New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension

Heterotopic autotransplantation of ovarian tissue in a large animal model: Effects of cooling and VEGF.

Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation site was monitored at days 2, 4, 6, and 7 post-grafting using color-Doppler ultrasonography. Ovarian grafts were recovered 7 days post-transplantation and subjected to histological analyses. The exposure of the ovarian fragments to VEGF before grafting was not beneficial to the quality of the tissue; however, the cooling process of the fragments reduced the acute hyperemia post-grafting. Cooled grafts compared with non-cooled grafts contained similar values for normal and developing preantral follicles, vessel density, and stromal cell apoptosis; lower collagen type III fibers and follicular density; and higher stromal cell density, AgNOR, and collagen type I fibers. In conclusion, VEGF exposure before autotransplantation did not improve the quality of grafted tissues. However, cooling ovarian tissue for at least 24 h before grafting can be beneficial because satisfactory rates of follicle survival and development, stromal cell survival and proliferation, as well as vessel density, were obtained

Conhecimento sobre aleitamento materno entre estudantes de Enfermagem e Medicina (Salvador, Bahia)

Even with all the described benefits of breastfeeding, we still observe that this practice is not the ideal all over the world, fact that leads more importance to the medical and nurse professionals about the adequate knowledge.Compare the knowledge about breastfeeding among medical and nurse students, in the beginning and final of the graduate course, 88 from the beginning and 85 from the end of the courses. Afterwards the questionnaire was stratificated  in eight blocks of questions, and each one has received a score according the number of questions. It hasn´t found statistical differences between the score averages of students from the beginning of the courses, but it was noted a significant difference between the knowledge in the end of both courses. The Medicine students presented at the end of course an averages rank higher than those of nursing students. There is an improvement of knowledge about breastfeeding in both graduate courses, but the differences need more investigation.Apesar da importância comprovada dos vários benefícios do aleitamento materno, tem-se observado a amamentação como uma prática ainda aquém da ideal entre muitas comunidades em todo o mundo, o que torna ainda mais importante o papel dos profissionais de medicina e de enfermagem na assistência puerperal, a fim de incentivar adequadamente o aleitamento materno. Este estudo teve como objetivo comparar o conhecimento sobre aleitamento materno dos estudantes de graduação, no início e no final dos cursos médico e de enfermagem. Foram aplicados 173 questionários, durante três dias, sendo 88 do início dos cursos (32 do primeiro ano de Enfermagem e 56 do primeiro ano de Medicina) e 85 do final dos cursos (47 dos sexto e sétimo semestres de Enfermagem e 38 dos décimo primeiro e décimo segundo semestres de Medicina). Posteriormente, o instrumento foi estratificado em oito blocos de perguntas, e cada um recebeu um escore de acordo com o número de questões. Não foram encontradas diferenças significativas entre as médias de escores de graduandos do início de curso, mas constatou-se que há diferença significativa entre o conhecimento dos grupos no início e no final dos cursos analisados. O grupo de estudantes de Medicina, no final do curso, apresentou uma média e um rank médio significativamente maiores, se comparados ao grupo no final do curso de Enfermagem. Concluiu-se que houve um aumento do conhecimento sobre o aleitamento materno durante o curso de graduação de ambos os cursos, porém a diferença do conhecimento observada entre os graduandos de final de curso de Medicina e Enfermagem precisa ser mais bem investigada

Links between plant and fungal communities across a deforestation chronosequence in the Amazon rainforest

Understanding the interactions among microbial communities, plant communities and soil properties following deforestation could provide insights into the long-term effects of land-use change on ecosystem functions, and may help identify approaches that promote the recovery of degraded sites. We combined high-throughput sequencing of fungal rDNA and molecular barcoding of plant roots to estimate fungal and plant community composition in soil sampled across a chronosequence of deforestation. We found significant effects of land-use change on fungal community composition, which was more closely correlated to plant community composition than to changes in soil properties or geographic distance, providing evidence for strong links between above- and below-ground communities in tropical forests. © 2014 International Society for Microbial Ecology All rights reserved

A strategy for the rapid identification of fungal metabolites and the discovery of the antiviral activity of pyrenocine a and harzianopyridon

The isolation and identification of bioactive metabolites from complex extracts obtained from microbial growth media is a time consuming, costly, and labor-intensive task. A strategy to rapidly identify secondary metabolites isolated from extracts obtained from the culture media of marine-derived and endophytic fungal strains is described. Identification was achieved by HPLC-UV-MS and 1H NMR analyses in combination with data obtained from the Dictionary of Natural Products. Among the compounds identified, (-)-naphthoquinoneimine, citreorosein, emodin, pyrenocine A and harzianopyridone displayed moderate to potent antiviral activity. (-)-Naphthoquinoneimine was isolated as the enantiomer of its previously reported dextrorotatory congener, while 6,7-dihydroxy-2,2-dimethyl-4-chromanone is herein reported for the first time as a natural product396720731CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPBEX 4498-14-32010/50190-2; 2013/50228-8; 2011/08064-2; 2008/00331-9; 2013/23153-

Identification of novel soybean microRNAs involved in abiotic and biotic stresses

<p>Abstract</p> <p>Background</p> <p>Small RNAs (19-24 nt) are key regulators of gene expression that guide both transcriptional and post-transcriptional silencing mechanisms in eukaryotes. Current studies have demonstrated that microRNAs (miRNAs) act in several plant pathways associated with tissue proliferation, differentiation, and development and in response to abiotic and biotic stresses. In order to identify new miRNAs in soybean and to verify those that are possibly water deficit and rust-stress regulated, eight libraries of small RNAs were constructed and submitted to Solexa sequencing.</p> <p>Results</p> <p>The libraries were developed from drought-sensitive and tolerant seedlings and rust-susceptible and resistant soybeans with or without stressors. Sequencing the library and subsequent analyses detected 256 miRNAs. From this total, we identified 24 families of novel miRNAs that had not been reported before, six families of conserved miRNAs that exist in other plants species, and 22 families previously reported in soybean. We also observed the presence of several isomiRNAs during our analyses. To validate novel miRNAs, we performed RT-qPCR across the eight different libraries. Among the 11 miRNAs analyzed, all showed different expression profiles during biotic and abiotic stresses to soybean. The majority of miRNAs were up-regulated during water deficit stress in the sensitive plants. However, for the tolerant genotype, most of the miRNAs were down regulated. The pattern of miRNAs expression was also different for the distinct genotypes submitted to the pathogen stress. Most miRNAs were down regulated during the fungus infection in the susceptible genotype; however, in the resistant genotype, most miRNAs did not vary during rust attack. A prediction of the putative targets was carried out for conserved and novel miRNAs families.</p> <p>Conclusions</p> <p>Validation of our results with quantitative RT-qPCR revealed that Solexa sequencing is a powerful tool for miRNA discovery. The identification of differentially expressed plant miRNAs provides molecular evidence for the possible involvement of miRNAs in the process of water deficit- and rust-stress responses.</p

Prevalência, fatores de risco e genótipos da hepatite C entre usuários de drogas

OBJECTIVE: To estimate prevalence of hepatitis C virus (HCV) infection and identify risk factors associated and circulating HCV genotypes and subtypes. METHODS: Study conducted including 691 drug users attending 26 charitable, private and public drug treatment centers in Goiânia and Campo Grande, central-western Brazil, between 2005 and 2006. Sociodemographic characteristics and risk factors for HCV infection were collected during interviews. Blood samples were tested for HCV antibodies (anti-HCV). Positive samples were submitted to HCV RNA detection by PCR with primers complementary to 5' NC and NS5B regions of viral genome and genotyped by line probe assay (LiPA) and direct nucleotide sequencing followed by phylogenetic analysis. The prevalence and odds ratio were calculated with 95% confidence intervals. Risk factors were first estimated in the univariate analysis (pOBJETIVO: Estimar la prevalencia y factores asociados a la infección por el virus de la hepatitis C en usuarios de drogas e identificar los genotipos y subtipos virales circulantes. MÉTODOS: Estudio realizado con 691 usuarios de drogas de 26 centros de tratamiento de uso de drogas filantrópicos, particulares y públicos de Goiania y Campo Grande (Centro-Oeste), entre 2005 y 2006. Datos sociodemográficos y factores de riesgo para infección por el HCV fueron obtenidos por medio de entrevistas. Muestras sanguíneas fueron evaluadas para la detección de anticuerpos para el HCV. Las muestras positivas fueron sometidas a la detección de RNA-HCV por la reacción en cadena de polimerasa con iniciadores complementarios a las regiones 5' NC y NS5B del genoma viral y genotipadas por el line probe assay (LiPA) y por secuenciación directa, seguido del análisis filogenético. Prevalencia y odds ratio fueron calculados con intervalo de 95% de confianza. Los factores de riesgo con pOBJETIVO: Estimar a prevalência e fatores associados à infecção pelo vírus da hepatite C em usuários de drogas e identificar os genótipos e subtipos virais circulantes. MÉTODOS: Estudo realizado com 691 usuários de drogas de 26 centros de tratamento de uso de drogas filantrópicos, particulares e públicos de Goiânia (GO) e Campo Grande (MS), entre 2005 e 2006. Dados sociodemográficos e fatores de risco para infecção pelo HCV foram obtidos por meio de entrevistas. Amostras sangüíneas foram testadas para a detecção de anticorpos para o HCV. As amostras positivas foram submetidas à detecção do RNA-HCV pela reação em cadeia da polimerase com iniciadores complementares às regiões 5' NC e NS5B do genoma viral e genotipadas pelo line probe assay (LiPA) e por seqüenciamento direto, seguido de análise filogenética. Prevalência e odds ratio foram calculados com intervalo de 95% de confiança. Os fatores de risco com

Increased exposure to sodium during pregnancy and lactation changes basal and induced behavioral and neuroendocrine responses in adult male offspring

Excessive sodium (Na+) intake in modern society has been associated with several chronic disorders such as hypertension. Several studies suggest that early life events can program physiological systems and lead to functional changes in adulthood. Therefore, we investigated behavioral and neuroendocrine responses under basal conditions and after 48 h of water deprivation in adult (60-day-old Wistar rats) male, Wistar rats originating from dams were offered only water or 0.15 mol/L NaCl during pregnancy and lactation. Early life salt exposure induced kidney damage, as shown by a higher number of ED-1 positive cells (macrophages/monocytes), increased daily urinary volume and Na+ excretion, blunted basal water intake and plasma oxytocin levels, and increased plasma corticosterone secretion. When challenged with water deprivation, animals exposed to 0.15 mol/L NaCl during early life showed impaired water intake, reduced salt preference ratio, and vasopressin (AVP) secretion. In summary, our data demonstrate that the perinatal exposure to excessive Na+ intake can induce kidney injury in adult offspring and significantly affect the key mechanisms regulating water balance, fluid intake, and AVP release in response to water deprivation. Collectively, these novel results highlight the impact of perinatal programming on the homeostatic mechanisms regulating fluid and electrolyte balance during exposure to an environmental stress (i.e. dehydration) in later life.Fil: Silva, Marcia S.. Universidade de Sao Paulo; BrasilFil: Lúcio Oliveira, Fabiana. Universidade de Sao Paulo; BrasilFil: Mecawi, Andre Souza. University of Malaya; MalasiaFil: Almeida, Lucas F.. Universidade de Sao Paulo; Brasil. Universidade Federal Rural do Rio de Janeiro; BrasilFil: Ruginsk, Silvia G.. Federal University of Alfenas; BrasilFil: Greenwood, Michael P.. University of Bristol; Reino UnidoFil: Greenwood, Mingkwan. University of Bristol; Reino UnidoFil: Vivas, Laura Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Elias, Lucila L. K.. Universidade de Sao Paulo; BrasilFil: Murphy, David. Universidade de Sao Paulo; Brasil. Universidade Federal Rural do Rio de Janeiro; BrasilFil: Antunes Rodrigues, José. Universidade de Sao Paulo; Brasi

A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

<p>Abstract</p> <p>Background</p> <p>Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd₂[<it>S_(-)</it>C², N-dmpa]₂(μ-dppe)Cl₂} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.</p> <p>Methods</p> <p>B16F10-Nex2 cells were treated <it>in vitro </it>with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated <it>in vitro </it>with C7a.</p> <p>Results</p> <p>Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages <it>in vitro</it>, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.</p> <p>Conclusions</p> <p>The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.</p