Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved) that were screened are Library of Pharmacologically Active Compounds (LOPAC1280), the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150 unique compounds, which inhibited >90% of B. burgdorferi growth at a concentration of <25 µM. These 150 unique compounds comprise many safe antibiotics, chemical compounds, and also small molecules from plant sources. Of the 150 unique compounds, 101 compounds are FDA approved. We selected the top 20 FDA-approved molecules based on safety and potency and studied their minimum inhibitory concentration and minimum bactericidal concentration. The promising safe FDA-approved candidates that show low minimum inhibitory concentration and minimum bactericidal concentration values can be chosen as lead molecules for further advanced studies.
The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates, which will be able to induce a broad range of immune responses in a heterogeneous HLA population. However, our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.
A series of umbelliferone analogues were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. Especially, 2-oxo-2-[(2-oxo-2H-chromen-7-yl)oxy]ethyl-2,4-dihydroxybenzoate (4e) bearing 2,4-dihydroxy substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with IC 50 value 8.96 mM and IC 50 value of kojic acid is 16.69. The inhibition mechanism analyzed by LineweaverBurk plots revealed that the type of inhibition of compound 4e on tyrosinase was noncompetitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compounds 4c and 4e may serve as a structural template for the design and development of novel tyrosinase inhibitors.
Background: Better knowledge of, good attitude towards and practicing prevention of mother-to-child transmission is highly effective intervention and has an enormous potential to improve both maternal and child health. Hence, this study tried to assess the knowledge, attitude, practice and factors associated with prevention of mother-to-child transmission of HIV/AIDS among pregnant mothers attending antenatal clinic. Methods: An institution-based cross-sectional study was conducted among pregnant mothers attending antenatal care clinic at Hawassa University Referral Hospital in 2012. A systematic random sampling technique was used to select 238 antenatal care attendees. Data were collected through structured pre-tested questionnaire. The data were entered into Epi Info and analyzed by using SPSS software for windows. Univariate, bivariate and multivariate analyses were done. Results: More than four-fifth (82.3%) mothers knew about prevention of mother-to-child transmission of HIV and 97.4% had good attitude towards it. Only about half (48.3%) of the respondents knew that antiretroviral drugs given for seropositive pregnant mothers could reduce the risk of transmission. Urbanite mothers were more knowledgeable than their rural counter parts (AOR=2.63, 95%CI (2.5, 5.31)). The odds of knowledge on prevention of mother-tochild transmission was about 3 times higher among multipara (AOR=2.64, 95%CI (2.02, 5.38)). It was also higher among women having their antenatal follow up for the current pregnancy (AOR=6.2, 95%CI (1.15, 9.44)). About 96% of mothers have been tested for HIV and the rest did not test due mainly to fear of stigma, discrimination and lack of confidentiality. Health Center delivery (AOR=1.2, 95%CI (1.73, 3.25)) and antenatal care visit of four and above for the current pregnancy (AOR=1.04, 95% CI (1.01, 2.49)) found to have statistically significant association. Conclusion: Women's empowerment, improving antenatal care services and male involvement were significant predictors of knowledge, attitude and uptake of prevention of mother-to-child transmission services and should be promoted through community mobilization. J o ur nal o f A ID S & Cli n ic a l R es earc h
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