The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK—carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity

The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.

During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77$2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia

The impact of charging for insecticide on the Gambian National Impregnated Bednet Programme.

During the second year of the Gambian National Impregnated Bednet Programme (NIBP) charges for insecticide ($0.50 per net) were introduced into the half of the primary health care villages in the country where insecticide have been provided free of charge the previous year. Free insecticide was provided in the remaining villages that had acted as controls during the previous year. In villages where insecticide was provided free, 77$2-3 for insecticide treatment for all the bednets in a household represents a substantial outlay. Further education on the benefits of treatment of nets and/or the provision of cheaper insecticide will be required before the full benefits of this powerful new malaria control measure can be fully realised in the Gambia

Determinants of delays in travelling to an emergency obstetric care facility in Herat, Afghanistan: an analysis of cross-sectional survey data and spatial modelling.

BACKGROUND: Women's delays in reaching emergency obstetric care (EmOC) facilities contribute to high maternal and perinatal mortality and morbidity in low-income countries, yet few studies have quantified travel times to EmOC and examined delays systematically. We defined a delay as the difference between a woman's travel time to EmOC and the optimal travel time under the best case scenario. The objectives were to model travel times to EmOC and identify factors explaining delays. i.e., the difference between empirical and modelled travel times. METHODS: A cost-distance approach in a raster-based geographic information system (GIS) was used for modelling travel times. Empirical data were obtained during a cross-sectional survey among women admitted in a life-threatening condition to the maternity ward of Herat Regional Hospital in Afghanistan from 2007 to 2008. Multivariable linear regression was used to identify the determinants of the log of delay. RESULTS: Amongst 402 women, 82 (20%) had no delay. The median modelled travel time, reported travel time, and delay were 1.0 hour [Q1-Q3: 0.6, 2.2], 3.6 hours [Q1-Q3: 1.0, 12.0], and 2.0 hours [Q1-Q3: 0.1, 9.2], respectively. The adjusted ratio (AR) of a delay of the "one-referral" group to the "self-referral" group was 4.9 [95% confidence interval (CI): 3.8-6.3]. Difficulties obtaining transportation explained some delay [AR 2.1 compared to "no difficulty"; 95% CI: 1.5-3.1]. A husband's very large social network (> = 5 people) doubled a delay [95% CI: 1.1-3.7] compared to a moderate (3-4 people) network. Women with severe infections had a delay 2.6 times longer than those with postpartum haemorrhage (PPH) [95% CI: 1.4-4.9]. CONCLUSIONS: Delays were mostly explained by the number of health facilities visited. A husband's large social network contributed to a delay. A complication with dramatic symptoms (e.g. PPH) shortened a delay while complications with less-alarming symptoms (e.g. severe infection) prolonged it. In-depth investigations are needed to clarify whether time is spent appropriately at lower-level facilities. Community members need to be sensitised to the signs and symptoms of obstetric complications and the urgency associated with them. Health-enhancing behaviours such as birth plans should be promoted in communities