Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes.

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice.

Dexamethasone Administration During Late Gestation Has No Major Impact on Lipid Metabolism, but Reduces Newborn Survival Rate in Wistar Rats.

A rise in plasma triacylglycerol levels is a common physiological occurrence during late gestation and excess of glucocorticoids (GCs) has been shown to impair lipid metabolism. Based on those observations, we investigated whether the administration of dexamethasone during the late gestational period could exacerbate this pregnancy associated hypertriacylglycerolemia in rats. For this, female Wistar rats were treated with dexamethasone (0.2 mg/kg of body mass in the drinking water on days 14-19 of pregnancy; DP group) or equivalent days in the virgin rats (DV group). Untreated pregnant rats (control pregnant group) and age-matched virgin rats (control virgin group) were used as controls. Functional, biochemical, and molecular analyses were carried out after treatment with GC and in the control groups. Euthanasia was performed on day 20 of pregnancy. The metabolic parameters of the mothers (dams) at the time of weaning and 6 months later, as well as newborn survival, were evaluated. We observed that neither dexamethasone nor pregnancy affected blood glucose or glucose tolerance. Hypertriacylglycerolemia associated with lipid intolerance or reduced hepatic triacylglycerol clearance was observed during the late gestational period. GC treatment caused a further increase in basal plasma triacylglycerol levels, but did not have a significant effect on lipid tolerance and hepatic triacylglycerol clearance in pregnant rats. GC, but not pregnancy, caused few significant changes in mRNA expression of proteins involved in lipid metabolism. Dexamethasone during pregnancy had no impact on lipid metabolism later in the dams' life; however, it led to intra-uterine growth restriction and reduced pup survival rate. In conclusion, GC exposure during the late gestational period in rats has no major impact on maternal lipid homeostasis, soon after parturition at weaning, or later in the dams' life, but GC exposure is deleterious to the newborn when high doses are administered at late gestation. These data highlight the importance of performing an individualized and rigorous control of a GC treatment during late pregnancy considering its harmful impact on the fetuses' health.

Selective regulation of hepatic lipid metabolism by the AMP-activated protein kinase pathway in late-pregnant rats.

The liver plays an essential role in maternal metabolic adaptation during late pregnancy. With regard to lipid metabolism, increased secretion of very low-density lipoprotein (VLDL) is characteristic of late pregnancy. Despite this well-described metabolic plasticity, the molecular changes underlying the hepatic adaptation to pregnancy remain unclear. As AMPK is a key intracellular energy sensor, we investigated whether this protein assumes a causal role in the hepatic adaptation to pregnancy. Pregnant Wistar rats were treated with vehicle or AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) for 5 days starting at gestational day 14. At the end of treatment, the rats were subjected to an intraperitoneal pyruvate tolerance test and in situ liver perfusion with pyruvate. The livers were processed for Western blot analysis, quantitative PCR, thin-layer chromatography, enzymatic activity, and glycogen content measurements. Blood biochemical profiles were also assessed. We found that AMPK and ACC phosphorylation were reduced in the livers of pregnant rats in parallel with a reduced level of hepatic gluconeogenesis of pyruvate. This effect was accompanied by both a reduction in the levels of hepatic triglycerides (TG) and an increase in circulating levels of TG. Treatment with AICAR restored hepatic levels of TG to those observed in nonpregnant rats. Additionally, AMPK activation reduced the upregulation of genes related to VLDL synthesis and secretion observed in the livers of pregnant rats. We conclude that the increased secretion of hepatic TG in late pregnancy is concurrent with a transcriptional profile that favors VLDL production. This transcriptional profile results from the reduction in hepatic AMPK activity.

Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.

Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GC levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis. Dexamethasone (DEX) was administered noninvasively to the mothers via drinking water between the 14th and the 19th days of pregnancy. Mothers were subjected to glucose and insulin tolerance tests at 1, 2, 3, 6, and 12 mo postweaning. Pregnant rats not treated with DEX and age-matched virgin rats were used as controls. Pancreatic islets were isolated at the 20th day of pregnancy and 12 mo postweaning in order to evaluate glucose-stimulated insulin secretion. The expression of the miR-29 family was also studied due to its responsiveness to GCs and its well-documented role in the regulation of pancreatic ß-cell function. Rats treated with DEX during pregnancy presented long-term glucose intolerance and impaired insulin secretion. These changes correlated with 1) increased expression of miR-29 and its regulator p53, 2) reduced expression of syntaxin-1a, a direct target of miR-29, and 3) altered expression of genes related to cellular senescence. Our data demonstrate that the use of DEX during pregnancy results in deleterious outcomes to the maternal metabolism, hallmarked by reduced insulin secretion and glucose intolerance. This maternal metabolic programming might be a consequence of time-sustained upregulation of miR-29s in maternal pancreatic islets.

Maternal melatonin programs the daily pattern of energy metabolism in adult offspring.

BACKGROUND: Shift work was recently described as a factor that increases the risk of Type 2 diabetes mellitus. In addition, rats born to mothers subjected to a phase shift throughout pregnancy are glucose intolerant. However, the mechanism by which a phase shift transmits metabolic information to the offspring has not been determined. Among several endocrine secretions, phase shifts in the light/dark cycle were described as altering the circadian profile of melatonin production by the pineal gland. The present study addresses the importance of maternal melatonin for the metabolic programming of the offspring. METHODOLOGY/PRINCIPAL FINDINGS: Female Wistar rats were submitted to SHAM surgery or pinealectomy (PINX). The PINX rats were divided into two groups and received either melatonin (PM) or vehicle. The SHAM, the PINX vehicle and the PM females were housed with male Wistar rats. Rats were allowed to mate and after weaning, the male and female offspring were subjected to a glucose tolerance test (GTT), a pyruvate tolerance test (PTT) and an insulin tolerance test (ITT). Pancreatic islets were isolated for insulin secretion, and insulin signaling was assessed in the liver and in the skeletal muscle by western blots. We found that male and female rats born to PINX mothers display glucose intolerance at the end of the light phase of the light/dark cycle, but not at the beginning. We further demonstrate that impaired glucose-stimulated insulin secretion and hepatic insulin resistance are mechanisms that may contribute to glucose intolerance in the offspring of PINX mothers. The metabolic programming described here occurs due to an absence of maternal melatonin because the offspring born to PINX mothers treated with melatonin were not glucose intolerant. CONCLUSIONS/SIGNIFICANCE: The present results support the novel concept that maternal melatonin is responsible for the programming of the daily pattern of energy metabolism in their offspring.

Efeito da cinesioterapia e eletroestimulação transvaginal na incontinência urinária feminina: estudo de caso / Effect of kinesiotherapy and transvaginal electrical stimulation in the urinary incontinence in women: case study

Embora a incontinência urinária não coloque diretamente a vida das pessoas em risco, é uma condição quepode trazer sérias implicações. Publicações recentes têm demonstrado melhora significativa no quadro clínicoe na qualidade de vida de mulheres incontinentes submetidas ao tratamento conservador. Portanto, o presenteestudo teve como objetivo avaliar o efeito do tratamento fisioterapêutico sobre a qualidade de vida de umamulher com incontinência urinária. Apresentação do caso: estudo de caso de uma mulher com incontinênciaurinária de esforço. Inicialmente foi realizada anamnese e exame físico, coletando-se dados como histórico dadoença e tonicidade dos músculos do assoalho pélvico; em seguida a paciente respondeu ao questionárioInternational Consultation on Incontinence Questionnaire - Short Form. Após 20 sessões de fisioterapiao mesmo exame físico e o mesmo questionário foram aplicados e os escores iniciais e finais, bem como osdados coletados nos exames físicos foram comparados. Resultados: a paciente apresentou aumento notônus muscular do assoalho pélvico e aumento no grau de força dos mesmos, melhora do quadro clínico e dasua qualidade de vida. Conclusão: O presente estudo concluiu que a fisioterapia, baseada em cinesioterapiae eletroterapia endovaginal, contribuiu para a melhora no quadro de incontinência urinária e, conseqüentemente,na melhora da qualidade de vida de paciente tratada.

Even though urinary incontinence does not directly threaten people’ lives, it is a condition that can bringserious implications. Recent publications have shown significant improvement in clinical and quality of lifeof incontinent women submitted to conservative treatment. Therefore, this study aimed to evaluate the effectof physiotherapeutic treatment on the quality of life of a woman with urinary incontinence. Presentation ofthe case: a case study of a woman with stress urinary incontinence. Initially, a careful anamnesis and aphysical examination were undertaken to collect data such as past medical history, course of the disease, andthe muscle tonus of the pelvic floor. Then, the patient was asked to answer the International Consultation onIncontinence Questionnaire - Short Form. After 20 sessions of physiotherapy the same physical examinationand the same questionnaire were undertaken again. The initial and final scores and data previously collectedwere compared. Results: The patient had an increase in muscle tonus of the pelvic floor and increased thestrength degree of limbs, improved the clinical picture and their quality of life. Conclusion: This studyconcluded that physiotherapy based on kinesitherapy and electrotherapy transvaginal contributed to theimprovement of the clinical picture of stress urinary incontinence and, consequently, improves the quality oflife of the patients treated.

Dípteros fanídeos vetores de ovos de Dermatobia hominis em Campo Grande, Mato Grosso do Sul / Fanniid diptera vectors of Dermatobia hominis eggs in Campo Grande, MS, Brazil

Determinou-se a importância epidemiológica de dípteros Fanniidae na infestaçäo de mosca-do-berne, por meio da identificaçäo das espécies presentes, da determinaçäo daquelas utilizadas por Dermatobia hominis na veiculaçäo de seus ovos, bem como, pelo conhecimento da dinâmica populacional das espécies mais abundantes. Foram utilizadas cinco armadilhas iscadas com fígado bovino cru deteriorado e colocadas em uma mata ciliar margeada por uma área de pastagem com presença constante de bovinos. O estudo foi desenvolvido em uma área da Embrapa Gado de Corte, em Campo Grande, Estado de Mato Grosso do Sul, Brasil, localizada a 20º27'S e 54º37'W. A captura dos insetos foi realizada semanalmente durante o período de 09/08/1999 a 03/08/2000. Foi capturado um total de 40.629 moscas da família Fanniidae, pertencendo a cinco espécies do gênero Fannia: F. pusio, F. heydenii, F. bahiensis e F. longipila, e uma a ser identificada. A espécie mais freqüente foi F. pusio, com 63,20 por cento do total capturado, seguida de F. heydenii, com 28,82 por cento. Somente 0,44 por cento do total de fêmeas de F. heydenii (45 exemplares) capturadas, principalmente nos meses de agosto e setembro, portavam ovos de D. hominis e o número médio, por indivíduo, foi de 15,98±7,13. Observaram-se ovos de D. hominis apenas na regiäo abdominal dos vetores. F. heydenii predominou no período seco (maio a setembro) e início do período chuvoso do ano (outubro e novembro). O número de exemplares portando ovos de D. hominis foi maior no final do período seco do ano, o que explica a alta incidência deste parasito em bovinos nos meses de setembro e outubro