Cytochrome P450 2E1 (CYP2E1) plays an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH) in animal models, but its role in the pathogenesis of human NASH is unclear. Therefore, we measured hepatic CYP2E1 activity and its correlates in a cohort of nondiabetic patients with NASH (NDN) and controls to explore its role in the pathogenesis of human NASH. Hepatic CYP2E1 activity was assessed using the oral clearance (CL PO ) of chlorzoxazone (CHZ) in 20 NDN and 17 age, gender, and body mass index (BMI)-matched controls. The relationship between hepatic CYP2E1 activity and demographic and anthropometric variables; fasting levels of insulin, glucose, lipids, and ␤-OH butyrate; insulin resistance; and nocturnal hypoxemia was assessed. Furthermore, expression of CYP2E1 in the peripheral lymphocytes was assessed using reverse transcription-polymerase chain reaction (RT-PCR). The CL PO of CHZ was significantly (P ‫؍‬ .03) greater in NDN (41 ؎ 12 L/h) compared with controls (33 ؎ 16 L/h). Lymphocyte CYP2E1 messenger RNA was significantly higher in NDN compared with controls (11.5 ؋ 10 3 ؎ 10 ؋ 10 3 vs. 2.6 ؋ 10 3 ؎ 1.2 ؋ 10 3 molecules/ g total RNA, respectively, P < .001). On univariate analysis, BMI, respiratory quotient, high-density lipoprotein, triglycerides, insulin, insulin resistance, hypoxemia, and ␤-OH butyrate significantly correlated with hepatic CYP2E1 activity. However, on stepwise regression analysis, only nocturnal hypoxemia (r ‫؍‬ 0.50, P ‫؍‬ .009) and ␤-OH butyrate (r ‫؍‬ 0.37, P ‫؍‬ .04) were independent predictors of hepatic CYP2E1 activity. In conclusion, hepatic CYP2E1 activity and lymphocyte CYP2E1 expression are enhanced in NDN. The significant correlations noted between CYP2E1 and hypoxemia and ␤-OH butyrate suggest that these factors play a role in increased CYP2E1 activity that is seen in patients with NASH. (HEPATOLOGY 2003;37:544-550.)

Recent advances in muscle biology concerning the discoveries of a large variety of proteins have been described in this review. The existence of polymorphism in several muscle proteins is now well established. Various isoforms of myosin not only account for the difference in physiological functions and biochemical activity of different fiber types or muscles, but also seem to differ in functional properties in food systems. The functionality of various muscle proteins, especially myosin and actin in the gelation process in modal systems which simulate structured meat products, is discussed at length. Besides, the role of different subunits and subfragments of myosin molecule in the gelation mechanism, and the various factors affecting heat-induced gelation of actomyosin in modal systems are also highlighted. Finally, the areas which need further investigation in this discipline have been suggested.

The influence of three levels of vitamin E in the diet of pigs on the subcellular deposition of u-tocopherol in the muscle

There was a marked increase in hepatic CYP2E1 activity in obese Type II diabetics as assessed by chlorzoxazone disposition. Increased expression of CYP2E1 mRNA in peripheral blood mononuclear cells was found in both types of diabetes mellitus. Adverse hepatic events associated with Type II diabetes may be in part a result of enhanced CYP2E1 expression and activity.