Improvement of Glycemic Control in Insulin-Dependent Diabetics with Depression by Concomitant Treatment with Antidepressants.

BACKGROUND It is still disputable whether negative effects of comorbid depression in diabetics can be diminished by successful treatment of depression. The primary aim of this study was to assess whether addition of antidepressants to existing insulin treatment would further improve glycemic control in these patients. A secondary objective was to assess whether such treatment impairs their lipid and inflammatory status. MATERIAL AND METHODS Total of 192 patients with poorly controlled diabetes (defined as HbA1c ≥8%) in the absence of any uncontrolled medical condition entered the 6-month run-in phase with optimization of diabetic therapy. Depression status was screened at the end of this phase by BDI-II depression testing. Patients with BDI-II ≥14 and psychiatric confirmation of depression (58 patients) entered the 6-month interventional phase with SSRI class antidepressants. RESULTS Fifty patients completed the study. During the run-in phase, HbA1c dropped from 10.0±1.8% to 8.5±1.2% (p<0.001), and during the interventional phase it dropped from 8.5±1.2% to 7.7±0.7% (p<0.001). BDI-II scores improved significantly from 30.4±13.2 to 23.5±11.0 (p=0.02) during the interventional phase. A positive linear correlation between improvement in depression scale and improvement in glycemic control was observed (R²=0.139, p=0.008). Lipid profile and inflammatory status did not change significantly during the interventional phase. CONCLUSIONS Patients with poorly controlled diabetes and comorbid depression might benefit from screening and treatment of depression with SSRI antidepressants by achieving an incremental effect on glycoregulation. This therapy did not have any adverse effects on lipid profile or inflammatory status.

Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method.

In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350mL/min yielding retention times of 1.7min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0µg/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 92.2 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.

Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology.

In this paper, the development of reversed-phase liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality by design (QbD) approach is presented. The defined analytical target profile (ATP) was the efficient baseline separation and the accurate determination of the investigated analytes. The selected critical quality attributes (CQAs) were the separation criterions between the critical peak pairs because the mixture complexity imposed a gradient elution mode. The critical process parameters (CPPs) studied in this research were acetonitrile content at the beginning of gradient program, acetonitrile content at the end of gradient program and the gradient time. Plan of experiments was defined by Box-Behnken design. The experimental domains of the three selected factors x1--content of the acetonitrile at the start of linear gradient, x2--content of the acetonitrile at the end of linear gradient and x3--gradient time (tG) were [10%, 30%], [48%, 60%] and [8 min, 15 min], respectively. In order to define the design space (DS) as a zone where the desired quality criteria is met providing also the quality assurance, Monte Carlo simulations were performed. The uniform error distribution equal to the calculated standard error was added to the model coefficient estimates. Monte Carlo simulation included 5000 iterations in each of 3969 defined grid points and the region having the probability π ≥ 95% to achieve satisfactory values of all defined CQAs was computed. As a working point, following chromatographic conditions suited in the middle of the DS were chosen: 22% acetonitrile at the start of gradient program, 55.5% acetonitrile at the end of gradient program end and the gradient time of 11.5 min. The developed method was validated in order to prove its reliability.

Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods.

In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50mm×4.0mm, 3µm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550µL/min and total run time 2min. Established methods were fully validated over the concentration range of 0.200-20.0µg/mL for DBS and 0.400-40.0µg/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.

Left and right atrial phasic function and deformation in untreated patients with prediabetes and type 2 diabetes mellitus.

To evaluate phasic function and deformation of the left atrium (LA) and right atrium (RA) in subjects with prediabetes and type 2 diabetes mellitus. This cross-sectional study included 50 untreated normotensive subjects with prediabetes, 60 recently diagnosed normotensive diabetic patients and 60 healthy controls of similar sex and age. All the subjects underwent laboratory analyses and complete echocardiographic examination including strain analysis. LA and RA reservoir and conduit function gradually decreased, while booster pump increased, from the healthy controls, throughout the prediabetics, to the diabetics. The strain analysis of atrial phasic function showed more regular pattern of progressive atrial function deterioration than conventional evaluation with total, active and passive atrial function. In the whole study population HbA1c correlated with LA passive emptying fraction (r = -0.38, p < 0.01), LA active emptying fraction (r = 0.36, p < 0.01), LA longitudinal strain during systole (r = -0.35, p < 0.01), RA passive emptying fraction (r = -0.42, p < 0.01), RA active emptying fraction (r = 0.38, p < 0.01), and RA longitudinal strain during systole (r = -0.32, p < 0.01). However, only LA passive emptying fraction (ß = -0.32, p < 0.01) and LA longitudinal strain during systole (ß = -0.28, p = 0.02) were independently associated with HbA1c among the LA parameters; whereas solely RA passive emptying fraction (ß = -0.37, p < 0.01) and RA active emptying fraction (ß = 0.31, p = 0.01) were independently associated with HbA1c among the RA parameters. LA and RA phasic functions are significantly impaired in the prediabetics and the diabetics. The parameter of glucose control correlated with LA and RA reservoir, conduit and pump atrial function.

Vigabatrin in dried plasma spots: validation of a novel LC-MS/MS method and application to clinical practice.

This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time. A relatively novel sample collection technique, DPS, was utilized, offering easy sample handling and analysis, using a sample in micro amount (∼5µL). Derivatized vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were extracted by liquid-liquid extraction (LLE) and determined in positive ion mode by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column (150×4.6mm, 5µm particle size) maintained at 30°C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550µL/min and total run time 4.5min. The assay exhibited excellent linearity over the concentration range of 0.500-50.0µg/mL, which is suitable for the determination of vigabatrin level after per os administration in children and youths with epilepsy, who were on vigabatrin therapy, with or without co-medication. Specificity, accuracy, precision, recovery, matrix-effect and stability were also estimated and assessed within acceptance criteria.

Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography.

In this paper, the capability of a polynomial-modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three-step procedure based on indirect modeling of peak width at 10% of peak height (W0.1), individual values of left-half width (A) and right-half width (B), number of theoretical plates (N), and tailing factor (Tf). The values of retention factors corresponding to the peak beginning (k(B)), peak apex (k(A)), peak ending (k(E)), and peak heights (H0) of the analytes were directly modeled. Then, the investigated experimental domain was divided to acquire a grid of appropriate density, which allowed the subsequent calculation of W0.1, A, B, N, and Tf. On the basis of the predicted results for Tf and N, as well as the defined criteria for the simulation the following conditions were selected: 33% acetonitrile/67% aqueous phase (55 mM perchloric acid, pH 2.2) at 40°C column temperature. Perfect agreement between predicted and experimental values was obtained confirming the ability of polynomial modified Gaussian model and three-step procedure to successfully simulate the real chromatograms in ion-interaction chromatography.

Subclinical hypothyroidism and left ventricular mechanics: a three-dimensional speckle tracking study.

CONTEXT: Subclinical hypothyroidism (SHT) is associated with left ventricular (LV) remodeling. The LV mechanics has not been previously assessed by two- and three-dimensional (2DE and 3DE) speckle tracking imaging in the SHT patients. OBJECTIVES: The objective of the study was to investigate LV mechanics by 2DE and 3DE speckle tracking in the SHT patients and evaluate the influence of levothyroxine therapy on LV remodeling. DESIGN: We conducted a prospective study. All SHT patients received levothyroxine therapy and were followed up for 1 year after the euthyroid state had been achieved. SETTING: The study was performed at a university hospital. PATIENTS: We included 54 untreated women with SHT and 40 healthy control women who were of similar age. MAIN OUTCOME MEASURES: The 2DE strain and strain rates, 3DE volumes, 3DE strain, and thyroid hormones levels were assessed. RESULTS: The 2DE LV longitudinal and circumferential strain and systolic and early diastolic strain rates were significantly decreased in the SHT patients before therapy in comparison with the controls or the SHT patients after therapy. The 3DE LV cardiac output and ejection fraction were significantly reduced in the SHT patients at baseline compared with the controls or patients after 1 year of treatment. The 3DE LV longitudinal and radial strains were significantly lower in the SHT group before treatment in comparison with the controls or patients after therapy, whereas the 3DE LV circumferential and area strains gradually increased from untreated SHT patients, among the treated SHT patients, to the controls. CONCLUSION: SHT significantly affects LV deformation assessed by 2DE and 3DE speckle tracking. The improvement of LV mechanics after 1 year of levothyroxine treatment is significant but incomplete.

Chemometrical tools in the study of the retention behavior of azole antifungals.

Certain chemometrical tools allow an efficient way to provide valuable data to evaluate the retention behavior of analytes in liquid chromatography. In this study of the retention behavior of azole antifungals, the experimental design was applied in combination with artificial neural networks (ANNs). Three potentially significant factors (methanol content, pH of the mobile phase and column temperature) were incorporated in the plan of experiments, defined by central composite design. As the system outputs, the retention factors of all six investigated substances (fluconazole, ketoconazole, bifonazole, clotrimazole, econazole and miconazole) were determined. The pattern for the analyzed behavior of the system was created by employing ANNs. The final, optimized topology of the highly predictive network was 3-8-6. Twelve experiments were used in a training set, whereas a back-propagation algorithm was optimal for network training. The ability of the defined network to predict the retention of the investigated azoles was confirmed by correlations higher than 0.9912 for all analytes. The presented approach allowed the adequate prediction of the retention behavior of azoles, in addition to the extraction of important information for a better understanding of the analyzed system.

Heart rate variability and increased risk for developing type 2 diabetes mellitus.

BACKGROUND/AIM: To our knowledge there are no data about the relationship between elevated risk for developing type 2 diabetes mellitus (DM2) and altered cardiac autonomic function. The aim of this study was to evaluate the association between heart rate variability (HRV) and slightly increased risk for DM2. METHODS: We evaluated 69 subjects (50.0 ± 14.4 years; 30 male) without DM2, coronary artery disease and arrhythmias. The subjects were divided into two groups according to the Finnish Diabetes Risk Score (FINDRISC): group I (n = 39) included subjects with 12 > FINDRISC ≥ 7; group II (n = 30) subjects with FINDRISC < 7. HRV was derived from 24-h electrocardiogram. We used time domain variables and frequency domain analysis performed over the entire 24-h period, during the day (06-22 h) and overnight (22-06 h). RESULTS: Standard deviation of the average normal RR intervals was significantly lower in the group with increased risk for DM2 compared to the group II (127.1 ± 26.6 ms vs 149.6 ± 57.6 ms; p = 0.035). Other time domain measures were similar in both groups. The group I demonstrated significantly reduced frequency domain measures, total power--TP (7.2 ± 0.3 ln/ms2 vs 7.3 ± 0.3 ln/ms2; p = 0.029), and low frequency--LF (5.9 ± 0.4 ln/ms2 vs 6.3 ± 0.6 In/ms2; p = 0.006), over entire 24 h, as well as TP (7.1 ± 0.3 In/ms2 vs 7.3 ± 0.3 In/ms2; p = 0.004), very low frequency (6.2 ± 0.2 In/ms2 vs 6.3 ± 0.2 In/ms2; p = 0.030), LF (5.9 ± 0.4 In/ms2 vs 6.2 ± 0.3 In/ms2; p = 0.000) and high frequency (5.7 ± 0.4 In/ms2 vs 5.9 ± 0.4 In/ms2; p = 0.011) during the daytime compared to the group II. Nocturnal frequency domain analysis was similar between the groups. The low diurnal frequency was independently related to elevated risk for diabetes mellitus (beta = -0,331; p = 0.006). CONCLUSION: The obtained results suggest that even slightly elevated risk for developing diabetes mellitus may be related to impaired HRV.

Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs.

In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances.

Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design.

In this article, a step-by-step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate-mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal-to-noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC-MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vigabatrin, pregabalin and gabapentin, respectively, while for signal-to-noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time-segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0 ng ml(-1)-10.0 × 10(3) ng ml(-1)).

Abnormalities in the serum phospholipids fatty acid profile in patients with alcoholic liver cirrhosis - a pilot study.

The fatty acid composition of serum phospholipids were analyzed in 20 patients with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable nutritional status); 25 healthy age and sex-matched adults were used as controls. Cirrhotic patients showed higher levels of palmitic acid and total saturated fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and docosahexaenoic acid were significantly lower (p<0.001) in patients with alcoholic cirrhosis compared to healthy controls. Significant changes were also found between patients stratified according to nutritional status. In particular, the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty acids was higher (p<0.01) in malnourished patients when compared to the patients with acceptable nutritional status. Furthermore, important changes in the levels of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were found in well-nourished patients with alcoholic cirrhosis as well. Our present data confirmed evidence that malnutrition is one of the factors that led to lower levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis. PUFA supplementation in the latter needs further investigation.

Metabolic syndrome and left ventricular function: is the number of criteria actually important?

BACKGROUND: Metabolic syndrome (MS) is a clustering of cardiovascular risk factors responsible for the development of target organ damage. The aim of this study was to determine the effect of the increasing number of MS risk factors on left ventricular function assessed by noninvasive methods. MATERIAL/METHODS: The study included 204 subjects with MS and 76 controls with no MS risk factors. MS was defined by the presence of 3 or more of ATP-NCEP III criteria. MS subjects were grouped according to the number of criteria they fulfilled: 3 criteria (n=91), 4 criteria (n=65) and 5 criteria (n=48). All subjects underwent laboratory blood tests, complete 2-dimensional, pulse and tissue Doppler echocardiography. Echocardiography was used to assess systolic (LVEF, sseptal), diastolic function, by pulse-wave Doppler (E/A ratio) and tissue Doppler imaging (E/e'average), and global left ventricular function (Tei index). Appropriate time intervals for the estimation of the Tei index were obtained by tissue Doppler. RESULTS: Transmitral E/A ratio decreased significantly and progressively from the 3 criteria to the 5 criteria group (0.82 ± 0.25 vs. 0.79 ± 0.24 vs. 0.67 ± 0.14, p<0.001). The transmitral E/E'average ratio was significantly and gradually increased from the 3 criteria to the 5 criteria group (7.76 ± 1.81 vs. 9.44 ± 2.35 vs. 10.82 ± 2.56, p<0.001). The left ventricle Tei index progressively increased from the 3 criteria to the 5 criteria group (0.43 ± 0.11 vs. 0.48 ± 0.10 vs. 0.54 ± 0.12, p<0.001). CONCLUSIONS: The increasing number of MS criteria is associated with cardiac diastolic dysfunction.

Feasibility of semi-quantitative assessment of left ventricular contractile reserve in dilated cardiomyopathy.

BACKGROUND: We and others have shown previously that left ventricular (LV) contractile reserve assessed quantitatively by high-dose dobutamine stress-echocardiography (DSE) has prognostic implications in patients with dilated cardiomyopathy. PURPOSE: To assess the feasibility of semi-quantitative assessment of LV contractile reserve by differently skilled operators in patients with dilated cardiomyopathy. METHODS: High-dose DSE was performed in 63 consecutive patients, mean age 50 ± 10 years and ejection fraction (EF) 19 ± 8%. LVEF was calculated 1) using Simpson's biplane formula, and 2) semi-quantitatively (5% increments) by novice and experienced echocardiographers, and by a DSE expert. Patients were considered to have preserved LV contractile reserve if LVEF dobutamine-induced change was ≥5%. RESULTS: Twenty-seven (45.8%) patients died during the 5-year follow-up. The feasibility of the assessment was 89%, 94%, and 98% for novice and experienced readers and DSE expert, respectively. Kaplan-Meier analysis showed that LV contractile reserve assessed semi-quantitatively by DSE expert and experienced reader achieved the best prognostic separation (log rank 19.63 and 18.99, respectively, p < 0.001 for both), followed by quantitative assessment (log rank 9.76, p = 0.0018) and assessment by novice reader (log rank 8.76, p = 0.012). Areas under the curves were similar for quantitative and semi-quantitative assessment of LV contractile reserve. CONCLUSIONS: Our data indicate that semi-quantitative assessment of LV contractile reserve is feasible by differently skilled operators.

[The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics].

INTRODUCTION: The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. OBJECTIVE: The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. METHODS: The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (GO), insulin (10) and lipid panel measurements (TC, HDL, LDL, TG) were taken after a 12-hour fasting. RESULTS: The protocol encompassed 40 patients (19 men and 21 women) treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis), Group B (18 patients, 45%, with a single-vessel disease) and Group C (16 patients, 40%, with multi-vessel disease). Presence of lower insulin sensitivity, higher 10 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F = 4.279, p = 0.023, A vs. C p = 0.012, B vs. C p = 0.038; 10: F = 3.461 p = 0.042, A vs. B p = 0.045, A vs. C p = 0.013; TC: F = 2.572, p = 0.09), while no significant difference was found for GO, LDL, HDL and TG. CONCLUSION: Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

[Myocardial performance index: prediction and monitoring of remodeling and functioning of the left ventricle after first myocardial infarction].

INTRODUCTION: Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and diastolic dysfunction after acute myocardial infarction over the long term. MATERIAL AND METHODS: Echocardiography was performed within the first week of hospitalization, after one, three and six months in 77 patients with first acute myocardial infarction. At the end of the study the patients were divided into group A and B with mild and severe left ventricular remodeling, respectively. RESULTS: Myocardial performance index was significantly lower in group A compared to B, at the beginning (0.62 vs. 0.75; p = 0.002), and at the end of study (0, 60 vs. 0, 69; p = 0.004). After six months, 31% of study patients developed LV systolic dysfunction with prevalence in group B (56% vs. 19%, p = 0.002). Myocardial performance index > or = 0.70 at first week after acute myocardial infarction is a strong predictive parameter for extensive early and late left ventricular remodeling and systolic dysfunction (p < 0.05), but it is not a valuable predictor of diastolic failure. DISCUSSION AND CONCLUSIONS: MPI obtained at first week of acute myocardial infarction was predictive for early and long term left ventricular remodeling and systolic dysfunction. Myocardial performance index had doubtful clinical use in assessing dynamics of remodeling and it was without clinical value in predicting diastolic function deterioration.

Impact of acute exercise on antioxidant enzymes activity and lipid status in blood of patients with hypertension.

BACKGROUND/AIM: Many studies support the hypothesis that oxidative stress is involved in the pathogenic process of a variety of diseases including hypertension. In humans, hypertension is also considered a state of oxidative stress that can contribute to the development of arteriosclerosis and other hypertension-induced organ damage. The aim of this study was to evaluate an influence of acute physical exercise on antioxidative enzymes activity and lipid status in patients with hypertension. METHODS: Fourty patients with hypertension and 20 age-matched controls were included in the study. To assess an influence of acute exercise on lipids and antioxidative enzymes activity the following parameters were determined at rest and immediately after the acute cardiopulmonary exercise cycloergometer test: triglycerides (TG), total cholesterol, low density cholesterol (LDL), oxidised LDL cholesterol (OxLDL), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and plasminogen activator inhibitor (PAI). RESULTS: In basal condition, hypertensive patients compared to the control group had increased, but not significantly, level of Ox LDL (88.61 +/- 14.06 vs 79.00 +/- 29.26 mmol/L), PAI (3.06 +/- 0.56 vs 2.6 +/- 0.35 U/mL) and activity of GSH-Px (50.22 +/- 15.20 vs 44.63 +/- 13.73 U/g Hb). After acute exercise test, there was significantly greater level of Ox LDL (79.0 +/- 29.26 vs 89.3 +/- 29.07 mmol/L; p < 0.05) only in the control group. GSH-Px activity was significantly decreased only in hypertensive patients after acute exercise (50.22 +/- 15.2 vs 42.82 +/- 13.42 U/g Hb; p < 0.05), but not in the controls. CONCLUSION: No significantly elevated Ox LDL, GSH-Px and PAI-1 levels were found in hypertensive patients during basal condition in comparison with healthy subjects. Decreased GSH-Px activity was associated with those in acute exercise only in hypertensive patients. It could be an important indicator of deficiency of physiological antioxidative defense mechanism in hypertensive patients during an acute exercise.

Clinical evaluation of oxidative stress in patients with diabetes mellitus type II -- impact of acute exercise.

BACKGROUND/AIM: Exercise is a well recognized model of oxidative stress and, also, an important tool in diabetes management. The aim of our study was to evaluate oxidative stress in patients with diabetes mellitus type 2 and to determine influence of acute exercise training on the investigated parameters. METHODS: To evaluate oxidative stress in the patients, we determinated following parameters: triglycerides (TG), total cholesterol, low density lipoprotein cholesterol (LDL), oxidized LDL cholesterol (Ox LDL), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), plasminogen activator inhibitor (PAI) which were measured at rest and immediately after the acute bout of cardiopulmonary exercise cycle-ergometer test. RESULTS: In basal condition, diabetic patients compared to controls have significant higher values of TG (3.12 +/- 1.09 vs 1.74 +/- 0.9 mmol/L, p < 0.01), Ox LDL (84.73 +/- 16.90 vs 79.00 +/- 29.26 mmol/L, p < 0.05) and SOD enzyme activity (913.38 +/- 120.36 vs 877.14 +/- 153.18 U/g Hb, p < 0.05). During the acute exercise test, there was significant increase of Ox LDL in both the study patients (from 84.73 +/- 16.90 to 92.33 +/- 23.29 mmol/L, p < 0.05) and in the control group (from 79.00 +/- 29.26 to 89.30 +/- 29.07 mmol/L, p < 0.05). SOD activity was significantly increased in both groups during exercise, in diabetic patients from 913.38 +/- 120.36 to 921.50 +/- 130.03 U/gHb, p < 0.05, and in the controls from 877.14 +/- 153.18 to 895.00 +/- 193.49, U/gHb, p < 0.05. GSH-Px activity was significantly increased only in the diabetic patients after the acute exercise (from 45.04 +/- 11.19 to 51.81 +/- 15.07 U/gHb, p < 0.01), but not in the controls (from 44.63 +/- 13.73 to 43.97 +/- 25.97 U/gHb, p = ns). PAI significantly decreased during the exercise test, only in the healthy subjects (from 2.60 +/- 0.35 to 2.22 +/- 0.65, p < 0.05). Type 2 diabetic patients with complications had only significant increase in GSH-Px activity (from 47.10 +/- 7.37 to 54.52 +/- 11.97 U/gHb, p < 0.01). CONCLUSION: Elevated Ox LDL, SOD and GSH-Px levels are associated with acute exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to preventing free radicals tissue damage. We hypothesize that a physical training program induces an enhance of muscular and liver antioxidant enzymes activity and reduces oxidative stress. Further studies are needed to explore the relationship between exercise and antioxidant system in diabetic patients with and without complications.

Effects of acute exercise on atherogenic lipids in untreated mild hypertensive patients.

BACKGROUND/AIM: Exercise can positively influence risk factors associated with cardiovascular disease. The mechanisms by which exercise reduces atherogenic risk remain unknown. The aim of the present study was to investigate the effect of acute exercise (cardiopulmonary exercise cycle ergometer test) on atherogenic lipids in untreated mild hypertensive patients with or without hypercholesterolemia. This testing allows determination of exercise capacity, peak heart rate, and ventilation per minute (VE), peak oxygen uptake (pVO2) and exercise time (ET). METHODS: The study group included 85 untreated mild hypertensive patients (according to VII Joint National Committee--JNC 7) divided into two subgroups: hypertensive hypercholesterolemic and hypertensive normocholesterolemic. The control grouip included 35 normotensive subjects divided into two subgroups: normotensive hypercholesterolemic and normotensive normocholesterolemic. Lipid profiles to determine were oxidized LDL (OxLDL)--a marker of oxidative stress, triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol, which were measured at rest and 30 minutes after the acute bout of cardiopulmonary exercise cycle ergometer test. Lipids profiles were measured by enzymatic methods. Oxidized LDL was determined by a commercially available sandwich ELISA (Mercodia AB, Uppsala, Sweden). C-reactive protein (CRP) was measured using chemiluminiscent methods (Immulite-DPC). RESULTS: In our study OxLDL was significantly higher in hypertensive patients with atherogenic lipid profiles in basal condition, compared to the hypertensive patients without atherogenic lipid profiles and controls. There was a significant difference in CRP (p < 0.001) between hypercholesterolemics (hypertensive and normotensive) and normocholesterolemics (hypertensive and normotensive). We found increased OxLDL after exercise in both groups (hypertensive patients and normotensive), but only in the hypertensive hypercholesterolemic patients the difference was statistically significant (90.47 +/- 15.31 vs. 105.94 +/- 14.17 IU/L, p < 0.001). Systolic and diastolic blood pressures were significantly higher during exercise only in the hypertensive patients. There were significantly lower values of pVO2 only in hypertensive hypercholesterolemic patients. There were no significant differences between hypertensive and normotensive ones for ET and VE. In hypertensive ones we found after exercise a negative correlation between pVO2 and OxLDL (r = -0.473; p < 0.05), and pVO2 and CRP (r = -0.478; p < 0.05). We also found in normotensive normocholesterolemic patients a positive correlation between VE and systolic blood pressure (r = 0.420; p < 0.05), a negative correlation between VE and OxLDL (r= -0.421; p < 0.05), and VE and CRP (r = -0.561; p < 0.05). CONCLUSION: This study showed that acute exercise induces and increases oxidative stress only in untreated mild hypertensive patients with atherogenic lipid profiles. These results imply the need to normalize atherogenic lipid profile in untreated patients with mild hypertension in order to prevent an increased lipid peroxidation under acute exercise.