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  • 1
    ISSN: 1432-0428
    Keywords: Insulin release ; glucagon release ; cyproheptadine ; tolbutamide ; arginine ; theophylline ; calcium ; perfused rat pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The tricyclic compound cyproheptadine (Periactinol®, Nuran®) inhibited glucose-induced insulin release from the perfused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of 14C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Pancreatic islets ; rats ; obese-hyperglycemic mice ; perifusion ; fluorescence ; reduced pyridine nucleotides ; D-glucose ; D-mannoheptulose ; L-lactate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In perifused pancreatic islets, the fluorescence of reduced pyridine nucleotides (NAD(P)H) was measured continuously. Elevation of glucose concentration in the medium from 0 – 5 mM to 20 mM led to an increase in NAD(P)H-fluorescence beginning 10–20 sec after change of medium. Perifusion with calcium-free media had no influence on this effect. It was, however, partially or completely blocked by 2-deoxy D-glucose, D-glucosamine, or D-mannoheptulose. D-mannose, but not D-fructose and L-lactate, enhanced NAD(P)H-fluorescence from pancreatic islets. Pyruvate caused but a small fluorescence increase. From these observations it is concluded that D-glucose leads to the increase of NAD(P)H-fluorescence by mediation of the phosphoglyceraldehyde dehydrogenase reaction.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Pancreatic islets ; obese-hyperglycemic mice ; perifusion ; insulin release ; reduced pyridine nucleotides ; L-leucine ; α-ketoisocaproic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The insulinotropic effects of L-leucine and α-ketoisocaproic acid have been compared in perifused isolated pancreatic islets. In contrast to α-ketoisocaproic acid (10 mM), L-leucine (10 mM) released less insulin in the presence than in the absence of glucose (5 mM). Changes of islet cell metabolism accompanying insulin release were studied by recording the fluorescence of reduced pyridine nucleotides. The traces of L-leucine-or α-ketoisocaproic acid-induced fluorescence increase differed both in the absence and in the presence of glucose (5 mM). When the medium perif using the islets contained 30 mM L-leucine, α-ketoisocaproic acid (10 mM) still triggered a significant insulin release. These results argue against an indirect action of α-ketoisocaproic acid via transformation to L-leucine. Isocaproic acid (10 mM), L-α-hydroxyisocaproic acid (10 mM) or α-ketoisovaleric acid stimulated no remarkable insulin release, demonstrating that the strong insulinotropic effect of α-ketoisocaproic acid is coupled both to its α-ketogroup and to the length of its carbon chain.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 56 (1978), S. 921-928 
    ISSN: 1432-1440
    Keywords: Antikonvulsiva ; Serum γGT Erhöhung ; Geschlechtsunterschied ; Klinische Merkmale ; DPH Sättigung ; Therapiebeginn ; Langzeitkontrollen ; Anticonvulsant drugs ; Serum γGT elevation ; Sex difference ; Clinical variables ; DPH saturation ; Initiation of therapy ; Long-term follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In 230 adult epileptic patients on long-term anticonvulsant therapy both serum drug levels and γ-glutamyl-transferase (γGT) activities were determined and presented in groups according to the drug or drug combination in use. The γGT activities measured never exceeded 250 U/l, there was a marked sex difference with lower values for females in all groups. The incidence of elevated γGT values was between 90 and 100% for patients treated with diphenylhydantoin (DPH), phenobarbital (Pb), primidone (Prim) and combinations (Comb.), but lower for patients treated with carbamazepine (Cz). In this group with Cz-therapy mean value and standard deviation of γGT values were also much lower than in the other groups. Only females with DPH alone and males with Pb alone showed a significant but slight correlation between drug levels and γGT. These findings permit the assumption that serum γGT is induced by treatment with DPH, Pb, Prim and Comb., to a lesser extent with Cz. Relating γGT elevation to clinical data other than anticonvulsant drug therapy (e.g. age, type of seizures, duration of illness, history of intoxication) did not produce any subgroup with specific and consistent behaviour of serum γGT. DPH-saturation did not appear to play an important part in γGT elevation, rather the strongest stimulus for γGT elevation seemed to derive from the initiation of anticonvulsant therapy and the highest levels of serum γGT were reached between 1 and 4 weeks before the highest anticonvulsant levels. With long-term anticonvulsant therapy there appeared to be a direct relationship between serum γGT and drug level for individual patients. Simultaneous estimations of serum drug levels and γGT activities are helpful for monitoring patient compliance during long-term anticonvulsant therapy.
    Notes: Zusammenfassung Bei 230 erwachsenen Anfallspatienten unter antikonvulsiver Langzeitmedikation wurden Serum Medikamentenspiegel und Serum-γ-Glutamyltransferase (γGT) Aktivitäten gemessen und entsprechend der eingenommenen Medikamente in Gruppen unterteilt. Die γGT Werte lagen in keinem Fall über 250 U/l. Es bestand ein deutlicher Geschlechtsunterschied, wobei Frauen in allen Gruppen niedrigere γGT Werte hatten. Das Vorkommen erhöhter γGT Werte lag bei Patienten in Behandlung mit Diphenylhydantoin (DPH), Phenobarbital (Pb), Primidon (Prim) und Kombinationen (Comb.) um 90–100%. Bei Patienten mit Carbamazepin (Cz)-Behandlung waren erhöhte γGT Werte seltener, auch Mittelwert und Standardabweichung der γGT Werte waren deutlich niedriger. Nur Frauen mit DPH-Monotherapie und Männer mit Pb-Monotherapie zeigten eine signifikante aber geringfügige Korrelation zwischen Medikamentenspiegel und γGT. Diese Ergebnisse lassen die Deutung zu, daß Serum γGT durch Behandlung mit DPH, Pb, Prim und Comb. induziert werden kann, zu einem geringeren Ausmaß auch durch Cz. Wenn man die Serum γGT Werte zu anderen klinischen Merkmalen (z.B. Alter der Patienten, Art der Anfälle, Erkrankungsdauer und Vorgeschichte von Überdosierungen) in Beziehung setzte, ergab sich kein spezifisches und konstantes Verhalten der γGT Werte für irgendeine dieser Untergruppen. DPH-Sättigung schien ebenfalls keine besondere Rolle für eine γGT Erhöhung zu spielen, vielmehr ergab sich offenbar der stärkste Anstoß für eine Erhöhung der Serum γGT aus der Einleitung einer antikonvulsiven Behandlung, wobei die höchsten γGT Werte zwischen 1 und 4 Wochen noch vor Auftreten der höchsten Antikonvulsivaspiegel beobachtet wurden. Unter Langzeitbehandlung zeichnete sich eine direkte Beziehung zwischen Serum γGT und Serum Antikonvulsivaspiegel für den einzelnen Patienten ab. Gleichzeitige Kontrollen von Antikonvulsiva-Serumspiegel und Serum γGT Aktivität erweisen sich als hilfreich zur Beurteilung der Einnahmezuverlässigkeit bei langfristigen Kontrollen.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0738
    Keywords: Cholinesterase ; Hepatic Damage ; D-Galactosamine-HCl ; Cholinesterase ; Leberschaden ; D-Galaktosamin-HCl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Verhalten der im Serum oder Plasma vorkommenden Cholinesterase bei schwerer Leberschädigung wurde untersucht. Hierzu wurden Kaninchen mit D-Galaktosamin-HCl (250 mg/kg i. v.) vergiftet. Es zeigte sich, daß die Aktivität der Cholinesterase (Substrate: Acetylcholinjodid, Butyrylthiocholinjodid) ähnlich wie die Aktivität der GOT und GLDH im Plasma am 1. Tag nach Vergiftung ansteigt. Am 10. Tag nach Vergiftung waren die Aktivitäten der geprüften Enzyme wieder auf Normalwerte abgesunken. Da gleichzeitig mit dem Anstieg der Cholinesteraseaktivität der Plasmaalbuminspiegel unter den Normalwert absank, scheint keine prinzipielle Korrelation zwischen Albuminsynthese und Cholinesteraseaktivität im Plasma zu bestehen.
    Notes: Abstract The influence of severe hepatic damage on Cholinesterase activity in plasma was tested. Rabbits were administered d-galactosamine-HCl (about 250 mg/kg i.V.). 1 day after intoxication the activity of cholinesterase in plasma (substrates: acetylcholine iodide, butyrylthiocholine iodide) increased, as did the activities of GOT and GLDH. 10 days after intoxication, the activities of the enzymes returned to normal values. Cholinesterase activity was not observed to fall below the normal range. Because the plasma albumin level decreased, while the cholinesterase activity increased, no general correlation seems to exist.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0014-5793
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Manganintoxikation ; Parkinsonismus ; MRT ; Verlaufskontrolle ; L-Dopa-Therapie ; Key words Manganese intoxication ; Parkinsonism ; MRI ; Follow-up study ; L-dopa treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Manganese intoxication is an unusual, severe form of intoxication. This report deals with a patient now 80 years old who accidentally ingested a solution of potassium permanganate for a period of at least 4 weeks 14 years ago. Since then, the patient suffers from a mild parkinsonian syndrome and distally accentuated polyneuropathies. Psychiatric disorders, especially demential or depressive symptoms, were not observed. Manganese analysis of his hair still shows a clear increase in manganese concentration. The MRI of his brain showed no pathological changes, in particular none of those often described with symmetric signal elevation in T1 in the area of the basal ganglia. In this study, we present clinical, laboratory, and neuroradiological findings. Unusual in this case with a short exposition is the long duration and clinical improvement without L-dopa treatment.
    Notes: Zusammenfassung Eine Manganintoxikation ist eine ungewöhnliche, schwere Intoxikationsform. Wir berichten über einen jetzt 80-jährigen Patienten, der vor 14 Jahren über die Dauer von mindestens 4 Wochen versehentlich Kaliumpermanganat eingenommen hatte. Der Patient leidet weiterhin unter einem leichten Parkinsonsyndrom und einer distal betonten Polyneuropathie. Psychiatrische St¨rungen, insbesondere ein dementielles oder depressives Symptom, fanden sich nicht mehr. Die Mangananalysen der Haare zeigen auch jetzt noch deutlich erhöhte Konzentrationen. Das MRT des Gehirns erbrachte keinen pathologischen Befund, insbesondere keine häufig bei Manganintoxikationen beschriebenen Veränderungen mit symmetrischen Signalanhebungen in T1-Wichtung im Bereich der Basalganglien (Globus pallidus). In einer aktuellen Untersuchung werden klinische, laborchemische sowie neuroradiologische Ergebnisse vorgestellt. Die Besonderheit des Falles erklärt sich aus einer kurzen Expositionsdauer mit einer langen Verlaufszeit und klinischer Befundbesserung ohne L-Dopa-Behandlung.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 33 (1974), S. 31-40 
    ISSN: 1432-0738
    Keywords: Nitrostigmine (Parathion, E 605) ; Organophosphates ; Liver ; Damage ; Liver Perfusion ; Nitrostigmin (Parathion, E 605) ; Organophosphate ; Leber ; schaden ; Perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Lebern männlicher gefütterter Ratten (Stamm Wistar, 170 bis 290 g KG) wurden mit einem hämoglobin- und albuminfreien Medium durchströmt. Nach einer Vorperfusion von 30 min wurde dem Medium entweder 12,5 mg/kg Nitrostigmin oder 0,1 ml/200 g KG Dimethylsulfoxid (Kontrollen) zugesetzt. Der Sauerstoffverbrauch der Leber und der Lactat/Pyruvat- und 3-Hydroxybutyrat/Acetoacetat-Quotient im Medium wurden durch Nitrostigmin ebensowenig beeinflußt wie die Abgabe der Glutamat-Oxalacetat-Transaminase und des Kaliums in das Perfusat. Auch die Produktion von Glucose, Lactat + Pyruvat und 3-Hydroxybutyrat + Acetoacetat wurde nicht verändert, ebensowenig die Cholerese. Die Aktivität der acetylcholinspaltenden Enzyme im Leberhomogenat wurde dabei deutlich gehemmt. Aus diesen Befunden wird geschlossen, daß Nitrostigmin in der Leber zu seinem aktiven Metaboliten umgesetzt wird, dabei aber weder Zellmembranen schädigt noch die energetische Situation der Leberzelle beeinflußt. Leberschäden nach Intoxikationen mit Nitrostigmin sind infolgedessen nur auf die vergiftungsbedingte Hypoxie als Folge der „endogenen Acetylcholinvergiftung” zurückzuführen.
    Notes: Abstract Livers of male well fed Wistar rats were perfused with an albumin- and hemoglobin-free medium in a recirculating system. After an equilibration period either 12.5 mg/kg body weight nitrostigmine or 0.5 ml/kg dimethylsulfoxide (controls) were added to the medium. The following parameters of liver function were not altered by nitrostigmine: Oxygen consumption, lactate/pyruvate and 3-hydroxibutyrate/acetoacetate ratios in the medium, output of potassium and aspartate aminotransferase, bile flow, glucose production, production of lactate plus pyruvate and production of ketone bodies. A liver homogenate was prepared after the end of the perfusion. The activity of acetylcholine cleaving enzymes in the homogenate was strongly depressed in the nitrostigmine treated livers. These results show, that neither nitrostigmine nor a metabolite nor the inhibition of acetylcholineesterases damaged liver cell membranes or influenced the energetic situation. Thus liver damage after nitrostigmine intoxication in vivo is due to the inhibition of respiration. This effect is caused by an “endogenous acetylcholine intoxication”.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 72 (1993), S. 76-76 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 250 (1965), S. 255-255 
    ISSN: 1432-1912
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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