GC-MS Profile, Antioxidant Activity, and In Silico Study of the Essential Oil from Schinus molle L. Leaves in the Presence of Mosquito Juvenile Hormone-Binding Protein (mJHBP) from Aedes aegypti.

Schinus molle is a medicinal plant used as an anti-inflammatory and for rheumatic pain in the traditional medicine of Peru. On the other hand, Aedes aegypti is the main vector of several tropical diseases and the transmitter of yellow fever, chikungunya, malaria, dengue, and Zika virus. In this study, the aim was to investigate the antioxidant activity in vitro and the insecticidal activity in silico, in the presence of the mosquito juvenile hormone-binding protein (mJHBP) from Aedes aegypti, of the essential oil from S. molle leaves. The volatile phytochemicals were analyzed by gas chromatography-mass spectrometry (GC-MS), and the profile antioxidants were examined by DPPH, ABTS, and FRAP assays. The evaluation in silico was carried out on mJHBP (PDB: 5V13) with an insecticidal approach. The results revealed that EO presented as the main volatile components to alpha-phellandrene (32.68%), D-limonene (12.59%), and beta-phellandrene (12.24%). The antioxidant activity showed values for DPPH = 11.42 ± 0.08 µmol ET/g, ABTS = 134.88 ± 4.37 µmol ET/g, and FRAP = 65.16 ± 1.46 µmol ET/g. Regarding the insecticidal approach in silico, alpha-muurolene and gamma-cadinene had the best biding energy on mJHBP (ΔG = -9.7 kcal/mol), followed by beta-cadinene (ΔG = -9.5 kcal/mol). Additionally, the volatile components did not reveal antioxidant activity, and its potential insecticidal effect would be acting on mJHBP from A. aegypti.

Asociación entre procrastinación y estrés académico en estudiantes peruanos de segundo año de medicina

Introducción: Los estudiantes universitarios de la carrera de medicina son una población expuesta a una alta carga académica, alta exigencia, gran demanda de tiempo y existen factores que pueden afectar la eficacia del desempeño académico, tales como el estrés y la procrastinación. Objetivo: Evaluar la asociación entre estrés y procrastinación en una muestra piloto de estudiantes de medicina en una universidad de Lima-Perú. Material y métodos: Se realizó un estudio analítico transversal, en donde se reclutó a estudiantes de medicina del curso Metodología de la Investigación en una universidad de la capital peruana. En ellos se midió el estrés y la procrastinación, ambos con test validados previamente, luego se relacionó estas variables y se las ajustó por su sexo y edad. Para la estadística analítica se utilizó los modelos lineales generalizados y se consideró a los valores p ≤ 0,05 como estadísticamente significativos. Resultados: Al realizar el análisis multivariado se encontró que hubo relación entre la procrastinación y el género masculino de los encuestados (p = 0,001), la edad (p = 0,035) y el estrés (p = 0,022). Conclusiones: La procrastinación mantiene en la muestra estudiada una importante asociación con el estrés que tienen los estudiantes, así como, con su género y edad(AU)

Introduction: University medical students are a population exposed to a high academic load, high level of exigency, high demand of time and there are factors that can affect the effectiveness of academic performance, such as stress and procrastination. Objective: Evaluate the association between stress and procrastination in a pilot sample of medical students at a university in Lima, Peru. Material and methods: A cross-sectional analytical study was conducted, where medical students from the Research Methodology course were recruited at a university in the Peruvian capital. In them, stress and procrastination were measured, both with previously validated tests, then these variables were related and adjusted according to their sex and age. For analytical statistics, generalized linear models were used and p-values ≤ 0.05 were considered statistically significant. Results: When performing the multivariate analysis, it was found that there was a relationship between procrastination and male gender (p = 0.001), age (p = 0.035) and stress (p = 0.022) of the respondents. Conclusions: Procrastination maintains in the sample studied an important association with the stress that students have, as well as with their gender and age(AU)

Carvacrol: An In Silico Approach of a Candidate Drug on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR Receptors in the Breast Cancer.

Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[α]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using in silico study the carvacrol on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynamic, and drug-likeness evaluation. A multilevel computational study to evaluate the antitumor potential of carvacrol focusing on the main targets involved in the breast cancer was carried out. The in silico study starts with protein-ligand docking of carvacrol followed by ligand pathway calculations, molecular dynamic simulations, and molecular mechanics energies combined with the Poisson-Boltzmann (MM/PBSA) calculation of the free energy of binding for carvacrol. As result, the in silico study led to the identification of carvacrol with strong binding affinity on mTOR receptor. Additionally, in silico drug-likeness index for carvacrol showed a good predicted therapeutic profile of druggability. Our findings suggest that mTOR signaling pathway could be responsible for its preventive effect in the breast cancer.

Histopathological evaluation of latex of Bellaco-Caspi, Himatanthus sucuuba (Spruce) Woodson on wound healing effect in BALB/C mice.

BACKGROUND AND AIM: Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) is a medicinal plant known as "Bellaco-Caspi" widely distributed in Loreto, Peru. In the Peruvian traditional medicine, the latex of the plant is used for the treatment of wounds, inflammation, ulcers, and other ailments. This study aims to evaluate the wound healing effect of the latex of H. sucuuba in BALB/C albino mice. MATERIALS AND METHODS: Thirty BALB/C male mice were used for wound healing study. In the experimental procedures, wound skin incision was performed at 2.0 cm in length until subcutaneous on the paravertebral of each animal. Under locally anesthetized with procaine cream, the treatment was conducted. All the mice were divided into three groups, the control group (A), zinc oxide cream (B), and H. sucuuba latex (C). The entire surface of the wound was treated for all the groups, and the treatments were performed daily for 15 days. The experiments were stopped on days 1, 7, and 15, respectively. RESULTS: The histopathological study of tissues revealed significant changes in wound healing effect in H. sucuuba latex compared to the control and B groups. Consequently, the mice treated with latex showed a significant reduction in epithelialization time and collagen formation. Furthermore, the latex showed a dose-dependent significant reduction of inflammation in the first 24 h of treatment. CONCLUSION: BALB/C mice treated with the latex of H. sucuuba possess a wound healing effect that can scientifically prove the traditional use of the plant as a wound healing agent.

TOCOSH FLOUR (Solanum tuberosum L.): A Toxicological Assessment of Traditional Peruvian Fermented Potatoes.

Potato tocosh is a naturally processed potato for nutritional and curative purposes from traditional Peruvian medicine. The aim of this study was to investigate the acute and sub-acute toxicity of tocosh flour (TF). For sub-acute toxicity, TF was administered orally to rats daily once a day for 28 days at doses of 1000 mg/kg body weight (BW). Animals were observed for general behaviors, mortality, body weight variations, and histological analysis. At the end of treatment, relative organ weights, histopathology, hematological and biochemical parameters were analyzed. For acute toxicity, TF was administered orally to mice at doses of 2000 and 5000 mg/kg BW at a single dose in both sexes. Body weight, mortality, and clinical signs were observed for 14 days after treatment. The results of acute toxicity showed that the median lethal dose (LD50) value of TF is higher than 2000 g/kg BW but less than 5000 mg/Kg BW in mice. Death and toxicological symptoms were not found during the treatment. For sub-acute toxicity, we found that no-observed-adverse-effect levels (NOAEL) of TF in rats up to 1000 g/kg BW. There were statistically significant differences in body weight, and relative organ weight in the stomach and brain. No differences in hematological and biochemical parameters were observed when compared with the control group. For sub-acute toxicity, histopathological studies revealed minor abnormalities in liver and kidney tissues at doses of 5000 mg/Kg. Based on these results, TF is a traditional Peruvian medicine with high safety at up to 1000 mg/kg BW for 28 days in rats.

Preventive effect of Oenothera rosea on N-methyl-N-nitrosourea-(NMU) induced gastric cancer in rats.

BACKGROUND: Currently, gastric cancer (GC) is considered a public health problem worldwide. Using medicinal plants for the prevention of chronic diseases such as cancer constitutes new alternatives in traditional medicine. Oenothera rosea (OR) could be an option, but it needs to be evaluated. AIM: The main objective of this study was to evaluate the protective effect of OR extract on N-methyl-N-nitrosourea (NMU)-induced GC in rats. METHODS: In total, 80 male Holtzman rats were randomized into five groups. Group A received the saline solution (5mL/kg), group B received NMU 500 µg/kg (cancer inductor) by oral administration for 16 weeks, and groups C, D, and E were treated with OR extract (100, 200, and 300 mg/kg, respectively) and NMU in order to evaluate the preventive effect on cancer induced by NMU for 16 weeks. Blood and histological samples of stomachs were collected to determine histopathological, biochemical, and hematological parameters between different experimental groups. RESULTS: Groups C, D, and E presented less histopathological changes such as anaplastic and hyperplastic cells, compared with group B. Hematological and biochemical parameters were recorded, and superoxide dismutase, malondialdehyde, and nitric oxide levels were statistically less than those of NMU group (P<0.05, P<0.01, and P<0.01). CONCLUSION: Considering the histopathological signs and the antioxidant activity in vivo as well as hematological and biochemical parameters of ethanolic extract of OR, we concluded that its administration in rats has a protective effect on GC, which is induced experimentally. This species could be studied in clinical trials for patients with GC in the future.

Efecto de la administración crónica del látex liofilizado de Croton lechleri Muell. Arg. "sangre de drago" en Rattus norvegicus var. Albinus / Effect of chronic administration of latex lyophilised Croton lechleri Muell. Arg. "sangre de drago" in Rattus norvegicus var. Albinus

Objetivo: Determinar si la administración crónica (90 días) del látex liofilizado de Croton lechleri Muell. Arg. "Sangre de drago" modifica los parámetros hematológicos y bioquimicos en Rattus norvegicus var albinus. Materiales y métodos: Se utilizó ratas con un peso corporal (p.c.) entre 150 g a 170 g, distribuidos en Grupo A (control) y Grupos B y C (experimentales), de 20 especímenes cada uno (10 hembras y 10 machos) a las que se administró por vía oral NaCl 0.9% y una dosis diaria de 100 y 200 mg de látex liofilizado/Kg p.c. respectivamente, durante 90 días. Se tomaron muestras de sangre cada 15 días para determinar parámetros hematológicos (hematocrito, linfocitos, leucocitos y segmentados) y bioquímicos (glucosa, urea, creatinina, colesterol total y perfil hepático). Resultados: Todos los valores se encontraron dentro del rango normal. Se encontraron diferencias significativas al comparar los grupos de estudio en los resultados de glucosa (Control vs Grupo I: p<0.001 y Grupo II: p=0.003) y creatinina (Grupo II vs Grupo I: p=0.008 y control: p<0.001). Los valores de bilirrubina total y proteínas totales variaron significativamente durante el tiempo de estudio (p=0.001 y p<0.001, respectivamente). El resto de parámetros no presentaron variaciones significativas por grupos (p>0.05). Conclusión: El látex liofilizado de Croton lechleri Muell. Arg. no generó toxicidad en los parámetros hematológicos y bioquímicos estudiados en Rattus norvegicus var Albinus.

Análisis de eficacia, seguridad y racionalidad de la combinación a dosis fija (CDF) de dos hipoglicemiantes orales (metformina + glimepirida) en publicaciones biomédicas, 2000-2012 / Analysis of efficacy, safety and rationality of the fixed dose combination (FDC) of two oral hypoglycemic agents (metformin + glimepiride) in biomedical publications, 2000-2012

Analizar los resultados de eficacia, seguridad y racionalidad de la combinación a dosis fija (CDF) de dos hipoglicemiantes orales (metformina + glimepirida) en publicaciones biomédicas, 2000-2012. Método: Se usó un estudio cuantitativo, revisión documental y retrospectivo, en el cual la unidad de análisis y la muestra fueron los estudios clínicos controlados aleatorizados (ECCA) y número total de publicaciones biomédicas desde el 2000-2012 respectivamente. Se realizó la búsqueda en bases de datos de evidencia científica: pubmed, EMBASE, Lilacs, "The ACP Journal Club", "Bandolier", "BMJ Evidence Updates", "The Cochrane Database of Systematic Reviews", etc., según los recomendado por el Centro de Medicina Basada en la Evidencia (MBE) de la "Duke University Medical Center Library" y Oxford University. Los criterios para evaluar la eficacia, seguridad y racionalidad fueron basados en las guías técnicas de la Administración de Alimentos y Medicamentos (FDA) de los Estados Unidos de América, Agencia Europea de Medicamentos (EMA) y OMS; para la valoración de la calidad de la publicación se usó JADAD y CONSORT. Resultados: No se encontró publicaciones de la CDF glimepirida/ metformina que hayan considerado criterios de eficacia y seguridad recomendado por la FDA y EMA. Para el análisis se consideró dos (02) publicaciones de eficacia y seguridad de la CDF, los que presentan baja calidad metodológica de acuerdo al cuestionario de Oxford Quality Score, Jadad (<3 puntos), y según CONSORT, sólo se transparentaron entre 48 por ciento a 76 por ciento de los 25 ítems recomendados para publicaciones biomédicas de estudios clínicos. Al valorar cada uno de los 02 artículos considerados, en el primero sólo un pequeño número de pacientes (n<=8) logró una reducción <=7 por ciento de HbA1c y se determinó un NNT de 22 cuando fue comparado con glimepirida después de 3 meses de tratamiento con glimepirida/metformina, y en el segundo artículo se determinó un NNT de 6 y 5...

Identificar e analizar os resultados da eficacia, sequrança e racionalidade da combinação a doses fixas (CDF) de dois hipoglicemiantes orais (metformina + glimepirida) reportadas em publiçacóes biomédicas, entre os anos de 2000 a 2012. Método: Usou-se um estudo quantitativo, revisão documental e retrospectivo; no qual a unidade da análise e da mostra foram os estudos clínicos controlados aleatorizados (ECCA) e o número total de publicacóes biomédicas desde 2000 até 2012 respectivamente. Realizou-se a busca nas bases de dados de evidencia científica: pubmed, EMBASE, Lilacs, "The ACP Journal Club", "Bandolier", "BMJ Evidence Updates", "The Cochrane Database of Systematic Reviews", etc, segundo as recornendcóes do Centro de Medicina Basada en la Evidencia (MBE, em Inglés Evidence Based Medice) da "Duke University Medical Center Library" e Oxford University. Os criterios para avaliar a eficacia, sequrança e racionalidade foram baseados nas guías técnicas da Administração de Alimentos e Medicamentos (FDA, em Ingles Food and Drug Administration) dos Estados Unidos da América, Agencia Europeia de Medicamentos (EMA, em Ingles European Medicine Agency) e OMS (Orqanizacáo Mundial da Saúde); para a valorizacáo da qualidade da publicacáo foi usado JADAD (JADAD, Ar. Oxford, 1996) e CONSORT (Consolidated Standart of Reporting Trials). Resultados: Não foi encontrada publicacóes da CDF glimepirida/metformina que tenham considerado criterios de eficacia e sequranca recomendado pela FDA e EMA. Para a análise foi considerado duas (02) publicacóes de efiçacia e sequrança da CDF, os que apresentam baixa qualidade metodológica de acordo ao questionário de Oxford Quality Score, Jadad (<3 pontos), e segundo CONSORT, só se transparentaram entre 48 por cento a 76 por cento dos 25 itens recomendados para publicacóes biomédicas de estudos clínicos. Ao valorar cada um dos dois artigos considerados, no primero só um pequeno número de pacientes (n<=58) logrou uma redução...

Implicacion del colesterol de membrana en la proliferacion, ciclo y diferenciacion de las celulas leucemicas humanas HL-60 / Membrane cholesterol involvement in HL-60 human leukaemia cell proliferation, cycle and differentiation

Introduccion El metabolismo del colesterol esta alterado en celulas leucemicas, existiendo controversia acerca del uso combinado de estatinas y agentes quimioterapeuticos en el tratamiento contra el cancer. En nuestro laboratorio habiamos demostrado con anterioridad como la deficiencia de colesterol mediante el uso de inhibidores distales de su biosontesis inducoa la diferenciacion de las celulas humanas HL-60 hacia granulocitos. Se desconoce hasta la fecha si la extraccion del colesterol de la membrana de estas celulas es capaz de producir un proceso de diferenciacion similar, lo que podria abrir una via mas hacia nuevas lineas terapeuticas. Material y metodos Las celulas HL-60 se mantuvieron en un medio libre de colesterol y se extrajo el colesterol de membrana mediante el uso (..) (AU)

Introduction Cholesterol metabolism is increased in leukaemia cells and, accordingly, the use of chemotherapeutic agents in combination with statins for cancer treatment is being evaluated. In our laboratory, we demonstrated that cholesterol deficiency, as produced by distal inhibitors of the cholesterol biosynthesis pathway, induces the differentiation of HL-60 human leukaemia cells through the granulocytic pathway. The aim of the present work was to determine whether the selective extraction of cholesterol from the cell membrane induces cell differentiation, which may open new possibilities in cancer therapy and other proliferative processes. Material and methods Promyelocytic HL-60 cells were maintained in a cholesterol-free medium. Cholesterol was extracted by incubating the cells in the presence of methyl-¦Â-cyclodextrin. Cholesterol cell content was measured by HPLC; cell proliferation was assessed by cell counting; cell cycle distribution was analysed by flow cytometry. Cell differentiation was assessed by measuring CD11c expression by flow cytometry and NADPH oxidase components by Western blot.ResultsTreatment with methyl-¦Â-cyclodextrin reduced the cholesterol content in cells, and resulted in cell proliferation inhibition, the induction of CD11c expression and the synthesis of p47phox and p67phox.Conclusions Selective extraction of membrane cholesterol in HL-60 cells triggers cell differentiation, as indicated by the expression of both CD11c and NADPH oxidase components.ResultsTreatment with methyl-¦Â-cyclodextrin reduced the cell cholesterol content and inhibited cell proliferation in a dose-dependent manner. As this treatment is prolonged, part of the cells die but a substantial proportion of cells survives and acquire differentiation markers, such as CD11c, p47phox and p67phox.(..) (AU)