Micronutrient status in lactating mothers before and after introduction of fortified flour: cross-sectional surveys in Maela refugee camp

Background Deficiency of micronutrients is common in refugee populations. Objectives Identify deficiencies and whether provided supplements and wheat flour fortified with 10 micronutrients impacts upon status among breast-feeding women from Maela refugee camp. Methods Two sequential cross-sectional studies were conducted in different groups of lactating mothers at 12 weeks postpartum. The first survey was before and the second 4-5 months after micronutrient fortified flour (MFF) had been provided to the camp (in addition to the regular food basket). Iron status and micronutrients were measured in serum, whole blood, and in breast milk samples. Results Iron and zinc deficiency and anemia were highly prevalent while low serum retinol and thiamine deficiency were rarely detected. Iron and zinc deficiency were associated with anemia, and their proportions were significantly lower after the introduction of MFF (21 vs. 35% with soluble transferrin receptor (sTfR)>8.5 mg/L, P = 0.042, and 50 vs. 73% with serum zinc<0.66 mg/L, P = 0.001). Serum sTfR, whole-blood thiamine diphosphate (TDP) and serum β-carotene were significant predictors (P<0.001) of milk iron, thiamine and β-carotene, respectively. Lower prevalence of iron deficiency in the MFF group was associated with significantly higher iron and thiamine in breast milk. Conclusions High whole-blood TDP and breast milk thiamine reflected good compliance to provided thiamine; high prevalence of iron deficiency suggested insufficient dietary iron and low acceptance to ferrous sulfate supplements. MFF as an additional food ration in Maela refugee camp seemed to have an effect in reducing both iron and zinc deficiency postpartum. © Springer-Verlag 2012

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Rationale Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. Objective The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Results Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Conclusions Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many \u201coff target\u201d effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence

Proteins with Complex Architecture as Potential Targets for Drug Design: A Case Study of Mycobacterium tuberculosis

Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only

Amplification of wildfire area burnt by hydrological drought in the humid tropics

Borneo’s diverse ecosystems, which are typical humid tropical conditions, are deteriorating rapidly, as the area is experiencing recurrent large-scale wildfires, affecting atmospheric composition1, 2, 3, 4 and influencing regional climate processes5, 6. Studies suggest that climate-driven drought regulates wildfires2, 7, 8, 9, but these overlook subsurface processes leading to hydrological drought, an important driver. Here, we show that models which include hydrological processes better predict area burnt than those solely based on climate data. We report that the Borneo landscape10 has experienced a substantial hydrological drying trend since the early twentieth century, leading to progressive tree mortality, more severe than in other tropical regions11. This has caused massive wildfires in lowland Borneo during the past two decades, which we show are clustered in years with large areas of hydrological drought coinciding with strong El Niño events. Statistical modelling evidence shows amplifying wildfires and greater area burnt in response to El Niño/Southern Oscillation (ENSO) strength, when hydrology is considered. These results highlight the importance of considering hydrological drought for wildfire prediction, and we recommend that hydrology should be considered in future studies of the impact of projected ENSO strength, including effects on tropical ecosystems, and biodiversity conservation

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

Application of multi‑method approach to assess groundwater–surface water interactions, for catchment management

Globally, the dependence of river systems to delayed discharge of subsurface water to augment flows during dry seasons is well documented. Discharge of fresh subsurface water can dilute concentrated river flow quality during reduced flow. Observed and reported results on the Berg River’s declining water quantity and quality are a concern to the regions socio-economic growth and environmental integrity. Understanding the role of subsurface water discharges on the quantity and quality of receiving surface water courses can improve their management during dry periods. A case study was designed and implemented in the upper Berg River catchment in the Western Cape Province of South Africa to assess the influence of groundwater–surface water interaction on water quantity and quality. This study aimed to quantify and characterize the quality of subsurface water available in the upper catchment to improve observed declining water quality downstream. Hydrograph separation provided estimates of water fluxes during 2012–2014 low and high flow periods, while hydrochemical analysis provided insights on impacts of major land use activity in this catchment on water resources. Hydrograph separation analysis indicated that the Berg River is 37.9% dependent on subsurface water discharges annually. Dominant Na–Cl-type water indicates the quality of water from the upper Berg River is largely affected by natural processes including short residence times of aquifer water, rock–water interactions and atmospheric deposition of NaCl ions. These results provide insights for suggesting management options to be implemented to protect subsurface water for continued dilution and water resources management in the lower catchments