Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

[Validation of a questionnaire to evaluate administrative causes of low reporting of adverse drug reactions]. / Validación de un cuestionario para evaluar causas administrativas de la baja notificación de reacciones adversas a los medicamentos.

Objective Design and validate a survey to determine the administrative causes that can influence low reporting of adverse drug reactions. Methods The questionnaire design was based on a review of the literature and on brainstorming. The variables considered to influence reporting were professional workload and the professional perception of drug surveillance control activities. To validate the hypothesis, 60 professionals were surveyed in a convenience sample. Reliability was calculated using Cronbach's alfa and the Kuder-Richardson coefficient. Content validity was measured using the Kendall coefficient, and criterion validity, through concordance with the established criterion. Results The survey-type questionnaire was composed of 15 questions divided into two parts: general information and administrative causes of low adverse drug reactions reporting. Cronbach's alfa was 0.87, the Kuder-Richardson coefficient was 0.9033, and overall validity was 1.51, resulting from 70% concordance and a rank correlation coefficient of 0.81. Conclusions The reliability of the validated survey was acceptable to high and validity was acceptable.

Validación de un cuestionario para evaluar causas administrativas de la baja notificación de reacciones adversas a los medicamentos / Validation of a questionnaire to evaluate administrative causes of low reporting of adverse drug reactions

RESUMEN Objetivo Diseñar y validar una encuesta para conocer las causas de tipo administrativo que pueden influir en la baja notificación de reacciones adversas a medicamentos (RAM). Métodos El cuestionario se diseñó a partir de una revisión bibliográfica y una tormenta de ideas. Las variables que se consideraron que pueden influir en la notificación fueron la carga de trabajo de los profesionales y su percepción del control de la actividad de farmacovigilancia. Para su validación, se encuestó a 60 profesionales de una muestra de conveniencia. La confiabilidad se calculó con la alfa de Cronbach y el coeficiente de Kuder Richardson. La validez de contenido se cuantificó con el coeficiente de Kendall y la de criterio, mediante la concordancia con el criterio establecido. Resultados El cuestionario tipo encuesta quedó constituido por 15 preguntas y estructurado en dos partes, información general y causas administrativas de la baja notificación de RAM. La alfa de Cronbach fue 0,87, el coeficiente de Kuder Richardson, 0,9033, y la validez total, 1,51, resultante de 70% de concordancia y un coeficiente de correlación por rangos de 0,81. Conclusiones La confiabilidad de la encuesta validada fue aceptable-elevada y su validez, aceptable.

ABSTRACT Objective Design and validate a survey to determine the administrative causes that can influence low reporting of adverse drug reactions. Methods The questionnaire design was based on a review of the literature and on brainstorming. The variables considered to influence reporting were professional workload and the professional perception of drug surveillance control activities. To validate the hypothesis, 60 professionals were surveyed in a convenience sample. Reliability was calculated using Cronbach’s alfa and the Kuder-Richardson coefficient. Content validity was measured using the Kendall coefficient, and criterion validity, through concordance with the established criterion. Results The survey-type questionnaire was composed of 15 questions divided into two parts: general information and administrative causes of low adverse drug reactions reporting. Cronbach’s alfa was 0.87, the Kuder-Richardson coefficient was 0.9033, and overall validity was 1.51, resulting from 70% concordance and a rank correlation coefficient of 0.81. Conclusions The reliability of the validated survey was acceptable to high and validity was acceptable.

Antitumor effects of electrochemical treatment.

Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas. This treatment is noted for its great effectiveness, minimal invasiveness and local effect. Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy. In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained. By this reason, researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells. Although, it is generally accepted this treatment induces electrolysis, electroosmosis and electroporation in tumoral tissues. However, action mechanism of this alternative modality on the tumor tissue is not well understood. Although the principle of Electrochemical treatment is simple, a standardized method is not yet available. The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process. The present work analyzes the latest and most important research done on the electrochemical treatment of tumors. We conclude with our point of view about the destruction mechanism features of this alternative therapy. Also, we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy. In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done. Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses.

BACKGROUND: Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. METHODS: The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. RESULTS: The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. CONCLUSION: The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.