Fabíola Satler

Vitamin D deficiency in girls from South Brazil: a cross-sectional study on prevalence and association with vitamin D receptor gene variants

BackgroundVitamin D deficiency has been associated with a multitude of disorders including diabetes, defective insulin secretion as well as rickets and poor bone health. Vitamin D is also a concern during childhood and adolescence and has been reported in girls from South Brazil. We determined the prevalence of vitamin D deficiency in girls from South Brazil and investigated whether the genotypic distribution of the BsmI, ApaI and TaqI polymorphisms of the VDR gene and their haplotypes were associated with vitamin D levels.MethodsCross-sectional study including 234 apparently healthy girls aged 7 to 18 years. Height and weight were measured for calculation of body mass index (BMI) percentiles for age. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed. Participants were genotyped for ApaI (rs7975232), TaqI (rs731236), and BsmI (rs1544410) SNPs.ResultsThe median and interquartile range (25-75%) of BMI percentile was 62.0 (33.3 – 84.9). The frequency of overweight/obesity was 24.9%. Circulating levels of 25(OH)D (≥ 30 ng/mL) were adequate in 9.4%; insufficient in 54.3% (20–29 ng/mL); and deficient in 36.3% (< 20 ng/mL). Genotype frequencies were GG = 47.0%, GA = 41.5%, and AA = 11.5% for BsmI; GG = 16.7%, GT = 52.6%, and TT = 30.8% for ApaI; TT = 46.2%, TC = 44.9% and CC = 9.0% for TaqI. Genotypes with no gene variance (ancestral wild genotype) of BsmI (GG vs. GA + AA, two-tailed Student’s t-test p < 0.001), ApaI (GG vs. GT + TT, two-tailed Student’s t-test p = 0.031) and TaqI (TT vs. TC + CC, two-tailed Student’s t-test p = 0.005) SNPs and the GGT haplotype (two-tailed Student’s t-test p = 0.036) were significantly associated with lower 25(OH)D levels.Conclusions25-hydroxyvitamin D deficiency and insufficiency were highly prevalent in this sample. The BsmI, ApaI and TaqI wild variants of the VDR gene, as well as the GGT haplotype, were associated with lower vitamin D levels, suggesting that VDR gene polymorphisms could be linked to higher susceptibility to vitamin D deficiency in a sub-population of children and adolescents.

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

Associação entre trauma por perda na infância e depressão na vida adulta

Observacoes clinicas efetuadas por psicanalistas sugerem que psicopatologias da idade adulta podem ter sido originadas na infância. Estudos publicados na ultima decada identificaram associacao entre trauma na infância e depressao na vida adulta. Vivencias traumaticas na infância, como a perda de vinculos afetivos devido a morte de pais ou de irmaos ou, ainda, a privacao de um ou de ambos os pais por separacao ou abandono constituem importantes fatores associados a depressao na vida adulta. O objetivo do presente artigo e revisar a literatura dos ultimos dez anos, considerando os fatores associados a depressao, particularmente aqueles relacionados aos estressores presentes na infância. A metodologia utilizada foi de busca on-line nas bases de dados Medline, PsycINFO, Cochrane e Lilacs, referentes ao periodo de maio de 1991 a maio de 2001. A maioria dos estudos incluidos nesta revisao encontrou uma associacao significativa entre trauma por perdas na infância e depressao na vida adulta, com variacao na intensidade das associacoes observadas.

Alternative parameters for echocardiographic assessment of fetal diastolic function

Alternative methods to assess ventricular diastolic function in the fetus are proposed. Fetal myocardial hypertrophy in maternal diabetes was used as a model of decreased left ventricular compliance (LVC), and fetal respiratory movements as a model of increased LVC. Comparison of three groups of fetuses showed that, in 10 fetuses of diabetic mothers (FDM) with septal hypertrophy (SH), the mean excursion index of the septum primum (EISP) (ratio between the linear excursion of the flap valve and the left atrial diameter) was 0.36 +/- 0.09, in 8 FDM without SH it was 0.51 +/- 0.09 (P=0.001), and in the 8 normal control fetuses (NCF) it was 0.49 +/- 0.12 (P=0.003). In another study, 28 fetuses in apnea had a mean EISP of 0.39 +/- 0.05 which increased to 0.57 +/- 0.07 during respiration (P<0.001). These two studies showed that the mobility of the septum primum was reduced when LVC was decreased and was increased when LVC was enhanced. Mean pulmonary vein pulsatility was higher in 14 FDM (1.83 +/- 1.21) than in 26 NCF (1.02 +/- 0.31; P=0.02). In the same fetuses, mean left atrial shortening was decreased (0.40 +/- 0.11) in relation to NCF (0.51 +/- 0.09; P=0.011). These results suggest that FDM may have a higher preload than normal controls, probably as a result of increased myocardial mass and LV hypertrophy. Prenatal assessment of LV diastolic function by fetal echocardiography should include analysis of septum primum mobility, pulmonary vein pulsatility, and left atrial shortening.

Estudo do encurtamento global do átrio esquerdo em fetos de mães diabéticas

OBJECTIVE: To test the hypothesis that left atrial shortening fraction is lower in fetuses of diabetic mothers than in fetuses of mothers with no systemic disease. METHODS: Forty-two fetuses of mothers with previous diabetes or gestational diabetes and 39 healthy fetuses of mothers with no systemic disease (controls) underwent echocardiographic examination. Their gestational ages ranged from 25 weeks to term. The left atrial shortening fraction was obtained with the following formula: (left atrial maximum diameter - left atrial minimum diameter)/left atrial maximum diameter. Data were compared using the Student t test, with an alpha level of 0.05. RESULTS: Mean left atrial shortening fractions in fetuses of diabetic mothers and in those in the control group were 0.39±0.15 and 0.51±0.11, respectively. This difference was significant with P < 0.001. CONCLUSION: Left atrial dynamics, with a reduction in global left atrial shortening, is increased in fetuses of diabetic mothers. We speculate that this parameter may be useful in assessing fetal left ventricular diastolic function.

Pulsatilidade venosa pulmonar em fetos de mães diabéticas: estudo doppler-ecocardiográfico pré-natal

OBJECTIVE To verify the hypothesis that the pulmonary vein pulsatility index is higher in fetuses of diabetic mothers than it is in normal fetuses of nondiabetic mothers. METHODS Twenty-four fetuses of mothers with either gestational or previous diabetes (cases), and 25 normal fetuses of mothers without systemic disease (control) were examined. Fetuses were examined through prenatal Doppler and color flow mapping. The pulmonary vein pulsatility index was obtained by placing the pulsed Doppler sample volume over the right superior pulmonary vein and applying the formula (systolic velocity - presystolic velocity)/mean velocity. RESULTS The mean gestational age of the study fetuses was 30.3 2.7 weeks, and gestational age of the controls was 29 3.3 weeks, with no significant difference in gestational age between groups (p=0.14). Fetuses of diabetic mothers had a mean pulmonary vein pulsatility index of 1.6 1, and those of the control group had an index of 0.86 0.27. CONCLUSION Fetuses of diabetic mothers had pulmonary vein pulsatility indexes (parameter easily obtained through Doppler echocardiography that may be related to fetal diastolic function) higher than those in fetuses of mothers with normal glycemia.

Fluxo no ducto venoso e hipertrofia miocárdica em fetos de mães diabéticas

OBJECTIVE To test the hypothesis that the pulsatility index of ductus venosus (PIDV) is greater in the fetuses of diabetic mothers (FDM) with myocardial hypertrophy (MH) than in the FDM with no MH and in the control fetuses of nondiabetic mothers (FNDM). Comparing the results with mitral and tricuspid diastolic peak flows. METHODS The cross-sectional study included fetuses with gestational ages ranging from 20 weeks to term, divided into the following 3 groups: 56 FDM with MH (group I), 36 FDM with no MH (group II), and 53 FNDM (group III, control). The Doppler echocardiogram assessed the PIDV through the ratio (systolic velocity - presystolic velocity)/mean velocity. The mitral and tricuspid E and A waves were also assessed. RESULTS The mean PIDV in groups I, II, and III were 1.13 +/- 0.64, 0.84 +/- 0.38, and 0.61 +/- 0.17, respectively. Using ANOVA and the Tukey test, a statistically significant difference was found in the 3 groups (P = 0.015 between groups I and II; P < 0.001 between groups I and III; and P = 0.017 between groups II and III). The mean mitral E wave was significantly greater in group I (0.39 +/- 0.12 m/s) than in groups II (0.32 +/- 0.08 m/s) (P = 0.024) and III (0.32 +/- 0.08 m/s) (P = 0.023). The mean tricuspid E wave was also greater in group I (0.43 +/- 0.1 m/s) than in group III (0.35 +/- 0.10 m/s) (P = 0.031). CONCLUSION The PIDV is significantly greater in FDM with MH than in FDM with no MH and in FNDM. Because the PIDV may represent modifications in ventricular compliance, this index may be a more sensitive parameter for assessing fetal diastolic function.

Dynamics of the Pulmonary Venous Flow in the Fetus and Its Association With Vascular Diameter

Background—The usual positioning of the Doppler sample volume to assess fetal pulmonary vein flow is in the distal portion of the vein, where the vessel diameter is maximal. This study was performed to test the association of the pulmonary vein pulsatility index (PVPI) with the vessel diameter. Methods and Results—Twenty-three normal fetuses (mean gestational age, 28.6±5.3 weeks) were studied by Doppler echocardiography. Pulmonary right upper vein flow was assessed adjacent to the venoatrial junction (“distal” position) and in the middle of the vein (“proximal” position). The vessel diameter was measured by 2D echocardiography with power Doppler, and the PVPI was obtained by the ratio (maximal velocity [systolic or diastolic peak]−minimal velocity [presystolic peak])/mean velocity. The statistical analysis used t test and exponential correlation studies. Mean distal diameter was 0.33±0.10 cm (0.11 to 0.57 cm), and mean proximal diameter was 0.16±0.08 cm (0.11 to 0.25 cm) (P <0.0001). Mean distal PVPI was 0.84±0.21 (0.59 to 1.38), and mean proximal PVPI was 2.09±0.59 (1.23 to 3.11) (P <0.0001). Exponential inverse correlation between pulmonary vein diameter and pulsatility index was highly significant (P <0.0001), with a determination coefficient of 0.439. Conclusions—In the normal fetus, the pulmonary venous flow pulsatility decreases from the lung to the heart, and this parameter is inversely correlated to the diameter of the pulmonary vein, which increases from its proximal to its distal portion. This study emphasizes the importance of the correct positioning of the Doppler sample volume, adjacent to the venoatrial junction, to assess pulmonary venous flow dynamics.

Vitamin D receptor gene polymorphisms and sex steroid secretion in girls with precocious pubarche in Southern Brazil: a pilot study.

BackgroundEvidence suggests that precocious pubarche (PP) girls may have higher risk of developing polycystic ovary syndrome (PCOS) at later ages. Vitamin D receptor (VDR) gene polymorphisms have been implicated in the risk of diabetes and PCOS, but little is known about the role of VDR in PP.AimTo assess the frequencies of VDR gene ApaI, TaqI, BsmI, and FokI polymorphisms and to determine whether these variants are associated with sex hormone concentrations in patients with PP and controls from southern Brazil.Subjects and methodsBlood was collected from 36 girls with PP and 197 controls for genotyping of BsmI and FokI polymorphisms using real-time PCR and of ApaI e TaqI polymorphisms using restriction fragment length polymorphism. Hormone levels were also determined.ResultsGenotype GG of the ApaI single nucleotide polymorphism (SNP) was more frequent in PP (30.6%) than in controls (16.2%) [odds ratio (OR): 2.269; confidence interval 95% (95%CI): 1.015-5.076; p=0.042]. This genotype was also associated with lower estradiol [35.30 (14.80–50.48) pg/ml vs 12.22 (6.49–23.69) pg/ml; p=0.025] and total testosterone levels (0.52 (0.39–0.84) ng/ml vs 0.20 (0.11–0.47) ng/ml; p=0.005) as compared with the TT + TG genotypes in girls with PP. The distribution of TaqI, BsmI, and Fokl SNP was similar in PP and controls, and no association was found between these polymorphisms and sex steroid levels.ConclusionsThe ApaI SNP of the VDR gene was associated with PP in the studied population and may modulate ovarian steroid secretion in these girls.

Association between left ventricular mass, androgens, adiposity and insulin resistance in girls with precocious pubarche: a case-control study.

Precocious pubarche (PP) has been linked to higher prevalence of metabolic disturbances and polycystic ovary syndrome (PCOS). The aim of the study was to assess echocardiographic parameters in PP girls and to analyse their relationship with androgens and insulin resistance (IR).