Effect of feeding β-sitosterol alone or in combination with cholestyramine during early life on subsequent response to cholesterol challenge in adult life in guinea-pigs

Abstract

I. Most subjects who have their large intestine removed and an ileostomy formed lead a healthy life after operation, although they are prone to a variety ofmetabolic problems. In order to determine the factors likely to lead to these metabolic disturbances a detailed assessment of ileostomy output and composition and of dietary intake in relation to nutritional and metabolic status has been made in a group of ileostomy patients living at home. 2.Thirty-six volunteers with established ileostomies (twenty-six ulcerative colitis (UC) patients and ten Crohn's colitis (CC) patients) made a 24 h collection of urine and ileostomy effluent and kept a 7 d record of dietary intake and the frequency w t h which they emptied their ileostomy bag. Blood was collected for haematological and biochemical indices of nutritional status and height, weight and skinfold thickness were measured.3. Effluent output for the whole group was 760+322 g/day (range 273-1612) and was very closely related to effluent sodium output (R 0.98). Stepwise multiple regression analysis of dietary and other variables identified the amount of ileum resected as the main determinant of both effluent output and effluent sodium. The CC group had significantly greater effluent output (1084+340 g/d) compared with the UC patients (635+215 g/d) (P < 0401); and excreted significantly more nitrogen, carbohydrate and sodium than the UC group.4. The CC patients particularly showed evidence of salt depletion. The mean (fm) 24 h urine Na loss for CC patients was 31 & 30 mmol and for UC patients 67 + 34 mmol (P c 0.01) with five of the ten CC patients v. four of the twenty-six patients with UC having raised urinary or plasma aldosterone levels. 5.All subjects had normal haematological and biochemical indices of nutritional status in the blood. Height and percentage body fat were also within the normal range when compared with a control population matched for age, sex and occupation, but patients with an ileostomy weighed on average 4.1 kg less than the controls. 6. These studies show that patients with an ileostomy come within the range of the normal population for most nutntional indices although are at increased risk of salt depletion. Effluent volume, which is probably the determining factor in most metabolic complications of ileostomy, is related more to the extent of the small bowel resection than to diet.

Guinea Pigs as Models to Study the Hypocholesterolemic Effects of Drugs

“…In a follow-up study conducted by the same laboratory (33), pretreated guinea pigs presented increased CYP7 activity and higher secretion of chenodeoxycholic acid, the major bile acid in the guinea pig. These findings suggest that enhancement of bile acid synthesis and excretion in neonatal life persists long after cholestyramine treatment is discontinued (33).…”

“…The US National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III emphasizes that patients with CHD, or who have a risk of CHD and LDL cholesterol (LDL-C) levels >130 mg/dL, should receive drug therapy with a goal of reducing LDL-C to <100 mg/dL (23). To date, guinea pigs have been used to analyze the effects of numerous drug treatments, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (6,7,(15)(16)(17)48,51,53,54,77), Acyl-CoA:Cholesterol Acyltransferase (ACAT) inhibitors (40,46), cholestyramine (27,33,80,87), fibric acids (47,82), probucol (35), and apical sodium co-dependent bile acid transporter (ASBT) inhibitors (83,84). The growing incidence of dyslipidemia in Western societies reinforces the need for an appropriate animal model for the evaluation of cholesterol lowering drugs.…”

Diet and metabolic development

“…on the individual early in life may alter the later development of that individual (1)(2)(3)(4)(5). Thus any adaptive response in adult life may be conditioned by the first adaptation to an external stimulus early in life (see Table 1).…”