Quick and simple LC-MS/MS method for the determination of simvastatin in human plasma: application to pharmacokinetics and bioequivalence studies

A simple, rapid, and sensitive method based on liquid chromatography-tandem mass spectrometry for the quantitative determination of simvastatin in human plasma was developed and validated. After a simple extraction with methyl tert-butyl ether, the analyte and internal standard (lovastatin) were analyzed using reverse-phase liquid chromatography, on a Kinetex C18 column (100 × 4.6 mm, 2.6 μm) using acetonitrile: ammonium acetate (2 mM + 0.025 % formic acid) (70: 30, v/v) as a mobile phase in a run time of 3.5 min. Detection was carried out using electrospray positive ionization mass spectrometry in the multiple-reaction monitoring mode. The method was linear over 0.04-40.0 ng/mL concentration range. The mean extraction recovery of simvastatin was 82% (RSD within 15%). Intraday and interday precisions (as relative standard deviation) were all ≤8,7% with accuracy (as relative error) of ±8%. This rapid and reliable method was successfully applied for a bioequivalence study of 40 mg of simvastatin orally disintegrating tablets in 44 healthy volunteers, showing that this method is suitable for the quantification of simvastatin in human plasma samples for pharmacokinetics and bioequivalence studies.Desenvolveu-e e validou-se um método simples, rápido e sensível baseado na cromatografia líquida acoplada à espectrometria de massas em tandem para a quantificação de sinvastatina em plasma humano. Após um simples preparo de amostras utilizando extração com éter metil-terc-butílico, o analito e seu padrão interno (lovastatina) foram analisados por cromatografia líquida de fase reversa, em uma coluna Kinetex C18 (100 mm x 4,6 mm x 2,6 μm), utilizando uma fase móvel composta de acetonitrila:acetato de amônio (2 mM + 0,025% ácido fórmico) (70:30, v/v) em tempo total de corrida de 3,5 min. A detecção foi realizada por espectrometria de massas utilizando a ionização por electrospray no modo positivo e monitorando os íons pelo sistema de monitoramento de reação múltipla. O método apresentou linearidade na faixa de 0,4 - 40,0 ng/mL. A recuperação média obtida para sinvastatina foi de 82% (DPR menor que 15%). A precisão intradia e interdias (como desvio padrão relativo) foi ≤8,7% com exatidão (como erro relativo) de ± 8%. Este método rápido e confiável foi aplicado com sucesso em um estudo de bioequivalência de comprimidos de desintegração oral de sinvastatina 40 mg em voluntários sadios, mostrando que este método é adequado para a quantificação de sinvastatina em plasma humano para estudos farmacocinéticos e bioequivalência

Acute inflammatory response to transgastric natural orifice transluminal endoscopic surgery peritoneoscopy: An experimental study in swine

OBJECTIVE: To investigate the impact of transgastric peritoneal access on plasma biomarkers of acute inflammatory response in comparison to laparoscopy. METHODS: This was a prospective and comparative study in a porcine model. Transgastric peritoneal access performed by natural orifice transluminal endoscopic surgery was compared with laparoscopy. Laparotomy and sham groups were used as positive and negative controls, respectively. Thirty-four pigs were assigned to receive transgastric natural orifice transluminal endoscopic surgery (n = 12), laparoscopy (n = 8), laparotomy (n = 8) or a sham procedure involving only anesthesia (n = 6). In the natural orifice transluminal endoscopic surgery group, peritoneoscopy was performed with a gastroscope via transgastric access. Blood samples were collected at baseline and 1, 3, 6, 9 and 24 h after the surgical procedure for measurement of interleukins 1β, 6 and 10 and tumor necrosis factor-α. A complete blood count was performed, and C-reactive protein levels were measured at baseline and at 24 h. RESULTS: All surgical and endoscopic procedures were performed without major complications. Peritoneal cavity inventory showed no signs of peritonitis in any animal. Interleukin 1β, interleukin 10 and tumor necrosis factor-α levels were below the threshold of detection. The mean level of interleukin 6 was statistically significantly higher in the laparotomy group than in the other groups (p;0.05). C-reactive protein analysis indicated significant increases in all groups, with no differences among the groups. Complete blood count analysis showed no differences among the groups. CONCLUSIONS: Based on the observed interleukin 6 patterns, the systemic inflammatory response resulting from transgastric peritoneal access by natural orifice transluminal endoscopic surgery is similar in intensity to the response that occurs after laparoscopy

Prevalência e fatores associados à polifarmácia em idosos residentes em Rio Branco, Acre, Brasil: estudo transversal de base populacional, 2014

Objective: To analyze the prevalence and factors associated with polypharmacy inelderly people living in Rio Branco, Acre, Brazil, in 2014. Methods: Cross-sectionalpopulation-based study, verification by complex sampling, with elderly people.Polypharmacy was defined as the concomitant use of five or more drugs. Results: Theprevalence of polypharmacy was 14.9% (95%IC 11,8;18,6), positively associated withfemales (OR=2.29 – 95%CI 1.41;3.74), white skin color (OR=1.61 – 95%CI 1.10;2.38),dependence (OR=1.65 – 95%CI 1.05;2.60), change in eating habits/diet use (OR=1.66 –95%CI 1,16;2.36), hospitalization in the last 12 months (OR=1.61 – 95%CI 1.02;2.53)and presence of the following self-reported morbidities: systemic arterial hypertension(OR=2.40 – 95%CI 1.33;4.34), diabetes mellitus (OR=2.17 – 95%CI 1.23;3.84),osteoporosis (OR=2.92 – 95%CI 1.84;4.64) and problems (OR=2.94 – 95%CI1.90;4.56). Conclusion: The polypharmacy in the elderly found in this study wasassociated with demographic and health conditions.Objetivo: Analisar a prevalência e os fatores associados à polifarmácia em idososresidentes em Rio Branco, Acre, Brasil, em 2014. Métodos: Estudo transversal de basepopulacional, obtido por amostragem complexa, com idosos. A polifarmácia foidefinida como o uso concomitante de cinco ou mais fármacos. Resultados: Aprevalência de polifarmácia foi de 14,9% (IC95% 11,8;18,6), associada positivamente aosexo feminino (OR=2,29 – IC95% 1,41;3,74), raça/cor da pele branca (OR=1,61 – IC95%1,10;2,38), dependência (OR=1,65 – IC95% 1,05;2,60), mudança de hábitos 3alimentares/uso de dieta (OR=1,66 – IC95% 1,16;2,36), internação nos últimos 12 meses(OR=1,61 – IC95% 1,02;2,53) e presença das seguintes morbidades autorreferidas:hipertensão arterial sistêmica (OR=2,40 – IC95% 1,33;4,34), diabetes mellitus (OR=2,17– IC95% 1,23;3,84), osteoporose (OR=2,92 – IC95% 1,84;4,64) e problemas cardíacos(OR=2,94 – IC95% 1,90;4,56). Conclusão: A polifarmácia em idosos encontrada nesteestudo esteve associada às condições demográficas e de saúde

O perfil de liderança de treinadores de natação brasileiros de categorias de base

Este estudo tem por objetivo avaliar a autopercepção de treinadores brasileiros de natação federados e verificar a existência de uma possível preferência destes profissionais por um determinado estilo de liderança de decisão e interação com seus atletas. A amostra foi composta por 66 treinadores com média de idade de 37,86 (±10,13) anos e média de tempo da prática profissional de 12,27 (±11,02) anos participantes de Campeonatos de Inverno organizados pela CBDA. Utilizou-se a Escala de Liderança Revisada para o Esporte (ELRE), versão autopercepção. Para análise estatística adotaram-se os testes de Friedman e o post hoc de Dunn com nível de significância de p<0,05. Os resultados evidenciaram que, quanto ao estilo de decisão, não houve diferença significativa entre os comportamentos autocrático e democrático (p=0,857). Quanto aos estilos de interação, observou-se que existem diferenças significativas entre os postos médios das dimensões treino-instrução e suporte social (p=0,032), reforço positivo e suporte social (p=0,037) e consideração situacional e suporte social (p=0,042) e que existe uma diferença significativa entre as dimensões: reforço positivo e consideração situacional (p=0,045). Conclui-se que o estilo decisão dos treinadores não pôde ser claramente delineado e que o estilo de interação está direcionado para ações que envolvem a melhoria do rendimento dos nadadores e incentivo ao alcance das metas estabelecidas

Acute inflammatory response to transgastric natural orifice transluminal endoscopic surgery peritoneoscopy: An experimental study in swine

OBJECTIVE: To investigate the impact of transgastric peritoneal access on plasma biomarkers of acute inflammatory response in comparison to laparoscopy.METHODS: This was a prospective and comparative study in a porcine model. Transgastric peritoneal access performed by natural orifice transluminal endoscopic surgery was compared with laparoscopy. Laparotomy and sham groups were used as positive and negative controls, respectively. Thirty-four pigs were assigned to receive transgastric natural orifice transluminal endoscopic surgery (n = 12), laparoscopy (n = 8), laparotomy (n = 8) or a sham procedure involving only anesthesia (n = 6). in the natural orifice transluminal endoscopic surgery group, peritoneoscopy was performed with a gastroscope via transgastric access. Blood samples were collected at baseline and 1, 3, 6, 9 and 24 h after the surgical procedure for measurement of interleukins 1 beta, 6 and 10 and tumor necrosis factor-alpha. A complete blood count was performed, and C-reactive protein levels were measured at baseline and at 24 h.RESULTS: All surgical and endoscopic procedures were performed without major complications. Peritoneal cavity inventory showed no signs of peritonitis in any animal. Interleukin 1 beta, interleukin 10 and tumor necrosis factor-alpha levels were below the threshold of detection. the mean level of interleukin 6 was statistically significantly higher in the laparotomy group than in the other groups (p 0.05). C-reactive protein analysis indicated significant increases in all groups, with no differences among the groups. Complete blood count analysis showed no differences among the groups.CONCLUSIONS: Based on the observed interleukin 6 patterns, the systemic inflammatory response resulting from transgastric peritoneal access by natural orifice transluminal endoscopic surgery is similar in intensity to the response that occurs after laparoscopy.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Gastroenterol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Expt Surg Div, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Infect & Parasit Dis Div, São Paulo, SP, BrazilUniv São Paulo, Coll Vet Med & Anim Sci, Dept Internal Med, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Div Gastroenterol, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Expt Surg Div, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Infect & Parasit Dis Div, São Paulo, SP, BrazilWeb of Scienc

Ovarian dysgerminoma causing multifocal metastases in young bitch

The ovarian neoplasias are unusual in canine species, mainly originated from germinative cells. Among these, dysgerminoma is a rare neoplasm in bitches, predominantly affecting senile and small and medium breeds. They are large, rounded, smooth surface, painless and firm in consistency. The clinical signs commonly demonstrated by patients with this neoplasia are abdominal distension and secondary signs of hyperestrogenism. The diagnosis should be based on the association of history, clinical signs, radiographic, ultrasonographic, cytological, histopathological and immunohistochemical exams. The treatment is the surgical castration and metastases are uncommon. Due to the rarity in bitches, specifically the young animals, this study aimed to describe a case of left ovarian dysgerminoma, of considerable size and adherence in adjacent organs, in a Brazilian Fila, whose showed considerable increase in abdominal volume and progressive weight loss. The diagnosis was confirmed by means of complementary x-ray, ultrasound, histopathological and immunohistochemical tests. Even with the recommended surgical treatment (castration), the patient demonstrated severe respiratory symptoms and increased abdominal volume after two months, and the complementary exams suggested pulmonary and multifocal metastases and the tutor chose euthanasia. As presented by the results, although rare in bitches, dysgerminoma should be included in the differential of ovarian neoplasias, including the young ones

Mowing and lowering the marandu palisadegrass sward height at late winter improve the sward structure

The structure of the sward is important because it influences the responses of plants and animals in grazing conditions. The objective with this work was to evaluate the structural characteristics of the Marandu palisade grass pasture (Brachiaria brizantha syn. Urochloa brizantha) during spring and summer, depending on the condition of the sward at the end of winter. Four grazing conditions at the end of winter were evaluated: short (24.1 cm), short (25.2 cm)/mown (8 cm), tall (49.0 cm) and tall (50.0 cm)/mown (8 cm). The foliar area index was lower in the tall pasture than in the tall/mown pasture. The mass and the volumetric density of dead stem were higher in the tall pasture, intermediate in the short pasture, and lower in mowed pastures. At the beginning of the grazing period, the live stem mass was higher in the tall pasture. At the beginning and middle of the grazing period, the volumetric density of dead leaf lamina was lower in mowed pastures. At the beginning of the pasture period, the short pasture had a higher tiller number (TN). In the middle of the grazing period, the short and short/mown pastures had higher TN. At the end of the pasture period, the lowest TN value occurred in the tall pasture. The tall pasture at the end of winter presents an unfavorable structure to the animal in grazing, while the mowing and reduction in the height of the marandu palisade grass improves the structure of the sward in spring and summer

Brazilian Sepsis Epidemiological Study (BASES study)

INTRODUCTION: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome METHODS: This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. RESULTS: For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. CONCLUSION: Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate