[Pathogenesis of inner environment changes in acute muscular compartment syndrome]. / Patogenéza zmien vnútorného prostredia pri akútnom svalovom kompartment syndróme.

Acute compartment syndrome results from a pressure increase within an anatomically defined space delineated by a non-elastic surrounding. Every muscle group, encased by fascia/bone, presents a compartment with a potential to develop increased pressure under certain conditions. Increase in pressure within the compartment causes a decrease in perfusion pressure, leading to ischemia and pathological utilisation of energy substrates on the cellular level. Initially, the malfunction of cellular metabolism is functional and reversible. Later progress of these changes leads into irreversible myonecrosis. Restitution of blood supply reverses the local ischemia, however, the following reperfusion syndrome associated with oxidative stress, leads to further pathological sequelae. Re-established blood circulation carries the end-products of myonecrosis and activated immunocompetent cells from the site of lesion into the whole body. Furthermore, locally activated endothelium becomes a significant source of systemic inflammatory mediators. Pro-inflammatory conditions induce the response of anti-inflammatory regulatory mechanisms and their mutual interaction determines both local and systemic outcome of the disease.

[Crush syndrome of today - rhabdomyolysis of intoxication]. / Crush syndróm súcasnosti - rabdomyolýza intoxikovaných.

Crush syndrome is a major issue in war-afflicted countries and in times of peace also in case of a mining accident. This syndrome is characterized by a number of symptoms originating from muscle damage - rhabdomyolysis - resulting from long-lasting entrapment of the body/extremities. Nowadays, crush syndrome seems to be a scarce condition. However, the rare incidence may rather be the result of poor diagnostic recognition. Although the war conflicts and mining accidents became seldom, increased incidence of rhabdomyolysis is progressively associated with world-wide drug consumption. Long-term immobilisation of intoxicated drug addicts frequently leads to muscle damage, mediated by a local pressure exerted on the extremities. Rhabdomyolysis may become clinically manifest in a form of an acute muscular compartment syndrome.

Cardiovascular risk and insulin resistance in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to cardiovascular and cerebrovascular diseases in previous studies. However, it remains unclear whether OSA relates to cardiovascular outcomes independently of obesity and/or insulin resistance. MATERIAL/METHODS: At a tertiary referral teaching hospital, this cross-sectional analysis of 98 subjects (28 without, 39 with mild-moderate, and 31 with severe OSA) aimed to determine whether OSA relates to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) cardiovascular risk independently of obesity and insulin resistance. OSA was diagnosed by attended polysomnography. The insulin resistance index (HOMA-IR) was based on a homeostasis model assessment method. RESULTS: Of the patients without to those with mild-moderate to those with severe OSA, significant increases were observed in NCEP ATP III risk [median (25%, 75% quartiles) from 2.0 (1.0, 8.0) to 3.0 (1.0, 12.0) to 16.0 (5.3, 20.0)%, p <0.001 for the trend] in association with increases in HOMA-IR (p<0.001), diastolic (p=0.039) and mean blood pressure (p=0.016), serum triglycerides (p=0.047), apolipoprotein B (p=0.039), plasma fibrinogen (p=0.013), and fasting glucose levels (p=0.002). Compared with subjects without sleep apnea, patients with severe OSA had significantly higher odds for NCEP ATP III risk higher than 10% (moderately high and high cardiovascular risk) (odds ratio: 4.06, 95% confidence interval: 1.02-16.25, p=0.048) after adjustment for body mass index and HOMA-IR. CONCLUSIONS: These findings suggest that severe OSA is related to higher cardiovascular risk independently of obesity and insulin resistance.

Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome.

BACKGROUND: The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome. METHODS: In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-alpha, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm. RESULTS: In patients who used CPAP for > or = 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-alpha (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 +/- 9.8 to 13.9 +/- 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy. CONCLUSIONS: In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Systemic inflammation and systemic oxidative stress in patients with acute exacerbations of COPD.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the inflammatory processes and oxidative stress are closely linked in the lung compartment. However, the relationships between systemic inflammation and parameters of oxidative stress in the systemic circulation during acute exacerbations of COPD remain to be explored. OBJECTIVE: To analyze relationships between erythrocytic glutathione peroxidase (GPx), a marker of systemic oxidative stress, and parameters reflecting systemic inflammation, such as circulating neutrophils, C-reactive protein (CRP), and interleukin (IL)-6, in patients with acute exacerbations of COPD. PATIENTS AND METHODS: We measured erythrocytic GPx activity, circulating neutrophil count, and serum high-sensitivity (hs) CRP and IL-6 in 177 patients admitted to the hospital due to an acute exacerbation of COPD (91 males, mean age 66.8+/-0.9 years, mean FEV1 45.3+/-1.3% predicted). RESULTS: From GOLD Stage II to Stage III and IV, erythrocytic GPx activity significantly decreased [mean+/-SEM: from 44.3+/-1.7 U/g Hb to 40.8+/-1.1 U/g Hb and to 38.4+/-1.5 U/g Hb, p = 0.037], while serum hsCRP increased [median (25th, 75th percentile): from 9.6 (3.0, 23.0) mg/l to 23.3 (6.4, 46.8) mg/l, and to 26.7 (6.5, 117.2) mg/l, p = 0.004]. Erythrocytic GPx activity was significantly inversely related to both, log neutrophil count (r = -0.219, p = 0.003) and log hsCRP (r = -0.199, p = 0.008). CONCLUSIONS: Our study suggests an association between systemic inflammation and systemic oxidative stress reflected by erythrocytic GPx in patients with acute exacerbations of COPD.

Beneficial effect of simvastatin treatment on LDL oxidation and antioxidant protection is more pronounced in combined hyperlipidemia than in hypercholesterolemia.

AIMS: Beneficial effects of statin treatment on cardiovascular morbidity and mortality has been not entirely explained by the reduction in LDL-cholesterol level. We hypothesised that antioxidant activity of statins may contribute to their salutary cardiovascular effects. The aim of the present study was to examine effect of simvastatin treatment on some parameters of LDL oxidation and antioxidant protection in patients with hypercholesterolemia and combined hyperlipidemia. Furthermore, we were interested, whether the effect of treatment is related to the type of hyperlipidemia. PATIENTS AND METHODS: Fourty-two patients (12 males, 30 females, mean age 60+/-10 years) were included in the present study. Fourteen patients had hypercholesterolemia defined as total cholesterol>5.0 mmol/l. Twenty-eight patients had combined hyperlipidemia defined by total cholesterol>5.0 mmol/l and triglycerides>1.7 mmol/l. Simvastatin was administered to patients during 8-week period in a daily dose of 20mg. Oxidation of LDL was measured by assessment of circulating conjugated diene (CD) and malondialdehyde (MDA) level. Antioxidant properties of blood were assessed based on measurement of total antioxidant status (TAS) and glutathione peroxidase (GPx) activity. RESULTS: Besides expected significant decrease in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels, simvastatin treatment also reduced significantly circulating CD by 41% (p<0.0001) and MDA level non-significantly by 6% (p=0.078). Simvastatin treatment resulted in an increase of GPx activity by 38% (p<0.0001), but did not have a significant effect on TAS. Patients with combined hyperlipidemia had significantly higher baseline CD (p<0.01) and consequently significantly greater absolute and relative decrease (46% versus 23%) in circulating CD (DeltaCD), when compared with patients with hypercholesterolemia. The increase in GPx activity was significant only in patients with combined hyperlipidemia (p<0.0001). In the multiple stepwise linear regression analysis, both baseline triglyceride (r(2)=0.32; p=0.004) and LDL cholesterol (r(2)=0.08; p=0.05) levels were significant independent predictors of DeltaCD after simvastatin treatment. CONCLUSION: Simvastatin treatment significantly reduced circulating conjugated diene level and led to an increase in glutathione peroxidase activity. These effects were more pronounced in patients with combined hyperlipidemia than in hypercholesterolemia. The results suggest that simvastatin possesses certain antioxidant properties, which may contribute to its beneficial cardiovascular effect.

Fenofibrate treatment reduces circulating conjugated diene level and increases glutathione peroxidase activity.

AIMS: Treatment with fibrates showed benefit in randomized trials predominantly in subgroups of patients with dyslipidaemia of metabolic syndrome. Post hoc analyses of these trials show that the effect of fibrates on lipid levels explains only minor part of the treatment benefit. The aim of the present study was to examine effect of fenofibrate on some parameters of oxidative stress. PATIENTS AND METHODS: The study group included 20 patients (6 males, 14 females) with combined dyslipidaemia. The average age was 54+/-10 years. Fenofibrate was given for 8 weeks in the dose of 300 mg daily. Lipid levels and parameters of oxidative stress were measured at baseline and after treatment period. RESULTS: Treatment with fenofibrate led to reduction of total cholesterol by 18%, LDL cholesterol and apoB by 17%, triglycerides by 46%, as well as increase of HDL cholesterol level by 10%. Among the measured parameters of oxidative stress, fenofibrate treatment significantly reduced level of circulating conjugated dienes (CD) in average by 42% (p < 0.0001) and also non-significantly reduced the production of malonaldehyde. Fenofibrate treatment led to an increase of the activity of antioxidant enzyme glutathione peroxidase (GPx) by 80% from baseline values (p = 0.001). CONCLUSION: Treatment with fenofibrate significantly reduced the level of conjugated dienes, a measure of LDL oxidation, and increased GPx activity. This finding could at least partially explain beneficial effect of fenofibrate treatment beyond that related to levels of commonly measured lipid parameters.

Interaction between angiotensin-converting enzyme genotype and glycaemic control influences lipoprotein levels in type 2 diabetes mellitus.

AIMS: To evaluate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on lipid levels in patients with Type 2 diabetes. PATIENTS AND METHODS: 109 patients with Type 2 diabetes were included. The patients were not on any lipid-lowering treatment. The groups with different ACE genotypes had similar ages, sex distributions, body mass indices, systolic blood pressures and indices of glycaemic control. ACE gene I/D polymorphism was determined using polymerase chain reaction. RESULTS: The mean apolipoprotein B (apoB) level was significantly higher in the group of DD homozygotes compared with the subjects with at least one insertion allele (DD: 1.21 +/- 0.25 g/l vs. ID + II: 1.04 +/- 0.27 g/l; P = 0.007). Significant correlations between glycated haemoglobin (HbA1c) and both apoB and cholesterol levels were found (r = 0.27; P < 0.01). For the apoB, this correlation was highly significant in the DD-genotype subgroup (r = 0.54; P < 0.01), and was not significant in the subgroup of patients with genotypes ID or II. In the multivariate analysis, HbA1c and the interaction of genotype DD with HbA1c were significant independent predictors of apoB (r2 = 0.17) and cholesterol levels. CONCLUSION: The present study showed that the interaction between the DD genotype of angiotensin-converting enzyme and chronic hyperglycaemia (expressed by HbA1c level) is related to higher plasma levels of atherogenic lipoproteins, such as apoB and cholesterol, in patients with Type 2 diabetes.