Adenovirus-36 infection and obesity related hormones in children

Obesity has a complex, multi-factorial etiology. Infectious agents have recently emerged as a possible contributor to the current obesity epidemic. Seven viruses have demonstrated an association with obesity in animals; however, Adenovirus-36 (Ad-36) is the only known virus associated with obesity in humans. The primary aim of this research was to determine the association between Ad-36 infection and the expression of obesity related hormones in children. Additionally, this study proposed to compare the mean three year change in the level of obesity related hormones between Ad-36 positive and negative children. This study utilized pilot data collected from 98 children at baseline and year three of the Project Heartbeat! cohort. Fasting serum samples were analyzed for the concentration of adiponectin, insulin and leptin. The crude analysis uncovered Ad-36 positive children had significantly lower mean concentrations of insulin (p=0.039) and leptin (p=0.038) at baseline compared to Ad-36 negative children. The results of the adjusted analysis indicated the leptin association with Ad-36 infection at baseline was statistically significant even after controlling for age, sex, ethnicity, and BMI percentile. The longitudinal evaluation revealed individuals with a history of Ad-36 infection experienced a larger mean decrease in adiponectin, a larger mean increase in leptin, and a smaller mean increase in insulin levels over a three year period compared to individuals without a history of infection. These results suggest Ad-36 infection may produce changes in hormone expression. The only statistically significant findings in the crude and adjusted longitudinal analysis occurred at baseline when the children were younger, suggesting physical changes that occur during sexual maturation may mask or enhance Ad-36 induced changes in hormone expression. Furthermore, the longitudinal analysis revealed the duration and course of Ad-36 infection may influence changes in the expression of obesity-related hormones. Taken together, the results of this pilot study are suggestive of an association between Ad-36 infection and the expression of obesity-related hormones.^

Hormones, genes, and behavior

With assays of hormone-sensitive behaviors, it is possible to demonstrate both direct and indirect actions of genes on mammalian social behaviors. Direct effects of estrogen receptor gene expression and progesterone receptor gene expression figure prominently in well analyzed neuroendocrine mechanisms for sex behavior, operating through a neural circuit that has been delineated. Indirect effects, notably the consequences of sexual differentiation, display complex dependencies. In a human condition, Kallmann syndrome, the data show a clear, indirect genetic influence on an important human social behavior, in which damage at chromosome Xp-22.3 works through at least six discrete steps to affect libido. Altogether, simplistic extrapolations from lower animals, especially during brief summaries for nonscientists, do not appear justified as we discover and conceptualize genetic influences on mammalian brain and behavior.

[the Use Of Fish On Buccal Smear To Investigate Mosaicism With A 45,x Cell Line: Study On Healthy Men And Patients With Disorders Of Sex Development].

To verify whether fluorescence in situ hybridization (FISH) of cells from the buccal epithelium could be employed to detect cryptomosaicism with a 45,X lineage in 46,XY patients. Samples of nineteen 46,XY healthy young men and five patients with disorders of sex development (DSD), four 45,X/46,XY and one 46,XY were used. FISH analysis with X and Y specific probes on interphase nuclei from blood lymphocytes and buccal epithelium were analyzed to investigate the proportion of nuclei containing only the signal of the X chromosome. The frequency of nuclei containing only the X signal in the two tissues of healthy men did not differ (p = 0.69). In all patients with DSD this frequency was significantly higher, and there was no difference between the two tissues (p = 0.38), either. Investigation of mosaicism with a 45,X cell line in patients with 46,XY DSD or sterility can be done by FISH directly using cells from the buccal epithelium.

Gonadal Hormones Modulate The Responsiveness To Local β-blocker-induced Antinociception In The Temporomandibular Joint Of Male And Female Rats.

We have previously demonstrated that blockade of β-adrenoreceptors (β-AR) located in the temporomandibular joint (TMJ) of rats suppresses formalin-induced TMJ nociceptive behaviour in both male and female rats, but female rats are more responsive. In this study, we investigated whether gonadal hormones modulate the responsiveness to local β-blocker-induced antinociception in the TMJ of rats. Co-administration of each of the selective β1 (atenolol), β2 (ICI 118.551) and β3 (SR59230A)-AR antagonists with equi-nociceptive concentrations of formalin in the TMJ of intact, gonadectomized and hormone-treated gonadectomized male and female rats. Atenolol, ICI 118.551 and SR59230A significantly reduced formalin-induced TMJ nociception in a dose response fashion in all groups tested. However, a lower dose of each β-AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and testosterone-treated gonadectomized male rats. In the female groups, a lower dose of β1 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact or gonadectomized rats treated with progesterone or a high dose of oestradiol; a lower dose of β2 -AR antagonist was sufficient to significantly reduce nociceptive responses in gonadectomized but not in intact and gonadectomized rats treated with low or high dose of oestradiol. Gonadal hormones may reduce the responsiveness to local β-blocker-induced antinociception in the TMJ of male and female rats. However, their effect depends upon their plasma level, the subtype of β-AR and the dose of β-blockers used.

Florivory and sex ratio in Annona dioica St. Hil. (Annonaceae) in the Pantanal at Nhecolândia, southwestern Brazil

Annona dioica St. Hil. is a species that grows to approximately 2 m tall and is very widespread in the cerrados. Individual plants of this androdioecious species produce numerous hermaphroditic or male flowers, but few fruits. The aim of this study was to determine the sex ratio among the plants and to compare the frequency of herbivory between male and hermaphroditic flowers. The fieldwork was done by studying flowering plants in grasslands used as pasture for cattle at Fazenda Nhumirim. One hundred and forty-seven male plants and 71 hermaphroditic plants were examined and produced a total of 194 and 94 flowers, respectively, during the study period. The male:hermaphrodite sex ratio was 2.07:1, and was similar to the male:hermaphrodite flower ratio of 2.06:1. The frequency of florivory rate in hermaphrodites was significantly higher than in male flowers (33.0%, n = 31, and 25.7%, n = 50, respectively; G = 14.83; d.f. = 1; p < 0.001). The mean fresh weights of male and hermaphroditic flowers were significantly different (8.38 ± 2.40 g vs. 6.93 ± 2.68 g, respectively; 0 ± SEM; n = 50 each; t = 2.479; d.f. = 49; p = 0.017). These results indicate that the low fruit set in this species can be explained by the sex ratio, the greater herbivory of hermaphroditic flowers and the probable absence of pollinators.

Multifunctional role of steroidogenic factor 1 and disorders of sex development

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.

The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies

FISH has been used as a complement to classical cytogenetics in the detection of mosaicism in sex chromosome anomalies. The aim of this study is to describe three cases in which the final diagnosis could only be achieved by FISH. Case 1 was an 8-year-old 46,XY girl with normal female genitalia referred to our service because of short stature. FISH analysis of lymphocytes with probes for the X and Y centromeres identified a 45,X/46,X,idic(Y) constitution, and established the diagnosis of Turner syndrome. Case 2 was a 21-month-old 46,XY boy with genital ambiguity (penile hypospadias, right testis, and left streak gonad). FISH analysis of lymphocytes and buccal smear identified a 45,X/46,XY karyotype, leading to diagnosis of mixed gonadal dysgenesis. Case 3 was a 47,XYY 19-year-old boy with delayed neuromotor development, learning disabilities, psychological problems, tall stature, small testes, elevated gonadotropins, and azoospermia. FISH analysis of lymphocytes and buccal smear identified a 47,XYY/48,XXYY constitution. Cases 1 and 2 illustrate the phenotypic variability of the 45,X/46,XY mosaicism, and the importance of detection of the 45,X cell line for proper management and follow-up. In case 3, abnormal gonadal function could be explained by the 48,XXYY cell line. The use of FISH in clinical practice is particularly relevant when classical cytogenetic analysis yields normal or uncertain results in patients with features of sex chromosome aneuploidy. Arq Bras Endocrinol Metab. 2012;56(8):545-51

Sex ratio and morphological characteristics of rufous gnateaters, Conopophaga lineata (Aves, Passeriformes) in Atlantic forest fragments

Unequal sex ratios lead to the loss of genetic variability, decreasing the viability of populations in the long term. Anthropogenic activities often disturb the natural habitats and can cause alterations in sex ratio and morphological characteristics of several species. Forest fragmentation is a major conservation concern, so that understanding its effects in natural populations is essential. In this study, we evaluated the sex ratio and the morphological characteristics of Rufous Gnateaters (Conopophaga lineata (Wied, 1831)) in small and large forest fragments in Minas Gerais, Brazil. Birds (n = 89) were sexed by plumage characteristics and molecular markers. The molecular analysis showed that plumage is not a totally reliable method for sexing Rufous Gnateaters. We observed that sex ratio did not differ between large and small forest fragments, but birds in small fragments had larger wings and tarsus. Wing and tarsus changes may affect the movement ability of individuals within and among forest fragments. In conclusion, Rufous Gnateaters have been able to survive in both small and large Atlantic rain forest fragments without altering their sex ratio, but morphological changes can be prejudicial to their long term survival.

Evaluating gene by sex and age interactions on cardiovascular risk factors in Brazilian families

Background: In family studies, it is important to evaluate the impact of genes and environmental factors on traits of interest. In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females. Methods: In this paper, extensions of the variance components model are used to evaluate heterogeneity in the genetic and environmental variance components due to the effects of sex and age (the cutoff between young and old was 43 yrs). The data analyzed were from 81 Brazilian families (1,675 individuals) of the Baependi Family Heart Study. Results: The models allowing for heterogeneity of variance components by sex suggest that genetic and environmental variances are not different in males and females for diastolic blood pressure, LDL-cholesterol, and HDL-cholesterol, independent of the covariates included in the models. However, for systolic blood pressure, fasting glucose and triglycerides, the evidence for heterogeneity was dependent on the covariates in the model. For instance, in the presence of sex and age covariates, heterogeneity in the genetic variance component was suggested for fasting glucose. But, for systolic blood pressure, there was no evidence of heterogeneity in any of the two variance components. Except for the LDL-cholesterol, models allowing for heterogeneity by age provide evidence of heterogeneity in genetic variance for triglycerides and systolic and diastolic blood pressure. There was evidence of heterogeneity in environmental variance in fasting glucose and HDL-cholesterol. Conclusions: Our results suggest that heterogeneity in trait variances should not be ignored in the design and analyses of gene-finding studies involving these traits, as it may generate additional information about gene effects, and allow the investigation of more sophisticated models such as the model including sex-specific oligogenic variance components.

Consequences for the Bovine Embryo of Being Derived from a Spermatozoon Subjected to Post-Ejaculatory Aging and Heat Shock: Development to the Blastocyst Stage and Sex Ratio

The objective was to determine whether aging of sperm caused by incubation at normothermic (38.5 C) or heat shock (40 C) temperatures for 4 h prior to oocyte insemination affects sperm motility, fertilizing ability, competence of the resultant embryo to develop to the blastocyst stage and blastocyst sex ratio. In the first experiment, the percent of sperm that were motile was reduced by aging (P<0.001) and the reduction in motility was greater for sperm at 40 C compared to sperm at 38.5 C (P<0.01). In the second experiment, oocytes were inseminated with aged sperm. A smaller percent of oocytes fertilized with sperm aged at either temperature cleaved by Day 3 after insemination than oocytes fertilized with fresh sperm (P<0.05). There was no effect of sperm aging on the percent of oocytes or cleaved embryos that developed to the blastocyst stage. Aging of sperm before fertilization at 38.5 C reduced the percent of blastocysts that were male (P=0.08). In the third experiment, incubation of sperm at 38.5 C or 40 C for 4 h did not reduce fertilizing ability of sperm as determined by pronuclear formation at 18 h post insemination. In conclusion, aging of sperm reduced cleavage rate and the percent of blastocysts that were males but had no effect on the developmental capacity of the. embryo. The effect of aging on cleavage rate may represent reduced motility and errors occurring after fertilization and pronuclear formation. Aging at a temperature characteristic of maternal hyperthermia had little additional effect except that polyspermy was reduced. Results indicate that embryo competence for development to the blastocyst stage is independent of sperm damage as a result of aging for 4 h at normothermic or hyperthermic temperatures.

PSA and androgen-related gene (AR, CYP17, and CYP19) polymorphisms and the risk of adenocarcinoma at prostate biopsy

The aim of the present study was to examine the impact of polymorphisms in prostate-specific antigen (PSA) and androgen-related genes (AR, CYP17, and CYP19) on prostate cancer (PCa) risk in selected high-risk patients who underwent prostate biopsy. Blood samples and prostate tissues were obtained for DNA analysis. Single-nucleotide polymorphisms in the 50-untranslated regions (UTRs) of the PSA (substitution A > G at position -158) and CYP17 (substitution T > C at 50-UTR) genes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism assays. The CAG and TTTA repeats in the AR and CYP19 genes, respectively, were genotyped by PCR-based GeneScan analysis. Patients with the GG genotype of the PSA gene had a higher risk of PCa than those with the AG or AA genotype (OR = 3.79, p = 0.00138). The AA genotype was associated with lower PSA levels (6.44 +/- 1.64 ng/mL) compared with genotypes having at least one G allele (10.44 +/- 10.06 ng/mL) (p = 0.0687, 95% CI - 0.3146 to 8.315, unpaired t-test). The multivariate analysis confirmed the association between PSA levels and PSA genotypes (AA vs. AG+GG; chi(2) = 0.0482) and CYP19 (short alleles homozygous vs. at least one long allele; chi(2) = 0.0110) genotypes. Genetic instability at the AR locus leading to somatic mosaicism was detected in one PCa patient by comparing the length of AR CAG repeats in matched peripheral blood and prostate biopsy cores. Taken together, these findings suggest that the PSA genotype should be a clinically relevant biomarker to predict the PCa risk.

The case of thyroid hormones: how to learn physiology by solving a detective case

Lellis-Santos C, Giannocco G, Nunes MT. The case of thyroid hormones: how to learn physiology by solving a detective case. Adv Physiol Educ 35: 219-226, 2011; doi:10.1152/advan.00135.2010.Thyroid diseases are prevalent among endocrine disorders, and careful evaluation of patients' symptoms is a very important part in their diagnosis. Developing new pedagogical strategies, such as problem-based learning (PBL), is extremely important to stimulate and encourage medical and biomedical students to learn thyroid physiology and identify the signs and symptoms of thyroid dysfunction. The present study aimed to create a new pedagogical approach to build deep knowledge about hypo-/hyperthyroidism by proposing a hands-on activity based on a detective case, using alternative materials in place of laboratory animals. After receiving a description of a criminal story involving changes in thyroid hormone economy, students collected data from clues, such as body weight, mesenteric vascularization, visceral fat, heart and thyroid size, heart rate, and thyroid-stimulating hormone serum concentration to solve the case. Nevertheless, there was one missing clue for each panel of data. Four different materials were proposed to perform the same practical lesson. Animals, pictures, small stuffed toy rats, and illustrations were all effective to promote learning, and the detective case context was considered by students as inviting and stimulating. The activity can be easily performed independently of the institution's purchasing power. The practical lesson stimulated the scientific method of data collection and organization, discussion, and review of thyroid hormone actions to solve the case. Hence, this activity provides a new strategy and alternative materials to teach without animal euthanization.

Exploiting pi-acceptors for the determination of thyroid hormones (T3 and T4) using a single interface flow system

A fully automated methodology was developed for the determination of the thyroid hormones levothyroxine (T4) and liothyronine (T3). The proposed method exploits the formation of highly coloured charge-transfer (CT) complexes between these compounds, acting as electron donors, and pi-acceptors such as chloranilic acid (CIA) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). For automation of the analytical procedure a simple, fast and versatile single interface flow system (SIFA)was implemented guaranteeing a simplified performance optimisation, low maintenance and a cost-effective operation. Moreover, the single reaction interface assured a convenient and straightforward approach for implementing job`s method of continuous variations used to establish the stoichiometry of the formed CT complexes. Linear calibration plots for levothyroxine and liothyronine concentrations ranging from 5.0 x 10(-5) to 2.5 x 10(-4) mol L(-1) and 1.0 x 10(-5) to 1.0 x 10(-4) mol L(-1), respectively, were obtained, with good precision (R.S.D. <4.6% and <3.9%) and with a determination frequency of 26 h(-1) for both drugs. The results obtained for pharmaceutical formulations were statistically comparable to the declared hormone amount with relative deviations lower than 2.1%. The accuracy was confirmed by carrying out recovery studies, which furnished recovery values ranging from 96.3% to 103.7% for levothyroxine and 100.1% for liothyronine. (C) 2009 Elsevier B.V. All rights reserved.

Occurrence of Sexual Hormones in Sediments of Mangrove in Brazil

The presence of sexual hormones (female estrogens) was assessed in sediments of a mangrove located in the urban region of southern Brazil. The estrogens are involved in human sexual reproduction. They act as the chemical messengers, and they are classified as natural and synthetic. The estrogens inputs in the environment are from treated and untreated sewage. The presence of estrogens in sewage is excretion from the female due to natural production and use of contraceptives (synthetic estrogens). With the indiscriminate release of sewage into the environment, estrogens can be found in rivers, lakes, and even in oceans. In this work, the presence of estrone (E1), 17-beta-estradiol (E2), and 17-alpha-ethynilestradiol (EE2) in eight sedimentary stations in Itacorubi mangrove located on Santa Catarina Island, south Brazil, was investigated. Historically, the Itacorubi mangrove has been impacted by anthropogenic activities because the mangrove is inserted in the urban area of the Florianopolis. The estrogen EE2, used as contraceptive, had the highest concentration in mangrove sediment, 129.75 +/- 3.89 ng/g. E2 was also found, with its concentration ranging from 0.90 +/- 0.03 to 39.77 +/- 1.19 ng/g. Following the mechanism, under aerobic or anaerobic conditions, E2 will first be oxidized to E1, which is further oxidized to unknown metabolites and finally to CO(2) and water (mineralized). EE2 is oxidized to unknown metabolites and also finally mineralized. Theoretically, under anaerobic conditions, EE2 can be reduced to E1 even in environments such as mangrove which is essentially anaerobic.

Influences of sex and age on biological rhythms of serum lipids and lipoproteins

Background: Few studies have evaluated seasonal variations of biochemical parameters routinely analyzed in clinical laboratories. Rhythmic patterns for lipids and lipoproteins have been demonstrated and have been the object of research, mainly because of their demonstrated association with coronary artery disease. This study evaluated the occurrence of biological rhythms on serum lipids and lipoproteins and the effects of sex and age on the rhythms in a Brazilian hospital outpatient population. Methods: Retrospective laboratory study was carried out to evaluate the results of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG), from individuals registered at a university referral hospital over 8years. The studied population was composed of individuals of both sexes and all ages totaling 38,579 participants and 301,934 measurements. Statistical analyses were carried out using the SAS program and the temporal analysis used the Cosinor method. Results: TG rhythm was present only in females. All other parameters were equally rhythmic in both sexes. Regarding age, HDL-C presented rhythms in all age groups, but TC and LDL-C showed seasonality only for those > 13years, TG did not present rhythms in all age groups. Conclusion: Effects of sex and age on biological rhythms detected in TC, LDL-C and HDL-C should be considered a significant cause of pre-analytical variation in these laboratory tests. (C) 2009 Elsevier B.V. All rights reserved.