Haitian, Chinese, Somali, Ethiopian, and Asian/Pacific Islander perspectives on research

Researchers often approach community-based organizations as an access point to engage underserved populations in studies. In this article, 5 representatives of community organizations present their perspectives on the complexity of researcher-community partnerships and the nuances of engaging Haitian, Ethiopian, Somali, Chinese, and Asian/Pacific Islander populations in research. Each representative presents recommendations for gaining trust and understanding within their communities and challenge researchers to move beyond seeking knowledge and into social action that improves the lives of their constituents.     

Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein

Expression of misfolded protein in cultured cells frequently leads to the formation of juxtanuclear inclusions that have been termed 'aggresomes'. Aggresome formation is an active cellular response that involves trafficking of the offending protein along microtubules, reorganization of intermediate filaments and recruitment of components of the ubiquitin proteasome system. Whether aggresomes are benevolent or noxious is unknown, but they are of particular interest because of the appearance of similar inclusions in protein deposition diseases. Here we present evidence that aggresomes serve a cytoprotective function and are associated with accelerated turnover of mutant proteins. We show that mutant androgen receptor (AR), the protein responsible for X-linked spinobulbar muscular atrophy, forms insoluble aggregates and is toxic to cultured cells. Mutant AR was also found to form aggresomes in a process distinct from aggregation. Molecular and pharmacological interventions were used to disrupt aggresome formation, revealing their cytoprotective function. Aggresome-forming proteins were found to have an accelerated rate of turnover, and this turnover was slowed by inhibition of aggresome formation. Finally, we show that aggresome-forming proteins become membrane-bound and associate with lysosomal structures. Together, these findings suggest that aggresomes are cytoprotective, serving as cytoplasmic recruitment centers to facilitate degradation of toxic proteins.     

Diagnostic detection of human immunodeficincy virus type-1 antibodies in urine, Jimma Hospital, south west Ethiopa

BACKGROUND: Testing for human immunodeficiency virus (HIV) specific antibodies continues to be the most important measure in diagnosis and HIV intervention. Detection of anti-HIV antibodies in serum or plasma samples are common strategies. However, body fluids such as urine and saliva could serve as an alternative sample for diagnosis of HIV infection. OBJECTIVE: To determine the diagnostic accuracy of Calypte HIV-1 urine EIA test kits for detection of HIV antibodies in urine sample. METHODS: Urine and serum samples were collected from a total of 365 subjects (HIV suspected (n=156), VCT clients (n=129) and 80 known HIV positive individuals at Jimma Hospital VCT center, OSSA, Red Cross and Mekaneyessus Jimma cohort sites in unlinked anonymous testing method. Urine sample were tested using Calypte HIV-1 urine EIA kits parallel to the golden standard method of testing serum samples by combination of Determine and Vironostica (Rapid test followed by ELISA) test algorithm. All discordant samples (by urine serum tests) were resolved using urine western blot (Calypte HIV-1 urine Western Blot). RESULT: Comparing the results obtained with a golden standard (HIV test algorithm) the sensitivity and specificity of urine EIA test kit were 99.5% (187/188) and 98.3% (174/177) respectively. Beside to this kappa's test of agreement showed perfect agreement with kappa 0.98. CONCLUSION: The result showed the utility of urine test as an alternative method for HIV antibody detection. Since the method of collection of urine specimen is non-invasive, it reduces occupational exposure for health professionals involved in collecting samples. Furthermore patient's stronger acceptance to give urine samples will make this test more applicable than serum or whole blood test.     

Development of resistance by Plasmodium falciparum to sulfadoxine/pyrimethamine in Amhara Region, Northwestern Ethiopia

Following the high rate of chloroquine-resistant Plasmodium falciparum, Ethiopia changed the national drug policy in 1999 from chloroquine to sulfadoxine/pyrimethamine (SP) as first line. However, the useful therapeutic lifespan of SP may be limited by the rapid emergence of resistance. We conducted a study between October and November 2001 to examine the current extent of SP resistance to P. falciparum in Amhara Region, Northern Ethiopia. A total of 93 patients with uncomplicated P. faliciparum malaria were studied from Habru (n=50) and Weizazirt (n=43) localities. Drug resistance was evaluated using the 14-day WHO in vivo test protocol. Parasitological resistance to SP was found to be 32.0% (16/50) and 4.7% (2/43) in Harbu and Weizazirt localities, respectively. The corresponding clinical failure rates were 20.0% (10/50) and 4.7% (2/43). Of the parasitological failure at Harbu, 9 patients were classified as RI, 6 as RII and one as RIII type response. Among the clinical failures, 7 were LTF while the remaining 3 were ETF. Nevertheless, there was hardly any patient with RII/RIII or ETF response, and only two patients each with RI and LTF response were seen from Weizazirt locality. Therefore, the study underscores the presence of varying level of SP resistance to P. falicparum in the areas studied. Whereas SP remains quite effective in the treatment of uncomplicated P. falciparum in Weizazirt locality, the observed high rate of resistance from Harbu is alarming and an area of concern.     

Hepatoprotective effect of the selective mineralocorticoid receptor antagonist, eplerenone against carbon tetrachloride-induced liver injury in rats

Background. Eplerenone is a selective mineralocorticoid receptor (MR) antagonist, and its potential protective role in cardiovascular injury has been reported by several studies. However, whether and how this drug can ameliorate hepatic injury in rats is unknown.Material and methods. The present study was conducted to investigate effect of eplerenone against liver injury induced by carbon tetrachloride (CCl₄) in rats. The biochemical liver function tests and oxidative stress parameters including malondialdehyde (MDA), reactive oxygen species (ROS), in addition to the reduced glutathione (GSH) levels were evaluated. Moreover, serum tumor necrotic factors (TNF-α) level and histopathological changes were examined.Results. Our results show that pre-treatment with eplerenone (4 mg/kg per day for 4 weeks) revealed attenuation in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase, (AST), alkaline phosphatase (ALP) and bilirubin levels that were enhanced by CCl₄. Further, pre-treatment with eplerenone inhibited the elevated hepatic MDA content and restored hepatic GSH to its normal level. The enhanced hepatic ROS production in CCl₄-treated group was markedly decreased by eplerenone administration. Eple-renone pre-treatment significantly attenuated the inflammatory responses caused by CCl₄ as evident by the decreased serum TNF-α level. Histopathological studies showed that eplerenone alleviated the liver damage and reduced the lesions caused by CCl₄.Conclusion. Collectively, the present study provides a proof to hepatoprotective actions of eplerenone via reducing oxidative stress and inflammatory responses in CCl₄-induced liver damage in rat model.     

Thalidomide does not modify the ability of cells in leprosy patients to incorporate [3H]-thymidine when incubated with M. leprae antigens

The immune response in reversal reaction, (RR) and in erythema nodosum leprosum (ENL) is characterized in vitro by an enhancement in lymphocyte blast transformation against M. leprae. As thalidomide is an effective treatment for ENL, this study assessed the effect of this drug on these phenomena. Mononuclear cells from patients attending the clinic at ALERT and from healthy staff were cultured for 5 days with integral M. leprae (IMl), or a modified Dharmendra antigen (Dhar), or PPD from M. tuberculosis. In one set of cultures, thalidomide was added once at the initiation of the culture; in the other set thalidomide was added a second time (2x), 18 h prior to harvesting the cells. The mononuclear cells, in the absence of thalidomide, from healthy staff, borderline tuberculoid patients (BT) and BT patients in RR (BT/RR) incorporated [3H]-thymidine best when cultured with PPD > Dhar > M. leprae. The cells from patients with ENL did not respond well to the M. leprae antigens. Thalidomide (2x) enhanced proliferation to Dhar in the BTRR group (Wilcoxon signed rank test, P < 0.05). No significant changes occurred for the other groups. Comparing PPD-stimulated cells treated with thalidomide once to those treated with thalidomide twice, thalidomide (2x) suppressed incorporation of [H3]-thymidine by the PPD-stimulated (P < 0.05) as well as IMl-stimulated (P < 0.05) cells in the healthy staff group. In the Dhar-stimulated cells from the healthy staff thalidomide significantly suppressed TNF-alpha (P < 0.05). A mixed effect was seen within and between the other groups, but there was a trend for thalidomide to suppress TNF-alpha induced by the M. leprae, Dhar and PPD antigens.     

Aflatoxin contamination of human breast milk and complementary foods in southern Ethiopia

Exposure to unsafe level of aflatoxin in early life may lead to growth faltering. However, the extent of contamination of breast milk and complementary foods is poorly examined. We determined aflatoxin M₁ (AFM₁) and B₁ (AFB₁) contamination of human breast milk and cereal‐based cooked complementary foods, respectively, among households having children 6–23 months of age in Sidama zone, southern Ethiopia. Data were collected through two cross‐sectional surveys implemented in the wet (n = 180) and dry (n = 180) seasons. Eligible households (n = 360) were recruited from three agroecological zones (lowland, midland and highland, each with sample size of 120) using a multistage sampling technique. AFB₁ and AFM₁ levels were determined using enzyme‐linked immunosorbent assay. Mann–Whitney U and Kruskal–Wallis tests were performed to compare aflatoxin levels between seasons and across the agroecological zones. Among 360 breast milk samples tested, 64.4% had detectable AFM₁ and 5.3% exceeded the 0.025 parts per billion (ppb) limit set by the European Union for infant milk. The median AFM₁ in the lowlands was significantly higher than in the other agroecological settings (P < 0.001). By season, AFM₁ was higher in breast milk samples collected in the dry season (P = 0.041). AFB₁ was detected in 96.4% of the food samples tested, and 95.0% had concentration exceeding the permissible European Union limit of 0.1 ppb. The median AFB₁ was significantly higher in the lowland (P = 0.002), but there was no difference between the seasons (P = 0.386). The study indicated that, in southern Ethiopia, foods intended for infants are heavily contaminated with AFB₁. Contamination of breast milk is also a significant health concern.