Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking.

Human serum albumin (HSA), the most abundant plasma protein is well known for its extraordinary binding capacity for both endogenous and exogenous substances, including a wide range of drugs. Interaction with the two principal binding sites of HSA in subdomain IIA (site 1) and in subdomain IIIA (site 2) controls the free, active concentration of a drug, provides a reservoir for a long duration of action and ultimately affects the ADME (absorption, distribution, metabolism, and excretion) profile. Due to the continuous demand to investigate HSA binding properties of novel drugs, drug candidates and drug-like compounds, a support vector machine (SVM) model was developed that efficiently predicts albumin binding.

Advanced glycation end products in myocardial reperfusion injury.

Advanced glycation end products (AGEs) are associated with cardiovascular diseases. Whether the AGE levels change during myocardial reperfusion injury is currently unknown. The aim of our study was to investigate the dynamics of AGEs in myocardial reperfusion injury and to discuss potential reasons for these changes.

[Natriuretic peptides in patients with aortic stenosis].

Introduction: The aim of this research was to, in patients with severe (tight) aortic stenosis (AoS), evaluate a) an association between clinical and some haemodynamic characteristics and natriuretic peptides (ANP, BNP) concentrations and b) usefulness of these hormones in the decision making on the next therapeutic steps.

Methods: Echocardiography and 6-minut exertion walking test were performed in 23 consecutive patients (12 men, 11 women; age 67 +/- 7 years) and 20 controls together with ANP and BNP measurements from three plasma samples before, immediately after and 20 minutes after the exertion test.

Results: There was high inter-individual variability in the ANP and BNP concentrations in patients with AoS.

Heart adrenoceptor gene expression and binding sites in the human failing heart.

Adrenergic regulation of the heart function is well documented by many studies. Catecholamines act through alpha(1)-, beta(1)-, beta(2)-, and beta(3)-adrenoceptors (ARs) in the heart. There are many findings about the changes of beta(1)- and beta(2)-AR in heart failure (HF).

Natriuretic peptides and endothelin-1 in patients undergoing coronary artery bypass grafting.

Off-pump coronary artery bypass grafting (CABG) is an alternative to conventional CABG using cardiopulmonary bypass. Off-pump technique reduces the complications of CABG performed with extracorporeal circulatory assistance (Lancey et al. 2000; Mack et al.

Delivery as a "physiological stress" and its influence on some parameters of oxidative stress.

Objectives: In healthy term newborns (HTN) to determine on the 1st and 5th day of life the activity of total antioxidant capacity (TAS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and to compare the values with the group of asphyxiated term newborns (ATN).

Patients/methods: The series consisted of 15 HTN and 24 ATN. In both groups TAS, MDA, GPX and SOD were investigated.

[The influence of chloroquine on some biochemical and hematological parameters in patients with critical limb ischemia].

CLI represents a major medical and social problem. The incidence is increasing and currently it was estimated 500-1000 per 1 million inhabitants. We carried out a clinical study (2000-2004) concerning monitoring of some hematological and biochemical markers during reperfusion in patients with CLI.

Antioxidant status of patients after on-pump and off-pump coronary artery bypass grafting.

Background: It has been convincingly established that cardiopulmonary bypass routinely used in cardiac surgery induces an oxidative stress. The extensive production of reactive oxygen species occurring during cardiopulmonary bypass has a deleterious effect on the endogenous antioxidant defense pool. The recovery of antioxidant enzyme activities as well as other antioxidatively substances is one of the important tasks for the effective defense of patients in the postoperative period.

An acute toxic neuropathy caused by organo-phosphate poisoning in hens.

Objective: Organophosphorus compounds can induce an acute toxic peripheral neuropathy. In hens, the acute peripheral neuropathy was induced by poisoning with organo-phosphorus compound (OPC)--tri-ortho-cresyl phosphate (TOCP).

Methods: In the course of an acute TOCP-induced toxic neuropathy in hens the activity of following enzymes was analysed: asparaginase, glutaminase, glutamat-dehydrogenase, AMP and adenosine deaminases and 5'nucleotidase; ALT (SGPT), AST (SGOT) and proteins levels were estimated.

Protection of newborn organism against effect of oxidative stress.

Objective: The aim of the present study was to investigate influence of oxidative stress on newborn organism, in terms of the dynamics of malondialdehyde (MDA) concentration changes and of the activities of selected antioxidants in asphyxial newborns on the 1st and 5th day of life.

Method: In the group of 62 preterm and term asphyxial newborns, characterized by the presence of asphyxial criteria and admitted within 24 hours of life, the plasma concentration of MDA and level of total antioxidant status (TAS) were followed.

Results: Dynamic changes of MDA signalized active process of lipoperoxidation (LP) and values of TAS were decreased in comparison with the capacity of adult patients.

Oxidative stress and antioxidant defense systems in patients after heart transplantation.

Heart transplantation ranks among those surgical interventions associated with ischemia-reperfusion injury to the donor heart as well as to the recipient. These events are connected with increased production of reactive oxygen species which evoke metabolic, structural and functional disturbances. Twenty-four transplant patients were investigated for oxidative stress (plasma levels of thiobarbituric acid reactive substances, TBARS) and antioxidant capacity (plasma total antioxidant status, TAS), and for activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) during the first year after heart transplantation.

[Regional biochemical and hematologic changes in patients after revascularization of the lower extremities in ischemia of the extremities].

Introduction: Surgical treatment of PAOD is related to iatrogenic ischaemia caused by arterial clamping and ischaemia which is result of natural development of the disease. The pathway of skeletal muscle reperfusion injury is complex and one of the most important factors related to injury is endothelial damage. The expected reason of endothelial damage is increased production of oxygen free radicals by prematurely activated PMN (polymorphonuclear) leukocytes (direct injury).

Cytokine levels in patients with a very low left ventricular ejection fraction after open heart surgery.

Introduction: Cardiopulmonary bypass and cardiac operations are obligatorily connected with systemic inflammatory reaction. Production of proinflammatory cytokines is responsible also for negative effects on the myocardial function.

Objective Of Study: Follow-up of the dynamic changes of proinflammatory and antiinflammatory cytokine levels in patients with left ventricular dysfunction during the first week after cardiac surgery.

[Parameters of energy metabolism in patients after vascular reconstructive surgical procedures].

Revascularization surgery in patients with peripheral arterial occlusive disease presents an acceptable clinical model for studying the rate of ischaemia-reperfusion injury of cells and other structures of skeletal muscle of the affected extremity. Validity of carefully chosen set of biochemical parameters for determination of this injury during and after surgery as well as in the early and late reperfusion periods and during the readaptation to situation after restoration of blood circulation was verified. Blood samples were taken from the regional common femoral vein which allowed to obtain information directly from the ischaemized extremity.

[Biochemical markers of perioperative myocardial infarct in non-cardiac surgery].

Perioperative myocardial infarction as well as other major cardiac events induced by myocardial ischemia during and after a more complex or long-lasting operation represents a permanent threat for a successful outcome. High number of cardiac ischemic events especially following major vascular surgery and in elder subjects requires early, sensitive and specific diagnostic markers. This review paper presents conventional as well as novel biochemical methods fulfilling the above mentioned criteria.

Participation of coenzyme Q10 in the rejection development of the transplanted heart: a clinical study.

Coenzyme Q10 and alpha-tocopherol concentrations were assessed in 28 endomyocardial biopsies from 22 patients and in 61 blood samples from 31 patients after heart transplantation with histologically confirmed signs of rejection. The values were compared to the group of 14 patients with cardiomyopathies of unclear etiology as candidates for heart transplantation. Blood analyses were also compared with 50 healthy persons.

Coenzyme Q10 depletion and mitochondrial energy disturbances in rejection development in patients after heart transplantation.

Unlabelled: Sixty endomyocardial biopsies (EMB) and whole blood or plasma samples from 34 patients after heart transplantation (HTx-pts) were studied. Acute rejection of the transplanted heart was histologically graded as: 0 (without), 0-1 (incipient), 1 (mild), 2 (moderate). The level of coenzyme Q10 (CoQ10) in 28 EMB was estimated by HPLC.

[The effect of uric acid, creatine phosphate and carnitine on lipid peroxidation in cerebral cortex and myocardium homogenates].

Background: Uric acid as the product of purine nucleotide degradation is an integrate component of blood plasma. This metabolite is considered to be one of the important naturally occurring antioxidants building up the antioxidation system of the organism. Creatine phosphate and carnitine are important substances participating in energy metabolism of the cells.

[Prognostic significance of biochemical markers in acute coronary syndromes].

The article reviews the possibilities of biochemical markers in coincidence with the assessment of prognosis in acute coronary syndromes and in the revealing of effectivity of their therapy. The current options of clinical biochemistry in many cases allow to supplement, confirm, or exclude the results of modern physical and other clinical examination methods and in this way to contribute to the accuracy of the diagnostic process, and enable to comment the prognosis and the risk measure of the patient. A significant progress has been achieved in the assessment of effectivity in thrombolytic therapy in acute myocardial infarction, where especially the series assessment of myoglobin levels or specific troponin cardiomarkers can facilitate the process of physician's decision as to the assessment of the subsequent procedure in the treatment of patients.

[Not Available].

The article reviews the possibilities of biochemical markers in coincidence with the assessment of prognosis in acute coronary syndromes and in the revealing of effectivity of their therapy. The current options of clinical biochemistry in many cases allow to supplement, confirm, or exclude the results of modern physical and other clinical examination methods and in this way to contribute to the accuracy of the diagnostic process, and enable to comment the prognosis and the risk measure of the patient. A significant progress has been achieved in the assessment of effectivity in thrombolytic therapy in acute myocardial infarction, where especially the series assessment of myoglobin levels or specific troponin cardiomarkers can facilitate the process of physician's decision as to the assessment of the subsequent procedure in the treatment of patients.

[Mitochondrial bioenergetics in patients before and after heart transplantation].

Background: The results of the study of biochemical and genetic characteristics of mitochondria in human medicine become widely used in practice. This is confirmed also by the Nobel Symposium which took place in 1994, and was dedicated to the problem of mitochondrial diseases and the effect of their therapy. Relatively rare is the information on the pathobiochemistry of heart muscle mitochondria in patients with cardiomyopathies.

[Coenzyme Q10 and alpha-tocopherol in patients after heart transplantation].

Pathobiochemical mechanisms which participate in the rejection of transplanted heart are not fully clarified. A significant role in this process can be played by endogenous antioxidants, especially coenzyme Q10 which aside from its antioxidative properties is inevitable for cellular bioenergy. The authors investigated the concentration of Q10 alpha-tocopherol in endomyocardial biopsies in the blood in 11 patients from 1 to 9 years of age after transplantation of the heart (HTx-pat) examined in UKVCH in Bratislava who were compared with the group of 13 patients with cardiopathies of unclear origin (KPNP-pat) as possible candidates for transplantation.

[Biochemical markers in acute myocardial infarct].

Exact and early diagnosis of acute myocardial infarction is essential for the subsequent routine management of this frequent cardiovascular disease. At present, the clinical biochemistry possesses a set of more or less cardiospecific protein markers for early detection of myocardial ischemic damage. After the admission of patient to the hospital, serial estimations of rather non-specific enzyme activities (creatine kinase, its MB-izoenzyme, lactate dehydrogenase, hydroxybutyrate dehydrogenase) are currently used for the detection of acute myocardial infarction and for the further monitoring of the patient and managing his therapy.

[Determination of coenzyme Q10 and alpha-tocopherol levels in patients with cardiopathies of unknown origin: perspectives in diagnosis].

The coenzyme Q10 (ubiquinone) plays an important role in bioenergetic conditions in myocardiac cells and together with alpha-tocopherol they act as endogenous antioxidants. Decreased levels in coenzyme Q10 were confirmed in some types of cardiomyopathies and in failing myocardium. Insufficiency of E vitamin is a risk factor in cardiovascular diseases.

[Metabolic study of mitochondria in myocardial biopsies in patients with cardiopathy of unknown origin].

Background: Mitochondrial cardiomyopathies are being studied as metabolic diseases of the cardiac muscle which represents a new approach in metabolic studies. The development of mitochondrial diseases is concomited by an impairment in complexes of mitochondrial respiratory chain, which so far could have been possibly studied exclusively on experimental animals. The method of skinned? fibers enables to measure the pathobiochemical processes in mitochondria in a small amount of bioptic myocardial tissue of patients.