A suitable and economical animal model of ovarian hormone deficiency can greatly enhance the understanding of postmenopausal-elevated risk of coronary heart disease. The male Golden Syrian hamster is a well-established small animal model of hypercholesterolemia, but the effect of ovariectomy on lipid profile in the female hamster is unclear. The objective of this study was to determine whether ovariectomized hamsters develop hypercholesterolemia and experience changes in body fat distribution consistent with changes observed in postmenopausal women. Twenty-two 90-day-old female Golden Syrian hamsters were divided into two groups and were either ovariectomized or sham-operated and given free access to a standard cholesterol-free laboratory diet for 65 days. Ovariectomized hamsters had significantly (P < 0.05) elevated serum total cholesterol concentrations (16.6%) as well as abdominal fat mass (56%; P< 0.01) despite equal food intake compared with the sham-operated group. In contrast, the mean intestinal weight and in vivo rate of sterol biosynthesis were significantly (P < 0.002 and P = 0.01, respectively) lower in the ovariectomized compared with the sham-operated group. In vivo rates of hepatic sterol biosynthesis were directionally lower (P = 0.1) in the ovariectomized group. No significant differences were observed in final body weight, serum triglycerides, or liver total cholesterol and lipids between the two groups. In conclusion, ovariectomized hamsters undergo changes in serum cholesterol and fat distribution similar to those experienced by postmenopausal women, and thus may serve as an appropriate model for postmenopausal hypercholesterolemia.

Journal Article↗

PubMed1997

Native and partially hydrolyzed psyllium have comparable effects on cholesterol metabolism in rats.

This study was conducted to determine whether the storage conditions and the levels of psyllium in the diet modulate its hypocholesterolemic effects. Seventy-five male Sprague-Dawley rats, age 90 d, were randomly divided into five treatment groups and were fed cholesterol-containing diets for 21 d. Diets included 10% cellulose (control); 5 or 10% psyllium stored 8 mo at 5 degrees C (PS5); or 5 or 10% psyllium stored 8 mo at 40 degrees C (PS40). The higher storage temperature caused a gradual decrease in molecular weight of the psyllium, as measured by changes in solution viscosity. Hepatic rates of sterol synthesis were significantly (P < 0.001) higher in all of the psyllium-fed rats compared with control rats [21 +/- 2, 312 +/- 35, 464 +/- 40, 328 +/- 49 and 439 +/- 57 nmol [3H]digitonin-precipitable sterol (DPS)/(g liver x h), respectively, for control, 5% PS5, 10% PS5, 5% PS40 and 10% PS40]. A similar trend was observed in intestinal rates of sterol synthesis, and the difference was significant (P < 0.05) for all treatment groups except the 5% PS5-fed group compared with the control group. Liver total cholesterol and total lipid concentrations were significantly lower in all psyllium-fed rats compared with controls. There were no significant differences in serum total cholesterol concentrations among the psyllium-fed groups, although serum cholesterol levels in both the PS5-fed groups were significantly (P < 0.05) lower than that in the control group (2.66 +/- 0.18, 2.62 +/- 0.15 and 3.26 +/- 0.12 mmol/L, respectively, for 5% PS5, 10% PS5 and control). Serum triglyceride and HDL cholesterol concentrations did not vary significantly among groups. The findings of this study indicate that the cholesterol-lowering activity of psyllium is unaltered by storage conditions shown to cause a moderate degree of hydrolysis.

Animals↗

PubMed1993

Cross-tolerance between carbamazepine and valproate on amygdala-kindled seizures.

Carbamazepine and valproate are two clinically used anticonvulsants which are also effective in the treatment of manic-depressive illness. Although the biochemical profiles of these drugs are markedly different, some mechanisms in common may be implied by their partially overlapping spectrum of therapeutic efficacy in seizure and affective disorders. Further evaluation of common biological targets of these agents was attempted by determining whether cross-tolerance would occur to the anticonvulsant effects of carbamazepine and valproate on amygdala-kindled seizures. It had previously been shown that tolerance to carbamazepine's anticonvulsant effects on amygdala-kindled seizures occurs only with contingent drug administration, i.e., it occurs only when the drug is injected before the kindling stimulation, and not when the drug is given after the seizure. In the current studies, rats that were made tolerant to carbamazepine showed cross-tolerance to valproate. Kindled rats given carbamazepine after each seizure stimulation (i.e., non-tolerant controls) did not show tolerance to valproate's anticonvulsant effects, indicating that the cross-tolerance between carbamazepine and valproate was also contingent. The clinical implications and potential common biochemical target mechanisms of the cross-tolerance between carbamazepine and valproate deserve further investigation.

Amygdala↗

PubMed1991

Lack of proconvulsant action of GABA depletion in substantia nigra in several seizure models.

The effect of intranigral application of a gamma-aminobutyric acid (GABA) synthesis inhibitor, was examined in 3 different rat seizure models. Bilateral intranigral infusion of isoniazid (150 micrograms) did not potentiate the effect of subcutaneous administration of a threshold dose (1.5 mg/kg) of the GABA antagonist bicuculline. Similarly, following pretreatment with intranigral isoniazid, neither severity nor latency to onset of seizures elicited by systemic injection of kainic acid (9 mg/kg) were modified. In addition, convulsive seizures evoked by the focal injection of bicuculline methiodide (40 ng) in an epileptogenic site within the deep prepiriform cortex (area tempestas) were not potentiated by intranigral isoniazid. These results were in sharp contrast to the marked potentiating effect of intranigral isoniazid (150 or 85 micrograms) on seizures induced by systemic administration of a subconvulsant dose of pilocarpine (150 mg/kg). In addition, we attempted to evoke a proconvulsant action from striatum. The striatum, origin of GABAergic projections to substantia nigra, is a region in which application of GABA antagonists have been found to be anticonvulsant in several seizure models. We therefore examined the effect of bilateral intrastriatal infusion of the GABA agonist, muscimol (5 ng) on the convulsant effect of threshold doses of systemically administered bicuculline (1.5 mg/kg). As was true with intranigral isoniazid, no proconvulsant effect was found using intrastriatal muscimol. Our data demonstrate that whereas striatonigral GABA circuitry can be activated by exogenous treatments so as to produce anticonvulsant actions in most seizure models, suppression of this circuitry does not potentiate convulsant activity in many of the same models.

Animals↗

PubMed1967

[Investigations of materno-fetal correlations of cattle. 2. The content of total nitrogen, urea, uric acid and creatinine of the amniotic and allantoic fluid].

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Amniotic Fluid↗