TERNARY PHASE DIAGRAM OF KETAMINE ((R,S)-2-(2-CHLOROPHENYL)-2-METHYLAMINOCYCLOHEXANONE) IN ETHANOL AND PRELIMINARY STUDIES AIMING AT ENANTIOSELECTIVE CRYSTALLIZATION OF S-KETAMINE

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Crystallization is an important industrial-scale process for the purification of enantiomers that depends on a phase diagram. In this work, the ternary phase diagram of R- and S-ketamine in ethanol was determined. The eutectic point indicated that crystallization of pure enantiomers from solutions containing more than 75% of the desired enantiomer is feasible. Solubility studies showed the feasibility of using temperature control to conduct the process. Batch crystallization of ketamine (S/R:80/20) solutions at 25 degrees C provided the isolation of S-ketamine (purity of 100%) with a yield from 65 to 70% and a productivity of 6.5 g/(1h).262427434Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UnicampFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Bayesian Inference For The Segmented Weibull Distribution

In this paper, we introduce a Bayesian approach for segmented Weibull distributions which could be a good alternative to analyze medical survival data in the presence of censored observations and covariates. With the obtained Bayesian estimated change-points we could get an excellent fit of the proposed model to any data sets. With the proposed methodology, it is also possible to identify survival times intervals where a covariate could have significantly different effects when compared to other lifetime intervals, an important point under a clinical view. The obtained Bayesian estimates are obtained using standard Markov Chain Monte Carlo methods. Some examples with real data sets illustrate the proposed methodology and its potential clinical value

Survivorship of Anopheles darlingi (Diptera: Culicidae) in Relation with Malaria Incidence in the Brazilian Amazon

We performed a longitudinal study of adult survival of Anopheles darlingi, the most important vector in the Amazon, in a malarigenous frontier zone of Brazil. Survival rates were determined from both parous rates and multiparous dissections. Anopheles darlingi human biting rates, daily survival rates and expectation of life where higher in the dry season, as compared to the rainy season, and were correlated with malaria incidence. The biting density of mosquitoes that had survived long enough for completing at least one sporogonic cycle was related with the number of malaria cases by linear regression. Survival rates were the limiting factor explaining longitudinal variations in Plasmodium vivax malaria incidence and the association between adult mosquito survival and malaria was statistically significant by logistic regression (P<0.05). Survival rates were better correlated with malaria incidence than adult mosquito biting density. Mathematical modeling showed that P. falciparum and P. malariae were more vulnerable to changes in mosquito survival rates because of longer sporogonic cycle duration, as compared to P. vivax, which could account for the low prevalence of the former parasites observed in the study area. Population modeling also showed that the observed decreases in human biting rates in the wet season could be entirely explained by decreases in survival rates, suggesting that decreased breeding did not occur in the wet season, at the sites where adult mosquitoes were collected. For the first time in the literature, multivariate methods detected a statistically significant inverse relation (P<0.05) between the number of rainy days per month and daily survival rates, suggesting that rainfall may cause adult mortality

Predictors of and reasons for pacifier use in first-time mothers: an observational study

Background: The use of pacifiers is commonplace in Australia and has been shown to be negatively associated with breastfeeding duration. In order to influence behaviour related to the use of pacifiers it is important to understand the reasons for their use. The primary aim of this observational study was to investigate who (if anyone) advises first-time mothers to give a pacifier and the reasons for which they first give (or try to give) a pacifier to their infant. Additionally, this study investigated the predictors of pacifier use and the relationship between pacifier use and breastfeeding duration. Methods: In total, 670 Australian first-time mothers recruited as part of the NOURISH trial completed a questionnaire regarding infant feeding and pacifier use. Results: Pacifiers were introduced by 79% of mothers, of whom 28.7% were advised to use a pacifier by their mother/mother-in-law with a further 22.7% being advised by a midwife. The majority of mothers used a pacifier in order to soothe their infant (78.3%), to help put them to sleep (57.4%) and to keep them comforted and quiet (40.4%). Pacifiers given to infants before four weeks (adjHR 3.67; 95%CI 2.14–6.28) and used most days (adjHR 3.28; 95%CI 1.92–5.61) were significantly associated with shorter duration of breastfeeding. Conclusions: This study identifies an opportunity for educating new mothers and their support network, particularly their infant’s grandmothers, with regards to potential risks associated with the early and frequent use of a pacifier, and alternative methods for soothing their infant, in order to reduce the use of pacifiers and their potentially negative effect on breastfeeding duratio

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Promoção, prevenção e cuidado da hipertensão arterial no Brasil

OBJETIVO: Estimar a prevalência de ações de promoção, prevenção e cuidado da hipertensão arterial em adultos e identificar sua associação com estado descompensado de hipertensão. MÉTODOS: Estudo epidemiológico transversal de base populacional realizado por meio de entrevista com 12.324 adultos, de 20 a 59 anos, em 100 municípios brasileiros. As variáveis independentes, consideradas como promoção, prevenção e cuidado, foram: ter recebido orientações sobre a manutenção do peso ideal e sobre atividade física; ter consultado um médico e ter realizado eletrocardiograma no último ano. Pressão arterial acima de 140/90 mmHg foi considerada estado descompensado, sendo a variável dependente para a avaliação da qualidade do cuidado. RESULTADOS: Do total, 16,3% (n = 2.004) referiram diagnóstico médico de hipertensão. As maiores prevalências de hipertensão foram observadas na categoria de idade de 50 a 59 anos, concentradas nas regiões Sudeste e Centro-Oeste. Mais da metade (66,1%) esteve em consulta médica por hipertensão no último ano, da qual metade (52,4%) realizou eletrocardiograma. Dos hipertensos que tiveram sua pressão arterial aferida na entrevista (74,6%), menos da metade (42,4%) apresentava cifras tensionais descompensadas. CONCLUSÕES: Não houve associação entre haver consultado médico no último ano e cifras tensionais descompensadas. A proporção de hipertensos descompensados foi significativamente menor entre os que foram orientados para manter o peso ideal, realizar atividade física e os que fizeram eletrocardiograma. Ser do sexo masculino, ter idade acima de 40 anos e habitar na região Sul mostraram-se associados a estado descompensado da hipertensão.OBJECTIVE: To estimate the prevalence of promotion, prevention and arterial hypertension care actions in adults and to identify their association with decompensated hypertension. METHODS: A population-based cross-sectional epidemiological study was conducted by interviewing 12,324 adults aged from 20 to 59 years, in 100 Brazilian cities. The independent variables considered as promotion, prevention and hypertension care were as follows: to have received guidance on ideal weight maintenance and physical activity practice; to have consulted a doctor; and to have had an electrocardiogram performed in the previous year. A blood pressure higher than 140/90 mm/Hg was considered to be decompensated, being the dependent variable adopted to assess quality of care. RESULTS: Of all participants, 16.3% (n = 2,004) reported a medical diagnosis of hypertension. The highest prevalences of hypertension were observed in the 50 to 59 year age group, primarily in the Southeast and Center-West regions. More than half (66.1%) of participants had a medical consultation about hypertension in the previous year, of which half (52.4%) had an electrocardiogram. Of all those with hypertension who had their blood pressure measured during interview (74.6%), less than half (42.4%) had decompensated values. CONCLUSIONS: There was no association between having consulted a doctor in the previous year and decompensated blood pressure values. The proportion of decompensated hypertensive participants was significantly lower among those who had received guidance on ideal weight maintenance and physical activity practice and those who had had an electrocardiogram performed. The following factors were associated with decompensated hypertension: to be male, to be aged more than 40 years and to live in the South region.OBJETIVO: Estimar la prevalencia de acciones de promoción, prevención y cuidado de la hipertensión arterial en adultos e identificar la asociación con el estado descompensado de hipertensión. MÉTODOS: Estudio epidemiológico transversal de base poblacional realizado a través de entrevista en 12.324 adultos, de 20 a 59 años, en 100 municipios brasileños. Las variables independientes, consideradas como promoción, prevención y cuidado fueron: haber recibido orientaciones sobre la manutención del peso ideal y actividad física; haber consultado un médico y haber realizado el electrocardiograma en el último año. Presión arterial por encima de 140/90 mm/Hg se consideró estado descompensado, siendo la variable dependiente para la evaluación de la calidad del cuidado. RESULTADOS: del total, 16,3% (n= 2.004) refirieron diagnóstico médico de hipertensión. Las mayores prevalencias de hipertensión se observaron en la categoría de edad de 50 a 59 años, concentradas en las regiones Sureste y Centro-Oeste. Más de la mitad (66,1%) estuvo en consulta médica por hipertensión en el último año, y la mitad de estos (52,4%) realizó electrocardiograma. De los hipertensos que chequearon la presión arterial en la entrevista, 74,6%, menos de la mitad (42,4%) presentó cifras tensionales descompensadas. CONCLUSIONES: No hubo asociación entre haber consultado el médico en el último año y cifras tensionales descompensadas. La proporción de hipertensos descompensados fue significativamente menor entre los que fueron orientados para mantener el peso ideal, realizar actividad física y los que hicieron electrocardiograma. Ser del sexo masculino, tener edad por encima de 40 años y habitar en la región Sur, se evidenciaron asociados al estado descompensado de la hipertensión