Community Case Management improves Use of Treatment for Childhood Diarrhea; Malaria and Pneumonia in a Remote District of Ethiopia

Background: Ethiopia's Health Extension Workers (HEW) deliver preventive interventions and treat childhood diarrhea and malaria; but not pneumonia. Most of Ethiopia's annual estimated 4 million childhood pneumonia cases go untreated. Objective: Evaluate the performance of volunteers in providing Community Case Management (CCM) for diarrhea; fever and pneumonia - in a pre-HEW setting in Liben Woreda; Oromiya Regional State. Methods: Save the Children supported Ministry of Health and communities to deliver child survival interventions from 1997-2006. We obtained permission in 2005 to train 45 volunteers from remote kebeles in CCM. We evaluated the strategy through reviewing registers and supervision records; examining CCM workers; focus group discussions; and three household surveys. Results: The CCM workers treated 4787 cases; mainly: malaria (36); pneumonia (26); conjunctivitis (14); and watery diarrhea with some dehydration (12). They saw 2.5 times more cases of childhood fever; pneumonia; and diarrhea than all the woreda's health facility staff combined. Quality of care was good. Conclusion: The availability; quality; demand; and use of CCM were high. These CCM workers were less educated and less trained than HEWs who perform complicated tasks (Rapid Diagnostic Tests) and dispense expensive antimalarial drugs like Coartemr. They should also treat pneumonia with inexpensive drugs like cotrimoxazole to help achieve Millennium Development Goal 4

Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury.

Inflammatory lung injury is probably regulated by the balance between proteases and protease inhibitors together with oxidants and antioxidants, and proinflammatory and anti-inflammatory cytokines. Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be up-regulated at the levels of mRNA and protein during lung inflammation in rats induced by deposition of IgG immune complexes. Using immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was shown to exist as a complex with 72- and 92-kDa metalloproteinases (MMP-2 and MMP-9). In inflamed lung both TIMP-2 and SLPI appeared to exist as enzyme inhibitor complexes. Lung expression of both TIMP-2 and SLPI appeared to involve endothelial and epithelial cells as well as macrophages. To assess how these endogenous inhibitors might affect the lung inflammatory response, animals were treated with polyclonal rabbit Abs to rat TIMP-2 or SLPI. This intervention resulted in significant intensification of lung injury (as revealed by extravascular leak of albumin) and substantially increased neutrophil accumulation, as determined by cell content in bronchoalveolar lavage (BAL) fluids. These events were correlated with increased levels of C5a-related chemotactic activity in BAL fluids, while BAL levels of TNF-alpha and chemokines were not affected by treatment with anti-TIMP-2 or anti-SLPI. The data suggest that endogenous TIMP-2 and SLPI dynamically regulate the intensity of lung inflammatory injury, doing so at least in part by affecting the generation of the inflammatory mediator, C5a.

Simultaneous evaluation of dexamethasone-induced apoptosis and micronuclei in rat primary spleen cell cultures.

Apoptosis or programmed cell death is a biological event that is biochemically and morphologically distinct from cellular necrosis. Nonetheless, its relationship has not been studied in terms of a cytogenetic endpoint such as micronucleus formation. In the present study, based on cytological observations, the incidence of dexamethasone-induced apoptotic cells was related to the frequency of micronucleated cells in vitro. Rat primary spleen cells were grown in 6-well plates with RPMI 1640 media using concanavalin A and lipopolysaccharide as mitogens. At culture initiation, the test agent dexamethasone (10, 20 or 40 microM) and a cytokinesis inhibitor cytochalasin B (3 micrograms/ml) were added. Cultures were harvested 18 h and 40 h later. Slides were prepared and stained with Diff-Quik stain. Frequencies of apoptotic cells and micronucleated binucleate cells were enumerated cytologically based on 500 cells per treatment from the same slides. The results showed a dose-dependent increase in the number of apoptotic cells in rat spleen cultures treated with dexamethasone. At 18 h, the percentages of apoptotic cells were 0.8, 1.6, 3.4 and 4.4 with 0, 10, 20 and 40 microM dexamethasone, respectively. The corresponding percentages of apoptotic cells at 40 h were: 2.8, 2.6, 5.6 and 10.4. However, at the same concentrations of dexamethasone, the micronucleus frequency in binucleate cells remained relatively unchanged. The phenomenon of apoptosis induced by dexamethasone was confirmed biochemically based on a characteristic DNA 'ladder' pattern by gel electrophoresis. These data suggest that dexamethasone at the concentrations which induced apoptosis did not produce cytogenetic damage. Also, these findings indicate that micronucleus formation and nuclear changes leading to apoptosis are separate events and these endpoints may not be closely correlated for dexamethasone.

A 70- to 80-kDa glial cell protein interacts with the AGGGAAGGGA domain of the JC virus early promoter only in the presence of the neighboring cis DNA elements.

The neurotropic virus JC (JCV) causes the demyelinating disease progressive multifocal leukoencephalopathy. JCV is transcriptionally regulated by both positive and negative cis elements. Previous studies have shown that the AGGGAAGGGA sequence, in isolation, interacts with a 53- to 56-kDa cellular protein and acts as a silencer for the late promoter. We have reexamined the role of the AGGGAAGGGA element in the glial cell-specific transcriptional regulation of JCV by studying it in a longer natural context of elements of the JCV early promoter. Transcriptional analysis in C6 glial cells of selectively mutated AGGGAAGGGA domains within the nt 98-153 region of the JCV early promoter revealed that both GGG regions in the AGGGAAGGGA sequence are required for glial cell-specific transcription. The interactions of cellular proteins with the AGGGAAGGGA domain were also found to be dependent upon the presence or absence of neighboring cis elements. The TATA region was found to facilitate the interaction of specific proteins with the AGGGAAGGGA domain. Domain-specific photocrosslinking studies revealed the binding of a glial cell protein of approximately 70-80 kDa to the AGGGAAAGGGA domain only when it was flanked by its neighboring cis elements, the TATA and NF-1 domains of the JCV promoter.