Relationship between thyroid dysfunction and chronic kidney disease in community-dwelling older adults

Objectives

Renal function has been shown to be influenced by thyroid status in animal models and human studies. We aimed to assess the cross-sectional association between thyroid hormones and function with prevalence of chronic kidney diseases (CKD) in older adults.

Study design

1571 Blue Mountains Eye Study participants aged ≥60 years were analyzed in 2002–4. Thyroid dysfunction was defined using serum thyrotropin (TSH) screen, followed by serum free T4 (FT4) assessment. Baseline biochemistry including serum creatinine was measured. Moderate CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m².

Results

After adjusting for age, sex, receipt of pension payment, body mass index, smoking, hypertension and diabetes, persons with any thyroid dysfunction (hyperthyroidism or hypothyroidism) had 84% higher likelihood of having CKD, odds ratio, OR, 1.84 (95% confidence intervals, CI, 1.03–3.31). Participants in the highest versus lowest quartile (reference) of serum TSH and FT4 had a significantly greater odds of prevalent CKD, OR 1.82 (95% CI 1.22–2.71), and OR 1.64 (95% CI 1.10–2.45), respectively. Similarly, among participants not receiving treatment for their thyroid dysfunction (n = 1329), those in the third and fourth quartiles of serum TSH had significantly greater odds of having prevalent CKD, OR 1.83 (95% CI 1.15–2.92) and OR 1.96 (95% CI 1.23–3.13), respectively, P_trend = 0.001. Significant associations were not observed between type of thyroid dysfunction (hyperthyroidism or hypothyroidism) and prevalent CKD.

Conclusions

Increasing serum TSH was associated with a greater likelihood of prevalent CKD among older adults, independent of the influence of age, diabetes and hypertension.     

Associations of killer cell immunoglobulin like receptors with rheumatoid arthritis among North Indian population

Introduction

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors (KIR) expressed on surface of natural killer cells and CD28 null T-cells which are present in synovial membrane of RA. The present study has evaluated associations of KIR genes with RA among North Indian population from Uttar Pradesh.

Materials and methods

KIR genotypes were determined in 100 RA cases and 100 healthy controls using sequence specific primer polymerase chain reaction (PCR-SSP) method.

Results

RA cases positive for KIR3DS1 (OR = 1.17, p-value = 0.0498) and KIR2DS2 (OR = 2.21, p-value = 0.0120) showed risk associations. While, KIR2DL2 (OR = 0.40, p-value = 0.0026), KIR2DL3 (OR = 0.44, p-value = 0.0283) and KIR3DL1 (OR = 0.32, p-value = 0.0012) showed protective associations. Increased incidence of BB genotype (45%) was revealed among cases. Risk association was noted against telomeric region (OR = 2.12, p = 0.0120) genes for RA. Pair-wise linkage disequilibrium (LD) analysis among RA cases revealed KIR2DS1-2DL1 (D′ = 0.83, r² = 0.36), KIR3DL1-3DS1 (D′ = 1, r² = 0.58) and KIR2DL1-2DL2 (D′ = 1, r² = 0.61) to be in significant LD. KIR3DS1 and KIR2DS3 genes showed significant risk associations among RA patients with extra-articular manifestations (OR = 5.14, p-value = 0.0018; OR = 3.79, p-value = 0.0106) and in limited range of motion in affected joints (OR = 14.91, p-value = 0.0001; OR = 2.95, p-value = 0.0126).

Conclusion

The KIR activating genes have risk association with RA in the present study.     

SNP/haplotype associations of CCR2 and CCR5 genes with severity of chagasic cardiomyopathy

Background

Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology.

Methods and results

This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (p_ad = 0.02; OR = 1.91, 95% CI = 1.10–3.30), the T allele of the rs1800024 of CCR5 (p_ad = 0.01; OR = 1.95, 95% CI = 1.13–3.38), and the HHF^∗2 haplotype (p = 0.03, OR = 1.65, 95% CI = 1.03–2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (p_ad = 0.009, OR = 0.52, 95% CI = 0.32–0.85) with protection. In addition, the allele G of rs1800023 (p_ad = 0.043, OR = 0.61, 95% CI = 0.38–0.98), and the HHC haplotype (p = 0.004, OR = 0.62, 95% CI = 0.44–0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (p_ad = 0.009; OR = 1.90, 95% CI = 1.17–3.08); and the allele T of rs1800024 of CCR5 (p_ad = 0.005, OR = 1.98, 95% CI = 1.22–3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed.

Conclusions

These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.     

Immunotoxic and hepatotoxic effects of perfluoro-n-decanoic acid (PFDA) on female Harlan Sprague–Dawley rats and B6C3F1/N mice when administered by oral gavage for 28 days

Poly- and perfluoroalkyl substances (PFAS) are chemically and thermally stable, hydrophobic, lipophobic compounds used in stain repellants and water and oil surfactants, and associated with immunosuppression and peroxisome proliferator activity. Perfluoro-n-decanoic acid (PFDA, (CF₃(CF₂)₈COOH), a fluorinated straight chain fatty acid compound, is reported to induce thymic atrophy and reversible bone marrow hypocellularity in rodent models. The objective of this study was to assess potential immunotoxicity of PFDA, due to its structural similarity to other immunosuppressive PFASs. Female Harlan Sprague–Dawley rats were exposed to 0–2.0?mg PFDA/kg by oral gavage daily for 28?d. Female B₆C₃F₁/N mice were exposed once/week to 0–5.0?mg PFDA/kg by gavage for 4?weeks. Animals were evaluated for effects on immune cell populations in spleen and bone marrow, and innate, humoral-, and cell-mediated immunity. Mice were also evaluated for resistance to Influenza virus. Treatment-related hepatocyte necrosis and hepatomegaly were observed in rats treated with 0.5?mg PFDA/kg/d. In mice, hepatomegaly (26–89%) was observed following exposure to ≥0.625?mg PFDA/kg/week, while splenic atrophy (20%) was observed at 5.0?mg PFDA/kg/week. At 5.0?mg PFDA/kg/week, total spleen cells, and Ig?+?and NK?+?cells were decreased (17.6–27%). At ≥ 1.25?mg PFDA/kg/week the numbers of splenic CD3⁺, CD4⁺, CD8⁺, and Mac3⁺ cells were decreased (10.5–39%). No changes were observed in leukocyte subpopulations in PFDA-exposed rats. Phagocytosis by fixed-tissue macrophages was decreased in liver (specific activity, 24–39%) at ≥0.25?mg PFDA/kg/d in rats. PFDA-induced effects on humoral- and cell-mediated immunity, host resistance, and bone marrow progenitor cells were limited. These data suggest that exposure to PFDA may induce adverse effects in rat liver in a manner consistent with the PFAS class, and may also alter the balance of immune cell populations in lymphoid tissues in mice.     

Persisting changes in basolateral amygdala mRNAs after chronic ethanol consumption

Adolescent alcohol use is common and evidence suggests that early use may lead to an increased risk of later dependence. Persisting neuroadaptions in the amygdala as a result of chronic alcohol use have been associated with negative emotional states that may lead to increased alcohol intake. This study assessed the long-term impact of ethanol consumption on levels of several basolateral amygdala mRNAs in rats that consumed ethanol in adolescence or adulthood. Male Long-Evans rats were allowed restricted access to ethanol or water during adolescence (P28, n = 11, controls = 11) or adulthood (P80, n = 8, controls = 10) for 18 days. After a sixty day abstinent period, the brain was removed and sections containing the basolateral amygdala were taken. In situ hybridization was performed for GABA_A α₁, glutamic acid decarboxylase (GAD₆₇), corticotropin releasing factor (CRF), and N-methyl-d-aspartate (NMDA) NR2A mRNAs. A significant decrease was observed in GABA_A α₁, GAD₆₇, and CRF, but not NR2A, mRNAs in adult rats that consumed ethanol in comparison to controls. No significant changes were seen in adolescent consumers of ethanol for any of the probes tested. A separate analysis for each probe in the piriform cortex ascertained that the changes after ethanol consumption were specific to the basolateral amygdala. These results indicate that chronic ethanol consumption induces age-dependent alterations in basolateral amygdala neurochemistry.     

Association of the suppressor of cytokine signaling 1 (SOCS1) gene polymorphisms with acute coronary syndrome in Mexican patients

Recent studies provide evidence on the emerging role of the SOCS1 gene in the development and progression of atherosclerotic lesions. This gene encodes for the suppressor of the cytokine signaling-1 protein that interacts directly with the Janus kinases that are essential intracellular mediators of the immune cytokine action. The aim of this study was to test for associations between SOCS1 gene single nucleotide polymorphisms (SNPs) and the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. Four SNPs [-3969 C > T (rs243327), -1656 G > A (rs243330), -820 G > T (rs33977706) and +1125 G > C (rs33932899)] of SOCS1 gene were determined for TaqMan genotyping assays in a group of 447 patients with ACS and 622 healthy controls. Under heterozygous model, the -3969 C > T (rs243327) SNP was associated with increased risk of ACS (OR = 1.45, P_Het = 0.021). On the other hand, under co-dominant and heterozygous models, the -1656 G/A (rs243330) SNP was associated with increased risk of ACS (OR = 1.47, P_Co-dom = 0.038 and OR = 1.50, P_Het = 0.013, respectively). Moreover, under co-dominant, dominant, and heterozygous models, the -820 T/G (rs33977706) SNP was associated with increased risk of ACS (OR = 1.59, P_Co-dom = 0.03, OR = 1.48, P_Dom = 0.028 and OR = 1.61, P_Het = 0.01). Finally, under co-dominant and heterozygous models, the +1125 G/C (rs33932899) SNP was associated with increased risk of ACS (OR = 1.54, P_Co-dom = 0.006, OR = 1.58, P_Het = 0.012, respectively). Models were adjusted for gender, age, body index mass, dyslipidemia, alcohol consumption, and smoking. In summary, our data suggests that the four studied polymorphisms of the SOCS1 gene play an important role as susceptibility markers for developing ACS.     

Correlation of changes in pain intensity with synovial fluid adenosine triphosphate levels after treatment of patients with osteoarthritis of the knee with high-molecular-weight hyaluronic acid

We sought to determine whether a clinical association exists between osteoarthritis (OA)-associated knee pain and adenosine triphosphate (ATP) levels in synovial fluid (SF). A total of 28 patients with 28 primary OA knees were included. They routinely received intra-articular injection of high-molecular-weight hyaluronic acid (HA) once weekly for 5 weeks (treated group). Eight patients without knee pain who had undergone an operation for anterior or posterior cruciate ligament reconstruction 2 years ago were also examined (control group). SF and blood ATP concentrations, total amount of ATP, total SF volume, and Visual Analogue Scale (VAS) scores in all patients were measured and we compared pre-treatment values with those 1 week after the final treatment. We evaluated the correlation of change in total ATP (??ATP) and change in VAS score (??VAS), ??VAS and change in SF volume (??SF), and ATP concentration in SF and blood. In the treated group, SF ATP concentration, total amount of ATP, SF volume, and VAS score were all significantly lower post-treatment than pre-treatment (p = 0.0005, 0.0003, 0.0022, and < 0.0001, respectively). In treated group, ??VAS was significantly associated with ??ATP (r = 0.56, p = 0.0032), ??SF was significantly associated with ??VAS (r = 0.78, p < 0.0001), and total amount of SF ATP and SF volume at pre-treatment were significantly higher than the control group (p < 0.0001, p < 0.0001) We demonstrated an association between SF ATP level changes and OA knee pain, which should facilitate a further understanding of OA pain mechanisms.     

Novel 8-(furan-2-yl)-3-benzyl thiazolo [5,4-e][1,2,4] triazolo [1,5-c] pyrimidine-2(3H)-thione as selective adenosine A2A receptor antagonist

Adenosine A_2A receptor (A_2AR) antagonists have emerged as potential drug candidates to alleviate progression and symptoms of Parkinson's disease (PD), and reduce the dopaminergic side effects. The synthesis of novel compound 8-(furan-2-yl)-3-benzyl thiazolo [5,4-e][1,2,4] triazolo [1,5-c] pyrimidine-2-(3H)-thione (BTTP) was carried out to evaluate the potential of BTTP as A_2AR antagonist using SCH58261, a standard A_2AR antagonist. The strong interaction of BTTP with A_2AR (ΔG = −12.46 kcal/mol and K_i = 0.6 nM) in silico analysis was confirmed by radioligand receptor binding studies showing high affinity (K_i = 0.004 nM) and selectivity with A_2AR (A_2A/A₁ = 1155-fold). The effect of CGS21680 (selective A_2AR agonist) induced cAMP concentration (0.1 pmol/ml) in HEK293 cells was antagonized with BTTP (0.065 pmol/ml) and SCH58261 (0.075 pmol/ml). Furthermore, BTTP pre-treated (5, 10 and 20 mg/kg) haloperidol-induced mice demonstrated significant attenuation in catalepsy and akinesia. BTTP induced elevation in the striatal dopamine concentration (2.90 μM/mg of tissue) was comparable to SCH58261 (2.92 μM/mg of tissue) at the dose of 10 mg/kg. The results firmly articulate that BTTP possesses potential A_2AR antagonist activity and can be further explored for the treatment of PD.     

Association study between single nucleotide polymorphisms in promoter region of AVPR1A and Korean autism spectrum disorders

To determine the association between arginine vasopressin receptor 1A gene (AVPR1A) and autism spectrum disorders (ASDs), we examined 3 single nucleotide polymorphisms (SNPs), namely, rs7294536, rs3759292, and rs10877969, in the promoter region of AVPR1A by using a family-based association test (FBAT) in 151 Korean trios. Our results demonstrated a statistically significant association between autism and SNPs (additive model: rs7294536, χ² = 9.328, df = 2, P = 0.002; rs10877969, χ² = 11.529, df = 2, P < 0.001) as well as between autism and haplotype analysis (additive model: χ² = 14.122, df = 3, P = 0.003). In addition, we found that ADI-R scores calculated by using a diagnostic algorithm for failure to develop peer relationships (A2) were higher in subjects having the AA genotype than in subjects having the AG and GG genotypes of rs7294536. Thus, our study provides evidence for a possible association between these SNPs and the phenotype of ASDs.     

Pregnancy decreases GABAergic inhibition of the hypothalamic paraventricular nucleus

Depressor responses to peripheral or central infusion of Angiotensin II type 1 (AT₁) receptor antagonists (AT₁X) are greater in pregnant (P) compared to nonpregnant (NP) animals. AT₁ and ionotropic excitatory amino acid (EAA) receptors contribute to pressor responses to GABA_A receptor blockade with bicuculline (Bic) in the paraventricular nucleus (PVN) of male rats. Therefore, we hypothesized that GABAergic inhibition is decreased and AT₁ receptors play a greater excitatory role in the PVN of P versus NP rats. Unilateral microinjection of Bic was performed before (Bic₁), after AT₁X (Bic₂), and after AT₁X + EAA blockade (kynurenate, Kyn) (Bic₃) in the PVN. Increases in mean arterial pressure (MAP: NP = 20 ± 2; P = 12 ± 2 mmHg), heart rate (HR: NP = 57 ± 6; P = 19 ± 6 beats/min) and renal sympathetic nerve activity (RSNA: NP = 70 ± 9; P = 33 ± 7%) due to Bic (Bic₁) were attenuated in P rats. Responses to AT₁X and Kyn alone were insignificant in both groups. In NP rats, AT₁X attenuated (+ 12 ± 4 mmHg), and AT₁X + Kyn further decreased the pressor response to Bic in the PVN (+ 6 ± 2 mmHg). In P rats AT₁X reduced the pressor response to Bic (+ 5 ± 1 mm Hg), and Kyn had no additional effect (+ 3 ± 1 mmHg). Effects of PVN Bic to alter the autospectra of RSNA were suppressed by prior AT₁X and Kyn in both groups. Thus, tonic GABAergic inhibition is decreased and the contribution of AT₁ receptors in the PVN may be greater in P rats.     

Regulatory role of 1, 25-dihydroxyvitamin D3 and vitamin D receptor gene variants on intracellular granzyme A expression in pulmonary tuberculosis

Vitamin D receptor (VDR) genotypes have been shown to be associated with differential susceptibility or resistance to tuberculosis. The influence of FokI, BsmI, ApaI and TaqI variants of VDR gene on 1, 25(OH)₂ D₃ modulated granzyme A expression of cytotoxic lymphocytes induced by culture filtrate antigen (CFA) of Mycobacterium tuberculosis was studied in 40 pulmonary tuberculosis (PTB) patients and 49 normal healthy subjects (NHS) by flow cytometry. In both the study groups, addition of 1, 25(OH)₂ D₃ (10^− 7M) significantly reduced the percentage of granzyme A positive cells in both unstimulated (NHS, p < 0.0001; PTB, p = 0.02) and stimulated culture conditions (CFA, NHS, p < 0.0001; PTB, p = 0.0001) which correlated positively with the IFN-γ levels (unstimulated, p = 0.01; CFA stimulated, p = 0.004) in NHS. The ApaI aa genotype and bbaaTT extended genotype were associated with a significantly decreased percentage of granzyme A positive cells in NHS (p < 0.05). Our results suggest that 1, 25(OH)₂ D₃ suppresses granzyme A probably by down-regulating Th1 cytokine response. Moreover, the VDR gene variants might regulate cytotoxic T-cell response via 1, 25(OH)₂ D₃ mediated suppression of granzyme A expression in tuberculosis.     

Septin 7 immunoexpression in papillary thyroid carcinoma: A preliminary study

Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers. The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this disease is present due to the resemblance of nuclear properties of the classical type (CVPTC). However, making use of ancillary molecular markers in the diagnosis of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC (FVPTC(e), n = 25), and CVPTC (n = 15), and benign hyperfunctioning thyroid nodules (HypN, n = 15) were used in this study. Nuclear, cytoplasmic, and overall (total) SEPT7 protein expression levels were determined by using immunohistochemistry. Nuclear, cytoplasmic, and overall SEPT7 expressions (p = 0.02, p = 0.001, p = 0.002, respectively) were significantly lower in FVPTC(e) tissues when compared to HypN. In CVPTC group, nuclear expression was significantly lower (p = 0.004) while overall and cytoplasmic expressions were not changed (p > 0.05). In HypN group, highest nuclear (mean = 2.73), cytoplasmic (mean = 2.86), and overall (mean = 2.86) expression scores were detected. Significantly lower SEPT7 expression in all expressional categories in FVPTC(e) group may be a sign of different molecular signature in this type of tissue.     

Major role of GABAA-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons

Using slice patch clamp recording, we examined the effects of general anesthetic propofol (2,6-diisoprophlphenol) on dual modality of GABA_A inhibition in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs): conventional quantal synaptic transmission (IPSCs, I_phasic) and persistent tonic form of inhibitory current (I_tonic). Propofol (10 μM) enhanced I_tonic as shown by an inward shift in I_holding (16.46 ± 2.93 pA, n = 27) and RMS increase (from 3.37 ± 0.21 pA to 4.68 ± 0.33 pA, n = 27) in SON MNCs. Propofol also prolonged the decay time of IPSCs with decreased IPSCs frequency but no significant changes in IPSCs amplitude. Overall, propofol (1–10 μM) caused much smaller increase in mean I_phasic than mean I_tonic at all tested concentrations. In consistent with the enhancement of GABA_A currents, propofol attenuated ongoing firing activities of SON MNCs by ∼65% of control. Selective inhibition of I_phasic by a GABA_A antagonist, gabazine (1 μM), failed to block the propofol suppression of the firing activities, while inhibition of I_tonic and I_phasic by bicuculline (20 μM) efficiently blocked the propofol-induced neurodepression in SON MNCs. Taken together, our results showed that propofol facilitated I_tonic with marginal increase in mean I_phasic, and this could be a mechanism reducing the intrinsic SON MNCs excitability during propofol anesthesia.     

Anatibant,a selective non-peptide bradykinin B2 receptor antagonist,reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury

Bradykinin, the main metabolite of the kallikrein-kinin system and one of the first mediators released during inflammation, is well known to increase the permeability of the blood brain barrier (BBB) by activation of kinin B₂ receptors and hence promote brain edema formation following traumatic brain injury (TBI). Anatibant^® (LF 16-0687), a selective non-peptide bradykinin B₂ receptor antagonist, reduces brain edema after experimental TBI, however, so far no data are available if Anatibant^® reduces also the sequels of brain edema formation, i.e. morphological brain damage. Therefore, we investigated the effect of Anatibant (3.0 mg/kg b.w.) on intracranial pressure (ICP) and contusion volume after experimental TBI. Male C57/Bl6 mice (25–28 g) were subjected to Controlled Cortical Impact trauma (CCI). Anatibant^® was administrated as a subcutaneous bolus 15 min and 8 h after TBI. ICP was measured 3, 6, and 10 h after injury and contusion volume was quantified 24 h after trauma. Our data demonstrate a significant reduction of ICP (16.6 ± 1.67 mmHg vs. 24.40 ± 3.58 mmHg; n = 6; p = 0.002) and of contusion volume 24 h after trauma (28.28 ± 5.18 mm³ vs. 35.0 ± 3.32 mm³n = 7; p = 0.003) in treated mice. Therefore we conclude, that inhibition of bradykinin B₂ receptors seems to be a promising treatment option, and might therefore be investigated in clinical trails for the treatment of TBI.     

Metabolic transitions at menopause: In post-menopausal women the increase in serum uric acid correlates with abdominal adiposity as assessed by DXA

Objectives

The present study aimed to investigate any associations between parameters of body fat mass distribution and levels of serum uric acid (sUA), a well-documented cardiovascular risk factor, among non-obese women ranging from pre- to post-menopausal status.

Methods

In this cross-sectional population-based study we assessed body fat distribution by dual-energy-X-ray absorptiometry (DXA), and sUA levels in 101 pre- and 134 post-menopausal non-obese apparently healthy women.

Results

Multivariate stepwise regression analysis revealed that sUA was independently associated to the indicators of overall fatness, i.e. body mass index (β = 0.339, p < 0.001) and DXA-assessed total and percentage body fat (β = 0.366, p < 0.001 and β = 0.412, p < 0.001, respectively), only among post-menopausal women. Within this sample subset, trunk (i.e. central) fat mass emerged as a strong predictor of sUA (β = 0.408, p < 0.001), after taking the potential confounders (including body mass index) into account.

Conclusion

Central fat accumulation was found to be independently associated with higher sUA levels among non-obese women in post- but not among those in pre-menopause.     

Relationships between serum uric acid,adiponectin and arterial stiffness in postmenopausal women

Objectives

Cardiovascular disease (CVD) is a leading cause of death in postmenopausal women. Elevated serum uric acid levels, hypoadiponectinemia and arterial stiffness are strongly associated with cardiovascular diseases. We investigated the relationships among uric acid, adiponectin and arterial stiffness in postmenopausal women.

Study design

9555 subjects who had the routine health check-ups, 841 postmenopausal women aged 50 years or older who had not had a menstrual period for more than 12 consecutive months were included in this study.

Main outcome measures

BMI, WC, and serum concentrations of uric acid, adiponectin, glucose, lipids (total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol) were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness.

Results

The subjects were stratified into three groups according to uric acid values. PWV values gradually increased and adiponectin level decreased with uric acid tertiles. Serum uric acid levels in postmenopausal women correlated significantly with age, BMI, WC, TG, HDL-C, insulin, HOMA-IR, adiponectin and PWV. Multiple regression analysis showed that WC (β = 0.141, P < 0.01), HOMA (β = 0.137, P < 0.01), adiponectin (β = −0.104, P < 0.01), and PWV (β = 0.129, P < 0.01) were independently correlated with uric acid levels. In multiple logistic regression analysis after adjusting for risk factors, uric acid was a significant contributor to increased PWV.

Conclusions

These findings indicate that serum uric acid is independently associated with adiponectin and arterial stiffness in postmenopausal women.     

Dehydroepiandrosterone in nails of infants: a potential biomarker of intrauterine responses to maternal stress

Easily accessible biomarkers for fetal stress biology are lacking. We here explore whether quantification of major fetal steroids, dehydroepiandrosterone (DHEA) or DHEA sulfate (DHEAS), with liquid chromatography/tandem mass spectrometry in infant nails is a tool to assess fetal stress biology in response to maternal stressful life events during pregnancy. Sufficient nail (≥1 mg) was available from 80 infants (93% of those providing samples). The concentration of DHEA, but not DHEAS, was increased in infants of mothers with stressful life events during pregnancy (DHEA: F_1,41 = 6.105, P = 0.018; DHEAS: F_1,77 = 0.767, P = 0.384). DHEA concentrations were not related to maternal stress before pregnancy (F_1,41 = 0.010, P = 0.922). Infant nail DHEA may be a fetal biological correlate of intrauterine exposure to maternal stress. The method promises the first non-invasive retrospective biomarker for intrauterine stress biology, opening new ways for research and clinical applications in fetal medicine, endocrinology, obstetrics, gynecology, and for understanding the developmental origins of health and disease.     

Estradiol reduces anxiety- and depression-like behavior of aged female mice

Beneficial effects of the ovarian steroid, 17β-estradiol (E₂), for affective behavior have been reported in young individuals, but less is known about the effects of E₂ among older individuals, and the capacity of older individuals to respond to E₂ following its decline. In the present study, the effects of acute E₂ administration to aged mice for anxiety-like and depression-like behaviors were investigated. Intact female C57BL/6 mice (N = 18) that were approximately 24 months old were administered vehicle (sesame oil, n = 9) or E₂ (10 μg, n = 9) subcutaneously 1 h prior to behavioral testing. Mice were tested for anxiety-like behavior (open field, elevated plus maze, mirror chamber, light-dark transition task, Vogel conflict task) and depression-like behavior (forced swim task). To assess the role of general motor behavior and coordination in these aged mice, performance in an activity monitor and rotarod task, and total entries made in tasks (open field, elevated plus maze, light-dark transition task) were determined. Mice administered E₂, compared to vehicle, demonstrated anti-anxiety behavior in the open field, mirror chamber, and light-dark transition task, and anti-depressive-like behavior in the forced swim task. E₂ also tended to have anti-anxiety effects in the elevated plus maze and Vogel task compared to vehicle administration, but these effects did not reach statistical significance. E₂ did not alter motor behavior and/or coordination in the activity monitor, open field, or rotarod tasks. Thus, an acute E₂ regimen produced specific anti-anxiety and anti-depressant effects, independent of effects on motor behavior, when administered to aged female C57BL/6 mice.     

Augmented peripheral chemoreflex in patients with heart failure and inspiratory muscle weakness

We hypothesized that heart failure patients with inspiratory muscle weakness (IMW) present greater peripheral chemoreflex responsiveness and augmented exercise ventilatory oscillation compared to patients with preserved inspiratory muscle strength. We studied 19 heart failure patients: 9 with IMW (maximal inspiratory pressure [PImax] < 70% of predicted) and 10 with preserved inspiratory muscle strength. Inspiratory muscle strength was measured via pressure transducer. Peripheral chemoreflex was evaluated by the single-breath CO₂ test. Exercise ventilatory oscillation was determined as the ratio between amplitude and mean of each oscillation during incremental exercise. Patients with IMW had greater peripheral chemoreflex response (0.11 ± 0.03 l min⁻¹ Torr⁻¹) than those with preserved inspiratory muscle strength (0.07 ± 0.03 l min⁻¹ Torr⁻¹, p = 0.02). Moreover, there was a significant and inverse correlation between PImax and peripheral chemoreflex response (r = −0.57, p = 0.01). Likewise, there was a significant and inverse correlation between PImax and ventilatory oscillations (r = −0.46, p = 0.04). Our findings indicate that IMW is linked to increased peripheral chemoreflex and augmented exercise ventilatory oscillation in patients with chronic heart failure.     

The concentrations of serum,plasma and platelet BDNF are all increased by treadmill VO2max performance in healthy college men

The most current human-based studies in which brain-derived neurotrophic factor (BDNF) levels in the peripheral blood system are analyzed use it as an indicator that represents BDNF levels in the CNS. However, whether circulating BDNF (serum and plasma) is positively or inversely associated with cardiorespiratory fitness levels (VO_2max) is still controversial, and no study has done to investigate exercise effects on the concentration of BDNF stored in circulating platelets which, in fact, store a large amount of circulating BDNF. Thus, the purpose of this study was to determine the relation between VO_2max and all circulating BDNF levels (serum, plasma and platelets) in college male students (N = 18; age, 19 ± 1 years; height, 173.22 ± 7.65 cm; weight, 78.25 ± 14.25 kg; body fat percent, 13.82 ± 5.68%). Dual X-ray energy absorptiometry whole body scan was used to measure their body composition. After the overnight fast, all participants were performed VO_2max test, and their blood was collected at rest and immediately after the exercise. Our data resulted in significant increases in platelet counts and serum, plasma and platelet BDNF levels immediately after the exercise (p < 0.01). VO_2max had a significant negative correlation with serum BDNF, plasma BDNF and platelet BDNF at rest (p < 0.05) but a significant positive correlation with serum, plasma BDNF, and platelet BDNF immediately after the exercise (p < 0.01). However, our data show no correlation between VO_2max and platelet count both at rest and immediately after the exercise. In conclusion, this is the first study showing that basal BDNF levels are inversely correlated with cardiorespiratory fitness levels but that the inverse correlations turn into positive correlations with all circulating BDNF levels immediately after the exercise. Moreover, it is the first time to provide evidence that platelet BDNF levels are also positively affected by the exercise. However, future studies will be needed to investigate what tissues provide BDNF into the circulating system and to elucidate the role of circulating BDNF.