notes: Abstract Among 15 chelating agents tested, sodium-2,3-dimercaptopropane-1-sulfonate (DMPS), 2,3-dimercaptopropanol (BAL), sodium-mercaptoethyliminodiacetate (MEIDA), and D-penicillamine (PA) exerted an influence on the excretion of Hg and its distribution in the organs. The excretion pattern, however, is different for these compounds, and, from the practical point of view, a favourable effect is exhibited only by DMPS which enhances the urinary excretion rate and lowers the Hg-concentration in all organs.
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  • 32
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    Archives of toxicology 35 (1976), S. 281-294 
    ISSN: 1432-0738
    Keywords: Dichlorvos ; Inhalation toxicity ; Rat ; Carcinogenesis ; Dichlorvos ; Inhalation-Toxizität ; Ratte ; Karzinogenese
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In den vorliegenden Untersuchungen wurde der Effekt von Dichlorvos-Inhalation in Beziehung zur Krebserzeugung bei Ratten (5 Wochen alte Carworth Farm E, 94–150 g) langfristig (2 Jahre) in Konzentrationen von 0, 0,05, 0,5 und 5 mg/m3 geprüft. Das Wachstum aller geprüften Tiere, im besonderen der männlichen, war verzögert. Bei Exposition in 5 mg/m3 war die Überlebensrate von Ratten erhöht. Die verschiedenen Gruppen zeigten keinen Unterschied in Futteraufnahme, Organgewichten, hämatologischen oder chemischen Bestimmungen, mit Ausnahme der Cholinesterase-Aktivität. Nach einer 2jährigen Inhalation wurden keine Unterschiede des Gehaltes an Acetylcholin und Cholin in einer kleineren Zahl weiblicher Tiere gefunden. Makro- oder mikroskopische Veränderungen in den Rattengeweben, die auf Dichlorvos zurückzuführen wären, wurden nicht beobachtet. Auch die Ultrastruktur der Lungengewebe von Kontrollratten und der Ratten in 5 mg/m3 zeigte keine Veränderungen, die von Dichlorvos abhängig waren. Die Ergebnisse einer “relative risk analysis” der vorliegenden Tumorversuchsreihe haben keine dosisabhängige Erhöhung des Tumorrisikos für Ratten beider Geschlechter gezeigt. Die Befunde sind in Übereinstimmung mit früheren und sprechen für die Unbedenklichkeit des Gebrauchs von Dichlorvos als Insektizid.
    Notes: Summary To determine the effects of dichlorvos vapour on the tumour incidence in rats, 5 week old Carworth Farm E strain rats weighing between 94 and 150 g were exposed to 0, 0.05, 0.5 and 5.0 mg/m3 in a 2-year inhalation study. The growth rate of all treated rats was depressed, particularly in the males. There was increased survival of the rats exposed to 5 mg/m3. There were no consistent differences in food intakes, organ weights, haematological or blood chemistry estimations, except in cholinesterase activities, amongst the various groups of rats. No compound-related differences were seen in acetylcholine and choline estimations carried out on a small number of female rats' brain tissues after two years' exposure. There were no gross or microscopical compound-related changes in the rats' tissues. Ultrastructural examination of the respiratory tissues of the rats from the control and 5 mg/m3 group showed no changes attributable to dichlorvos. The results of a relative risk analysis of the tumour data showed that no dose-related increase in tumour risk was established for rats of either sex. These data confirm the results of earlier studies supporting the safety of insecticidal uses of dichlorvos.
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  • 33
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    Archives of toxicology 37 (1976), S. 39-46 
    ISSN: 1432-0738
    Keywords: Cadmium ; Carbonic anhydrase ; Hemoglobin ; Blood ; Testes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die bei Säugetieren durch Cadmium (Cd) hervorgerufenen Hodenschäden beruhen angeblich auf einer Hemmung der Carboanhydratase (CAH). Da Cd dosisabhängig die Hodendurchblutung beeinflußt, könnte jedoch durch eine Verminderung der Zahl CAH-reicher Erythrocyten eine Hemmung der CAH im Hoden vorgetäuscht werden. Wir bestimmten deshalb CAH-Aktivitäten und Hämoglobin (Hb)-Gehalt im Blut und im Hoden von unbehandelten und Cd-behandelten Sprague-Dawley-Ratten. Entsprechende Untersuchungen wurden an Ratten-Hoden durchgeführt, die vorher über die a. testicularis perfundiert worden waren. Die Ratten erhielten Cd intraperitoneal als CdCl2 jeweils in Einzeldosen von 1,5, 3,0 und 5,0 mg Cd2+/kg Körpergewicht. 1. Die Untersuchungen an perfundierten Hoden zeigten deutlich, daß die im Hodengewebe bestimmten CAH-Aktivitäten nicht einer Hoden-CAH sondern vielmehr der Erythrocyten-CAH zuzuordnen sind. 2. Bei den Cd-behandelten Ratten beobachteten wir kurze Zeit (0,25–1,0 h) nach der Cd-Zufuhr zunächst reversible Durchblutungsänderungen. Sie bestanden in Abhängigkeit von der Cd-Dosis sowohl in einer vorübergehenden Abnahme (1,5 mg Cd2+/kg) als auch in einer Zunahme (3,0 bzw. 5,0 mg Cd2+/kg) des Hb-Gehaltes im Hoden. 3. Unabhängig von diesen geringfügigen Durchblutungsänderungen kam es später (14–24 h nach 1,5 mg Cd2+/kg, 7–14 h nach 3,0 mg Cd2+/kg und 1–3 h nach 5,0 mg Cd2+/kg) zu den bekannten hämorrhagischen Hodenveränderungen mit einer starken Zunahme des Hb-Gehaltes und der CAH-Aktivität. 4. Anhand der Korrelationen zwischen CAH-Aktivität und Hb-Gehalt im Blut und im Hoden konnte eine Hemmung der CAH als primäre Ursache der Cd induzierten Hodenschäden ausgeschlossen werden.
    Notes: Abstract The cadmium-induced (Cd) damage of mammalian testes is thought to be correlated with an inhibition of carbonic anhydrase (CAH) by Cd. Since Cd causes dose-dependent changes in blood flow of the testes, an inhibition of CAH in the testes could be simulated by a decrease of CAH-rich erythrocytes. Therefore, CAH activities and hemoglobin (Hb) content were determined in blood and testes of untreated and Cd-treated Sprague-Dawley rats as well as in testes perfused via the testicular artery. Cd was intraperitoneally applied as CdCl2 in single doses of 1.5, 3.0, and 5.0 mg Cd2+/kg b.w., respectively. 1. The experiments on perfused testes clearly demonstrated that the CAH activities originate from erythrocytes rather than from a tissue located enzyme. 2. The alterations in blood circulation occurring shortly (0.25–1.0 h) after the Cd administration were characterized by a dose-dependent, transient decrease (1.5 mg Cd2+/kg) as well as an increase (3.0 and 5.0 mg Cd2+, respectively) of the Hb content in the testes. 3. Independent of these minor alterations in a later state (14–24 h after 1.5 mg Cd2+/kg, 7–14 h after 3.0 mg Cd2+/kg, and 1–3 after 5.0 mg Cd2+/kg), Cd induced the well known hemorrhagic alterations of the testes with a high increase of Hb content and CAH activity. 4. By means of the correlations between CAH activities and Hb content in blood and testes an inhibition of the CAH by Cd as the primary cause for the tissue damage of the testes could largely be excluded.
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  • 34
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    Archives of toxicology 36 (1976), S. 31-42 
    ISSN: 1432-0738
    Keywords: Carbromal ; Bromoethylbutyramide ; Ethylbutyrylurea ; Bromide ; Rat ; Humans ; Gaschromatography ; Carbromal ; Carbromid ; Äthylbutyrylharnstoff ; Gesamtbromid ; Ratte ; Mensch ; Gaschromatographie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Interpretation toxischer Effekte von Carbromal erforderte Daten über die im Organismus wirksamen Substanzen. Diese Information kann mit einem einfachen gaschromatographischen Verfahren erhalten werden, mit dem Carbromal und seine sedierend wirksamen Metabolite Carbromid und Äthylbutyrylharnstoff spezifisch, quantitativ und sehr empfindlich in Geweben erfaßt werden können. Bei Einsatz verschiedener Detektorsysteme (Flammenionisations- bzw. Elektroneneinfangdetektor) liegt die untere Nachweisgrenze bei 2–3 nMol der genannten Stoffe je Gramm Gewebe. Die Methode wird in Versuchen an der Ratte demonstriert, bei denen in Serum und Gehirn die Resorption und Elimination von Carbromal einschließlich seiner Biotransformation zu Carbromid und Äthylbutyrylharnstoff verfolgt wurden. Es traten nennenswerte Mengen der Metabolite Carbromid und Äthylbutyrylharnstoffe auf, die sich wie Carbromal gleichmäßig zwischen Serum und Gehirn verteilen, jedoch länger im Organismus nachweisbar waren als Carbromal. Nach Aufnahme einer therapeutischen Carbromaldosis (1 g = 4,22 mMol) durch vier gesunde Versuchspersonen traten 30 min nach Ingestion die höchsten Carbromalkonzentrationen im Serum auf (bis 30 nMol/ml). Sie fielen rasch ab, in 24 Std auf 3–4 % der Höchstwerte. Neben Carbromal fanden sich im Serum 4–5 Std nach Aufnahme erhebliche Mengen von Carbromid (bis 20 nMol/ml), aber nur geringe Mengen an Äthylbutyrylharnstoff (2–3 nMol/ml). Beide Metabolite konnten wie bei der Ratte länger im Serum gemessen werden als unverändertes Carbromal. Parallelbestimmungen des Gesamtbromidgehaltes in Serum und Gehirn der Ratte und im Serum des Menschen zeigten, daß die Konzentrationen der hypnotisch aktiven Substanzen rasch abfielen, während anorganisches Bromid wesentlich langsamer ausgeschieden wurde.
    Notes: Abstract To analyze the toxic effects of carbromal it was necessary to have information on the concentrations of carbromal and of its metabolites in the organism. This information can be obtained by a simple method based on gaschromatography that allows rapid, specific, sensitive and quantitative estimation of carbromal and of its hypnotically active metabolites bromoethylbutyramide and ethylbutyrylurea. Employing different detectors (flame ionisation or electron capture detector) the limit of detection for carbromal and of its two metabolites was 2–3 nmoles/g of tissue. The method was used to study in rats the absoption and elimination of carbromal including biotransformation of carbromal to bromoethylbutyramide and ethylbutyrylurea. Both metabolites, significant amounts of which were found in serum and brain, distribute evenly between serum and brain as does carbromal. Both metabolites were detectable in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of l g (4.2 mmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3–4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2–3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of these metabolites were recorded 4–5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal. Carbromal was given orally to 4 healthy volunteers at a dose of l g (4.2 mmoles). Highest serum concentrations (30 nmoles/ml) were found 30 min after ingestion. Serum concentrations declined rapidly. Twenty-four hours later 3–4% of the values were present in the serum. Beside carbromal considerable amounts (up to 20 nmoles/ml) of bromoethylbutyramide were detected but only small amounts (2–3 nmoles/ml) of ethylbutyrylurea. Peak concentrations of hese metabolites were recorded 4–5 h after ingestion of carbromal. As was the case in rats both metabolites were present in the organism for a longer time than carbromal. Parallel determination of total bromide in rat tissues and in human serum showed that the concentrations of the hypnotically active compounds declined rapidly while inorganic bromide was eliminated much more slowly.
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  • 35
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    European journal of clinical pharmacology 10 (1976), S. 183-187 
    ISSN: 1432-1041
    Keywords: Hydralazine ; bioavailability ; pharmacogenetics ; first pass effect ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary After oral administration of a single 50 mg dose of hydralazine (Apresoline®), the serum half-life (T1/2) and bioavailability (AUC0−∞) were assessed in 16 healthy volunteers. The half-life was 2.57±0.14 h (S.E.) in 10 slow acetylators of sulphadimidine, and 2.18±0.15 h in 6 fast acetylators (difference not statistically significant). AUC0−∞ was significantly higher in slow acetylators, at 1.04±0.10 µg·hour·ml−1, compared to 0.66±0.12 µg·hour·ml−1 in the fast acetylators (p〈0.025). Treatment with Apresoline® 25 mg tid produced minimum serum concentrations at steady-state of 57.3±7.3 ng·ml−1 and 33.4±4.2 ng·ml−1 in 8 slow and 5 fast acetylators, respectively (p〈0.05). The corresponding maximum concentrations were 228.8±20.3 ng·ml−1 and 147.6±15.0 ng·ml−1 in slow and fast acetylators, respectively (p〈0.025). First-pass metabolism of hydralazine could explain the difference in bioavailability of the drug between fast and slow acetylators, without any corresponding difference in the elimination rate of the drug in the post-distributive phase.
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  • 36
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    European journal of clinical pharmacology 10 (1976), S. 337-341 
    ISSN: 1432-1041
    Keywords: Amitriptyline ; pharmacokinetics ; intravenous infusion ; two compartment model ; biological half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.
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  • 37
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    European journal of clinical pharmacology 10 (1976), S. 55-58 
    ISSN: 1432-1041
    Keywords: Penicillin V ; bioavailability ; pharmacokinetics ; dose ranging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary An absorption study was performed in ten healthy volunteers to test the bioavailability of various doses of two penicillin V-K preparations: Isocillin® (Hoechst AG, Federal Republic of Germany), — tablets of 600 000 and 1.2 Mega U; V-Cillin® (Eli Lilly, USA), — tablets of 200 000, 400 000 and 800 000 U. The serum concentrations and elimination of the active substance in urine were measured for six hours after administration. Independently of the source of the preparation, a strict linear relation between the dose and the area under the serum curve (AUC), or between the dose and the urinary elimination, was demonstrated by regression analysis. The dose-dependent increase in the AUC was highly significant (p〈0.01) in the range tested, i.e. between 200 000 and 1.2 Mega U. The relative elimination of active substance in urine lay within narrow limits for all doses (35.7–41.3%). Thus, both compounds proved to have the same bioavailability.
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  • 38
    ISSN: 1432-1041
    Keywords: Ampicillin ; bioavailability ; pharmacokinetics ; branded products ; proprietary preparations ; capsule formulation ; tablet formulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and bioavailability of three different brands of ampicillin were studied in 10 volunteers. After intravenous administration ampicillin can be described adequately by a two-compartment open pharmacokinetic model. The half-life during the α-phase was 9 min and the β-half-life was in the range 50–60 min, independent of the mode of administration. Absolute bioavailability was determined from the ratio of the areas under the serum concentration curves obtained after oral and intravenous administration of equal doses. Bioavailability was also estimated by analysis of variance. The results indicated absolute availability of the three products of 39–54%. One of the products, a capsule formulation, showed a significantly lower bioavailability than the others, which were tablet formulations.
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  • 39
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    European journal of clinical pharmacology 10 (1976), S. 263-271 
    ISSN: 1432-1041
    Keywords: Butobarbital ; pharmacokinetics ; plasma concentration ; oral administration ; accumulation ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in five healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to one-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6 to 41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20–25% of its initial value, probably because of enzyme induction. It was concluded that butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.
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  • 40
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    European journal of clinical pharmacology 10 (1976), S. 293-295 
    ISSN: 1432-1041
    Keywords: Bendroflumethiazide ; diuretics ; GLC ; thiazides ; plasma level ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A GLC method for determination of bendroflumethiazide has been developed, using extractive methylation. Cyclopenthiazide was used as internal standard. The maximal plasma concentration (56–107 ng/ml) after bendroflumethiazide 10 mg given orally to four healthy volunteers was seen at 2–2.5 h. On the slope between 4 and 10 h T1/2 averaged 2.7 h.
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  • 41
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; drug interaction ; phenprocoumon ; pharmacokinetics ; pharmacodynamics ; sulphonylureas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various antidiabetic treatments on the kinetics and efficacy of a single oral dose of 12 mg phenprocoumon were studied in 71 hospitalized patients, 58 with adult-onset diabetes mellitus and 13 non-diabetic aged patients, and 13 healthy young volunteers. Treatment for one week or longer with insulin or the antidiabetic sulphonylureas tolbutamide, glibenclamide or glibornuride, altered neither the plasma level (1.29 – 1.40 µg/ml at zero time) nor the half-life of phenprocoumon (5.2 – 6.8 d) compared to treatment by diet alone. The mean half-life of phenprocoumon was significantly shorter in non-diabetic aged patients (4.2 d) than in diabetic patients of the same age (5.1 – 6.8 d), or in young healthy volunteers (5.7 d). The efficacy of a single dose of phenprocoumon (maximal reduction of Quick-values by 34 – 47% after 48 to 72 hrs) in diabetic patients treated with diet, or diet and antidiabetic drugs, was the same as in non-diabetic aged patients. In healthy young volunteers phenprocoumon was half as effective as in aged patients.
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  • 42
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    European journal of clinical pharmacology 10 (1976), S. 63-68 
    ISSN: 1432-1041
    Keywords: Phenazone ; pharmacokinetics ; injuries ; surgery ; operation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The elimination rate of phenazone after a single oral dose has been studied before and after elective operations. In a group of patients with different illnesses the elimination rate was increased on the fourth to seventh days after operation but was unchanged on the second and third days. The change in elimination rate was highly significant in a standardized group of nine patients with a ligament injury in one knee studied on the fourth or fifth postoperative day. Possible reasons for the changes are discussed.
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  • 43
    ISSN: 1432-2072
    Keywords: Response inhibition ; Taurine ; DRL schedule ; Rat ; Response transients ; Defecation ; Frustration ; Temporal discrimination ; Sudden reinforcement schedule changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats habituated to DRL 6-s schedules that required response inhibition in order to obtain reward did not alter their total responses or efficiency ratios (response/reinforcement) when placed ad libitum (orally) on 0.9% taurine (1.1±0.4 g/kg/24-h) relative to controls. In three separate experiments, taurine-administered rats did show significantly poorer adjustment profiles (higher response/reinforcement ratios) during the 15 min immediately following step-like increases in inhibition time demand to DRL 12 s. The effect was transient and was not significant in subsequent sessions. Taurine rats had been habituated to a DRL schedule intended to induce ‘frustration’ before the step-change did not differ from the taurine group maintained on the normal DRL schedule. No significant differences were noted between taurine and control groups, either before or after taurine administration or before or after the step-change in inhibition demand, with respect to defecation in the test chamber, daily fluid consumption, body weight or total responses. We concluded that oral taurine may inhibit learning during labile periods of adjustment following sudden changes of input demand but does not influence a well learned or established response pattern. These results imply taurine's role in the brain as a ‘stabilizer’ against short-term input fluctuations.
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  • 44
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    Psychopharmacology 50 (1976), S. 95-102 
    ISSN: 1432-2072
    Keywords: Prostaglandins A1, E1, E2, F1α, F2α ; Intraventricular administration ; Rat ; Narcosis ; Catalepsy ; Amphetamine ; α ; MT ; PCPA ; Biogenic amines ; Turnover
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostaglandins (PGs) injected into the right lateral brain ventricle (i.v.c.) of the rat increased the sleeping time induced by hexobarbital, chloral hydrate, and ethanol. PGE1 and PGE2 intensified chlorpromazine-induced catalepsy, inhibited amphetamine hyperactivity, and significantly depressed the amphetamine-induced stereotypy. NA concentrations were decreased by PGE1 and PGE2 and were increased by PGF2α. PGF2α increased both 5-HT and 5-HIAA levels in rat brain. “Total” ACh concentrations were increased by PGF1α and PGF2α. PGE1, PGE2, and PGF2α enhanced the turnover of NA, DA, and 5-HT. PGE2 counteracted the decreased activity induced by α-MT and abolished the hypothermic action of α-MT. PGF2α had little effect on the activity of PCPA pretreated rats, whereas the higher doses of PGF2α increased body temperature in these animals.
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  • 45
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    Psychopharmacology 48 (1976), S. 153-158 
    ISSN: 1432-2072
    Keywords: Ethanol ; Tolerance ; Rat ; Behavioral augmentation ; Rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The phenomenon of behavioral augmentation of tolerance (BAT) to ethanol (EtOH) in the rat was replicated in studies using the moving belt test of intoxication. Rats performing the test daily under the influence of EtOH (2.2 or 2.5 g/kg i.p.) developed tolerance more rapidly than those receiving the same dose after each daily session on the belt. However, both groups reached the same maximum level of tolerance. Acceleration of tolerance by BAT was proportional to the frequency of performance under the influence of EtOH when total exposure to EtOH was held constant. The degree of tolerance produced by BAT could not be increased by daily gavage with a large dose (6 g/kg) of EtOH. After termination of EtOH administration, tolerance produced by BAT was lost at the same rate, whether or not daily alcohol-free sessions on the belt test were given. These findings are consistent with the hypothesis that BAT and conventionally produced tolerance differ only in rate.
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  • 46
    ISSN: 1432-2072
    Keywords: Locomotor activity ; Tyrosine hydroxylation ; Catecholamines ; Ontogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A combined biochemical and behavioral study was performed postnatally on albino rats. An almost linear increase in total motor activity was observed from 1 to 15 days of age followed by a pronounced decrease in motor activity between days 15 and 18. The in vivo rate of tyrosine hydroxylase activity in whole brain was estimated by means of measuring accumulation of L-3,4-dihydroxyphenylalanine (Dopa) after administration of an inhibitor of aromatic amino acid decarboxylase NSD 1015. Additionally, Dopa accumulation was studied in regional brain areas in 10 and 14-day-old animals. A slight gradual increase in the amount of Dopa accumulation in whole brain was observed from 1 to 10 days of age, followed by a pronounced increase between 10 and 14 days. Regional studies revealed that the increase in Dopa accumulation was primarily located to striatum. The data suggest an involvement of central catecholamine neurons possibly dopaminergic, terminating in striatum. The decrease in motor activity observed after 15 days of age is interpreted as involvement of maturing inhibitory pathways of noncatecholaminergic origin.
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  • 47
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    Psychopharmacology 46 (1976), S. 103-109 
    ISSN: 1432-2072
    Keywords: Clozapine ; Rat ; Brain ; Tryptophan ; Serotonin ; Neuroleptic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleepinducing properties of this drug.
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  • 48
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    Naunyn-Schmiedeberg's archives of pharmacology 292 (1976), S. 267-270 
    ISSN: 1432-1912
    Keywords: Rat ; Hamster ; Hepatic microsomal drug metabolism ; Glucocorticoid interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of some glucocorticoids on hepatic microsomal biphenyl and aniline hydroxylations were investigated in rat and hamster. Steroids were either added to the standard incubation mixture or given as a single dose intraperitoneally before preparation of the liver microsomes for enzyme determination. The addition of steroids in vitro enhanced biphenyl-2-hydroxylation activity in hepatic microsomes of rat but not of hamster and the most pronounced effect was obtained with betamethasone. A similar species difference in the effects of betamethasone on this enzyme was also observed after administration of a single dose of the steroid in vivo.
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  • 49
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    Naunyn-Schmiedeberg's archives of pharmacology 293 (1976), S. 277-283 
    ISSN: 1432-1912
    Keywords: Pentetrazol ; Rat ; Pharmacokinetics ; Food ; Smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It was the aim of this investigation to find out why pentetrazol (PTZ) administered orally to rats has considerably lower convulsive effectiveness than PTZ injected parenterally. It could be demonstrated that PTZ is distributed to and eliminated from all organs analyzed, without any sign of storage or of redistribution. Biological halftime was found to be about 3.5 h after subcutaneous injection. PTZ is absorbed slowly from the gastrointestinal tract because PTZ given orally is retained in the stomach for many hours. PTZ absorption is slow from the stomach while it is rapid from the small intestine. Food taken in before and after PTZ administration decreases the rate of PTZ absorption. Retention in the stomach of PTZ given orally is probably due to delayed gastric emptying since PTZ is able to reduce the basal tone and the acetylcholine-induced contractions of isolated preparations of the fundus of the stomach.
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  • 50
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    Cell & tissue research 171 (1976), S. 285-296 
    ISSN: 1432-0878
    Keywords: Prostate ; Rat ; Castration ; Nuclear alterations ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The fine structure of the nuclei of epithelial cells of the dorsal lobe of the rat prostate were studied 2, 3, 5, 7 and 21 days after castration. The nucleolus appears to undergo a progressive disorganisation with partial fragmentation and dispersion of its normal components. Changes in the nucleoplasm were primarily reflected by a condensation of chromatin, particularly along the nuclear membrane and adjacent to the nucleolus. Later, different types of intranuclear inclusions were observed. After 21 days, the nuclei were characterized by an irregular outline with large indentation. Within the nucleoplasm aggregates of coarse granular chromatin were found. No cell necrosis was observed, indicating that androgen deprivation results in a remodeling of the cell to a less active state with marked cellular alterations and cessation of secretion, but apparently with some of their basic functions still intact. Injections of testosterone completely reverse the castrated-induced alterations. The changes observed are assumed to be due to the withdrawal of the androgenic stimulus, with a direct influence on the secretory function of the cell. The findings support the view that the stimulating secretory effect of androgen is mediated via an intranuclear androgen receptor, probably located in the nucleolus-associated-chromatin. It is also proposed that the secretory function of the epithelial cells of the prostatic complex, initiated by androgens, may be regulated by an intranuclear secretory center.
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  • 51
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    Cell & tissue research 173 (1976), S. 529-542 
    ISSN: 1432-0878
    Keywords: Capillaries ; Cerebral cortex ; Endothelial cells ; Intraendothelial lumen ; Interendothelial lumen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Developing blood vessels in rat cerebral cortex were studied at a number of stages between 3 and 28 days postnatal, in an attempt to obtain data on the mechanisms by which the lumen is established within cords of mesodermal cells. A combination of techniques was utilized in an attempt to elucidate these mechanisms. These were: (a) aldehyde fixation and block staining with phosphotungstic acid; (b) aldehyde perfusion followed by perfusion of a lead solution and post-fixation in osmium tetroxide; (c) conventional preparation of tissue with aldehyde and osmium fixation. Support for interendothelial lumen formation was readily forthcoming, including vessels with junctions between two or more endothelial cells cut transversely. There was some support for intraendothelial lumen formation, in the form of “seamless” endothelial cells. Other features noted included the presence of free ribosomes and vacuoles in the endothelial cells, endothelial flaps, sprouts and tendrils, intraluminal debris, endothelial degeneration and a junction with a nonendothelial cell. Large numbers of endothelial vacuoles were noted, many of them occurring at the abluminal edge of the cells. These vacuoles may be involved in the formation of intraendothelial lumina and also in the enlargement of both types of lumina. This study provides evidence that besides the well-established inter-endothelial lumen formation, intraendothelial mechanisms may also be operative in rat cerebral cortex. The techniques employed in this study offer the potential for clarifying these and related issues.
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  • 52
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    Cell & tissue research 168 (1976), S. 261-270 
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Exercise ; Rat ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Four groups of male rats were exercised for periods of 2, 4, 6, and 8 weeks with controls in each group. As a result of chronic exercise there was an increase in the width of the zona fasciculata of the adrenal cortex. Also, there was an increase in the number and size of the mitochondria, and an increase in the quantity of smooth endoplasmic reticulum, and during the first 4 weeks of exercise an increase in the number of lipid droplets in the zona fasciculata. The close relationship between the smooth endoplasmic reticulum and the mitochondria, and the relationship between the smooth endoplasmic reticulum and the lipid droplets suggests a possible means for a transport mechanism for movement of precursors between these organelles.
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  • 53
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    Cell & tissue research 168 (1976), S. 303-314 
    ISSN: 1432-0878
    Keywords: Supraependymal cells ; Third ventricle ; Hypothalamus ; Hypophyseotropic area ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The supraependymal cells (SEC) are a normal component of the wall of the cerebral ventricles. In the hypothalamic area of the third ventricle they are restricted, in healthy animals, to the ependymal projection of the hypophyseotropic area. Here the SEC show great polymorphism. In addition to bipolar, multipolar and stellate or spider-like cells, transitional forms between these types can be seen. Their perikarya and processes can either remain at some distance from the ependyma or be in close contact with it. The processes may protrude between the ependymal cells or show surface differentiations that resemble the thin cytoplasmic folds of the mesenchymal wandering cells. Considering this and the variations in the number of cells, for example during the ovarian cycle, the SEC can be interpreted as mesenchymal cells, probably related to microglial cells of the subependymal layer. It is suggested that the SEC have a phagocytotic function and may be involved in the normal renewal of the ependyma. A definitive explanation for the restriction of the SEC to the hypophyseotropic area as well as the elucidation of their function remain to be found.
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  • 54
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    Cell & tissue research 168 (1976), S. 117-131 
    ISSN: 1432-0878
    Keywords: Retino-hypothalamic projection ; Suprachiasmatic nucleus ; Rat ; Axonal iontophoresis/cobalt precipitation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The technique of cobalt sulfide precipitation combined with Timm's sulfide-silver method for intensification of heavy metals was used to delineate the retino-hypothalamic projection of the rat. Freshly isolated rat brains were dissected and a solution of cobaltous chloride was applied to one of the cut optic nerves. Sixteen hours later, after cobalt ions had passed into the brain along the entire length of the optic fibers, the preparation was treated with ammonium sulfide to precipitate the cobalt as cobalt sulfide. In thick light microscopic sections, cobalt-filled axons were visualized as black fibers against a light gold background. Such fibers were observed to leave the posterior medial portion of the optic chiasm and, after arching dorsally, to project into the posterior fifth of the suprachiasmatic nucleus (SCN), as well as into the rostral part of the arcuate nucleus. Neither bifurcation of these axons nor looping of the axons back to the chiasm was seen. Most fibers projected to the SCN contralateral to the filled nerve, but the projection represented less than 0.1 % of the total number of fibers in one optic nerve. These observations are considered to be graphic evidence of a retino-hypothalamic projection. The interpretation of the cobalt method is discussed, as are the functions of the connections that have been observed.
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  • 55
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    Cell & tissue research 170 (1976), S. 43-60 
    ISSN: 1432-0878
    Keywords: Interdigitating cells ; Lymph node ; Rat ; Ultrastructure ; Cytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Electronmicroscopic and cytochemical studies were performed to localize interdigitating reticulum cells (IDC) in the popliteal lymph node of the rat. The morphological features of the IDC of the rat correspond to those described for other species, but also show similarities to normal macrophages in the rat. This is considered to be an argument in favour of the common origin of IDC's and macrophages. Ultrahistochemical studies with horseradish peroxidase (HRP) reveal no phagocytotic capacity of IDC's. After perfusion fixation containing ruthenium red (RR) the surface coat stains heavily: RR is also found deep in the membrane invaginations of the IDC, indicating the presence of polyanionic sialoglyco-proteins. The post-capillary-venules (PVC) are very permeable to both HRP and RR. The phosphotungstic acid-chromic acid stain (PTA-CrA) also reveals glycoproteins in the surface coat; these glycoproteins are susceptible to α-neuraminidase, whereas glycoproteins in the Golgi complexes, lysosomes and in the vesicular complexes of IDC are not. The glycoproteins of the latter are susceptible to 0.1 N NaOH. These findings indicate that IDC produce different kinds of glycoprotein, one of which may be secreted and act as a factor for stimulating peripheral T-lymphocytes. Intimate contact between IDC's and PCV's could be observed. It is therefore conceivable that IDC's play an important role in the homing of T-lymphocytes.
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  • 56
    ISSN: 1432-0878
    Keywords: Median eminence ; Rat ; Monoamine ; ZIO reaction ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The reaction of nerve endings in the median eminence of the rat to zinc iodide-osmium tetroxide (ZIO) staining was examined electron microscopically under normal and experimental conditions. The experimental condition of catecholamine exhaustion in the nerve endings was induced by the administration of H44/68 and reserpine. Vesicles in the terminals of catecholaminergic nerves reacted similarly to ZIO staining in both normal and experimental material. The majority of synaptic vesicles in various terminals gave a positive ZIO reaction. The neurosecretory elementary granules, however, failed to react with ZIO. On the other hand, some nerve terminals in the external layer of the median eminence showed a strong positive reaction in the cytoplasmic matrix, in mitochondria as well as in synaptic vesicles. These findings strongly suggest that the ZIO-positive substance in nerve terminals is not the transmitter itself, i.e. the monoamine, but rather represents a range of substances commonly found in various kinds of synaptic vesicles and is probably proteinaceous in nature. A brief discussion is also given on the difference in ZIO reactivity between neurosecretory elementary granules and small vesicles in the hypothalamo-hypophyseal tract.
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  • 57
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    Cell & tissue research 166 (1976), S. 407-412 
    ISSN: 1432-0878
    Keywords: Pituitary primordium ; Cytodifferentiation ; Rat ; Organ culture ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Rathke's pouches isolated from rat fetuses on day 12 were maintained in organ culture for 9 days and investigated immunohistochemically to test whether or not the hypothalamus is involved in the cytodifferentiation of the adenohypophysis. The unlabeled antibody enzyme method demonstrated that the cultured tissue contains different types of glandular cells, i.e., adrenocorticotropin (ACTH)-, growth hormone (GH)-, luteinizing hormone (LH)-, thyrotropin (TSH)-, and prolactin-producing cells. Indirect evidence was also obtained to indicate the presence of melanocyte stimulating hormone (MSH)-cells. These findings suggest that adenohypophysial primordial cells of rats start to synthesize their respective hormones without stimuli from neurosecretory substances of the brain which are known to be essential for the maintenance of the secretory activity of the adult gland.
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  • 58
    ISSN: 1432-0878
    Keywords: Microtubules ; Tractus hypophyseus ; Diabetes insipidus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Evidence has already been adduced suggesting that an increase in microtubular number occurs in the tractus hypophyseus of rats stressed by the administration of hypertonic saline, and of rats with congenital diabetes insipidus (CDI). Since the tractus hypophyseus in these animals shows high secretory activity, it seems likely that the microtubular increase reflects the participation of microtubules in axoplasmic transport. To exclude, however, a congenital microtubular abnormality in CDI, affected newborn rats were examined. In these, the microtubular number was normal, thus suggesting that the increase in microtubular number seen in adult animals was not a congenital morphological abnormality. However, by 4 days of age there was a slight but statistically significant increase in microtubular number in affected rats, a change probably attributable to increased secretory activity.
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  • 59
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    Cell & tissue research 171 (1976), S. 375-379 
    ISSN: 1432-0878
    Keywords: Corpus luteum ; Autografts ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rat ovary has been transplanted successfully to subcutaneous tissue areas by several investigators. Light microscopy has revealed that corpora lutea in ovarian autografts are formed by luteinization of intact follicles and contain entrapped ova. In the present study, corpora lutea from autografted ovaries in castrate rats were obtained at metestrus and examined electron microscopically to determine whether their cellular morphology correlated with the normal progesterone levels in these animals. Cellular features usually accepted as regressive were apparent. The findings suggest either structural luteolysis is occurring before functional luteolysis or that the adrenal has increased steroidogenic activity in the castrate with ovarian autografts to account for the normal progesterone levels.
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  • 60
    ISSN: 1432-0878
    Keywords: Portal vein ; Rat ; Adrenergic innervation ; Postnatal ; Ontogenesis ; Histofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The postnatal development of the adrenergic innervation pattern in the rat portal vein has been studied with the histochemical fluorescence method of Hillarp and Falck. Stretch preparations and transverse freeze-dried sections of intact portal veins were studied from rats during the first 5 weeks of life and from adult rats. Orientation of undifferentiated smooth muscle cells into two layers was observed at 4 days of age. Dominance of the thick outer longitudinal muscle layer was apparent at two weeks of age. A terminal adrenergic nerve plexus with some varicosities was restricted outside the media at the end of the first week. Ingrowth of penetrating non-terminal adrenergic nerve fibers through the longitudinal muscle layer occurred during the second week of age when the main terminal nerve plexus was developing between the two muscle layers. After 3 weeks of age the adult pattern of a two-dimensional adrenergic plexus between the muscle was established. In the adult rat pharmacological treatment with nialamide and noradrenaline revealed the thin, penetrating non-terminal adrenergic nerve fibers in the longitudinal muscle layer which were poorly visible otherwise. The present observations strongly indicate that the main adrenergic plexus between the two muscle layers emanates directly from the outer axonal plexus. These findings are discussed regarding possible trophic interactions between ingrowing sympathetic adrenergic vasomotor nerves and maturing vascular smooth muscle.
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  • 61
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    Cell & tissue research 172 (1976), S. 195-203 
    ISSN: 1432-0878
    Keywords: Spleen ; Rat ; Marginal sinus ; Marginal zone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The marginal sinus in the spleen of the Wistar rat surrounds the follicle and has more numerous PAS positive fibers on the inner wall than on the outer wall. India ink- and lead oxide-gelatin were injected into the abdominal aorta. It was found that much of the india ink-gelatin accumulated in the marginal sinus, the marginal zone, and part of the red pulp, while most of the lead oxide-gelatin collected in the marginal sinus. Ultrastructurally, the capillaries of the follicle were found to open into the marginal sinus. Regions not perforated by the marginal sinus lie between the follicle and the marginal zone. The wall of the marginal sinus is discontinuous and the discontinuities are wider on the marginal zone side than on the follicle side. The relationship of these findings is discussed.
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  • 62
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    Cell & tissue research 173 (1976), S. 1-15 
    ISSN: 1432-0878
    Keywords: Carotid body ; Rat ; Innervation ; Three-dimensional reconstruction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The innervation of the carotid body of adult rats was studied by means of serial ultrathin sections. A single branching nerve fiber innervates 12 chief cells through several kinds of terminals (vesicle-containing, mitochondrial sack, and calyx-type) in en-passant and bouton forms. Two types of synaptic contacts between nerve terminals and chief cells are found; type 1 in which chief cells are postsynaptic, and type 2 in which chief cells are presynaptic. Since a single nerve fiber (possibly from the glossopharyngeal nerve) forms both types of synapses with type 2 predominating, the nerve fiber is considered basically sensory or centripetal. In addition to their synaptic connections with sensory nerve fibers, chief cells located in the periphery of this organ are in synaptic relation with dendrites of a few ganglion cells adjacent to these cells. Here the chief cells are presynaptic. A few synaptic contacts between two adjacent chief cells are seen, and so are direct contacts between chief cells and preganglionic efferent nerve fibers terminating on ganglion cells.
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  • 63
    ISSN: 1432-0878
    Keywords: Exocytosis, endocytosis ; Freeze-etching ; Electron microscopy ; Membrane particles, rosettes ; Neurohypophysis, neurosecretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Images have been obtained from freeze-etch replicas of neurohypophyses which are consistent with the view that orderly arranged aggregates of membrane particles occur in regions where fragments of membrane are being added to and taken away from the plasma membrane during secretion. Aggregates of particles included rosette-like and necklace-like patterns similar to those described by other authors at sites of exocytosis and endocytosis.
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  • 64
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    Cell & tissue research 165 (1976), S. 239-248 
    ISSN: 1432-0878
    Keywords: Superior cervical ganglion ; Rat ; Catecholamines ; Paraganglionic cells ; Monoamine synthesis inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Monoamine storage sites in paraganglionic (PG-)cells of the rat superior cervical ganglion were investigated by electron and fluorescence microscopy following treatment with p-chlorophenylalanine (pCPA), disulfiram or guanethidine respectively. Dense core vesicles in PG-cells are significantly decreased (p〈 0.001) in number following pCPA, and in the majority of these cells following disulfiram and guanethidine. However in a minor portion of PG-cells the latter agents cause an increase in number and in size of dense core vesicles, in parallel with structural alterations. In agreement with these electron microscopic findings fluorescence microscopic and cytophotometric evaluations reveal a general decrease in catecholamine content with few cells showing an increase. The findings provide a morphological basis for the assumption, that monoamine storage sites in PG-cells can be decreased by inhibition of monoamine synthesis, following administration of pCPA, disulfiram and guanethidine. However the two types of responses of PG-cells which occur after disulfiram and guanethidine demonstrate a functional heterogeneity of this cell system in the rat superior cervical ganglion which is discussed.
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  • 65
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    Cell & tissue research 166 (1976), S. 135-143 
    ISSN: 1432-0878
    Keywords: Synaptic ribbons ; Pineal organ ; Rat ; Ultracytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The synaptic complexes of the rat pinealocytes are neither cholinergic nor adrenergic. In the synaptic vesicles, a neurotransmitter carrier substance of lipid nature reacting with OsO4-Zn I2 mixture (similar to that present in both cholinergic and adrenergic vesicles) was not found. In addition, there were no indications of glucose-6-phosphatase or thiamine-pyrophosphatase activity in the synaptic vesicles. Thus, it appears that the synaptic vesicles do not originate from the rough or smooth endoplasmic reticulum. The synaptic ribbons do not contain carbohydrates, are of protein nature and possess some chemical resemblance to microtubules and microtubular bouquets. Appropriate ultracytochemical reactions have not shown detectable quantities of sodium and calcium ions in pinealocyte synaptic complexes.
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  • 66
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    Cell & tissue research 168 (1976), S. 411-418 
    ISSN: 1432-0878
    Keywords: Luteinizing hormone-releasing hormone ; Hypothalamus ; Rat ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of radioactivity in the rat hypothalamus after intraventricular injection of tritiated luteinizing hormone-releasing hormone (LH-RH) was studied by autoradiography and compared with that expected from Fick's second law which defines the character of ordinary diffusion. The results suggest that LH-RH penetrates through the ependyma and thin subependymal layer in the median eminence and into the suprachiasmatic area by ordinary diffusion. By contrast, concentration of radioactivity in outer layers of the median eminence is increased and, therefore, can not be explained by the diffusion law. In this region incorporation of radioactivity into cell bodies was demonstrated. In the subependymal layer of the median eminence a few rows of silver grains seemingly located in cellular processes were also observed. The diffusion coefficient in the periventricular zone was lower than that in the deeper tissue. It is suggested that the ependymal-subependymal complex of the third and lateral ventricles acts as a passive membrane towards LH-RH contained in the cerebrospinal fluid. The significance of this mechanism for the intrahypothalamic transport of RHs is discussed.
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  • 67
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    Cell & tissue research 168 (1976), S. 549-559 
    ISSN: 1432-0878
    Keywords: Hypothalamic-hypophysial-adrenal axis ; Rat ; Development ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The adrenal glands of decapitated and encephalectomized fetal rats were investigated electron microscopically and compared to those of normal intact fetal rats. Although the adrenal cortices did not show three zones (zona glomerulosa, fasciculata, and reticularis) on the 16.5th day of gestation when the decapitation or encephalectomy was carried out in utero, the zonation was recognized in fetuses operated on the 21.5th day of gestation. The same was true for normal control fetuses. However, cytoplasmic characteristics suggesting steroidogenesis in the cortical cells were reduced to various degrees in the encephalectomized or decapitated fetuses, especially in the latter ones. The change in cytoplasmic appearance was more conspicuous in the inner portion of the cortex. This result suggests that for the maintenance of normal adrenocortical function the hypothalamus may be indispensable even during the prenatal life of rats.
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  • 68
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    Cell & tissue research 173 (1976), S. 179-191 
    ISSN: 1432-0878
    Keywords: Epiglottis ; Rat ; Elastic cartilage ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Chondrocytes of the rat epiglottis contain large amounts of glycogen and lipids, which often make the cells resemble fat cells. The content of lipids is interpreted as being related to the function of the cells. The membranes of some of the large vacuoles are stained with ruthenium red. The cells give rise to long cytoplasmic processes. As in hyaline cartilage the intercellular substance consists of a fine network containing proteoglycan granules together with thicker cross striated fibers. Furthermore elastic fibers are found, consisting of amorphous and microfibrillar parts. In the matrix, both lysosome-like granules and more or less empty vesicles are observed. Accumulations of a finely particulate electron dense material and of a translucent amorphous material containing membrane bound granules are found in some lacunae situated in the outer part of the cartilage. These accumulations are possibly related to the development of collagenous and elastic fibers.
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  • 69
    ISSN: 1432-0878
    Keywords: Liver ; Rat ; Sinusoid ; Pit cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Pit cells — a new type of cell first described here and so named because they contain highly characteristic granules — are situated in the wall of rat liver sinusoids, and have hyaloplasmic pseudopodia intermingling with the microvilli of the parenchymal cells. The characteristic granules are mainly situated at one side of the nucleus, the other side showing organelle-free hyaloplasm. Pit cells are also found in portal tracts and in granuloma-like cellular aggregates. They also occur in rat peripheral blood, although there are morphological differences between cells in these two sites. Pit cells can be regarded as regular inhabitants of the sinusoidal wall, and therefore belong to the series of sinusoidal cells, i.e., the endothelial (Wisse, 1972), Kupffer (Widmann et al., 1972; Wisse and Daems, 1970; Wisse, 1974a,b), and fat-storing cells (Ito, 1973). Pit cells do not phagocytose and do not react to a great number of experimental conditions, to which endothelial and Kupffer cells do react (Wisse, 1972, 1974b). Mitosis has been observed in a pit cell. The function of pit cells remains obscure, but an endocrine function is suggested by the morphology of their highly characteristic granules.
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  • 70
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    Cell & tissue research 173 (1976), S. 543-554 
    ISSN: 1432-0878
    Keywords: Prostate ; Rat ; Dog ; Basal cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the basal cells of rat lateral and ventral prostate and of dog prostate has been studied. Basal cells from both species appear as undifferentiated cells, characterised by a lack of cytoplasmic organelles and a poorly developed Golgi complex and endoplasmic reticulum. The presence of cytoplasmic filaments and micropinocytosis is not considered to be sufficient evidence to assume any similarity to myoepithelium, as has been previously suggested. Basal cells are instead considered to be precursors of secretory epithelial cells.
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  • 71
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    Cell & tissue research 174 (1976), S. 83-97 
    ISSN: 1432-0878
    Keywords: 6-hydroxydopamine ; Extraneuronal effects ; Rat ; Adrenal ; Tissue culture ; Electron microscopy ; Microspectrofluorimetry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The effects of various concentrations of 6-hydroxydopamine (6OHDA) on rat adrenocortical cells in tissue culture were studied with phase contrast and electron microscopy. With 40 mg/l of 6-OHDA the first signs of alteration as revealed by microcinematography appeared in isolated cortical cells as early as 15 min after addition of the drug. There was a cessation of movement of cell organelles and an immobilisation of membrane undulations followed by the development of dark inclusion bodies. The cells underwent increasing shrinkage and collapsed by 11/2 h. Chromaffin cells were not affected until 45 min after exposure to the drug and neurons were the most resistant population. However 61/2 h after application of the drug most cells in the culture were dead. 6-OHDA applied in different doses and to adrenal expiants did not alter the sequence of events. Ultrastructurally cortex cells underwent damage along two lines: they either showed lytic changes or developed various types of dense bodies before reaching the lytic stage. Treatment of cortical cells with 40 mg/l 5-or 6-OHDA followed by exposure to buffered 2% glyoxylic acid and heat did not produce a fluorescence within the cells. Microspectrofluorimetry on amine models with noradrenaline, 5- and 6-OHDA revealed that neither 5-nor 6-OHDA are capable to form a fluorophore with glyoxylic acid.
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  • 72
    ISSN: 1432-0878
    Keywords: Ovarian autografts ; Autonomic innervation ; Ovarian steroids ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Ovaries were removed from female rats and immediately autografted into a subcutaneous pouch in the flank in order to quantitate the relationship of graft re-innervation, steroid secretion and vaginal smear pattern. Animals were killed at three time periods: three days after grafting, on the first day a cornified vaginal smear appeared and at the first metestrus. In addition, control animals were killed at metestrus. Plasma samples were obtained from all rats and analyzed for estradiol-17β and progesterone concentration by radioimmunoassay. At the first day of vaginal cornification after grafting, plasma estradiol-17β (45.8±4.0 pg/ml) was elevated in comparison to controls at metestrus (24.0±2.6 pg/ml), but plasma progesterone (21.5±4.0 ng/ml) was not different (30.6±1.7 ng/ml). Subsequently, at the first metestrus following grafting, plasma estradiol-17β (23.0±3.5 pg/ml) was comparable to control values. In contrast, progesterone was decreased (17.5±1.9 ng/ml). A definite correlation was detected between the vaginal smear and plasma levels of steroid hormones in the castrated female rat with subcutaneous ovarian autografts. Histochemical techniques were used to study the adrenergic and cholinergic innervations of grafts three days after grafting, at the first day of vaginal cornification, and at the first metestrus. No correlation was shown between density of adrenergic or cholinergic innervation and plasma levels of estradiol-17β and progesterone or onset of a cycling vaginal smear.
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  • 73
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    Cell & tissue research 172 (1976), S. 133-144 
    ISSN: 1432-0878
    Keywords: Cornea ; Nerves ; Rat ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ultrastructure of the corneal nerves of the rat was studied in tissue fixed by immersion in and by perfusion with glutaraldehyde-containing fixatives. Of the four types of axonal terminal identified in the nerves, those with the features of adrenergic and cholinergic terminals were confined to the nerves at the limbus and were concentrated in the perivascular plexuses. The remaining two types of terminal were found on axons located in all parts of the cornea and on both intraepithelial axons and axons in the stromal nerves. Of these, one contained the numerous mitochondria which occur in the terminals of axons associated with known mechanoreceptors and the second contained variable and often small numbers of both clear and large dense-cored vesicles. While most of the mitochondria-containing terminals were seen in nerves located near the periphery, vesicle-containing terminals were numerous in all of the nerves, and especially in those in the avascular cornea. In material fixed by immersion in glutaraldehyde-paraformaldehyde, the vesicle-containing terminals appeared to be dilated, but in material fixed by perfusion there was little evidence of any increase in the diameter of the axons in the terminal regions. The structure of the terminals was compared with that of the terminals of axons identified in the nerves of the skin and the urinary tract and the differences in the vesicle content of the terminals to those reported in other studies of the corneal nerves was related to the use of different fixation procedures. The possibility that axons possessing such terminals are identical with the beaded axons and both the cholinesterase-positive and fluorescent axons demonstrated in light microscopical studies of the corneal nerves is discussed, and the widespread distribution of the axons in the cornea is equated with the hypothesis that they are afferent in nature and represent the peripheral receptors for pain impulses.
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  • 74
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 199-230 
    ISSN: 1573-8744
    Keywords: disopyramide ; antiarrhythmic ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of the antiarrhythmic disopyramide, 4-diisopropylamino-2-phenyl-2-(2-pyridyl)butyramide phosphate, and its monodealkylated metabolite were investigated in seven volunteers after intravenous (1 and 2 mg/kg) and oral (3 and 6 mg/kg) administration. Unchanged drug (52%) and the monodealkylated metabolite (25%) were renally excreted on intravenous administration. The pharmacokinetics of disopyramide were first order and dose independent only when referenced to the drug not bound to plasma proteins since this binding was dose dependent. The apparent half-lives of the α and β phases on intravenous administration were 2 min and 4.5 hr, respectively. The apparent volumes of distribution of the central and peripheral compartments, referenced to unbound disopyramide in the plasma, were 9 and 80 liters, respectively. The half-life of absorption of oral aqueous disopyramide phosphate was 30 min with a lag time of 16 min and an apparent first-pass metabolism of 16% of the absorbed dose, consistent with the hepatic efficiency of 14%. The renal and metabolic clearances were 125 and 111 ml/min, respectively. Graphical and computer analysis of the plasma and urine data showed dose-independent first-order pharmacokinetics of plasma unbound drug in a two-compartment-body model to give two metabolites and a first-pass transformation of a fraction of the oral dose. The absorption efficiency of unchanged drug was 83%.
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  • 75
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 337-353 
    ISSN: 1573-8744
    Keywords: bioavailability ; pharmacological data ; pharmacokinetics ; modeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The use of data deriving from monitoring the time variation of the intensity of pharmacological effect(s) following dosing can often present an advantageous alternative to the more conventional approach of using chemical or radiological assay of blood and/or urine level data for bioavailability evaluations of drug products: bioavailability studies can be performed with drugs where no assay exists. A relatively simplified discussion of the general theoretical principles on which the use of pharmacological data is based and a stepwise description of the approach for its routine application in bioavailability studies are presented. Approaches for computing rates and extents of drug bioavailability vs. time profiles on analog and digital computers are qualitatively described and quantitatively presented in a subsequent report. The concept of preabsorption (gastrointestinal bioavailability) is introduced and biophasic availability of drugs to local sites of action is discussed.
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  • 76
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    Journal of pharmacokinetics and pharmacodynamics 4 (1976), S. 355-375 
    ISSN: 1573-8744
    Keywords: deconvolution ; bioavailability ; pharmacokinetics ; modeling ; pharmacological data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mathematical expressions and approaches to the computation of rates and extents of drug bioavailability for implementation on analog and digital computers are derived. The equivalency of expressions derived on the basis of assuming compartment models to an approach based on using experimentally determined weighting functions is demonstrated. The relative merits of the two techniques are discussed: their application for use with temporal pharmacological data is emphasized. The applicability of the computational techniques to determining the availability of drugs at local sites of action (biophasic availability) and to computing preabsorptive drug release into the gastrointestinal contents (gastrointestinal bioavailability) is pointed out. An approach to computationally predicting in vivo blood level or pharmacological response vs. time profiles from in vitro dissolution testing results is presented and its limitations are discussed.
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  • 77
    ISSN: 1573-8744
    Keywords: pharmacokinetics ; compartmental model ; phenol red ; phenol red glucuronide ; dogfish (Squalus acanthias)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A flow-limited multicompartment model simulates the distribution and disposition of phenol red in the dogfish after intravenous administration. Glucuronide conjugate, as well as parent compound, was found in urine and bile, but not in plasma, kidney, or liver tissue. An apparent 4-hr lag in phenol red appearance in the gall bladder was simulated using two stirred tanks connected in series to represent the bile ducts. The model should facilitate use of the dogfish in pharmacokinetic studies of drugs, environmental contaminants, and other xenobiotics.
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    Langenbeck's archives of surgery 343 (1976), S. 267-274 
    ISSN: 1435-2451
    Keywords: Coloncarcinoma ; Cholecystectomy ; Rat ; 1,2-Dimethylhydrazine ; Bile ; Acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die experimentelle Studie gilt dem Coloncarcinom und dem Problem seiner möglichen Entstehung nach einer vorausgegangenen Cholecystektomie. Die Ergebnisse zeigen, daß die 1,2-Dimethylhydrazin (DMH) induzierte Dickdarmkanzerogenese der Maus durch die Entfernung der Gallenblase signifikant gesteigert werden kann. 70% der cholecystektomierten Tiere, denen 10mal 15 mg/kg DMH subcutan injiziert wurde, hatten nach 20 Wochen einen Dickdarmkrebs. Dagegen wiesen nur 16% der nichtoperierten Tiere (bei sonst gleichen Bedingungen) ein Coloncarcinom auf. Als Ursache des karzinogenen Einflusses der Cholecystektomie wird die verstärkte Bildung sekundärer Gallensäuren durch die Darmbakterien, sowie der Fortfall der Resorptionsständigkeit der Gallenblase für lebergängige Karzinogene diskutiert. Den klinischen Hintergrund für diese experimentelle Studie bildet die Tatsache, daß 10% aller Dickdarmkrebskranken in der chirurgischen Anamnese eine Cholecystektomie aufweisen.
    Notes: Summary The influence of cholecystectomy on the development of carcinoma of the colon is investigated. The experimental results show a significant high rate of carcinoma of the colon induced by subcutaneous injection of 1,2-Dimethylhydrazin (DMH) in the mouse after cholecystectomy. After 10 weekly injections of 15 mg/kg DMH 70% of the animals with cholecystectomy developed carcinoma. Only 16% of the mice with similar treatment but without cholecystectomy had carcinoma. The cocarcinogenic effect of cholecystectomy is assumed to be due to the increased production of secondary bile salts by the colonic bacteria and the lacking of the resorptive function of the gall bladder for some carcinogenic substances passing through the liver. The background of this experimental studies is the clinical findings that 10% of patients with carcinoma of the large bowels had a cholecystectomy previously.
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  • 79
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    Biopolymers 15 (1976), S. 1-14 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The template directed synthesis of poly[d(A-T)] from the nucleoside triphosphates in the presence of DNA polymerase I is carried out continuously in a stirred flow reactor for the first time. The initial objective is to test the kinetic stability of the established steady states at various flow rates. Graphical analysis predicts instable steady states for certain high flow rates. As a consequence of instabilities multiple steady states and steady-state hysteresis may occur. Steady-state hysteresis has now been found experimentally. For a different enzyme fraction of low exonuclease activity we found the steady-state absorbance at 260 nm to be almost invariant with flow rate at high enzyme concentrations even if the flow rate was increased by a large factor. We call this phenomenon kinetic buffering. Relaxation of a large flow perturbation approaches the steady state in a sigmoidal fashion. Concentration oscillations at 260 nm occurred in one experiment using an enzyme fraction of low exonuclease activity after perturbing the steady state by monomer (dATP). Advantages of the stirred flow reactor method over serial transfer are discussed.
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  • 80
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The far-ultraviolet circular dichroic spectrum of the 39-residue peptide hormone porcine corticotropin and the biologically active fragment corticotropin 1-24 is negative from 250 nm to 195 nm in water, but in 6M guanidinium chloride a positive band appears at about 225 nm. The temperature and guanidinium chloride dependence of this spectral transition indicates the absence of any stable ordered secondary structure in corticotropin and the spectrum is seen to be in only partial agreement with results using the model peptide chromophore, Ala-Ala-Ala. Using oligopeptides containing aromatic amino acid residues sandwiched between glycyl residues, it is shown that the shape and intensity of the corticotropin 225 nm positive band which appears in 6M guanidinium chloride is in agreement with the far-ultraviolet transitions of the aromatic chromophores in the hormone. Curve resolution of the near-ultraviolet circular dichroic spectrum of corticotropin and comparison of the rotational strengths of the phenylalanyl and tyrosyl bands reveals no evidence for increased rotational freedom in 6M guanidinium hydrochloride. Spectral changes are observed, however, in the transitions arising from the single tryptophan. This study suggests that corticotropin in aqueous solution may serve as a better model for the circular dichroic spectrum of the aperiodic regions in globular proteins than either synthetic homopolypeptides or reference proteins for which spectral and X-ray diffraction data are available.
    Additional Material: 6 Ill.
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  • 81
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    Biopolymers 15 (1976), S. 131-152 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An all-order classical coupled oscillator theory in which monomer band shapes are explicity taken into account is applied to the calculations of polynucleotide circular dichroism. Calculations are shown for ApA and oligoadenylic acid of varying chain lengths, in both RNA and B-DNA geometry, and the advantages of this theory are assessed. By introducing an effective dielectric constant, good agreement with measured spectra is obtained. Variations in monomer parameters are tested in an attempt to eliminate remaining discrepancies between calculated and measured spectra.
    Additional Material: 6 Ill.
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  • 82
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    Biopolymers 15 (1976), S. 203-218 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Raman Spectra of bovine serum albumin have been obtained in the solute state, in alkaline and acidic solutions, and in the gel. The reversible denaturations of bovine serum albumin solutions by heat, acid's, and alkali were studied and a new mechanism for heat denaturation has been proposed based on a continuous unfolding of the α-helices.
    Additional Material: 10 Ill.
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  • 83
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    Biopolymers 15 (1976), S. 219-225 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: New techniques in laser Raman spectroscopy are used to obtain spectra of aqueous solutions of lysozylme for frequency shifts as small as 5 cm-1. In addition, Raman measurements are made on two crystalline forms of hen egg white lysozyme. The spectra obtained from the solution and from the crystal are found to be similar for frequencies above 100 cm-1. However, a low-frequency band at 25 cm-1 observed in crystalline lysozyme is not found in the solution, indicating that this band cannot be attributed to an internal molecular vibration.
    Additional Material: 4 Ill.
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  • 84
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    Biopolymers 15 (1976), S. 257-263 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The adsorption of protein films on polystyrene latex spheres was studied by optical mixing spectroscopy. With this technique, we show that both the hydrodynamic thickness of protein films and their optical density can be measured. Thus, we found that films of the glycoproteins isolated from the human erythrocyte membrane were four times as thick as films of either human serum albumin or bovine serum albumin for about the same surface coverage. This result suggests an end-on orientation for the adsorbed glycoprotein molecules, which is consistent with the model proposed by others for the orientation of these molecules at the surface of the red blood cell itself.
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  • 85
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    Biopolymers 15 (1976), S. 293-299 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Solvent binding to bovine serum albumin in 2-chloroethanol-water mixed solvents of different composition, measured previously by Inoue and Timasheff (Biopolymers (1972) 11, 737-43) is applied to a hydrodynamic study of the solvated protein.From sedimentation and diffusion data, the apparent molecular weight of the solvated protein particle can be calculated, provided an average partial specific volume, computed from the composition of the particle, is introduced in Svedberg's equation. The unsolvated molecular weight of the protein can than be calculated by subtraction of the bound solvent. Further data on the hydrodynamic particle (f/fmin and axial ratio of the equivalent ellipsoid) are readily calculated from these experiments, and reinforce the supposition that 2-chloroethanol is a strong helix-inducing solvent.
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  • 86
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    Biopolymers 15 (1976) 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 87
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    Biopolymers 15 (1976), S. 403-414 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We have carried out a detailed study of ligand binding of ferrihemoglobins under various conditions. Our results show that n varies with time and that this variation is paralleled by changes in the spectrum of methemoglobin. This suggests some form of structural perturbation. The time-dependent value of n is discussed in terms of the observed spectral changes accompanying prolonged equilibration.
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  • 88
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    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The nmr titration curves of chemical shifts versus pH were observed for the protons of various histidine-containing di- and tripeptides. With these results, the macroscopic pKa values and the chemical shifts intrinsic to each ionic species were determined by a computer curve-fitting based on a simple acid dissociation sequence. The pKa value of the imidazole ring in N-acetyl-L-histidine methylamide was assumed to represent the intrinsic (or unperturbed) pKa of the imidazole rings of histidine having peptide linkages at both the CO and NH sides. The pKa values of the imidazole rings observed for most di- and tripeptides were reasonably reproduced by simple calculations using the intrinsic value and the perturbations due to the CO2- and NH3+ groups located at various positions. Some other factors affecting the pKa value of the imidazole ring are also discussed.
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  • 89
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    Biopolymers 15 (1976) 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 90
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The hyperchromic and hypochromic changes in the intensity of the amide-I and amide-III lines of polypeptides and certain ring vibrations of the bases of polynucleotides are shown to be related to similar changes in the lower energy uv absorption bands. The selection rules strictly limit the pairs of excited electronic states that can contribute to the elements of the polarizability matrix. An energy-dependent term in this equation weights the contribution of the pairs of electronic transitions in favor of those involving the lower energy transitions. For both polypeptides and polynucleotides, there is a large hypochromic inensity change in the first π → π* exciton band upon the coil-to-helix transition. Through the selection rules, certain conformationally sensitive Raman lines are shown to derive their intensity predominantly from this band and hence also display hypochromism. Again, through an application of the selection rules, certain Raman lines can be demonstrated to depend predominantly for their intensity upon the n → π* transition, and consequently have the opposite hyperchromic intensity change upon the same conformational transition.
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  • 91
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    Biopolymers 15 (1976), S. 301-315 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Transient electric birefringence experiments have been performed on well-characterized highly monodisperse samples of tobacco mosaic virus (TMV). Experiments and calculations are presented that show that the sensitivity and accuracy of the traditional transient electric birefringence technique can be enhanced by several orders of magnitude through the use of a low-powered laser and crystal polarizing optics, signal averaging, and digital data processing. Measurements of the field-free decay of the birefringence yield for the rotational diffusion coefficient, DR = 318 ± 3 sec-1. The length of the rodlike virion, calculated from the Broersma equation with this value of DR and a rod diameter of 15 nm, is 292.5 ± 1.0 nm. Measurements of the growth of the birefringence when an electric field is applied across the sample yield μ2/kT(α∥ - α⊥) = 0.47 ± 0.07, where μ is the permanent dipole moment (assumed parallel to the symmetry axis of the virus) and α∥ - α⊥ is the electrical polarizability anistropy of the virus. Using the value of α∥ - α⊥ measured by O'Konski et al., we then obtain μ = 2.5 × 10-14 esu cm.
    Additional Material: 6 Ill.
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  • 92
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The high-resolution nmr spectrum of baker's yeast tRNACUALeu, a recently sequenced non-denaturable tRNA, has been compared with the spectra of the native and denatured conformers of the closely related species tRNAUUGLeu. Because of the presence of many common base pairs in the different tRNA's, it is possible to assign most of the low-field resonances to specific secondary-structure base pairs. A comparison of the observed positions of the various resonances with those predicted by a semiempirical ring-current shift theory shows a root-mean-square deviation of 0.14, 0.11, and 0.12 ppm for tRNAUUGLeu (native), and tRNAUUGLeu (denatured), respectively. These results support the ring-current shift theory currently used to interpret the low-field nmr spectra of the tRNA molecules. Differences between the predicted and observed positions of some resonances provide new evidence for higher order effects such as shifts from second nearest neighbors, anomalous shifts exerted by G·U base pairs, and tertiary-structure effects. A model that was previously proposed for the denatured conformer of tRNAUUGLeu is also supported.
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  • 93
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    Biopolymers 15 (1976) 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 94
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The molecular theory of the previous paper in this series is extended to determine the effect of divalent metal ions on helix stability relative to coil at fixed ionic strength and nucleotide phosphate concentration. Specification of the state of condensed counterions, as well as their concentration, is essential for the solution of this problem, and it is assumed that they translate freely within a thin cylindrical shell close to the polynucleotide. As a function of divalent counterion concentration mB2+ the relative stability of the helix is highly nonlinear. Although the overall trend is that the helix stability increases with addition of divalent metal ion, there is a narrow concentration range for which it decreases slightly. The behavior of the relative stability as a function of mB2+ is determined by the translational degrees of freedom of the counterions, both univalent and divalent, both condensed and uncondensed. Detailed comparison of the theory with data is not given here, but it is pointed out that the calculated values of the relative stability are consistent with the order of magnitude of the observed effect Mg2+ on the melting temperature.
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  • 95
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    Biopolymers 15 (1976), S. 503-506 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: X-ray diffraction studies have been made on the polytripeptide poly(L-prolyl-L-α-phenylglycyl-L-proline). Its structure has been found to be helical, with a poly(L-proline) II conformation, packed in an orthorhombic lattice, space group P21212, with a = 14.3 Å, b = 13.5 Å, and c = 9.4 Å.
    Additional Material: 1 Ill.
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  • 96
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
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  • 97
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    Biopolymers 15 (1976), S. 591-594 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 5 Ill.
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  • 98
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    Biopolymers 15 (1976) 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 99
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    Biopolymers 15 (1976), S. 649-653 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stability constant of the complex of tRNA with 50S subunits of ribosomes was compared in ordinary and heavy water. A considerable effect (about fourfold) was observed, showing the importance of hydrogen bonds in this interaction. In addition, the isotope effect of complementary polynucleotide interaction was measured for two examples. In the case of the binary complex of heptainosinic acid oligomers with poly(C) in the presence of 10-3 M MgCl2, the transfer from ordinary to heavy water gave an increase of the stability constant of about 5%. But in the case of a ternary complex of hexaadenylic acid with poly(U) under the same conditions, the stability constant in D2O increased threefold. The isotope effect depends strongly on magnesium ion concentration and is possibly due to some specific mechanism of magnesium ion complexing involving water molecules.
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  • 100
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    Biopolymers 15 (1976), S. 999-1000 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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