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  • Articles: DFG German National Licenses  (54)
  • 1980-1984  (54)
  • 1
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty seven insulin-dependent diabetics, and six non-diabetic subjects undergoing elective surgery have been studied. Twelve diabetics received continuous glucose-insulin-potassium (GIK) infiion for at least 4 hours after surgery terminated. Six diabetic patients having morning surgery received a proportion of their morning insulin dose with intravenous glucose (25 g) before surgery and the remaining jve operated on in the afternoon received their morning insulin with breakfast. Non-GIK groups were combined and compared with GIK. Postoperative diabetic treatment was the same in both groups. Plasma glucose changes were studied in all patients and other metabolites whenever possible.Mean pre-operative glucose, non-esterjedfatty acid, and 3-hydroxybutyrate concentrations were similar in GIK and non-GIK groups. Four hours postoperatively plasma glucose, and 3-hydroxybutyrate values were lower in the GIK group than in the non GIK group (p 〈 0.05) as were mean plasma non-esterfed fatty acid levels. Plasma glucose concentration was also lower in GIK subjects at 72 hours postoperatively (p 〈 0.01). At other times measured metabolic variables were similar in both GIK and non GIK groups.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 37 (1982), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Plasma levels of acebutolol and its major human metabolite, diacetolol, were determined before, during and after aortocoronary bypass grafting in 10 patients who had received a chronic oral regimen of acebutolol 200 mg t.d.s. for at least 6 days before surgery, a 200 mg dose with the premedication and 5–10 mg intravenously immediately before intubation. It was found that this regimen produced beta-adrenoceplor antagonist levels which were within the range in which attenuation of hypertension and tachydysrhythmiu occurs. These effective plasma levels were sustained throughout surgery and persisted into the early recovery period.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La transplantation pancréatique chez les animaux d'expérience rendus diabétiques permet de maintenir la glycémie à la normale sans pour autant que le test de tolérance au glucose revienne à la normale. Ce fait ainsi que les anomalies hormonales et métaboliques n'est pas sans retentir sur l'efficacité des greffes pour contrôler le diabète et ses complications. Le but de cette étude fut de prouver l'existence de ces anomalies et d'apprécier leur évolution au fil du temps. Douze de ces chiens d'expérience servirent de base à l'étude un mois et trois mois après qu'aient été injectés des auto-greffes de pancréas dans leur rate. Un groupe de 33 chiens normaux sert de base au contrôle. Le dosage dans le sang du glucose, du lactate, du pyruvate, de l'alanine, du glycérol, du 3-hydroxybutyrate, du cholestérol, des acides gras, de l'insuline, du glucagon, du cortisol fut pratiqué sur les chiens en état de jeun et après injection intraveineuse d'une quantité déterminée de glucose. Après un mois la tolérance au glucose (K) était réduite mais le taux chez les animaux à jeun du glycérol, du cholestérol, des acides gras et de la 3-hydroxybutyrate était élevé. Après trois mois une amélioration significative de la tolérance au glucose fut observée et le métabolisme intermédiaire était redevenu normal. Une élévation signifcative du débit insulinique provoqué par le glucose au niveau du sang périphérique fut constatée entre le premier et le troisième mois. Les valeurs du glucagon et du cortisol ne varièrent pas au cours de cette étude. Cette expérience démontre une amélioration fonctionnelle au cours du temps de ce type de transplantation. Ce fait est d'une importance considérable pour la pratique clinique puisqu'aussi bien la transplantation d'un segment de pancréas n'entraîne pas cet effet favorable.
    Abstract: Resumen Los transplantes pancreáticos en animales diabéticos de gran tamaño son capaces de mantener euglicemia en el estado de ayuno, pero no logran una tolerancia normal a la glucosa. Este y otros defectos hormonales y metabólicos determinan la eficacia de estos transplantes en cuanto a su capacidad de controlar o de revertir las complicaciones de la diabetes. El propósito de este estudio fue el de observar si tales defectos existen, y cómo éstos pueden ser modificados a lo largo del tiempo. Doce perros fueron estudiados entre uno y tres meses después de haber recibido autotransplantes intraesplénicos de fragmentos pancreáticos digeridos con colagenasa. 33 animales normales sirvieron como controles. Glucosa sanguínea, lactato, piruvato, alanina, glicerol, 3-hidroxibutirato, colesterol, ácidos grasos libres, insulina, glucagón y cortisol fueron determinados en el estado de ayuno y después de una carga de glucosa intravenosa. Al final del primer mes la depuración de glucosa (K) apareció reducida, junto con altos niveles de ayuno de glicerol, colesterol, ácidos grasos libres y 3-hidroxibutirato. A los tres meses se había producido una mejoría significativa de K y el metabolismo intermediario había regresado al estado normal. Se observó un aumento de significación en la producción de insulina en respuesta a estimulación con glucosa según medición realizada en la sangre periférica entre uno y tres meses después del transplante. Los perfiles de glucagón y cortisol aparecieron normales a lo largo del estudio. Con este método de transplante se demuestra una mejoría funcional con el paso del tiempo, lo cual es un hecho de importancia considerable para futuros estudios clínicos, hecho que, se sabe, no ocurre después de transplantes con segmentas de páncreas.
    Notes: Abstract Pancreatic transplants in large experimental diabetic animals maintain fasting euglycemia, but do not achieve normal glucose tolerance. This and other hormonal and metabolic defects influence the efficacy of these grafts to control or reverse the complications of diabetes. The aim of this study was to see if such defects exist, and how they might alter with time. Twelve dogs were studied 1 and 3 months after receiving intrasplenic autotransplants of collagenase-dispersed pancreatic fragments. Thirty-three normal animals acted as controls. Blood glucose, lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate, cholesterol, free fatty acids, dinsulin, glucagon, and cortisol were determined in the fasting state and following an intravenous glucose load. At 1 month, glucose clearance (K) was reduced and there were elevated fasting levels of glycerol, cholesterol, free fatty acids, and 3-hydroxybutyrate. At 3 months, significant improvements in K had occurred and intermediary metabolism returned to normal. There was a significant increase in glucosestimulated insulin output measured in peripheral blood between 1 and 3 months. Profiles for glucagon and cortisol were normal throughout the study. Unlike segmental pancreatic transplants, the pancreatic islet graft demonstrates functional improvement with time, a feature of considerable importance for future clinical studies.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 322 (1983), S. 298-309 
    ISSN: 1432-1912
    Keywords: Heterogeneity of rat hepatocytes ; Selective acinar damage ; Carbon tetrachloride ; N-Hydroxy-2-acetylaminofluorene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Heterogeneity of rat hepatocytes with respect to transport function can in principle by studied by selective acinar damage of periportal (acinar zone 1) and perivenous (acinar zone 3) cells. Meaningful conclusions from such studies can be drawn only if the acinar selectivity of the toxins employed is clearly demonstrated. Therefore, transmission and scanning electron microscopy, enzyme histochemistry and determination of the increase of the activities in serum of glutamate-pyruvate transaminase, glutamate dehydrogenase and alkaline phosphatase were performed 24 h after the administration of 90 μmol/kg N-hydroxy-2-acetylamino-fluorene (N-OH-AAF) to damage zone 1 and 2.1 mmol/kg carbon tetrachloride (CCl4) to damage zone 3. N-OH-AAF administration resulted in strongly elevated serum enzyme activities. Histochemically, a decrease of enzyme activities in a very limited number of cells in zone 1 (5–20% of the acinus) was found. The remaining cells of zone 1 showed either increased or normal activities, and zone 3 cells appeared normal. Ultrastructurally, zone 3 cells were intact, but zone 1 cells exhibited several signs of damage: among others, induction of RER into fingerprints, numerous small vesicles, and widened bile canaliculi; some necrotic cells were present. CCl4 administration resulted in a relatively smaller rise of serum enzyme activities than N-OH-AAF, and in a decrease of histochemically detectable enzyme activities in zone 3 (20–50% of the acinus), while zone 1 cells appeared normal. Ultrastructurally, no changes were observed in zone 1, but zone 3 cells were necrotic or revealed swollen ER occupying most of the cytoplasmic space. Scanning EM showed no damage to the sinusoidal lining after both N-OH-AAF and CCl4-pretreatment. Bile canaliculi were normal after CCl4-pretreatment. It is concluded that administration of these doses of N-OH-AAF and CCl4 results in damage that is restricted to zone 1 and zone 3 respectively and therefore, enables further studies concerning the heterogeneity of hepatocytes with respect to transport functions. This study introduces N-OH-AAF as a new tool for the selective destruction of zone 1 of the liver acinus, with a better reproducibility of the hepatic lesion and a lower general toxicity compared with previously used toxins such as allylalcohol.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: Heterogeneity of rat hepatocytes ; Selective acinar damage ; Bile acid transport ; DBSP transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study is to investigate the heterogeneity of rat hepatocytes with respect to transport of organic anions, and whether this is due to a difference in localization of the cells in the acinus, and/or to intrinsic cellular differences between the hepatocytes. Periportal (zone 1) cells were selectively damaged by injection of 90 μmol/kg (i.v.) N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and zone 3 cells by administration of 2.1 mmol/kg (p.o.) carbon tetrachloride (CCl4). Endogenous bile acid concentrations in systemic and portal blood and in bile were determined in vivo. Both in vivo and in the isolated perfused liver transport of 3H-taurocholate and dibromosulfophthalein (DBSP) was measured. In vivo, biliary excretion rate of bile acids was only 19% lower after zone 1 injury as compared to controls, but this occurred at strongly elevated concentrations in portal and systemic blood (decreased clearance). However, after zone 3 damage a 17% lower biliary excretion rate of bile acids was accompanied by only moderately elevated concentrations in blood, thus clearance was not markedly changed. Both in vivo and in perfusion zone 1 injury resulted in a decreased bile flow and in a severe inhibition of 3H-taurocholate transport. This is probably due to an inhibition of liver to bile transport, since the liver to medium concentration ratio was not affected. Both, plasma to liver as well as liver to bile transport of DBSP was strongly decreased after N-OH-AAF-pretreatment. On the contrary, zone 3 damage did not significantly affect bile flow, 3H-taurocholate or DBSP transport. It is concluded that bile acid transport in vivo is mainly a zone 1 function, but zone 3 cells can be recruited for uptake, although their biliary excretion capacity is lower. The observed heterogeneity in DBSP transport may be due to intrinsic cellular differences, rather than to differences in acinar localization of the hepatocytes.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0001-9593
    Topics: Linguistics and Literary Studies , History
    Notes: Annunzi bibliografici
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 39 (1983), S. 573-576 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Hydrogen ion mobility in gastric mucus has been found to be reduced to a greater extent than that hitherto suspected, though at low pH (〈4) and in buffer this mobility increases. Mucus, at an optimized pH, may therefore protect the gastric mucosa from acid digestion by providing a diffusion barrier.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Metabolic control ; artificial pancreas ; lactate ; pyruvate ; glycerol ; non-esterified fatty acids ; total ketone bodies ; glucose turnover ; glucose recycling ; glucagon ; growth hormone ; Type 1 diabetes ; subcutaneous insulin therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin infusion system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3±0.7 compared with 5.6±0.3 mmol/l on feedback control and 5.5.±0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94±0.04 on subcutaneous insulin, 0.91±0.04 on feedback control and 0.74±0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600–1800 h) was normal on feedback control (1.41±0.20 versus 1.55±0.18 mg · kg-1 · min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04±0.09 mg · kg-1 · min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Diabetes ; streptozotocin ; rats ; diabetic ketoacidosis ; insulin receptors ; insulin sensitivity ; insulin resistance ; Scatchard analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin sensitivity in vivo and insulin binding in vitro to adipocytes have been studied in streptozotocin diabetic rats with ketoacidosis. Insulin sensitivity in vivo measured as the acute (20 min) fall in blood glucose in response to an insulin infusion of 1 U/kg body weight per hour correlated positively with arterial blood pH (r=0.92, p 〈 0.01: n=38). At pH 〈 6.9 there was no fall in blood glucose. For studies of insulin binding to adipocytes ketoacidotic animals were divided into a group with moderate ketoacidosis (pH 〉 7.0) and a second group with severe ketoacidosis (pH 〈 6.9). Insulin binding to adipocytes was maximal in cells from both ketoacidotic and from normal rats at pH 7.6–7.8. Total binding was decreased in the diabetic rats (p 〈 0.01) and this was more marked in the severely diabetic group (p 〈 0.001) at all pHs studied. At pH 7.4, 125I-insulin binding was decreased in diabetics compared with normal rats (0.89±0.14 versus 2.0±0.24% with 2×105 cells/ml: n=6; p 〈 0.01) and also in the severe compared with the moderate ketoacidotic rats (0.5± 0.08%/2×105 cells; n=6, p 〈 0.05). Equilibrium binding studies showed that there was a small decrease in apparent affinity in adipocytes from both groups of diabetics (KD = 2.8±0.2×10-9 mol/l, n =6 in moderate ketoacidosis; 2.5±0.3×10-9 mol/l, n=6 in severe ketoacidosis) compared with control animals (KD = 1.8±0.15×10-9 mol/l, n= 6). Scatchard analysis revealed that there was also a decrease in receptor concentration which was greater in the severely ketoacidotic group. These findings may explain in part the insulin resistance of severe ketoacidosis.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Human insulin ; insulin activity ; insulin pharmacokinetics ; glucose clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of semi-synthetic human insulin has been compared with porcine insulin in normal man using an euglycaemic glucose clamp at two different insulin infusion rates. In a two hour infusion insulin levels plateaued for both types of insulin at 44–48 mU/l (infusion rate 0.05 U kg body weight-1 h-1) and 22–24 mU/l (0.02 U kg-1 h-1), giving identical metabolic clearance rates. The glucose delivery required to maintain euglycaemia in the second hour of insulin infusion was 13.9±2.1 g (mean±SEM) and 14.7±1.5 g (NS) at the lower dose for porcine and human insulins respectively, and 27.1±2.5 and 28.0±2.9 g (NS) at the higher dose. The potency ratio for human, compared with porcine, insulin was 1.06 ±0.12. No differences were seen in the time of onset of action of the insulins, serum half-life or distribution space. The responses of blood lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were identical. No untoward reactions occurred. The activity and disposal of this semi-synthetic human insulin are indistinguishable from porcine insulin in normal euglycaemic man.
    Type of Medium: Electronic Resource
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