Atmospheric CO2 concentrations over the last glacial termination.

A record of atmospheric carbon dioxide (CO2) concentration during the transition from the Last Glacial Maximum to the Holocene, obtained from the Dome Concordia, Antarctica, ice core, reveals that an increase of 76 parts per million by volume occurred over a period of 6000 years in four clearly distinguishable intervals. The close correlation between CO2 concentration and Antarctic temperature indicates that the Southern Ocean played an important role in causing the CO2 increase. However, the similarity of changes in CO2 concentration and variations of atmospheric methane concentration suggests that processes in the tropics and in the Northern Hemisphere, where the main sources for methane are located, also had substantial effects on atmospheric CO2 concentrations.

Variations in atmospheric N2O concentration during abrupt climatic changes

Nitrous oxide (N2O) is an important greenhouse gas that is presently increasing at a rate of 0.25 percent per year. Records measured along two ice cores from Summit in Central Greenland provide information about variations in atmospheric N2O concentration in the past. The record covering the past millennium reduces the uncertainty regarding the preindustrial concentration. Records covering the last glacial-interglacial transition and a fast climatic change during the last ice age show that the N2O concentration changed in parallel with fast temperature variations in the Northern Hemisphere. This provides important information about the response of the environment to global climatic changes.

[Does serum HCV-RNA-positive hepatitis C differ from serum HCV-RNA-negative hepatitis C?]. / Unterscheidet sich die Serum-HCV-RNA-positive von der Serum-HCV-RNA-negativen chronischen Hepatitis C?

Viral RNA is detectable in the serum of the majority but not all patients with chronic hepatitis C. Whether the viremic form differs from the non-viremic form of the disease is unknown. We therefore compared histology (modified Knodell score) and liver function (conventional liver function tests, galactose elimination capacity and aminopyrin breath test) of viremic (n = 45) and non-viremic (n = 37) patients with chronic hepatitis C. Neither the total histologic score, nor any of the individual histologic parameters assessed differed significantly in serum HCV RNA positive and negative patients. Compared to non-viremic subjects, patients with detectable HCV RNA in serum had slightly higher transaminases (p = ns), lower serum albumin (p < 0.05) and decreased galactose elimination capacity (p < 0.05). This trend towards more severe functional hepatic impairment in serum HCV RNA positive patients persisted when cirrhotics and non-cirrhotics were analyzed separately; it fell just short of reaching statistical significance, however, most probably due to the small number of subjects per patient group. The median age of serum HCV RNA positive cirrhotics was 17 years, and that of serum HCV RNA negative cirrhotics 22 years higher than that of the respective non-cirrhotics. Biochemical (transaminases) and histological (intralobular and piece-meal necrosis) markers of disease activity, as well as metabolic functional reserve (aminopyrin breath test, galactose elimination capacity) and histologic severity of fibrosis correlated only loosely (Rs = 0.24-0.56), albeit significantly (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Colchicine does not inhibit secretin-induced choleresis in rats exhibiting hyperplasia of bile ductules: evidence against a pivotal role of exocytic vesicle insertion.

Based on studies in the pig, secretin choleresis has been proposed to be initiated by colchicine-inhibitable, exocytic insertion into the basolateral cholangiocyte membrane of intracytoplasmatic vesicles containing a H+ ATPase. Formal proof of this hypothesis in the intact liver of other species, however, is lacking. The effect of the microtubule inhibitor colchicine on the ductular bile formation and HCO3- secretion induced by secretin was, therefore, explored in a secretin-responsive rat model characterized by marked hyperplasia of bile ductules. While colchicine pretreatment significantly decreased basal bile flow from 142.1 +/- 8.8 to 83.4 +/- 8.2 microliters.min-1.kg-1 (p < 0.001) and basal biliary erythritol clearance from 112.7 +/- 6.3 to 69.9 +/- 7.0 microliters.min-1.kg-1 (p < 0.05), it did not significantly affect basal biliary [HCO3-], nor basal biliary bile acid output. Moreover, colchicine did not alter the effects of secretin. Thus, the secretin-induced increments in bile flow, biliary [HCO3-] and biliary HCO3- output averaged 58.2 +/- 13.6 microliters.min-1.kg-1, 16.6 +/- 3.1 mM and 5.3 +/- 1.4 mumol.min-1.kg-1 in vehicle-pretreated controls and 78.4 +/- 12.0 microliters.min-1.kg-1, 16.1 +/- 2.7 mM and 5.1 +/- 0.5 mumol.min-1.kg-1 in colchicine-pretreated animals (all p values = n.s.), respectively. This suggests that, at least in the rat model used, microtubule-dependent mechanisms are involved in basal, bile acid independent canalicular, but not in secretin-induced ductular, bile formation. Inasmuch as microtubule-dependent mechanisms are required for vesicle movement, this argues strongly against an absolute requirement for exocytic vesicle insertion in the ductular choleresis induced by secretin.

Hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during rat liver regeneration.

In hepatocytes in vitro, Na+/H+ exchange, an important regulator of intracellular pH, is activated by epidermal growth factor, but its activity during liver regeneration in vivo is unknown. We therefore compared activity and regulation of Na+/H+ exchange in hepatocytes isolated after two-thirds partial hepatectomy or sham surgery, respectively, by measuring intracellular pH (fluorimetry) and steady state Na+/H+ exchange mRNA levels (Northern blotting). Resting intracellular pH increased from 7.06 +/- 0.02 to 7.12 +/- 0.02 (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Na+/H+ exchange-mediated rates of intracellular pH recovery from an acid load increased from 0.075 +/- 0.018 to 0.151 +/- 0.018 pH units/min (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Because intracellular buffering capacity was not affected, this reflects increased Na+/H+ exchange activity. The inverse relationship between Na+/H+ exchange activity and intracellular pH was shifted by about 0.1 pH units toward more alkaline pH values 2 hr but not 20 hr after partial hepatectomy, whereas steady-state Na+/H+ exchange mRNA levels remained unchanged. In conclusion, hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during liver regeneration induced in the rat by partial hepatectomy.

[Increased liver enzymes: what should be done?]. / Erhöhte Leberenzyme: was nun?

The transaminases, alkaline phosphatase (AP) and gamma-glutamyl transferase (G-GT) are most widely used as indicators of hepatobiliary disease. Elevated serum levels of transaminases (AST and ALT) usually indicate hepatocellular damage. ALT elevations, however, can also be of extrahepatic origin (muscle). The ratio of the transaminases in serum (AST/ALT) and the mitochondrial isoenzyme of AST are frequently higher in alcoholic than in non-alcoholic liver diseases. Serum activities of AP and G-GT are elevated in cholestasis: Both enzymes, however, are not liver-specific and G-GT activity is induced by alcohol and certain drugs. A hepatic enzyme pattern (predominant transaminase elevation) should be discriminated from a cholestatic pattern (predominant AP and G-GT elevation). The most frequent diagnoses in asymptomatic patients with accidentally detected, mostly mild to moderate transaminase elevations are: alcoholic liver disease, (mostly chronic) viral hepatitis, and already much less frequently, drug induced liver disease and non-alcoholic steatosis. Solely if the respective investigations are negative or/and the transaminases stay elevated for greater than or equal to 6 months despite strict alcohol abstinence, omission of any potentially hepatotoxic drug or weight reduction are further steps justified.