Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21International Symposium on Microsomes and Drug Oxidations (MDO)

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

Abdominoplasty Access for Desmoid Tumor Resection in the Rectus Abdominis Muscle

No abstract available.

La respuesta serológica en la leishmaniasis cutánea americana en relación con inmunoterapia y quimioterapia / The serologic response in the american cutaneous leishmaniasis in relation with immunotherapy and chimioterapia

En el presente trabajo se evaluó la respuesta de anticuerpos contra Leishmania en especie con leishmaniasis cutánea americana, antes y después del tratamiento con quimioterapia (antimoniato de meglumine, Glucantime) o inmunoterapia con la vacuna combinada desarrollada por Convit y colaboradores. Para ello se estudiaron muestras de sueros de pacientes con leishmaniasis cutánea localizada tratados con inmunoterapia (n=39) o quimioterapia (n=34) mediante el ensayo inmunoenzimático ELISA. Se encontró que los niveles de anticuerpos disminuyeron en ambos grupos después de la curación clínica (p<0,001; prueba "t" de Student para datos apareados). Adicionalmente, al estudiar sueros tomados a diferentes tiempos después de la curación clínica, no se encontraron diferencias significativas en los niveles de anticuerpos en personas tratadas con las dos formas de terapia ni en relación a los niveles de anticuerpos contra Leishmania en sueros control de áreas endémicas o no endémicas. Por lo tanto, ambas formas de tratamiento parecen lograr resultados similares en base a este criterio, reflejo de la carga parasitaria

Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis

Delayed-type hypersensitivity (DTH) and antibodies against Leishmania have been studied in 207 Venezuelan patients with localized, muco-cutaneous and diffuse forms of American cutaneous leishmaniasis, representing the clinical spectrum of this disease. Muco-cutaneous disease appears to be related to inadequate immunomodulation or defective killing mechanisms; about 40 percent of these patients show exaggerated DTH, which is inversely related to antibody levels and is more pronounced in less extensive lesions. Patients with diffuse disease present severe antigen-specific immunodeficiency, apparently limited to T cell-mediated protection, DTH and its in vitro correlates. Treatment of patients with diffuse cutaneous leishmaniasis using a combination of chemotherapy and combined vaccine immunotherapy (heat-killed promastigotes plus BCG) has induced clinical inactivity and positive DTH in about one third of these patients, accompanied by marked lowering of antibody levels. These results are discussed in terms of Type 1 T cell responses, protective in cell-mediated immune reactions, and Type 2 T cell responses, non-protective in cell-mediated reactions, in the spectrum of leishmaniasis. Factors related to the induction of favorable Type 1 responses to intracellular pathogens are discussed in terms of a possible mechanism of the combined vaccine efficacy and priorities in vaccine development

Situación actual en inmunoterapia de Leishmania / Current situation in inmunotherapy of the Leishmaniasis

En un ensayo clínico controlado, con evaluación a ciegas y asignación al azar, se ha evaluado la eficacia terapéutica de una combinación de B.C.G. con promastigotes de L.Mexicana amazonensis muertos por calor (Inmunoterapia) en comparación con Antimoniaco de Meglumine (Quimioterapia) y un tercer grupo vacunado con B.C.G. solamente, con un total de 171 pacientes de Leishmaniasis Cutánea localizada (99 Inmunoterapia, 46 Quimioterapia y 26 con BCG). Los resultados obtenidos son comparables en los dos primeros grupos, tanto en el porcentaje de curación (más del 95% a las 32 semanas) como en el tiempo promedio de curación (alrededor de 17 semanas, en cambio en el grupo con BCG solamente los porcentajes de curación son muy bajos (38,5% a las 32 semanas) y el tiempo promedio de curación mucho más prolongado (26 semanas). Los efectos secundarios fueron leves e infrecuentes (menos del 5%) en inmunoterapia y con BCG solo, pero muy frecuente (48%) y severos en quimioterapia. Resultados preliminares indican así mismo buena eficacia terapéutica de la inmunoterapia en pacientes cutáneos y mucosos del área intermedia del espectro clínico-inmunológico y en pacientes con L.Cutánea Difusa (LCD). en este trabajo se discuten los fundamentos de la inmunoterapia en Leishmaniasis en base al espectro de deficiencias de inmunidad celular y se plantean las perspectivas de la inmunoprofilaxis en base a estos conceptos

New projections in the development of a vaccination model using two microorganisms and its application in leishmaniasis and leprosy

Conventional vaccination is oriented toward the prevention of disease in individuals capable of developing normal immune responses. A new model of vaccination employing two microorganisms has been described for the correction of variable degrees of antigen-specifit deficiency in the development of effective cell-mediated immunity in two diseases, leprosy and cutaneous leishmaniasis, both of which are characterized by a spectrum of clinical manifestations. A schematic representation of the immunologic defect in the severe and progressive forms of these diseases and a possible mechanism for its correction using this vaccine model are presented. Immunotherapeutic and immunoprophylactic applications of the model are described, with particular reference to recent experience in the immunotherapy of localized cutaneous leishmaniasis. The efficacy, virtual absence of secondary effects, ease of administration and low cost of this therapeutic modality indicate that it offers an important option or field use in endemic of leishmaniasis