Considering the decrease of disease burden caused by intestinal schistosomiasis in many endemic settings, more sensitive diagnostic methods are needed to plan and monitor control measures. We conducted a cross-sectional survey in a rural community in northeast Brazil (317 inhabitants). A combined approach including repeated faecal examinations and ELISA testing was applied. In a first round, single stool samples were collected from 305 (96.2%) participants. Three Kato-Katz (KK) smears were prepared from each sample, and IgG ELISA was performed from serum samples. In the 85 cases of negative KK smears, but positive ELISA results, three additional faecal samples were collected in a second round, and another five KK smears prepared. In the first round of KK analysis, 11/287 (3.8%; 95% confidence interval; 1.92-6.75) were positive. After examining up to eight smears per individual (second round), prevalence of schistosomiasis increased to 8.7% (95% confidence interval: 5.9-12.5). In total, 96/287 (33.4%, 95% confidence interval: 28.0-39.2) samples were positive by ELISA testing. There were no false negative ELISA results. Specificity, positive and negative predictive values of ELISA as compared to up to eight KK smears from three stool samples (reference diagnosis) were 72.9%, 26.0% and 100%, respectively. A single KK smear detected only 12% of the 25 infections; this increased to 44% (three smears, one stool sample), 84% (five smears, three stool samples) and 96% (six smears, four stool samples). We conclude that in low-endemic areas in Brazil the use of KK continues being an important tool. The additional benefit of preparing more than six KK smears from repeated stool samples is negligible. ELISA may be useful for screening populations, with subsequent confirmation of diagnosis by KK or other more sensitive, but highly specific methods.
Cell cycle control genes are frequently mutated in cancer cells, which usually display higher rates of proliferation than normal cells. Dysregulated mitosis leads to genomic instability, which contributes to tumor progression and aggressiveness. Many drugs that disrupt mitosis have been studied because they induce cell cycle arrest and tumor cell death. These antitumor compounds are referred to as antimitotics. Vinca alkaloids and taxanes are natural products that target microtubules and inhibit mitosis, and their derivatives are among the most commonly used drugs in cancer therapy worldwide. However, severe adverse effects such as neuropathies are frequently observed during treatment with microtubule-targeting agents. Many efforts have been directed at developing improved antimitotics with increased specificity and decreased likelihood of inducing side effects. These new drugs generally target specific components of mitotic regulation that are mainly or exclusively expressed during cell division, such as kinases, motor proteins and multiprotein complexes. Such small molecules are now in preclinical studies and clinical trials, and many are products or derivatives from natural sources. In this review, we focused on the most promising targets for the development of antimitotics and discussed the advantages and disadvantages of these targets. We also highlighted the novel natural antimitotic agents under investigation by our research group, including combretastatins, withanolides and pterocarpans, which show the potential to circumvent the main issues in antimitotic therapy.
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