The Plasma Level of Proprotein Convertase FURIN in Patients with Suspected Infection in the Emergency Room: A Prospective Cohort Study

There is an increasing need for novel biomarkers that enable better diagnostic and prognostic stratification of patients with suspected infection. A proprotein convertase enzyme FURIN is upregulated upon immune cell activation, and it promotes infectivity by cleaving and activating pathogens. In this study, we determined FURIN levels in plasma using ELISA from 537 patients that were admitted to emergency room with suspected infection. Patients were sorted to high‐ and low‐level FURIN groups with a cut‐off level of 370 pg/ml. The study cohort included five diagnostic groups: Group 1, no systemic inflammatory response syndrome (SIRS, n = 59 patients); Group 2, bacterial infection without SIRS (n = 67); Group 3, SIRS, but no bacterial infection (n = 308); Group 4, sepsis without organ failure (n = 308); and Group 5, severe sepsis (n = 49). Statistically significant associations were not found between the plasma level of FURIN and the prevalence of sepsis (P = 0.957), diagnostic group of a patient (P = 0.737) or the bacteria in blood culture (P = 0.499). Additionally, the concentration of FURIN did not predict the severity or case fatality of the infectious disease. However, statistically significant associations were found between high plasma level of FURIN and diagnosed rheumatic disease (P < 0.001) as well as with the prevalence of non‐smokers (P = 0.034). Thus, albeit the plasma level of FURIN does not predict the severity of infectious disease, it may be of use in the diagnostics of autoimmune diseases.     

High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica

Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five consecutive days after hospitalization. Receiver operating characteristic (ROC) analysis revealed that the maximum PTX3 level >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for detecting platelet level <50 × 10⁹/l, with an area under the curve (AUC) value of 0.78 (95% confidence interval [CI] 0.63–0.94). High PTX3 level was also associated with several other variables reflecting the severity of the disease: patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 × 10⁹/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine (282 vs. 124 μmol/l, p = 0.007) levels than patients with low maximum PTX3 level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to patients with low PTX3 level. High plasma PTX3 levels are associated with thrombocytopenia and the overall severity of NE.     

Decreased paraoxonase activity in critically ill patients with sepsis

Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus, limiting production of proinflammatory mediators. Systemic inflammatory response in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL) concentrations. The objective of this study was to investigate serum paraoxonase 1 activities in critically ill patients with sepsis and after recovery. Serum paraoxonase 1 arylesterase/paraoxonase activities, concentration of total cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient controls without sepsis (n = 30) were analyzed. Paired convalescent samples were also taken 1 week after recovery (n = 11). In septic patients, both arylesterase (88.3 ± 36.5 vs. 162.1 ± 44.8 kU/l, P < 0.001) and paraoxonase (75.2 ± 50.0 vs. 125.2 ± 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared to controls. Both activities normalized after recovery. Negative correlation was found between CRP and both arylesterase (r = −0.676, P < 0.001) and paraoxonase (r = −0.401, P < 0.01) as well as positive correlation between HDL-C and both arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01) paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative correlation with CRP offers a potentially useful marker of sepsis progress and recovery in critically ill patients.     

Defensiveness and metabolic syndrome: Impact of sex and age

The association between defensiveness and metabolic burden, as well as the moderating effects of sex and age were evaluated in 199 healthy working men (N = 81) and women (N = 118), aged 20–64 years (M = 41; S.D. = 11.45). Defensiveness (Marlowe–Crowne Social Desirability Scale) and parameters of metabolic syndrome (MS; waist circumference, HDL, triglycerides, glucose, 24 h ambulatory blood pressure) were obtained. In men, defensiveness was inversely related to MS burden (Beta = −.288; p = .001), as well as to individual measures of SBP, DBP, glucose and waist circumference (p < .05). In older women, high defensiveness was associated with a greater MS burden (p = .050) and glucose level (p = .005) while the reverse was true in younger women (p = .012). In conclusion, defensiveness was associated with a worse metabolic profile in older women but may be protective for men and younger women. Understanding the pathophysiological processes underlying these associations could elucidate sex and age differences and inform prevention efforts.     

Associations between clinical features and therapy with macrophage subpopulations and T cells in inflammatory lesions in the aorta from patients with Takayasu arteritis

Takayasu arteritis (TAK) is a large-vessel granulomatous vasculitis; the inflammatory infiltration in arteries comprises macrophages, multi-nucleated giant cells, CD4⁺ and CD8⁺ T cells, γδ T cells, natural killer (NK) cells and neutrophils. However, it is unknown which subtype of macrophages predominates. This study aims to evaluate macrophages subpopulations in the aorta in TAK. Immunohistochemistry was performed in the aorta from TAK patients (n = 22), patients with atherosclerotic disease (n = 9) and heart transplant donors (n = 8) using the markers CD68, CD86, CD206, CD3, CD20 and CD56. Active disease was observed in 54·5% of patients and active histological lesions were found in 40·9%. TAK patients presented atherosclerotic lesions in 27·3% of cases. The frequency of macrophages, M1 macrophages, T, B and NK cells was higher in the aorta from TAK and atherosclerotic patients compared to heart transplant donors. In TAK, macrophages and T cells were the most abundant cells in the aorta, and the expression of CD206 was higher than CD86 (P = 0·0007). No associations were found between the expression of cell markers and active disease or with atherosclerotic lesions. In TAK patients, histological disease activity led to higher T cell counts than chronic fibrotic lesions (P = 0.030), whereas prednisone use was associated with lower T cell counts (P = 0·035). In conclusion, M1 macrophages were more frequent in TAK and atherosclerotic patients compared to heart transplant donors, while M2 macrophages dominated M1 macrophages in TAK. T cells were associated with histological disease activity and with prednisone use in TAK.     

Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia

Factors predisposing to the phenotypic features of high total cholesterol (T-Cho) in human plasma have not been clearly defined. Here we report an association between two variations in the apolipoprotein B48 receptor gene (APOB48R) and plasma T-Cho levels among 352 adult individuals in Japan. By analyzing phenotypic associations between age- and gender-adjusted levels of plasma T-Cho, low-density lipoprotein (LDL) cholesterol (LDL-C), and high-density lipoprotein (HDL) cholesterol (HDL-C), we detected a significant correlation between genotypes of the A419P variation and adjusted T-Cho levels. Among homozygous G-allele carriers (n=265), heterozygous carriers (n=78), and homozygous minor C-allele carriers (n=9), T-Cho levels were 2.43±0.21 mg/cm³, 2.48±0.24 mg/cm³, and 2.63±0.21 mg/cm³, respectively, indicating a codominant T-Cho-elevating effect of the minor C-allele (r=0.15, P=0.007). A similar effect was detected for c.934-960/del (r=0.13, P=0.015). Linkage disequilibrium (LD) analysis detected significant LD among eight variant sites that included neighboring loci. Our results indicate that variations in APOB48R and nearby genes are among the many factors involved in hypercholesterolemia. The etiological studies should now include consideration of this novel aspect of the mechanism(s) leading to hypercholesterolemic disease.     

Parameters of high-density lipoproteins in patients with arterial hypertension in combination with other components of metabolic syndrome

Parameters of HDL (concentrations of cholesterol, apoprotein A1, and phospholipids and phospholipid composition) determining their functional properties were studied in patients with arterial hypertension in combination with other components of metabolic syndrome (abdominal obesity, hyperlipidemia, and impaired glucose tolerance). Patients with isolated arterial hypertension did not differ from the control group by the concentration of apoprotein A1 and HDL cholesterol, but had lower content of HDL phospholipids and changed phospholipid composition: lower ratio of phosphatidylcholine and higher relative contents of lysophosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. Parameters of HDL in patients with arterial hypertension associated with other components of metabolic syndrome did not differ from those in patients with isolated arterial hypertension. The observed changes in HDL in patients with arterial hypertension alone or in combination with other components of metabolic syndrome can impair functional capacity of HDL in reverse cholesterol transport, which increases the risk of atherosclerosis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 3, pp. 289–292, March, 2007     

Endurance training enhances ABCA1 expression in rat small intestine

The purpose of this study was to investigate liver and intestinal ABCA1 expression and plasma HDL-C level in response to treadmill-running training in rats. Twenty adult Wistar male rats (17–18 weeks old, 300–322 g) were divided into control (n = 10) and Training (n = 10) groups. Training group trained at 25 m/min (0% grade) for 60 min/day, 5 days/week for 12 weeks. Rats were killed 48 h after the last session of training. The intestinal and liver ABCA1 mRNA expression was found to be significantly higher in trained compared to control group (P < 0.006 and P < 0.024, respectively). Intestine and liver ATP concentrations remained unchanged. Plasma HDL-C, HDL2-C, Apo A-1, pre-β HDL-C concentration, LCAT activity, TC/HDL-C and LDL-C/HDL-C ratio significantly increased in trained group (P < 0.01, P < 0.006, P < 0.001, P < 0.001 P < 0.067, P < 0.02, and P < 0.03, respectively). However, other lipoprotein concentrations were unchanged. In conclusion, we found that endurance training induced significant elevation in plasma HDL-C and HDL2-C concentrations, accompanied by higher plasma Apo A-1, pre-β HDL-C concentrations, LCAT activity and ABCA1 mRNA expressions in rat intestine, and liver.     

An investigation of the etiology and follow-up findings in 35 children with overgrowth syndromes,including biallelic SUZ12 variant

Overgrowth-intellectual disability (OGID) syndromes are clinically and genetically heterogeneous group of disorders. The aim of this study was to examine the molecular etiology and long-term follow-up findings of Turkish OGID cohort. Thirty-five children with OGID were included in the study. Single gene sequencing, clinical exome analysis, chromosomal microarray analysis and whole exome sequencing were performed. Five pathogenic copy number variants were detected in the patients; three of them located on chromosome 5q35.2 (encompassing NSD1), others on 9q22.3 and 22q13.31. In 19 of 35 patients; we identified pathogenic variants in OGID genes associated with epigenetic regulation, NSD1 (n = 15), HIST1H1E (n = 1), SETD1B (n = 1), and SUZ12 (n = 2). The pathogenic variants in PIK3CA (n = 2), ABCC9 (n = 1), GPC4 (n = 2), FIBP (n = 1), and TMEM94 (n = 1) which had a role in other growth pathways were detected in seven patients. The diagnostic yield was 31/35(88%). Twelve pathogenic variants were novel. The common facial feature of the patients was prominent forehead. The patients with Sotos syndrome were observed to have milder intellectual disability than patients with other OGID syndromes. In conclusion, this study showed, for the first time, that biallelic variants of SUZ12 caused Imagawa-Matsumoto syndrome, monoallelic variants in SETDIB resulted in OGID. Besides expanded the phenotypes of very rare OGID syndromes caused by FIBP and TMEM94.     

Patients with antiphospholipid syndrome display endothelial perturbation

BackgroundThere is strong evidence that antiphospholipid antibodies (aPL) perturb endothelium both in vitro and in experimental animal models. by inducing a vasculopathy and an endothelial pro-inflammatory/coagulant phenotype. However, few contrasting studies raised the issue about the possibility to detect a comparable endothelial perturbation in anti-phospholipid syndrome (APS) patients. The aim of this observational case-control study was to evaluate several parameters of endothelial perturbation in patients with APS and without any other atherosclerosis risk factor.Patients and MethodsWe investigated plasma levels of soluble adhesion molecules (s-ICAM-1, s-VCAM-1, s-E-selectin), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays in 40 selected APS patients and 40 age- and sex-matched healthy subjects. In addition, we evaluated circulating endothelial cells by flow cytometry and brachial artery flow-mediated vasodilation. Patients and controls were free of conditions known to affect both the biological and the functional endothelial parameters.ResultsPlasma levels of sTM, s-E-selectin and s-VCAM-1 did not differ from controls, while a significant increase in s-ICAM-1 (P = 0.029), t-PA (P = 0.003) and vWF titres (P = 0.002) was found. Circulating mature endothelial cells were also significantly higher in patients than in controls (P = 0.05) and decreased during both vitamin K antagonists (P = 0.001) and antiplatelet (P = 0.032) treatments. Mean brachial artery flow-mediated vasodilation responses were significantly impaired compared to healthy subjects (P = 0.0001).ConclusionsAs a whole these findings indicate that APS patients display an endothelial perturbation in the absence of other detectable traditional risk factors for atherosclerosis.     

Increased Levels of Interferon‐Inducible Protein 10 (IP‐10) in 22q11.2 Deletion Syndrome

The 22q11.2 deletion syndrome (22q11.2 DS), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:4000 births. These patients may suffer from affection of many organ systems with cardiac malformations, thymic hypoplasia or aplasia, hypoparathyroidism, palate anomalies and psychiatric disorders being the most frequent. The incidence of autoimmune diseases is increased in older patients. The aim of the present study was to examine a cytokine profile in patients with 22q11.2 DS by measuring a broad spectrum of serum cytokines. Patients with a proven deletion of chromosome 22q11.2 (n = 55) and healthy individuals (n = 54) recruited from an age‐ and sex‐comparable group were included in the study. Serum levels of 27 cytokines, including chemokines and growth factors, were analysed using multiplex technology. Interferon‐inducible protein 10 (IP‐10) was also measured by ELISA to confirm the multiplex results. The 22q11.2 DS patients had distinctly and significantly raised levels of pro‐inflammatory and angiostatic chemokine IP‐10 (P < 0.001) compared to controls. The patients with congenital heart defects (n = 31) had significantly (P = 0.018) raised serum levels of IP‐10 compared to patients born without heart defects (n = 24). The other cytokines investigated were either not detectable or did not differ between patients and controls.     

Evaluation of milk haptoglobin and amyloid A in high producing dairy cattle with clinical and subclinical mastitis in Shiraz

Mastitis is one of the most common diseases in dairy cattle and results in considerable loss of animals. This study was designed to evaluate milk haptoglobin (Hp) and milk amyloid A (MAA) as an inflammatory indicator for clinical and subclinical mastitis of cattle in dairy farms in Shiraz, Iran. Forty-three subclinical mastitic cows with a positive California Mastitis Test (CMT) and no clinical signs of mastitis, 28 clinical mastitic cows, and 10 healthy cows with negative CMT were selected. After confirmation of clinical and subclinical mastitis by bacterial identification, milk samples were taken from four quarters of each cow and mixed, and one sample was taken from the pooled milk. The most dominant isolated bacterium from clinical and subclinical samples was Staphylococcus aureus (n = 25; 35.2%). The most dominant isolated bacterium from clinical (19/28) and subclinical (11/43) samples was Staphylococcus spp. Of isolated bacteria of milk in cattle with clinical mastitis, 67.8% (n = 19) was S. aureus. There was no bacterial growth in 37.1% (n = 16) of cattle with subclinical mastitis. Of isolated bacteria of milk in cattle with subclinical mastitis, 13.9% (n = 6) and 11.6% (n = 5) was S. aureus and Staphylococcus epidermidis, respectively. There were significant differences (P < 0.05) in concentrations of milk Hp, MAA, and somatic cell count between clinically healthy cattle and cows with clinical and subclinical mastitis. The concentrations of milk Hp, MAA, and somatic cell count in clinical mastitic cows were significantly higher than those in subclinical mastitic cows and control group. The optimal cutoff point was set, using the receiver operating characteristic curve analysis method, to >13.43 μg/ml for MAA, >9.71 ng/ml for milk Hp, and >14 × 10⁴ cell per millilitre for somatic cell count with corresponding 100% sensitivity and 100% specificity for MAA, 83.72% sensitivity and 100% specificity for milk Hp, and 88.37% sensitivity and 100% specificity for somatic cell count. The results of this study reveal that MAA is a sensitive factor for diagnosis of subclinical mastitis in cattle.     

Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study

Handgrip strength is a strong indicator of total body muscle strength and is a predictor of poor outcomes in older adults. The aging suppressor gene klotho encodes a single-pass transmembrane protein that is secreted as a circulating hormone. In mice, disruption of klotho expression results in a syndrome that includes sarcopenia, atherosclerosis, osteoporosis, and shortened lifespan, and conversely, overexpression of klotho leads to a greater longevity. The objective was to determine whether plasma klotho levels are related to skeletal muscle strength in humans. We measured plasma klotho in 804 adults, ≥65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Grip strength was positively correlated with plasma klotho at threshold <681 pg/mL. After adjusting for age, sex, education, smoking, physical activity, cognition, and chronic diseases, plasma klotho (per 1 standard deviation increase) was associated with grip strength (beta = 1.20, standard error = 0.35, P = 0.0009) in adults with plasma klotho <681 pg/mL. These results suggest that older adults with lower plasma klotho have poor skeletal muscle strength.     

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2–6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18–1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10–1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55–6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.     

Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality

The risk of premature death is high among patients on haemodialysis (HD patients). We previously determined that immunoglobulin (Ig)M antibodies against phosphorylcholine (anti-PC) are negatively associated with increased risk of cardiovascular disease (CVD), atherosclerosis, some autoimmune diseases and mortality among HD patients in this cohort. Here, we also study other subclasses and isotypes of anti-PC in HD patients in relation to mortality, inflammation and gender. The study group is a cohort of 209 prevalent HD patients [median age = 66 years, interquartile range (IQR) = 51–74], vintage time = 29 months (IQR = 15–58; 56% men) with a mean follow-up period of 41 months (IQR = 20–60). Fifty-six per cent were men. We also divided patients into inflamed C-reactive protein (CRP) > 5·6 mg/ml and non-inflamed CRP. Antibody levels were determined by in-house enzyme-linked immunosorbent assay. IgG1 anti-PC below median was significantly associated with increased all-cause mortality (after adjustment for confounders: P = 0·02), while IgG, IgA and IgG2 anti-PC were not associated with this outcome. Among non-inflamed patients, IgM and IgG1 anti-PC were significantly associated with mortality (P = 0·047 and 0·02). IgG1 anti-PC was significantly associated with mortality among men (P = 0·03) and trending among women (P = 0·26). IgM (as previously reported) and IgG1 anti-PC are negatively associated with survival among HD patients and non-inflamed HD patients, but among inflamed patients there were no associations. IgG, IgA or IgG2 anti-PC were not associated with survival in these groups and subgroups. Further studies are needed to determine if raising anti-PC levels, especially IgM and IgG1 anti-PC, through immunization is beneficial.     

Plasma characteristic metabolites of pediatric community-acquired pneumonia in traditional Chinese medicine syndrome differentiation

Community-acquired pneumonia (CAP) is the leading cause of lower respiratory tract infections in children. Heat syndrome (HS) and cold syndrome (CS) are two main syndrome types of pediatric CAP in traditional Chinese medicine (TCM). This study aimed to identify plasma metabolic profiles in pediatric CAP and to further select potential biomarkers to distinguish between HS and CS. An ultra-performance liquid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry method was applied to plasma samples of 296 patients and 55 healthy controls (HC). The samples were divided into the discovery group (n = 213, HS = 160, CS = 23, HC = 30) and the validation group (n = 138, HS = 93, CS = 20, HC = 25). The orthogonal partial least-squares discriminant analysis, the value of fold change, and Kruskal–Wallis test with false discovery rate correction (q-value <0.05) were applied to identify differential plasma metabolites. The area under the ROC curve (AUC) was used to evaluate the diagnostic performance of the screened metabolites. The results showed that the plasma levels of aspartic acid, phenylalanine, arginine, lysoPC20:1, lysoPE16:0, lysoPE18:0, and PE (16:0_22:6) were increased in CS compared with HC. The plasma levels of PC (18:1_18:1), PC (20:4_20:4), PE (16:0_18:2), lysoPE20:4, lysoPE18:2, and lysoPE22:6 were decreased, whereas, the plasma level of ceramide (d18:1_24:1) was increased in HS compared with HC. There were 13 differential metabolites in CS (AUC = 0.995) and 15 differential metabolites in HS (AUC = 0.954), compared with HC. A panel of seven biomarkers, including LysoPC20:1, lysoPE16:0, lysoPE18:2, lysoPE20:4, lysoPE22:6, PC (18:1_18:1), and PC (20:4_20:4) showed good discrimination between HS and CS with an AUC of 0.982. Altered plasma amino acids and lipids may provide an objective basis for TCM syndrome differentiation in pediatric CAP.     

Homocystéine et paramètres du syndrome métabolique et du risque cardiovasculaire chez 2045 militaires : étude EPIMIL

The aim of this present study is to investigate a possible relationship between plasma homocystein and biological indicators of metabolic syndrome and cardiovascular risk in a prospective epidemiological study; EPIMIL involving 2045 military subjects 20–58 years of age. Homocysteinemia measurements have been performed using automated chemiluminescent enzyme immunoassay on Immulite 2000^TM (DPC). According to NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel) definition, the prevalence of metabolic syndrome was 9%. Homocysteinemia was slightly related to some markers as cholesterol (R = 0,04, p = 0,05), triglycerides (R = 0,06, p = 0,004), free fatty acids (R = 0,06, P = 0,004). When fasting homocysteinemia above 15 μmol/l (7,5% of the population), there is no relationship with syndrome metabolic components and cardiovascular risk biological markers except for cholesterol and blood pressure. The follow up of the EPIMIL population for ten years would predict if plasma homocysteine is or not an independent factor in the complex pathomecanism of atherosclerosis.     

Short-term exercise training improves aerobic capacity with no change in arterial function in obesity

The aim of the study is to determine the effects of short-term high-intensity exercise on arterial function and glucose tolerance in obese individuals with and without the metabolic syndrome (MetSyn). Obese men and women (BMI > 30 kg/m²; 39–60 years) with and without MetSyn (MetSyn, n = 13; Non-MetSyn, n = 13) participated in exercise training consisting of ten consecutive days of treadmill walking for 1 h/day at 70–75% of peak aerobic capacity. Changes in aerobic capacity, flow-mediated dilation (FMD), and arterial stiffness using central and peripheral pulse wave velocity (PWV) measurements were assessed pre- and post-training. These measurements were obtained fasting and 1-h post-test meal while the subjects were hyperglycemic. Aerobic capacity improved for both groups [Non-MetSyn 24.0 ± 1.6 vs. 25.1 ± 1.5 mL/(kg min); MetSyn 25.2 ± 1.8 vs. 26.2 ± 1.7 mL/(kg min), P < 0.05]. There was no change in body weight. FMD decreased by ~20% (P < 0.05) for both groups during acute hyperglycemia (MetSyn, n = 11; Non-MetSyn, n = 10), while hyperglycemia increased central PWV and not peripheral PWV. Exercise training did not change FMD in the fasted or challenged state. Central and peripheral PWV were not altered with training for either group (MetSyn, n = 13; Non-MetSyn, n = 13). A 10-day high-intensity exercise program in obese individuals improved aerobic capacity and glucose tolerance but no change in arterial function was observed. Acute hyperglycemia had a deleterious effect on arterial function, suggesting that persons with impaired glucose homeostasis may experience more opportunities for attenuated arterial function on a daily basis which could contribute to increased cardiovascular risk.     

Differential serum cytokine profile in patients with systemic lupus erythematosus and posterior reversible encephalopathy syndrome

Systemic lupus erythematosus (SLE) patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory concerning the physiopathology of PRES suggests that there is brain–blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic oedema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyse the expression of different serum cytokines, as well as vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L), in patients with PRES/systemic lupus erythematosus (SLE) and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care centre in México City. We included 32 subjects (healthy controls, n = 6; remission SLE, n = 6; active SLE, n = 6 and PRES/SLE patients, n = 14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by magnetic resonance imaging (MRI). Serum samples were obtained during the first 36 h after the PRES episode and were analysed by cytometric bead array, Luminex multiplex assay or enzyme‐linked immunosorbent assay (ELISA). Interleukin (IL)‐6 and IL‐10 levels were significantly higher in PRES/SLE patients (P = 0·013 and 0·025, respectively) when compared to the other groups. Furthermore, IL‐6 and IL‐10 levels displayed a positive correlation (r = 0·686, P = 0·007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL‐6 and IL‐10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE‐associated neuropsychiatric syndromes.     

Diversity and association of HLA/KIR receptors with type 2 diabetes in South India

The present study was undertaken to delineate the association(s) of KIR–HLA combination in South Indian Type 2 diabetes mellitus (T2DM) patients. The T2DM patients (n = 343) and healthy controls (n = 309) were genotyped for KIR/HLA ligands by PCR‐SSP method. The increased frequency of activatory KIR (aKIR) 2DS2 (OR = 1.91; p < 2.91 × 10^?4) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR = 0.38; p < 1.55 × 10^?5) and aKIRs 2DS1 (OR = 0.60; p < 0.001) and 3DS1 (OR = 0.52; p < 5.83 × 10^?5) were decreased in patients suggesting protective associations. The C1/C2 combinatorial analysis has revealed an increased frequency of C1⁺/C2^? in T2DM patients (OR = 1.62; p < 0.014). The KIR “AB” genotype (OR = 2.41; p < 3.87 × 10^?5) was observed to be higher in patients. However, the “BB” genotype (OR = 0.32; p < 4.71 × 10^?7) was increased in controls. The KIR motifs, “Tel‐B/B” (OR = 1.84; p < 0.007), were observed higher among patients. However, the frequency of “Tel‐A/B” motif genotype was decreased in patients (OR = 0.56; p < 3.13 × 10^?4). The iKIR/HLA combinations such as 2DL2/3 +C1 and 3DL2+A3/A11 were increased in patients (OR = 3.90; p < 7.5 × 10^?5) suggesting susceptible associations. On the contrary, the aKIR+HLA combinations such as 2DS2+C1, 2DS1+C2 and 3DS1+Bw4 were less frequent in patients (OR = 0.32; p < 4.2 × 10^?4) suggesting protective associations. Thus, the present study clearly establishes the positive and negative associations of different KIR–HLA receptor combinations with T2DM in South India.