Development and validation of a stability-indicating UPLC method for rosuvastatin and its related impurities in pharmaceutical dosage forms

The present work describes a novel stability-indicating reversed-phase ultra performance liquid chromatography method for the separation and quantification of rosuvastatin (RSV) and its related impurities in the pharmaceutical dosage forms under forced degradation conditions. An unknown degradation impurity detected in the acid degradation was identified by using quadrupole time-of-flight mass spectrometry. The chromatographic separation was carried out on C-18 column (100 x 2.1 mm, 1.7 μm) using isocratic elution with methanol and 0.1% trifluoroacetic acid (50:50). The total run time was 12 min within which RSV as well as all related impurities and degradation products were separated. The developed method was validated for RSV and related impurities in pharmaceutical dosage forms.

Discursos médicos em construção: um estudo com residentes em Obstetrícia/Ginecologia do Instituto Fernandes Figueira/Fiocruz

Este estudo discute a construção do discurso especializado, a partir do verbalizado por médicos após dois anos de residência médica em Obstetrícia/Ginecologia no Instituto Fernandes Figueira, Fundação Oswaldo Cruz. A pesquisa foi operacionalizada em duas etapas: observação participante de reuniões clínicas da Obstetrícia e da Ginecologia e construção de fontes orais. Foi realizada análise semiótica das notas de campo e do material transcrito das entrevistas. Os resultados giram em torno de dois eixos: a caracterização do perfil do médico obstetra/ginecologista e a convivência com o normal e o estranho no contato com as pacientes, como integrantes da construção do discurso especializado, no ambiente escolhido para a pesquisa. Conclui-se que a residência conduz ao discurso especializado, escudado, principalmente, na utilização de exames complementares, como os que fornecem imagens, visto que tais exames são percebidos como revelando objetivamente o corpo real. Tal fato infunde segurança nos residentes, mas, por outro lado, afasta-os da atenção à escuta da história da paciente e da composição da narrativa médica, fragmentando o processo de exercício da semiologia clínica

Initial development of two eucalyptus hybrid submitted to irrigation

The eucalyptus offers several advantages compared to other forestry species and, by using the irrigation can increase productivity and decrease production time. The objective of the present study was to evaluate two hybrid eucalyptus (Grancam and Urograndis), no irrigation, dripping and micro sprinkler irrigated at 90, 120, 150 and 180 days after transplanting (DAT). The experiment was conducted at the experimental irrigation area in the State University of Mato Grosso do Sul, in the municipality of Aquidauna - State of MS, Brazil. The experimental design was randomized blocks, split plot with four blocks and two replications within each block, and the plots were composed by irrigation treatments (dripping, micro sprinkler irrigate and dry) and the subplots the hybrids (Grancam and Urograndis).The total area of the experiment had 3 hectares, where each plot consisted of 1 ha. It was evaluated plant height, stem diameter and canopy, stem basal area, the relationship between height and stem diameter, the relationship between height and canopy diameter and stem volume. Data were subjected to analysis of variance and compared by Tukey test at 5% probability. Irrigation systems and dripping sprinkle provide greater plant height, stem diameter, canopy diameter, stem basal area and stem volume.

The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence. Methods : we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p<0.05, 95% CI and calculations of sensitivity, specificity and accuracy of these immunomarkers in predicting recurrence. Results : the series comprised 83 patients aged between 16 and 86 years (35±11.7), divided into two groups: 30 with HG-CIN recurrence (study group) and 53 without recurrence (control group). Mean age, parity, smoking and conization technique were similar in both groups. The p53 expression was present in 43% of the study group and 57% of the control group, and the p16 was present in 43% of the study group and in 57% of the control group (p>0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%. Conclusion : immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.

Lesões cervicais intraepiteliais de alto grau: avaliação dos fatores determinantes de evolução desfavorável após conização

OBJETIVO: Avaliar os fatores determinantes de evolução desfavorável da neoplasia intraepitelial cervical (NIC), tratada por conização. MÉTODOS: Foi feito um estudo retrospectivo com acompanhamento de pacientes, com diagnóstico cito-histológico de NIC, tratadas por conização (técnica clássica e cirurgia de alta frequência), no período de janeiro de 1999 a janeiro de 2006. Os pacientes foram divididos em dois grupos: Estudo (evolução desfavorável: persistência, recorrência ou progressão da lesão) e Controle (cura clínica, amostra aleatória dentro do grupo conizado), num seguimento mínimo de 18 meses. Foram feitas análises estatísticas uni e bivariada das variáveis, usando-se teste das proporções (teste do c2 ou teste exato de Fischer) e considerando-se valor p£0,05. RESULTADOS: Quarenta e oito pacientes apresentaram recorrência ou progressão da doença (grupo estudo) e 65 apresentaram cura clínica (grupo controle). A idade e a paridade foram semelhantes nos dois grupos, conforme média e desvio padrão calculados. Não houve diferença entre os grupos quanto ao hábito de fumar e ao método anticoncepcional utilizado. O percentual de recorrência nessa amostra foi de 14,6%. Somente margens excisionais comprometidas por lesão foram preditoras de recorrência/progressão da doença (p<0,001). A técnica de conização, o cirurgião, o grau da NIC, a presença de extensão glandular e o volume de colo uterino retirados não foram determinantes de evolução desfavorável da doença, após o tratamento cirúrgico, nesta amostra. CONCLUSÃO: A recidiva/persistência ou progressão de NIC2 e 3, pós-tratamento cirúrgico por conização, foi relacionada apenas à margens excisionais comprometidas do produto de conização.

Colpotomia no tratamento da gestação ectópica

OBJETIVO: Relatar o uso da colpotomia para o tratamento de gestações ectópicas. MÉTODOS: Estudo transversal retrospectivo. Foram incluídos todos os casos internados com suspeita clínico-laboratorial de gestação ectópica que não preenchiam critérios para tratamento medicamentoso com Methotrexato no período de fevereiro de 2007 a agosto de 2008. Foram analisadas variáveis demográficas, história ginecológica e características associadas ao tratamento foram obtidas através de revisão de prontuário. RESULTADOS: Dezoito mulheres foram incluídas no estudo. A média de idade foi de 27±5,2 anos. Todos os casos apresentavam gestação ectópica rota e todas as pacientes foram submetidas à salpingectomia parcial. O tempo cirúrgico variou de 30 a 120 minutos (média de 64,5 minutos), sendo contabilizado desde o momento de entrada da paciente na sala cirúrgica até o horário da saída. Nenhuma paciente apresentou infecção pós-operatória. O tempo médio de internação foi de 40± 14,3 horas. As medicações utilizadas no período pós-operatório foram semelhantes em todos os casos, sendo baseadas em anti-inflamatório não esteroide, dipirona, paracetamol e meperidina, conforme a necessidade. A dieta foi reintroduzida 8 horas após o término da cirurgia. CONCLUSÕES: A utilização da colpotomia no tratamento da gestação ectópica apresentou bons resultados, com ausência de complicações importantes e tempo de internação curto. O instrumental cirúrgico básico para a realização desse procedimento é relativamente comum a todos os hospitais, e a técnica cirúrgica é reprodutível.

Development of a three-dimensional nonlinear viscoelastic constitutive model of solid propellant

A three dimensional nonlinear viscoelastic constitutive model for the solid propellant is developed. In their earlier work, the authors have developed an isotropic constitutive model and verified it for one dimensional case. In the present work, the validity of the model is extended to three-dimensional cases. Large deformation, dewetting and cyclic loading effects are treated as the main sources of nonlinear behavior of the solid propellant. Viscoelastic dewetting criteria is used and the softening of the solid propellant due to dewetting is treated by the modulus decrease. The nonlinearities during cyclic loading are accounted for by the functions of the octahedral shear strain measure. The constitutive equation is implemented into a finite element code for the analysis of propellant grains. A commercial finite element package ‘ABAQUS’ is used for the analysis and the model is introduced into the code through a user subroutine. The model is evaluated with different loading conditions and the predicted values are in good agreement with the measured ones. The resulting model applied to analyze a solid propellant grain for the thermal cycling load.

Efeitos de produtos químicos na transpiração e no potencial da água de seringueira (Hevea brasiliensis Muell . Arg. cv.RRIM 600)

Um experimento foi realizado em condições de campo, em Piracicaba (SP), visando avali ar a eficiência de diferentes produtos químicos, em aplicação foliar, na taxa transpiratória e no potencial da água de folhas das plantas de seringueira (He Yea brasiliens is cv. RRIM 600) com 1,5 ano de idade. Os tratamentos utilizados foram: polissulfetc, de polietileno (Good-rite peps) 0,04 %, oxietileno docosanol (Oed green) 2%, caulim (silicato de aluminio) 3%, e atrazine 50 ppm, alem do controle. Através do método da pesagem rápida de folhas desta cadas, com balança de torço tipo Jung, verificou-se a perda de água pelas plantas de seringueira foi restringida significativamente pelo anti-transpirante metabólico (atrazine) com relação ao controle, aos formadores de filme e ao refletor. Polissulfeto de polietileno apresentou as menores amplitudes de variações na taxa respiratória. Atrazine também promoveu a manutenção do potencial da água das folhas mais alto (-7,8 bars) com relação ao controle (-14,8 bars), de acordo com determinações efe tuadas através da Câmara de Scholander.

Postangioplasty restenosis: a practical model in the porcine carotid artery

Transluminal coronary angioplasty is a routine therapeutic intervention in coronary heart disease. Despite the high rate of primary success, restenosis continues to be its major limitation. Porcine models have been considered to be the most adequate experimental models for studying restenosis. One limitation of porcine models is the need for radiological guidance and the expenses involved. The objective of the present study was to adapt an experimental model of angioplasty in the porcine carotid artery that does not require radiological equipment. Eight animals were used to develop the technique of balloon injury to the common carotid artery by dissection without radiological guidance. This technique was then employed in six other animals. Under anesthesia, the left common carotid artery was dissected and incised at the carotid sinus for insertion of an over-the-wire angioplasty balloon towards the aorta. Overstretch injury of the carotid artery was performed under direct visualization. After 30 days, the arteries were excised and pressure-fixated. Uninjured carotid arteries from 3 additional animals were used as controls. A decreased luminal area associated with intimal hyperplasia and medial reaction was observed in all injured arteries. Immunohistochemistry identified the intimal hyperplastic cells as smooth muscle cells. Computerized morphometry of the ballooned segments revealed the following mean areas: lumen 2.12 mm2 (± 1.09), intima 0.22 mm2 (± 0.08), media 3.47 mm2 (± 0.67), and adventitia 1.11 mm2 (± 0.34). Our experimental model of porcine carotid angioplasty without radiological guidance induced a vascular wall reaction and permitted the quantification of this response. This porcine model may facilitate the study of vascular injury and its response to pharmacological interventions

Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

The regulation of bladder function is influenced by central serotonergic modulation. Several genetic polymorphisms related to serotonin control have been described in the literature. T102C polymorphism of the serotonin receptor 2A gene (5-HT2A) has been shown to be associated with certain diseases such as non-fatal acute myocardial infarction, essential hypertension, and alcoholism. In the present study, we examined the association between 5-HT2A gene polymorphism and urinary incontinence in the elderly. A case-control study was performed in 298 elderly community dwellers enrolled in the Gravataí-GENESIS Project, Brazil, which studies gene-environmental interactions in aging and age-related diseases. Clinical, physical, biochemical, and molecular analyses were performed on volunteers. 5-HT2A genotyping was determined by PCR-RFLP techniques using the HpaII restriction enzyme. The subjects had a mean age of 68.05 ± 6.35 years (60-100 years), with 16.9% males and 83.1% females. The C allele frequency was 0.494 and the T allele frequency was 0.506. The CC genotype frequency was 21.78%, the CT genotype frequency was 55.24% and the TT genotype frequency was 22.98%. We found an independent significant association between the TT genotype (35.7%) and urinary incontinence (OR = 2.06, 95%CI = 1.16-3.65). Additionally, urinary incontinence was associated with functional dependence and systolic hypertension. The results suggest a possible genetic influence on urinary incontinence involving the serotonergic pathway. Further investigations including urodynamic evaluation will be performed to better explain our findings.

Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity

Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Variation of glucoraphanin and glucobrassicin: anticancer components in Brassica during processing

Effects of cold storage and three common cooking practices, blanching, sauteing, and microwave cooking at different time intervals, on the content of glucosinolate (GSL) anticancer components in six Brassica vegetables were investigated. Eleven GSLs including progoitrin, glucoraphanin, sinigrin, glucoalyssin, gluconapin, glucobrassicanapin, glucoerucin, glucobrassicin, 4-methoxyglucobrassicin, gluconasturtiin, and neoglucobrassicin were quantified using LC-MS and HPLC. Storage at 4 ºC indicated no significant loss of GSLs in broccoli, kohlrabi, and cabbage, and approximately 90-100% of the total concentration of aliphatic and indolyl GSLs were detected. Interestingly, glucoraphanin and glucobrassicin, known as a cancer prevention agents, increased approximately above 50% in broccoli, kohlrabi, and cabbage, while the amount of glucobrassicin decreased by 5% in cauliflower for 5 days at 4 ºC. Blanching of broccoli at 120 sec significantly (36%) decreased total GSLs; however, sautéing and microwaving decreased by13-26%. Individual GSLs have different response at blanching. These findings suggest that different processing methods for each vegetable would be preferred to preserve the nutritional qualities.