Se desarrolló una microemulsión (ME) para la aplicación tópica de anfotericina B (AmB). Las ME son sistemas versátiles que facilitan la solubilización de principios activos y, además, presentan muchas ventajas para aplicar fármacos en forma tópica. La AmB posee muy baja solubilidad en agua, por lo cual se realizó una evaluación de su solubilidad en distintos aceites y surfactantes. Se confeccionaron diagramas ternarios de fase y se seleccionó una ME-gel que puede ser aplicada tópicamente sin el agregado de agentes espesantes. Se solubilizó hasta 1 mg/g de AmB y el fármaco permaneció estable durante al menos 90 días a 4 °C y a temperatura ambiente, por lo cual esta formulación sería apropiada como un medicamento magistral. El estudio in vitro de permeación en piel mostró que la dosis aplicada penetró completamente (flujo estimado de difusión 10,16 +/- 0,01 µg/cm²/h) y permaneció retenida en la misma durante el tiempo de estudio sin detectarse AmB en el compartimento receptor. La actividad antifúngica y antileishmania in vitro fue adecuada. La AmB es una droga de segunda línea en el tratamiento de la leishmaniasis cutánea; sin embargo, no se dispone de preparados para uso tópico. Esta formulación sería útil para el tratamiento local de las infecciones de piel, evitando efectos adversos sistémicos.

The aim of the present work was to develop a ME for topical delivery of Amphotericin B (AmB). Microemulsions (MEs) are versatile systems to solubilize drugs due to the presence of both a hydrophobic and a hydrophilic region, as well as a distinctive interface composed of surfactant and cosurfactant. MEs have been reported for many advantages for topical application of drugs. Considering that AmB has very low water solubility a screening of surfactants and oils was performed. A gel-like ME system, that can be applied topically without the need for thickeners agents, was selected. AmB was incorporated up to 1 mg/g and remained stable for at least 90 days both at 4 °C and room temperature, so this formulation would be appropriate as a compounding medication. An in vitro skin penetration test was performed, the applied dose penetrated (10.16 +/- 0.01 µg/cm²/h as estimated flux) and remained completely within the skin during the assay; AmB was not detected in the receptor compartment. In vitro antifungal and antileishmanial activity was tested and drug showed proper activity. AmB is a second line drug for the treatment of cutaneous leishmaniasis, but topical dosage forms are still lacking. This system is potentially useful for the treatment of skin infections avoiding drug toxic systemic effects.

background: Increased blood pressure variability is a novel risk factor for the development of target organ injury both in hyperten-sive and normotensive subjects, so its reduction should be considered as a new therapeutic goal. Objective: The aim of this study was to evaluate the effect of long-term oral carvedilol treatment on blood pressure, blood pressure variability and target organ injury in the left ventricle and thoracic aorta in a model of blood pressure liability. Methods: Twelve male Wistar rats submitted to sinoaortic denervation were treated during 8 weeks with a single dose of carvedilol 30 mg/kg or vehicle. At the end of treatment, echocardiographic evaluation and blood pressure and short-term variability measure-ments were performed. Left ventricular and thoracic aortic weights were determined and histological samples were prepared from both tissues. Metalloproteinase MMP-2 and transforming growth factor β (TGF-β) were quantified in the left ventricle and thoracic aorta. results: Carvedilol reduced systolic blood pressure and its variability in sinoaortic-denervated rats compared with the control group (126±5 vs. 142±11 mmHg, p<0.05; SD: 2.9±0.5 vs. 6.0±0.5 mmHg; p<0.05). A lower amount of connective tissue was found in carvedilol-treated animals. The expression of TGF-β decreased in both organs after carvedilol treatment. Conclusions: Chronic carvedilol treatment significantly reduces systolic blood pressure and its short-term variability in sinoaortic-denervated rats, decreasing the degree of left ventricular fibrosis.

introducción: El incremento en la variabilidad de la presión arterial resulta un nuevo factor de riesgo para el desarrollo de daño de órgano blanco en individuos tanto hipertensos como normotensos, por lo que se postula que su reducción debe considerarse una posible nueva meta terapéutica. Objetivos: Evaluar el efecto del tratamiento a largo plazo con carvedilol sobre la presión arterial, su variabilidad y el daño de órgano blanco en el ventrículo izquierdo y la aorta torácica en el modelo de la labilidad de presión. Material y métodos: Se incluyeron 12 ratas Wistar macho sometidas a desnervación sinoaórtica, las cuales fueron tratadas durante 8 semanas con una única administración diaria de carvedilol 30 mg/kg o vehículo. Finalizado el tratamiento se realizó la medición de la presión arterial y de la variabilidad a corto plazo y la evaluación ecocardiográfica. Se determinó el peso del ventrículo y de la aorta torácica y se realizaron preparados histológicos sobre ambos tejidos. Se cuantificó la expresión de metaloproteinasa 2 (MMP-2) y factor de crecimiento transformante β (TGF-β) en el ventrículo izquierdo y la aorta torácica. resultados: El carvedilol redujo la presión arterial sistólica y su variabilidad en las ratas con desnervación sinoaórtica en comparación con el grupo control (126 ± 5 vs. 142 ± 11 mm Hg, p < 0,05; DE: 2,9 ± 0,5 vs. 6,0 ± 0,5 mm Hg; p < 0,05). Se evidenció menor cantidad de tejido conectivo en los animales tratados con carvedilol. La expresión de TGF-β se encuentra disminuida en ambos órganos luego del tratamiento con carvedilol. Conclusiones: El tratamiento crónico con carvedilol reduce significativamente la presión arterial y su variabilidad a corto plazo en ratas con desnervación sinoaórtica, disminuyendo el grado de fibrosis del ventrículo izquierdo.

The flowers of the Chiliotrichum diffusum (G. Forst.) Kuntze, Asteraceae, have long been used in traditional medicine and rituals. In this study, the anti-inflammatory and antinociceptive activities of a decoction of the flowers were evaluated and a phytochemical analysis was performed by HPLC-DAD. In order to evaluate the antinociceptive activity, the acetic acid-induced abdominal writhing and hot plate tests were used. The anti-inflammatory activity was evaluated using carrageenaninduced rat paw oedema. The decoction induced a significant anti-inflammatory effect (inhibition of 56.0% at 3 h) and produced significant inhibition on nociception in the acetic acid test (ED50 35 mg/kg i.p.; ED50 709 mg/kg p.o.). In the hot plate test, the antinociceptive activity of the extract employed at 500 mg/kg i.p. was significantly suppressed by pretreatment with naloxone (5 mg/kg). HPLC analysis showed the presence of chlorogenic acid, caffeic acid, hyperoside, isoquercitrin, quercitrin, afzelin, quercetin, apigenin and kaempferol. The decoction of C. diffusum proved to have antinociceptive and anti-inflammatory effects that may be related to the presence of the flavones, flavonols and phenolic acids identified. The opiod system seems to be involved in the mechanism of antinociception of the extract.

Capsicum species, Solanaceae, have been used for centuries as food additives by populations of different regions of the world. Capsaicin (trans-methyl-N-vainillyl-nonenamide) is the main pungent compound extracted from the red hot pepper fruit (Capsicum spp.). The capsaicin content was determined by means of a HPLC method. The results showed that Capsicum chacoense Hunz., contains similar amounts of capsaicin (13.9 mg/100 g of dry fruit) in comparison with Capsicum baccatum L. (12.6 mg/100 g) and Capsicum annum L. (10.1 mg/100 g). Dichloromethane (CH2Cl2) and ethanol (EtOH) extracts of C. chacoense elicited a 46% and 38 % of inhibition on the arachidonic acid (AA) pathway in ear edema respectively while the CH2Cl2 and EtOH extracts of C. baccatum inhibited 52% and 35% the arachidonic acid response respectively.

A atividade antiinflamatória de extratos éter petróleo, diclorometânico e metanólico de Heterotheca subaxillaris var. latifolia, foi testada pelo método de edema induzido pelo 12-O-tetradecanoil phorbol acetato (TPA) na orelha do camundongos e pelo método do edema de pata induzido por carragenina em ratos. O extrato diclorometânico mostrou atividade antiinflamatória significativa (91% inibição) no edema de orelha induzido por TPA (administração tópica de 1 mg/orelha). Não houve efeitos significativos no teste do edema induzido pela carragenina. O fracionamento bioguiado das frações ativas levou ao isolamento dos flavonoides majoritários santina, pectolinaringenina, 3,6-dimetoxi-5, 7,4 '-trihidroxiflavona e hispidulina.

The anti-inflammatory activity of the petroleum ether, dichloromethane and methanol extracts from Heterotheca subaxillaris var. latifolia were assayed using 12-O-tetradecanoyl phorbol acetate (TPA) induced ear edema test in mice and carrageenan-induced paw edema test in rats. The dichloromethane extract showed a significant anti-inflammatory activity (91% of inhibition) in TPA-induced ear edema test (topical administration at 1 mg/ear). No effects were seen on carragenan-induced edema. Bio-guided fractionation deal to the isolation of the major flavonoids santin, pectolinaringenin, 3,6-dimethoxy-5,7,4'-trihydroxyflavone and hispidulin present in the active fractions.

O extrato aquoso das partes aéreas de Lippia integrifolia foi ensaiado quanto aos seus efeitos colerético e antiespasmódico. Doses de 250, 500 e 750 mg/kg administradas oralmente em ratos aumentaram significativamente o fluxo biliar e a saída de ácidos biliares. O extrato também exibiu uma significativa redução das contrações induzidas por acetilcolina, CaCl2 e KCl em jejuno isolado de rato. O conteúdo total de derivados dos ácidos cafeoilquínicos, expressado como ácido clorogênico foi de 0.10% w/v através de determinação espectrofotométrica.

The aqueous extract of the aerial parts of Lippia integrifolia has been assayed for its choleretic and antispasmodic effects. Doses of 250, 500 and 750 mg/kg administered orally in rats significantly increased the bile flow and the bile acid output. The extract also showed a significant reduction of the contractions induced by acetylcholine, CaCl2 and KCl on isolated rat jejunum. The total caffeoyl quinic acids derivatives content, expressed as chlorogenic acid was 0.10% w/v by spectrophotometric determination.