To determine how insulin deficiency leads to hypercholesterolemia, we examined cholesterol absorption, synthesis, and utilization in streptozocin-induced diabetic rats fed a grain-based diet ad libitum. Absorbed dietary cholesterol was determined from measurement of dietary cholesterol intake and previous data for cholesterol fractional absorption. Daily rates of cholesterol synthesis in the small intestine, liver, and periphery were calculated from recovery of labeled sterols after injection of 3H2O at six times during 24 h. Utilization of cholesterol for growth, fecal excretion, and bile acid synthesis were also determined. Absorbed dietary cholesterol in diabetic rats was double that in control rats. The contribution of absorbed cholesterol to total cholesterol production (sum of absorbed dietary cholesterol) and endogenous cholesterol synthesis) in control rats was 24% compared to 48% in diabetic rats. The increase in diabetic rats was due to overeating and, to a lesser extent, to increased fractional absorption. Overeating also induced intestinal hypertrophy and a twofold increase in cholesterol synthesis by the small intestine to 24% of whole-body production in diabetic rats. Consequently, the small intestine accounted for 72% of daily cholesterol input in diabetic rats compared to 37% in control rats, with diet accounting for two-thirds of the cholesterol input via the small intestine in both groups. In response to this increased input from the intestine, cholesterol synthesis in the periphery was 39% of whole-body production in control rats compared to 22% in diabetic rats, and synthesis in the liver was 26 and 6% of total cholesterol production in control and diabetic rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between methylphenidate (MP) oral dose and plasma concentration to social and cognitive behaviors was studied in 25 boys diagnosed as having "attention deficit disorder with hyperactivity". Children were administered successive 1-week treatment conditions under the following schedule of fixed oral doses given twice daily: placebo; 0.25 mg/kg; 0.50 mg/kg; 1.0 mg/kg; placebo. Teacher and parent ratings showed increased improvement in social behavior as a function of MP dose. No drug effects were obtained on cognitive performance. MP plasma concentrations were significantly associated with oral dose and with measures of social behavior. No relationship was found with cognitive behavior. Side effects at the largest dose were severe enough to require discontinuation of treatment for five children, but were relatively mild for the remaining children.
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