Insignificant effect of desflurane-fentanyl-thiopental on hepatocellular integrity--a comparison with total intravenous anaesthesia using propofol-remifentanil

BACKGROUND AND OBJECTIVE: Inhalational anaesthetics have been associated with hepatotoxicity. Even desflurane, with its low solubility in blood and tissues, and its minimal hepatic biotransformation, is known to affect hepatic integrity. The effects of propofol on hepatic function are, however, a matter of controversy. Alpha-glutathione S-transferase (alpha-GST), a sensitive and specific biomarker for hepatic integrity, was measured to assess the influence of total intravenous anaesthesia (TIVA) with propofol vs. anaesthesia with desflurane. METHODS: Forty-two patients scheduled for elective prostatectomy were randomly allocated to receive either desflurane, fentanyl and thiopental (desflurane group) or propofol and remifentanil (TIVA group). Depth of anaesthesia was guided by bispectral index. Plasma concentrations of alpha-GST and aminotransferases were measured before induction of anaesthesia (TO), at the end of surgery (T1), as well as 2 h (T2) and 24 h (T3) postoperatively. Haemodynamic parameters and bispectral index values were documented. RESULTS: alpha-GST increased significantly in the desflurane group from TO (3.0 +/- 2.2 microg L(-1)) to T1 and T2 (5.5 +/- 4.3 and 5.6 +/- 3.7 microg L(-1), respectively), whereas no changes were seen in the TIVA group. alpha-GST values above the normal upper limit (> 7.5 microg L(-1)) were seen in 24% of the patients receiving desflurane. Aminotransferases remained unchanged in both groups throughout the study period. CONCLUSIONS: The use of propofol as part of a TIVA regimen seems to have no influence on hepatocellular function during and after surgery. In contrast, patients receiving desflurane showed a transient slight, but significant, increase of alpha-GST to above the normal upper limit after anaesthesia, although this was without further clinical relevance.     

Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoids

Congenital lack of proopiomelanocortin (POMC) causes obesity and glucocorticoid deficiency. The responses of Pomc-/- and wild-type mice to the administration of corticosterone were compared. In study 1, mice were given corticosterone-supplemented water (CORT) for 10 days, resulting in plasma CORT levels within the physiological range, with partial suppression of hypothalamic corticotropin-releasing hormone expression to a similar degree between genotypes. Body weight, fat mass, and food intake increased in CORT-treated Pomc-/- but not wild-type mice. CORT increased plasma insulin levels 50-fold in Pomc-/- versus 14-fold in wild-type mice (P < 0.01) and increased hypothalamic agouti-related protein (AgRP) expression by more than 200% in Pomc-/- versus 40% in wild type (P < 0.05). In study 2, mice were given CORT from weaning, and Pomc-/- but not wild-type mice developed hyperglycemia, ketonuria, and hepatic steatosis by 8-12 weeks. Thus, Pomc-/- mice are hypersensitive to the adverse metabolic effects of glucocorticoids. Additionally, as the levels of plasma CORT achieved, especially in study 1, were not grossly supraphysiological, we conclude that glucocorticoid deficiency may afford Pomc-/- mice some protection from the full adverse consequences of melanocortin deficiency. This may occur through a mechanism involving the suppression of AgRP by the hypoadrenal state.     

Zur natürlichen Ausscheidung von metachromasiegebenden Substanzen im Urin Hautkranker unter besonderer Berücksichtigung der Urticaria pigmentosa

Zusammenfassung Die natürliche Ausscheidung von metachromasiegebenden Substanzen wurde bei 130 Probanden nach der bekannten Methode mit Toluidinblau verfolgt. Bei hautgesunden Personen ergab sich ein Normalbereich von 15,83–26,43 mg pro 24 Std-Urin, in den sich der größte Teil von Dermatosen verschiedener Genese einordnen ließ. Nur bei den Probanden mit Urticaria pigmentosa konnte eine signifikante Erhöhung (38,23±8,20 mg/d) festgestellt werden.Chromatographische Untersuchungen ergaben, daß die ausgeschiedenen SMPS nicht dem. Heparin oder Uroheparin, sondern dem Chondroitinsulfat entsprechen.Das Zahlenmaterial wurde teilweise der in Vorbereitung befindlichen Dissertation von Bahr und Schmeisser entnommen.     

Pathology of viral leukoencephalomyelitis of goats

Summary The morphologic changes of viral leukoencephalomyelitis of goats (VLG), an afebrile paralytic disease of 2–4 month old kids, were studied in 13 naturally infected goats: 11 during the first 5–22 days of clinical disease and two that survived 8 months and 3 years after onset of clinical signs. Lesions in the early clinical phase of the disease included interstitial pneumonia and widely disseminated myelinoclastic perivascular lesions in the brain and spinal cord. In the central nervous system, hypertrophied and hyperplastic reticulin fibers of the vascular sheath encompassed an inflammatory cell infiltrate composed of lymphocytes, plasma cells, and macrophages. Occasionally, malacia occurred, and several animals had transverse myelitis. Neuronal necrosis and neuronophagia were not features of the disease. Lesions were most frequent in the subpia and subependyma. Pulmonary lesions were not present in goats that survived the initial clinical phase of the disease, but myelin had disappeared from large areas of the spinal cord and from small foci in the brain. Nodular accumulations of mononuclear cells and small perivascular cuffs were also present in the central nervous system. VLG resembles visna in the topographic distribution and myelinoclastic nature of its lesions. Like visna, it bears some resemblance to post-infectious encephalitis of man.This work was supported by PHS grant FR 5465 and NIH grants 5T01GM00414 and RR00515.     

Diet, metabolism and lifespan in Drosophila

Dietary restriction (DR) by dilution of the food medium can extend lifespan in Drosophila. DR results in a state that is characterized by reduced fecundity, increased starvation resistance and higher total lipid levels. In the past, each of these correlated phenotypes has been proposed to play a causal role in the lifespan-extending effects of food reduction. However, more recent data show that each phenotype can be uncoupled from the long-lived state to varying extents. In this mini-review, we summarize the principal findings of the effects of DR on Drosophila in order to address what these phenotypes can tell us about the physiological remodeling required for Drosophila to be long-lived. Current data indicate lifespan-extension by DR is likely to involve both enhancement of various defense and detoxification mechanisms and a complex range of metabolic alterations that make energy available for these processes.