RESUMO

BACKGROUND: The parasite Leishmania infantum causes zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease. Leishmania infantum parasites are transmitted between hosts during blood-feeding by infected female phlebotomine sand flies. With a principal reservoir host of L. infantum being domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models. METHODS: We have developed a stochastic, spatial, individual-based mechanistic model of L. infantum transmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fitted distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters. RESULTS: We computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence of L. infantum infection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected with L. infantum parasites. CONCLUSIONS: Establishing the model parameters with the highest sensitivity of average L. infantum infection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.

Assuntos

RESUMO

Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) is an evergreen shrub that grows the throughout high mountains from Guatemala, Mexico and Southern states of US. Its leaves and roots have been used therapeutically for inflammation-related conditions from Aztec times, but systematic studies of its anti-inflammatory activity are lacking and no specific active components have been identified. In this study, methanol, n-hexane, CH2Cl2, ethyl acetate and methanol/water (6:4) extracts, luteolin, diosmetin, verbascoside, martynoside, pensteminoside, globularisicin and plantarenaloside isolated from this plant were evaluated by determining their inhibitory effects on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Ethyl acetate extract, luteolin, and diosmetin exhibited potent anti-inflammatory and antioxidant activities. The results indicated that luteolin and diosmetin suppressed the LPS induced production of nitric oxide (NO), through the down-regulation of inducible nitric oxide synthases (iNOS) and cyclo-oxygenase 2 (COX-2) protein expressions and showed a potent antioxidant activity against DPPH, TBARS and DCFH. The inhibition of enzymes and NO production by selected extracts and compounds was dose-dependent with significant effects seen at concentration as low as 50 ìM. Thus, luteolin and diosmetin may provide a potential therapeutic approach for inflammation associated disorders.

Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) es un arbusto perenne que crece a lo largo de las montañas altas de Guatemala, México y los estados del sur de los EE.UU.. Sus hojas y raíces se han utilizado terapéuticamente para afecciones relacionadas con inflamación desde la época de los aztecas, pero no existen estudios sistemáticos de su actividad anti-inflamatoria y ninguno de los metabolitos activos específicos han sido identificados. En este estudio, los extractos de metanol, n-hexano, CH2Cl2, acetato de etilo y metanol/agua (6:4), junto con, luteolina, diosmetina, verbascósido, martynoside, pensteminoside, globularisicin y plantarenaloside, aislados desde esta planta se evaluaron mediante la determinación de sus efectos inhibitorios sobre la producción de mediadores proinflamatorios en macrófagos murinos activados con lipopolisacárido (LPS)-RAW 264,7. El extracto de acetato de etilo, luteolina y diosmetina exhibieron una potente actividad anti-inflamatoria y antioxidante. Los resultados indican que luteolina y diosmetina suprimen la producción de óxido nítrico (NO), a través de la regulación de óxido nítrico sintasa-inducible (iNOS) y la ciclooxigenasa-2 (COX-2) ambas expresiones de proteínas. Ademas mostró una potente actividad antioxidante contra DPPH, TBARS y DCFH. La inhibición de las enzimas y la producción de NO por los extractos seleccionados y compuestos es dependiente de la dosis con efectos significativos visto en una concentración tan baja como 50 mM. Por lo tanto, luteolina y diosmetina puede proporcionar un enfoque terapéutico potencial para transtornos asociados a los procesos de inflamación.

Assuntos

RESUMO

Various extracts of the aerial parts of Barkleyanthus salicifolius (Asteraceae) and Penstemon gentianoides (Scrophulariaceae) have been used in folk medicine to treat many ailments, particularly inflammation and migraine. Neither the bioactive components responsible nor the mechanisms involved have been evaluated. Here are reported antioxidant activities of their methanol, dichloromethane, and ethyl acetate extracts. Samples were evaluated for oxygen radical absorption capacity (ORAC), ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging, and inhibition of the formation of thiobarbituric acid reactive species (TBARS), a measure of lipid peroxidation. Antioxidant activities were strongly correlated with total polyphenol content. The most active extracts from P. gentianoides in scavenging DPPH radicals and inhibiting TBARS formation were the methanol extract (A) and a further ethyl acetate extract of this (E). Partition E was further divided into eight fractions, and both E and the fractions were compared for activity against butylated hydroxytoluene, quercetin, and tocopherol. Partition E and the most active fractions, 5 and 6, were found to have I(50) values of 14.1, 38.6, and 41.8 ppm, respectively, against DPPH and 18.5, 26.0, and 12.7 ppm, respectively, against TBARS formation. Consistent with this finding, partition E and fractions 4-6 had the greatest ORAC and FRAP values. These results show that these plants could be useful antioxidant sources.

Assuntos