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INTRODUCTION: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. METHODS: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. RESULTS: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. CONCLUSIONS: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria.
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Antimaláricos/farmacología , Minociclina/análogos & derivados , Plasmodium falciparum/efectos de los fármacos , Proteínas/farmacología , Brasil , Humanos , Minociclina/farmacología , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/aislamiento & purificación , TigeciclinaRESUMEN
Introduction: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. Methods: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. Results: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. Conclusions: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria. .
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Humanos , Antimaláricos/farmacología , Minociclina/análogos & derivados , Plasmodium falciparum/efectos de los fármacos , Proteínas/farmacología , Brasil , Minociclina/farmacología , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/aislamiento & purificaciónRESUMEN
Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45 (51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded.
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Antígenos HLA-G/metabolismo , Hepacivirus/inmunología , Hepatitis C Crónica/inmunología , Hígado/metabolismo , Adulto , Anciano , ADN Viral/análisis , Progresión de la Enfermedad , Femenino , Genotipo , Antígenos HLA-G/genética , Antígenos HLA-G/inmunología , Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/patología , Hepatitis C Crónica/fisiopatología , Hepatitis C Crónica/virología , Humanos , Evasión Inmune , Inmunohistoquímica , Hígado/inmunología , Hígado/patología , Hígado/virología , Masculino , Persona de Mediana Edad , Regulación hacia Arriba , Adulto JovenRESUMEN
Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 µg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity.