Antinociceptive activity of Ipomoea imperati (Vahl) Griseb., Convolvulaceae

Ipomoea imperati (Vahl) Griseb., Convolvulaceae, is used in folk medicine for the treatment of inflammation, swelling and wounds, as well as to treat pains after childbirth and for stomach problems. Administration of ethanol extract, lipid and aqueous fraction of I. imperati(300, 100 and 200 mg/kg) significantly inhibited the abdominal constriction in mice induced by acetic acid; increased the sleeping time evoked by pentobarbital sodium and showed a significant activity by inhibiting formalin-induced paw edema in mice. The same dose of I. imperatialso raised the pain of mice in the hot-plate test and increased the latency at all observation times. The pre-treatment of the animals with naloxone (5 mg/kg, i.p.) suggested the participation of the opioid system in the antinociceptive effect of Ipomoea imperati.

Controle da adipogênese por ácidos graxos

A obesidade é um dos principais problemas de saúde pública. Indivíduos obesos são mais suscetíveis a desenvolver doenças cardiovasculares e diabetes melito tipo 2. A obesidade resulta do aumento no tamanho e no número de adipócitos. O balanço entre adipogênese e adiposidade determina o grau de obesidade do indivíduo. Adipócitos maduros secretam adipocinas, tais como TNFα, IL-6, leptina e adiponectina, e lipocina, o ácido palmitoleico ω-7. A produção de adipocinas é maior na obesidade, o que contribui para o estabelecimento de resistência periférica à insulina. O conhecimento dos eventos moleculares que regulam a diferenciação dos pré-adipócitos e de células-tronco mesenquimais em adipócitos (adipogênese) é importante para o entendimento da gênese da obesidade. A ativação do fator de transcrição PPARγ é essencial na adipogênese. Certos ácidos graxos são ligantes de PPARγ e podem, assim, controlar a adipogênese. Além disso, alguns ácidos graxos atuam como moléculas sinalizadoras em adipócitos, regulando sua diferenciação ou morte. Dessa forma, a composição lipídica da dieta e os agonistas de PPARγ podem regular o balanço entre adipogênese e morte de adipócitos e, portanto, a obesidade.

Changes in parents' and self-reports of behavioral problems in Brazilian adolescents after behavioral treatment with urine alarm for nocturnal enuresis

PURPOSE: Compare parents' reports of youth problems (PRYP) with adolescent problems self-reports (APSR) pre/post behavioral treatment of nocturnal enuresis (NE) based on the use of a urine alarm. MATERIALS AND METHODS: Adolescents (N = 19) with mono-symptomatic (primary or secondary) nocturnal enuresis group treatment for 40 weeks. Discharge criterion was established as 8 weeks with consecutive dry nights. PRYP and APSR were scored by the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR). RESULTS: Pre-treatment data: 1) Higher number of clinical cases based on parent report than on self-report for Internalizing Problems (IP) (13/19 vs. 4/19), Externalizing Problems (EP) (7/19 vs. 5/19) and Total Problem (TP) (11/19 vs. 5/19); 2) Mean PRYP scores for IP (60.8) and TP (61) were within the deviant range (T score ≥ 60); while mean PRYP scores for EP (57.4) and mean APSR scores (IP = 52.4, EP = 49.5, TP = 52.4) were within the normal range. Difference between PRYP' and APSR' scores was significant. Post treatment data: 1) Discharge for majority of the participants (16/19); 2) Reduction in the number of clinical cases on parental evaluation: 9/19 adolescents remained within clinical range for IP, 2/19 for EP, and 7/19 for TP. 3) All post-treatment mean scores were within the normal range; the difference between pre and post evaluation scores was significant for PRYP. CONCLUSIONS: The behavioral treatment based on the use of urine alarm is effective for adolescents with mono-symptomatic (primary and secondary) nocturnal enuresis. The study favors the hypothesis that enuresis is a cause, not a consequence, of other behavioral problems.

Causas mal definidas de morte e óbitos sem assistência

OBJETIVOS: Este trabalho estuda a distribuição dos óbitos por causas mal definidas no Brasil, no ano de 2003, entre as quais identifica a proporção de mortes sem assistência. MÉTODOS: Os dados provieram do Sistema de Informações Sobre Mortalidade, coordenado pelo Ministério da Saúde. As causas mal definidas de morte compreenderam as incluídas no "Capítulo XVIII - Sintomas, sinais e achados anormais de exames clínicos e de laboratório não classificados em outra parte" da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde, décima revisão, capítulo este no qual a categoria R98 identificava a "morte sem assistência". RESULTADOS: No Brasil, em 2003, a causa básica de 13,3% dos óbitos foi identificada como mal definida, sendo que as proporções maiores ocorreram nas Regiões Nordeste e Norte. Do total de causas mal definidas no país, 53,3% corresponderam a mortes sem assistência, proporção esta que superou 70% nos Estados do Maranhão, Piauí, Rio Grande do Norte, Pernambuco, Bahia, Paraíba e Alagoas. CONCLUSÃO: Dada a estrutura descentralizada para o levantamento dos óbitos no país, identifica-se a maior responsabilidade dos municípios e, em seguida, dos Estados para o aprimoramento da qualidade das estatísticas de mortalidade.

Um enfoque sanitário sobre a demanda judicial de medicamentos

No Brasil, apesar dos avanços da assistência farmacêutica, permanecem falhas na garantia do acesso dos cidadãos aos medicamentos pelo Estado. Nos últimos anos, vem crescendo a reivindicação de medicamentos por parte do cidadão via sistema judiciário. Os objetos dessas solicitações são tanto os medicamentos em falta na rede pública como aqueles ainda não incorporados pelo Sistema Único de Saúde. Este fenômeno pode ser analisado sob diferentes perspectivas, inclusive a sanitária, entendida aqui como os desfechos sobre a saúde dos indivíduos que demandam estes medicamentos. O presente texto busca discutir as principais características das demandas judiciais frente aos seguintes aspectos: o uso racional de medicamentos, o uso de evidências científicas para a indicação terapêutica proposta e o quanto as demandas se justificam diante do conceito de acesso adotado pelo campo da assistência farmacêutica. Ponderações podem ser feitas no sentido de minimizar os riscos à saúde dos demandantes de medicamentos por via judicial, sobretudo quando o objeto da ação são medicamentos não pertencentes às listas de fornecimento público, ou com uso off label, ou desprovidos de registro no país. Considera-se que o Judiciário, a partir do fornecimento de medicamentos, busca garantir a saúde dos demandantes, e assim a dignidade da pessoa humana. Cabe ressaltar que este objetivo só será atingido quando a garantia da saúde estiver associada aos aspectos que certificam a segurança do paciente, inclusive no uso de medicamentos.

Surface dental enamel lead levels and antisocial behavior in Brazilian adolescents

Lead poisoning has been reportedly linked to a high risk of learning disabilities, aggression and criminal offenses. To study the association between lead exposure and antisocial/delinquent behavior, a cross-sectional study was conducted with 173 Brazilian youths aged 14\201318 and their parents (n = 93), living in impoverished neighborhoods of Bauru-SP, with high criminality indices. Self-Reported Delinquency (SRD) and Child Behavior Checklist (CBCL) questionnaires were used to evaluate delinquent/antisocial behavior. Body lead burdens were evaluated in surface dental enamel acid microbiopsies. The dental enamel lead levels (DELL) were quantified by graphite furnace atomic absorption spectrometry (GFAAS) and phosphorus content was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Logistic regression was used to identify associations between DELL and each scale defined by CBCL and SRD scores. Odd ratios adjusted for familial and social covariates, considering a group of youths exposed to high lead levels (\2265 75 percentile), indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rule-breaking behavior and externalizing problems (CI 95 per cent). High DELL was not found to be associated with elevated SRD scores. In conclusion, our data support the hypothesis that high-level lead exposure can trigger antisocial behavior, which calls for public policies to prevent lead poisoning

Nutrition and health: the issue is not food, nor nutrients, so much as processing [Invited commentary]

Orthodox teaching and practice on nutrition and health almost always focuses on nutrients, or else on foods and drinks. Thus, diets that are high in folate and in green leafy vegetables are recommended, whereas diets high in saturated fat and in full-fat milk and other dairy products are not recommended. Food guides such as the US Food Guide Pyramid are designed to encourage consumption of healthier foods, by which is usually meant those higher in vitamins, minerals and other nutrients seen as desirable.What is generally overlooked in such approaches, which currently dominate official and other authoritative information and education programmes, and also food and nutrition public health policies, is food processing. It is now generally acknowledged that the current pandemic of obesity and related chronic diseases has as one of its important causes increased consumption of convenience including pre-prepared foods(1,2). However, the issue of food processing is largely ignored or minimised in education and information about food, nutrition and health, and also in public health policies.A short commentary cannot be comprehensive, and a general proposal such as that made here is bound to have some problems and exceptions. Also, the social, cultural, economic and environmental consequences of food processing are not discussed here. Readers comments and queries are invited

Combining Legendre's Polynomials and Genetic Algorithm in the Solution of Nonlinear Initial-Value Problems

This work develops a method for solving ordinary differential equations, that is, initial-value problems, with solutions approximated by using Legendre's polynomials. An iterative procedure for the adjustment of the polynomial coefficients is developed, based on the genetic algorithm. This procedure is applied to several examples providing comparisons between its results and the best polynomial fitting when numerical solutions by the traditional Runge-Kutta or Adams methods are available. The resulting algorithm provides reliable solutions even if the numerical solutions are not available, that is, when the mass matrix is singular or the equation produces unstable running processes.

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A > G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot (R) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan (R) Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%: 1.3-8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

Increased Endothelial Cell-Leukocyte Interaction in Murine Schistosomiasis: Possible Priming of Endothelial Cells by the Disease

Background and Aims: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. Methodology and Principal Findings: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF). Nitric oxide (NO) donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS) increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. Conclusion/Significance: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially explained by a reduced eNOS expression. In addition, our data show that the disease primes endothelial cells in vivo, which keep the acquired phenotype in culture.

Increased CLA content in organic milk fermented by bifidobacteria or yoghurt cultures

This study investigates the kinetics of acidification, fatty acid (FA) profile and conjugated linoleic acid (CLA, C18:2 c9, t11) content in fermented milks prepared from organic and conventional milk. Fermented milks were manufactured with five mixed cultures: four different strains of Bifidobacterium animalis subsp. lactis (BL04, B94, BB12 and HN019) and Lactobacillus delbrueckii subsp. bulgaricus LB340, in co-culture with Streptococcus thermophilus TA040. The composition of milk was evaluated, and the kinetics of acidification was followed by continuous pH measurement using the Cinac system. The profile of FA, including CLA, was analyzed by gas chromatography. The chemical composition of conventional and organic milk was similar, with the exception of protein and Fe, the concentrations of which were higher in the organic milk. The rate of acidification was significantly influenced by the type of milk and the bacterial strain used. Co-cultures St-HN019 and St-BB12 showed higher maximal acidification rates in both milks. Final counts of S. thermophilus (9.0-10.1 log(10) colony forming units (CFU) . mL(-1), L)actobacillus bulgaricus (8.2-8.5 log(10) CFU . mL(-1)) and B. animalis subsp. lactis strains (8.3-9.3 log(10) CFU . mL(-1)) did not differ significantly in either milk. Unexpectedly, all fermented organic milks contained significantly higher amounts of CLA than the same milk before fermentation, whereas CLA amounts did not change during fermentation of conventional milk. Regardless of the type of milk, CLA was found to be significantly positively correlated with trans-vaccenic acid and negatively correlated with linoleic acid. Moreover, the CLA contents were significantly higher in fermented milks showing shorter fermentation times.

An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations

Background: Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers. Results: In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10(-5) for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers. Conclusions: Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies.

Activation of Neural and Pluripotent Stem Cell Signatures Correlates with Increased Malignancy in Human Glioma

The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal-and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.

Increased myoepithelial cells of bronchial submucosal glands in fatal asthma

Background: Fatal asthma is characterised by enlargement of bronchial mucous glands and tenacious plugs of mucus in the airway lumen. Myoepithelial cells, located within the mucous glands, contain contractile proteins which provide structural support to mucous cells and actively facilitate glandular secretion. Objectives: To determine if myoepithelial cells are increased in the bronchial submucosal glands of patients with fatal asthma. Methods: Autopsied lungs from 12 patients with fatal asthma (FA), 12 patients with asthma dying of non-respiratory causes (NFA) and 12 non-asthma control cases (NAC) were obtained through the Prairie Provinces Asthma Study. Transverse sections of segmental bronchi from three lobes were stained for mucus and smooth muscle actin and the area fractions of mucous plugs, mucous glands and myoepithelial cells determined by point counting. The fine structure of the myoepithelial cells was examined by electron microscopy. Results: FA was characterised by significant increases in mucous gland (p = 0.003), mucous plug (p = 0.004) and myoepithelial cell areas (p = 0.017) compared with NAC. When the ratio of myoepithelial cell area to total gland area was examined, there was a disproportionate and significant increase in FA compared with NAC (p = 0.014). Electron microscopy of FA cases revealed hypertrophy of the myoepithelial cells with increased intracellular myofilaments. The NFA group showed changes in these features that were intermediate between the FA and NAC groups but the differences were not significant. Conclusions: Bronchial mucous glands and mucous gland myoepithelial cell smooth muscle actin are increased in fatal asthma and may contribute to asphyxia due to mucous plugging.

Increased Levels of NOTCH1, NF-kappa B, and Other Interconnected Transcription Factors Characterize Primitive Sets of Hematopoietic Stem Cells

As previously shown, higher levels of NOTCH1 and increased NF-kappa B signaling is a distinctive feature of the more primitive umbilical cord blood (UCB) CD34+ hematopoietic stem cells (HSCs), as compared to bone marrow ( BM). Differences between BM and UCB cell composition also account for this finding. The CD133 marker defines a more primitive cell subset among CD34+ HSC with a proposed hemangioblast potential. To further evaluate the molecular basis related to the more primitive characteristics of UCB and CD133+ HSC, immunomagnetically purified human CD34+ and CD133+ cells from BM and UCB were used on gene expression microarrays studies. UCB CD34+ cells contained a significantly higher proportion of CD133+ cells than BM (70% and 40%, respectively). Cluster analysis showed that BM CD133+ cells grouped with the UCB cells ( CD133+ and CD34+) rather than to BM CD34+ cells. Compared with CD34+ cells, CD133+ had a higher expression of many transcription factors (TFs). Promoter analysis on all these TF genes revealed a significantly higher frequency ( than expected by chance) of NF-kappa B-binding sites (BS), including potentially novel NF-kappa B targets such as RUNX1, GATA3, and USF1. Selected transcripts of TF related to primitive hematopoiesis and self-renewal, such as RUNX1, GATA3, USF1, TAL1, HOXA9, HOXB4, NOTCH1, RELB, and NFKB2 were evaluated by real-time PCR and were all significantly positively correlated. Taken together, our data indicate the existence of an interconnected transcriptional network characterized by higher levels of NOTCH1, NF-kappa B, and other important TFs on more primitive HSC sets.