Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products.

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

Molecular pathology of acute kidney injury in a choline-deficient model and fish oil protective effect.

PURPOSE: The aim of this work was to investigate the potential protective effects of fish oil on the basis of kidney transcriptomic data on a nutritional experimental model. METHODS: Male weanling Wistar rats were divided into four groups and fed choline-deficient (CD) and choline-supplemented (CS) diets with vegetable oil (VO) and menhaden oil (MO): CSVO, CDVO, CSMO and CDMO. Animals were killed after receiving the diets for 6 days. Total RNA was purified from the right kidney and hybridized to Affymetrix GeneChip Rat Gene 1.0 ST Array. Differentially expressed genes were analyzed. RESULTS: All CSVO, CSMO and CDMO rats showed no renal alterations, while all CDVO rats showed renal cortical necrosis. A thorough analysis of the differential expression between groups CSMO and CDMO was carried out. There were no differential genes for p < 0.01. The analysis of the differential expression between groups CSVO and CSMO revealed 32 genes, 11 were over-expressed and 21 were under-expressed in CSMO rats. CONCLUSIONS: This work was part of a large set of experiments and was used in a hypothesis-generating manner. The comprehensive analysis of genetic expression allowed confirming that menhaden oil has a protective effect on this nutritional experimental model and identifying 32 genes that could be responsible for that protection, including Gstp1. These results reveal that gene changes could play a role in renal injury.

Especies medicinales, su estado de conservacion y usos, de la compañia Pikysyry, Departamento de Cordillera, Paraguay / Medicinal species, conservation status and uses, Pikysyry company Departament of Cordillera, Paraguay

RESUMEN: El presente trabajo se desarrolló dentro del marco del Proyecto: " Estudio de la flora y vegetación de la compañía Pikysyry , Departamento de Cor dillera, Paraguay ", y tiene por objetivo, determinar las plantas medicinales, presentes en la mencionada zona de estudio, su estado de conservación y usos. Se realizaron viajes al sitio de muestreo entre los meses de julio y noviembre del año 2007, se colectaron aquellas plantas que se emplean con fines medicinales, se elaboraron ejemplares de herbario y se determinaron taxonómicamente. Como resultado se han encontrado 15 especies medicinales, de 15 familias diferentes; de ellas una especie, Piper r egnelii (Piperaceae), se encuentra en la lista de especies en peligro de extinción. Las afecciones para las cuales se emplean estas especies son diversos: 4 especies se reportan para afecciones respiratorias, 3 para afecciones digestivas, 2 para bajar niveles de colesterol, 2 como hipotensoras, 2 para afecciones hepáticas; y como antidiabético, antidiarréico, anticanceroso, afecciones del corazón, para lavar heridas, herpes, fuego de San Antonio y apendicitis; una especie cada una. Las hojas y la parte aérea constituyen las partes de la planta mayormente empleadas. Se contribuye así, con el conocimiento de especies empleadas en la medicina tradicional y las especies citadas y sus usos sirven de referencia para la región. Palabras clave: plantas medicinales, conservación, Paraguay.

Antiplasmodial and leishmanicidal activities of 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives.

Malaria and leishmaniasis are two of the World's most important tropical parasitic diseases. Thirteen new 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives (CPCQs) were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against erythrocytic forms of Plasmodium falciparum and axenic forms of Leishmania infantum. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. None of the tested compounds was efficient against Plasmodium, but two of them showed good activity against Leishmania. Toxicity on VERO was correlated with leishmanicidal properties.

Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas.

OBJECTIVE: To assess the effect of irinotecan-eluting stents (IS) on neointimal growth in the aortas of hypercholesterolemic rabbits and to determine other local histopathological effects such as necrosis, fibrin, and inflammatory reaction. METHODS: Phosphorylcholine-coated stents were deployed in the aortas of hypercholesterolemic rabbits. Group 1 (control; n = 8) received unloaded stents, group 2 (n = 7) and group 3 (n = 9) received IS with 0.046 mg and 1.29 mg of irinotecan, respectively. Eight weeks after implantation the rabbits were killed. Neointimal thickness (NT) was assessed by morphometry. Semiquantitative injury score (from 0 to 3+) was used to analyze inflammatory infiltrate, fibrin deposits, and necrosis in the stented segments. RESULTS: NT was reduced only in high-doses IS (G1, 167.4 +/- 20.8 mu; G2, 170.24 +/- 21.2 mu; G3, 111.56 +/- 12.7 mu; P < 0.05, G3 vs G1 and G2). Necrosis decreased significantly with IS [1.00 +/- 0.10 in G1 to 0.33 +/- 0.07 and 0.02 +/- 0.01 in G2 and G3, respectively] only in the media layer. The inflammatory infiltrate was present in the three layers of aortas from G1, but only decreased significantly in the intimae layer of the high-dose group [1.50 +/- 0.15 in G1 vs 1.00 +/- 0.18 in G3, P < 0.05]. CONCLUSION: Stents loaded with high-dose irinotecan inhibit NT in the aortas of hypercholesterolemic rabbits. This effect was accompanied by decreased inflammatory infiltrate and media necrosis.