Neuroendocrine actions and regulation of hypothalamic neuropeptide Y during lactation.

The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroendocrine regulation of energy balance with controls over anterior and posterior pituitary hormone secretion. Further, reciprocal signaling to the NPY/AgRP system by leptin and ghrelin is responsible for the changes in expression of these hypothalamic peptides in lactating animals, and thus, may contribute to regulation of food intake and the various neuroendocrine adaptations of lactation.

Circulating adiponectin levels, body composition and obesity-related variables in Prader-Willi syndrome: comparison with obese subjects.

BACKGROUND: People with obesity and/or the metabolic syndrome have an increased risk for developing diabetes and cardiovascular disease and may have low adiponectin levels. The obesity associated with Prader-Willi syndrome (PWS) would be expected to have similar complications. However, it was recently reported that, despite their adiposity, people with PWS have reduced visceral fat and are less likely to develop diabetes mellitus or the metabolic syndrome compared with people with simple obesity. OBJECTIVE: To determine if plasma adiponectin levels and other variables relevant to diabetes and cardiovascular risk are different in a cohort of PWS subjects with known genetic subtypes compared with age-, sex- and weight-matched control subjects. RESULTS: Fasting plasma glucose, C-peptide, triglycerides, leptin and cholesterol levels were similar in PWS and obese subjects. Our 20 PWS subjects (mean age = 27.7 years) had higher percent body fat (54.1 vs 48.5%) determined by DEXA measurements and lower percent lean mass (45.9 vs 51.5%) compared with 14 obese controls (mean age = 26.9 year). Plasma adiponectin levels were significantly higher in PWS (15.5 +/- 8.2 microg/ml) than in obese controls (7.5 +/- 2.7 microg/ml). A significant positive correlation was found with insulin sensitivity in PWS subjects (r = 0.75, P = 0.0003) but not in obese controls (r = 0.36, P = 0.20). DISCUSSION: Our study confirmed an earlier observation of higher adiponectin levels in PWS subjects and less insulin resistance proportionate to their obesity status than found in subjects with simple obesity. Furthermore, no differences were seen in PWS subjects with the chromosome 15 deletion or maternal disomy 15. The reported excessive visceral adiposity in subjects with simple obesity compared with PWS may be associated with decreased production and lower circulating levels of adiponectin.

Differential effects of methamphetamine on expression of neuropeptide Y mRNA in hypothalamus and on serum leptin and ghrelin concentrations in ad libitum-fed and schedule-fed rats.

Relatively little is known concerning the interaction of psychostimulants with hypothalamic neuropeptide systems or metabolic hormones implicated in regulation of energy balance. The present studies tested whether methamphetamine alters the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP), two important orexigenic neuropeptides, or proopiomelanocortin (POMC), the precursor for the anorexigenic peptide alpha-melanocyte-stimulating hormone, or the secretion of leptin, insulin and ghrelin, concomitant with inhibition of food intake. Female rats were either fed ad libitum (AL) or placed on a scheduled feeding (SF) regimen, with access to food limited to 4 h/day. Administration of (+/-)-methamphetamine (7.5 mg/kg, i.p.) 2 h prior to food presentation significantly inhibited food intake in SF animals, but did not affect intake in AL animals. In a separate study, AL and SF animals were killed just prior to expected food presentation, and expression of NPY, AgRP and POMC mRNAs in hypothalamus was determined using in situ hybridisation; concentrations of leptin, insulin and ghrelin in serum were determined with radioimmunoassays. In saline-treated, SF controls, NPY and AgRP mRNA expression in arcuate nucleus and serum ghrelin were significantly elevated, and serum leptin and insulin were significantly reduced. Methamphetamine reversed the up-regulation of NPY mRNA expression observed in the SF condition, without affecting AgRP mRNA or the serum concentrations of metabolic hormones. However, in AL animals, NPY mRNA expression in arcuate and dorsomedial nuclei was significantly increased by methamphetamine, which also reduced serum leptin and insulin and increased serum ghrelin concentrations. These findings suggest that the inhibition of NPY expression in SF animals may be a mechanism underlying the anorexigenic effect of methamphetamine seen in this condition. The increase in NPY expression produced by methamphetamine in AL animals may be mediated by the ability of this drug to decrease secretion of leptin and insulin and increase secretion of ghrelin.

Role of leptin in orexigenic neuropeptide expression during lactation in rats.

The expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP), both of which are important neuropeptides involved in regulation of energy balance and hormone secretion, is up-regulated in the arcuate nucleus during lactation in rodents. The present study tested whether reductions in circulating insulin and/or leptin that occur in lactation provide the critical signals to these systems. Lactating female rats received 3-day infusions of either bovine insulin or recombinant rat leptin via Alzet Osmotic minipumps implanted subcutaneously in regimens designed to restore serum concentrations of these hormones to the higher non-lactating level. Compared to non-lactating rats in diestrus, lactating rats displayed significantly lower serum concentrations of insulin and leptin, and significantly increased NPY peptide concentrations in the paraventricular nucleus (PVN) and median eminence, and AgRP mRNA in the arcuate nucleus. Infusion of leptin in lactating females significantly increased serum concentrations of leptin and significantly reduced NPY concentrations in the PVN and median eminence, and decreased NPY and AgRP mRNAs in the arcuate nucleus. The same effects were produced by infusion of insulin in lactating rats, which restored both insulin and leptin concentrations in serum. The levels of pro-opiomelanocortin mRNA in the arcuate nucleus were not different in non-lactating and lactating females, and were not altered by leptin or insulin treatment. These findings support the hypothesis that the reduction in circulating leptin during lactation contributes to increased expression of NPY and AgRP in hypothalamic systems involved in the behavioural and neuroendocrine adaptations to lactation.

Non-typhi salmonella in children with severe malaria.

OBJECTIVE: To determine the association between Plasmodium falciparum malaria and non-typhi Salmonella in children. DESIGN: Cross-sectional hospital based study. SETTING: Kilifi District Hospital (KDH) between January 1997 and June 2001. SUBJECTS: Children aged between three months to 123 months (mean age 28.28 months) and who had been admitted to the paediatric or High Dependency Research Ward (HDRW) of the KDH. METHODS: A total of 19, 118 blood cultures routinely obtained for all admissions and 1,820 clinically indicated stools samples were obtained from 9,147 children admitted with malaria. The specimens were cultured and antibiotic sensitivity done using standard laboratory procedures with stringent internal and external quality control in place. RESULTS: The total bacterial pathogens isolated from blood and stool were 1,395/19,118 (7.3%) and 342/1,820 (19%) respectively. Non-typhi salmonella consisted of 260/1,395 (18.6%) of the positive blood cultures and 92/324 (28.4%) of the stool cultures out of which a total of 101 NTS occurred in children with severe malaria. Out of the 9,147 malaria cases admitted, 101/9,147 (1.10%) had concomitant NTS infection. NTS with severe malaria as a proportion of all malaria admissions for the period varied between 0.8% and 1.5%. There was a significant association (p-value=0.032) between clinical outcome of death and female sex of the patient. The NTS isolates which occurred with severe malaria showed various levels of antibiotic resistance. They were resistant to ampicillin (35%), chloramphenicol (18%), gentamicin (22%), cefuroxime (29%), sulphamethoxazole-trimethoprim (39%), ciprofloxacin (3%), cefotaxime (14%), amoxycillin-clavulanic acid (26%) and tobramycin (18.0%). Multidrug resistance (MDR) was seen in 34 (33.6%) of the isolates. CONCLUSIONS: NTS and severe malaria occurring together are a problem in this area and that a large number of the isolates are MDR. An elaborate case-controlled study is required to elucidate the chain of events of both NTS and malaria parasite co-existence.

Performance of West African Dwarf goats fed dehydrated poultry manure as a dry season supplement.

The performance of West African Dwarf goats fed dehydrated poultry manure when grazing maturing pastures was studied during 2 dry season months on the Accra Plains of Ghana. Twenty-eight goats (4 bucks and 24 does) were randomly selected and divided into 4 groups of one buck and 6 does each. Animals had access to pasture and, in addition, each group was randomly assigned to one of 4 supplementary dietary treatments: (1) 100% straw; (2) 60% straw + 40% molasses; (3) 50% straw + 40% molasses + 10% dehydrated poultry manure; (4) 40% straw + 40% molasses + 20% dehydrated poultry manure. Weight gains and efficiency of feed utilisation were significantly affected by diet type (P < 0.01). The goats fed Diets 3 and 4 gained more (P < 0.01) and utilised their diets more efficiently (P < 0.01) than goats fed Diets 1 and 2. Goats fed Diet 2 performed better than those fed Diet 1 in both traits. Dehydrated poultry manure (incorporated with molasses) supplementation improved the overall performance of goats grazing low quality natural pastures.