Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception

ObjectivesProinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.Design and methodsSerum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.ResultsIL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p = 0.032, Mann–Whitney test) and presented a trend for lower levels of pain (p = 0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR = 4.074, p = 0.010, Pearson χ² test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p = 0.053, Pearson χ² test).ConclusionsOur results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.     

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

Pro-inflammatory cytokine profile of critically ill septic patients following therapeutic plasma exchange

Severe sepsis involves a generalized inflammatory response, mediated by a number of various cytokines and factors. Plasma exchange (PE) has been proposed as a therapeutic approach to improve survival of patients with severe sepsis and septic shock. The theory is that removing harmful excessive endogenous inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe sepsis, twelve patients received PE plus conventional sepsis treatment. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were assayed before and after each session of PE.ResultsThere were no significant changes in cytokine plasma levels after each PE session compared to pre-procedure levels. Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before the 2nd and 3rd PE sessions were lower than baseline levels (p = 0.011 and p = 0.012, respectively). All patients tolerated PE therapy well without any adverse effects or homodynamic instability. The results of this study showed that PE does not have a direct and rapid effect on plasma level of TNF-α, IL-1β and IL-6.     

Increased serum levels of microvesicles in nonvalvular atrial fibrillation determinated by ELISA using a specific monoclonal antibody AD-1

BackgroundMicrovesicles are involved in different pathological processes such as inflammation, coagulation and tumor progression. We intended to establish an immunoaffinity capture method for detecting microvesicles and bioactive effectors carried on them using a specific homemade monoclonal antibody AD-1. By this method we investigated the association of inflammation with platelet activation in patients with nonvalvular atrial fibrillation (NVAF).MethodsA case–control study of 90 Chinese subjects selected in 3 groups: control, paroxysmal AF, and persistent AF. After capturing the microvesicles of serum using a specific monoclonal antibody AD-1, the amounts of LAP, IL-1β and P-selectin loaded on these microvesicles were quantified by either enzyme activity assay (LAP) or ELISA respectively.ResultsCompared with normal controls, the patients with persistent AF showed significantly increased serum levels of microvesicles (P < 0.001), microvesicle-bound IL-1 β (P = 0.019) and microvesicle-bound P-selectin (P = 0.001). The latter two were significantly correlated with each other (r² = 0.371, r = 0.616, P < 0.001). The microvesicle-bound IL-1β (β = 0.570, P < 0.001) and body weight (β = 0.427, P = 0.002) were as independent predictors of platelet activation.ConclusionsThe method was easy and reproducible. Inflammation may be involved in the activation of platelets in NVAF.     

The relationship between the levels of gonadotropic hormones and OPG,leptin, TGF-β1 and TGF-β2 in Chinese adult women

BackgroundThe relationship between the levels of gonadotropic hormones and bone metabolism-related cytokines in Chinese women is unclear. We investigated the relationship between FSH and LH and OPG, leptin, TGF-β1, and TGF-β2 in Chinese women.MethodsA cross-sectional study of 694 Chinese women, aged 20 to 82 y was conducted. Levels of serum FSH, LH, OPG, leptin, TGF-β1, and TGF-β2 were determined.ResultsIn premenopausal females, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels seemly showed no correlation with the cytokine levels. In perimenopausal females, serum FSH and LH levels showed significant positive correlation with osteoprotegerin (OPG) and transforming growth factor-β2 (TGF-β2) levels (r = 0.286 to 0.405, all P = 0.000), whereas they showed negative correlation with TGF-β1 levels (r = ? 0.413 and ? 0.354, all P = 0.000). In postmenopausal females, FSH and LH levels showed positive correlation with OPG levels (r = 0.247 and 0.241, all P = 0.000), negative correlation with leptin and TGF-β1 levels (r = ? 0.234 to ? 0.319, all P = 0.000), and no correlation with TGF-β2 levels. Multiple linear regression stepwise analysis revealed the following results. In premenopausal females, 2.0% and 1.5% of the changes in LH could be explained by OPG and leptin, respectively, while 1.9% of the changes in OPG could be explained by LH. In perimenopausal females, the determinants of OPG and TGF-β1 on FSH were 10.9% and 17.0%, respectively, and the determinants of OPG, TGF-β1 and TGF-β2 on LH were 4.5%, 4.9% and 16.4%, respectively. The determinants of FSH and LH on OPG were 14.5% and 2.5%, respectively. The determinant of FSH on TGF-β1 was 4.5%, while the determinant of LH on TGF-β2 was 16.4%. In postmenopausal females, the determinants of leptin and OPG on FSH were 10.2% and 2.8%, respectively, and the determinants of OPG and TGF-β1 on LH were 5.8% and 2.3%, respectively. The determinant of FSH on OPG, leptin and TGF-β1 were 6.1%, 3.4% and 9.2%.ConclusionsThese results indicate that age-related gonadotropic hormone levels are associated with changes in OPG, TGF-β1, TGF-β2 and leptin, and change with menopausal status.     

Dysregulation of TH type cytokines in the patients of Parthenium induced contact dermatitis

BackgroundParthenium contact dermatitis is a major health problem caused by a cosmopolitan weed Parthenium hysterophorus. It is a T cell-mediated immune injury and disease manifests as itchy erythematous papules, papulovesicular and plaque lesions on exposed areas of the body. We studied the involvement of T_H1/T_H2/T_H17/Treg type responses by assaying various cytokines in Parthenium dermatitis.MethodsThe study includes 50 patients of Parthenium dermatitis confirmed by patch testing and 50 healthy subjects. The serum levels of T_H1, T_H2, T_H17 and Treg cytokines were estimated by high sensitivity sandwich ELISA and were compared statistically between groups using ANOVA.ResultsThe mean concentration of T_H1 cytokines (p < 0.001) and IL-17 (p < 0.001) were increased significantly as compared to controls. In contrast, decrease in levels of IL-10 (p < 0.002) and TGF-β (p < 0.001) were significant and levels of IL-4 (p < 0.262) were insignificant whereas no alterations in the total IgE concentrations (p < 0.976) was observed.ConclusionThe induction of T_H1 and T_H17 cytokines reinforce the need of detailed analysis of immune dysregulation in Parthenium dermatitis and might add some insight in the pathogenesis, diagnosis and current treatment modalities of this disease.     

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.     

Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects

BackgroundSeveral studies have reported that serum concentrations of carotenoids and adiponectin are inversely associated with the risk for cardiovascular disease (CVD). However, no studies have investigated the association between serum concentrations of adiponectin and carotenoids in the general population.MethodsWe investigated cross-sectionally whether serum carotenoids are associated with serum high molecular weight (HMW) adiponectin and some inflammatory markers in 437 Japanese subjects (116 men and 321 women) who attended a health examination.ResultsIn multiple linear regression analysis adjusted for confounding factors, serum β-carotene concentrations were significantly associated with serum HMW adiponectin concentrations in both sexes (standardized β coefficient = 0.197, p = 0.036 for men; standardized β coefficient = 0.146, p = 0.012 for women). Serum α-carotene and β-carotene concentrations were significantly associated with serum C-reactive protein (CRP) concentrations in men. In women, there were significant negative associations between serum carotenoids concentrations and serum interleukin-6 (IL-6) concentrations. Additional adjustment for serum concentrations of IL-6 or CRP did not significantly affect the association between carotenoids and HMW adiponectin in non-smoking men as well as in women.ConclusionSerum β-carotene concentrations were positively associated with serum HMW adiponectin concentrations even after adjustment for possible confounding factors including inflammatory markers.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: Adhesion molecules and cytokines in acute pancreatitis

ObjectivesTo assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP).MethodsSingle center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place.ResultsTotally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p = 0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p = 0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p = 0.03).ConclusionsSoluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.     

Lemon balm: A promising herbal therapy for patients with borderline hyperlipidemia—A randomized double-blind placebo-controlled clinical trial

ObjectiveMelissa officinalis is a perennial herb from the Lamiaceae family which has shown to have modulating effects on serum lipid profile. The aim of the current study is to explore the effects of M. officinalis supplementation on serum biochemical parameters of patients with borderline hyperlipidemia.Methods58 hyperlipidemic patients were allocated randomly to 2 groups: first group received capsules containing 1000 mg M. officinalis leaf powder (MO group), and the second group received placebo capsules (P group) 3 times per day for 2 months. Fasting blood glucose (FBG), HDL, LDL, Triglyceride, Creatinine and liver function enzymes including AST and ALT were evaluated before and after study.ResultsThe mean of LDL in MO group significantly decreased compared with P group after the supplementation (P = 0.02). Although the level of Cholesterol, FBG, HDL, Triglyceride, Creatinine and ALT did not show significant difference between two groups after 2 months (P ≥ 0.05), the level of AST exhibited a significant difference between two groups (P = 0.009).ConclusionsOur findings demonstrated that M. officinalis supplementation as a rich source of antioxidants and bioactive compounds can be effective in remission of LDL and AST levels in patients with borderline hyperlipidemia.     

Serum resistin: A biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics,tumor markers,inflammatory and metabolic parameters

ObjectivePrevious few studies have shown that resistin is significantly elevated in breast cancer (BC) patients. Therefore, we investigated whether serum resistin could be used as a potential diagnostic and prognostic tool for postmenopausal BC (PBC), taking into account clinicopathological features, serum tumor markers, anthropometric, metabolic, and, for the first time, inflammatory parameters.MethodsSerum resistin, tumor markers (CA 15–3 and CEA), metabolic, anthropometric and inflammatory parameters (TNF-α, IL-6, hsCRP) were determined in 103 postmenopausal women with incident, pathologically confirmed, invasive BC, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL).ResultsMean serum resistin was significantly higher in cases than in controls and patients with BBL (p < 0.001). In patients, resistin was significantly associated with tumor and inflammatory markers, cancer stage, tumor size, grade and lymph node invasion but not with anthropometric, metabolic parameters and hormone receptor status. Multivariable regression analysis revealed that serum IL-6 (p = 0.02) and cancer stage (p = 0.048) were the strongest determinants of serum resistin in cases adjusting for demographic, metabolic and clinicopathological features. Although resistin's diagnostic performance was low based on ROC curve analysis [0.72, 95% CI: 0.64–0.79], it could, however, represent a BC biomarker reflecting advanced disease stage and inflammatory state.ConclusionFurther prospective and longitudinal studies are needed to evaluate whether serum resistin could be used as a prognostic tool in BC monitoring and management. More research is essential to elucidate resistin's ontological role in the association between obesity, representing a chronic low-grade subclinical inflammation, and PBC.     

Genetic variants of human urea transporter-2 are associated with metabolic syndrome in Asian population

BackgroundA previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort.MethodsFive HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy–Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study.ResultsAmong those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9 × 10^?4 ≤ p ≤ 0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p = 0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p = 0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction.ConclusionThe results have provided evidence that the HUT2 gene may play a certain role in developing MetS and its related traits in Asian population. Further investigation of the HUT2 gene influencing MetS and its related traits will be warranted.     

Long-term high-intensity interval training associated with lifestyle modifications improves QT dispersion parameters in metabolic syndrome patients

BackgroundQT dispersion (QTd) is a marker of myocardial electrical instability, and is increased in metabolic syndrome (MetS). Moderate intensity continuous exercise (MICE) training was shown to improve QTd in MetS patients.ObjectivesTo describe long-term effects of MICE and high-intensity interval exercise training (HIIT) on QTd parameters in MetS.MethodsSixty-five MetS patients (53 ± 9 years) were assigned to either a MICE (60% of peak power output [PPO]), or a HIIT program (alternating phases of 15–30 s at 80% of PPO interspersed by passive recovery phases of equal duration), twice weekly during 9 months. Ventricular repolarization indices (QT dispersion = QTd, standard deviation of QT = sdQT, relative dispersion of QT = rdQT, QT corrected dispersion = QTcd), metabolic, anthropometric and exercise parameters were measured before and after the intervention.ResultsNo adverse events were noted during exercise. QTd decreased significantly in both groups (51 vs 56 ms in MICE, P < 0.05; 34 vs 38 ms in HIIT, P < 0.05). Changes in QTd were correlated with changes in maximal heart rate (r = ?0.69, P < 0.0001) and in heart rate recovery (r = ?0.49, P < 0.01) in the HIIT group only. When compared to MICE, HIIT training induced a greater decrease in weight, BMI and waist circumference. Exercise capacity significantly improved by 0.82 and 1.25 METs in MICE and HIIT groups respectively (P < 0.0001). Lipid parameters also improved to the same degree in both groups.ConclusionIn MetS, long-term HIIT and MICE training led to comparable effects on ventricular repolarization indices, and HIIT might be associated with greater improvements in certain cardiometabolic risk factors.     

Effects of telephone-based motivational interviewing in lifestyle modification program on reducing metabolic risks in middle-aged and older women with metabolic syndrome: A randomized controlled trial

BackgroundLifestyle modification is often difficult for middle-aged and older women living in the community who are at high risk of physical inactivity and metabolic syndrome.ObjectivesTo examine the effects of telephone-based motivational interviewing in a 12-week lifestyle modification program on physical activity, MetS, metabolic risks (fasting plasma glucose, blood pressure, triglyceride, high-density lipoprotein, and central obesity), and the number of metabolic risks in community-living middle-aged and older women diagnosed with metabolic syndrome.Research design and methodA randomized controlled trial was conducted. Recruited were 328 middle-aged and older women from a community health center in Taiwan. Eligible women medically diagnosed with metabolic syndrome (n = 115) were randomly assigned to one of three groups: The experimental group received an individualized telephone delivered lifestyle modification program that included motivational interviewing delivered by an experienced nurse. The brief group received a single brief lifestyle modification counseling session with a brochure. The usual care group received standard care. Physical activity was assessed with the International Physical Activity Questionnaire and metabolic risks were determined by serum markers and anthropometric measures at pre- and post-intervention. One hundred women completed the study and an intention-to-treat analysis was performed. Generalized estimating equations were used to examine the intervention effects.ResultsWomen in the experimental group increased physical activity from 1609 to 1892 MET-min/week (β = 846, p = .01), reduced the percentage of diagnosed with metabolic syndrome to 81.6% (β = −0.17, p = .003), and decreased the number of metabolic risks from 4.0 to 3.6 (β = −0.50, p < .001), compared to the usual care group (4.4–4.6). There was not a reduction in the percentage of diagnosed with metabolic syndrome in the brief group, but they had fewer metabolic risks after 12 weeks (mean = 4.0 vs. 4.6, β = −0.2, p = .02) compared to the usual care group.ConclusionsMotivational interviewing as a component of an individualized physical activity and lifestyle modification program has positive benefit in reducing metabolic risks in middle-aged and older women.     

Predictive value of osteocalcin in bone metastatic differentiated thyroid carcinoma

ObjectivesTo evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC).Design and methodsSerum samples from DTC patients with (DTC BM+, n = 19) or without bone metastases (DTC BM?, n = 19), and matched healthy volunteers (n = 30) were tested for serum osteocalcin with electrochemiluminescent immunoassay.ResultsOsteocalcin was higher in DTC BM+ than in DTC BM? patients (+ 35.8%, p = 0.002), acting as an independent risk factor for bone metastases (R² = 0.142, p = 0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 μg/L.ConclusionsSerial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.     

Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model

Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain presents an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n = 8) and in suspected early stage cases (n = 5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n = 5). In APP_SWE/PS1_?E9 transgenic mice (AD-Tg; n = 18) but not in non-Tg wt mice (n = 10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n = 4 mice per group). In live AD-Tg mice (n = 24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n = 11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high-resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies.     

Paraoxonase activity in athletes with depleted iron stores and iron-deficient erythropoiesis

ObjectiveThe aim of this study was to evaluate how conditions that precede anaemia (iron store depletion and iron-deficient erythropoiesis) affect human serum paraoxonase PON1 activity.Design and methodsBased on haemoglobin, transferrin saturation and serum ferritin values 119 athletes were divided into three groups: with iron depletion, with deficient erythropoiesis and controls. The following parameters were measured: paraoxonase activity towards paraoxon (POase) and diazoxon (DZOase), lipid hydroperoxides (LOOH), the pro-oxidant-antioxidant balance (PAB), red blood cells (RBC) and lipid status.ResultsSignificant differences were found between athletes with different stages of iron deficiency and controls with respect to PON 1 activity and oxidative stress status parameters (Wilks' Lambda = 0.712, F = 5.241, p < 0.001, η² = 0.156). There was no significant difference between the PON1 192 Q and R polymorphism distribution in the two groups of athletes with different stages of iron deficiency and controls (χ² = 1.086; p = 0.896). PON1 activity was positively correlated with RBCs, haemoglobin, transferrin saturation (p < 0.001) and ferritin (p = 0.037) and negatively correlated with LOOH (p = 0.044) in all three study groups.ConclusionsDeficient erythropoiesis in athletes contributes to impaired PON1 activity. In contrast, iron depletion, regardless of increased oxidative stress, does not affect PON1 activity.     

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.     

Association of C-reactive protein and metabolic syndrome in a rural Chinese population

ObjectiveTo explore the relationship between C-reactive protein (CRP) and metabolic syndrome (MetS) in a rural Chinese population.Design and methodsWe performed a population-based cross-sectional study.ResultsThe median CRP was 0.90 mg/L. After exclusion of subjects with a CRP value > 10 mg/L, The median CRP with 0, 1, 2, 3, 4, and 5 components of MetS were 0.61, 0.61, 0.73, 1.07, 1.51, and 1.16 mg/L (P = 0.029 for linear trend) in men, and were 0.37, 0.45, 0.62, 1.10, 1.52, and 2.17 mg/L (P = 0.002 for linear trend) in women, respectively. After adjustment for potential confounders, compared with those without components of MetS, those with 1, 2, 3, 4, and 5 components of MetS had ORs of 1.39, 1.08, 1.84, 2.65, and 1.21 for elevated CRP in men and 1.91, 2.06, 3.10, 4.06, and 6.01 in women, respectively.ConclusionIn this rural Chinese population, the CRP concentration was lower than that of Caucasians and strongly related to the MetS, especially in women.