Total serum IL-12 and IL-12p40, but not IL-12p70, are increased in the serum of older subjects; relationship to CD3(+)and NK subsets

Interleukin 12 (IL-12), a central cytokine acting on T and natural killer (NK) cells, directs proliferation of activated T lymphocytes towards a Th1 phenotype. The heterodimeric molecule IL-12p70, equates with IL-12 biological activity, while IL-12p40 may antagonize IL-12 and inhibit cytotoxic T lymphocyte (CTL) generation in vitro. This study characterizes age-related changes in serum total IL-12, IL-12p70 and IL-12p40 relating them with CD3(+), NK and related subsets from subjects, aged 30-96 years. Total IL-12, IL-12p40 and the IL-12p40/IL-12p70 ratio, but not IL-12p70, increased significantly with age (P

Cardiovascular disease risk profiles among 'healthy' siblings of patients with early-onset cardiovascular disease:Application of the new SCORE system

BACKGROUND: Cardiovascular disease (CVD) occurs more frequently in individuals with a family history of premature CVD. Within families the demographics of CVD are poorly described. DESIGN: We examined the risk estimation based on the Systematic Coronary Risk Evaluation (SCORE) system and the Joint British Guidelines (JBG) for older unaffected siblings of patients with premature CVD (onset ≤55 years for men and ≤60 years for women). METHODS: Between August 1999 and November 2003 laboratory and demographic details were collected on probands with early-onset CVD and their older unaffected siblings. Siblings were screened for clinically overt CVD by a standard questionnaire and 12-lead electrocardiogram (ECG). RESULTS: A total of 790 siblings was identified and full demographic details were available for 645. The following siblings were excluded: 41 with known diabetes mellitus; seven with random plasma glucose of 11.1 mmol/l or greater; and eight with ischaemic ECG. Data were analysed for 589 siblings from 405 families. The mean age was 55.0 years, 43.1% were men and 28.7% were smokers. The mean total serum cholesterol was 5.8 mmol/l and hypertension was present in 49.4%. Using the SCORE system, when projected to age 60 years, 181 men (71.3%) and 67 women (20.0%) would be eligible for risk factor modification. Using JBG with a 10-year risk of 20% or greater, 42 men (16.5%) and four women (1.2%) would be targeted. CONCLUSIONS: Large numbers of these asymptomatic individuals meet both European and British guidelines for the primary prevention of CVD and should be targeted for risk factor modification. The prevalence of individuals defined as eligible for treatment is much higher when using the SCORE system. © 2007 European Society of Cardiology.

In vitro effects of the pyrethroid S-bioallethrin on lymphocytes and basophils from atopic and nonatopic subjects

Synthetic pyrethroids are increasingly used as insecticides and marketed as having relatively low human toxicity. The aim of this study was to examine the in vitro effects of the synthetic pyrethroid S-bioallethrin on human blood lymphocytes and basophils in atopic individuals and nonatopic control subjects. S-bioallethrin caused inhibition of lymphocyte proliferation after a 72-h culture period in a concentration-dependent manner. The inhibition of the lymphocyte proliferation by S-bioallethrin at the concentration 6.5 mu M correlated well with the total serum IgE values (r= -0.89, P

Dyslipidemia and Diabetic Macular Edema: A Systematic Review and Meta-Analysis

Topic: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME). 

Clinical Relevance: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been reported as a risk factor for its development. A systematic review with a meta-analysis was undertaken to examine the evidence of an association between dyslipidemia and DME. 

Methods: We defined eligibility criteria as randomized controlled trials (RCTs) and cohort, case-control, and cross-sectional studies reporting on the relationship between blood lipid levels and DME. We performed a literature search in MEDLINE, PubMed, and Embase from inception to September 2014. We used the NewcastleeOttawa scale to assess the quality of case-control, cross-sectional, and cohort studies, and the Cochrane risk of bias tool for RCTs. 

Results: The search strategy identified 4959 publications. After screening, we selected 21 articles for review (5 cross-sectional, 5 cohort, 7 case-control, and 4 RCTs). Meta-analysis of case-control studies revealed that mean levels of total serum cholesterol (TC), low-density lipoproteins (LDLs), and serum triglycerides (TGs) were significantly higher in patients with DME compared with those without DME (TC: 30.08; 95% confidence interval [CI], 21.14e39.02; P < 0.001; LDL: 18.62; 95% CI, 5.80e31.43; P < 0.05; TG: 24.82; 95% CI, 9.21e40.42; P < 0.05). Meta-analysis of RCTs did not show significant risk in worsening of hard exudates and severity of DME in the lipid-lowering group compared with placebo (hard exudates: relative risk, 1.00; 95% CI, 0.47e2.11; P ¼ 1.00; DME: relative risk, 1.18; 95% CI, 0.75e1.86; P ¼ 0.48). 

Conclusions: Despite evidence from the cohort studies and meta-analysis of the case-control studies suggesting a strong relationship between lipid levels and DME, this was not confirmed by the meta-analysis that included only prospective RCTs. Therefore, given the significant public health relevance of the topic, the relationship between lipid levels and DME deserves further investigation.

Early alterations in serum creatine kinase and total cholesterol following high intensity eccentric muscle actions

Aim. The purpose of this experiment was to assess the levels of muscle soreness, serum total cholesterol (TC) and creatine kinase (CK) in the first 48 hours following fatiguing eccentric exercise performed with the triceps brachii.

Restoration of adipose function in obese, glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein β upregulation

Obese AT (adipose tissue) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The present study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and ATMs (AT macrophages). In addition, a pilot randomized placebo controlled trial using the PPAR (peroxisome-proliferator-activated receptor) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=28) were randomized to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16+ monocyte levels via flow cytometry. A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number, the latter was determined via assessment of CD68 expression by IHC (immunohistochemistry) and real-time PCR. Subcutaneous AT mRNA expression of CEBPß (CCAAT enhancer-binding protein ß), SREBP1c (sterol-regulatory-element-binding protein 1c), PPAR?2, IRS-1 (insulin receptor substrate-1), GLUT4 (glucose transporter type 4) and TNFa (tumour necrosis factor a) were also assessed. Comparisons were made between obese and lean controls (n=16) at baseline, and pre- and post-PPAR agonist treatment. Obese individuals had significantly increased adipocyte cell surface, percentage CD14+/CD16+ monocyte numbers and ATM number (all P=0.0001). Additionally, serum TNF-a levels were significantly elevated (P=0.017) and adiponectin levels reduced (total: P=0.0001; high: P=0.022) with obesity. ATM number and percentage of CD14+/CD16+ monocytes correlated significantly (P=0.05). Pioglitazone improved adiponectin levels significantly (P=0.0001), and resulted in the further significant enlargement of adipocytes (P=0.05), without effect on the percentage CD14+/CD16+ or ATM number. Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPß mRNA. The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels, supports the centrality of AT to the cardiometabolic derangement underlying the development of T2D (Type 2 diabetes) and CVD (cardiovascular disease).

Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing

Background Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown.

Serum eosinophil cationic protein (ECP):reference values in healthy nonatopic children

BACKGROUND: Although serum ECP concentrations have been reported in normal children, there are currently no published upper cutoff reference limits for serum ECP in normal, nonatopic, nonasthmatic children aged 1-15 years.
METHODS: We recruited 123 nonatopic, nonasthmatic normal children attending the Royal Belfast Hospital for Sick Children for elective surgery and measured serum ECP concentrations. The effects of age and exposure to environmental tobacco smoke (ETS) on the upper reference limits were studied by multiple regression and fractional polynomials.
RESULTS: The median serum ECP concentration was 6.5 microg/l and the 95th and 97.5 th percentiles were 18.8 and 19.9 microg/l. The median and 95th percentile did not vary with age. Exposure to ETS was not associated with altered serum ECP concentrations (P = 0.14).
CONCLUSIONS: The 95th and 97.5 th percentiles for serum ECP for normal, nonatopic, nonasthmatic children (aged 1-15 years) were 19 and 20 microg/l, respectively. Age and exposure to parental ETS did not significantly alter serum ECP concentrations or the normal upper reference limits. Our data provide cutoff upper reference limits for normal children for use of serum ECP in a clinical or research setting.
PMID: 10604557 [PubMed - indexed for MEDLINE]

Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners

Adrenomedullin (AM) is an important regulatory peptide involved in both physiological and pathological states. We have previously demonstrated the existence of a specific AM-binding protein (AMBP-1) in human plasma. In the present study, we developed a nonradioactive ligand blotting assay, which, together with high pressure liquid chromatography/SDS-polyacrylamide gel electrophoresis purification techniques, allowed us to isolate AMBP-1 to homogeneity. The purified protein was identified as human complement factor H. We show that AM/factor H interaction interferes with the established methodology for quantification of circulating AM. Our data suggest that this routine procedure does not take into account the AM bound to its binding protein. In addition, we show that factor H affects AM in vitro functions. It enhances AM-mediated induction of cAMP in fibroblasts, augments the AM-mediated growth of a cancer cell line, and suppresses the bactericidal capability of AM on Escherichia coli. Reciprocally, AM influences the complement regulatory function of factor H by enhancing the cleavage of C3b via factor I. In summary, we report on a potentially new regulatory mechanism of AM biology, the influence of factor H on radioimmunoassay quantification of AM, and the possible involvement of AM as a regulator of the complement cascade.

A time-resolved immunoassay to measure serum antibodies to the rotavirus VP6 capsid protein

The rotavirus (RV) inner capsid protein VP6 is widely used to evaluate immune response during natural infection and in vaccine studies. Recombinant VP6 from the most prevalent circulating rotavirus strains in each subgroup (SG) identified in a birth cohort of children in southern India [SGII (G1P[8]) and SGI (G10P[11])] were produced. The purified proteins were used to measure VP6-specific antibodies in a Dissociation-Enhanced Lanthanide Fluorometric Immunoassay (DELFIA). The ability of the assay to detect a =2 fold rise in IgG level in a panel of serum samples from a longitudinal study was compared to a gold standard virus-capture ELISA. A strong association was observed between the assays (p