Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity

ObjectiveInsulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity.Design and methodsWe studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic–hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79 ± 2.01 mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33 ± 1.66 mg/kg fat-free mass/min).ResultsWe observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11 ± 603.10 vs 4141.91 ± 755.37 pg/mL, p = 0.001). Serum BDNF was positively related to insulin sensitivity (r = 0.43, p = 0.003). This correlation remained significant after adjustment for other estimated parameters.ConclusionsSerum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

ObjectivesWe investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).Design and methodsTwo groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m²) and obese subjects (BMI ≥ 30 kg/m²) (20 each).ResultsPlasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p < 0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA_IR). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p < 0.001).ConclusionVisfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA_IR which may reflect its effects on hepatic insulin sensitivity.     

Serum soluble Fas levels in patients with autoimmune rheumatic diseases

Objective:The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases.Patients and methods:We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n = 32), rheumatoid arthritis (RA, n = 28), Sjögren's syndrome (SS, n = 20) systemic sclerosis (SSc, n = 21), polymyositis/dermatomyositis (PM/DM, n = 15). Patients with osteoarthritis (OA, n = 20) and healthy volunteers (n = 20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals) + 2 SD were considered as elevated.Results:The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found.Conclusions:The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.     

Gingival crevicular fluid PGE2, IL-1beta, t-PA, PAI-2 levels in type 2 diabetes and relationship with periodontal disease

ObjectivesTo evaluate if type 2 diabetes mellitus increase gingival crevicular fluid (GCF) levels of prostaglandin E₂ (PGE₂), interleukin-1beta (IL-1ß), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-2 (PAI-2).Design and methodsSeventeen type 2 diabetic patients with periodontal disease (DM), 17 otherwise healthy periodontally diseased patients (PD) and 17 systemically and periodontally healthy control subjects (H) were enrolled. Clinical periodontal measurements were recorded at six sites/tooth. GCF samples were analyzed by ELISA. Data were tested by statistical tests.ResultsDM group revealed lower IL-1ß levels than PD group (p < 0.01). PGE₂, t-PA and PAI-2 levels were similar in DM and PD groups (p > 0.05). PGE₂, t-PA levels were higher in DM and PD groups than H group (p < 0.05). PAI-2 level was higher in DM group than H group (p < 0.05). GCF total amount of PGE₂ in DM group exhibited significant correlations with all clinical periodontal measurements (p < 0.05).ConclusionType 2 diabetes in this study seems not to increase GCF levels of the evaluated inflammatory mediators.     

BDNF Val66Met polymorphism is associated with unstable angina

BackgroundBrain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of coronary artery disease (CAD). The human BDNF Val66Met polymorphism has been shown to be associated with altered susceptibility to neuropsychiatric disorders. However it is unknown whether this polymorphism plays a role in cardiovascular disease.MethodsGenotyping of BDNF Val66Met polymorphism was carried out in 513 controls, 628 unstable angina pectoris (UAP) and 276 stable angina pectoris (SAP) patients. The plasma concentrations of BDNF and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA. The general clinical data in patients and controls were obtained.ResultsThere was a significant association between genotype and allele frequency of the BDNF Val66Met polymorphism and UAP (all P < 0.05). Multivariate logistic regression analysis revealed that the BDNF_Met/Met genotype had a protective effect on the occurrence of UAP after controlling for known risk factors of CAD (OR 0.53, P = 0.005). Subjects with BDNF_Met/Met genotype also had decreased plasma hsCRP levels compared with the Val carriers (P < 0.01).ConclusionThe BDNF_Met/Met genotype has a protective effect on the occurrence of UAP, which might in part be due to the decreased plasma hsCRP level in BDNF_Met/Met carriers. To our knowledge, this is the first study that demonstrates the link between BDNF Val66Met polymorphism and CAD.     

Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population

BackgroundGABA_A receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also.MethodsWe investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABA_A receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods.ResultsThe GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P = 0.018), CC (P = 0.0001) genotype and for C allele (P = 0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P = 0.012), TT (P = 0.778) genotype and for variant T allele (P = 0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism.ConclusionOverall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABA_A receptor in epilepsy susceptibility in north Indian population.     

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease

ObjectivesWe sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) – an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis – are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD).Design and methodsSerum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls.ResultsFGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130 pg/mL) than in controls (median: 210 pg/mL, P < 0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r = ? 0.25, P < 0.05) but not after adjustment for potential confounders (β = ? 0.18; t = 1.78, P = 0.08).ConclusionsThis pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.     

Correlations of creatine and six related pyrimidine metabolites and diabetic nephropathy in Chinese type 2 diabetic patients

ObjectivesThe assessment of the clinical significance of creatine, cytosine, cytidine, uridine, thymine, thymidine, and 2′-deoxyuridine concentrations in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between pyrimidine metabolites and disease.Design and methodsThe study group consisted of 119 subjects, which were divided to three groups: control (n = 31), type 2 diabetes without nephropathy (DM, n = 23), and with nephropathy (DN, n = 65). Levels of related metabolites were measured in plasma of all participants.ResultsThere is a significant increase in levels of cytosine (P < 0.001), cytidine (P < 0.001), and thymidine (P = 0.016) with DN compared to DM. The levels of uridine, thymine, 2′-deoxyuridine, and creatine did not change.ConclusionsThe levels of cytosine, cytidine, and thymidine may be useful for monitoring the progression of DM and evaluating the treatment.     

Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer

ContextPatients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient’s symptom burden.ObjectivesTo examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.MethodsA retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.ResultsThe median age was 63 years (range 24–79), and 62% were men (n = 48). Most patients had gastrointestinal (n = 33, 43%) or thoracic (n = 21, 27%) malignancies and were Caucasian (n = 46, 60%). The median random cortisol level was 19.1 μg/dL (Q1–Q3, 13.4–23.8 [normal, 4.3–22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P = 0.032) and symptoms including pain (0.50, P < 0.001), fatigue (0.29, P = 0.012), nausea (0.34, P = 0.003), depression (0.24, P = 0.032), and anxiety (0.25, P = 0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n = 28) was 20.6 μg/dL (Q1–Q3, 16.6–25.4) and significantly correlated with pain (0.55, P = 0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥30 mg/day had a mean random cortisol level of 20.6 μg/dL (P = 0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (?0.52, P = 0.001).ConclusionIn patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.     

Usefulness of glycated albumin as an indicator of glycemic control status in patients with hemolytic anemia

BackgroundIn patients with hemolytic anemia (HA), glycated hemoglobin (HbA_1C) presents lower values in relation to glycemia because the lifespan of erythrocytes is shortened, whereas glycated albumin (GA) is not affected. In the present study, we examined the usefulness of GA as an indicator of glycemic control status in patients with HA.MethodsWe enrolled 21 patients with HA. A total of 202 patients with type 2 diabetes mellitus (T2DM) without complications were used as controls.ResultsWe identified a significant correlation between GA and HbA_1C in the patients with HA. However, in a comparison between the patients with HA and those with T2DM, the regression line showed a leftward shift in the former group. There was a significant positive correlation between hemoglobin (Hb) and HbA_1C in the patients with HA (R = 0.541, p = 0.025), although there was no significant correlation between Hb and GA. There was an inverse correlation between Hb levels and GA/HbA_1C ratio (R = ? 0.710, p = 0.001). The measured HbA_1C levels were lower than the HbA_1C levels estimated from mean plasma glucose levels, whereas the GA/3 levels were close to the estimated HbA_1C levels.ConclusionsGA is a useful indicator of glycemic control status in patients with HA.     

Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

Self-compassion in patients with persistent musculoskeletal pain: relationship of self-compassion to adjustment to persistent pain

ContextSelf-compassion entails qualities such as kindness and understanding toward oneself in difficult circumstances and may influence adjustment to persistent pain. Self-compassion may be a particularly influential factor in pain adjustment for obese individuals who suffer from persistent pain, as they often experience heightened levels of pain and lower levels of psychological functioning.ObjectivesThe purpose of the present study was to examine the relationship of self-compassion to pain, psychological functioning, pain coping, and disability among patients who have persistent musculoskeletal pain and who are obese.MethodsEighty-eight obese patients with persistent pain completed a paper-and-pencil self-report assessment measure before or after their appointment with their anesthesiologist.ResultsHierarchical linear regression analyses demonstrated that even after controlling for important demographic variables, self-compassion was a significant predictor of negative affect (β = ?0.48, P < 0.001), positive affect (β = 0.29, P = 0.01), pain catastrophizing (β = ?0.32, P = 0.003), and pain disability (β = ?0.24, P < 0.05).ConclusionThe results of this study indicate that self-compassion may be important in explaining the variability in pain adjustment among patients who have persistent musculoskeletal pain and are obese.     

Influence of diabetes on homocysteine-lowering therapy in chronic hemodialysis patients

IntroductionThe effect of homocysteine (Hcy)-lowering therapy may be different in hemodialysis (HD) patients with and without diabetes mellitus (DM).MethodsStable HD patients with uremia were administered folic acid and vitamin B for 3 months. The impact of treatment was compared in patients with and without DM.ResultsA total of 61 patients (31 men and 30 women) aged 56 ± 13 y completed the study. Among these, 44 patients (72%) did not have DM and 17 (28%) had DM. At baseline, total Hcy and high-sensitivity C-reactive protein (hsCRP) levels were similar. After treatment, the levels of total Hcy and hsCRP were significantly decreased in the nondiabetic group (total Hcy level decreased from 33.63 ± 14.13 μmol/l to 18.94 ± 8.46 μmol/l, p < 0.001; hsCRP level decreased from 0.58 mg/dl [range, 0.21–1.05 mg/dl] to 0.22 mg/dl [range, 0.11–0.53 mg/dl], p < 0.001) but not in the diabetic group (total Hcy level decreased from 34.97 ± 17.12 μmol/l to 29.53 ± 11.36 μmol/l, p = 0.057; hsCRP level decreased from 0.80 mg/dl [range, 0.24–1.47 mg/dl] to 0.49 mg/dl [range, 0.45–0.98 mg/dl], p = 0.28). Serial monitoring of total Hcy level showed a more sustained effect of therapy on patients without DM.ConclusionFolic acid and vitamin B administration significantly lower total Hcy and hsCRP levels in HD patients without DM but not in those with DM.     

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BackgroundLRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians.MethodsTo evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD.ResultsThe prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively).ConclusionOur data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.     

A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese

BackgroundAdrenomedullin, a vasodilatory peptide, facilitates the differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese population.MethodsFour SNPs were genotyped in 1391 subjects without dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included impaired fasting glucose, impaired glucose tolerance, and diabetes according to the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia.ResultsIn stepwise logistic regression, the SNP rs11042725 was a significant independent predictor of the development of dysglycemia (OR = 1.31, P = 0.012), together with baseline age (P < 0.001), plasma triglycerides (P < 0.001), body mass index (P = 0.004), 2-h glucose after oral glucose tolerance test (P < 0.001), homeostasis model assessment of insulin resistance index (P = 0.045), and follow-up duration (P = 0.009). The association was more significant in women (P = 0.002) and in subjects without regular exercise (P = 0.001).ConclusionsOur study suggests a potential role of genetic variants in the ADM gene in the development of dysglycemia in our local Chinese population.     

The HindIII polymorphism in the lipoprotein lipase gene predicts type 2 diabetes risk among Chinese adults

ObjectiveWe aimed to investigate the polymorphism HindIII of the lipoprotein lipase (LPL) gene to explore whether it had a potential role in susceptibility to type 2 diabetes mellitus (T2DM) among Han Chinese, and whether this effect was influenced by regulating LPL or other risk factors.MethodsOverall, 654 Han Chinese adults were selected from a community-based cross-sectional study using a stratified cluster random sampling. Genotyping was performed using the PCR–RFLP technique, and the metabolic variables were measured using standard methods.ResultsIndividuals with the HindIII H?/H? genotype tended to have higher pre-heparin LPL (PrLPL) and lower triglyceride levels but an unexpected higher prevalence of T2DM compared with the H+/H+ genotype carriers. The association between the H?/H? genotype and T2DM risk remained unchanged across all subgroups of lipids/glucose-related RF. In a recessive model, the H?/H? genotype conferred a 2.12-fold increased risk [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.18–8.27] for T2DM after controlling for age and sex, and increased further after additionally adjusting for traditional RFs, and PrLPL (OR = 4.45; 95% CI = 1.51–13.07).ConclusionsThis study indicated that Chinese adults with the LPL gene HindIII H?/H? genotype had a significantly increased risk of T2DM, even if they had favorable lipid profiles.     

The alarm secretory leukocyte protease inhibitor increases with progressive metabolic dysfunction

BackgroundSecretory leukocyte protease inhibitor (SLPI) is an alarm antiprotease secreted by neutrophils and mucous membranes that potently inhibits the inflammatory cascade; however, the role of SLPI in human disease remains largely unknown. We hypothesized that SLPI is related to chronic low-grade inflammatory diseases, such as metabolic syndrome (MS) or type-2 diabetes (T2DM).MethodsWe examined associations between circulating SLPI (ELISA) and quantitative traits of MS (ATPIII criteria) in 261 Caucasian men with various degrees of metabolic dysfunction. Subjects had neither MS nor T2DM (n = 140), either diagnosis (n = 44) or both diagnoses (n = 77).ResultsCirculating SLPI increased with progressive metabolic dysfunction, with a mean increase of 4.4 ng/ml (95% IC 2.4 to 6.3 ng/ml; p < 0.001) for each unit increase in the criteria used to define MS. Circulating SLPI showed independent associations with uric acid [β = 5.1 (95% CI 3.4 to 6.7), p < 0.00001], serum lipids, pulse pressure and inflammatory markers.ConclusionsCirculating SLPI increases with progressive metabolic dysfunction and is related to metabolic and inflammatory parameters in men.     

Lymphocytic enzymes and lipid peroxidation in patients with metabolic syndrome

ObjectivesMetabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as _γ-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS.Design and methodsThe adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n = 38) and healthy volunteers (n = 41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses.ResultsADA (p < 0.05), DPP-IV and AChE (p < 0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p = 0.0002; r = 0.5945), TBARS levels and ADA (p = 0.0021; r = 0.5172) and DPP-IV activities (p = 0.0022; r = 0.5010).ConclusionsOur findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.