Childhood consumption of dietary polyunsaturated fat lowers risk for coronary artery atherosclerosis in African green monkeys

This study was designed to test the hypothesis that consumption of diets enriched in polyunsaturated fatty acids beginning at birth and continuing into young adulthood would lower the risk for atherosclerotic coronary heart disease early in life through their effects on plasma lipid and apolipoprotein concentrations while supporting good health and normal development. Accordingly, African green monkeys (n = 140) were raised on atherogenic diets (0.8 mg cholesterol per kcal) enriched with either saturated or n-6 polyunsaturated fatty acids. Breast milk from mothers fed the polyunsaturated fat diet became enriched in polyunsaturated fatty acids relative to the saturated group; thus, the period of nursing also reflected the dietary fatty acid shift. Age, gender, and dietary fat type independently affected plasma lipid and apolipoprotein concentrations. Age effects were similar for all lipid and lipoprotein variables; the concentrations were low immediately after birth, increased dramatically during the first 4-6 months of life, and then attained levels similar to those of adult animals by 2 years of age. Significant differences by gender were found such that females maintained lower total plasma cholesterol concentrations and higher high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations. Dietary fat effects were age dependent. Before weaning at 5 months of age, total plasma cholesterol and apoB concentrations were lower in animals consuming polyunsaturated fat, and this pattern was maintained into young adulthood. Lower concentrations of plasma triglycerides, HDL cholesterol, and apoA-I for polyunsaturated fat-fed animals were found only in the postweaning period (6-60 months of age). Since this pattern of response to dietary polyunsaturated fat in the juvenile animals was similar to that for adult animals fed these same diets in which there was less atherosclerosis and because subsequent studies have documented less coronary artery atherosclerosis in the polyunsaturated fat-fed juveniles, we conclude that early dietary intervention was beneficial in this group for lowering the risk of coronary artery atherosclerosis. The results in this primate model support the concept that intervention to modify coronary heart disease risk that is initiated early in childhood will have beneficial effects.     

Effect of treatment with BCG on the course of visceral leishmaniasis in BALB/c mice

Intravenous inoculation of BCG was found to be both prophylactic and therapeutic in BALB/c mice against challenge with amastigotes of Leishmania donovani. Spleens and livers of mice inoculated with BCG maintained total parasite burdens at significantly lower levels when compared to controls. BCG administered intravenously 14 days prior to and on the same day of protozoan challenge was more protective than vaccine given 30 and 14 days prior to challenge. A level of 10(7) viable units of BCG provided more protection against challenge with parasites than did 10(6) viable units. BCG given the same route as the challenge dose of amastigotes provided more protection than if administered via some other route. BCG given to mice with an already established infection was shown to significantly reduce their parasite burdens.     

Changes in asthma severity in Manitoba

OBJECTIVE: To assess changes in the severity of physician-diagnosed asthma between 1983 and 1988. DESIGN: Cross-sectional studies examining the frequency of markers of asthma severity: hospitalizations, ICU admissions, hospital emergency department visits, multiple physician contacts, and referrals to specialists in patients aged 0 to 14 years, 14 to 34 years, and > or = 35 years separately. SETTING: Physicians' claims data from the universal Provincial Health Insurance Plan for fiscal years 1983 and 1988. PATIENTS: All patients with the diagnosis of asthma, bronchitis, and COPD identified from the Manitoba Health database. MEASUREMENTS: The markers of severity were related to the prevalence of patients seeing a physician and receiving a diagnostic label of asthma, COPD, or bronchitis. RESULTS: The number of patients with physician-diagnosed asthma increased by 36.4% over the 5 years. In 1983, 11% of asthmatics were hospitalized during the year and 8% were hospitalized in 1988 (-2.5%; 95% confidence interval [CI], -3.2 to -1.8%). During both years, about 75% of the patients hospitalized were in hospital once only. Mean and median duration of hospital stay declined. The percentage of asthmatics seen in the hospital emergency departments declined slightly in all age groups, the total being 21% in 1983 and 18% in 1988 (-3.5%; 95% CI, -4.5 to -2.5%). About one third of the patients with asthma were seen only once by a physician during both of the years examined, 43 to 45% of them being seen on three or more occasions during both years. Referrals to specialists for all asthmatics increased from 12 to 14% (1.9%; 95% CI, 1.0 to 2.8%) from 1983 to 1988. This was almost entirely due to an increase from 11 to 16% (5.1%; 95% CI, 4.0 to 6.2%) in the youngest age group, an increase not accompanied by an increase in any other marker of severity. Changes in asthma severity were similar to changes in the severity in patients with bronchitis and COPD. CONCLUSION: No increase in severity of asthma was seen between 1983 and 1988, but the prevalence of the diagnostic label of asthma increased substantially.     

L-arginine attenuates platelet reactivity in hypercholesterolemic rabbits

Platelets are capable of producing nitric oxide (NO) through the L-arginine-NO synthase pathway. Acute exposure to supraphysiological concentrations of L-arginine in vitro increases the production of NO by platelets and is associated with an increase in platelet cyclic GMP (cGMP) levels and a reduction in platelet aggregation. The purpose of this study was to determine if chronic oral administration of L-arginine decreases platelet aggregation in hypercholesterolemic animals and to determine if this effect is mediated by the metabolism of L-arginine to NO. Male New Zealand White rabbits were fed normal chow (Con), a 1% cholesterol diet (Chol), or a 1% cholesterol diet supplemented with a sixfold enrichment of dietary L-arginine (Arg) or L-methionine (Met). After 10 weeks, cholesterol levels were equally increased in Chol and Arg animals, whereas plasma arginine levels were doubled in the Arg group. There was no difference in maximum aggregation initiated by ADP (100 mumol/L) between washed platelets from Con, Met, and Chol animals, but aggregation of platelets from Arg animals was significantly decreased (P < .05). In aggregating platelets from Arg animals, cGMP levels were significantly higher than the other groups (P < .05). When platelets were incubated ex vivo with the NO synthase inhibitor NG-monomethyl-L-arginine, the effects of dietary L-arginine were reversed. Chronic dietary supplementation of L-arginine decreases platelet aggregation in hypercholesterolemic rabbits. This effect appears to be due to the metabolism of L-arginine to NO.