ALTERED SYMPATHETIC CONTROL OF NUTRIENT MOBILIZATION DURING PHYSICAL EXERCISE AFTER LESIONS IN THE VMH

To study the impact of obesity on sympathetic nervous regulation of nutrient mobilization, obese rats and lean controls were subjected to physical exercise. Male Wistar rats, rendered obese by bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) were subjected to 15 min swimming. Permanent cardiac catheters allowed frequent blood sampling. At rest, glucose, free fatty acids (FFA), and insulin concentrations were elevated in the obese animals, whereas catecholamine levels were similar in both groups. During exercise, glucose concentrations reached higher values in the lesioned rats, whereas these animals did not display the normal FFA increment. Plasma insulin concentrations were suppressed in both groups, and the rate of suppression was very similar when expressed as percentage change from resting levels. There was no difference in plasma epinephrine responses during swimming, but the increase in norepinephrine was diminished in the obese animals. The results suggest that obesity after VMH lesion leads to reduced stimulation of lipolysis by norepinephrine and a predominant mobilization of glucose during exercise, both favoring glucose utilization and the accumulation of fat

EXERCISE-INDUCED SYMPATHETIC FFA MOBILIZATION IN VMH-LESIONED RATS IS NORMALIZED BY FASTING

This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean controls were deprived of food for 48 h and submitted to 15 min of swimming. Food-deprived lean and obese rats displayed increased free fatty acid mobilization and utilization, whereas blood glucose concentrations were decreased. Basal plasma insulin levels were reduced by fasting in both groups, when compared with the ad libitum situation, but remained higher in the obese animals. Fasting augmented the norepinephrine response of the obese rats, resulting in equal profiles in lean and obese animals. These results indicate that VMH-lesioned animals are able to increase the sympathetic activation of adipose tissue during exercise to overcome an energy deficiency. Therefore, the function of the VMH in the regulation of the sympathetic nervous system controlling metabolism can be taken over by redundant mechanisms. The reduced sympathetic activity in ad libitum fed VMH-lesioned animals is therefore likely to be the result of the altered metabolism

Immuno-virological and toxicity outcomes of HIV-infected patients after 48 months of ART in Phnom Penh, Cambodia

Mexico AIDS Conference 200

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Is rejection a diffuse or localized process in small-bowel transplantation?

Utilization of endoscopy to both visualize and selectively biopsy an intestinal allograft has become the standard for early recognition and treatment of intestinal allograft rejection. Despite the widespread acceptance of the need for selective mucosal biopsies, it has not been shown that the histological features of intestinal allograft rejection are either localized or occur as part of a more diffuse phenomenon within a tubular allograft. To resolve these issues, 88 ileoscopies were performed in 12 small-bowel allograft recipients and mucosal biopsy samples were obtained at 5, 10, and 15 cm, respectively, from the ileal stoma. Each mucosal biopsy was labeled, processed, and evaluated individually for the presence and severity of any evidence for allograft rejection. The data obtained suggest that intestinal allograft rejection is a diffuse process, and biopsies obtained randomly from an ileal graft are likely to demonstrate evidence of allograft rejection when such is present. © 1994 Springer-Verlag New York Inc

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs