Menstrual cycle and reproductive aging alters immune reactivity,NGF expression,antioxidant enzyme activities,and intracellular signaling pathways in the peripheral blood mononuclear cells of healthy women

Reproductive senescence in women is a process that begins with regular menstrual cycles and culminates in menopause followed by gradual development of diseases such as autoimmune diseases, osteoporosis, neurodegenerative diseases, and hormone-dependent cancers. The age-associated impairment in the functions of neuroendocrine system and immune system results in menopause which contributes to subsequent development of diseases and cancer. The aim of this study is to characterize the alterations in immune responses, compensatory factors such as nerve growth factor (NGF) and antioxidant enzyme activities, and the molecular mechanisms of actions in the peripheral blood mononuclear cells (PBMCs) of young (follicular and luteal phases), middle-aged, and old healthy women. Peripheral blood mononuclear cells were isolated from young women in follicular and luteal phases of the menstrual cycle (n = 20; 22.6 ± 2.9 yrs), middle-aged women (n = 19; 47.1 ± 3.8 yrs; perimenopausal) and old (n = 16; 63.2 ± 4.7 yrs; post-menopausal) women and analyzed for Concanavalin (Con A)-induced proliferation of lymphocytes and cytokine (IL-2 and IFN-γ) production, expression of NGF, p-NF-κB, p-ERK, p-CREB, and p-Akt, antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), glutathione-S-transferase (GST)], extent of lipid peroxidation, and nitric oxide (NO) production. Serum gonadal hormones (17β-estradiol and progesterone) were also measured. A characteristic age- and menstrual cycle-related change was observed in the serum gonadal hormone secretion (estrogen and progesterone), T lymphocyte proliferation and IFN-γ production. Salient features include the age-related decline observed in target-derived growth factors (lymphocyte NGF expression), signaling molecules (p-ERK/ERK and p-CREB/CREB ratios) and compensatory factors such as the activities of plasma and PBMC antioxidant enzymes (SOD and catalase) and NO production. Further, an age-associated increase in p-NF-κB expression and lipid peroxidation was observed. Also, serum 17β-estradiol levels were positively correlated with IFN-γ production, SOD activity and NGF expression in the PBMCs. These results suggest that alterations in the levels of gonadal hormones are associated with immunosenescence characterized by decreased IFN-γ production and proliferation of T lymphocytes, decline in NGF expression, SOD and catalase activities, NO production, and signaling mechanisms and thus, may increase the incidence of diseases and cancer in women.     

Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth

Vitamin B₁₂ and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B₁₂ and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B₁₂ and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B₁₂ and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n = 8 each): control, vitamin B₁₂ deficient, vitamin B₁₂ deficient + omega-3 fatty acid, vitamin B₁₂ supplemented, vitamin B₁₂ supplemented + omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B₁₂ deficiency showed lower (p < 0.05) pup brain mRNA and protein levels (p < 0.01) of VEGF, higher (p < 0.01) HIF-1 alpha protein levels, lower (p < 0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B₁₂ deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B₁₂ supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B₁₂ supplemented group showed higher (p < 0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B₁₂ and omega-3 fatty acids both influence the levels and expression of neurotrophins and angiogenic factors in the offspring brain suggesting a possible benefit of combined maternal supplementation of these vital nutrients.     

The non-linear association between low-level lead exposure and maternal stress among pregnant women

BackgroundNeuro-developmental impairments in the developing fetus due to exposure to low-level lead have been well documented. However, few studies have investigated the relation between maternal stress levels and low-level lead exposure among pregnant women.ObjectivesTo investigate the relation between maternal blood lead and stress levels during index pregnancy.Methods1931 pregnant women (gestational week 28–36) were investigated using stratified-cluster-sampling in Shanghai in 2010. Maternal life event stress and emotional stress were assessed using “Life-Event-Stress-Scale-for-Pregnant-Women” (LESPW) and “Symptom-Checklist-90-Revised” (SCL-90-R), respectively. Maternal whole blood lead levels were determined, and other data on covariates were obtained from maternal interviews and medical records. Two piecewise linear regression models were applied to assess the relations between blood lead and stress levels using a data-driven approach according to spline smoothing fitting of the data.ResultsMaternal blood lead levels ranged from 0.80 to 14.84 μg/dL, and the geometric mean was 3.97 μg/dL. The P-values for the two piecewise linear models against the single linear regression models were 0.010, 0.003 and 0.017 for models predicting GSI, depression and anxiety symptom scores, respectively. When blood lead levels were below 2.57 μg/dL, each unit increase in log10 transformed blood lead levels (μg/dL) was associated with about 18% increase in maternal GSI, depression and anxiety symptom scores (P_GSI = 0.013, P_depression = 0.002, P_anxiety = 0.019, respectively). However, no significant relation was found when blood lead levels were above 2.57 μg/dL (all P-values > 0.05).ConclusionOur findings suggested a nonlinear relationship between blood lead and emotional stress levels among pregnant women. Emotional stress increased along with blood lead levels, and appeared to be plateaued when blood lead levels reached 2.57 μg/dL.     

Maternal mood scores in mid-pregnancy are related to aspects of neonatal immune function

BackgroundAlthough there are recognised associations between psychological and immune function, the effects of maternal depressive symptoms on fetal immune development have not been investigated.MethodsThis study examined the relationship between maternal depression scores as assessed by the Beck Depression Inventory (BDI) in the second trimester and measure of neonatal immune function measured in cord blood. This study was conducted in a cohort of women (n = 83) who had received either fish oil containing 3.7 g/day n-3 polyunsaturated fatty acid (n-3PUFA) or a placebo from 20 weeks gestation as part of a randomised controlled trial.ResultsAt 20 weeks gestation, prior to the intervention, 22% of women in the study manifested mild to moderate depressive symptoms (BDI ?10). Neonates of these women had higher lymphoproliferative responses to a range of stimuli (including egg ovalbumin and cat allergen) compared with neonates of women with normal BDI scores (<10). These neonates also showed higher spontaneous cytokine production including (IL-6 and IL-10) and higher stimulated cytokine responses to both bacterial antigens and allergens. These patterns were evident after allowing for maternal age and education, parity, gestation, infant gender, delivery method and neonatal n-3/n-6 PUFA status.ConclusionThis exploratory study supports the notion that maternal mood in pregnancy may have the potential to influence fetal immune development. Further studies are needed to determine the significance of this.     

Protective effects of tadalafil on experimental spinal cord injury in rats

Tadalafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Nitric oxide (NO) functions as a retrograde neurotransmitter in the spinal cord, and postsynaptic structures respond to NO by producing cGMP. The concentrations of cGMP in the spinal cord are controlled by the actions of PDE. The aim of the study was to evaluate and compare the effects of the use of both methylprednisolone and tadalafil on serum and tissue concentrations of NO, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue glutathione peroxidase (GSH-Px) activity in rats with spinal cord injury (SCI). SCI was induced in Wistar albino rats by dropping a 10 g rod from a 5.0 cm height at T8–10. The 28 rats were randomly divided into four equal groups: tadalafil, methylprednisolone, non-treatment and sham groups. Rats were neurologically tested at 24 hours after trauma. At the end of the experiment, blood samples were collected and spinal cord tissue samples were harvested for biochemical evaluation. The tissue level of NO was increased in the tadalafil group compared with the non-treatment and methylprednisolone groups (p < 0.05). The tissue levels of SOD and GSH-Px did not differ between the groups. Serum levels of NO were higher in the tadalafil group than in the non-treatment group (p < 0.05). The increase in serum SOD levels was greater in the tadalafil group than the methylprednisolone group. Serum MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group (p > 0.05). Tissue MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group and sham groups (p > 0.05). Although there was no difference in neurological outcome scores between the tadalafil, methylprednisolone and non-treatment groups (p > 0.05), the animals in the tadalafil and methylprednisolone groups tended to have better scores than the non-treatment group. Thus, tadalafil appears to be beneficial in reducing the effects of injury to the spinal cord by increasing tissue levels of NO and serum activity of SOD.     

Sleep disturbance and cardiometabolic risk factors in early pregnancy: a preliminary study

BackgroundCardiometabolic (CM) risk factors are linked to increased morbidity. Disturbed sleep is associated with CM risk factors in late pregnancy, but little is known about sleep in early pregnancy and CM risk factors.MethodsDiary and actigraphy-assessed sleep information, as well as CM outcomes (blood pressure (BP) and body mass index (BMI)), were collected thrice from pregnant women (N = 161) in early pregnancy: T1 (10–12 weeks), T2 (14–16 weeks) and T3 (18–20 weeks). The sleep variables evaluated included sleep onset latency (SOL), wake after sleep onset (WASO) and total sleep time (TST). Sleep variables were dichotomised using established clinical cut-offs.ResultsBMI and BP significantly changed across time. Women with persistent SOL ⩾ 20 min had greater BMI than women without persistent SOL ⩾ 20 min prior to covariate adjustment at T1 and T2, but at T3 the BMI values converged. Similar results were observed for persistent WASO ⩾ 30 min. Persistently long WASO, as measured by actigraphy, was associated with elevated SBP, after controlling for covariates.ConclusionsConsistent with anecdotal evidence, it appears as if a subset of women report substantial difficulty initiating and maintaining sleep during early pregnancy and this may augment the risk of higher BP and BMI. Understanding these relationships is important as CM risk factors are linked to maternal and infant morbidity. Assessing sleep in early pregnancy may bestow time necessary for appropriate intervention.     

Prenatal maternal stress in relation to the effects of prenatal lead exposure on toddler cognitive development

ObjectiveTo evaluate the effects of maternal lead exposure during pregnancy on toddler cognitive development and the potential effect modification by maternal stress.MethodsWe conducted a prospective birth-cohort study in Shanghai from 2010 to 2012 and investigated 225 mother-infant pairs. The mothers were recruited in mid-to-late pregnancy and children were followed up until 24–36 months old. A self-administered Symptom Checklist-90-Revised Scale (SCL-90-R) was used to assess maternal emotional stress during pregnancy. Maternal whole blood lead levels were measured during gestational weeks 28–36. The toddlers’ cognitive levels were assessed using the Gesell Development Scale. Multiple linear regression models were established to explore the main effects of prenatal lead exposure on toddlers’ cognitive abilities and the modifying effects of maternal stress. Covariate information was collected through interviews, questionnaires and medical records.ResultsThe mean maternal blood lead concentration was 3.30 (95%CI: 3.05, 3.57) μg/dL. After adjusting for relevant confounders, no significant associations of maternal blood lead concentrations with toddlers' cognitive levels were observed in all five domains of the Gesell scale (P > 0.05). However, the interaction between prenatal maternal blood lead and stress was significant in the domains of adaptive behavior, language and social behavior. When stratified by maternal stress levels, compared with non-significant associations (P > 0.05) among low (P1-P75) prenatal stress group, adverse associations between maternal blood lead concentrations (log10-transformed) and toddlers’ cognitive levels were observed among high (P75-P100) prenatal stress group in the domains of language (β = −33.82, 95%CI: −60.04, −7.59), social behavior (β = −41.00, 95%CI: −63.11, −18.89) and adaptive behavior (β = −17.93, 95%CI: −35.83, −0.03).ConclusionPrenatal maternal stress may exacerbate the deleterious effects of prenatal exposure to lead on toddler cognitive development.     

Mercury,APOE, and children's neurodevelopment

The benefit of the nutritious elements in fish is insufficient for explaining the controversial finding regarding prenatal mercury (Hg) exposure and neurodevelopment; the varying frequency of susceptible genes among these populations may shed light on these observations. However, limited studies have been reported on the association between genetic susceptibility of prenatal Hg exposure and child development. Apolipoprotein E (APOE, protein; Apoe, gene) is a major protein transporter expressed in the brain. The Apoe epsilon 4 (ɛ4) allele is associated with poor neural repair function and is a risk factor associated with Alzheimer disease. We conducted a prospective cohort study in 2004 and 2005. In this study, 168 subjects were recruited at delivery and followed up at two years of age, and genetic polymorphisms of Apoe were included to assess genetic susceptibility and to determine the relationship between Hg concentrations in cord blood and neurodevelopment. The results showed that adverse effects on neurodevelopment were consistently associated with prenatal Hg exposure in all subtests of Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) among ɛ4 carriers as assessed by both simple linear and multiple linear regression models. After controlling for confounding factors, statistical significance was found in the subtests of cognition tests (β = −8.47, 95% confidence interval (CI) = −16.10 to −0.84), social tests (β = −11.02, 95% CI = −20.85 to −1.19) and the whole test of CDIIT (β = −10.45, 95% CI = −17.36 to −3.54) in a multiple linear regression model. Additionally, the interaction effect between gene polymorphisms of Apoe and Hg levels was significant in the whole test CDIIT and subtests of cognition, language and fine motor tests. In conclusion, Apoe modifies the adverse effects of cord blood Hg on neurodevelopment at the age of two years.     

Acute traumatic cervical cord injury in patients with os odontoideum

We retrospectively reviewed acute cervical cord injury after minor trauma in 10 patients with os odontoideum. Their clinical history, neurological symptoms, radiological investigations, follow-up period, American Spinal Injury Association impairment classification and motor score were reviewed. Before their traumatic injury, three patients were asymptomatic and seven reported myelopathic symptoms, including four patients with neck pain, two patients with unsteadiness and one patient with dizziness. Falls were the most common cause of injury (n = 6), followed by minor motor vehicle accidents (n = 3) and assault (n = 1). MRI and dynamic cervical lateral radiographs showed that all patients had atlantoaxial instability and cord compression. Most patients had spinal cord thinning and hyperintensity on T2-weighted MRI. Spinal cord compression was posterior (n = 5), or both anterior and posterior (n = 5). All patients underwent posterior rigid screw fixation and fusion, including atlantoaxial fusion (n = 8) and occipitocervical fusion (n = 2). We conclude that patients with asymptomatic or myelopathic atlantoaxial instability secondary to os odontoideum are at risk for acute spinal cord injury after minor traumatic injury. Fixation and fusion should be undertaken as prophylactic treatment for patients at risk of developing myelopathy and to avoid the neurological deterioration associated with acute traumatic cervical cord injury.     

Physical activity and self-determined motivation of adolescents with and without autism spectrum disorders in inclusive physical education

The main purpose of this study was to compare the objectively measured physical activity (PA) and the motivation process between adolescents with (n = 25) and without (n = 75) autism spectrum disorders (ASD) in inclusive physical education (PE); and assess the associations of the PA levels to a sequence of motivational processes. Independent t-tests revealed significant PA and motivational process differences between adolescents with and without ASD. External regulation was positively correlated with the percentage of time that adolescents with ASD spent in moderate PA (r₂₅ = 0.58, p < .01) and moderate-to-vigorous PA (r₂₅ = 0.50, p < .05), and this extrinsic motive was associated with their needs of being attached or related in the class (r₂₅ = 0.53, p < .01). No significant associations of PA in PE on the motivational sequences of adolescents without ASD were observed. It is concluded that adolescents with ASD had less PA levels in PE and lower motives toward PE than adolescents without ASD, and external regulation was important in facilitating PA participation in adolescents with ASD.     

Tired telomeres: Poor global sleep quality,perceived stress,and telomere length in immune cell subsets in obese men and women

Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean = 35.4, SD = 3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b = −56.8 base pairs per one point increase in PSQI, SE = 20.4, p = 0.007) and CD4+ T cells (b = −37.2, SE = 15.9, p = 0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and disease risk in obese individuals.     

The effectiveness of dexmedetomidine in experimental spinal cord injury compared to methylprednisolone in rats

The present study aimed to investigate the neuroprotective efficacy of dexmedetomidine in a rat experimental spinal cord injury model. The rats (n = 40) were equally divided into four groups: G1, G2, G3, and G4. Rats in the G1 group underwent a laminectomy only. For the rats in the G2, G3, and G4 groups, spinal cord injury was induced by placing an aneurysm clip extradurally for 60 s at T10. The rats in G2 did not receive any post-injury treatment. Immediately after trauma was induced, rats in G3 were given methylprednisolone (30 mg/kg) and in G4, dexmedetomidine (10 μg/kg), both intraperitoneally. The rats were sacrificed under anesthesia 24 hours later and 1.5 cm lengths of injured spinal cord were obtained. Malonyldialdehyde values were significantly increased in G2 compared to G1, G3 and G4 (p < 0.05). The neuronal cell count in G1 was significantly higher than in G2 and G3 (p = 0.0001; p = 0.007). G4 had higher cell counts compared to G2 and G3 (p = 0.0001; p = 0.05). These findings indicated that dexmedetomidine might have neuroprotective effects in spinal cord injury.     

Clinical presentation,imaging findings,and prognosis of spinal dural arteriovenous fistula

Spinal dural arteriovenous fistula (SDAVF) is a relatively common acquired vascular malformation of the spinal cord. Assessment of a SDAVF is often difficult because of non-specific findings on non-invasive imaging modalities. Diagnosis of a SDAVF is often delayed, and some patients receive unnecessary treatment and treatment delays, often resulting in a poor outcome. The aim of this study was to characterize the clinical presentation, typical imaging findings, and long-term outcome of SDAVF. Forty patients (13 women, 27 men; mean age 58.18 ± standard deviation 14.75 years) who were treated at our hospital from June 1992 to March 2014 were retrospectively reviewed. We investigated the baseline characteristics, clinical presentation, imaging findings, treatment modalities, and outcome of the patients. The most common clinical presentation was a sensory symptom (80%), followed by motor weakness (70%), and sphincter dysfunction (62.5%). Roughly one-third (32.5%) of patients had a stepwise progression of fluctuating weakness and sensory symptoms, but the most common presentation was chronic progressive myelopathic symptoms (47.5%). Thirty-four patients (85%) had T2 signal change on the spinal cord MRI, indicative of cord edema. Thirty-eight patients had typical perimedullary vessel flow voids on T2-weighted MRI. Twenty-eight patients were treated with endovascular embolization, five patients underwent surgery, and four patients underwent both. Clinical outcome was determined by severity of initial deficit (p = 0.008), extent of cord edema (p = 0.010), treatment failure (p = 0.004), and a residual fistula (p = 0.017). SDAVF causes a treatable myelopathy, so early diagnosis and intervention is essential.     

Pre-eclampsia and nasal CPAP: Part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: Preliminary findings

BackgroundPre-eclampsia is a leading cause of maternal–fetal morbidity and mortality. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. This prospective, longitudinal study was designed to characterize sleep-related breathing patterns in pregnant women with pre-eclampsia risk factors, and to describe the effects of early nasal CPAP therapy in these patients.MethodsTwelve pregnant women with pre-eclampsia risk factors underwent polysomnography to characterize sleep-related breathing abnormalities and baseline blood pressure determination. Patients with airflow-limitation underwent nasal CPAP titration and were treated with optimal pressures. Periodic assessments of CPAP compliance and tolerance, sleep quality, and blood pressure control were performed until delivery or pre-eclampsia onset. CPAP retitration was performed between weeks 20 and 22 of pregnancy.ResultsMean respiratory disturbance index was 8.5 ± 2.6 events/h of sleep, and initial nasal CPAP pressures were 5–6 cm H₂O with an increase to 6–9 cm H2O after recalibration. All subjects with chronic hypertension maintained blood pressures below 140/90 with a mean diurnal blood pressure of 122 ± 2.5 mm Hg over 83 ± 1.5 mm Hg. Patient characteristics of obesity and prior pre-eclampsia were associated with pregnancies complicated by spontaneous abortion, premature delivery, or pre-eclampsia.ConclusionsEarly application of nasal CPAP in pregnant women alleviated sleep-related breathing disturbances but was not sufficient to prevent negative pregnancy outcomes. Obesity and prior pre-eclampsia appeared to be important factors and were associated with the worst complications. However, nasal positive pressure may still be beneficial to decrease severity of outcomes, particularly if individualized to patient risk factors, more particularly hypertension at pregnancy onset.     

Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample

ObjectiveThe literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6), interleukin-8 (IL-8) and depression in a population-based sample of older women who were followed for 17 years.Methods86 dementia-free women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF IL-6 and CSF IL-8 were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria.ResultsAt baseline, women with ongoing major (n = 10) or minor depression (n = 9) had higher levels of CSF IL-6 (p = 0.008) and CSF IL-8 (p = 0.007) compared with those without depression (n = 67). Higher CSF IL-8 was related to higher MADRS score (p = 0.003). New cases of depression were observed in 9 women during follow-ups. No associations between CSF cytokine levels and future depression could be shown in women without depression at baseline.ConclusionHigher levels of CSF IL-6 and IL-8 were associated with current depression in this population-based sample. CSF IL-6 and CSF IL-8 may play a role in depression in late life.     

Anthropometric indexes,insulin resistance,and serum leptin and lipid levels in women with cryptogenic epilepsy receiving topiramate treatment

We aimed to investigate the effects of topiramate monotherapy on anthropometric indexes, insulin resistance, and serum leptin and lipid levels in 33 premenopausal women (mean age ± standard deviation: 26.7 ± 7.1 years) with cryptogenic epilepsy. Body mass index (BMI), waist circumference and serum leptin, insulin and lipid levels were measured at baseline and at 6 months after initiation of topiramate. We found reductions in BMI (p < 0.001), waist circumference (p < 0.001) and serum high-density lipoprotein (HDL) cholesterol levels (p = 0.011). We also found significant improvements in insulin resistance (p = 0.023), but not in serum leptin levels (p = 0.45). Our results suggest that topiramate treatment in women with epilepsy is associated with reduced BMI and waist circumference and improvement in insulin resistance; however, according to our data, topiramate treatment is also associated with lower HDL cholesterol levels, which may substantially increase vascular disease.     

Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring

ObjectiveThe aim of this study was to examine the association between maternal serum vitamin D status in first trimester and risk of ASD at age 3–7 years in the offspring.MethodsUsing a case-control design, 68 children diagnosed with ASD and 68 sex and age matched typically-developing children were included. Archived maternal blood samples from the first trimester of pregnancy (11–13 weeks gestational age) were identified for those participants. Maternal serum levels of 25 hydroxyvitamin D3 [25(OH) D], unmetabolized folic acid (FA), vitamin B12, homocysteine (HCY) and High Sensitivity C Reactive protein (CRP) were measured from those samples. We examined the associations between those factors in pregnancy and diagnosis of ASD with logistic regression using SPSS.ResultsMothers in autistic group had significantly lower maternal serum levels of 25(OH) D than in typically-developing group [19.2(IQR: 15.8–22.9)ng/ml vs. 24.3(19.3–27.3)ng/ml, P < 0.001], with 55.9% and 29.4% being vitamin D deficient, respectively (P < 0.001). Levels of 25(OH) D increased with decreasing severity of ASD as defined by the CARS score (r = − 0.302, P < 0.001). Maternal first trimester serum levels of 25(OH) D in the lower 3 quartiles (quartile 1, 2, 3) (compared to the highest quartile) was associated with increased odds of ASD diagnosis in offspring [OR (95% CI) Q1: 1.36(0.84–2.58, P = 0.25); Q2: 2.68(1.44–4.29, P = 0.006); Q3:3.99(2.58–7.12, P < 0.001)].ConclusionsLower first trimester maternal serum levels of 25(OH) D were associated with increased risk of developing autism in offspring. If these findings are confirmed, this may present an opportunity for prenatal intervention to reduce the risk for ASD.     

Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes

PurposeTo investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies.MethodsThis was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n = 51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n = 81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test.ResultsCompared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P = 0.049) and those not requiring valproic acid (77% vs. 56%, P = 0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P = 0.018) and changes in antiepileptic drugs (24% vs. 41%, P = 0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations.ConclusionFor women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs.     

Gender differences in the association of sleep apnea and inflammation

Over the last 15 years, many studies have established an association of sleep apnea with inflammation and metabolic aberrations. However, no controlled studies have examined potential gender effects in this association. We recruited 120 middle-aged, predominantly non-obese mild-to-moderate sleep apneics and controls (62 males, 58 females). All participants underwent a clinical history, physical examination, and 1-night 8-h polysomnography recording and provided a single fasting blood sample for assessment of interleukin-6 (IL-6), tumor necrosis factor receptor 1 (TNFR1), C-reactive protein (CRP), leptin, and adiponectin levels. Among non-sleep apneics, females had higher levels of TNFR1 (p = 0.01), CRP (p = 0.005), leptin (p < 0.001), and adiponectin (p < 0.001) compared to males, independent of age and body mass index. When analyzed separately by gender, sleep apneic men had elevated TNFR1 (p = 0.04), CRP (p = 0.06) and IL-6 (p = 0.11) relative to control men; in sleep apneic females, only CRP was elevated (p = 0.04). Furthermore, CRP was associated with apnea severity in a dose–response manner (p-linear = 0.04 in both genders) and was independently associated with comorbid hypertension in apnea (p-linear = 0.005 for women; p-linear = 0.09 for men). In conclusion, although women have naturally higher levels of inflammatory and metabolic markers than men, sleep apneic men appear to have a more severe inflammatory profile compared to women. Our findings suggest that these markers should be analyzed and interpreted separately in men and women, and that a single measure of plasma CRP appears to be a clinically-useful marker of apnea severity and comorbid cardiovascular morbidity.