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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Rat ; energy metabolism ; NAD-redox state ; oxidative stress ; sorbitol dehydrogenase inhibitor ; streptozotocin-diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Studies of the role of sorbitol dehydrogenase in nerve functional deficits induced by diabetes reported contradictory results. We evaluated whether sorbitol dehydrogenase inhibition reduces metabolic abnormalities and enhances oxidative stress characteristic of experimental diabetic neuropathy. Methods. Control and streptozotocin-diabetic rats were treated with or without sorbitol dehydrogenase inhibitor (SDI)-157 (100 mg · kg–1· day–1, in the drinking water, for 3 weeks). Sciatic nerve free mitochondrial (cristae and matrix) and cytosolic NAD+: NADH ratios were calculated from the β-hydroxybutyrate, glutamate and lactate dehydrogenase systems. Concentrations of metabolites, e. g. sorbitol pathway intermediates and variables of energy state were measured in individual nerves spectrofluorometrically by enzymatic procedures. Results. The flux through sorbitol dehydrogenase (manifested by nerve fructose concentrations) was inhibited by 53 % and 74 % in control and diabetic rats treated with SDI compared with untreated control and diabetic groups. Free NAD+:NADH ratios in mitochondrial cristae, matrix and cytosol were decreased in diabetic rats compared with controls and reduction in either of the three variables was not prevented by sorbitol dehydrogenase inhibitor. Phosphocreatine concentrations and phosphocreatine:creatine ratios were decreased in diabetic rats compared with controls and were further reduced by the inhibitor. Malondialdehyde plus 4-hydroxyalkenals concentration was increased and reduced gluthathione concentration was reduced in diabetic rats compared with the control group, and changes in both variables were further exacerbated by sorbitol dehydrogenase inhibitor. Neither NAD-redox and energy states nor lipid aldehyde and reduced gluthathione concentrations were affected by treatment with the inhibitor in control rats. Conclusion/interpretation. Inhibition of sorbitol dehydrogenase does not offer an effective approach for prevention of oxidation and metabolic imbalances in the peripheral nerve that is induced by diabetes and is adverse rather than beneficial. [Diabetologia (1999) 42: 1187–1194]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Quantitative Spectroscopy and Radiative Transfer 31 (1984), S. 315-322 
    ISSN: 0022-4073
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Solid State Ionics 36 (1989), S. 193-195 
    ISSN: 0167-2738
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    FEBS Letters 262 (1990), S. 215-218 
    ISSN: 0014-5793
    Keywords: HbSS ; K^+ transport ; Red cell
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 343 (1977), S. 195-204 
    ISSN: 1435-2451
    Keywords: Colorectal carcinoma ; Concomitant disease ; Tumor complications ; Causes of death ; Residual tumor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurden 200 nach operativen Eingriffen wegen eines Colon- und Rectumcarcinoms während des Klinikaufenthaltes aufgetretene und obduzierte Todesfälle ausgewertet. Nur 38,5% dieser Kranken konnten radikal operiert werden. 94,5 % der Verstorbenen waren über 50, 82,5 % über 60, 40,5 % über 70 und 10% über 80 Jahre alt. Bei den 200 Verstorbenen bestanden präoperativ 263 vom Tumorleiden unabhängige Begleitkrankheiten und belastende Faktoren. Bei 50% der Todesfälle lagen ein fortgeschrittenes Tumorleiden mit Metastasierung, bei 38% ein Ileus, bei 11% eine Peritonitis, bei 6,5% eine Absceßbildung oder schwere Blutung präoperativ vor. Als Todesursachen fanden sich Pneumonie (24,5%), Peritonitis (22%), Lungenarterienembolie (15,5%), Tumorkachexie (14%), Herzversagen (9,5%), Ileus (5,5%) und verschiedene Ursachen (9%). 1/3 der Todesfälle waren bis zum 6., die Hälfte bis zum 9. und z/3 bis zum 13. postoperativen Tag eingetreten. Ansatzpunkte zur Verringerung der Operationsletalität sind vor allem im Einsatz aller internistischen und anaesthesiologischen Möglichkeiten bei der Vorbereitung, Narkose und Nachbehandlung der Patienten, insbesondere der Pneumonie und Thromboembolie-Prophylaxe gegeben, während chirurgisch-technische Probleme in den Hintergrund treten.[/p]
    Notes: Summary Analysis of the clinical and autopsy reports of 200 deaths following surgery for colorectal cancer from 1956 to 1974, at the Dept. of Surgery, University of Heidelberg, revealed that pneumonia (24.5 %) was the most common cause of death followed by peritonitis (22%), pulmonary embolism (15.5 %), advanced tumor disease (14%), cardiac failure (9.5%), ileus (5.5%), and others (9%). The explanation for the postoperative mortality rate of 12% (cancer of colon) and 13.2% (cancer of rectum) lies in the fact that 82.5% of those who died postoperatively were beyond the age of 60, and 40.5 % beyond 70 years at the time of surgery. Moreover, in 50.5% advanced tumors with regional and/or distant metastases were found. In 55.5% severe preoperative complications (ileus: 38%, peritonitis: 11%, abscess formation or hemorrhage: 6.5%) required an emergency operation. Only 38.5% of the procedures were considered for cure. Besides the need for early recognition of the cancer, intensification of pre- and postoperative treatment appears to be the predominant task in the effort to decrease postoperative mortality.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 169 (1939), S. 93-120 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Die Ansicht, daß Morphin sowohl beim Versuchstier wie beim Menschen “darmlähmend” wirkt, ist in neueren Arbeiten bereits mehrfach einer Revision unterzogen worden. Die Aufgabe der vorliegenden Arbeit bestand darin, die Darmwirkung des Morphins im Tierexperiment als eine “heilsame” auf den paralytischen Darm nachzuweisen. Zahlreiche Vorversuche wurden zunächst angestellt, um eine Darmparalyse zu erzeugen, die der beim Menschen nach Laparotomien oder Bauchfellentzündungen beobachteten möglichst ähnlich sein sollte. Die verschiedensten Verfahren wurden zu diesem Zwecke angewandt, doch gelang es weder durch Bakterientoxine oder Bakterienaufschwemmungen, weder durch eine chemische noch durch eine mechanische Schädigung des Darmes (Lufteinblasung, Quetschung, Abkühlung und Austrocknung), eine merkliche Darmlähmung zu erzielen, die eine Erprobung der Morphinwirkung ermöglicht hätte. Es mußte deshalb auf den mechanischen Ileus zurückgegriffen werden, der zum mindesten im Endstadium dem paralytischen Ileus entspricht. Hierbei ergab sich nun die Tatsache, daß Tiere unter regelmäßiger Morphindarreichung im Durchschnitt über doppelt so lange lebten wie die entsprechenden Kontrolltiere. Diese Erscheinung läßt sich dadurch erklären, daß das Morphin die Leistungsfähigkeit des Darmes erheblich länger aufrecht erhält, als es bei den unbehandelten Tieren der Fall ist. Durch mehrere Versuchsreihen, in denen eine besondere Form der Darmmotilität, die Rheokinetik, geprüft wurde, gelang es, nachzuweisen, daß Morphin die Leistungsfähigkeit des normalen wie des durch einen mechanischen Darmverschluß geschädigten Darmes erhöht. Soweit Ergebnisse des Tierexperiments auf die Verhältnisse am Krankenbett übertragen werden können, darf deshalb der Schluß gezogen werden: Die Zurückhaltung im Gebrauch von Morphin bei Zuständen von Darmlähmung ist nicht gerechtfertigt, denn Morphin wirkt auf den Tonus des Darms und seine Rheokinetik steigernd. Es besitzt daher bei der Prophylaxe und Behandlung von paralytischen Zuständen am Darm großen Wert.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2013
    Keywords: Human sweat duct ; Cl− conductance ; Cl− channel blockers ; Cystic fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To characterize the chloride conductance of human sweat duct the effect of various analogues of diphenylamine-2-carboxylate was investigated on the transepithelial potential difference (PDT) and resistance (R T ) of isolated microperfused sweat ducts. Although the most powerful analogues which block Cl− channels in various secretory and absorptive epithelia were ineffective, a number of analogues (in particular Cl substituted ones) were found which at high concentrations significantly and reversibly increased PDT andR T . The data suggest that the main chloride conductance pathway of sweat duct epithelium resides in the cell membranes rather than in the tight junctions. In addition the different blocking spectra of the chloride conductances of sweat duct and tracheal epithelium (Welsh MJ, Science 232:1648, 1986) suggest that the combined impairment of both conductances in cystic fibrosis does not result from a molecular defect in the Cl− channels.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2013
    Keywords: Colon ; Rabbit ; NPPB ; Chloride channel blockers ; Chloride secretion ; Secretory diarrhoea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Arylaminobenzoates were examined in rabbit colon mounted in an Ussing chamber. The open-circuit transepithelial voltage (V te) and resistance (R te) were measured and the equivalent short-circuit current (I SC=V te/ R te) was calculated. After serosal (s) and mucosal (m) addition of indomethacin (1 μmol/l) I SC was −71±11 (n = 118) μA/cm2. Amiloride (0.1 mmol/l, m) inhibited this current and reversed the polarity to + 32±4 (n=118) μA/cm2. In the presence of amiloride and indomethacin, prostaglandin E2 (1 μmol/l, s), known to induce Cl− secretion, generated an I SC of -143 ± 8 (n = 92) μA/cm2. The arylaminobenzoate and Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) reduced I SC reversibly with a half-maximal inhibition (IC50) at approximately 0.35 mmol/l and 0.2 mmol/l for mucosal and serosal application respectively. To test whether the poor effect was caused by mucus covering the luminal surface, dose/response curves of the mucosal effect were repeated after several pretreatments. Acidic pH on the mucosal side reduced IC50 to approximately 0.1 mmol/l. A similar effect was observed after N-acetyl-l-cysteine (m) preincubation. Pretreatment with N-acetyl-l-cysteine (m) and carbachol (s), in order to exhaust mucus secretion, and l-homocysteine (m) were more effective and reduced IC50 to approximately 50 μmol/l. To test whether this effect of NPPB was caused by non-specific effects, the two enantiomers of 5-nitro-2-(+/−1-phenylethylamino)-benzoate were tested of which only the (+) form inhibited the Cl− conductance in the thick ascending limb of the loop of Henle (TAL). In the present study the (+) enantiomer inhibited significantly more strongly than the (−) form. This suggests that the inhibitory effect of NPPB, even though it requires rather high concentrations, is probably due to Cl− channel inhibition. For other arylaminobenzoates the sequence of potencies was different from that determined for the TAL. The present data indicate that substances that have been designed to block the Cl− conductance of the TAL segment also inhibit reversibly but with much lower affinity the PGE2-induced Cl− secretion in rabbit colon.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2013
    Keywords: Cell volume ; Intracellular pH ; ras oncogene ; Calcium oscillations ; Cell membrane potential ; Bradykinin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In NIH 3T3 fibroblasts expressing the Ha-ras oncogene (+ras) bradykinin leads to sustained oscillations of cell membrane potential due to oscillations of intracellular Ca2+ with subsequent activation of Ca2+-sensitive K+ channels. In cells not expressing the oncogene (-ras), bradykinin leads only to a single transient hyperpolarization of the cell membrane. The present study has been performed to elucidate the possible interaction of cell volume, intracellular pH and bradykinin-induced oscillations of the cell membrane potential. Bradykinin leads to cell shrinkage and intracellular alkalinization of both +ras cells and −ras cells. Inhibition of Na+/H+ exchanger by HOE 694 abolishes the bradykinin-induced alkalinization but does not significantly interfere with the bradykinin-induced oscillations of cell membrane potential. In contrast, prevention of bradykinin-induced cell shrinkage by simultaneous reduction of extracellular osmolarity blunts the oscillations. Thus, cell shrinkage stimulates bradykinin-induced oscillations of cell membrane potential. On the other hand, cell shrinkage alone does not elicit oscillations unless, in addition, Ca2+ entry is stimulated by ionomycin.
    Type of Medium: Electronic Resource
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