Maternal nerve growth factor levels during pregnancy in women with preeclampsia: A longitudinal study

Preeclampsia (PE) is characterized by hypertension and proteinuria. Improper development of the placenta due to altered angiogenesis is the main culprit in PE. Nerve growth factor (NGF) is an angiogenic factor which is expressed and localized in the placenta. Our earlier cross sectional study has shown altered NGF levels at delivery in women with PE. However, there are no studies on NGF levels in PE early in pregnancy before manifestation of the disease. Thus, there is a need to examine the role of NGF in vascular development during different stages of gestation in PE. A longitudinal study was carried out where pregnant women were enrolled from two major hospitals from Pune, Bharati hospital and Gupte hospital. They were followed at three different time points [16–20 weeks (T1), 26–30 weeks (T2) and at delivery (T3)] during pregnancy and maternal blood at every time point and cord blood at delivery was collected and processed. This study included normotensive women (n = 88) and women with PE (n = 48). NGF levels were measured from maternal and cord plasma using the Emax Immuno Assay System (Promega). The data was analyzed using the SPSS/PC+ package (Version 20.0, Chicago, IL, USA). Maternal NGF levels did not change at all time points while cord NGF levels were higher (p < 0.05) in women with PE. Further, maternal NGF levels were negatively associated with blood pressure while cord NGF levels were positively associated with baby head circumference. Our data suggests that there may possibly be a compensatory role for NGF in the foeto-placental circulation in PE.     

Objective sleep interruption and reproductive hormone dynamics in the menstrual cycle

ObjectivesWomen report greater sleep disturbance during the premenstrual phase of the menstrual cycle and during menses. However, the putative hormonal basis of perceived menstrual cycle-related sleep disturbance has not been investigated directly. We examined associations of objective measures of sleep fragmentation with reproductive hormone levels in healthy, premenopausal women.MethodsTwenty-seven women with monthly menses had hormone levels measured at two time points during a single menstrual cycle: the follicular phase and the peri-ovulatory to mid-luteal phase. A single night of home polysomnography (PSG) was recorded on the day of the peri-ovulatory/mid-luteal-phase blood draw. Serum progesterone, estradiol, and estrone levels concurrent with PSG and rate of change in progesterone (PROGslope) from the follicular blood draw to PSG were correlated with log-transformed wake after sleep onset (lnWASO%) and number of wakes/hour of sleep (lnWake-Index) using linear regression.ResultsSleep was more fragmented in association with a steeper PROGslope (lnWASO% p = 0.016; lnWake-Index p = 0.08) and higher concurrent estrone level (lnWASO% p = 0.03; lnWake-Index p = 0.01), but the effect of estrone on WASO was lost after accounting for PROGslope. WASO% and Wake-Index were not associated with concomitant progesterone or estradiol levels.ConclusionsA steeper rate of rise in progesterone levels from the follicular phase through the mid-luteal phase was associated with significantly greater WASO, establishing a link between reproductive hormone dynamics and sleep fragmentation in the luteal phase of the menstrual cycle.     

Epstein–Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis

Epstein–Barr virus-induced gene 3 (EBI3) associates with p28 and p35 to form the immunomodulatory cytokines IL-27 and IL-35, respectively. Infection of EBI3 ?/? mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality that was not associated with impaired ability to control viral replication but enhanced T cell and macrophage infiltration into the CNS. IFN-γ secretion from virus-specific CD4 + and CD8 + T cells isolated from infected EBI3 ?/? mice was augmented while IL-10 expression muted in comparison to infected WT mice. These data demonstrate a regulatory role for EBI3-associated cytokines in controlling host responses following CNS viral infection.     

Sex differences in the relationship between obesity,C-reactive protein,physical activity,depression, sleep quality and fatigue in older adults

Fatigue is a serious health concern in the elderly. Sex differences exist in adiposity, systemic inflammation, physical activity/fitness and fatigue; however, the relations among these variables remain inadequately characterized impeding the development of fatigue prevention strategies. Measures of adiposity, C-reactive protein, physical activity, aerobic fitness, fatigue, sleep quality and depression were obtained from 127 community-dwelling older adults. Although similar in age (70 y) and BMI (28.0 kg/m²) women (n = 80) reported 63% greater fatigue than men (p = 0.04). Adiposity (r = 0.44), CRP (r = 0.29), physical activity (r = ?0.26) and fitness (r = ?0.41) were related to fatigue in women (all p < 0.05), but not in men. Depression was also related to fatigue in women (r = 0.37), and was the only variable related to fatigue in men (r = 0.42). In women, fatigue was independently explained (all p < 0.05) by CRP (6.6%), depression (6.3%), physical activity (5.8%), and adiposity (3.9%); however, in men, only depression explained variance in fatigue (12.0%). CRP was 40% higher and adiposity 12% higher in women reporting fatigue compared to those with no fatigue; no such differences existed in men. Obese women perceived a greater degree of fatigue than non-obese women, but this was not the case in men. Women report more fatigue than men which was independently associated with inflammation, depression, physical activity and adiposity, whereas in men the only independent predictor was depression. Strategies to prevent fatigue may differ in older women and men, especially with regard to inflammation, physical activity and adiposity.     

Evaluation of periodontitis in hospital outpatients with major depressive disorder. A focus on gingival and circulating cytokines

An imbalance in stimulated cytokine production is associated with the etiopathogenesis of numerous diseases such as major depressive disorder (MDD) and periodontal disease. Increased cytokine levels have been reported in the gingival crevicular fluid (GCF) of patients with MDD. Thirty-six outpatients with MDD participated in this study. Each outpatient was age-matched (±3 years) with a healthy control (n = 36). The patients were controlled for race and smoking habits. Unstimulated and stimulated interleukin 6 (IL-6), interleukin 1β (IL-1β), and interferon-γ (INF-γ) production in whole blood culture (WBC) and IL-6 and IL-1β levels in the GCF were evaluated. Circulating levels of IL-6 and IL-1β (unstimulated) as well as GCF IL-1β were modestly lower in MDD patients, compared to the levels in age-matched controls (Mann–Whitney, p = 0.002, 0.0075, ANCOVA, p = 0.025, respectively). In the unstimulated group, there was no correlation between the levels of circulating IL-6 and GCF IL-6 (r = 0.07, p = 0.67), and between the levels of circulating IL-1β and the IL-1β level in the CGF (r = −0.08, p = 0.63). In the LPS stimulation group, there was no correlation between the levels of circulating levels of IL-6 and GCF IL-6 (r = 0. 02, p = 0.91) or between the circulating IL-1β and GCF IL-1β (r = 0.13, p = 0.42). We observed modest immunosuppression in MDD patients (evaluated by no stimulation whole blood culture [WBC]), especially in patients with melancholic depression, chronic depression, and severe depression.     

Social role conflict predicts stimulated cytokine production among men,not women

ObjectiveTo assess whether perceived role conflict is associated with stimulated pro-inflammatory cytokine production and glucocorticoid sensitivity, and whether these associations are moderated by sex.Methods153 healthy adults (aged 45.8 ± 5.5 years, 78% female) listed their 3 main social roles and indicated the amount of role conflict they perceived between each pair of social roles. Subsequently, participants underwent blood draws and leukocyte response to microbial challenge and glucocorticoid sensitivity were assessed by incubating whole blood with lipopolysaccharide (LPS) in the presence or absence of hydrocortisone. Stimulated levels of Interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNFα) were measured.ResultsMultiple regression analyses controlling for sociodemographics revealed significant sex × role conflict interactions for LPS-stimulated production of IL-1β, IL-6, and TNFα (all interaction ps < 0.05), and a marginal interaction on LPS-stimulated IL-8 production (interaction p < 0.10). Greater perceived role conflict was associated with greater pro-inflammatory cytokine production in response to microbial stimulation only among men, not women. There also were significant sex × role conflict interactions with respect to glucocorticoid sensitivity for IL-1β, IL-6, and TNFα production (all interaction ps < 0.05) and a marginal interaction for IL-8 (interaction p < 0.10). Greater perceived role conflict was unrelated to glucocorticoid sensitivity among women, but associated with less sensitivity to glucocorticoid signaling among men.ConclusionsPerceived social role conflict, indicating greater perceived demand across multiple social roles, may take a greater toll on the regulation of inflammatory processes among men compared to women.     

Cytokine-induced depression during IFN-α treatment: The role of IL-6 and sleep quality

Depressive symptoms, poor sleep quality, and systemic markers of inflammation (e.g., interleukin (IL)-6) are frequently associated. Interferon-alpha (IFN-α) therapy results in Major Depressive Disorder (MDD) in some people, offering the possibility to elucidate the relationship of MDD to sleep and inflammation during treatment. In particular, delineating the temporal relations among these factors could help inform their causal relationships. To this end, a cohort of 95 non-depressed hepatitis C patients was followed prospectively for four consecutive months during IFN-α therapy. We found that higher pre-treatment levels of circulating IL-6 predicted incidence of MDD (X²(1) = 7.7; p < 0.05). Time-lagged mixed-effect analyses supported uni-directional associations in which IL-6 predicted next month’s PSQI scores (F(47, 11.6) = 78.4; p < 0.0005), and PSQI scores predicted next month’s depressive Beck Depression Inventory-II (BDI) scores (F(16, 22.6) = 3.4; p < 0.005). In addition, on any given month of treatment, IL-6 levels predicted BDI symptoms the following month (F(16, 97.5) = 7.3; p < 0.0005), and conversely BDI predicted next month’s IL-6 (F(14, 7.4) = 5.2; p < 0.05) – providing evidence for a positive feedback relationship between depressive symptoms and systemic inflammation. These data provide further evidence that high levels of inflammation and poor sleep quality may be risk factors for IFN-α induced depression. Furthermore, these findings highlight the complex temporal relationships that exist among sleep, depression, and inflammation, and support the need for further prospective investigations to elucidate the dynamics that underlie depression during IFN-α treatment.     

Association between depressive symptoms and fibrosis markers: The Cardiovascular Health Study

ObjectiveFibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above.MethodsFibrosis markers and depressive symptoms were assessed in 870 participants (age = 80.9 ± 5.9 yrs, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D ? 8). Covariates included demographic and clinical variables.ResultsDepression was associated with higher levels of PIP (median = 411.0, inter-quartile range (IQR) = 324.4–472.7 ng/mL vs. 387.6, IQR = 342.0–512.5 ng/mL, p = 0.006) and CITP (4.99, IQR = 3.53–6.85 vs. 4.53, IQR = 3.26–6.22 μg/L, p = 0.024), but not PIIIINP (4.07, IQR = 2.75–5.54 μg/L vs. 3.58, IQR = 2.71–5.01 μg/L, p = 0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p = 0.014; WBC, p = 0.075; fibrinogen, p = 0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers.ConclusionsDepression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role.     

Treatment of elderly primary insomnia patients with EVT 201 improves sleep initiation,sleep maintenance,and daytime sleepiness

ObjectiveTwo doses of EVT 201, a partial positive allosteric modulator of the GABA_A system, were evaluated in elderly primary insomnia patients with daytime sleepiness.Patients and methodsParticipants were 149 elderly patients with DSM-IV primary insomnia including evidence of daytime sleepiness (53 males, 96 females; mean age 71.3 yrs, range 65–86 yrs). A randomized, multicentre, double-blind, placebo-controlled, parallel-group design was used to assess the hypnotic efficacy of EVT 201 1.5 and 2.5 mg during seven consecutive nights. Polysomnography (PSG) was performed on nights 1, 6 and 7 of treatment. Daytime assessments on Day 8 included the multiple sleep latency test (MSLT), Rey Auditory Verbal Learning Test (RAVLT), Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS). The primary endpoint was total sleep time (TST) and the key secondary endpoint was mean MSLT latency.ResultsCompared to placebo, EVT 201 1.5 and 2.5 mg increased TST (30.9, 56.4 min, respectively; p = 0.0001, p < 0.0001); reduced wake after sleep onset (WASO; ?15.2, ?36.1 min, respectively; p = 0.014, p < 0.0001); reduced latency to persistent sleep (LPS; ?15.9, ?19.9 min, respectively; p = 0.009, p = 0.001). The 2.5 mg dose also reduced WASO in hours 5–8 (?16.3 min, p = 0.001). Both doses also improved subjective sleep quality and usual subjective efficacy measures. A significantly longer mean MSLT latency was observed on Day 8 with both doses, compared to placebo (2 min increase; p = 0.03, both doses). The PVT, RAVLT, and POMS did not differ among treatment groups. No serious or unexpected treatment emergent adverse events were noted.ConclusionEVT 201 improved PSG measures of sleep onset and sleep maintenance and significantly reduced daytime physiological sleep tendency. These findings suggest that treatment of primary insomnia in older patients has the potential to improve daytime sleepiness as well as sleep.     

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.     

Disturbed dreaming during the third trimester of pregnancy

ObjectiveThe majority of women develop sleep impairments during pregnancy, but alterations in dream experiences remain poorly understood. This study aimed to assess prospectively and comparatively the recall of dreaming and of disturbed dreaming in late pregnancy.MethodsFifty-seven nulliparous, third-trimester pregnant women (mean age ± SD, 28.7 ± 4.06 years) and 59 non-pregnant controls (mean age ± SD, 26.8 ± 4.21 years) completed demographics and psychological questionnaires. A 14-day prospective home log assessed sleep and dream characteristics and the Sleep Disorders Questionnaire measured retrospective dream and disturbed dream recall.ResultsEven though pregnant and non-pregnant women showed similar prospective dream recall (P = 0.47), pregnant women reported prospectively more bad dreams (P = 0.004). More pregnant women (21%) than non-pregnant women (7%) reported a nightmare incidence exceeding moderately severe pathology (>1/week) (P = 0.03). Pregnant women also reported overall lower sleep quality (P = 0.007) and more night awakenings (P = 0.003). Higher prospective recall of bad dreams (r = −0.40, P = 0.002) and nightmares (r = −0.32, P = 0.001) both correlated with lower sleep quality in pregnant women.ConclusionsLate pregnancy is a period of markedly increased dysphoric dream imagery that may be a major contributor to impaired sleep at this time. Further polysomnographic assessments of pregnant women are needed to clarify relationships between sleep and disturbed dream production in this population.     

Maternal immune activation leads to activated inflammatory macrophages in offspring

Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation (MIA) models. More recently, permanent changes in T cell cytokine responses were reported in children with autism and in offspring of MIA mice; however, the cytokine responses of other immune cell populations have not been thoroughly investigated in these MIA models. Similar to changes in T cell function, we hypothesized that following MIA, offspring will have long-term changes in macrophage function. To test this theory, we utilized the poly (I:C) MIA mouse model in C57BL/6J mice and examined macrophage cytokine production in adult offspring. Pregnant dams were given either a single injection of 20 mg/kg polyinosinic–polycytidylic acid, poly (I:C), or saline delivered intraperitoneally on gestational day 12.5. When offspring of poly (I:C) treated dams reached 10 weeks of age, femurs were collected and bone marrow-derived macrophages were generated. Cytokine production was measured in bone marrow-derived macrophages incubated for 24 h in either growth media alone, LPS, IL-4/LPS, or IFN-γ/LPS. Following stimulation with LPS alone, or the combination of IFN-γ/LPS, macrophages from offspring of poly (I:C) treated dams produced higher levels of IL-12(p40) (p < 0.04) suggesting an increased M1 polarization. In addition, even without the presence of a polarizing cytokine or LPS stimulus, macrophages from offspring of poly (I:C) treated dams exhibited a higher production of CCL3 (p = 0.05). Moreover, CCL3 levels were further increased when stimulated with LPS, or polarized with either IL-4/LPS or IFN-γ/LPS (p < 0.05) suggesting a general increase in production of this chemokine. Collectively, these data suggest that MIA can produce lasting changes in macrophage function that are sustained into adulthood.     

Low intensity microwave radiation induced oxidative stress,inflammatory response and DNA damage in rat brain

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n = 6 in each group): group I consisted of sham exposed (control) rats, group II–IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2 h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration.Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (p < 0.05). Whereas, levels of reduced glutathione (GSH) and superoxide dismutase (SOD) were found significantly decreased in microwave exposed groups (p < 0.05). A significant increase in levels of pro-inflammatory cytokines (IL-2, IL-6, TNF-α, and IFN-γ) was observed in microwave exposed animal (p < 0.05). Furthermore, significant DNA damage was also observed in microwave exposed groups as compared to their corresponding values in sham exposed group (p < 0.05). In conclusion, the present study suggests that low intensity microwave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure.     

Decreased IFN-γ and IL-12 levels in panic disorder

ObjectiveThe aim of this study is to assess the measures of proinflammatory cytokines in patients with panic disorder in comparison with the healthy subjects.MethodsTwenty three patients with panic disorder with or without agoraphobia and twenty three controls were recruited for the study. Plasma samples of all subjects were analyzed for TNF-α, IFN-γ, IL-1β, IL-2, IL-6, and IL-12 concentrations and NK-cell activity is measured in the peripheral blood samples of the subjects.ResultsWe found significant differences on the mean values of IL-12 (p = 0.01) and IFN-γ (p = 0.02) between the panic disorder and control groups. In a logistic regression analysis, IFN-γ values were significant statistical predictors of the presence of panic disorder (B = ? 0.07, SE = 0.03, p = 0.04).ConclusionThe most important implication of our results is to suggest a relation between panic disorder and low levels of IFN-γ, compatible with the results of the animal studies showing that IFN-γ plays a role by acting to regulate the development of anxiety-like behaviors.     

Prenatal maternal anxiety predicts reduced adaptive immunity in infants

Prenatal anxiety has been linked with altered immune function in offspring in animal studies, but the relevance for human health is unknown. We examined prenatal maternal anxiety as a predictor of adaptive immunity in infants at 2 and 6 months of age as part of a prospective longitudinal study. The humoral immune response to hepatitis B vaccine was assessed at 2 months (n = 80) and 6 months (n = 76) of age. Prenatal anxiety predicted lower hepatitis B antibody titers at 6 months of age independent of obstetric and socio-demographic covariates; the effects were limited to those infants who had not completed the 3-dose vaccine series (for transformed titer values, r = −.36, p < .05). Cell-mediated immune responses at 2 (n = 56) and 6 (n = 54) months of age were examined by ELISpot assays for interferon(IFN)-γ, interleukin(IL)-2, and IL-4 responder cell frequencies to three antigens: hepatitis B surface antigen, tetanus toxoid, and phytohaemagglutinin (PHA). Prenatal maternal anxiety was associated with reduced IFN-γ and increased IL-4 responder cell frequencies at 6 months of age, independent of obstetric and socio-demographic covariates. No effect of prenatal anxiety was found on adaptive immunity at 2 months of age. The findings provide the first demonstration in humans that prenatal anxiety alters adaptive immunity in the infant.     

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.     

Byproducts of protein,lipid and DNA oxidative damage and antioxidant enzyme activities in seizure

PurposeTo get more insight into molecular mechanisms underlying oxidative stress and its role in different types of seizure, in this study, oxidative byproducts of proteins, lipids and DNA, as well as, antioxidant enzyme activities were studied in adult patients with epilepsy.MethodsStudy was performed in 60 patients with epilepsy and in 25 healthy controls. Plasma protein reactive carbonyl derivatives (RCD) and protein thiol groups (P-SH), byproducts of oxidative protein damage, as well as antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Urinary 8-epi-prostaglandin F_2α (8-epi-PGF_2α) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), representative byproducts of lipid and DNA oxidative damage, respectively, were determined by enzyme immunoassay.ResultsRCD levels were significantly increased (p = 0.001), while P-SH content was decreased in patients with first seizure (p = 0.052) compared to controls, independently of the seizure type. Urinary 8-epi-PGF_2α and 8-OHdG were significantly increased in patients with epilepsy (p = 0.001 and p = 0.001). Rise in 8-epi-PGF_2α was more pronounced in patients with generalized tonic–clonic seizure (GTCS) compared to those with partial seizure (PS). Both SOD and GPX activity were significantly increased in epileptic patients compared to controls (p = 0.001 and p = 0.001), but only SOD activity was significantly higher in patients with GTCS than in those with PS.ConclusionsData on enhanced protein, lipid and DNA oxidation, together with upregulated antioxidant enzyme activities, confirm the existence of systemic oxidative stress in patients with epilepsy. It might be speculated that post-translational modification to existing functional proteins, particularly alterations to ion channels, might be at least partially responsible for acute early changes in neuronal networks.     

Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: Relationship with interleukin-6

Cross-sectional studies have found that an elevated ratio of arachidonic acid to omega-3 fatty acid is associated with depression, and controlled intervention studies have found that decreasing this ratio through administration of omega-3 fatty acids can alleviate depressive symptoms. Additionally, arachidonic acid and omega-3 fatty acids have opposing effects on inflammatory signaling. Exogenous administration of the inflammatory cytokine interferon-alpha (IFN-α) can trigger a depressive episode in a subset of vulnerable people, though associated risk factors remain poorly understood. Using a within-subject prospective design of 138 subjects, we examined whether baseline long-chain omega-3 (docosahexaenoic acid – DHA; eicosapentaenoic acid – EPA) and omega-6 (arachidonic acid – AA; di-homo-gamma-linolenic acid – DGLA) fatty acid status was associated with depression vulnerability in hepatitis C patients treated with IFN-α. Based on the literature, we had specific a priori interest in the AA/EPA + DHA ratio. Lower baseline DHA predicted depression incidence (p = 0.04), as did elevated DGLA (p = 0.02) and an elevated AA/EPA + DHA ratio (p = 0.007). The AA/EPA + DHA ratio predicted depression even when controlling for other critical variables such as sleep quality and race. A higher AA/EPA + DHA ratio was positively associated with both increasing Montgomery-Asperg Depression Rating Scores over time (F = 4.0; p < 0.05) as well as interleukin-6 levels (F = 107.4; p < 0.05) but not C-reactive protein. Importantly, omega-3 and omega-6 fatty acid status was not associated with sustained viral response to IFN-α treatment. These prospective data support the role of fatty acid status in depression vulnerability and indicate a potential role for omega-3 fatty acids in the prevention of inflammation-induced depression.     

Interferon-α acutely impairs whole-brain functional connectivity network architecture – A preliminary study

Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated.Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4 h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency.IFN-α was associated with a significant reduction in global network connectivity (node degree) (p = 0.033) and efficiency (p = 0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p > 0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire.IFN-α rapidly induced a profound shift in whole brain network structure, impairing global functional connectivity and the efficiency of parallel information exchange. Correlations with multiple indices of mood change support a role for global changes in brain functional connectivity architecture in coordinated behavioral responses to IFN-α.