Regional muscle oxygenation differences in vastus lateralis during different modes of incremental exercise

Background

Near infrared spectroscopy (NIRS) is used to assess muscle oxygenation (MO) within skeletal muscle at rest and during aerobic exercise. Previous investigations have used a single probe placement to measure MO during various forms of exercise. However, regional MO differences have been shown to exist within the same muscle which suggests that different areas of the same muscle may have divergent MO. Thus, the aim of this study was to examine whether regional differences in MO exist within the same muscle during different types of incremental (rest, 25, 50, 75, 100 % of maximum) exercise (1 leg knee extension (KE), 2 leg KE, or cycling).

Methods

Nineteen healthy active males (Mean ± SD: Age 27 ± 4 yrs; VO_2max: 55 ± 11 mL/kg/min) performed incremental exercise to fatigue using each mode of exercise. NIRS probes were placed on the distal and proximal portion of right leg vastus lateralis (VL). Results were analyzed with a 3-way mixed model ANOVA (probe × intensity × mode).

Results

Differences in MO exist within the VL for each mode of exercise, however these differences were not consistent for each level of intensity. Comparison of MO revealed that the distal region of VL was significantly lower throughout KE exercise (1 leg KE proximal MO – distal MO = 9.9 %; 2 leg KE proximal MO – distal MO = 13 %). In contrast, the difference in MO between proximal and distal regions of VL was smaller in cycling and was not significantly different at heavy workloads (75 and 100 % of maximum).

Conclusion

MO is different within the same muscle and the pattern of the difference will change depending on the mode and intensity of exercise. Future investigations should limit conclusions on MO to the area under assessment as well as the type and intensity of exercise employed.

     

NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study

Objectives

N-terminal B?type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity.

Methods

In this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO₂peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves).

Results

A total of 306 ACHD patients with pulmonary valve replacement (PVR, n = 139), aortic valve replacement (n = 141), mitral valve replacement (n = 21) or tricuspid valve replacement (n = 5) were investigated. The majority of patients (77?%) were in NYHA class I or II. Elevated NT-proBNP levels (cut-off ≥125 pg/ml) were found in 50?% of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (p = 0.029) and VO₂max (p < 0.001). In PVR patients, NT-proBNP levels were associated with lower VO₂peak, also after adjustment for age, gender and age at valve replacement in a multivariate model (p = 0.015).

Conclusions

In patients with ACHD and a prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, a higher NT-proBNP level was associated with a lower VO₂peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.

     

Peak exercise capacity estimated from incremental shuttle walking test in patients with COPD: a methodological study

Background

In patients with COPD, both laboratory exercise tests and field walking tests are used to assess physical performance. In laboratory tests, peak exercise capacity in watts (W peak) and/or peak oxygen uptake (VO₂ peak) are assessed, whereas the performance on walking tests usually is expressed as distance walked. The aim of the study was to investigate the relationship between an incremental shuttle walking test (ISWT) and two laboratory cycle tests in order to assess whether W peak could be estimated from an ISWT.

Methods

Ninety-three patients with moderate or severe COPD performed an ISWT, an incremental cycle test (ICT) to measure W peak and a semi-steady-state cycle test with breath-by-breath gas exchange analysis (CPET) to measure VO₂ peak. Routine equations for conversion between cycle tests were used to estimate W peak from measured VO₂ peak (CPET). Conversion equation for estimation of W peak from ISWT was found by univariate regression.

Results

There was a significant correlation between W peak and distance walked on ISWT × body weight (r = 0.88, p < 0.0001). The agreement between W peak measured by ICT and estimated from ISWT was similar to the agreement between measured W peak (ICT) and W peak estimated from measured VO₂ peak by CPET.

Conclusion

Peak exercise capacity measured by an incremental cycle test could be estimated from an ISWT with similar accuracy as when estimated from peak oxygen uptake in patients with COPD.

     

Production of a therapeutic protein by fusing it with two fragments of the carboxyl-terminal peptide of human chorionic gonadotropin β-subunit in <Emphasis Type="Italic">Pichia pastoris</Emphasis>

Objective

To produce a therapeutic protein (endostatin) by fusion with two fragments of the carboxyl-terminal peptide (CTP) of the human chorionic gonadotropin β-subunit in Pichia pastoris.

Results

Two CTP sequences were fused to the C-terminal of human endostatin, and the fusion protein (endo-CTP) was expressed by P. pastoris. Endo-CTP inhibited proliferation of endothelial cells with an IC₅₀ of 7 μg ml^?1, and 30 % of cells were annexin V-positive after treatment with 20 μg endo-CTP ml^?1 for 48 h. Migration of endothelial cells was inhibited by endo-CTP in a concentration-dependent manner. The half-life of endo-CTP in Sprague–Dawley rats was much longer than that of its commercial counterpart (Endostar).

Conclusion

A long-acting endostatin can be produced using CTP technology.

     

Femoral artery remodeling after aerobic exercise training without weight loss in women

Background

It is currently unclear whether reductions in adiposity mediate the improvements in vascular health that occur with aerobic exercise. The purpose of this longitudinal study of 13 healthy women (33 ± 4 years old) was to determine whether 14 weeks of aerobic exercise would alter functional measures of vascular health, namely resting aortic pulse wave velocity (aPWV, an index of arterial stiffness), femoral artery diameter (D_FA), and femoral artery blood flow (BF_FA) independent of changes in adiposity.

Methods

Aerobic fitness was assessed as VO₂peak normalized to fat-free mass, and adiposity (percent body fat) was determined by dual energy x-ray absorptiometry. Serum concentrations of proteins associated with risk for cardiovascular disease, including C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and leptin, were also measured. Subjects cycled for 50 minutes, 3 times per week.

Results

Aerobic fitness normalized to fat-free mass increased 6% (P = 0.03) whereas adiposity did not change. Resting D_FA increased 12% (P < 0.001) and resting shear rate decreased 28% (P = 0.007). Aortic PWV, and serum sICAM-1, CRP and leptin did not change with training.

Conclusion

Significant reductions in adiposity were not necessary for aerobic exercise training to bring about improvements in aerobic fitness and arterial remodeling. Peripheral arterial remodeling occurred without changes in central arterial stiffness or markers of inflammation.

     

The relationships among endurance performance measures as estimated from VO<Subscript>2PEAK</Subscript>, ventilatory threshold,and electromyographic fatigue threshold: a relationship design

Background

The use of surface electromyography has been accepted as a valid, non-invasive measure of neuromuscular fatigue. In particular, the electromyographic fatigue threshold test (EMG_FT) is a reliable submaximal tool to identify the onset of fatigue. This study examined the metabolic relationship between VO_2PEAK, ventilatory threshold (VT), and the EMG_FT, as well as compared the power output at VO_2PEAK, VT, and EMG_FT.

Methods

Thirty-eight college-aged males (mean ± SD = 22.5 ± 3.5 yrs) performed an incremental test to exhaustion on an electronically-braked cycle ergometer for the determination of VO_2PEAK and VT. Each subject also performed a discontinuous incremental cycle ergometer test to determine their EMG_FT value, determined from bipolar surface electrodes placed on the longitudinal axis of the vastus lateralis of the right thigh. Subjects completed a total of four, 2-minute work bouts (ranging from 75–325 W). Adequate rest was given between bouts to allow for subjects' heart rate to drop within 10 beats of their resting heart rate. The EMG amplitude was averaged over 10-second intervals and plotted over the 2-minute work bout. The resulting slopes from each successive work bout were used to calculate EMG_FT.

Results

Power outputs and VO₂ values from each subject's incremental test to exhaustion were regressed. The linear equations were used to compute the VO₂ value that corresponded to each fatigue threshold. Two separate one-way repeated measure ANOVAs indicated significant differences (p < 0.05) among metabolic parameters and power outputs. However, the mean metabolic values for VT (1.90 ± 0.50 l·min^-1) and EMG_FTVO₂(1.84 ± 0.53 l·min^-1) were not significantly different (p > 0.05) and were highly correlated (r = 0.750). Furthermore, the mean workload at VT was 130.7 ± 37.8 W compared with 134.1 ± 43.5 W at EMG_FT (p > 0.05) with a strong correlation between the two variables (r = 0.766).

Conclusion

Metabolic measurements, as well as the power outputs at VT and EMG_FT, were strongly correlated. The significant relationship between VT and EMG_FT suggests that both procedures may reflect similar physiological factors associated with the onset of fatigue. As a result of these findings, the EMG_FT test may provide an attractive alternative to estimating VT.

     

Untargeted metabolomics analysis of ischemia–reperfusion-injured hearts ex vivo from sedentary and exercise-trained rats

Introduction

The effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential.

Objectives

To identify novel metabolic changes that occur parallel to these mitochondrial alterations, we performed non-targeted metabolomics analysis on hearts from sedentary and exercise-trained rats challenged with isolated heart ischemia–reperfusion injury (I/R).

Methods

Eight-week old Sprague–Dawley rats were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity progressively increased to 1 h at 30 m/min up a 10.5% incline, 75–80% VO_2max). The recovery of pre-ischemic function for sedentary rat hearts was 28.8?±?5.4% (N?=?12) compared to exercise trained hearts, which recovered 51.9%?±?5.7 (N?=?14) (p?<?0.001).

Results

Non-targeted GC–MS metabolomics analysis of (1) sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts challenged with global ischemia–reperfusion (I/R) injury; and (4) exercise-trained rat hearts challenged with global I/R (10/group) revealed 15 statistically significant metabolites between groups by ANOVA using Metaboanalyst (p?<?0.001). Enrichment analysis of these metabolites for pathway-associated metabolic sets indicated a?>?10-fold enrichment for ammonia recycling and protein biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise-trained hearts post-I/R further identified significant differences in three metabolites (oleic acid, pantothenic acid, and campesterol) related to pantothenate and CoA biosynthesis (p?≤?1.24E?05, FDR?≤?5.07E?4).

Conclusions

These studies shed light on novel mechanisms in which exercise-induced cardioprotection occurs in I/R that complement both the mitochondrial stabilization and antioxidant mechanisms recently described. These findings also link protein synthesis and protein degradation (protein quality control mechanisms) with exercise-linked cardioprotection and mitochondrial susceptibility for the first time in cardiac I/R.

     

Increased circulating RANTES in type 2 diabetes

Aim

The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients.

Methods

A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA₁c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD? Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al.

Results

RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA₁c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient’s age, diabetes duration, waist circumference, 1,5-AG, HbA₁c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels.

Conclusion

Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

     

Swimming exercise to control precocious maturation in male seabass (<Emphasis Type="Italic">Dicentrarchus labrax</Emphasis>)

Background

Male European seabass, already predominant (~?70%) in cultured stocks, show a high incidence (20–30%) of precocious sexual maturation under current aquaculture practices, leading to important economic losses for the industry. In view of the known modulation of reproductive development by swimming exercise in other teleost species, we aimed at investigating the effects of sustained swimming on reproductive development in seabass males during the first year of life in order to determine if swimming could potentially reduce precocious sexual maturation.

Methods

Pre-pubertal seabass (3.91?±?0.22 g of body weight (BW)) were subjected to a 10 week swimming regime at their optimal swimming speed (U_opt) in an oval-shaped Brett-type flume or kept at rest during this period. Using Blazka-type swim tunnels, U_opt was determined three times during the course of the experiment: 0.66 m s^??1 at 19?±?1 g BW, 10.2?±?0.2 cm of standard length (SL) (week 1); 0.69 m s^??1 at 38?±?3 g BW, 12.7?±?0.3 cm SL (week 5), and also 0.69 m s^??1 at 77?±?7 g BW, 15.7?±?0.5 cm SL (week 9). Every 2 weeks, size and gonadal weight were monitored in the exercised (N?=?15) and non-exercised fish (N?=?15). After 10 weeks, exercised and non-exercised males were sampled to determine plasma 11-ketotestosterone levels, testicular mRNA expression levels of genes involved in steroidogenesis and gametogenesis by qPCR, as well as the relative abundance of germ cells representing the different spermatogenic stages by histological examination.

Results

Our results indicate that sustained swimming exercise at U_opt delays testicular development in male European seabass as evidenced by decreased gonado-somatic index, slower progression of testicular development and by reduced mRNA expression levels of follicle stimulating hormone receptor (fshR), 3-beta-hydroxysteroid dehydrogenase (3βhsd), 11-beta hydroxysteroid dehydrogenase (11βhsd), estrogen receptor-beta (erβ2), anti-mullerian hormone (amh), structural maintenance of chromosomes protein 1B (smc1β), inhibin beta A (inhba) and gonado-somal derived factor 1 (gsdf1) in exercised males as compared with the non-exercised males.

Conclusions

Swimming exercise may represent a natural and non-invasive tool to reduce the incidence of sexually precocious males in seabass aquaculture.

     

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer’s disease

Introduction

There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives

The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Methods

Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

Results

Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

Conclusion

In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.

     

The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males

Background

It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.

Methods

Ten normally active and nine endurance-trained males (VO_2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO₂ = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).

Results

The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.

Conclusion

Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.

     

The negative effect of ANGPTL8 on HDL-mediated cholesterol efflux capacity

Background

It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression.

Methods

Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H³-cholesterol loading THP-1 cell models.

Results

ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2–836.8) vs 458.2 (356.8–755.6), P?=?0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58?±?2.06 vs 12.51?±?2.83%, P?<?0.0001; DM: 13.62?±?2.57 vs 12.34?±?3.16%, P?=?0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r?=???0.188, P?<?0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β?=???0.143, P?=?0.023).

Conclusion

ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.

     

Treatment of pulmonary arterial hypertension in congenital heart disease in Singapore versus the Netherlands: age exceeds ethnicity in influencing clinical outcome

Background

Advanced treatment of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is increasingly applied worldwide following the—mainly Western world based—international PAH-CHD guidelines. However, studies comparing clinical presentation and outcome after the initiation of PAH-specific treatment are lacking. We aimed to analyse this in a Singaporean and Dutch cohort of PAH-CHD patients.

Methods

Adult CHD patients starting PAH-specific therapy, enrolled in two nationwide registries, were analysed. Patients received phosphodiesterase-type-5 inhibitors, endothelin receptor antagonists, or a combination. Change in six-minute walk test (6MWT) during follow-up was analysed using linear mixed model analysis. Determinants for mortality were assessed using Cox proportional hazard analyses.

Results

A total of 74 patients, 45 Dutch (mean age 47?±?14 years) and 29 Singaporean (mean age 41?±?14 years) were analysed. Despite a lower 6MWT (312 versus 395 metres, p?=?0.01) and peak VO₂ (35 versus 49?% of predicted, p?=?0.01) at baseline in Singaporean patients, the treatment effect was similar in the two populations. Age at initiation of therapy (per 5 year lower age, β?=?+?4.5, p?=?0.017) was the strongest predictor of improvement in exercise capacity, corrected for ethnicity, baseline 6MWT, sex and CHD defect.

Conclusions

Patients from Singapore had a worse clinical performance at baseline compared with the PAH-CHD patients from the Netherlands. No relation between ethnicity and improvement in 6MWT after PAH-specific therapy was found. Age at initiation of PAH-specific therapy was the strongest predictor of treatment efficacy and mortality, emphasising the need for early initiation of treatment in these patients.

     

Adolescents with metabolic syndrome have a history of low aerobic fitness and physical activity levels

Purpose

Metabolic syndrome (MS) is a clustering of cardiovascular disease risk factors that identifies individuals with the highest risk for heart disease. Two factors that may influence the MS are physical activity and aerobic fitness. This study determined if adolescent with the MS had low levels of aerobic fitness and physical activity as children.

Methods

This longitudinal, exploratory study had 389 participants: 51% girls, 84% Caucasian, 12% African American, 1% Hispanic, and 3% other races, from the State of North Carolina. Habitual physical activity (PA survey), aerobic fitness (VO₂max), body mass index (BMI), blood pressure, and lipids obtained at 7–10 y of age were compared to their results obtained 7 y later at ages 14–17 y.

Results

Eighteen adolescents (4.6%) developed 3 or more characteristics of the MS. Logistic regression, adjusting for BMI percentile, blood pressure, and cholesterol levels, found that adolescents with the MS were 6.08 (95%CI = 1.18–60.08) times more likely to have low aerobic fitness as children and 5.16 (95%CI = 1.06–49.66) times more likely to have low PA levels.

Conclusion

Low levels of childhood physical activity and aerobic fitness are associated with the presence of the metabolic syndrome in adolescents. Thus, efforts need to begin early in childhood to increase exercise.

     

Evaluation of insulin-like growth factor-I in postmenopausal women with breast cancer treated with raloxifene

Background

The objective of this study was to evaluate serum IGF-I levels in postmenopausal women with breast cancer treated primarily with raloxifene.

Methods

Twenty-two postmenopausal patients with operable, stage I or II, estrogen receptor-positive carcinomas participated in this study. Following confirmation of diagnosis, the patients received 60 mg of raloxifene for 28 days prior to definitive surgery. Blood samples were collected for evaluation of serum IGF-I levels prior to initiating medication and following a 28-day treatment course. Student's t-test for paired samples was used in the statistical analysis. Significance was established at p < 0.05.

Results

Mean serum IGF-I levels pre- and post-raloxifene treatment were 143.7 ± 9.7 ng/ml and 94.8 ± 7.6 ng/ml, respectively. This reduction in serum IGF-I levels following treatment with raloxifene was statistically significant (p < 0.001).

Conclusion

Raloxifene significantly reduced serum IGF-I levels in postmenopausal women with breast cancer.

     

Evaluation of protein Z plasma level in beta-thalassemia major patients in Ahvaz city in Iran

Objectives

Thrombotic episodes occurred frequently in beta-thalassemia major (BTM) patients, leading to hypercoagulability of plasma. Protein Z (PZ) is a vitamin-K-dependent anti-coagulation factor that plays a role in the human homeostatic process. The objective of the current study is to investigate the distribution pattern of PZ plasma concentrations between BTM patients and the normal population in Ahvaz city, the center of Khuzestan province, southwest of Iran.

Material and Methods

Forty confirmed BTM patients and 40 healthy volunteers were evaluated for complete blood count (CBC) indices and PZ plasma levels. CBC samples were measured using an automated cell counter, and PZ was assayed with an immunoassay method. Statistical analysis was conducted using SPSS software. The ROC curve and binary logistic regression estimated the sensitivity, specificity, and Odd’s ratio for PZ measurement.

Results

The mean±SD of the PZ plasma level in normal individuals was 1.68±0.63 μg/mL, and in BTM patients, it was 1.10±0.52 μg/mL. This shows a significant reduction of PZ in BTM patients statistically (CI = 0.99; p<0.001). Further, the mean±SD of the PZ plasma levels in BTM patients who received washed red blood cells was not significantly different from that of patients undergoing packed red blood cell therapy (CI = 0.95; p = 0.320). The area under the curve (AUC) for PZ was 0.759 (p = 0.00). The cut-off value = 1.4 μg/mL of the PZ plasma level had at least 70% sensitivity and specificity in BTM patients.

Discussion

Several epidemiologic studies have shown thromboembolism episodes in BTM patients. In the current study, PZ was reduced significantly in BTMs.

Conclusion

We noticed that BTMs have lower plasma PZ concentration might be predisposed to BTM.

     

Detection of potential new biomarkers of atherosclerosis by probe electrospray ionization mass spectrometry

Introduction

Atherosclerotic diseases are the leading cause of death worldwide. Biomarkers of atherosclerosis are required to monitor and prevent disease progression. While mass spectrometry is a promising technique to search for such biomarkers, its clinical application is hampered by the laborious processes for sample preparation and analysis.

Methods

We developed a rapid method to detect plasma metabolites by probe electrospray ionization mass spectrometry (PESI-MS), which employs an ambient ionization technique enabling atmospheric pressure rapid mass spectrometry. To create an automatic diagnosis system of atherosclerotic disorders, we applied machine learning techniques to the obtained spectra.

Results

Using our system, we successfully discriminated between rabbits with and without dyslipidemia. The causes of dyslipidemia (genetic lipoprotein receptor deficiency or dietary cholesterol overload) were also distinguishable by this method. Furthermore, after induction of atherosclerosis in rabbits with a cholesterol-rich diet, we were able to detect dynamic changes in plasma metabolites. The major metabolites detected by PESI-MS included cholesterol sulfate and a phospholipid (PE18:0/20:4), which are promising new biomarkers of atherosclerosis.

Conclusion

We developed a remarkably fast and easy method to detect potential new biomarkers of atherosclerosis in plasma using PESI-MS.

     

Plaque volume and plaque risk profile in diabetic vs. non-diabetic patients undergoing lipid-lowering therapy: a study based on 3D intravascular ultrasound and virtual histology

Background

Coronary atherosclerosis progresses faster in patients with diabetes mellitus (DM) and causes higher morbidity and mortality in such patients compared to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque phenotype during lipid-lowering therapy in DM versus non-DM patients using advanced intracoronary imaging.

Methods

We analyzed data from 61 patients with stable angina pectoris included to the PREDICT trial searching for prediction of plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin daily). Geometrically correct, fully 3-D representation of the vascular wall surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue characterization was obtained via fusion of two-plane angiography and IVUS-VH. Frame-based indices of plaque morphology and virtual histology analyses were computed and averaged in 5 mm long baseline/follow-up registered vessel segments covering the entire length of the two sequential pullbacks (baseline, 1-year). We analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score (LAPS).

Results

Despite reaching similar levels of LDL cholesterol (DM 2.12 ± 0.91 mmol/l, non-DM 1.8 ± 0.66 mmol/l, p = 0.21), DM patients experienced, compared to non-DM ones, higher progression of mean plaque area (0.47 ± 1.15 mm² vs. 0.21 ± 0.97, p = 0.001), percent atheroma volume (0.7 ± 2.8% vs. ? 1.4 ± 2.5%, p = 0.007), increase of LAPS (0.23 ± 1.66 vs. 0.13 ± 1.79, p = 0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non-DM patients reached significant decrease of LDL cholesterol. Plaque changes were more pronounced in PIT (pathologic intimal thickening) compared to TCFA with increased plaque area in both phenotypes in DM patients.

Conclusion

Based on detailed 3D analysis, we found advanced plaque phenotype and further atherosclerosis progression in DM patients despite the same reached levels of LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier: NCT01773512

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.