The steroid metabolome in lamotrigine-treated women with epilepsy

Background

Epilepsy in women may be associated with reproductive disorders and alterations in serum steroid levels. Some steroids can be induced by epilepsy and/or treatment with antiepileptic drugs; however, there are still limited data available concerning this effect on the levels of other neuroactive steroid metabolites such as 3a-hydroxy-5a/b-reduced androstanes.

Aim

To evaluate steroid alterations in women with epilepsy (WWE) on lamotrigine monotherapy.

Subjects and methods

Eleven WWE and 11 age-matched healthy women underwent blood sampling in both phases of their menstrual cycles (MCs). The steroid metabolome, which included 30 unconjugated steroids, 17 steroid polar conjugates, gonadotropins, and sex hormone-binding globulin (SHBG), was measured using gas chromatography–mass spectrometry (GC–MS) and radioimmunoassay (RIA).

Results

WWE had lower cortisol levels (status p < 0.001), but elevated levels of unconjugated 17-hydroxypregnenolone (status p < 0.001). Progesterone was higher in the follicular menstrual phase (FP) in WWE than in the controls (status × menstrual phase p < 0.05, Bonferroni multiple comparisons p < 0.05), whereas 17-hydroxyprogesterone was higher in WWE in both menstrual phases (status p < 0.001). The steroid conjugates were mostly elevated in WWE. The levels of 5α/β-reduced androstanes in WWE that were significantly higher than the controls were etiocholanolone (status p < 0.001), 5α-androstane-3α,17β-diol (status p < 0.001), and the 5α/β-reduced androstane polar conjugates (status p < 0.001).

Conclusions

WWE showed a trend toward higher circulating 3α-hydroxy-5α/β-reduced androstanes, increased activity of 17α-hydroxylase/17,20 lyase in the Δ⁵-steroid metabolic pathway, and increased levels of the steroid polar conjugates.     

Skeletal development of non-institutionalized children with low Intelligence Quotients

Children of both sexes with mild mental retardation show delays in skeletal maturation and cortical bone growth, but boys in general are more affected than girls. Skeletal age for both sexes is below normal in the younger age groups, but approaches normality at adolescence. None of the measures of IQ is significantly correlated with any of the regional measures of skeletal age in the hand-wrist. The approach toward normality of skeletal development in this population at adolescence is reflected in their normal time of first appearance of the adductor sesamoid. Anomalies of the hand-wrist reflect irregularities in comparing normal and low-IQ children. Only brachymesophalangy V displays significantly higher frequencies in the low-IQ groups. Due to the cross-sectional nature of the study and the different methods of classifying anomalies, little can be said about the other comparisons. Growth in cortical bone reflects a consistent trend for both the humerus and second metacarpal. While measures of total diameter and total cross-sectional area do appear to be below normal standards, the measures of the marrow do not. This finding accounts for a decreased cortical bone thickness and cross-sectional area in the low-IQ sample. All measures of the humerus correlate significantly with two IQ scores in the boys and all three scores in the girls. Measures of the total metacarpal and marrow area show significant correlations with the three IQ scores among low-IQ boys, while only measures of total metacarpal area show significant correlations with verbal IQ in low-IQ girls. The degree of mental deficiency, then, is only irregularly associated with deficits of bone size for age.     

Assessment of the physical development and physical fitness of children and youths with simple body height deficiency

The aim of this work is an analysis of the process of growth and an assessment of the physical fitness of children and youths with short stature. The material contains results of a long-term investigation of the growth of boys and girls with the diagnosis: simple body height deficiency (hypostatura simplex). The investigation was carried out in Swietokrzyskie Province, Poland, in the years 1980-1997. It comprised 471 individuals: 143 girls aged 5-18 years and 328 boys aged 5-19 years. A different degree of the skeleton age is connected with a different dynamic of growth of short-stature girls and boys. Pubescent increase in the rate of growth occurs in individuals with a considerable retardation of the bone age later, particularly among boys. The growth process lasts longer in them, therefore, the final body height is achieved later and it is greater in individuals whose bone age is concordant with the calendar age. The level of physical working capacity of short-stature children does not show any significant difference in comparison with that in individuals with correct body height, and relative values of the indicators of physical fitness, related to body mass, are even higher in short-stature children. Individuals with a greater body height deficiency are characterised by a lower level of physical fitness.     

Intelligence and genetic markers in Chilean children.

Genetic markers and total intelligence quotient (IQ) assessed by WISC (Wechsler Intelligence Scale for Children) were studied in children of both sexes from Santiago, Chile. Heterozygous boys for phosphoglucomutase 1 (PGM) and heterozygous girls for haptoglobin (Hp) had lower IQ than homozygotes. For ABO system, B girls had lower and B boys had higher IQ than children with other ABO phenotypes. These differences were highly significant with the two tailed t'-test (Student's t-test with the Welch-Satterthwaite correction for degrees of freedom), and most of them remained significant after the correction for multiple comparisons. Girls had greater variance of IQ than boys. Relationships between homozygotes and heterozygotes were found in two independent studies. Thus, the genetic relationship found here seems likely to be a true biotic effect.     

Associations of physical activity and inactivity with body tissue composition among healthy Polish women and women after mastectomy

The aim of the study is to determine the relationship between physical activity and body composition among healthy women and women who have had mastectomy. This is in order to establish whether physical activity of women after breast cancer treatment improves composition and distribution of body mass components to a degree which will allow to achieve the body composition of healthy women.     

The physical phenotype of girls and women with Turner syndrome is not X-imprinted

Certain behavioral and metabolic aspects of Turner syndrome (TS) are attributed to X-chromosome genomic imprinting. To investigate the possible contribution of imprinting to the physical features of the TS phenotype in live-born individuals, we genotyped the single normal X-chromosome in subjects with TS who all underwent a comprehensive evaluation as part of the NIH genotype–phenotype protocol. All had physical examinations, auxological measurements and imaging of the renal and cardiovascular systems. Absolute height and height as a percent of predicted height was the same in X^M (n = 56) and X^P (n = 23) subjects that had reached final height and were not growth hormone treated. Interestingly, adult height was significantly correlated with maternal but not paternal heights in both X^M and X^P groups. Neck webbing was found in 35% of the X^M (n = 133) and 22% of the X^P (n = 50) groups (P = 0.11). Renal anomalies were present in 24% of X^M and 25% of X^P groups (P = 0.9). Bicuspid aortic valve was found in 26% of X^M and 24% of X^P groups (P = 0.83), and any cardiovascular anomaly (abnormal aortic valve, aortic coarctation, elongated transverse aortic arch, anomalous pulmonary venous connection, left superior vena cava) affected 55% of X^M and 52% of X^P groups. Thus, we found no evidence for X-linked genomic imprinting effects on stature or lymphatic, renal or cardiovascular development in TS. Our sample size was sufficient to exclude such effects within 95% confidence limits. We did demonstrate a selective maternal effect on final stature that was independent of X-chromosome origin, suggesting potential autosomal imprinting effects on growth revealed by X monosomy.     

Bone mineralization and physical development of children

A cross-sectional study of BMD and physical development values in children of various age-specific groups was carried out. In all, the study included 357 children (194 boys and 163 girls) aged from 5 to 16 years. The study did not include children with inherited or acquired diseases of the musculoskeletal system, chronic diseases of the liver or kidneys, diabetes, thyrotoxicosis or malabsorption syndrome or professional athletes. BMD values were estimated by dual X-ray absorbtiometry (DXA) of the lumbar part of the spine (L2-L4) using a "DPX-MD+" device equipped with a "child" software program. Out of all the examined children, 58.9% had harmonic physical development, and 13.1% had a decreased body height and body mass. It was revealed that BMC and BMD values in the lumbar part of the spine intensively increased with age. BMC closely correlates with body height (r = 0.8; p < 0.000) and body mass (r = 0.7; p < 0.000). BMD also correlates with anthropometric parameters. The lowest BMC and BMD values and Z-score as well can be found in children with a low body height and body mass (<10th percentile).     

Characteristic features of EchoCG parameters in men and women with different geometric configurations

An echocardiographic study of 190 subjects in the second period of adult age (108 women and 82 men) has been conducted. The absolute and relative sizes of the left ventricle (LV), left atrium (LA), right ventricle (RV), myocardium mass, and LV mass index were determined. Morphological changes in the heart detected by echocardiography (EchoCG) depended on the geometric configuration of the LV. The size of the RV was significantly increased in women with hypertrophy of the myocardium of the LV. All the EchoCG parameters with the exception of relative wall thickness (RWT) were gender-dependent. The gender-dependent differences in LV remodeling included higher values of LV mass index in men, different dynamics of the LV mass index (LVMI) in subjects with different geometric configurations of the LV, and more pronounced elevation of the index in women with eccentric hypertrophy of the LV (LV EG), in particular. The functional capacity of the heart was lower in men than in women.     

Associations of physical activity with gut microbiota in pre-adolescent children

[Purpose] To determine whether physical activity (PA), primarily the recommended 60 minutes of moderate-to-vigorous PA, is associated with gut bacterial microbiota in 10-year-old children.[Methods] The Block Physical Activity Screener, which provides minutes/day PA variables, was used to determine whether the child met the PA recommendations. 16S rRNA sequencing was performed on stool samples from the children to profile the composition of their gut bacterial microbiota. Differences in alpha diversity metrics (richness, Pielou’s evenness, and Faith’s phylogenetic diversity) by PA were determined using linear regression, whereas beta diversity (unweighted and weighted UniFrac) relationships were assessed using PERMANOVA. Taxon relative abundance differentials were determined using DESeq2.[Results] The analytic sample included 321 children with both PA and 16S rRNA sequencing data (mean age [SD] =10.2 [0.8] years; 54.2% male; 62.9% African American), where 189 (58.9%) met the PA recommendations. After adjusting for covariates, meeting the PA recommendations as well as minutes/day PA variables were not significantly associated with gut richness, evenness, or diversity (p ≥ 0.19). However, meeting the PA recommendations (weighted UniFrac R² = 0.014, p = 0.001) was significantly associated with distinct gut bacterial composition. These compositional differences were partly characterized by increased abundance of Megamonas and Anaerovorax as well as specific Christensenellaceae_R-7_group taxa in children with higher PA.[Conclusion] Children who met the recommendations of PA had altered gut microbiota compositions. Whether this translates to a reduced risk of obesity or associated metabolic diseases is still unclear.     

Genetic risks for children of women with myotonic dystrophy

In genetic counseling, the recommended risk estimate that any heterozygous woman with myotonic dystrophy (DM) will have a congenitally affected child is 3%-9%. However, after already having had such an offspring, a DM mother's risk increases to 20%-37%. The risks of 10% and 41%, respectively, calculated in this study are similar to the estimates in the literature. However, our data on clinical status of the mothers demonstrate that only women with multisystem effects of the disorder at the time of pregnancy and delivery are likely to have congenitally affected offspring. No heterozygous woman with polychromatic lens changes but no other clinically detectable multisystem involvement had a congenitally affected child. In addition, our data suggest that the chance of having a more severely affected child increases with greater severity of maternal disease. The findings of this study are relevant for genetic counseling, as the risk of having a congenitally affected child for women with classical manifestations of the disease is shown to be higher than predicted by the overall risk estimate for any heterozygous woman. We consider it appropriate to give these classically affected women risk figures which approach the recurrence risk given to mothers with congenitally affected children. However, the risk of having a congenitally affected child for heterozygous women with no multisystem involvement appears to be minimal. Our findings support the earlier proposed hypothesis of maternal metabolites acting on a heterozygous offspring. Neither genomic imprinting nor mitochondrial inheritance is able to explain the correlation between the clinical status of heterozygous mothers and that of their children.     

Design and physical features of inductive coaxial copper vapor lasers

A physical model of a copper vapor laser pumped by a pulse-periodic inductive (electrodeless) discharge is considered. The feasibility of efficient laser pumping by an inductive discharge and reaching high output parameters comparable to those of conventional copper vapor lasers pumped by a longitudinal electrode discharge is demonstrated. The design and physical features of an inductive copper vapor laser with an annular working volume are discussed.     

Meiotic transmission rates correlate with physical features of rearranged centromeres in maize.

The centromere of the maize B chromosome was used as a model to study the physical features of a functional centromere. Pulsed-field gel electrophoresis was previously used to determine the organization of a repetitive sequence (referred to as the B-specific repeat) localized in the centromeric region of the maize B chromosome. The centromere is composed mostly of this repeat. In this report, a collection of 25 B chromosome derivatives that suffered from misdivision of the centromere was examined for the content and organization of the B repeat. Meiotic transmission of these derivatives was also determined and compared with rearrangements within the centromere. This analysis revealed that there is a strong correlation between the size of the centromere and meiotic transmission. In addition, the loss of a particular PmeI fragment of 370 kb considerably reduced meiotic transmission. This sequence contains a 55-kb EcoRI fragment that is also present in all but four derivatives. Because the centromere of the maize B chromosome can be divided by successive misdivisions to derivatives with centromeres of <300 kb, it should be possible for artificial chromosomes to be produced in maize.