Antimyotoxic Activity of Synthetic Peptides Derived from Bothrops atrox Snake Gamma Phospholipase A2 Inhibitor Selected by Virtual Screening.

BACKGROUND: Several studies have aimed to identify molecules that inhibit the toxic actions of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been shown to be efficient in this assignment. OBJECTIVE: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ (atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic activities. METHODS: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B. atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides. RESULTS: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results observed in molecular docking. CONCLUSION: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic effects of PLA2s.

Guía de práctica clínica para la evaluación y el manejo de la hemorragia digestiva alta en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the evaluation and management of upper gastrointestinal bleeding for the Peruvian Social Security (EsSalud)

Objetivo: Proveer recomendaciones clínicas basadas en evidencia para la evaluación y el manejo de pacientes con hemorragia digestiva alta (HDA) en el seguro social del Perú (EsSalud). Materiales y métodos: Se conformó un grupo elaborador local (GEG-Local) conformado por especialistas en gastroenterología y metodólogos. El GEG-Local formuló 11 preguntas clínicas a ser respondidas por la presente guía de práctica clínica (GPC). Se buscaron y seleccionaron GPC de HDA publicadas a partir del 2012, que respondieran a las preguntas planteadas y obtuvieran un puntaje mayor a 60% en los dominios 1 y 3 del instrumento Appraisal of Guidelines for Research and Evaluation II (AGREE-II). Durante septiembre del 2017 se realizaron búsquedas bibliográficas en Pubmed, para actualizar 9 preguntas clínicas de las GPC preseleccionadas, y para responder 2 preguntas de novo. La calidad de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG-Local revisó la evidencia y formuló las recomendaciones, los puntos de buenas prácticas clínicas y el flujograma de evaluación y manejo, usando la metodología GRADE Finalmente, la GPC fue aprobada con Resolución N° 80-IETSI-ESSALUD-2017. Resultados: La presente GPC abordó 11 preguntas clínicas, divididas en cuatro temas: valoración de riesgo, manejo inicial, manejo de HDA no variceal, y manejo de HDA variceal. En base a dichas preguntas se formularon 10 recomendaciones (7 recomendaciones fuertes y 3 recomendaciones débiles), 24 puntos de buena práctica clínica, y 2 flujogramas. Conclusión: Este artículo es el resumen de la GPC de EsSalud, en la cual se valoró la evidencia científica disponible sobre evaluación y manejo de HDA.

Objective: To provide evidence-based clinical recommendations for the evaluation and management of patients with upper gastrointestinal bleeding (UGB) in the Peruvian Social Security (EsSalud). Materials and methods: A local guideline development group (local GDG) was established, including specialists in gastroenterology and methodologists. The local GDG formulated 11 clinical questions to be answered by this clinical practice guide (CPG). We searched and selected CPG of UGB published from 2012, which answered the posed questions and obtained a score higher than 60% in domains 1 and 3 of the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. During September 2017, bibliographic searches were conducted in Pubmed, to update 9 clinical questions of the preselected CPGs, and to answer 2 de novo questions. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG reviewed the evidence and formulated the recommendations, points of good clinical practice and the flowchart of evaluation and management, using the GRADE methodology Lastly, the CPG was approved with Resolución N° 80-IETSI-ESSALUD-2017. Results: This CPG addressed 11 clinical questions, divided into four themes: risk assessment, initial management, management of non-variceal UGB, and management of variceal UGB. Based on these questions, 10 recommendations (7 strong recommendations and 3 weak recommendations), 24 points of good clinical practice, and 2 flow charts were formulated. Conclusion: This article is the summary of the EsSalud' CPG, where the available scientific evidence on evaluation and management of UGB was evaluated.

Administración accidental de aceite puro esencial de arbol de té (Melaleuca alternifolia) en lactantes / Accidental pure essential tea tree oil (Melaleuca alternifolia) administration in two infants

El aceite de árbol de té es una sustancia que se obtiene mediante la destilación de las hojas y ramas frescas del árbol Melaleuca alternifolia. En los últimos años se ha popularizado su uso sobre todo como agente antiinfeccioso tópico en una gran variedad de enfermedades. Se trata de una sustancia natural que tiene un potencial efecto tóxico demostrado sobre todo si se ingiere. Presentamos dos casos de pacientes atendidos en nuestro Servicio de Urgencias tras administración e ingestión accidental de aceite esencial de árbol de té, en ambos casos los padres confundieron el envase con el de la vitamina D. La atención de estos pacientes nos llevó a realizar una búsqueda bibliográfica de casos publicados de intoxicación por ingesta de aceite de árbol de té y a poner de manifiesto la ausencia de advertencias de seguridad en los envases de aceite de árbol de té que actualmente se comercializan en nuestro país (AU)

Tea tree oil is an essential oil obtained by steam distillation of the leaves and terminal branches of Melaleuca alternifolia. In recent years, it has become popular as an antimicrobial agent against a large number of diseases. It is a natural substance that has a potential toxic effect especially if ingested. We report two cases of infants who came to our Emergency Department because they were accidentally given tea tree oil. In both cases parents mistook the tea tree oil bottle with the D vitamin bottle. The care of these patients led us to perform a literature search of published cases of tea tree oil poisoning and highlight the absence of safety warnings on tea tree oil packages currently marketed in our country (AU)

Snake venom PLA2s inhibitors isolated from Brazilian plants: synthetic and natural molecules.

Ophidian envenomation is an important health problem in Brazil and other South American countries. In folk medicine, especially in developing countries, several vegetal species are employed for the treatment of snakebites in communities that lack prompt access to serum therapy. However, the identification and characterization of the effects of several new plants or their isolated compounds, which are able to inhibit the activities of snake venom, are extremely important and such studies are imperative. Snake venom contains several organic and inorganic compounds; phospholipases A2 (PLA2s) are one of the principal toxic components of venom. PLA2s display a wide variety of pharmacological activities, such as neurotoxicity, myotoxicity, cardiotoxicity, anticoagulant, hemorrhagic, and edema-inducing effects. PLA2 inhibition is of pharmacological and therapeutic interests as these enzymes are involved in several inflammatory diseases. This review describes the results of several studies of plant extracts and their isolated active principles, when used against crude snake venoms or their toxic fractions. Isolated inhibitors, such as steroids, terpenoids, and phenolic compounds, are able to inhibit PLA2s from different snake venoms. The design of specific inhibitors of PLA2s might help in the development of new pharmaceutical drugs, more specific antivenom, or even as alternative approaches for treating snakebites.

Comparative efficacies of terbinafine and fluconazole in treatment of experimental coccidioidal meningitis in a rabbit model.

A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of terbinafine (TBF) and fluconazole (FCZ). Hydrocortisone acetate-treated New Zealand White male rabbits were infected intracisternally with either 2.2 x 10(4) or 6.4 x 10(4) Coccidioides immitis arthroconidia. Oral treatment with polyethylene glycol 200 (PEG) twice daily (n = 8), TBF twice daily (n = 9; 200 mg/kg of body weight/day), or FCZ once daily (n = 8; 80 mg/kg/day) began on day 5 and continued for 21 days. Mean survival times were 20, 24, and 32 days for rabbits treated with PEG, TBF, and FCZ, respectively. All of the FCZ-treated animals (100%; P = 0.003), 56% of the TBF-treated animals (P = 0.4), and 25% of the PEG-treated animals survived the length of the study. Both FCZ and TBF were effective at reducing the incidence of paresis. Only FCZ was effective at reducing most neurological and systemic signs. FCZ treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of CSF fungal cultures compared with those for PEG-treated controls, but TBF treatments had no significant effect on these parameters. Neither drug affected CSF glucose levels. Mean serum TBF levels by bioassay were within the range of 3.5 to 6.2 microgram/ml at 1, 2, and 4 h postdosing and 0.35 to 7.0 microgram/ml at 14 h postdosing. No TBF was detected in CSF. Mean FCZ levels (24 to 25.5 h postdosing) by bioassay were 16.4 to 19.2 and 13.5 to 19.2 microgram/ml in serum and CSF, respectively. The reduction in the numbers of CFU in the spinal cord and brain was over 100-fold (P = 0.0005) in FCZ-treated animals and 2-fold (P

Triaging patients in the latent phase of labor.

Many pregnant women who present to a hospital triage area, office, or clinic setting, or seek advice from a midwife by telephone, require early labor assessment. This article reviews parameters for normal and abnormal latent phase labor and discusses triage assessment and management strategies for the patient in latent phase labor.

Interexaminer agreement for applied kinesiology manual muscle testing.

Two trials of the interexaminer reliability of Applied Kinesiology manual testing were conducted. On the first trial three clinicians, each with greater than ten years of experience with muscle testing procedures, tested 32 healthy individuals to estimate their agreement on the strength or weakness of right and left piriformis and right and left hamstring muscles. Significant agreement between examiners was found for piriformis muscles, but little significant agreement was noted when hamstrings were tested. In a second study, the same three examiners tested 53 subjects for strength or weakness of the pectoralis and tensor fascia lata muscles bilaterally. Significant interjudge agreement was found for pectoralis muscles, but no significant concordance could be found when the tensor fascia lata was examined.