A Pilot Study Assessing the Impact of a Fortified Supplementary Food on the Health and Well-Being of Crèche Children and Adult TB Patients in South Africa

The South African population faces many of the global concerns relating to micronutrient deficiency and the impact this has on health and well-being. Moreover, there is a high prevalence of HIV infection, compounded by a high level of co-infection with TB.This pilot study evaluates the impact of a fortified supplementary food on the health and well-being of a cohort of crèche children, aged 3 to 6, and adult TB patients drawn from the Presidential Node of Alexandra, Johannesburg, South Africa. A further aim of this study was to evaluate the sensitivity and validity of non-invasive indicators of nutritional status in a field-based population sample.The investigational product, e’Pap, is supported by extensive anecdotal evidence that whole grain cereals with food-style nutrients constitute an effective supplementary food for those suffering from the effects of food insecurity, poor health and well-being, and coping with TB and HIV infection.The results indicate a beneficial effect of e’Pap for both study populations, and particularly for adult TB patients, whose baseline data reflected severe food insecurity and malnutrition in the majority of cases. There is evidence to suggest statistically significant improvements in key micronutrient levels, well-being and energy, hand-grip strength, the Bioelectrical Impedance Analysis (BIA) Illness Marker, and certain clinical indicators. Although Body Mass Index (BMI) and Mid Upper Arm Circumference (MUAC) are frequently used as standard measures to evaluate the efficacy of nutritional interventions, these indicators were not sufficiently sensitive in this study. Nor does weight gain necessarily indicate improved nutritional status. Hand-grip strength, lean body mass, and the BIA Illness Marker seem to be more useful indicators of change in nutritional status.     

The home range of ship rats (Rattus rattus) in beech forest in the Eglinton Valley,Fiordland, New Zealand: A pilot study

Abstract

Three male and two female ship rats (Rattus rattus) were radio‐tagged and tracked in beech (Nothofagus) forest in the Eglinton Valley, Fiordland, New Zealand over two field periods in 1996 and 2000. The home range of each animal was calculated using the minimum convex polygon method. Ranges of three male rats were 7.5, 9.1, and 11.4 ha whereas those of the female rats were 0.89 and 0.27 ha. The home ranges recorded for male rats were considerably larger than those reported from other studies in non‐beech forest. Ship rats are important predators of forest birds, and home range information could be used to provide a guide for trap or bait station spacing in beech forests. To carry out rat control in beech forests effectively, further studies are needed to determine if the results of this pilot study are typical, and if home ranges of ship rats change with season, or at various stages of the beech mast cycle.     

Autophagy and mesenchymal cell fibrogenesis

Autophagy is a catabolic pathway essential for cellular energy homeostasis that involves the self-degradation of intracellular components in lysosomes. This process has been implicated in the pathophysiology of many human disorders, including infection, cancer, and fibrosis. Autophagy is also recognized as a mediator of survival and proliferation, and multiple pathways induce autophagy under conditions of cellular stress, including nutrient and energy depletion. High autophagic activity has been detected in fibrogenic cells from several tissues; however the role of autophagy in fibrogenesis and mesenchymal cells varies greatly in different tissues and settings, with contributions uncovered to energy metabolism and collagen turnover by fibrogenic cells. Because several chemical modulators of autophagy have already been identified, autophagy regulation constitutes a potential target for antifibrotic therapy. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.     

Physiologic and molecular consequences of endothelial Bmpr2 mutation

Background

Pulmonary arterial hypertension (PAH) is thought to be driven by dysfunction of pulmonary vascular microendothelial cells (PMVEC). Most hereditary PAH is associated with BMPR2 mutations. However, the physiologic and molecular consequences of expression of BMPR2 mutations in PMVEC are unknown.

Methods

In vivo experiments were performed on adult mice with conditional endothelial-specific expression of the truncation mutation Bmpr2^delx4+, with age-matched transactivator-only mice as controls. Phenotype was assessed by RVSP, counts of muscularized vessels and proliferating cells, and staining for thromboses, inflammatory cells, and apoptotic cells. The effects of BMPR2 knockdown in PMVEC by siRNA on rates of apoptosis were assessed. Affymetrix expression arrays were performed on PMVEC isolated and cultured from triple transgenic mice carrying the immortomouse gene, a transactivator, and either control, Bmpr2^delx4+ or Bmpr2^R899X mutation.

Results

Transgenic mice showed increased RVSP and corresponding muscularization of small vessels, with histologic alterations including thrombosis, increased inflammatory cells, increased proliferating cells, and a moderate increase in apoptotic cells. Expression arrays showed alterations in specific pathways consistent with the histologic changes. Bmpr2^delx4+ and Bmpr2^R899X mutations resulted in very similar alterations in proliferation, apoptosis, metabolism, and adhesion; Bmpr2^delx4+ cells showed upregulation of platelet adhesion genes and cytokines not seen in Bmpr2^R899X PMVEC. Bmpr2 mutation in PMVEC does not cause a loss of differentiation markers as was seen with Bmpr2 mutation in smooth muscle cells.

Conclusions

Bmpr2 mutation in PMVEC in vivo may drive PAH through multiple, potentially independent, downstream mechanisms, including proliferation, apoptosis, inflammation, and thrombosis.     

Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation

Human tissue inflammation is terminated, at least in part, by the death of inflammatory neutrophils by apoptosis. The regulation of this process is therefore key to understanding and manipulating inflammation resolution. Previous data have suggested that the short-lived pro-survival Bcl-2 family protein, Mcl-1, is instrumental in determining neutrophil lifespan. However, Mcl-1 can be cleaved following caspase activity, and the possibility therefore remains that the observed fall in Mcl-1 levels is due to caspase activity downstream of caspase activation, rather than being a key event initiating apoptosis in human neutrophils.We demonstrate that apoptosis in highly purified neutrophils can be almost completely abrogated by caspase inhibition with the highly effective di-peptide caspase inhibitor, Q-VD.OPh, confirming the caspase dependence of neutrophil apoptosis. Effective caspase inhibition does not prevent the observed fall in Mcl-1 levels early in ultrapure neutrophil culture, suggesting that this fall in Mcl-1 levels is not a consequence of neutrophil apoptosis. However, at later timepoints, declines in Mcl-1 can be reversed with effective caspase inhibition, suggesting that Mcl-1 is both an upstream regulator and a downstream target of caspase activity in human neutrophils.