Analysis of a dose-response assay in Scaptotrigona bipunctatabees, Lepeletier, 1836 (Hymenoptera: Apidae) using the logistic regression model under the Bayesian approach

This paper shows the results of a dose-response study in Scaptotrigona bipunctatabees, Lepeletier, 1836 (Hymenoptera: Apidae) exposed to the insecticide Fastac Duo. The aim was to evaluate the lethal concentration that causes the death of 50% of bees (LC50) and investigate the odd of mortality after exposure to different concentrations, using the logistic regression model under the Bayesian approach. In this approach, it is possible to incorporate a prior information and gives more accurate inferential results. Three independent dose-response experiments were analyzed, dissimilar in their lead time according to guidelines from the Organisation for Economic Co-operation and Development (OECD), in which each assay contained four replicates at the concentration levels investigated, including control. Observing exposure to the agrochemical, it was identified that the higher the concentration, the greater the odd of mortality. Regarding the estimated lethal concentrations for each experiment, the following values were found, 0.03 g a.i. L-1, for 24hours, 0.04 g a.i. L-1, for 48hoursand 0.06 g a.i. L-1for 72hours, showing that in experiments with longer exposure times there was an increase in LC50. Concluding, the study showed an alternative approach to classical methods for dose-response studies in Scaptotrigona bipunctatabees exposed to the insecticide Fastac Duo.

Estimated glomerular filtration rate and drug dose adjustment in patients in an intensive care unit in Brazil

Objectives. This study sought to compare the estimated glomerular filtration rate and the indication of dose adjustment of antimicrobials when using Cockcroft-Gault or Modification of Diet in Renal Disease. Methods. A cross-sectional study was performed with patients admitted to the intensive care unit of a Brazilian general hospital. The glomerular filtration rate was calculated for patients on all days using the Cockcroft-Gault and Modification of Diet in Renal Disease equations. The difference in estimated glomerular filtration and the dose adjustment indication of antimicrobials were assessed. Results. A total of 631 patients were included in this study. The median estimated glomerular filtration was significantly higher when estimated using Modification of Diet in Renal Disease (100.3 mL/ min/1.73 m2) than the estimation by Cockcroft-Gault (83.2 mL/min) [p<0.001]. Greater differences in estimations produced by the two formulae were observed in patients at extremes of weight and age, and a different dose adjustment was indicated for all antimicrobials assessed. Conclusions. These results demonstrate a significant difference in estimated glomerular filtration rate values when calculated using either Cockcroft-Gault or Modification of Diet in Renal Disease as well as in the indication of dose adjustment in an intensive care unit

Antitumor efficacy of EDTA co-treatment with cisplatin in tumor-bearing mice

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×106 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na+, K+ and Ca2+). The results showed that the i.p LD50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.

The appropriate use of human albumin in a Brazilian University Hospital: therapeutic indication and dosage regimen

The objective of the study was to evaluate the use of human albumin in a Brazilian university hospital, in compliance with the institutional protocol and other clinical guidelines, taking into account the therapeutic indications and the dosage regimens. Data was obtained from the pharmacy dispensing records of human albumin, the requests for use it and, when available, the patient's records between January and October 2017. After evaluation the therapeutic indications and the dosage regimens were classified as "appropriate" and "inappropriate". The analysis of 98 requests showed that, when compared to the institutional protocol, 54 (55.1%) requests had an inappropriate therapeutic indication. However, when a comparison was made between 25 medical records (54 requests) and other clinical guidelines, it was observed that the therapeutic indication had none classified as inappropriate. In addition, 16 (29.7%) requests were considered inappropriate in relation to dosage regimens. From these results, it was possible to conclude that although the use of human albumin in the hospital was associated to a clinical protocol, it was outdated. Thus, it is possible to affirm that not only the adoption of a clinical protocol, but its periodical updating is an important strategy to promote the rational use of drugs.

The effects of different doses of caffeine on performance, rating of perceived exertion and pain perception in teenagers female karate athletes

ABSTRACT The present study set to examine the effects of different doses of caffeine on performance, rating of perceived exertion (RPE), and pain perception in female teenager athletes of karate. Ten female karate athletes (16.8±1.23 years; height 1.59±0.28 m; body-mass 57.73±8.33 kg; BMI 22.71±3.05 kg/m2) participated in the study. A double-blind, randomized, and crossover counterbalanced design was used. In three sessions (with an interval of seven days'), ten female karate athletes ingested low dose (2 mg/kg), moderate dose (5 mg/kg) caffeine, and placebo. Sixty minutes after consumption, they performed the tests as below: one repetition maximum and 60% of one repetition maximum in the leg press, explosive power test, and anaerobic RAST test. After the tests, the participants' RPE (6-20 scale) and pain perception (0-10 scale) were recorded using various categorical scales. The results showed that caffeine ingestion at moderate dose significantly reduced RPE and pain perception values compared with the placebo during muscular endurance test (P=0.0001 and P=0.039, respectively). The findings suggest that caffeine dose of 5 mg/kg body mass appears to improve RPE and pain perception in female teenager athletes of karate. The dose of 2 mg/kg body mass does not confer any additional improvement in performance.

Analysis of extemporaneous oral liquid from commercially available drugs in hospital

ABSTRACT The objective of this study was to identify drugs that received dose adjustments (DA) and pharmaceutical alternatives (PA) that avoid DA, and calculate the economic percentage of this replacement. A descriptive, observational and cross-sectional study was performed in a second level hospital. The pharmacy and nursing services was accompanied to identify the drugs that received DA and the compounding techniques. After identifying all the drugs that received DA, was identified in the Brazilian market the corresponding pharmaceutical alternative, with the Drugs Price List of Brazilian Health Regulatory Agency. For those drugs that was not available any PA, was performed a research of studies that describe compounding techniques in international scientific databases. Was identify 88 drugs that received DA, and these, 50 do not have any PA. Were identified compounding techniques to 40 drugs. Although any drug has your own particularity of compounding, the compounding techniques can be grouped in five categories. The standardization of 29 drugs can reduce in 28% the DA procedure and cost saving of 34,85%/month. We can conclude that every three drugs prescribed, one received DA and every three DA, one can be avoided by the selection of 29 PA, saving cost as well. The use and standardization of five techniques would attend the pharmaceutics recommendations for better dissolution, bioavailability and patient safety.

Quantification and stress degradation studies of cefepime/tazobactam in dry injection form by an RP-HPLC method

A simple, specific, precise, accurate, linear, rapid, economic and validated stability indicating an RP-HPLC method for the simultaneous quantification of cefepime and tazobactam in a dry injection dosage form has been developed. Separation was performed on a 5 µm ACE C18 column with phosphate buffer, pH adjusted to 4.5 with phosphoric acid: methanol (70:30) at a flow rate of 1 mL/min and at a temperature of 25 °C. Regression analysis showed linearity at a detector wavelength of 290 nm in the range of 200-600 μg/mL for cefepime and 25-75 μg/mL for tazobactam. All of the analytes were adequately resolved with acceptable tailing. The percentage content found for cefepime was 99.98% and of tazobactam was 99.49% in the parenteral formulation. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and system suitability according to ICH guidelines. Stress degradation studies were performed on the placebo and drug products, drugs of interest were well resolved from the degradation products. The developed method was effectively applied for the simultaneous quantification of cefepime and tazobactam in a dry injection formulation.

Desenvolveu-se método específico, preciso, exato, linear, rápido e econômico, de validação de estabilidade, indicando o método de CLAE-FR para a quantificação simultânea de cefepima e tazobactam na forma de dosagem injetável seca. A separação foi realizada em coluna C18 de ACE 5 mM com tampão fosfato, pH ajustado para 4,5 com ácido fosfórico:metanol (70:30), em fluxo de 1 mL/min e temperatura de 25 °C. A análise de regressão mostrou linearidade no detector de comprimento de onda de 290 nm, na faixa de 200-600 μg/mL, para cefepima, e 25-75 μg/mL, para tazobactam. Todos os analitos foram, adequadamente, resolvidos com cauda aceitável. O teor percentual encontrado na formulação parenteral foi de 99,98%, para cefepima, e de 99,49%, para o tazobactam. O método foi validado em termos de linearidade, precisão, exatidão, especificidade, robustez e adequação do sistema de acordo com as diretrizes ICH. Estudos de degradação por estresse foram realizados no grupo placebo e nos medicamentos e os fármacos de interesse foram bem resolvidos a partir dos produtos de degradação. O método desenvolvido foi efetivamente aplicado para quantificação simultânea de cefepima e tazobactam na formulação injetável seca.

Myostatin: genetic variants, therapy and gene doping

Since its discovery, myostatin (MSTN) has been at the forefront of muscle therapy research because intrinsic mutations or inhibition of this protein, by either pharmacological or genetic means, result in muscle hypertrophy and hyperplasia. In addition to muscle growth, MSTN inhibition potentially disturbs connective tissue, leads to strength modulation, facilitates myoblast transplantation, promotes tissue regeneration, induces adipose tissue thermogenesis and increases muscle oxidative phenotype. It is also known that current advances in gene therapy have an impact on sports because of the illicit use of such methods. However, the adverse effects of these methods, their impact on athletic performance in humans and the means of detecting gene doping are as yet unknown. The aim of the present review is to discuss biosynthesis, genetic variants, pharmacological/genetic manipulation, doping and athletic performance in relation to the MSTN pathway. As will be concluded from the manuscript, MSTN emerges as a promising molecule for combating muscle wasting diseases and for triggering wide-ranging discussion in view of its possible use in gene doping.

Desde sua descoberta, a miostatina (MSTN) entrou na linha de frente em pesquisas relacionadas às terapias musculares porque mutações intrínsecas ou inibição desta proteína tanto por abordagens farmacológicas como genéticas resultam em hipertrofia muscular e hiperplasia. Além do aumento da massa muscular, a inibição de MSTN potencialmente prejudica o tecido conectivo, modula a força muscular, facilita o transplante de mioblastos, promove regeneração tecidual, induz termogênese no tecido adiposo e aumenta a oxidação na musculatura esquelética. É também sabido que os atuais avanços em terapia gênica têm uma relação com o esporte devido ao uso ilícito de tal método. Os efeitos adversos de tal abordagem, seus efeitos no desempenho de atletas e métodos para detectar doping genético são, contudo, desconhecidos. O objetivo da presente revisão de literatura foi discutir biossíntese, variantes genéticas, manipulação genética e farmacológica, e doping relacionado à via da MSTN. Como será concluído do manuscrito, a MSTN emerge como uma molécula promissora para combater doenças atróficas musculares e para gerar muitas discussões devido à sua possível utilização em doping genético.

Estudio farmacocinético de la asociación atorvastatina 40 mg + ezetimibe 10 mg tabletas / I study farmacocinetico of the association of atorvastatina 40 mg ezetimibe of 10 mg tablets

Determinar la Biodisponibilidad en una dosis única, de Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, con evaluación de los parámetros farmacocinéticos de concentración máxima en el organismo (C Máx), área bajo la curva de los niveles en el organismo (AUC 0→t y AUC 0 →∞)tiempo en alcanzar la concentración máxima (T Máx), tiempo de vida media (t 1/ 2) y constante de eliminación (Ke). El estudio de Biodisponibilidad se desarrolló mediante la determinación de la magnitud y la velocidad de la absorción “in vivo” de la asociación Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, fabricadopor Laboratorios La Santé S.A, en voluntarios sanos. 12 voluntarios sanos, hombres y mujeres, con edades comprendidas entre los 18 y 55 años, con un peso de ± 15% del apropiado según la edad y la talla, que cumplieron a cabalidad con todos los exámenes clínicos efectuados antes del estudio para su selección y que no presentaron alguna anomalía en su historia médica, recibieron una dosis única de la asociación 40 mg de Atorvastatina + 10 mg de Ezetimibe tabletas, fabricado por Laboratorios La Santé S.A. vía oral con administración de 240 mL de agua. Después de su administración se tomaron muestras de sangre de cada voluntario a los siguientes tiempos: 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 36.0, 48.0 y 72.0 horas. El análisis de las muestras se realizó por Cromatografía Líquida de Alta Resolución (HPLC) con detección UV, previa extracción de los analitos (extracción líquido/líquido), en el Laboratorio bioanalítico de Delivery Technologies. La determinación de la magnitud y la velocidad de la absorción “in vivo” de Atorvastatina 40 mg + Ezetimibe 10 mg tabletas, se evaluó comparando con los parámetros farmacocinéticos ya reportados en estudios previos de estos principios activos por separados...

To determine the bioavailability in a single dose of Atorvastatin 40 mg + Ezetimibe 10 mg tablets, with assessment of pharmacokinetic parameters of maximum concentration body (C max), area under the curve of the levels in the organism (AUC 0 → t and AUC 0 → ∞), time to reach maximum concentration (T max), half-life (t 1 / 2) and elimination constant (Ke). The bioavailability study was conducted by  determining the magnitude and rate of absorption in vivo of the association Atorvastatin 40 mg + Ezetimibe 10 mg tablets manufactured by Laboratorios La Sante SA, in healthy volunteers. 12 healthy volunteers, men and women, aged between 18 and 55, with a weight of ± 15%  according to the age and size, which fully met  with all the clinical examinations performed prior to study and not presenting any anomaly in these tests, received a single dose of the association Atorvastatin 40 mg + Ezetimibe 10 mg tablets, manufactured by Laboratorios La Santé SA, with oral administration of 240 mL of water. After administration of the drug. blood samples were taken from each volunteer at the following times: 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 36.0, 48.0 and 72.0 hours. The sample analysis was performed by High Resolution liquid chromatography (HPLC) with UV detection after extraction of analytes (liquid-liquid extraction) in the bioanalytical laboratory of Delivery Technologies. The determination of the magnitude and absorption rate in vivo of Atorvastatin 40 mg + Ezetimibe 10 mg tablets, was evaluated by comparing with the Pharmacokinetic parameters reported in previous studies of these drug by separate. Adverse Events Report: In general, there were no serious adverse events during the course of this study. According to the results and considering the pharmacokinetic parameters reflecting the amount of Atorvastatin and Ezetimibe absorbed bythe body and the speed...

HPLC method development for the simultaneous analysis of amlodipine and valsartan in combined dosage forms and in vitro dissolution studies

A simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C18 column (ODS 2, 10 μm, 200 x 4.6 mm) and a mobile phase of phosphate buffer (pH 3.6 , 0.01 mol L-1):acetonitrile: methanol (46:44:10 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min-1 and at ambient temperature. The injection volume was 20 μL and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 - 50 μg mL-1 for amlodipine, and 0.05 - 50 μg mL-1 for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.

Desenvolveu-se método de HPLC rápido e reprodutível para a determinação simultânea de anlodipino e valsartana em suas formas de associação e para os estudos de dissolução dos fármacos. Utilizaram-se coluna C18 (ODS 2, 10 μm, 200 x 4,6 mm) e fase móvel tampão fosfato (pH 3,6, 0,01 mol L-1):acetonitrila: metanol para a separação e a quantificação. As análises foram efetuadas com velocidade de fluxo de 1 mL min-1 e à temparatura ambiente O volume de injeção foi de 20 μL e utilizou-se detector de ultravioleta a 240 nm. Sob essas condições, anlodipino e valsartana foram eluídas a 7,1 min e 3,4 min, respectivamente. O tempo total de corrida foi menor que 9 min. O método desenvolvido foi validado de acordo com a literatura e se mostrou linear na faixa de 0,1-50 μg mL-1 para anlodipino e de 0,05-50 μg mL-1 para valsartana. O método desenvolvido foi aplicado com sucesso para ensaios de controle de qualidade de associações de anlodipino e valsartana e nos estudos de dissolução in vitro.

Intervenção farmacêutica e prevenção de eventos adversos / Pharmaceutical intervention and prevention of drug related problems

No presente estudo, são relatadas as intervenções realizadas pelo serviço de farmácia junto ao corpo clínico de uma instituição pública federal, referência nacional para cirurgias de alta complexidade em ortopedia no Rio de Janeiro. Realizou-se estudo retrospectivo no qual foram analisadas as intervenções farmacêuticas realizadas entre junho de 2004 e junho de 2005. O serviço de farmácia atendeu 13,6% dos 5476 pacientes internados neste período. Dos pacientes atendidos, 30,4% necessitaram de pelo menos uma intervenção deste profissional junto ao corpo clínico em algum momento da sua internação, perfazendo um total de 227 intervenções. Os médicos foram os profissionais mais contatados (71,1%), seguidos dos enfermeiros (16,9%) e auxiliares de enfermagem (4,6%). Dos problemas detectados, 84,1% correspondiam a erros, dos quais 49,5% foram prevenidos com as intervenções. A análise dos erros encontrados nos permite sugerir alguns dos principais problemas relacionados a medicamentos apresentados pelos pacientes da instituição. Das intervenções realizadas, 70% foram aceitas, sendo este percentual de 60% para as intervenções relacionadas à prescrição. Os resultados sugerem que as intervenções farmacêuticas foram ferramentas efetivas para a prevenção de eventos adversos, reforçando a importância da assistência farmacêutica para a qualidade da assistência hospitalar.

In the present study, we describe the pharmaceutical interventions performed by the pharmacy service of a publicorthopaedic hospital at Rio de Janeiro, Brazil. In a retrospective study, we analysed the pharmaceutical interventions performed during a year (from june 2004 to june 2005). The pharmacy service assisted 13.6% of the5476 patients that were submitted to internation. In 30.4 % of the patients that were directly assisted by the pharmacist was identified the necessity of pharmaceutical interventions, reaching 227 interventions during the period of the study. The physicians were the most requested professionals (71.1%), followed by nurses 16.9%. Eighty four percent of the problems that were detected were related to potential medication errors. Forty nine percent of these errors were prevented by the pharmacists. It was possible to predict some of the potential drug related problems that could be related to these patients as well. Seventy percent of the pharmaceutical interventions were accepted by the professionals. For the interventions related to prescription,sixty percent were accepted. The results suggest that pharmaceutical interventions were effective to prevent drug adverse events, reinforcing the important role of pharmacists in hospital assistance.