Detection of cutaneous leishmaniasis in three communities of Oti Region,Ghana

BackgroundCutaneous leishmaniasis (CL) is the most common type of leishmaniasis, a neglected tropical disease caused by parasites of the genus Leishmania. In Ghana, some studies in the Volta region have detected Leishmania parasites among persons with skin ulcers.Methodology/Principal findingsUsing a cross-sectional study design, the prevalence of CL in three communities of the Oti Region of Ghana was investigated. Demographic and epidemiological data were obtained by a structured interviewer administered questionnaire. A total of 426 (12.4%) out of 3,440 participants screened had at least one skin ulcer. Of 595 skin ulcers sampled and tested by PCR for Leishmania infection, 150 (25.2%) ulcers from 136 individuals tested positive, accounting for an overall CL prevalence of 31.9% among persons with skin ulcers. Individual community CL prevalence of 23.2%, 29.8%, and 36.8% was observed in Ashiabre, Keri, and Sibi Hilltop respectively among persons with skin ulcers.Conclusions/SignificanceConfirmation of CL in the study area suggests an active cycle of transmission of Leishmania infection. The observation of skin ulcers which tested negative to Leishmania infection suggests a need to test for additional causes of skin ulcers such as Treponema pallidum pertenue and Mycobacterium ulcerans in the study area.     

Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil

5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, we report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. We found that 10 μM 5-FU and 10 μM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-κB (NF-κB), and this observation was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-κB activation, whereas inactivation of NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates the activation of NF-κB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.