Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis

Introduction

Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2^gt/gt) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters.

Material and methods

We performed long-term-ECG recordings in transgenic CAP2 deficient mice (C57BL/6) to detect spontaneous arrhythmias. In vivo electrophysiological studies by right heart catheterization and ex vivo epicardial mapping were used to analyze electrophysiological parameters, the inducibility of arrhythmias, and conduction velocities. Expression and distribution of cardiac connexins and the amount of cardiac fibrosis were evaluated.

Results

Spontaneous ventricular arrhythmias could be detected in Cap2^gt/gt during the long-term-ECG recording. Cap2^gt/gt showed marked conduction delays at atrial and ventricular levels, including a reduced heart rate (421.0 ±40.6 bpm vs. 450.8 ±27.9 bpm; p < 0.01), and prolongations of PQ (46.3 ±4.1 ms vs. 38.6 ±6.5 ms; p < 0.01), QRS (16.2 ±2.6 ms vs. 12.6 ±1.4 ms; p < 0.01), and QTc interval (55.8 ±6.0 ms vs. 45.2 ±3.3 ms; p = 0.02) in comparison to wild type mice. The PQ prolongation was due to an infra-Hisian conduction delay (HV: 9.7 ±2.1 ms vs. 6.5 ±3.1 ms; p = 0.02). The inducibility of ventricular tachycardias during the electrophysiological studies was significantly elevated in the mutant mice (inducible animals: 88% vs. 33%; p = 0.04). Cap2^gt/gt showed more abnormal distribution of connexin43 compared to WT (23.0 ±4.7% vs. 2.9 ±0.8%; p < 0.01). Myocardial fibrosis was elevated in Cap2^gt/gt hearts (9.1 ±6.7% vs. 5.5 ±3.3%; p < 0.01).

Conclusions

Loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in Cap2^gt/gt are associated with alterations in myocardial connexins and fibrosis.     

Changes in left ventricular ejection fraction and coronary flow reserve after coronary microembolization

Introduction

Although coronary microembolization (CME) is a frequent phenomenon in patients undergoing percutaneous coronary intervention, few data are available on the changes in left ventricular ejection fraction (LVEF) and coronary flow reserve (CFR) after CME.

Material and methods

In this study, six miniature swine of either sex (body weight 21-25 kg) were used to prepare a CME model. After coronary angiography, 1.2 × 10⁵ microspheres (42 µm) were selectively infused into the left anterior descending artery via an infusion catheter. Left ventricular ejection fraction was evaluated using transthoracic echocardiography; myocardial blood flow was measured using coloured microspheres; and CFR and coronary pressure were measured using Doppler and a pressure wire.

Results

Left ventricular ejection fraction was 0.77 ±0.08 at baseline, 0.69 ±0.08 at 2 h, 0.68 ±0.08 at 6 h, and 0.76 ±0.06 at 1 week (2 h vs. baseline p < 0.05; 6 h vs. baseline p < 0.01). After CME, left ventricular end systolic volume (LVESV) and end diastolic volume (LVEDV) were significant larger 1 week later (p < 0.01 for both), while CFR was significantly reduced at 6 h (1.24 ±0.10 at 6 h vs. 1.77 ±0.30 at baseline, p < 0.01) and myocardial blood flow remained unchanged. Serum ET-1 level was significantly higher only at 6 h after CME (6 h vs. baseline p < 0.05).

Conclusions

Reduction of CFR and LVEF is significant at 6 h after CME and recovers 1 week later with left ventricular dilation.     

Aberrant expression of cytokine interleukin 9 along with interleukin 4 and interferon γ in connective tissue disease-associated interstitial lung disease: association with severity of pulmonary fibrosis

Introduction

Connective tissues diseases (CTDs) are a heterogeneous group of disorders that share certain clinical characteristics and disturbed immunoregulation. Interstitial lung diseases (ILDs), also known as diffuse parenchymal lung diseases, are among the most serious pulmonary complications associated with CTDs. Interleukin 9 (IL-9), IL-4 and interferon γ (IFN-γ) – cytokines with important roles in autoimmune disease – were studied in CTD patients and CTD-ILD patients.

Material and methods

Sixty-one hospitalized untreated CTD patients were recruited, and 20 healthy volunteers were enrolled as controls. The 61 CTD patients were divided into a simple CTD group and a CTD-ILD group, and the plasma protein IL-9, IL-4 and IFN-γ levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results

The results indicate that the serum IL-9 levels were significantly higher in CTD-ILD and simple CTD patients than they were in healthy controls (each p < 0.05) and that the levels were elevated in CTD-ILD patients compared with simple CTD patients (p < 0.05). The IL-4 levels were higher in CTD-ILD patients than they were in the simple CTD patients (p < 0.05) and healthy controls (p < 0.01). In addition, the serum IL-9 levels were negatively correlated with the level of IFN-γ (r² = 0.34, p = 0.01), the estimated percentage of predicted forced vital capacity (FVC%) (r² = 0.36, p = 0.00) and the estimated percentage of predicted diffusing capacity (DLCO%) (r² = 0.27, p = 0.04) and were positively correlated with the IL-4 level (r² = 0.31, p = 0.01).

Conclusions

Interleukin-9 may play an important role in the pathogenesis of CTD and may contribute to the progression of interstitial lung injury in CTD patients.     

Daily assessment of arterial distensibility in a pediatric population before and after smoking cessation

OBJECTIVES:

Cigarette smoking is an important modifiable cardiovascular risk factor associated with increased stiffness of the large arteries in adulthood. This study aimed to 1) evaluate arterial distensibility and echocardiographic measures in adolescent smokers before and after participation in a successful smoking cessation program and to 2) compare the findings obtained with data from a control population of healthy non-smokers.

METHODS:

A total of 31 young smoking subjects (58.1% male; range: 11-18 years old; mean: 16.5±1.4 years old; mean tobacco consumption: 2.6±0.6 years) were examined before commencing and after taking part for at least 1 year in a smoking cessation program (mean: 1.4±0.3 years). Arterial stiffness was measured using the previously validated QKd_100-60 method. Twenty-four-hour ambulatory blood pressure monitoring and transthoracic echocardiography were also performed.

RESULTS:

(Smokers before abuse cessation vs. smokers after abuse cessation) systolic blood pressure: p<0.004; diastolic blood pressure: p<0.02; mean blood pressure: p<0.01; QKd_100-60 value: 183±5 vs. 196±3 msec, p<0.009; p = ns for all echocardiographic parameters. (Smokers after abuse cessation vs. controls) systolic blood pressure: p<0.01; diastolic blood pressure: p<0.03; mean blood pressure: p<0.02; QKd_100-60 value: 196±3 vs. 203±2 msec, p<0.04; p<0.02, p<0.01, and p<0.05 for the interventricular septum, posterior wall, and left ventricular mass, respectively.

CONCLUSIONS:

Despite successful participation in a smoking cessation program, arterial distensibility improved but did not normalize. This finding underlines the presence of the harmful effect of arterial rigidity in these individuals, despite their having quit smoking and their young ages, thus resulting in the subsequent need for a lengthy follow-up period.     

The roles of connective tissue growth factor in the development of anastomotic esophageal strictures

Introduction

The aim of this study was to investigate the roles of connective tissue growth factor (CTGF) in the development of anastomotic strictures after surgical repair of the esophagus.

Material and methods

Tissues collected from the patients were divided into three groups based on the results of endoscopy and clinical grading. Patients without dysphagia after esophagectomy were used as the control population. The protein levels of CTGF, TGF-β1, Smad2, and Smad4 were determined by immunohistochemistry (IHC) and western blot analyses, while the mRNA levels of the two growth factors were evaluated by real-time polymerase chain reaction.

Results

Compared with the control group, significantly increased (p < 0.01) levels of CTGF and TGF-β1 protein were observed in the anastomotic stenosis (AS) group, and levels of the two proteins detected by the IHC and western blot analyses were also significantly increased with the increasing severity of stenosis (p < 0.05). The mRNA levels of CTGF and TGF-β1 in the tissues collected from the patients with stenosis were significantly up-regulated (p < 0.05) as compared with those from the control group. In addition, the levels of Smad2 and Smad4 protein were also significantly increased (p < 0.05) with the increasing severity of stenosis, and the protein levels were positively correlated with the levels of CTGF (r = 0.59, p < 0.05) and TGF-β1 (r = 0.63, p < 0.05).

Conclusions

Inhibition of CTGF protein or mRNA expression may be a distinctive and effective therapy for the treatment of postoperative anastomotic strictures.     

Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome

Introduction

Visfatin is an adipokine secreted by visceral adipose tissue with insulin-mimetic properties. Higher circulating visfatin levels were reported in type 2 diabetes. The aim of this study was to analyse circulating visfatin and insulin levels and the visfatin/insulin ratio in obese women with and without metabolic syndrome (MetS).

Material and methods

The study involved 92 obese women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS group consisted of 71 subjects (age: 52.8 ±9.4 years, body mass index [BMI]: 39.1 ±5.6 kg/m², waist circumference: 109.6 ±11.4 cm and fat mass: 52.0 ±12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 ±9.5 years, BMI: 36.3 ±5.2 kg/m², waist circumference: 104.7 ±11.0 cm and fat mass: 45.2 ±10.7 kg). In addition to anthropometric measurements and assessment of serum glucose and lipids, plasma concentrations of visfatin were estimated by enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and visfatin/insulin ratio were calculated.

Results

In the MetS group significantly higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar visfatin levels were observed than in the non-MetS group. As a consequence of the significantly higher plasma insulin concentration the visfatin/insulin ratio was significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio correlated inversely with anthropometric parameters such as body mass, BMI, body fat and waist circumference (r = –0.41, p = 0.0003; r = –0.42, p = 0.0002; r = –0.29, p = 0.01; r = –0.23, p = 0.04, respectively).

Conclusions

We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.     

The effects of L-thyroxin replacement therapy on bone minerals and body composition in hypothyroid children

Introduction

Prolonged treatment with levothyroxine 4 (L-T4) is a well known risk factor for osteoporosis. Patients on L-T4 replacement occasionally have a subnormal TSH, which carries a risk of development of bone loss. Thyroid hormones directly affect bone cells, stimulating osteoclastic and osteoblastic activity with a predominance of bone resorption and decrease of bone mineral density (BMD).

Material and methods

The study included 35 hypothyroid patients with mean age 11.57 ±5.06, while 26 age- and sex-matched children served as controls. Dual energy X-ray absorptiometry (DXA) was done to detect the bone mineral density (BMD), bone mineral content (BMC) and Z score in lumbar and femur neck regions. Body composition was also studied by DXA. Calcium, phosphorus, osteocalcin as a bone formation marker, osteoprotegerin as an indicator of osteoclast activity and urinary deoxypyridinoline as a bone collagen breakdown marker were assessed.

Results

No significant differences were detected in lumbar Z score (−0.12 ±0.66) and femur Z score (−0.17 ±0.58) compared to controls (−0.33 ±0.74 and −0.21 ±0.53 respectively). Bone mineral density and BMC were not significantly different from controls. No significant difference was detected between cases and controls in body composition. A positive correlation was detected between BMD and age (r=0.857, p<0.01), and with the period of treatment (r=0.766, p<0.01). A positive correlation was found between BMD and total body fat (r=0.693, p<0.01), and with abdominal fat (r=0.667, p<0.01).

Conclusions

Levothyroxine 4 treatment in hypothyroid children does not alter bone metabolism and body composition.     

Left ventricular diastolic abnormalities and the impact of hepatitis C virus infection in multitransfused Egyptian children

Introduction

The aim of the study was to evaluate left ventricular cardiac systolic and diastolic functions by echocardiography in multitransfused children and the possible risk of hepatitis C virus infection as an additional factor impairing cardiac functions in these patients.

Material and methods

Echocardiographic studies of left ventricular function in 80 multitransfused patients aged 3 to 15 years with no clinical evidence of heart failure were included in our study. Anti-hepatitis C virus antibody was present in the sera of 25 of them. Twenty age and sex matched normal subjects were studied as a control.

Results

Results showed left ventricular systolic abnormalities in 15 cases (18%). Nine cases were HCV seropositive. Dilatation of left ventricle and impaired systolic function guided by FS (fractional shortening) was significantly reduced compared to normal subjects'' mean FS (p<0.01). Systolic dysfunction is significantly observed in hepatitis C virus seropositive cases (mean FS 29±7.9 vs seronegative cases 31.4±10 (p<0.035). Restrictive left ventricular diastolic abnormalities were detected in 45 patients (56.25%). Diastolic dysfunction was represented in prolonged isovolumic relaxation time in comparison to the control group (p<0.03) and higher E wave (p<0.001) also increased the ratio of early to late diastolic velocity (E/A ratio, 2.03±0.59 vs 1.6±0.27, p<0.05). No significant difference in diastolic functions was found between HCV seropositive and seronegative groups. There is a weak negative correlation between left ventricular FS and serum ferritin level (r=0.77, p<0.001).

Conclusions

Multitransfused children are more liable to left ventricular diastolic dysfunction suggested by impaired relaxation probably due to iron overload and anaemia. Hepatitis C virus infection is an additional factor which might share in impairing left ventricular systolic function. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain serum ferritin at <1000 ng/ml.     

Matrix metalloproteinases in type 2 diabetes and non-diabetic controls: effects of short-term and chronic hyperglycaemia

Introduction

The role of matrix metalloproteinases (MMPs) in type 2 diabetes mellitus (DM) is not clear as increased activation of MMPs in the vasculature contrasts with decreased activity of MMPs in the kidneys, contributing to development of nephropathy.

Material and methods

We measured serum MMP-2 and MMP-9 in 22 subjects with type 2 DM age (mean ± SD) 56.7 ±16.8 years, BMI 31.8 ±4.6 kg/m², HbA_1c 8.45 ±1.78% and in 32 controls, age 39.2 ±16.0 years, BMI 35.2 ±8.5 kg/m². In 15 subjects with 2 DM we also measured MMP-2 and MMP-9 at discharge from hospital and after 3 months (n = 8). In controls, MMP-2 and -9 were also measured during 75 g oral glucose tolerance test (OGTT).

Results

Concentrations of MMP-2 and MMP-9 were lower in subjects with type 2 DM (219 ±62 ng/ml vs. 305 ±63 ng/ml and 716 ±469 ng/ml vs. 1285 ±470 ng/ml, for MMP-2 and MMP-9, respectively, p < 0.05). MMP-9 concentrations fell at 120 min of OGTT from 1675 ±372 ng/ml to 1276 ±422 ng/ml (p < 0.05). In diabetic subjects there was a correlation between MMP-9 and HbA_1c (r = 0.51, p< 0.05). In subjects with diabetes there was a fall of HbA_1c from 9.77 ±1.76% to 8.36 ±1.54% (p < 0.01), at three months post-discharge. There was no difference in MMP-2, but there was a fall in MMP-9 at three months post-discharge in comparison to concentrations observed at admission (854 ±560 ng/ml vs. 500 ±235 ng/ml, p= 0.02).

Conclusions

Matrix metalloproteinases in type 2 and MMP-9 concentrations were lower in subjects with 2 DM than in non-diabetic controls. Regulation of MMPs appears to be complex as hyperglycaemia during OGTT results in a decrease in MMP-9, while chronic hyperglycaemia, reflected by HbA_1c, correlates with MMP-9 concentrations in subjects with 2 DM.     

Changes in the activity of connective tissue matrix enzymes in the metabolic syndrome

Introduction

Early atherosclerotic changes in the endothelium associated with metabolic syndrome are generated with the participation of inflammatory cells, cytokines and enzymes of the extracellular matrix. The study is aimed at a comparison between the activity of inflammatory agents, tumour necrosis factor α (TNF-α) and the enzymes of the connective tissue matrix in the blood of healthy female patients as well as those suffering from the metabolic syndrome.

Material and methods

The examination included 35 women with metabolic syndrome (MS). The control group (C) comprised 35 healthy women. Lipidogram, C-reactive protein level (CRP), fasting glucose level (FGL), matrix metalloproteinase (MMP)-8 and -9 activity, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TNF-α levels in blood were determined.

Results

As compared with the control group, the level of inflammatory factors and the activity of extracellular matrix enzymes in the metabolic syndrome were statistically higher (p < 0.05) and concerned the following parameters: TNF-α (pg/ml): MS 6.59 ±3.18, C 4.78 ±2.91; CRP (mg/dl): MS 2.18 ±2.04, C 1,26 ±1.35; TIMP-1 (ng/ml): MS 265.5 ±2.9, C 205.4 ±72.6; MMP-9 (ng/ml): MS 198.2 ±138.6, C 138.6 ±116.1. Statistically significant correlations were also found between TIMP-1 and the following factors: BMI (R = 0.400, p < 0.001), waist/hip ratio (WHR) (R = 0.278, p < 0.05), waistline (R = 0.417, p < 0.001), FGL (R = 0.290, p < 0.05), HDL cholesterol (R = –0.253, p < 0.05) and triglycerides (R = 0.269, p < 0.05).There were positive correlations of MMP-9 with FGL (R = 0.446, p < 0.001) and waistline (R = 0.260, p < 0.05); MMP-8 with FGL (R = 0.308, p < 0.05); and CRP with BMI (R = 0.370, p < 0.01), WHR (R = 0.325, p < 0.01) and waistline (R = 0.368, p < 0.01).

Conclusions

Metabolic syndrome is connected with higher activity of cytokines (TNF-α), inflammatory markers (CRP) and matrix enzymes (MMP-9, MMP-8, TIMP-1).     

Latent autoimmune diabetes in adults in a population-based cohort of Polish patients with newly diagnosed diabetes mellitus

Introduction

Latent autoimmune diabetes in adults (LADA) is a slowly developing form of autoimmune diabetes characterized by the presence of type 1 diabetes-associated autoantibody. The aim of this study was to determine the incidence and characteristics of LADA in a population-based cohort of Polish patients with newly-diagnosed diabetes.

Material and methods

The study cohort was taken from the resident population of the city Białystok, Poland, during the period 1 January to 31 December 2003, aged 20-64 years. During this period we identified 231 cases of diabetes. We measured glutamic acid decarboxylase (GADA) and insulin antibody (IAA), insulin, C peptide and glycated hemoglobin (HbA_1c). Diagnosis of LADA was made according to Immunology Diabetes Society and Action LADA criteria.

Results

The incidence of LADA was 10 per year per 100 000 people. The proportion of patients with LADA was 8.9% among newly diagnosed cases with diabetes. Patients with LADA were younger at diagnosis (48.5 ±9.4 years vs. 54.8 ±10.6 years, p < 0.01), had lower body mass index (26.9 ±9.3 kg/m² vs. 29.5 ±5.2 kg/m², p < 0.05), C peptide (126 ±127 pmol/l vs. 446 ±592 pmol/l, p < 0.001), and were less insulin resistant (HOMA IR 0.94 ±0.85 vs. 3.6±4.4, p < 0.001) compared to patients with type 2 diabetes. Glycated hemoglobin and fasting glucose were similar in patients with LADA and type 2 diabetes.

Conclusions

In addition to GAD, anti-insulin antibodies are useful for diagnosing autoimmune diabetes in adults. Patients with LADA have similar glucose control parameters (HbA_1c) compared to patients with type 2 diabetes, although they are usually younger and have a lower body mass index. Patients with LADA make up a significant proportion of newly diagnosed people with diabetes mellitus in a Polish population.     

Increased Serum Cathepsin K in Patients with Coronary Artery Disease

Purpose

Cathepsin K is a potent collagenase implicated in human and animal atherosclerosis-based vascular remodeling. This study examined the hypothesis that serum CatK is associated with the prevalence of coronary artery disease (CAD).

Materials and Methods

Between January 2011 and December 2012, 256 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. A total of 129 age-matched subjects served as controls.

Results

The subjects'' serum cathepsin K and high sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher serum cathepsin K levels compared to the controls (130.8±25.5 ng/mL vs. 86.9±25.5 ng/mL, p<0.001), and the patients with acute coronary syndrome had significantly higher serum cathepsin K levels compared to those with stable angina pectoris (137.1±26.9 ng/mL vs. 102.6±12.9 ng/mL, p<0.001). A linear regression analysis showed that overall, the cathepsin K levels were inversely correlated with the high-density lipoprotein levels (r=-0.29, p<0.01) and positively with hs-CRP levels (r=0.32, p<0.01). Multiple logistic regression analyses shows that cathepsin K levels were independent predictors of CAD (odds ratio, 1.76; 95% confidence interval, 1.12 to 1.56; p<0.01).

Conclusion

These data indicated that elevated levels of cathepsin K are closely associated with the presence of CAD and that circulating cathepsin K serves a useful biomarker for CAD.     

Characteristics of Pulmonary Vein Enlargement in Non-Valvular Atrial Fibrillation Patients with Stroke

Purpose

The association between pulmonary vein (PV) dilatation and stroke in non-valvular atrial fibrillation (AF) patients remains unknown.

Materials and Methods

We examined the left atrium (LA) and PV in control (n=138) and non-valvular AF patients without (AF group, n=138) and with non-hemorrhagic stroke (AF with stroke group, n=138) using computed tomography.

Results

The LA, LA appendage (LAA), and all PVs were larger in the AF than control patients. The orifice areas of the LAA (5.6±2.2 cm² vs. 4.7±1.7 cm², p<0.001), left superior PV (3.8±1.5 cm² vs. 3.4±1.2 cm², p=0.019), and inferior PV (2.3±1.0 cm² vs. 1.8±0.7 cm², p<0.001) were larger in the AF with stroke than in the AF only group. However, right PVs were not different between the two groups. In a multivariate analysis, the orifice areas of the left superior PV [odds ratio (OR) 1.25, 95% confidence interval (CI) 1.03-1.51, p=0.02], left inferior PV (OR 1.97, 95% CI 1.41-2.75, p<0.001), and LAA (OR 1.30, 95% CI 1.13-1.50, p<0.001) were independent predictors of stroke.

Conclusion

Compared to the right PVs, the left PVs and LAA exhibited more significant enlargement in patients with AF and stroke than in patients with AF only. This finding suggests that the remodeling of left-sided LA structures might be related to stroke.     

Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method

Purpose

The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method.

Materials and Methods

Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients.

Results

Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days).

Conclusion

Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients'' conveniences.     

Two-dimensional speckle-tracking echocardiography assessment of left ventricular remodeling in patients after myocardial infarction and primary reperfusion

Introduction

Left ventricular remodeling (LVR) is the most prognostically important consequence of acute myocardial infarction (AMI). The aim of the study was to assess the value of speckle tracking echocardiography in the prediction of left ventricular remodeling in patients after AMI and primary coronary angioplasty (PCI).

Material and methods

Eighty-eight patients (F/M = 31/57 patients; 63.6 ±11 years old) with coronary artery disease (CAD) and successful PCI were enrolled and divided into group I with ST-elevation myocardial infarction or non-ST elevation myocardial infarction and group II with stable angina pectoris. Conventional and speckle tracking echocardiography was performed 3 days (baseline), 30 days and 90 days after PCI. Patients were divided into 2 groups based on the presence of LVR (increase of LV end-diastolic and/or end-systolic volume > 20%) at 3 months follow-up.

Results

At initial presentation, 2-chamber longitudinal strain (9.4 ±3.5% vs. –11.6 ±3.6%, p < 0.04) and 4-chamber transverse strain (10.4 ±8.2% vs. 15.6 ±8%, p < 0.003) were lower in the LVR+ group compared to the LVR– group. LV wall motion score index did not differ between the two groups. After 30 days, circumferential apical and basal strain (–15.58 ±8.9% vs. –25.53 ±8.8%, p < 0.001; –15.02 ±5.6 vs. –19.78 ±6.3, p < 0.008), radial apical strain (9.96 ±8.4% vs. 14.15 ±5.5%, p < 0.03), 4-chamber longitudinal strain (–8.7 ±5.8% vs. –13.47 ±3.9%, p < 0.005), 4-chamber transverse strain (10.5 ±8.1% vs. 16.7 ±8.3%, p < 0.03), apical rotation (3.84 ±2.5° vs, 5.66 ±3.2°, p < 0.04) and torsion (6.15 ±4.1° vs. 8.98 ±4.6°, p < 0.03) were significantly decreased in the LVR+ group compared to the LVR– group. According to ROC analysis, circumferential apical strain > –15.92% (sensitivity 93%, specificity 59%, positive predictive value 90%) was the most powerful predictor of remodeling after primary PCI in AMI.

Conclusions

Our results suggest that impaired indices of LV deformation detected 3 days and 30 days after AMI may provide important predictive value in LV remodeling and patients’ follow-up.     

Exhaled eicosanoids and biomarkers of oxidative stress in exacerbation of chronic obstructive pulmonary disease

Introduction

Eicosanoids and oxidants play an important role in inflammation, but their role in chronic obstructive pulmonary disease (COPD) is uncertain. In this study we hypothesized that levels of exhaled leukotrienes, prostaglandins and biomarkers of oxidative stress are increased in infectious exacerbations of COPD and that they decrease after antibiotic therapy.

Material and methods

Cysteinyl-leukotrienes (LTs), leukotriene B₄ (LTB₄), prostaglandin E₄, hydrogen peroxide (H₂O₂) and 8-isoprostane were measured in exhaled breath condensate (EBC) in 16 COPD patients with infectious exacerbations (mean age 64 ±12 years, 13 male) on day 1, during antibiotic therapy (days 2-4), 2-4 days after therapy and at a follow-up visit when stable (21-28 days after therapy).

Results

There was a significant fall in concentration of cys-LTs, LTB₄ and 8-isoprostane at visit 3 compared to day 1 (cys-LTs: 196.5 ±38.4 pg/ml vs. 50.1 ±8.2 pg/ml, p < 0.002; LTB₄: 153.6 ±25.5 pg/ml vs. 71.9 ±11.3 pg/ml, p < 0.05; 8-isoprostane: 121.4 ±14.6 pg/ml vs. 56.1 ±5.2 pg/ml, p < 0.03, respectively). Exhaled H₂O₂ was higher on day 1 compared to that at visits 2 and 3 (0.74 ±0.046 µM vs. 0.52 ±0.028 µM and 0.35 ±0.029 µM, p < 0.01 and p < 0.01, respectively). Exhaled PGE₂ levels did not change during exacerbations of COPD. Exhaled eicosanoids and H₂O₂ in EBC measured at the follow-up visit (stable COPD) were significantly higher compared to those from healthy subjects.

Conclusions

We conclude that eicosanoids and oxidants are increased in infectious exacerbations of COPD. They are also elevated in the airways of stable COPD patients compared to healthy subjects.     

Left ventricular hypertrophy amplifies the QT,and Tp-e intervals and the Tp-e/ QT ratio of left chest ECG

Objective

To evaluate the changes in Tp-e interval (an interval from the peak to the end of the T wave), QT interval and Tp-e/QT ratio of the body surface ECG in patients with left ventricular hypertrophy (LVH).

Methods

The Tp-e interval and QT interval were measured on body surface ECGs in 42 patients without either hypertension or LVH (control group), 41 patients having hypertension but not LVH (non-LVH group), and 38 patients with both hypertension and LVH (LVH group).

Results

The mean corrected QT (QTc) interval, and mean corrected Tp-e[T(p-e)c] interval were significantly longer in the LVH group (0.430±0.021s vs. 0.409±0.019s, p < 0.01; 0.098±0.013s vs. 0.088±0.011s, respectively) than those in the control group. The Tp-e/QT ratio was also amplified in LVH group (0.232±0.028 vs.0.218±0.027) (p < 0.05).

Conclusion

LVH increased the QT interval, Tp-e interval and Tp-e/QT ratio of the body surface ECG.     

Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats

Introduction

β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabradine or metoprolol had any effect on rat HR and blood pressure (BP).

Material and methods

The experiments were performed in hyper- and normocholesterolemic outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5% cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1% methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4) simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6) simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4-week period. HR and BP measure were provided by an Isotec pressure transducer connected to a direct current bridge amplifier. For the further lipid profile examination, 0.25 ml of blood samples were taken.

Results

After administration of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic rats the mean HR was significantly reduced as compared to rats receiving simvastatin (312.0 ±30.2 min⁻¹ vs. 430.7 ±27.8 min⁻¹, p<0.05); (329.8 ±24.2 min⁻¹ vs. 420.5 ±9.2 min⁻¹, p<0.05) or ivabradine alone (312.0 ±30.2 min⁻¹ vs. 350.2 ±16.0 min⁻¹, p<0.05); (329.8 ±24.2 min⁻¹ vs. 363.0 ±21.7 min⁻¹, p<0.05).

Conclusions

Concomitant administration of simvastatin with ivabradine intensified slowing of HR, although it did not influence BP in normo-and hypercholesterolemic rats. Statin-induced intensification of HR deceleration after metoprolol administration was not observed.     

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma,adenoma and hyperplastic polyp

Introduction

Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps.

Material and methods

In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16).

Results

Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed.

Conclusions

Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.     

Preoperative Serum Anti-Mullerian Hormone Level in Women with Ovarian Endometrioma and Mature Cystic Teratoma

Purpose

To investigate whether preoperative serum anti-mullerian hormone (AMH) levels are lower in women with ovarian endometrioma and in women with mature cystic teratoma of the ovaries.

Materials and Methods

In a tertiary university hospital, a retrospective case-control study was performed. Serum AMH levels between an advanced (stage III and IV) endometrioma group (n=102) and an age- and body mass index (BMI)-matched control group were compared. Serum AMH levels between an ovarian mature cystic teratoma group (n=48) and age- and BMI-matched controls were also compared.

Results

Absolute serum AMH and multiples of the median for AMH (AMH-MoM) relevant to Korean standards were lower in the endometrioma group than controls, but this was not statistically significant (mean±SEM, 2.9±0.3 ng/mL vs. 3.3±0.3 ng/mL, p=0.28 and 1.3±0.1 vs. 1.6±0.1, p=0.29, respectively). Specifically, the stage IV endometriosis group (n=51) exhibited significantly lower serum AMH and AMH-MoM (2.1±0.3 vs. 3.1±0.4 ng/mL, p=0.02 and 1.1±0.1 vs. 1.7±0.2, p=0.03, respectively). Serum AMH and AMH-MoM levels were similar between stage III endometriosis and controls (3.7±0.5 vs. 3.4±0.5 ng/mL and 1.6±0.2 vs. 1.5±0.2, respectively), as well as between the mature cystic teratoma group and controls (4.0±0.5 ng/mL vs. 4.0±0.5 ng/mL and 1.6±0.2 vs. 1.6±0.3, respectively). Interestingly, AMH-MoM level was negatively correlated with endometriosis score with statistical significance (r²=0.13, p<0.01).

Conclusion

In women with advanced ovarian endometrioma, preoperative serum AMH values tended to be lower than those for age and BMI-matched controls. Notably, stage IV endometrioma appeared to be closely associated with decreased ovarian reserve, even before operation. Clinicians should keep this information in mind before undertaking surgery of ovarian endometrioma.