Coronary aspirate TNFα reflects saphenous vein bypass graft restenosis risk in diabetic patients

Background

Patients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device.

Methods

SVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6?months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined.

Results

Patients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4?mg, P<0.05). The TNFα concentration in particulate debris and coronary aspirate plasma was higher in patients with than without DM (15.9±6.6 vs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, P<0.05), whereas total calcium and vasoconstrictors were not different. Patients with DM had a greater percent diameter stenosis 6?months after stent implantation than those without DM (22.17±5.22 vs. 6.34±1.11%, P<0.05). The increase in TNFα immediately after stent implantation correlated with restenosis 6?months later (r=0.69, P<0.05).

Conclusion

In diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process.

Trial registration

URL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884     

Coronary microcirculatory dysfunction is associated with left ventricular dysfunction during follow-up after STEMI

Background

Coronary microvascular resistance is increased after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), which may be related in part to changed left ventricular (LV) dynamics. Therefore we studied the coronary microcirculation in relation to systolic and diastolic LV function after STEMI.

Methods

The study cohort consisted of 12 consecutive patients, all treated with primary PCI for a first anterior wall STEMI. At 4 months, we assessed pressure-volume loops. Subsequently, we measured intracoronary pressure and flow velocity and calculated coronary microvascular resistance. Infarct size and LV mass were assessed using magnetic resonance imaging.

Results

Patients with an impaired systolic LV function due to a larger myocardial infarction showed a higher baseline average peak flow velocity (APV) than the other patients (26?±?7 versus 17?±?5 cm/s, p?=?0.003, respectively), and showed an impaired variable microvascular resistance index (2.1?±?1.0 versus 4.1?±?1.3 mmHg?cm^?1?s^?1, p?=?0.003, respectively). Impaired diastolic relaxation time was inversely correlated with hyperaemic APV (r?=??0.56, p?=?0.003) and positively correlated with hyperaemic microvascular resistance (r?=?0.48, p?=?0.01). LV dilatation was associated with a reduced variable microvascular resistance index (r?=?0.78, p?=?0.006).

Conclusion

A larger anterior myocardial infarction results in impaired LV performance associated with reduced coronary microvascular resistance variability, in particular due to higher coronary blood flow at baseline in these compromised left ventricles.     

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

Background

Ectonucleotidase dependent adenosine generation has been implicated in preconditioning related cardioprotection against ischemia-reperfusion injury, and treatment with a soluble ectonucleotidase has been shown to reduce myocardial infarct size (IS) when applied prior to induction of ischemia. However, ectonucleotidase treatment according to a clinically applicable protocol, with administration only after induction of ischemia, has not previously been evaluated. We therefore investigated if treatment with the ectonucleotidase apyrase, according to a clinically applicable protocol, would reduce IS and microvascular obstruction (MO) in a large animal model.

Methods

A percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40 min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9 mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI.

Results

No differences were observed between the apyrase group and saline group with respect to IS/AAR (75.7 ± 4.2% vs 69.4 ± 5.0%, p = NS) or MO (10.7 ± 4.8% vs 11.4 ± 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.

Conclusion

Apyrase treatment according to a clinically applicable protocol, with administration of apyrase after induction of ischemia, does not reduce myocardial infarct size or microvascular obstruction.     

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study)

Background

Microalbuminuria and subsequent progression to proteinuria and nephropathy is associated with increased oxidative stress, increased inflammatory cytokines and increased cardiovascular (CVD) risk. The common functional IL-6 -174G>C gene variant is also associated with elevated levels of inflammatory cytokines and CVD risk.

Methods

The aim of this study was to examine the association between the IL-6 -174G>C gene variant with plasma total antioxidant status (TAOS) in 552 subjects with type 2 diabetes in relation to urinary protein excretion.

Results

In subjects free from CVD, there was a significant interaction between urinary protein excretion (normoalbuminuria/ microalbuminuria/proteinuria) and the -174C allele (compared to -174GG) in determining plasma TAOS (p value for interaction = 0.03). In the -174C allele carriers there was a significant association between plasma TAOS and urinary protein excretion: normalbuminuria v microalbuminuria v proteinuria: 44.30% ± 11.32 vs. 39.74% ± 14.83 vs. 37.93% ± 16.42, ANOVA p = 0.025. In those with CVD, no interaction or association was observed with the -174C allele (p = 0.246).

Conclusion

The IL-6 -174G>C gene variant is associated with differences in plasma oxidative stress in response to altered protein excretion in subjects with type 2 diabetes.     

Urine metabolites are associated with glomerular lesions in type 2 diabetes

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

     

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

Introduction

Autoantibodies against C1q correlate with lupus nephritis. We compared titers of anti-C1q and anti-dsDNA in 70 systemic lupus erythematosus patients with (n = 15) or without (n = 55) subsequent biopsy-proven lupus nephritis.

Methods

The 15 patients with subsequent lupus nephritis had anti-C1q assays during clinical flares (mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), 10.0 ± 4.7; range, 3 to 22) before the diagnosis of lupus nephritis (median, 24 months; range 3 to 192). Among the 55 others, 33 patients had active lupus (mean SLEDAI, 10.3 ± 6.2; range, 4 to 30) without renal disease during follow-up (median 13 years; range 2 to 17 years) and 22 had inactive lupus (mean SLEDAI, 0; range, 0 to 3).

Results

Anti-C1q titers were elevated in 15/15 (100%) patients who subsequently developed nephritis (class IV, n = 14; class V, n = 1) and in 15/33 (45%) patients without renal disease (P < 0.001). The median anti-C1q titer differed significantly between the groups (P = 0.003). Anti-C1q titers were persistently positive at the time of glomerulonephritis diagnosis in 70% (7/10) of patients, with no difference in titers compared with pre-nephritis values (median, 147 U/ml; interquartile range (IQR), 69 to 213 versus 116 U/ml; 50 to 284, respectively). Titers decreased after 6 months' treatment with immunosuppressive drugs and corticosteroids (median, 76 U/ml; IQR, 33 to 106) but remained above normal in 6/8 (75%) patients. Anti-dsDNA antibodies were increased in 14/15 (93.3%) patients with subsequent nephritis and 24/33 (72.7%) patients without nephritis (P = ns). Anti-C1q did not correlate with anti-dsDNA or the SLEDAI in either group.

Conclusions

Anti-C1q elevation had 50% positive predictive value (15/30) and 100% (18/18) negative predictive value for subsequent class IV or V lupus nephritis.     

Early repolarization with horizontal ST segment may be associated with aborted sudden cardiac arrest: a retrospective case control study

Background

Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.

Methods and Results

One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10). QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; P < 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, P = 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, P = 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (P < 0.004).

Conclusions

QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.

Trial registration

Clinicaltrial.gov registration NCT01031797     

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans

Objective:

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Design and methods:

The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6‐7 days on a weight‐maintenance diet (control, C; n = 55) and 6‐7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10).

Results:

F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI.

Conclusions:

Short‐term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short‐term regulation of hepatic glucose metabolism by simple carbohydrates.     

The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study

Introduction

Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods

We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA.

Results

Patients with pSS showed increased plasma level of total MPs (mean ± SEM 8.49 ± 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 ± 1.05 n PS Eq, P = 0.004) and SLE (7.3 ± 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 ± 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum β2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P ≤ 0.006).

Conclusions

Plasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.     

Myeloid related protein induces muscle derived inflammatory mediators in juvenile dermatomyositis

Introduction

The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.

Methods

In this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.

Results

Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.

Conclusions

This study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.     

Predicting the efficacy of the nitrification inhibitor dicyandiamide in pastoral soils

Aims

Identification of soil, environmental, or microbial properties linked with efficacy of the nitrification inhibitor dicyandiamide (DCD) in high and low-input pastoral farming system soils.

Methods

Soils were collected from under 25 pastures. Potential nitrification rate (PRN) was quantified in the presence and absence of DCD, and percentage efficacy of DCD in reducing PNR calculated. PNR and %DCD efficacy were statistically tested (REML analysis) for relationships to a suite of edaphic (33), environmental (5), and microbiological (8) variables. Microbiological properties included measurement of bacterial and archaeal ammonia monooxygenase genes (amoA qPCR) and soil DNA content.

Results

DCD reduced PRN by an average of 36 %. The percent DCD efficacy was not related to system intensity, soil type, nor PNR (all P?>?0.05). However the numbers of bacterial amoA genes (r?=?0.46; P?<?0.05), and ratios of bacterial:archaeal amoA (r?=??0.53; P?<?0.05), were strongly correlated to %DCD efficacy. In both high and low input systems, models best explaining variance in %DCD efficacy fitted AOA: AOB g soil^?1 as the first varaible (P?<?0.05).

Conclusions

Characterisation of soils based on ammonia oxidising communities may increase the ability to predict the % efficacy of DCD between sites and provide for more targeted application of this nitrification inhibitor.     

Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes

Background

Fluctuations in blood glucose level cause endothelial dysfunction and play a critical role in onset and/or progression of atherosclerosis. We hypothesized that fluctuation in blood glucose levels correlate with vascular endothelial dysfunction and that this relationship can be assessed using common bedside medical devices.

Methods

Fluctuations in blood glucose levels were measured over 24?hours by continuous glucose monitoring (CGM) on admission day 2 in 57 patients with type 2 diabetes mellitus. The reactive hyperemia index (RHI), an index of vascular endothelial function, was measured using peripheral arterial tonometry (EndoPAT) on admission day 3.

Results

The natural logarithmic-scaled RHI (L_RHI) correlated with SD (r=?0.504; P<0.001), the mean amplitude of glycemic excursions (MAGE) (r=?0.571; P<0.001), mean postprandial glucose excursion (MPPGE) (r=?0.411; P=0.001) and percentage of time ≥200?mg/dl (r=?0.292; P=0.028). In 12 patients with hypoglycemia, L_RHI also correlated with the percentage of time at hypoglycemia (r=?0.589; P=0.044). L_RHI did not correlate with HbA1c or fasting plasma glucose levels. Furthermore, L_RHI did not correlate with LDL cholesterol, HDL cholesterol, and triglyceride levels or with systolic and diastolic blood pressures. Finally, multivariate analysis identified MAGE as the only significant determinant of L_RHI.

Conclusions

Fluctuations in blood glucose levels play a significant role in vascular endothelial dysfunction in type 2 diabetes.

Trial registration

UMIN000007581     

Chronic arthritis leads to disturbances in the bone collagen network

Introduction

In this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by chronic inflammation is associated with an imbalance in bone turnover and also a disorganization of the bone type I collagen network.

Methods

Serum, vertebrae and femur bones were collected from eight-month-old polyarthritis SKG mice and controls. Strength of the femoral bones was evaluated using three-point bending tests and density was assessed with a pycnometer. Bone turnover markers carboxy-terminal collagen cross-linking telopeptides (CTX-I) and amino-terminal propeptide of type I procollagen (PINP) were measured in serum. The organization and density of bone collagen were analyzed in vertebrae using second-harmonic generation (SHG) imaging with a two-photon microscope and trabecular bone microstructure was assessed by scanning electron microscope (SEM).

Results

Femoral bones of SKG mice revealed increased fragility expressed by deterioration of mechanical properties, namely altered stiffness (P = 0.007) and reduced strength (P = 0.006), when compared to controls. Accordingly, inter-trabecular distance and trabecular thickness as observed by SEM were reduced in SKG mice. PINP was significantly higher in arthritic mice (9.18 ± 3.21 ng/ml) when compared to controls (1.71 ± 0.53 ng/ml, P < 0.001). Bone resorption marker CTX-I was 9.67 ± 3.18 ng/ml in arthritic SKG mice compared to 6.23 ± 4.11 ng/ml in controls (P = 0.176). The forward-to-backward signal ratio measured by SHG was higher in SKG animals, reflecting disorganized matrix and loose collagen structure, compared to controls.

Conclusions

We have shown for the first time that chronic arthritis by itself impairs bone matrix architecture, probably due to disturbed bone remodeling and increased collagen turnover. This effect might predispose patients to bone fragility fractures.     

Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

Background

Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium.

Methods

We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean ± standard deviation) between the groups by a variance analysis and post hoc test.

Results

Desflurane 6% (84 ± 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 ± 8% of baseline, P < 0.0001). N-mercaptopropionylglycine (54 ± 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 ± 9% of baseline), HOE140 (58 ± 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 ± 9% of baseline) and bradykinin (83 ± 4% of baseline) induced postconditioning (P < 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 ± 8 and 58 ± 5% of baseline, respectively).

Conclusions

In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B₂ receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production.     

Herbs in exercise and sports

Background

Central administration of ??-amino butyric acid (GABA) induces lower body temperature in animals in hot ambient air. However, it is still unknown whether oral GABA administration affects temperature regulation at rest in a hot environment in humans. Therefore, in the present study, we specifically hypothesized that systemic administration of GABA in humans would induce hypothermia in a hot environment and that this response would be observed in association with decreased heat production.

Methods

Eight male participants drank a 200-ml sports drink with 1 g of GABA (trial G) or without GABA (trial C), then rested for 30 minutes in a sitting position in a hot environment (ambient air temperature 33°C, relative humidity 50%).

Results

We found that changes in esophageal temperature from before drinking the sports drink were lower in trial G than in trial C (-0.046 ± 0.079°C vs 0.001 ± 0.063°C; P < 0.05), with lower heat production calculated by oxygen consumption (41 ± 5 W/m² vs 47 ± 8 W/m²; P < 0.05).

Conclusions

In this study, we have demonstrated that a single oral administration of GABA induced a larger decrease in body core temperature compared to a control condition during rest in a hot environment and that this response was concomitant with a decrease in total heat production.     

Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults

Background

Heart type fatty acid binding protein (H-FABP) has been closely associated with acute coronary syndrome, cardiac abnormalities, stroke, and obstructive sleep disorder in previous studies. The aim of this study was to evaluate and compare the serum H-FABP levels and carotid artery intima-media thickness (CIMT) between patients with prediabetes and control subjects.

Research design and methods

We measured serum H-FABP levels in 58 prediabetic patients, 29 with impaired fasting glucose (IFG) and 29 with impaired glucose tolerance (IGT) and 28 age-, sex- and body mass index-matched control subjects using a sandwich enzyme-linked immunosorbent assay (ELISA), and in order to measure CIMT, all participants underwent high-resolution B-mode ultrasonography.

Results

Serum H-FABP levels were significantly elevated in pre-diabetic patients when compared with that of control subjects (IFG: 32.5 ± 34.2 ng/dL, IGT: 45.4 ± 45.8 ng/dL, control: 16.8 ± 14.9 ng/dL; p = 0.011). The difference in means of H-FABP levels between patients with IGT or IFG and control subjects was significant (p = 0.010 and p = 0.009, respectively). CIMT was higher in the pre-diabetic groups compared with the control group (IFG: 0.6 ± 0.1, IGT: 0.6 ± 0.1, control: 0.5 ± 0.1; p < 0.001), and H-FABP level was positively correlated with CIMT (p < 0.001, rho = 0.626).

Conclusion

Our results indicate that patients with pre-diabetes are at increased risk for cardiovascular disease. In addition, serum H-FABP levels could represent a useful marker for myocardial performance in patients with IFG and IGT.     

Epicardial adipose tissue assessed by cardiac magnetic resonance imaging in patients with heart failure due to dilated cardiomyopathy

Objective:

We sought to investigate the association of the EAT with CMR parameters of ventricular remodelling and left ventricular (LV) dysfunction in patients with non‐ischemic dilated cardiomyopathy (DCM).

Design and Methods:

One hundred and fifty subjects (112 consecutive patients with DCM and 48 healthy controls) underwent CMR examination. Function, volumes, dimensions, the LV remodelling index (LVRI), the presence of late gadolinium enhancement (LGE) and the amount of EAT were assessed.

Results:

Compared to healthy controls, patients with DCM revealed a significantly reduced indexed EAT mass (31.7 ± 5.6 g/m² vs 24.0 ± 7.5 g/m², p<0.0001). There was no difference in the EAT mass between DCM patients with moderate and severe LV dysfunction (23.5 ± 9.8 g/m² vs 24.2 ± 6.6 g/m², P = 0.7). Linear regression analysis in DCM patients showed that with increasing LV end‐diastolic mass index (LV‐EDMI) (r = 0.417, P < 0.0001), increasing LV end‐diastolic volume index (r = 0.251, P = 0.01) and increasing LV end‐diastolic diameter (r = 0.220, P = 0.02), there was also a significantly increased amount of EAT mass. However, there was no correlation between the EAT and the LV ejection fraction (r = 0.0085, P = 0.37), right ventricular ejection fraction (r = 0.049, P = 0.6), LVRI (r = 0.116, P = 0.2) and the extent of LGE % (r = 0.189, P = 0.1). Among the healthy controls, the amount of EAT only correlated with increasing age (r = 0.461, P = 0.001), BMI (r = 0.426, P = 0.003) and LV‐EDMI (r = 0.346, P = 0.02).

Conclusion:

In patients with DCM the amount of EAT is decreased compared to healthy controls irrespective of LV function impairment. However, an increase in LV mass and volumes is associated with a significantly increase in EAT in patients with DCM.     

Implication of Urinary Complement Factor H in the Progression of Immunoglobulin A Nephropathy

Background

After activation, the complement system is involved in the pathogenesis of Immunoglobulin A nephropathy (IgAN). Complement factor H (CFH) is a crucial inhibitory factor of the alternative pathway of the complement system. The study investigated the effects of urinary CFH levels on IgAN progression.

Methods

A total of 351patients with IgAN participated in this study. They were followed up for an average of 51.8±26.6 months. Renal outcome was defined as a composite endpoint, that included instances of end-stage renal disease (ESRD),≥ 50% decline in estimated glomerular filtration rate (eGFR) or doubling of plasma creatinine levels. Urinary CFH levels were measured by enzyme-linked immunosorbent assay and calculated as the ratio of urinary CFH over creatinine (uCFH/uCr).

Results

In the whole cohort, uCFH/uCr values were associated with disease progression either as continuous [log(uCFH/uCr)] or categorical traits (dichotomous and quartile variables) after adjusting for eGFR, proteinuria, mean arterial blood pressure, histological grading and immunosuppressive therapy in the Cox proportional hazard model. Kaplan-Meier analysis showed that higher uCFH/uCr values at baseline predicted worse renal outcome during follow-up (log-rank, P<0.001). Receiver operating characteristic curve (ROC) analysis showed that log(uCFH/uCr) had predictive value for renal outcome (area under curve [AUC]=0.745), and the AUC increased to 0.805 after being incorporated into baseline eGFR and proteinuria. In subgroup analysis with eGFR≥60 mL/min/1.73m², log(uCFH/uCr) had better predictive value (AUC= 0.724, P=0.002) for renal outcome compared to eGFR (AUC = 0.582, P=0.259) and proteinuria (AUC = 0.615, P=0.114).

Conclusions

Urinary CFH levels are associated with renal function decline and increased urinary CFH levels are a risk factor for progression of IgA nephropathy.     

Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

Background

Endothelin-1 and angiotensin II are strong vasoconstrictors. Patients with ischemic heart disease have elevated plasma levels of endothelin-1 and angiotensin II and show increased vascular tone. The aim of the present study was to examine the endothelin and angiotensin II receptor expression in subcutaneous arteries from patients with different degrees of ischemic heart disease.

Methods

Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ET_A) and type B (ET_B), and angiotensin type 1 (AT₁) and type 2 (AT₂) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro pharmacology.

Results

ET_A and, to a lesser extent, ET_B receptor staining was observed in the healthy vascular smooth muscle cells. The level of ET_B receptor expression was higher in patients undergoing CABG surgery (250% ± 23%; P < 0.05) and in the patients with angina pectoris (199% ± 6%; P < 0.05), than in the healthy controls (100% ± 28%). The data was confirmed by Western blotting. Arteries from CABG patients showed increased vasoconstriction upon administration of the selective ET_B receptor agonist sarafotoxin S6c, compared to healthy controls (P < 0.05). No such difference was found for the ET_A receptors. AT₁ and, to a lesser extent, AT₂ receptor immunostaining was seen in the vascular smooth muscle cells. The level of AT₁ receptor expression was higher in both the angina pectoris (128% ± 25%; P < 0.05) and in the CABG patients (203% ± 41%; P < 0.05), as compared to the healthy controls (100% ± 25%). The increased AT₁ receptor expression was confirmed by Western blotting. Myograph experiment did however not show any change in vasoconstriction to angiotensin II in CABG patients compared to healthy controls (P = n.s).

Conclusion

The results demonstrate, for the first time, upregulation of ET_B and AT₁ receptors in vascular smooth muscle cells in ischemic heart disease. These receptors may play a role in the pathophysiology of ischemic heart disease and could provide important targets for pharmaceutical interventions.