RESUMEN
BACKGROUND: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. METHODS: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. RESULTS: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. CONCLUSION: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.
RESUMEN
BACKGROUND: The potential of secondary metabolites extracted from Streptomyces sp. to treat bacterial infections including infections with Staphylococcus aureus is previously documented. The current study showed significant antimicrobial activities associated with endophytic Streptomyces sp. isolated from medicinal plants in Peninsular Malaysia. OBJECTIVES: The current study aimed to determine anti-methicillin-resistant-Staphylococcus aureus (MRSA) activities of Streptomyces sp. isolates. MATERIALS AND METHODS: Disc diffusion and Minimum Inhibitory Concentration (MIC) assay were used to determine the antibacterial activity of Streptomyces sp. isolates. Optimization of fermentation parameters for the most potent anti-MRSA extract in terms of medium type, pH, aeration rate, and culture period was also carried out. Lastly, toxicity of the extract against Chang liver cells was determined employing the MTT, 2- (3, 5- diphenyltetrazol-2-ium-2-yl) -4, 5-dimethyl -1, 3 - thiazole; bromide assay. RESULTS: The results indicated Streptomyces sp. SUK 25 isolates showed the most potent anti-MRSA activity. Disc diffusion assay revealed that spread plate technique was more efficient in screening anti-MRSA activity compared to pour plate (P < 0.05). To determine anti-MRSA MIC of Streptomyces sp. SUK 25, Thronton media was used. Therefore, MIC was determined as 2.44 ± 0.01 µg/mL, and accordingly, the lowest MIC was 1.95 µg/mL based on a seven-day culture, pH7, and aeration rate of 140 rpm. The crude extract was not toxic against Chang liver cells (IC50 = 43.31 ± 1.24 µg/mL). CONCLUSIONS: The Streptomyces sp. SUK 25 culturing was optimized using Thronton media, at pH 7 and aeration of 140 rpm. Further isolation and identification of bioactive compounds will develop anti-MRSA therapeutics.
RESUMEN
BACKGROUND: Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance. METHOD: Three ß-carbolin derivatives, namely, harmalin, harmol and harmalol were tested for their anti-plasmodial and CQ resistance reversal effects against P. falciparum 3D7 and K1. SYBRE Green-1 based drug sensitivity assay and isobologram analysis were used to screen the mentioned effects respectively. RESULTS: All of them showed moderate anti-plasmodium effect and harmalin was the most effective as compared to the others in reversing CQ resistance and tolerance. CONCLUSION: The mentioned phytochemicals are not ideal to be used as conventional antimalarials and only harmalin can be suggested to reverse CQ resistance in P. falciparum K1.
RESUMEN
BACKGROUND: Sulphadoxine-pyrimethamine (SP) has been in use for the treatment of uncomplicated falciparum malaria in Malaysia since the 1970s and is still widely employed in spite of widespread clinical resistance. Resistance to SP is known to be mediated by mutations in the pfdhfr and pfdhps genes. The aim of the present study was to investigate the distribution of pfdhfr and pfdhps gene polymorphism in Plasmodium falciparum field isolates from Kalabakan, Sabah, in northern Borneo. METHODS: A total number of 619 individuals were screened from 23 study sites of which 31 were positive for P. falciparum. Analysis of restriction fragment length polymorphisms (RFLP) was used to identify polymorphism in the pfdhfr and pfdhps genes at positions 16, 51, 59, 108, 164 and 437, 540, 581, respectively. RESULTS: All samples had at least one mutation in each of the genes associated with drug resistance. The prevalence of pfdhfr 59arg, 164leu and 108asn were 100%, 80.65% and 58.06%, respectively. Pfdhps mutants 437gly and 581gly accounted for 100% and 74.19% respectively. In pfdhfr, the most common mutant genotypes were combination 59arg + 164leu (22.58%) and 59arg + 108asn + 164leu (51.61%). In pfdhps the most common genotype was 437gly + 581gly (74.19%). One individual (3.22%) harboured parasites with four pfdhfr (16 val + 59arg + 108asn + 164leu) and two pfdhps (437gly + 581gly) mutations. The highest quintuple pfdhfr/pfdhps (41.94%) was three pfdhfr (59arg + 108asn + 164gly) and two pfdhps (437gly + 581gly). CONCLUSION: The data suggest a high prevalence of genetic variations conferring resistance to SP which can predict treatment failure before becoming clinically evident. In areas like this, the use of SP may no longer be indicated.