Measurement of melatonin in body fluids: Standards, protocols and procedures

Background and Purpose: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body's endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues. Data Identification: A search of the English-language literature (Medline) and a systematic review of published articles were carried out. Study Selection: Articles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review. Data Extraction: The authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures). Results of Data Synthesis: Melatonin measurements are useful for evaluating problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. They have also become an important tool for psychiatric diagnosis, their use being recommended for phase typing in patients suffering from sleep and mood disorders. Additionally, there has been a continuous interest in the use of melatonin as a marker for neoplasms of the pineal region. Melatonin decreases such as found with aging are or post pinealectomy can cause alterations in the sleep/wake cycle. The development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids has increasingly been shown to have direct relevance for clinical decision making. Conclusions: Due to melatonin's low concentration, as well as the coexistence of numerous other compounds in the blood, the routine determination of melatonin has been an analytical challenge. The available evidence indicates however that these challenges can be overcome and consequently that evaluation of melatonin's presence and activity can be an accessible and useful tool for clinical diagnosis. © Springer-Verlag 2010.

Progesterone restores the female prostate activity in ovariectomized gerbil and may act as competitor of testosterone in intraprostatic environment

Aims Little is known about the effect of progesterone on gerbil female prostate. It is known that normal oscillation in the progesterone and estradiol levels during the estrous cycle phases influence the morphophysiology of this gland. The present study aims to evaluate the isolated effect of prolonged administration of progesterone combined or not with testosterone on the prostate of ovariectomized female gerbil. Main methods To observe the morphological changes caused by castration in the prostate of different groups stereologic analyses of all prostate compartments, analysis of nuclear area and perimeter, and morphometric measurements of epithelial and smooth muscle cells layers were used. In addition, immunocytochemistry was performed to investigate the distribution of the androgen, estrogen alfa and beta and progesterone receptors in different prostatic compartments. Key findings This study demonstrated that both treatments partially recovered the structure of the gland. In the group treated with progesterone plus testosterone a higher incidence of epithelial and stromal disorders occurred, besides the absence of secretory activity. Thus, treatment only with progesterone showed better results in the restoration of glandular homeostasis mainly seen by the regulation of the secretory activity. Significance Collectively, the findings of this study indicate that progesterone may have a significant role on the maintenance of prostate morphophysiology, and showed an interesting evidence of hormonal competition between progesterone and testosterone. © 2013 Elsevier Inc.

Correlação entre 6-sulfatoximelatonina, distúrbios do sono e citocinas inflamatórias em Transtornos do Espectro do Autismo (TEA)

Pós-graduação em Fonoaudiologia - FFC

Brief Report: The lincRNA Hotair Is Required for Epithelial-to-Mesenchymal Transition and Stemness Maintenance of Cancer Cell Lines

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Three-Dimensional Sonographic Assessment of Placental Volume and Vascularization in Pregnancies Complicated by Hypertensive Disorders

Objectives-The purpose of this study was to evaluate the association between placental volumes, placental vascularity, and hypertensive disorders in pregnancy.Methods A prospective case-control study was conducted between April 2011 and July 2012. Placental volumes and vascularity were evaluated by 3-dimensional sonographic, 3-dimensional power Doppler histographic, and 2-dimensional color Doppler studies. Pregnant women were classified as normotensive or hypertensive and stratified by the nature of their hypertensive disorders. The following variables were evaluated: observed-to-expected placental volume ratio, placental volume-to-estimated fetal weight ratio, placental vascular indices, and pulsatility indices of the right and left uterine and umbilical arteries.Results Sixty-six healthy pregnant women and 62 pregnant women with hypertensive disorders were evaluated (matched by maternal age, gestational age at sonography, and parity). Placental volumes were not reduced in pregnancy in women with hypertensive disorders (P > .05). Conversely, reduced placental vascularization indices (vascularization index and vascularization-flow index) were observed in pregnancies complicated by hypertensive disorders (P < .01; P < .01), especially in patients with superimposed preeclampsia (P = .04; P = .02). A weak correlation was observed between placental volumes, placental vascular indices, and Doppler studies of the uterine and umbilical arteries.Conclusions Pregnancies complicated by hypertensive disorders are associated with reduced placental vascularity but not with reduced placental volumes. These findings are independent of changes in uterine artery Doppler studies. Future studies of the prediction of preeclampsia may focus on placental vascularity in combination with results of Doppler studies of the uterine arteries.

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

Prevalence of excessive daytime sleepiness and associated factors in women aged 35-49 years from the "Pindamonhangaba Health Project" (PROSAPIN)

OBJETIVO: Estimar a prevalência da sonolência diurna excessiva (SDE) e identificar os fatores associados em mulheres de 35 a 49 anos de idade do "Projeto de Saúde de Pindamonhangaba" (PROSAPIN). MÉTODOS: O estudo foi observacional transversal com 372 mulheres com idade entre 35 e 49 anos selecionadas aleatoriamente da Estratégia Saúde da Família (ESF) do município de Pindamonhangaba, São Paulo, onde é desenvolvido o "Projeto de Saúde de Pindamonhangaba" (PROSAPIN). A SDE foi avaliada por entrevista utilizando a Escala de Sonolência de Epworth e os fatores associados por meio de questões que investigaram as características sócio-demográficas, a história ginecológica, a presença de comorbidades, o estilo de vida, a rotina de sono e o uso de medicamentos capazes de alterar o estado de alerta, além de mensuradas as variáveis antropométricas. Estimou-se a prevalência da SDE com intervalo de confiança de 95% (IC 95%) e foram identificados os fatores associados por meio de um modelo de regressão logística múltipla realizado no Programa Stata, versão 10.0. RESULTADOS: A prevalência da SDE foi de 18,5% (IC 95%: 14,7- 22,9) e os fatores associados foram: profissão relacionada a serviços domésticos (OR = 2,2; IC 95%: 1,1-4,3), nível de atividade física acima da média da população estudada (OR = 1,9; IC 95%: 1,1-3,4); e a presença de características sugestivas de ansiedade (OR = 1,9; IC 95%: 1,1-3,4). CONCLUSÃO: A prevalência da SDE em mulheres de 35 a 49 anos do PROSAPIN foi elevada e associada à característica sociodemográfica, à presença de comorbidades e ao estilo de vida.

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. (C) 2012 International Society for Advancement of Cytometry

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Background: The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods: The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use. Results: The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use. Conclusions: Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Criminal career-related factors among female robbers in the State of Sao Paulo, Brazil, and a presumed 'revolving-door' situation

Introduction: Risk-taking behaviors, family criminality, poverty, and poor parenting have been frequently associated with an earlier onset of criminal activities and a longer criminal career among male convicts. Objective: This study aims to identify factors related to the onset and recurrence of criminal behavior among female robbers in the State of Sao Paulo - Brazil. Method: It was a cross-sectional study carried out inside a feminine penitentiary in Sao Paulo. From June 2006 to June 2010, 175 inmates convicted only for robbery were recruited to be evaluated about family antecedents of criminal conviction, alcohol and drug misuse, impulsiveness, depressive symptoms, and psychosocial features. Results: Having family antecedents of criminal conviction consistently predicted an earlier onset of criminal activities and a longer criminal career among female robbers. Drug use in youth and the severity of drug misuse were significantly related to the initiation and recurrence of criminal behavior, respectively. Discussion: Prisons must systematically screen detainees and provide treatments for those with health problems in general. Children of inmates should obtain help to modify the negative consequences of their parents' incarceration in order to mitigate the negative consequences of pursuing this 'static' factor.

The perception of sleep quality in kidney transplant patients during the first year of transplantation

OBJECTIVE: Poor sleep quality is one of the factors that adversely affects patient quality of life after kidney transplantation, and sleep disorders represent a significant cardiovascular risk factor. The objective of this study was to investigate the prevalence of changes in sleep quality and their outcomes in kidney transplant recipients and analyze the variables affecting sleep quality in the first years after renal transplantation. METHODS: Kidney transplant recipients were evaluated at two time points after a successful transplantation: between three and six months (Phase 1) and between 12 and 15 months (Phase 2). The following tools were used for assessment: the Pittsburgh Sleep Quality Index; the quality of life questionnaire Short-Form-36; the Hospital Anxiety and Depression scale; the Karnofsky scale; and assessments of social and demographic data. The prevalence of poor sleep was 36.7% in Phase 1 and 38.3% in Phase 2 of the study. RESULTS: There were no significant differences between patients with and without changes in sleep quality between the two phases. We found no changes in sleep patterns throughout the study. Both the physical and mental health scores worsened from Phase 1 to Phase 2. CONCLUSION: Sleep quality in kidney transplant recipients did not change during the first year after a successful renal transplantation.

Parent psychopathology and offspring mental disorders: results from the WHO World Mental Health Surveys

Background Associations between specific parent and offspring mental disorders are likely to have been overestimated in studies that have failed to control for parent comorbidity. Aims To examine the associations of parent with respondent disorders. Method Data come from the World Health Organization (WHO) World Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the Composite International Diagnostic Interview and parent disorders with informant-based Family History Research Diagnostic Criteria interviews. Results Although virtually all parent disorders examined (major depressive, generalised anxiety, panic, substance and antisocial behaviour disorders and suicidality) were significantly associated with offspring disorders in multivariate analyses, little specificity was found. Comorbid parent disorders had significant sub-additive associations with offspring disorders. Population-attributable risk proportions for parent disorders were 12.4% across all offspring disorders, generally higher in high- and upper-middle-than low-/lower-middle-income countries, and consistently higher for behaviour (11.0-19.9%) than other (7.1-14.0%) disorders. Conclusions Parent psychopathology is a robust non-specific predictor associated with a substantial proportion of offspring disorders.

Psychiatric comorbidities in temporal lobe epilepsy: Possible relationships between psychotic disorders and involvement of limbic circuits

Objective: Mounting evidence suggests that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological and connectivity changes might contribute to the development of psychosis and to the potential neurobiological mechanisms that cause schizophrenia-like psychosis in TLE patients. Methods: In this review, clinical and neuropathological findings, especially brain circuitry of the limbic system, were examined together to enhance our understanding of the association between TLE and psychosis. Finally, the importance of animal models in epilepsy and psychiatric disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Damage and deregulation among critical anatomical regions, such as the hippocampus, amygdala, thalamus, and the temporal, frontal and cingulate cortices, might predispose TLE brains to psychosis. Studies of the effects of kindling and injection of neuroactive substances on behavior and electrophysiological patterns may offer a model of how limbic seizures in humans increase the vulnerability of TLE patients to psychiatric symptoms.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Lifetime Prevalence, Age and Gender Distribution and Age-of-Onset of Psychiatric Disorders in the Sao Paulo Metropolitan Area, Brazil: Results from the Sao Paulo Megacity Mental Health Survey

Objectives: To estimate prevalence, age-of-onset, gender distribution and identify correlates of lifetime psychiatric disorders in the Sao Paulo Metropolitan Area (SPMA). Methods: The Sao Paulo Megacity Mental Health Survey assessed psychiatric disorders on a probabilistic sample of 5,037 adult residents in the SPMA, using the World Mental Health Survey Version of the Composite International Diagnostic Interview. Response rate was 81.3%. Results: Lifetime prevalence for any disorder was 44.8%; estimated risk at age 75 was 57.7%; comorbidity was frequent. Major depression, specific phobias and alcohol abuse were the most prevalent across disorders; anxiety disorders were the most frequent class. Early age-of-onset for phobic and impulse-control disorders and later age-of-onset for mood disorders were observed. Women were more likely to have anxiety and mood disorders, whereas men, substance use disorders. Apart from conduct disorders, more frequent in men, there were no gender differences in impulse-control disorders. There was a consistent trend of higher prevalence in the youngest cohorts. Low education level was associated to substance use disorders. Conclusions: Psychiatric disorders are highly prevalent among the general adult population in the SPMA, with frequent comorbidity, early age-of-onset for most disorders, and younger cohorts presenting higher rates of morbidity. Such scenario calls for vigorous public health action.