Anticonvulsant Activity of Diospyros Fischeri Root Extracts

Diospyros fischeri Gurke (Ebenaceae) is used in traditional medicine for the treatment of epilepsy. Dichloromethane, ethylacetate, and ethanol extracts of the roots, at doses between 100 and 1600 mg/kg BW, inhibited convulsions induced by the γ-aminobutyric acid type A (GABAa) receptor antagonist, pentylenetetrazole (PTZ), in a dose dependent manner. The extracts also exhibited low toxicity against brine shrimps giving LC₅₀ values between 45.4 and 95.4 µg/ml. These results provide evidence for the potential of D. fischeri extracts to treat absence seizures, especially given their seemingly innocuous nature.     

Laminin Isoforms and Laminin-Producing Cells in Rat Anterior Pituitary

Laminin is a key component of the basement membrane and is involved in the structural scaffold and in cell proliferation and differentiation. Research has identified 19 laminin isoforms, which are assemblies of α, β, and γ chains (eg, the α1, β1, and γ1 chains form the laminin 111 isoform). Although laminin is known to be present in the anterior pituitary, the specific laminin isoforms have not been identified. This study used molecular biological and histochemical techniques—namely, RT-PCR, immunohistochemistry, and in situ hybridization—to identify the laminin isoforms and laminin-producing cells in rat anterior pituitary. RT-PCR showed that laminin α1, α3, and α4 genes were expressed in anterior pituitary. Immunohistochemistry revealed laminin α1 in gonadotrophs and laminin α4 in almost all vascular endothelial cells. Laminin α3 was seen in a subset of vascular endothelial cells. We then performed in situ hybridization to localize β and γ chains in these cells and found that laminin β1, β2, and γ1 were expressed in gonadotrophs and that laminin β1 and γ1 were expressed in endothelial cells. In conclusion, we identified gonadotroph-type (laminin 111 and 121) and vascular-type (laminin 411 and 311) laminin isoforms in rat anterior pituitary.     

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania

Objective To describe the contribution of paediatric HIV and of HIV co‐infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. Methods During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV‐1 RNA PCR was performed on those aged <18 months. HIV‐infected patients also received serum cryptococcal antigen testing and had their CD4‐positive T‐lymphocyte count and percent determined. Results A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV‐infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV‐uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Conclusion Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over‐diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co‐infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.     

Data safety and monitoring boards for African clinical trials

The recent increase in funding for diseases endemic in resource-poor countries has led to a progressive rise in the number of trials conducted in Africa for product development purposes or to answer important questions on reduction of disease burden. This causes an increasing demand for data safety monitoring boards (DSMBs) within Africa, where there is currently a shortage of appropriately skilled people. To address this, and in line with capacity-building efforts directed at improved quality research, AMANET invited the authors to create a curriculum and to train selected Africans with the skills required for members of DSMBs. Based on experience, the facilitators made an overview of clinical trial designs, a comprehensive review of data safety monitoring guidelines and other relevant DSMB governance issues. The wealth of guidelines and recommendations available for establishing and running DSMBs focus mainly on trials set in developed countries. The authors drew from these guidelines a practical summary of those relevant for Africa. This interactive process enabled recommendation of a straightforward set of principles to guide the establishment of DSMBs in Africa, which strike that essential balance between protecting trial participants and allowing investigators to answer their scientific questions.