Evaluation of cytokines,oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia – A controlled cross-sectional study

ObjectivesPrevious studies measuring serum levels of biomarkers of inflammation/oxidative stress and neurotrophins levels in fibromyalgia (FM) have rendered inconsistent results. In the present study, our aim was to explore the levels of interleukins, oxidative stress markers and brain-derived neurotrophic factor (BDNF) in patients with FM in relation to depression and severity of disease.MethodsIn a prospective controlled cross-sectional study, serum concentrations of IL-6, IL-8, IL-10, TNF-α, thiobarbituric acid reactive substances (TBARS), protein carbonyl and BDNF were measured in 69 FM patients and 61 healthy controls (all women). In the FM group, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS) were applied. Mann Whitney’s and Spearman correlation tests were used for statistical analysis.ResultsThe FM patients demonstrated a significant impact of the disease on quality of life (FIQ 70.2 ± 17.8) and most of them had depression at some level (82.6% and 87.0% as assessed by BDI and HDRS, respectively). Most biomarkers (IL-6, IL-8, TNF-α, TBARS and protein carbonyl) and BDNF did not differ significantly between patients and controls, but the IL-10 levels were higher in FM patients (adjusted p = 0.041). Among FM patients, there was no correlation of HDRS, FIQ, and BDI scores with any biomarker tested here.ConclusionWe observed no significant differences in biomarkers between FM patients and controls, except for higher levels of IL-10 (an anti-inflammatory cytokine) in patients. The levels of biomarkers were not correlated with parameters of disease and depression severity.     

Monocyte chemoattractant protein-1-2518 G/A polymorphism,plasma levels,and premature stable coronary artery disease

Background We examined the -2518G/A polymorphism of the MCP-1 gene, its plasma levels, and premature stable CAD in a Chinese population. Methods The study comprised 132 patients with premature stable CAD (cases) and 153 controls. Genotypes were determined by ligase detection reaction-polymerase chain reaction sequencing and grouping. Plasma MCP-1 level was detected with enzyme-linked immunosorbent assay. Results No differences were found between genotype distribution and allele frequencies of MCP-1 gene -2518 G/A polymorphism (AA:18.1%; AG:51.5%; GG:30.3% in cases; AA:16.3%; AG:52.9%; GG:30.7% in controls; P = 0.918). The G allele prevalence was 0.561 in cases and 0.572 in controls (P = 0.786). No significant difference was found in plasma MCP-1 level between cases and controls [(47.50 ± 26.65) vs. (41.05 ± 15.71) pg/ml, P = 0.272)] or among the 3 genotypes [AA, (43.49 ± 10.50) pg/ml; AG, (46.09 ± 25.08) pg/ml; GG, (40.03 ± 18.13) pg/ml; P = 0.381]. Logistic regression analysis confirmed the lack of association between MCP-1-2518 G/A single nucleotide polymorphism and premature stable CAD after adjustment for confounding parameters. Conclusions The MCP-1-2518 G/A single nucleotide polymorphism does not affect plasma levels of MCP-1 or susceptibility to premature stable CAD in a Chinese population.     

The Association of Decreased Serum Gdnf Level with Hyperglycemia and Depression in Type 2 Diabetes Mellitus

Objective: Comorbidity of diabetes and depression is a critical problem. Decreased glial-derived neurotrophic factor (GDNF) has been demonstrated in depression, but no evidence of a relationship between GDNF and diabetes has been shown. The present studies were designed to investigate the relationship between GDNF and metabolism.Methods: In Study 1, we performed a case-control study in which subjects with type 2 diabetes mellitus (T2DM), prediabetes (p-DM), and normal glucose tolerance (NGT) were included. In Study 2, we performed a cross-sectional study in 296 patients having pre-existing diabetes in whom the levels of serum GDNF, blood glucose, blood lipids, blood pressure, body mass index, scores from the Patient Health Questionnaire (PHQ-9), the EuroQol-5 scale, and the diabetes distress scale were measured, as well as single-nucleotide polymorphisms of GDNF including rs884344, rs3812047, and rs2075680.Results: In Study 1, serum GDNF concentration was significantly lower in the T2DM group than in the NGT group (NGT: 11.706 ± 3.918 pg/mL; p-DM: 10.736 ± 3.722 pg/mL; type 2 diabetes mellitus &lsqb;T2DM group]: 9.884 ± 2.804 pg/mL, P = .008). In Study 2, significantly decreased serum GDNF levels were observed in subjects with poor glycemic control or depression (glycated hemoglobin &lsqb;HbA1c] <7.0% without depression: 11.524 ± 2.903 pg/mL; HbA1c ≥7.0% without depression: 10.625 ± 2.577 pg/mL; HbA1c <7.0% with depression: 10.355 ± 2.432 pg/mL; HbA1c ≥7.0% with depression: 8.824 ± 2.102 pg/mL, P = .008). Double-factor variance analysis showed that glycemic control and depression were independent factors for the GDNF level. Moreover, the serum GDNF level was significantly inversely associated with the fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1c, and PHQ-9 score.Conclusion: Glycemic dysregulation was an independent factor for the GDNF level. These findings suggest that GDNF level might be involved in the pathophysiology of T2DM and depression through various pathways.Abbreviations: BP = blood pressure; CHO = cholesterol; DDS = diabetes distress scale; DM = diabetes mellitus; EQ-5D = the health-related dimensions of the EuroQol-5 scale; FPG = fasting plasma glucose; GDNF = glial-derived neurotrophic factor; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NGT = normal glucose tolerance; PHQ-9 = Patient Health Questionnaire; p-DM = prediabetes; PPG = postprandial plasma glucose; SNP = single-nucleotide polymorphism; T2DM = type 2 diabetes mellitus; TG = triglyceride     

Decreased levels of alpha‐synuclein in cerebrospinal fluid of patients with clinically isolated syndrome and multiple sclerosis

Cerebrospinal fluid (CSF) α‐synuclein (ASYN) levels are emerging as a possible biomarker in a number of neurodegenerative conditions; however, there has been little study of such levels in demyelinating conditions with neurodegeneration such as multiple sclerosis (MS). In this study, we aimed to assess CSF ASYN levels in MS spectrum [clinically isolated syndrome (CIS) and MS] patients and compare them to those obtained in control subjects with benign neurological conditions (BNC). We used a recently developed, ultra‐sensitive sandwich enzyme‐linked immunosorbent assay to measure and compare CSF ASYN levels in three categories of subjects: BNC (n = 38), CIS (n = 36) and MS [Relapsing Remitting (RRMS, n = 22) and Primary Progressive (PPMS, n = 15)]. We also performed secondary analyses, including relationship of CSF ASYN levels to aging, gender, presence of CSF oligoclonal bands (OB) and gadolinium (Gd)‐enhancing demyelinating lesions on T1‐weighted MRIs. CSF ASYN levels were found to be significantly lower in the CIS (78.2 ± 7.5 pg/mL), RRMS (76.8 ± 5.1 pg/mL), and PPMS (76.3 ± 6.7 pg/mL) groups compared to the BNC (125.7 ± 13.6 pg/mL) group. Secondary analyses did not reveal additional correlations. Our results suggest that in a cohort of CIS and MS patients, CSF ASYN levels are decreased, thus providing another possible link between MS and neurodegeneration. Future studies will need to be performed to confirm and extend these findings, to lead to a fuller understanding of the possible biological link between ASYN and MS.

     

Enhanced proinflammatory response of mononuclear cells to in vitro LPS-challenge in patients with ventricular fibrillation in the setting of acute myocardial infarction

Aims. Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death. A potential role of intrinsic, subclinical inflammatory states in patients suffering from ischemia-related VF has not been investigated yet. The aim of the present study was (i) to examine serum levels of proinflammatory markers in VF survivors and (ii) to evaluate basal and lipopolysaccharide (LPS)-stimulated interleukin-8-mRNA (IL-8-mRNA) levels in patients with and without VF complicating AMI. Methods. Twenty-five patients with a history of VF during AMI and a control group of 25 AMI patients without VF were included. Blood samples were taken remote from AMI with a mean of 590 days. Circulating serum levels of IL-8, IL-6, soluble E-selectin (sE-selectin), tissue factor activity (TFA), tissue inhibitor of matrix-metalloproteinase-1 (TIMP-1) and matrix-metalloproteinase-9 (MMP-9) were measured. Mononuclear cells were isolated by density gradient centrifugation. The cells were stimulated with lipopolysaccharide (LPS) from Escherichia coli (700 ng/mL). IL-8-mRNA levels in mononuclear cells were determined by a colorimetric mRNA quantification assay. Results. Serum levels (median; range) of IL-8 (VF: 2.24 pg/mL; <0.10–19.3 pg/mL versus controls: 0.10 pg/mL; <0.10–7.7 pg/mL; p = 0.014), IL-6 (VF: 0.68 pg/mL; <0.05–2.9 pg/mL versus controls: 0.23 pg/mL; <0.05–1.8 pg/mL; p = 0.042) and TIMP-1 (VF: 229 ng/mL; 144–348 ng/mL versus controls: 186 ng/mL; 126–263 ng/mL; p = 0.014) were significantly higher among patients with VF as compared to controls. Baseline IL-8-mRNA concentrations of blood mononuclear cells were significantly higher among patients with VF (257 amol/mL; 52–2672 amol/mL) as compared to patients without VF (37 amol/mL, 3.2–770 amol/mL; p < 0.01). IL-8-mRNA levels after LPS-challenge were significantly higher among patients with VF (3503 amol/mL; 215–13,573 amol/mL) than in patients without VF (1003 amol/mL; 208–3386 amol/mL; p < 0.01). Conclusions. Circulating IL-8, IL-6, and TIMP-1 concentrations as well as IL-8-mRNA expression in mononuclear cells at baseline and after LPS-challenge are increased among patients with a history of VF in the setting of AMI as compared to patients without VF. These findings indicate an enhanced inflammatory response to a proinflammatory stimulus in VF survivors. The magnitude of this increased acute phase reactants may indicate a novel pathway of arrhythmogenesis in patients with AMI.     

Effects of lifestyle physical activity on perceived symptoms and physical function in adults with fibromyalgia: results of a randomized trial

Introduction  

Although exercise is therapeutic for adults with fibromyalgia (FM), its symptoms often create obstacles that discourage exercise. We evaluated the effects of accumulating at least 30 minutes of self-selected lifestyle physical activity (LPA) on perceived physical function, pain, fatigue, body mass index, depression, tenderness, and the six-minute walk test in adults with FM.     

Association of plasma leptin,pro‐inflammatory adipokines and cancer‐related fatigue in early‐stage breast cancer patients: A prospective cohort study

Cancer‐related fatigue (CRF) is subjective and has wide inter‐individual variability. Given that leptin is commonly associated with fatigue syndrome, its use as a potential biomarker for CRF is being investigated. The primary objective of this study was to evaluate the association between leptin and CRF in early‐stage breast cancer patients receiving chemotherapy. In a prospective cohort study, patients completed assessments at baseline (T1), during chemotherapy (T2) and after chemotherapy (T3). Levels of plasma leptin and adipokines were measured using a Luminex bead‐immunoassay and CRF was measured using the Multi‐Dimensional Fatigue Symptom Inventory‐Short Form (MFSI‐SF). Data were analysed longitudinally using a generalised estimating equation incorporating clinically relevant parameters and pro‐inflammatory adipokines. The analysis included 136 patients (mean age ± SD = 51.5 ± 8.8 years; 69.1% receiving anthracycline‐based chemotherapy). More patients experienced CRF at T3 (23.8%) than at T2 (13.8%) compared to baseline. An increase was observed in the median plasma leptin level at T2, followed by a decrease at T3 (T1: 4.07 ng/mL, T2: 4.95 ng/mL and T3: 3.96 ng/mL). In the multivariate model, the change in leptin levels over time was significantly associated with the total MFSI‐SF score (β = ?0.15, P = 0.003) after adjusting for the tumour necrosis factor‐α (TNF‐α) level, anxiety, depression, insomnia, age, menopausal status and type of chemotherapy. This is the first study to report leptin as a biomarker that predicts the onset of CRF over time. Future studies are required to validate the findings.     

ST2 blockade mitigates peritoneal fibrosis induced by TGF‐β and high glucose

Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 in PF using patient samples along with mouse and cell‐based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure (P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate‐induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human peritoneal mesothelial cells (HPMCs), transforming growth factor‐β treatment increased ST2, fibronectin, β‐galactosidase and Snail protein levels and decreased E‐cadherin level. Anti‐ST2 antibody administration reversed the up‐regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose (100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.     

B-type natriuretic peptide in children with atrial or ventricular septal defect: a cardiac catheterization study

In this study, we investigated the relationship between plasma B-type natriuretic peptide (BNP) levels and hemodynamics from cardiac catheterization in pediatric patients with atrial or ventricular septal defect. A total of 59 patients were studied including 80% of patients had Qp/Qs > 1.5 and 25% of patients had pulmonary hypertension. The mean BNP value and BNP z-score were 10.9?±?11.2 pg/mL and ?0.28?±?1.7 (?2.85 to 3.29), respectively. There was a statistically significant linear correlation between BNP value and the size of defects (r?=?0.303, p?=?0.002) and a trend toward to positive correlation between BNP value and Qp/Qs ratio (r?=?0.183, p?=?0.166) among all patients. To identify patients with a Qp/Qs ratio >1.5, the sensitivity and specificity were 28%, 100% in all patients at a plasma BNP cut-off point of 15 pg/mL. We concluded that a BNP > 15 pg/mL would help identify patients who need further intervention.     

The relationship between chronotype,sleep disturbance,severity of fibromyalgia,and quality of life in patients with fibromyalgia

ABSTRACT

Patients with fibromyalgia (FM) report high levels of sleep disturbance and chronic diffuse musculoskeletal pain. These patients experience diminished quality of life (QoL) due to pain and other comorbidities. Chronotype preferences have been suggested as a potential factor connecting increased severity of FM, sleep disturbances, and poor overall QoL. The present study is the first study examining the possible association between chronotype preferences, sleep disturbance, severity of FM, and QoL in patients with FM.

One hundred drug-free patients diagnosed with FM participated in this cross-sectional study. Of them, 79 (79%) were females and 21 (21%) were males. The mean age was 41.65 ± 9.17 years (range: 21–62 years). The severity of FM symptoms, chronotype preferences, and QoL was evaluated using the Fibromyalgia Impact Questionnaire (FIQ), Morningness-Eveningness Questionnaire (MEQ), and World Health Organization Questionnaire on Quality of Life: Short Form (WHOQOL-BREF). The participants’ anxiety/depressive symptoms and sleep problems were assessed using the Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI).

The participants were classified according to their MEQ scores as evening type (score: 16–41), neither type (score: 42–58), and morning type (score: 59–86). It was found that there were significant differences in the FIQ score between the three groups (p < .001). It was determined that the total PSQI score was significantly higher in the evening type than the other two types (p < .05). It was found that there were significant differences in the general health, physical health, psychological, and environmental domain scores of the WHOQOL-BREF between the three groups (p < .05). It was detected that there were significant correlations between MEQ scores, WHOQOL-BREF subscale scores, FIQ scores, HADS-A and HADS-D scores, and PSQI scores. According to hierarchical regression analysis, eveningness preference explained an additional 21.9% of the variation in FM severity, thereby causing a statistically significant change in R-squared.

Our results indicated that eveningness preference was directly related to increased FM symptom severity and poorer QoL. Based on these findings, neglecting to take chronotype preference into account may not result in optimal response to standard treatment for some patients with FM.     

IL2-330G polymorphic allele is associated with decreased risk of Helicobacter pylori infection in adulthood

We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B-511C → T, IL1B-31 T → C, IL1RN allele 2, IL2-330 T → G, TNFA-307 G → A, TLR2Arg677Trp, TLR2Arg753Gln, TLR4Asp299Gly, and TLR5^392STOP polymorphisms were determined in 541 blood donors. IL2-330 T → G allele carriers had a decreased H. pylori infection risk (OR = 0.63, 95% CI = 0.43–0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-γ and IL-10/TGF-β levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori-positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-γ = 18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10 = 6.99 vs. 14.17 pg/mL, TGF-β = 45.88 vs. 93.44 pg/mL) (p < 10⁻³ for all). In conclusion, in the context of H. pylori infection, IL2-330 T → G polymorphism is functional and is associated with decreased risk of infection in adults.     

Clinical symptoms in fibromyalgia are better associated to lipid peroxidation levels in blood mononuclear cells rather than in plasma

Background

We examined lipid peroxidation (LPO) in blood mononuclear cells (BMCs) and plasma, as a marker of oxidative damage, and its association to clinical symptoms in Fibromyalgia (FM) patients.

Methods

We conducted a case–control and correlational study comparing 65 patients and 45 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Beck Depression Inventory (BDI). Oxidative stress was determined by measuring LPO in BMCs and plasma.

Results

We found increased LPO levels in BMCs and plasma from FM patients as compared to normal control (P<0.001). A significant correlation between LPO in BMCs and clinical parameters was observed (r = 0.584, P<0.001 for VAS; r = 0.823, P<0.001 for FIQ total score; and r = 0.875, P<0.01 for depression in the BDI). We also found a positive correlation between LPO in plasma and clinical symptoms (r = 0.452, P<0.001 for VAS; r = 0.578, P<0.001 for FIQ total score; and r = 0.579, P<0.001 for depression in the BDI). Partial correlation analysis controlling for age and BMI, and sex, showed that both LPO in cells and plasma were independently associated to clinical symptoms. However, LPO in cells, but not LPO in plasma, was independently associated to clinical symptoms when controlling for depression (BDI scores).

Discussion

The results of this study suggest a role for oxidative stress in the pathophysiology of fibromyalgia and that LPO in BMCs rather than LPO in plasma is better associated to clinical symptoms in FM.     

肝癌疼痛与血浆VEGF、BDNF、FGF-2水平的相关性研究

目的:研究肝癌疼痛与血浆血管内皮生长因子(VEGF)、脑源性神经营养因子(BDNF)、纤维细胞生长因子-2(FGF-2)水平的相关性。方法:选择我院2018年10月～2019年7月收治的30例肝癌疼痛患者作为研究对象,依据疼痛程度分为4例轻度疼痛组、19例中度疼痛组、7例重度疼痛组,同期纳入30例肝癌无痛患者和30例健康对照组,比较各组血浆VEGF、BDNF和FGF-2水平,并分析肝癌疼痛患者血浆VEGF、BDNF和FGF-2水平和数字评分法(NRS)评分的相关性。结果:肝癌疼痛组血浆VEGF、BDNF、FGF-2水平显著高于肝癌无痛组及对照组(P0.05)。重度疼痛组血浆VEGF、BDNF、FGF-2水平显著高于中度疼痛组及轻度疼痛组(P0.05)。治疗后,肝癌疼痛患者血浆VEGF、BDNF、FGF-2水平显著低于治疗前(P0.05)。肝癌疼痛患者血浆VEGF、BDNF、FGF-2水平和NRS评分呈显著正相关(r值分别为0.619、0.571、0.563,P值均0.001)。结论:肝癌疼痛患者血浆VEGF、BDNF和FGF-2水平较肝癌无痛者明显上升,且和疼痛程度显著相关。     

Association of plasma exosomes with severity of organ failure and mortality in patients with sepsis

Current sepsis biomarkers may be helpful in determining organ failure and evaluating patient clinical course; however, direct molecular biomarkers to predict subsequent organ failure have not yet been discovered. Exosomes, a small population of extracellular vesicles, play an important role in the inflammatory response, coagulation process and cardiac dysfunction in sepsis. Nonetheless, the association of plasma exosome with severity and mortality of sepsis is not well known. Therefore, the overall levels of plasma exosome in sepsis patients were assessed and whether exosome levels were associated with organ failure and mortality was evaluated in the present study. Plasma level of exosomes was measured by ELISA. Among 220 patients with sepsis, 145 (66%) patients were diagnosed with septic shock. A trend of increased exosome levels in control, sepsis and septic shock groups was observed (204 µg/mL vs 525 µg/mL vs 802 µg/mL, P < 0.001). A positive linear relationship was observed between overall exosome levels and Sequential Organ Failure Assessment (SOFA) score in the study cohorts (r value = 0.47). When patients were divided into two groups according to best cut‐off level, a statistical difference in 28‐ and 90‐day mortality between patients with high and low plasma exosomes was observed. Elevated levels of plasma exosomes were associated with severity of organ failure and predictive of mortality in critically ill patients with sepsis.     

Increased plasma macrophage inflammatory protein (MIP)-1α and MIP-1β levels in type 1 Gaucher disease

Pancytopenia, hepatosplenomegaly and skeletal complications are hallmarks of Gaucher disease. Monitoring of the outcome of therapy on skeletal status of Gaucher patients is problematic since currently available imaging techniques are expensive and not widely accessible. The availability of a blood test that relates to skeletal manifestations would be very valuable. We here report that macrophage inflammatory protein (MIP)-1α and MIP-1β, both implicated in skeletal complications in multiple myeloma (MM), are significantly elevated in plasma of Gaucher patients. Plasma MIP-1α of patients (median 78 pg/ml, range 21–550 pg/ml, n = 48) is elevated (normal median 9 pg/ml, range 0–208 pg/ml, n = 39). Plasma MIP-1β of patients (median 201 pg/ml, range 59–647 pg/ml, n = 49) is even more pronouncedly increased (normal median 17 pg/ml, range 1–41 pg/ml, n = 39; one outlier: 122 pg/ml). The increase in plasma MIP-1β levels of Gaucher patients is associated with skeletal disease. The plasma levels of both chemokines decrease upon effective therapy. Lack of reduction of plasma MIP-1β below 85 pg/ml during 5 years of therapy was observed in patients with ongoing skeletal disease. In conclusion, MIP-1α and MIP-1β are elevated in plasma of Gaucher patients and remaining high levels of MIP-1β during therapy seem associated with ongoing skeletal disease.     

Repeated hyperthermia exposure increases circulating Brain Derived Neurotrophic Factor levels which is associated with improved quality of life,and reduced anxiety: A randomized controlled trial

ContextHyperthermia is known to be beneficial to patients affected by various diseases. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. Little is known about BDNF changes after repeated exposure to hyperthermia.ObjectiveTo investigate the effect of a repeated hyperthermia exposure programme (HTC) on serum BDNF in healthy humans.Design, setting, participantsRandomized, single-blind, controlled trial in healthy humans conducted at Sechenov University Physiology Laboratory between December 2016 and November 2018. The treatment period was 10 weeks. Researchers analysing serum BDNF and questionnaires data were blinded to participants allocation.ParticipantsWere 34 healthy male (age 20.2 ± 1.6 years).InterventionRepeated Hyperthermia exposure programme, HTC, versus Light Intermittent Exercise, LIE, programme as control (10 weeks).Main outcome measureChange in BDNF from baseline to final visit three days after treatment completion.Results25 participants were analyzed. One participant withdrew before signing the informed consent and 8 participants (n = 3 in HTC and n = 5 in LIE) could not undertake the first assessment and were excluded. Mean change in BDNF was higher in HTC group vs LIE after both time points (after 12 and after 24 sessions). After 24 sessions BDNF was 30170 (SD 5268) pg/ml in HTC group a value that was significantly higher than 24104 (SD 2876) pg/ml measured in LIE group. BDNF concentrations were significantly higher than baseline values in HTC group only, 30170 (SD 5268) vs 26710 (SD 5437) pg/ml.ConclusionA 10-week programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating BDNF compared to a programme consisting of intermittent light intensity exercise.     

Utility of Adrenocorticotropic Hormone in Assessing the Response to Transsphenoidal Surgery for Cushing’s Disease

ObjectivesTo compare adrenocorticotrophic hormone (ACTH) and cortisol dynamics in subjects with Cushing’s disease (CD) following transsphenoidal surgery (TSS) and to determine the value of early postoperative ACTH levels in predicting subsequent hypocortisolemia.MethodsFollowing TSS for CD, serum cortisol and plasma ACTH were measured every 6 hours in the absence of empiric glucocorticoid coverage.ResultsA total of 26 subjects (25 female) underwent 28 operations. Hypocortisolemia was achieved in 21 (81%) subjects after the initial TSS. Repeat TSS was performed in 2 subjects, resulting in hypocortisolemia in 1. Subjects who achieved hypocortisolemia had significantly lower ACTH levels by 19 hours postoperatively (P = .007). Plasma ACTH fell to < 30 pg/mL in 86% and < 20 pg/mL in 82% of subjects who subsequently achieved hypocorti- solemia. Plasma ACTH declined to < 30 pg/mL by a mean of 10 hours and to < 20 pg/mL by 13 hours prior to hypo- cortisolemia. Follow-up data were available on 25 patients for a median of 23 months. Three subjects who achieved initial surgical remission had disease recurrence at 19, 24, and 36 months; all of these subjects had a postoperative nadir serum cortisol levels < 3 μg/dL and plasma ACTH < 20 pg/mL.ConclusionFollowing TSS for CD, plasma ACTH declined prior to achievement of hypocortisolemia in most subjects. In the majority, the ACTH level reached a nadir of < 20 pg/mL. Low early postoperative ACTH levels predict early hypocortisolemia but may not accurately predict long-term remission. (Endocr Pract. 2014;20:1159-1164)     

The −112G > A polymorphism of the secretoglobin 3A2 (<Emphasis Type="Italic">SCGB3A2</Emphasis>) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves’ disease in subsets of patients with elevated levels of immunoglobulin E

The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility locus to several autoimmune and inflammatory diseases, including asthma and Graves’ disease (GD). Recently, association between the marker rs1368408 (−112G > A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls. The marker rs1368408 was studied using a TaqMan allele discrimination assay. Serum levels of UGRP1 and immunoglobulin E (IgE) were assessed using enzyme-linked immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2 and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 × 10⁻⁵) was shown. Both affected and non-affected carriers of the higher risk genotype A/A had significantly decreased levels of serum UGRP1 compared to the subjects homozygous for G/G (93 ± 37 pg/ml vs. 132 ± 45 pg/ml, P = 0.0011 for GD patients; 77 ± 28 pg/ml vs. 119 ± 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were significantly higher in non-affected subjects homozygous for A/A compared to control individuals homozygous for G/G (153 ± 46 IU/ml vs. 122 ± 40 IU/ml, P = 0.0095). Our data suggest that the carriage of the SCGB3A2 −112A/A variant increases the risk for GD in subsets of patients with elevated levels of IgE, a hallmark of allergic asthma. Therefore, the SCGB3A2 −112G > A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and GD on chromosome 5q31-33.     

Raised Interleukin‐6 Levels in Obese Patients

Objective: Obese patients demonstrate a variety of biochemical, metabolic, and pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor‐α and interleukin‐6 (IL‐6) may have a direct effect on glucose and lipid metabolism. Hypoxemia in itself induces release of IL‐6. The aim of this study was to examine the relationship between IL‐6 levels in healthy volunteers (control group) and three different groups of obese patients: patients without obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of <93%). Research Methods and Procedures: We measured serum IL‐6 levels in 25 obese patients (body mass index of >35 kg/m²) and 12 healthy women. Results: The results demonstrate statistically significant differences in serum IL‐6 levels between the control group (1.28 ± 0.85 pg/mL) and obese patients without OSAS (7.69 ± 5.06 pg/mL, p < 0.05) and with OSAS (5.58 ± 0.37 pg/mL, p < 0.0005). In the patients with OHS, IL‐6 concentrations were highest (43.13 ± 24.27 pg/mL). Discussion: We conclude that serum IL‐6 is increased in obese patients. The highest IL‐6 levels were found in the patients with OHS.     

Coenzyme Q10 supplementation alleviates pain in pregabalin-treated fibromyalgia patients via reducing brain activity and mitochondrial dysfunction

Although coenzyme Q10 (CoQ10) supplementation has shown to reduce pain levels in chronic pain, the effects of CoQ10 supplementation on pain, anxiety, brain activity, mitochondrial oxidative stress, antioxidants, and inflammation in pregabalin-treated fibromyalgia (FM) patients have not clearly elucidated. We hypothesised that CoQ10 supplementation reduced pain better than pregabalin alone via reducing brain activity, mitochondrial oxidative stress, inflammation, and increasing antioxidant levels in pregabalin-treated FM patients. A double-blind randomised placebo-controlled trial was conducted. Eleven FM patients were enrolled with 2 weeks wash-out then randomly allocated to 2 treatment groups; pregabalin with CoQ10 or pregabalin with placebo for 40 d. Then, patients in CoQ10 group were switched to placebo, and patients in placebo group were switched to CoQ10 for another 40 d. Pain pressure threshold (PPT), FM questionnaire, anxiety, and pain score were examined. Peripheral blood mononuclear cells (PBMCs) were isolated to investigate mitochondrial oxidative stress and inflammation at day 0, 40, and 80. The level of antioxidants and brain positron emission tomography (PET) scan were also determined at these time points. Pregabalin alone reduced pain and anxiety via decreasing brain activity compared with their baseline. However, it did not affect mitochondrial oxidative stress and inflammation. Supplementation with CoQ10 effectively reduced greater pain, anxiety and brain activity, mitochondrial oxidative stress, and inflammation. CoQ10 also increased a reduced glutathione levels and superoxide dismutase (SOD) levels in FM patients. These findings provide new evidence that CoQ10 supplementation provides further benefit for relieving pain sensation in pregabalin-treated FM patients, possibly via improving mitochondrial function, reducing inflammation, and decreasing brain activity.