The comparison of the effects of ketamine and etomidate on cardiodynamics, biochemical and oxidative stress parameters in Wistar male rats.

It is well known the use of ketamine and etomidate in clinical practice; however, the difference in the systemic effects of these two anesthetic agents is still debatable. Thus, in the present study we aimed to compare their effects on heart, and other organs through estimation of cardiodynamics, biochemical and hematological parameters. Male Wistar rats were divided in 2 groups containing of 2 subgroups (n = 7 in each subgroup, n = 28 in total): (1) bolus injection of anesthetic ketamine (40 mg/kg b.w., i.p. n = 14); (2) bolus injection of anesthetic etomidate (20 mg/kg b.w., i.p. n = 14). The experiments were done in vitro in one subgroup of each group: cardiodynamic variables (dp/dtmax, dp/dtmin, heart rate), coronary flow, oxidative stress in coronary effluent and cardiac tissue homogenate, and in vivo in another subgroup: biochemical and hematological parameters, and oxidative stress in haemolysate. Significantly increased left ventricular contractility (dp/dtmax) and relaxation (dp/dtmin) were noticed in etomidate group. Creatinine (CREA), HDL cholesterol and folate were significantly higher in etomidate group, whereas amylase (AMY) and eosinophils in ketamine group. Our results suggested that ketamine has more antioxidant potential compared to etomidate, and etomidate has more favorable effects regarding cardiac performance.

The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 µmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats 1.

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 µmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 µmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmax were noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

Comparison of short-term and medium-term swimming training on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats.

The aim of present study was to evaluate the effects of 3- and 6-week swimming exercise on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into 8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that swam for 6 weeks and their respective sedentary controls; normotensive animals that swam for 3 weeks; normotensive animals that swam for 6 weeks and their respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl solution) diet for 4 weeks, and these animals did not drink tap water during the experimental protocol. After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary perfusion pressure (40-120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in LV, systolic, and diastolic left ventricular pressure, and heart rate. Coronary flow was measured flowmetrically. Findings of the present study may help in better understanding of short- to medium-term exercise-induced direct effects on cardiac function and perfusion. Generally viewed, swimming of both durations did not change myocardial function and perfusion in hypertensive and normotensive conditions.

Effects of atorvastatin and simvastatin on oxidative stress in diet-induced hyperhomocysteinemia in Wistar albino rats: a comparative study.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

Correlation between oxidative stress and G6PD activity in neonatal jaundice.

Fetal distress represents a pathophysiological condition in which oxygen is not available to the fetus in sufficient quantities. In cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency, under conditions of oxidative stress, the residual G6PD and complimentary antioxidant mechanisms may become insufficient to neutralize the large amounts of ROS and to prevent severe hemolysis. Alteration in the oxidant-antioxidant profile is also known to occur in neonatal jaundice. The study group included 22 neonates presented with fetal distress during labor and 24 neonates with no evidence of fetal distress (control group). Umbilical cord blood samples were taken immediately after delivery, and the following blood tests were carried out after birth and at discharge from the hospital: erythrocyte count, total bilirubin, G6PD activity, and parameters presenting oxidative status [thiobarbituric acid reactive substances (TBARS), NO, O2 (-), H2O2, SOD, CAT, O2 (-)/SOD, and H2O2/CAT]. There were no significant differences in TBARS and NO values among neonates with or without fetal distress. However, the values of O2 (-), H2O2, SOD, O2 (-)/SOD, and H2O2/CAT among neonates born after fetal distress were significantly higher than in neonates without fetal distress (p < 0.01). In neonates with fetal distress, the total number of RBCs at delivery was significantly lower, accompanied with higher bilirubin content. Also neonates with fetal distress had lower activity of G6PD and lower CAT activity. Higher values of oxidative stress parameters in newborns delivered after fetal distress do not indicate strictly what occurred first-oxidative stress or basic lower G6PD activity.

The importance of the blood levels of homocysteine, folic acid and vitamin B12 in children with malignant diseases.

PURPOSE: Hyperhomocysteinemia is associated with carcinogenesis. Since only little research exists on hyperhomocysteinemia and malignancy in children, the possible relationship between homocysteine and childhood malignancies remains unknown. The aim of the present study was to determine the serum levels of homocysteine, folic acid and vitamin B12 in children with malignant and benign tumors prior to therapy (surgical treatment and/or chemotherapy), and after treatment of malignant diseases as well. METHODS: Forty-six children with newly diagnosed malignant diseases (solid tumors and lymphoproliferative/myeloproliferative (LP/MP) malignancies) and 6 children with benign tumors were included in the present study. The patient age ranged between 2 months and 18 years. RESULTS: Significantly increased homocysteine concentrations were identified in children with malignant diseases compared with those with benign tumors (p<0.01). The plasma concentration of homocysteine in children with malignant diseases decreased significantly following treatment (p<0.05). Before treatment, the concentration of folic acid in children with malignant solid tumors was significantly higher than in children with malignant LP/MP diseases (p<0.01). Following treatment, the concentration of folic acid was significantly decreased (p<0.05) in children with malignant solid tumors, while it was not significantly increased in children with malignant LP/MP diseases (p<0.05). The concentration of vitamin B12 in children with malignant diseases (solid tumors and LP/MP diseases) increased significantly following treatment (p<0.01), while it increased substantially (p<0.01) in patients with solid malignancies following treatment. CONCLUSION: Homocysteine could be a marker of malignancy in children. Further research is needed to establish the importance of homocysteine, folic acid and vitamin B12 in pediatric malignant diseases.

Distal venous arterialization and reperfusion injury: focus on oxidative status.

In patients with unreconstructable arterial occlusive disease distal venous arterialization (DVA) seems to be a promising option in the treatment. The goals of this prospective study were to assess clinical efficiency and possible impact of DVA on tissue damage by estimating oxidative status of patients with critical limb ischemia treated with this procedure. The subjects were 60 randomized patients: 30 were undergoing DVA and 30 were treated with antiaggregation therapy. During the mean follow-up period (6.13 ± 4.32 months for DVA vs. 6.74 ± 0.5 months for antiaggregation therapy) survival (p < 0.01), limb salvage (p < 0.001), pain relief (p < 0.001) and wound healing (p < 0.001) rates were significantly different between the two groups of patients in favor of the DVA group. Ten minutes after declamping we observed a decreasing trend in the lactate level in the blood of the deep venous system (p < 0.001). Also, on postoperative day 7 digital systolic pressure and digital-brachial index were higher than before the operation (p < 0.001). In blood samples collected immediately before and successively at 1, 3, 5 and 10 min postoperatively, prooxidative status (thiobarbituric acid reactive substances, O(2)(-), H(2)O(2) and nitric oxide) and antioxidative enzymes (superoxide dismutase, catalase and glutathione reductase) were determined spectrophotometrically. Using the nonparametric Friedman test, we noted statistically nonsignificant differences (p > 0.05) in values of both prooxidative parameters and enzymes of the antioxidative defense system, before and successively at 1, 3, 5 and 10 min after operation. These results indicate that there was no statistically significant reperfusion injury after revascularization, which could have been expected after this surgical procedure, thus confirming its validity in these patients.

Tolerability and toxicity of lipidosterolic extract of American dwarf palm Serenoa repens in Wistar rats: well-known extract, new insight.

BACKGROUND AND OBJECTIVES: Serenoa repens extracts (SrE) have been used for centuries in the treatment of benign prostatic hyperplasia (BPH). According to recommendations that each product should be examined separately, including its tolerability and toxicity, we conducted this study in order to broaden the current cognition about tolerability and toxicity of SrE, in particular of German brand ProstamolunoR. MATERIALS AND METHODS: Twenty-four adult male Wistar rats were randomly distributed into 4 groups of 6 animals. The first control group (O) received water (1 ml/kgBW) and second control group (OO) received olive oil (1 ml/kgb.w.) every day for 30 days. The third and fourth group of rats (SR5 and SR10) were treated with SrE (150 and 300 mg/kgb.w. daily) dissolved in olive oil. Tolerability and toxicity of SrE were estimated on the basis of daily monitoring of behavior, body weight gain (BWG), relative weight of liver, left kidney, prostate and left testis, and values of general biochemical parameters. Total liver proteins (TLP) and glutathione content in hepatocyte suspension were also determined. RESULTS: BWG was significantly unchanged in SR5 and SR10 compared to both controls in all intervals of measurement and at the end of treatment (p > 0.05). LW/BW ratio was significantly higher in SR10 compared with O (p < 0.01). Creatinine and potassium were significantly higher in SR5 compared to O (p < 0.05), but in SR10 were significantly higher compared to both control groups (p < 0.01). TLP content was significantly higher in SR5 compared to OO (p < 0.01). The content of glutathione in homogeneous suspension of hepatocytes didn't alter significantly. CONCLUSIONS: Obtained results have expanded the current state of knowledge about the tolerability and toxicity of SrE, in particular of Prostamol-unoR. For the adoption of a more precise conclusion about its tolerability and toxicity, it should be excluded possible limiting factors that we identified in this study.

Pharmacodynamic action of a commercial preparation of the mushroom Coprinus comatus in rats.

The pharmacodynamic effect of a 7-day oral treatment with a suspension of Coprinus comatus at doses of 0.835 and 1.670 g/kg in rats was studied. Changes in body weight, bile secretion and hypoglycaemic action were examined together with antipyretic activity and paw oedema tests. Such treatments resulted in a significantly lower increase in the body weight of tested animals (15.73 ± 8.36 g/rat in the untreated group, 8.44 ± 8.23 g/rat (p < 0.05) and 3.18 ± 7.93 g/rat (p < 0.05), for C. comatus 0.835 and 1.67 g/kg, respectively). Hypoglycaemic action was evident only in the glucose load test (6.79 ± 0.61 to 9.70 ± 1.16 (p < 0.05) in the untreated group and 6.47 ± 0.35 to 7.27 ± 0.76 for C. comatus 1.67 g/kg). Histological examination of pancreas cross-sections suggested certain protective functions of the mushroom suspension in alloxan poisoning. In the antipyretic test, a significantly lower increase in body temperature was observed in the mushroom-pretreated rats. In the paw oedema test, no decrease in oedema induced by formalin injection was observed following treatment with C. comatus.

Influence of bile acid derivates on tramadol analgesic effect in mice.

Influence of two newly synthesized bile acids derivates, namely sodium salt of monoketocholic acid MKH-Na and methyl ester of monoketocholic acid MKH-Me on tramadol (12.5 mg/kg oral and intramuscular) analgesic effect was examined in this research. Analgesic effect was measured by antinociceptive hot plate method. Interaction was estimated by detection of changes in analgesic effect of tramadol combined with bile acids (subcutaneous administration of 4 mg/kg 20 min before tramadol) compared to analgesic effect of the same dose of tramadol given alone. Hydrosoluble sodium salt of monoketocholic acid did not show interaction with tramadol, regardless of the route of administration of tramadol. However, methyl ester of monoketocholic acid increased the analgesic effect of tramadol when it was given intramuscularly. After oral administration of tramadol, methyl ester of monoketocholic acid decreased the analgesic effect of tramadol. According to the time point when interaction reached statistically significant difference, it can be presumed that after intramuscular administration of tramadol, methyl ester of monoketocholic acid increases tramadol absorption and transport to brain and in that way increases its analgesic effect. The analgesic effect of tramadol after oral administration was decreased, which could be explained by the induction of tramadol metabolism in the liver, but should be examined in more details.

Antioxidant enzymes activities and plasma levels of oxidative stress markers in B-chronic lymphocytic leukemia patients.

PURPOSE: Overproduction of reactive oxygen species (ROS) intermediates above the functional capability of cellular antioxidants may result in instability of important macromolecules and represents the molecular basis of many diseases including inflammation processes, cardiovascular alterations, cancer etc. The purpose of this study was to determine plasma level of superoxide anion, hydrogen-peroxide and malondialdehyde (MDA) as markers of oxidative stress and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as antioxidant enzymes in B-chronic lymphocytic leukemia (B-CLL) patients. METHODS: The study included 29 untreated B-CLL patients in stage A, and 21 in stages B and C, classified according to the Binet system; 31 healthy volunteers formed the control group. After centrifugation of heparinized peripheral blood, plasma levels of all investigated parameters were determined using spectrophotometric methods. RESULTS: Plasma CAT activity was increased in B-CLL patients compared with control subjects; also, progression of disease was related with significantly higher plasma activity of CAT. Also, B-CLL patients showed significantly higher plasma concentration of MDA compared with controls. No statistically significant differences of superoxide anion and hydrogen peroxide as well as plasma activity of SOD and GPx between the tested groups were noted. CONCLUSION: Increase of CAT activity in B-CLL patients indicates that there is stimulation of the antioxidant enzyme system, while the increase of MDA concentration shows increased lipid peroxidation level. According to these results it could be concluded that an imbalance exists between oxidants and antioxidants in the plasma of B-CLL patients.

A polyphasic approach assigns the pathogenic Erwinia strains from diseased pear trees in Japan to Erwinia pyrifoliae.

AIMS: Bacterial shoot blight of pear in Japan (BSBP) is caused by Erwinia strains which were formerly associated with the species Erwinia amylovora, the causative agent of fire blight. The description of Erwinia pyrifoliae as a pear pathogen in Korea renewed a possible connection of the pear pathogens in both countries. METHODS AND RESULTS: Nucleotide sequence analysis of the 16S rRNA, the house keeping genes gpd and recA, as well as DNA-DNA hybridization kinetics and microbiological assays place the pear pathogens from Japan into the species E. pyrifoliae described as the causative agent of Asian pear blight in Korea. CONCLUSIONS: Erwinia pyrifoliae strains from Korea and the pear pathogenic Erwinia strains from Japan belong taxonomically into the same species, but show slight divergences in nucleotide sequences used for classification. The allocation is not only supported by microbiological properties, but also by a host range restricted to pear observed before by others. SIGNIFICANCE AND IMPACT OF THE STUDY: The data suggest that the BSBP disease observed at the island of Hokkaido was not fire blight and unify BSBP in Japan with the pear pathogenic species E. pyrifoliae from Korea.

Interaction of diclofenac and ketoprofen with cardioactive drugs in rats.

The interaction of diclofenac and ketoprofen, both applied intraperitoneally in a dose of 8 mg/kg for twenty-eight days, was assessed with cardioactive drugs in rats. Interaction was assessed on the basis of ECG records after the infusion of adrenaline, verapamil or lidocaine to the rats treated with diclofenac or ketoprofen vs control. The infusion time was measured in seconds to the moment of the appearance of the first heart reaction to the infusion of the cardioactive drug, then to the appearance of more frequent changes in the ECG record, and finally, to the occurrence of the toxic effect. It was also measured the plasma concentrations of sodium and potassium ions. As well as diclofenac and ketoprofen concentration, 2 hours after single and 28th dose. ECG patterns revealed no occurrence of cardiotoxic action of diclofenac and ketoprofen. The treatment with diclofenac caused significantly lower sodium plasma concentrations whereas the concentration of potassium was increased. Diclofenac concentrations were the same after a single and multiple doses, whereas concentrations of ketoprofen were significantly higher after a single dose than after its multiple applications.

Evaluation of cerebrovascular insult types and their localization in patients due to the presence of elevated body temperature.

BACKGROUND: The Aim of our study was to present and analyze the distribution of cerebrovascular insult types and their localization in patients with normal body temperature by means of computerized tomography, and in those with elevated body temperature by means of neuroradiographic findings. METHODS: In our study we evaluated 103 patients that suffered a cerebrovascular insult and were treated at Special Hospital for Cerebrovascular disorders "Saint Sava" in Belgrade. All patients were divided into two groups due to the presence of elevated body temperature. RESULTS: Fever as a complication in period after acute cerebrovascular insult is presented in almost every fifth patient. In the group of patients with fever, the most common presentation was acute ischemic cerebrovascular insult, namely in 45.63%, while in the group of patients with normal body temperature, the most common presentation was lacunar infarction, namely in 46.60% of participants. The most frequent localization of cerebrovascular insult is in cortex and subcortex regions. CONCLUSIONS: It should be stated that some patients with specific types of cerebrovascular insult as well as their localization are at higher risk for development of complications. This study suggests that appropriate diagnostics as well as prevention and management of in-hospital complications could improve the short-term and long-term prognoses after stroke (Tab. 3, Ref. 14).

Oxidative stress accelerates spontaneous apoptosis of B-chronic lymphocytic leukemia lymphocytes.

PURPOSE: B-chronic lymphocytic leukemia (B-CLL) is characterized by the progressive accumulation of small immature B lymphocytes which do not undergo apoptosis due to an underlying defect. One potential mechanism of defective apoptosis could be irregular oxidative stress. The goal of our investigation was to determine in vitro production of oxidative stress markers by lymphocytes of B-CLL patients. PATIENTS AND METHODS: 30 untreated stage A B-CLL patients, as well as 20 stage B and C patients and 30 healthy volunteers as a control group were examined. Nitric oxide (NO), superoxide anion, hydrogen peroxide and malondialdehyde (MDA) were measured by spectrophotometry in supernatants of lymphocytes cultures of all 3 investigational groups. The method applied for detecting apoptosis was fluorescence microscopic analysis using acridine orange/ethidium bromide (AO/EB) double staining. RESULTS: In vitro lymphocyte production of superoxide anion, hydrogen peroxide and MDA was increased in B-CLL patients, while there were no statistical significantly differences of NO production among the tested groups. Compared with the spontaneous apoptosis observed in control subjects lymphocytes, B-CLL lymphocytes showed increased percentages of apoptotic cells after incubation for 24 h. Disease progression was not followed with significant differences in spontaneous apoptosis of B-CLL lymphocytes. CONCLUSION: This intensive oxidative stress markers production in cultures of B-CLL lymphocytes could be one of the potential mechanisms in the pathogenesis of abnormal apoptosis.

Homocysteine, folic acid and coronary artery disease: possible impact on prognosis and therapy.

Within the past four decades, the efforts of investigators worldwide have established the amino acid homocysteine (Hcy) as an important factor in arteriosclerosis and ageing. The amino acid homocysteine is a unique candidate for the study of different age-related pathological conditions, namely vascular diseases, dementia disorders and late-life depression, due to its multiple roles in different pathways leading to atherosclerosis and neurotoxicity. Especially, the role of homocysteine in predicting risk for atherothrombotic vascular disease has been evaluated in several observational studies in a large number of patients. These studies show that the overall risk for vascular disease is small, with prospective, longitudinal studies reporting a weaker association between homocysteine and atherothrombotic vascular disease compared to retrospective case-control and cross-sectional studies. Furthermore, randomised controlled trials of homocysteine-lowering therapy have failed to prove a causal relationship. On the basis of these results, there is currently insufficient evidence to recommend routine screening and treatment of elevated homocysteine concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.

Anti-nociceptive and anti-inflammatory properties of 5alpha-reductase inhibitor finasteride in experimental animals.

Finasteride is a potent drug which has been prescribed for the management of benign prostatic hyperplasia (BPH) for more than 20 years. Recent studies indicate that finasteride, as 5alpha-reductase inhibitor, can influence some central effects such as analgesia, neurosteroidogeneses and behavior. The purpose of this study was to investigate the analgesic effect of finasteride, to determine whether finasteride interact with morphine analgesia in tail-flick test and to examine the anti-inflammatory effect of this drug. Adult male Wistar rats (280-330 g) were used for the both of experiments. Tests were assessed on groups of 6 animals. The first control group (O) received water (1 ml/kg, p.o.), the second control group (OO) received the vehicle (olive oil, 1 ml/kg, p.o.) and the third group (F) received finasteride (0.5 mg/kg, p.o.) suspended in olive oil, every morning for 30 days. After 30 days of treatment, tail-flick test and formalin-induced foot paw edema test were performed. Finasteride increased the average latency in seconds in comparison to both controls (10.06 vs. 9.16 and 8.66 s). It was 9.83% higher depression of pain in group F in comparison to O and 16.17% in comparison to OO, but the anti-nociceptive effect of finasteride at applied dose didn't significantly differ compared to both controls (p > 0.05). Chronic pre-treatment with finasteride didn't interact with analgesic effect of morphine compared to O (p > 0.05), but compared to OO finasteride fastened, increased and prolonged the analgesic effect of morphine at all measuring intervals, achiving statistical significance in 60 min (p < 0.01). Finasteride also exhibited significant anti-inflammatory action (p < 0.05) in comparison to OO, but It was not significantly different from the control O. Finasteride didn't exert analgesic action, it increased morphine antinociception and showed chronic anti-inflammatory effect to some extent. This might be a useful contribution to highlight the pathogenesis of BPH. There is the need for further studies in order to confirm these results with more details.

Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. II: study in healthy volunteers.

The pharmacokinetics of a new verapamil retard tablet formulation have been investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given orally at a single new or standard retard tablet dose of 240mg and at a single intravenous dose of 5mg. Plasma verapamil concentrations were determined by HPLC. New retard tablets produced peak plasma verapamil concentrations of 81.34+/-5.69microg/l, time to peak plasma concentrations of 4.91+/-0.89h and an AUC (0-24h) of 1291+/-103.4h x microg/l, with a terminal phase half-life of 55.1+/-14.9h. After intravenous administration verapamil exhibited biphasic elimination kinetics with a terminal plasma half-life of 2.36+/-0.42h and systemic clearance of 34.32+/-5.81 l/h. Bioavailability of the new peroral retard formulation ranged from 19.49+/-4.41% to 67.69+/-11.70%. Absorption rates and amounts were evaluated by means of the spline-convolutional method. Input rates for the new verapamil retard formulation ranged from 0.77+/-0.20mg/h to 5.57+/-1.58mg/h. The cumulative amount of verapamil input was 39.17+/-9.71% for the new retard tablets. All pharmacokinetic parameters for the new verapamil retard tablet formulation, were in reasonable agreement with the data obtained on already registered verapamil retard formulations, indicating their bioequivalence.

The role of hydrogen sulfide in homocysteine-induced cardiodynamic effects and oxidative stress markers in the isolated rat heart.

This study aimed to assess the role of H2S in homocysteine-induced cardiodynamic effects in the isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique. The maximum and minimum rates of pressure in the left ventricle (dp/dt max, dp/dt min), systolic and diastolic left ventricular pressures (SLVP, DLVP), heart rate (HR), and coronary flow (CF) were measured. A spectrophotometrical method was used to measure the following oxidative stress markers: index of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), nitrite level (NO2-), superoxide anion radicals (O2•-), and hydrogen peroxide (H2O2) concentrations. The administration of 10 µmol/l DL-homocysteine (DL-Hcy) alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. The administration of 10 µmol/l DL-propargylglycine (DL-PAG) decreased all cardiodynamic parameters and increased the concentration of O2•-. The co-administration of DL-Hcy and DL-PAG induced a significant decrease in all estimated cardiodynamic parameters and decreased the concentration of NO2- and O2•- but increased the levels of TBARS and H2O2. Homocysteine shows a lower pro-oxidative effect in the presence of hydrogen sulfide (H2S), which indicates a potential anti-oxidative capacity of H2S.