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Biomedical subjects

P Dickson

Publications and source records attributed to P Dickson.

5 recordsLinked to original sources

Lesions dorsal to the suprachiasmatic nuclei abolish split activity rhythms of hamsters.

Constant light exposure (LL) can result in "splitting" of circadian rhythms into two components coupled about 12 hr apart. Splitting has been interpreted as evidence for the presence of two main oscillators or groups of oscillators underlying circadian rhythms. Abolition of splitting after unilateral suprachiasmatic nucleus ablation suggested that each suprachiasmatic nucleus could correspond to one of these component oscillators. We examined whether lesions outside the suprachiasmatic nuclei (SCN) would abolish split activity rhythms of hamsters in LL. Wheel-running activity was recorded for 3 months after surgery. Tissue damage was assessed by Klüver-Barrera staining. Damage to areas dorso-caudal to the SCN was able to abolish the split condition. Bilateral damage to the anterior SCN, partial unilateral SCN ablation or unilateral periventricular damage also abolished the split pattern. These results indicate that destruction of one SCN is not essential for the elimination of split rhythms since lesions dorsal to the SCN or partial bilateral SCN damage are also effective. Indirect lesion effects on SCN function or damage to extra-SCN oscillators may account for the loss of the split condition.

Animals

Phenobarbital induction and acetaminophen hepatotoxicity: resistance in the obese Zucker rodent.

The obese Zucker rodent appears to lack a significant induction response after phenobarbital pretreatment. Induction of the hepatic cytochrome P-450 system with phenobarbital is known to enhance acetaminophen hepatotoxicity. The purpose of this study was to evaluate the influence of phenobarbital enzyme induction on acetaminophen hepatotoxicity in the obese and lean Zucker rodent. A preliminary study was performed evaluating the pharmacokinetics of acetaminophen in both the obese and lean Zucker rats. Data were utilized to calculate appropriate loading doses of acetaminophen during the subsequent hepatotoxicity study. Phenobarbital enzyme-inducing regimens were administered p.o. to achieve similar steady-state phenobarbital plasma concentrations. Control rats received appropriate placebo solutions. Serum hepatic transaminase enzymes and histologic evidence of hepatocellular necrosis were utilized to evaluate hepatic damage after p.o. administration of 1300 mg of acetaminophen to both obese and lean Zucker rats. Obese Zucker control animals had approximately 2.5 times the total hepatic glutathione content compared to their lean control (164.9 +/- 43.2 vs. 65.3 +/- 18.4 mumol/whole liver). Obese Zucker animals receiving only acetaminophen showed a trend toward a reduced incidence of hepatocellular necrosis compared to similarly treated lean littermates. Obese Zucker rodents pretreated with phenobarbital had an even more pronounced resistance to acetaminophen-induced hepatocellular necrosis (P less than .01) when compared to similarly treated lean littermates. Thus, acetaminophen hepatotoxicity is reduced in the obese Zucker rat and pretreatment with phenobarbital offers further protection against hepatocellular damage. We suggest that the previously unrecognized increase in hepatic glutathione plays a major role in the resistance of the obese Zucker rat to acetaminophen hepatotoxicity.

Acetaminophen

Enuresis.

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Age Factors