The Quantitative Liver Function as Measured by the Galactose Elimination Capacity

ABSTRACT. Quantitative liver function was estimated by determination of the galactose elimination capacity (GEC) in 29 patients with steatosis, 50 with cirrhosis and 42 control patients without clinical history or signs of liver disease. In patients with steatosis and cirrhosis, clinical signs of liver disease were recorded and the most common liver tests were carried out. The degree of histological changes was investigated in needle liver biopsies performed in a close relation to the GEC determinations. A positive correlation between GEC and body weight and body surface area was observed in all three patient groups. GEC (absolute value, per kg body weight and per m² body surface area) was significantly different (p<0.001) between the three groups, but was without diagnostic value due to a broad scattering of results in each group. This may be due to methodological errors in the determination of GEC, but also to the large biological variation in normal man and the pathophysiological conditions in patients with liver disease. Neither in patients with steatosis nor in patients with cirrhosis could significant relations be found between GEC and clinical signs of liver disease or the degree of severity of histological changes assessed semiquantitatively. In patients with cirrhosis but not in patients with steatosis, GEC was significantly correlated with the majority of the most commonly utilized liver tests.     

Regional analyses of the reversal process in the neonatal galactose cataract

Reversal of the galactose cataract in neonatal rat lenses involves a decrease in lenticular galactitol, a recovery of existing fiber contour and interdigitation, and a production of new fibers. The onset of neonatal cataractogenesis appeared at 7 days when the young were nursed by mothers placed on a 50% galactose diet at the time of delivery. On the 7th day, the mothers were returned to a normal diet and reversal of the neonatal cataract was monitored for the remainder of the nursing period. After 5 days on a normal diet, cataract reversal was incomplete; this is evidenced by an abnormal fiber contour with decreased number of interdigitating processes, the presence of galactitol and decreased lens size. Fiber alterations were most pronounced in the anterior superficial cortex (0–200 μm from the capsule). As the reversal period progressed for an additional 8 days, lenticular galactitol declined and normalization of anterior superficial and supranuclear cortical fibers occurred.Growth of the normal and reversal lenses was compared by determining the number of fiber lamellae produced per day. As new fibers were formed, by the anterior lens epithelium, the radius of the lenses increased with time; the increase in lens radius and the average fiber width were measured for the juvenile lenses (12–63 days) and the reversal lenses (12–20 days). The number of fiber lamellae produced during each growth period was calculated. Normal lens growth was a consistent 1 fiber lamella/day. During the reversal period, lens growth was increased with respect to normal; the source of the rapid generation of new fibers may be the differentiation of equatorial, multilayered epithelial cells which were induced by the galactose feeding.     

Inability of galactose to mobilize insulin in galactokinase-deficient individuals

Summary Oral galactose loading in two galactokinase-deficient adults produced the expected high and prolonged rise of galactose in peripheral blood, but no rise of circulating immunoreactive insulin.Aided by: Julius Klaus-Stiftung Zürich; Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung (Grant 3990).     

Pharmacokinetics of diazepam in disordered liver function

Summary The plasma elimination curves of diazepam following intravenous administration of 10 mg were studied in nine patients with cirrhosis of the liver and four patients without liver disease. The data were analyzed according to a two compartment model. The mean biological half-life (T/2) of diazepam was increased five-fold in patients with cirrhosis compared to the controls (164 hours vs. 32.1 hours). The plasma clearance of diazepam could be correlated neither with a quantitative measure of liver function, as estimated by galactose elimination capacity, nor to semiquantitative measures of liver function, such as serum albumin and prothrombin. It is suggested that the plasma clearance of diazepam is an inaccurate index of its rate of hepatic metabolism due to the complex kinetics of the drug.     

柑橘黄酮对D-半乳糖衰老模型小鼠抗氧化作用

目的观察柑橘黄酮(CitrusFlavonoids,Cf)的体内抗氧化作用。方法用D-半乳糖建立小鼠衰老模型,同时分别灌胃给予不同剂量(200,600mg·kg-1·d-1)的柑橘黄酮。给药42d后处死小鼠,取皮肤及肝脏测定超氧化物歧化酶(SOD)、丙二醛(MDA),取皮肤测定羟脯氨酸(Hydroproline,HYD)含量。结果柑橘黄酮使D-半乳糖致衰老小鼠皮肤和肝脏SOD酶活性显著升高(P<0.05,P<0.01),MDA含量显著降低(P<0.05,P<0.01)。结论柑橘黄酮具有一定的抗氧化作用。     

Pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations

Aims/hypothesis: Thickening of the basement membrane and selective loss of pericytes are early events in diabetic retinopathy. We aimed at checking whether pericyte interaction with extracellular matrix produced by endothelial cells is influenced by the hexose concentrations in which endothelial cells are cultured. Methods: Conditioned extracellular matrixes were obtained by growing human umbilical vein endothelial cells in media containing 28 mmol/l hexoses (d-glucose, d-galactose, l-glucose), which undergo different intracellular processing, before and after adding the inhibitors of protein glycation thiamine or aminoguanidine. Having removed the endothelium, bovine retinal pericytes were grown on such matrixes and, in separate experiments, on laminin, fibronectin or type IV collagen. Pericyte adhesion was determined by cell counts 18 h after seeding. Results: Reduced adhesion was observed on matrixes produced in high d-glucose, high d-galactose and high l-glucose. Both thiamine and aminoguanidine restored impaired pericyte adhesion when added to high d-glucose and high d-galactose, but not l-glucose. Laminin, fibronectin and type IV collagen did not consistently modify pericyte adhesion. Conclusions/interpretations: Pericyte adhesion is impaired on extracellular matrix produced by endothelium in high hexose concentrations. This could result from excess protein glycation, corrected by aminoguanidine and thiamine, rather than altered glycoprotein composition. [Diabetologia (2002) 45: 416–419] Received: 28 June 2001 and in revised form: 16 November 2001     

Recombinant probiotics for treatment and prevention of enterotoxigenic Escherichia coli diarrhea

BACKGROUND & AIMS: We have developed a therapeutic strategy for gastrointestinal infections that is based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. The aim of this study was to apply this to the development of a recombinant probiotic for treatment and prevention of diarrheal disease caused by enterotoxigenic Escherichia coli strains that produce heat-labile enterotoxin. METHODS: This was achieved by expressing glycosyltransferase genes from Neisseria meningitidis or Campylobacter jejuni in a harmless Escherichia coli strain (CWG308), resulting in the production of a chimeric lipopolysaccharide capable of binding heat-labile enterotoxin with high avidity. RESULTS: The strongest heat-labile enterotoxin binding was achieved with a construct (CWG308:pLNT) that expresses a mimic of lacto-N-neotetraose, which neutralized > or = 93.8% of the heat-labile enterotoxin activity in culture lysates of diverse enterotoxigenic Escherichia coli strains of both human and porcine origin. When tested with purified heat-labile enterotoxin, it was capable of adsorbing approximately 5% of its own weight of toxin. Weaker toxin neutralization was achieved with a construct that mimicked the ganglioside GM2. Preabsorption with, or coadministration of, CWG308:pLNT also resulted in significant in vivo protection from heat-labile enterotoxin-induced fluid secretion in rabbit ligated ileal loops. CONCLUSIONS: Toxin-binding probiotics such as those described here have considerable potential for prophylaxis and treatment of enterotoxigenic Escherichia coli-induced travelers' diarrhea.