Acute renal failure in tropical Africa.

Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect.     

Complementary antiviral efficacy of hydroxyurea and protease inhibitors in human immunodeficiency virus-infected dendritic cells and lymphocytes

Dendritic cells are susceptible to human immunodeficiency virus (HIV) infection and may transmit the virus to T cells in vivo. Scarce information is available about drug efficacy in dendritic cells because preclinical testing of antiretroviral drugs has been limited predominantly to T cells and macrophages. We compared the antiviral activities of hydroxyurea and two protease inhibitors (indinavir and ritonavir) in monocyte-derived dendritic cells and in lymphocytes. At therapeutic concentrations (50 to 100 microM), hydroxyurea inhibited supernatant virus production from monocyte-derived dendritic cells in vitro but the drug was ineffective in activated lymphocytes. Concentrations of hydroxyurea insufficient to be effective in activated lymphocytes cultured alone strongly inhibited supernatant virus production from cocultures of uninfected, activated lymphocytes with previously infected monocyte-derived dendritic cells in vitro. In contrast, protease inhibitors were up to 30-fold less efficient in dendritic cells than in activated lymphocytes. Our data support the rationale for testing of the combination of hydroxyurea and protease inhibitors, since these drugs may have complementary antiviral efficacies in different cell compartments. A new criterion for combining drugs for the treatment of HIV infection could be to include at least one drug that selectively targets HIV in viral reservoirs.     

Drought-induced shifts in the floristic and functional composition of tropical forests in Ghana

The future of tropical forests under global environmental change is uncertain, with biodiversity and carbon stocks at risk if precipitation regimes alter. Here, we assess changes in plant functional composition and biomass in 19 plots from a variety of forest types during two decades of long-term drought in Ghana. We find a consistent increase in dry forest, deciduous, canopy species with intermediate light demand and a concomitant decrease in wet forest, evergreen, sub-canopy and shade-tolerant species. These changes in composition are accompanied by an increase in above-ground biomass. Our results indicate that by altering composition in favour of drought-tolerant species, the biomass stocks of these forests may be more resilient to longer term drought than short-term studies of severe individual droughts suggest.     

Fine-root morphological trait variation in tropical forest ecosystems: an evidence synthesis

Plant Ecology - Key functions of fine roots are often related to their morphological traits, yet little is known about the patterns and controls on fine-root morphological traits in the tropical...     

Effects of aurothiomalate and gold(III) complexes on spontaneous motility of isolated human oviduct

Organic gold complexes have different biological activity, depending on their potential for interactions with key functional molecules.The aim of this study was to investigate potential of several newly synthesized organic gold complexes to influence spontaneous motility of the Fallopian tubes.The effects of [Au(bipy)Cl(2)](+) (dichloride(2,2'-bipyridyl)aurate(III)-ion), aurothiomalate, [Au(DMSO)(2)Cl(2)]Cl and DMSO on spontaneous motility of Fallopian tubes were tested on the isolated tube segments in vitro. Aurothiomalate (from 2.9?×?10(-9) to 4.9?×?10(-4)?M/l), [Au(bipy)Cl(2)]Cl (from 3.3?×?10(-9) to 4.2?×?10(-5)?M/l) and DMSO (from 1.9?×?10(-8) to 1.0?×?10(-5)?M/l) did not affect spontaneous contractions of the isolated Fallopian tube ampulla, while [Au(DMSO)(2)Cl(2)]Cl (from 2.9?×?10(-9) to 4.2?×?10(-5)?M/l) showed concentration-dependent increase (stimulation) of spontaneous contractions of the isolated Fallopian tube isthmus, and remained without effect on the isolated ampulla.The drugs designed as organic gold complexes with weaker bonds between the gold itself and organic part of a molecule could adversely affect motility of the Fallopian tubes, and theoretically fertility of women taking such drugs in their reproductive age.     

Beneficial effect of TRAIL on HIV burden, without detectable immune consequences

Background

During uncontrolled HIV disease, both TNF-related apoptosis inducing ligand (TRAIL) and TRAIL receptor expression are increased. Enhanced TRAIL sensitivity is due to TRAIL receptor up-regulation induced by gp120. As a result of successful antiretroviral therapy TRAIL is down-regulated, and there are fewer TRAIL-sensitive cells. In this setting, we hypothesized that all cells that contain virus, including those productively- and latently-infected, have necessarily been “primed” by gp120 and remain TRAIL-sensitive, whereas uninfected cells remain relatively TRAIL-resistant.

Methods and Findings

We evaluated the immunologic and antiviral effects of TRAIL in peripheral blood lymphocytes collected from HIV-infected patients with suppressed viral replication. The peripheral blood lymphocytes were treated with recombinant TRAIL or an equivalent amount of bovine serum albumin as a negative control. Treated cells were then analyzed by quantitative flow cytometry, ELISPOT for CD4+ and CD8+ T-cell function, and limiting dilution microculture for viral burden. Alterations in the cytokine milieu of treated cells were assessed with a multiplex cytokine assay. Treatment with recombinant TRAIL in vitro reduced viral burden in lymphocytes collected from HIV-infected patients with suppressed viral load. TRAIL treatment did not alter the cytokine milieu of treated cells. Moreover, treatment with recombinant TRAIL had no adverse effect on either the quantity or function of immune cells from HIV-infected patients with suppressed viral replication.

Conclusions

TRAIL treatment may be an important adjunct to antiretroviral therapy, even in patients with suppressed viral replication, perhaps by inducing apoptosis in cells with latent HIV reservoirs. The absence of adverse effect on the quantity or function of immune cells from HIV-infected patients suggests that there is not a significant level of “bystander death” in uninfected cells.     

HIV-1-specific T cell precursors with high proliferative capacity correlate with low viremia and high CD4 counts in untreated individuals

Evidences have recently suggested that the preservation of vaccine-induced memory rather than effector T cells is essential for better outcome and survival following pathogenic SIV challenge in macaques. However, an equivalent demonstration in humans is missing, and the immune correlates of HIV-1 control have been only partially characterized. We focused on the quantification of Ag-specific T cell precursors with high proliferative capacity (PHPC) using a peptide-based cultured IFN-gamma ELISPOT assay (PHPC assay), which has been shown to identify expandable memory T cells. To determine which responses correlate with viral suppression and positive immunologic outcome, PBMC from 32 chronically untreated HIV-1-infected individuals were evaluated in response to peptide pools, representing the complete HIV-1 Gag, Nef, and Rev proteins, by PHPC and IFN-gamma ELISPOT assay, which instead identifies effector T cells with low proliferative capacity. High magnitude of Gag-specific PHPC, but not ELISPOT, responses significantly correlated with low plasma viremia, due to responses directed toward p17 and p15 subunits. Only Gag p17-specific PHPC response significantly correlated with high CD4 counts. Analysis of 20 additional PBMC samples from an independent cohort of chronically untreated HIV-1-infected individuals confirmed the correlation between Gag p17-specific PHPC response and either plasma viremia (inverse correlation) or CD4 counts (direct correlation). Our results indicate that the PHPC assay is quantitatively and qualitatively different from the ELISPOT assay, supporting that different T cell populations are being evaluated. The PHPC assay might be an attractive option for individual patient management and for the design and testing of therapeutic and prophylactic vaccines.     

Optic nerve regeneration screen identifies multiple genes restricting adult neural repair

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