Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100%) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages

Evaluation of Antibacterial Activity and Phytoconstituents of the Aqueous Leaves Extract of Alchornea Cordifolia

Alchornea cordifolia Schum and Thonn. (Euphorbiaceae) is a plant widely used in traditional medicines of Ghana for the treatment of skin and other infections. This study evaluated the antibacterial properties and phytoconstituents of the aqueous leaves extract of A. cordifolia with particular reference to methicillin-resistant Staphylococcus aureus (MRSA). Minimum inhibitory and bactericidal concentrations (MIC and MBC) of the aqueous leaves extract of the plant were evaluated against 32 clinical isolates of MRSA and controls by the microdilution technique in Iso-sensitest broth. Growth and time-kill curves were also carried out using spectroscopy at 490 nm and viable cell counts method. Mean diameter of zones of inhibition ranged 18-30 mm of the aqueous extract of the plant were found against MRSA. MIC and MBC values ranged 1.6-3.1 mg/ml and 6.5-12.5 mg/ml of the aqueous leaves extract of A. cordifolia were found against the 32 clinical isolates of MRSA with most of the strains having MIC value of 3.1 mg/ml and MBC value of 12.5 mg/ml. Growth and time-kill curves indicate bacteriostatic activity of the plant extract on MRSA. Phytochemical analysis of the extract showed low concentrations of alkaloids and saponins but very high concentrations of tannins present in the leaves of the plant. From the results of the study, aqueous leaves extract of A. cordifolia may contain antibacterial compounds that justify its usage in traditional medicine

Trophic ecology of common elasmobranchs exploited by artisanal shark fisheries off south-western Madagascar

Knowledge of the trophic ecology and interactions of marine top predators is fundamental for understanding community structure and dynamics as well as ecosystem function. We examined the feeding relationships of 4 heavily exploited elasmobranchs caught in coastal artisanal shark fisheries in south-western Madagascar in 2009 and 2010—Sphyrna lewini, Loxodon macrorhinus, Carcharhinus falciformis and Rhynchobatus djiddensis—using stable isotope (δ15N and δ13C) analysis. Relative trophic position (indicated by δ15N) and foraging location (indicated by δ13C) differed among species. Isotopic niche width was highly variable: more pelagic species, such as S. lewini and C. falciformis, had the broadest isotopic niches while the benthic R. djiddensis had the narrowest. A high percentage of niche overlap occurred between R. djiddensis and 2 of the species, C. falciformis (93.2%) and L. macrorhinus (73.2%), and to a lesser extent S. lewini (13.3%). Relative trophic position of S. lewini significantly increased with size, suggesting a dietary shift with age. Sex differences in δ15N values were observed in L. macrorhinus, suggesting intraspecific niche partitioning. Variation in stable isotope values among these 4 highly exploited elasmobranch species indicates trophic structuring, likely driven by differences in diet and habitat use as well as by size and sex. This study provides the first baseline information on the trophic ecology of elasmobranchs caught in artisanal fisheries from south-western Madagascar

GP/GPN partner* perspectives on clinical placements for student nurses in general practice: can a community of practice help to change the prevailing culture within general practice?

Background: The UK Government document 5 year forward view describes the need to move chronic disease management from secondary to primary care, which will require a significant increase in the numbers of General Practice Nurses (GPNs). Until recently, there has been no specific recruitment strategy to address this increased need. In recent times, a number of solutions have been suggested to address this impending GPN recruitment crisis. For example, Health Education England (HEE) commission General Practitioners (GPs), who are members of the Advanced Training Practice Scheme (ATPS), to provide placements for student nurses within general practice. Methods: A descriptive qualitative study was undertaken, in which data were collected using semi-structured interviews with 16 GPs and 2 GPN partners∗. Qualitative analysis used a framework approach and themes were cross-checked within the team and member checking was undertaken with a convenience sample of GPs. The research had ethical approval and anonymity and confidentiality were maintained. Results: From the GP perspective, there were two key themes that emerged from the data. The first theme of 'fishing in the same small pond' included succession planning for the general practice workforce, the 'merry go round' of poaching staff from other practices, and the myths and misunderstandings that have grown up around general practice nursing. The second theme, 'growing your own', looked at the impact of the student nurse placements as a means to address the crisis in GPN recruitment. There was recognition of the need for cultural change in the way that GPNs are recruited, and that the ATPS was one way of helping to achieve that change. There were however a number of challenges to sustaining this cultural shift, such as the financial constrains placed upon the GP practice, and the need to function as a 'small business'. Conclusions: Despite all the challenges, the evidence is that, through the Community of Practice (CoP), the ATPS scheme is beginning to 'bear fruit', and there is a subtle but discernible move by GPs from a 'why would we?' to 'why wouldn't we?' invest in education and training for nurses in general practice. N.B. The term GPN partner∗denotes a GPN who is a 'full partner' in the practice business, holding the same NHS contracts and the same status as a GP. For the purposes of the paper itself, the term GP will be used to denote both types of partner

Coxsackievirus B3 infects and disrupts human induced-pluripotent stem cell derived brain-like endothelial cells

Coxsackievirus B3 (CVB3) is a significant human pathogen that is commonly found worldwide. CVB3 among other enteroviruses, are the leading causes of aseptic meningo-encephalitis which can be fatal especially in young children. How the virus gains access to the brain is poorly-understood, and the host-virus interactions that occur at the blood-brain barrier (BBB) is even less-characterized. The BBB is a highly specialized biological barrier consisting primarily of brain endothelial cells which possess unique barrier properties and facilitate the passage of nutrients into the brain while restricting access to toxins and pathogens including viruses. To determine the effects of CVB3 infection on the BBB, we utilized a model of human induced-pluripotent stem cell-derived brain-like endothelial cells (iBECs) to ascertain if CVB3 infection may alter barrier cell function and overall survival. In this study, we determined that these iBECs indeed are susceptible to CVB3 infection and release high titers of extracellular virus. We also determined that infected iBECs maintain high transendothelial electrical resistance (TEER) during early infection despite possessing high viral load. TEER progressively declines at later stages of infection. Interestingly, despite the high viral burden and TEER disruptions at later timepoints, infected iBEC monolayers remain intact, indicating a low degree of late-stage virally-mediated cell death, which may contribute to prolonged viral shedding. We had previously reported that CVB3 infections rely on the activation of transient receptor vanilloid potential 1 (TRPV1) and found that inhibiting TRPV1 activity with SB-366791 significantly limited CVB3 infection of HeLa cervical cancer cells. Similarly in this study, we observed that treating iBECs with SB-366791 significantly reduced CVB3 infection, which suggests that not only can this drug potentially limit viral entry into the brain, but also demonstrates that this infection model could be a valuable platform for testing antiviral treatments of neurotropic viruses. In all, our findings elucidate the unique effects of CVB3 infection on the BBB and shed light on potential mechanisms by which the virus can initiate infections in the brain