Low cost of locomotion in lizards that are active at low temperatures.

The nocturnality hypothesis of K. Autumn and coworkers states that nocturnal geckos have evolved a low energetic cost of locomotion (C(min)). A low C(min) increases maximum aerobic speed and partially offsets the decrease in maximum oxygen consumption caused by activity at low nocturnal temperatures. We tested whether a low C(min) is unique to nocturnal geckos or represents a more general pattern of convergent evolution among lizards that enables nocturnality and/or cold-temperature activity. We measured C(min) in four carefully selected lizard species from New Zealand (two nocturnal and two diurnal; n=5-9 individuals per species), including a nocturnal and diurnal gecko (a low C(min) is a gecko trait and is not related to nocturnality), a nocturnal skink (a low C(min) is related to being nocturnal), and a diurnal skink active at low temperatures (a low C(min) is related to being active at low body temperatures). The C(min) values of the four species measured in this study (range=0.21-2.00 mL O(2) g(-1) km(-1)) are lower than those of diurnal lizards from elsewhere, and the values are within or below the 95% confidence limits previously published for nocturnal geckos. A low C(min) increases the range of locomotor speeds possible at low temperatures and provides an advantage for lizards active at these temperatures. We accepted the hypothesis that nocturnal lizards in general have a low C(min) and provide evidence for a low C(min) in lizards from cool-temperate environments. The low C(min) in lizards living at high latitudes may enable extension of their latitudinal range into otherwise thermally suboptimal habitats.

Bile acids in the assessment of hepatocellular function.

Bile acids, which are synthesized in the liver from cholesterol, are important in the production of bile flow, excretion of cholesterol, and intestinal digestion and absorption of fats and fat-soluble vitamins. Increases and/or alterations in concentrations of bile acids in serum are specific and sensitive indicators of hepatobiliary disorders. Synthesis of bile acids in hepatocytes involves steps in endoplasmic reticulum, cytosol, mitochondria, and peroxisomes. Other important hepatocellular processes involving bile acids include active uptake by the basolateral membrane, intracellular transport, P-450-mediated conjugations and hydroxylations, and canalicular secretion. Hydrophobic bile acids produce hepatotoxicity in vivo and in vitro. In experimental and epidemiologic studies, some of these forms have been identified as causative agents in the development of colon and liver (experimental only) cancer. Conversely, several hydrophilic forms, primarily ursodeoxycholic acid, have demonstrated cytoprotective properties in a variety of clinical and experimental hepatobiliary diseases and disorders. Because bile acids can have dramatically different properties and effects, determination of mechanisms of action of these compounds has become an active area of research. Primary isolated hepatocytes provide an opportunity to investigate bile acid-related functions and effects in well-designed, carefully controlled studies. Short-term cultures have been used to study a variety of issues related to bile acids, including cytotoxicity, synthesis, and hepatocellular processing. With these systems, however, many functions of mature hepatocytes, including those pertaining to bile acids, can be lost when cultures are maintained for more than several days. Recent developments in culture techniques permit long-term maintenance of functionally stable, differentiated cells. Pertaining to bile acid research, these systems remain to be fully characterized but, in appropriate situations, they should provide important alternatives to in vivo studies and short-term in vitro assays.

Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction.

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCI4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4 hepatotoxicity is due to decreased water and feed intake.