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Kalman Toth

Publications and source records attributed to Kalman Toth.

At least 19 recordsLinked to original sources
PubMed2006

Clopidogrel resistance: role of body mass and concomitant medications.

INTRODUCTION: Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this has made antiplatelet therapy the cornerstone of cardiovascular disease management. Recent studies have described the phenomenon of clopidogrel resistance but the possible mechanisms are still unclear. PATIENTS AND METHODS: The aim of this study was to compare the characteristics (risk profile, previous diseases, medications, hemorheological variables and plasma von Willebrand factor and soluble P-selectin levels) of patients in whom clopidogrel provided effective platelet inhibition with those in whom clopidogrel was not effective in providing platelet inhibition. 157 patients with chronic cardio- and cerebrovascular diseases (83 males, mean age 61+/-11 yrs, 74 females, 63+/-13 yrs) taking 75 mg clopidogrel daily (not combined with aspirin) were included in the study. RESULTS: Compared with clopidogrel-resistant patients (35 patients (22%), patients who demonstrated effective clopidogrel inhibition had a significantly lower BMI (26.1 vs. 28.8 kg/m2, p<0.05). Patients with ineffective platelet aggregation were significantly more likely to be taking benzodiazepines (25% vs. 10%) and selective serotonin reuptake inhibitors (28% vs. 12%) (p<0.05). After an adjustment to the risk factors and medications BMI (OR 2.62; 95% CI: 1.71 to 3.6; p<0.01), benzodiazepines (OR 5.83; 95% CI: 2.53 to 7.1; p<0.05) and SSRIs (OR 5.22; 95% CI: 2.46 to 6.83; p<0.05) remained independently associated with CLP resistance. There was no significant difference in the rheological parameters and in the plasma levels of adhesive molecules between the two examined groups. CONCLUSION: The background of ineffective clopidogrel medication is complex. Drug interactions may play a role on clopidogrel bioavailability, on the other hand, the significant difference in BMI between the two examined groups suggests that clopidogrel therapy should be weight-adjusted.

Benzodiazepines↗
PubMed2006

PARP inhibition prevents postinfarction myocardial remodeling and heart failure via the protein kinase C/glycogen synthase kinase-3beta pathway.

The inhibition of glycogen synthase kinase-3beta (GSK-3beta) via phosphorylation by Akt or protein kinase C (PKC), or the activation of mitogen-activated protein kinase (MAPK) cascades can play a pivotal role in left ventricular remodeling following myocardial infarction. Our previous data showed that MAPK and phosphatidylinositol-3-kinase/Akt pathways could be modulated by poly(ADP-ribose)polymerase (PARP) inhibition raising the possibility that cardiac hypertrophic signaling responses may be favorably influenced by PARP inhibitors. A novel PARP inhibitor (L-2286) was tested in a rat model of chronic heart failure following isoproterenol-induced myocardial infarction. Subsequently, cardiac hypertrophy and interstitial collagen deposition were assessed; additionally, mitochondrial enzyme activity and the phosphorylation state of GSK-3beta, Akt, PKC and MAPK cascades were monitored. PARP inhibitor (L-2286) treatment significantly reduced the progression of postinfarction heart failure attenuating cardiac hypertrophy and interstitial fibrosis, and preserving the integrity of respiratory complexes. More importantly, L-2286 repressed the hypertrophy-associated increased phosphorylation of panPKC, PKC alpha/betaII, PKC delta and PKC epsilon, which could be responsible for the activation of the antihypertrophic GSK-3beta. This work provides the first evidence that PARP inhibition beneficially modulates the PKC/GSK-3beta intracellular signaling pathway in a rat model of chronic heart failure identifying a novel drug target to treat heart failure.

Animals↗
PubMed2006

Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables.

BACKGROUND AND OBJECTIVE: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. METHODS: 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. RESULTS: Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). CONCLUSIONS: The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.

Adrenergic beta-Antagonists↗
PubMed2006

Hemorheological parameters and aging.

BACKGROUND: There is increasing evidence that impaired hemorheological parameters are associated with increased risk of cardio- and cerebrovascular events. The aim of our present study was to examine the relationship of these parameters to the advancing age. METHODS: The data of 6236 cardio- and cerebrovascular patients (3774 males, mean age 59.8 +/- 13.2 years and 2462 females, mean age 60.9 +/- 12.8 years) were included into this analysis. Males and females were divided into three groups, A < 45 years of age (young), B 45-65 years (middle-aged), C > 65 years (old). To exclude the effect of risk profile, previous diseases and medication, 623 patients (397 males, mean age 60.2 +/- 12.7 yrs and 226 females, mean age 60.5 +/- 12.4 yrs) were selected from the examined group with matching parameters. Blood was collected after an overnight fasting. Hematocrit, fibrinogen, red blood cell aggregation, plasma and whole blood viscosity were determined. RESULTS: All the measured parameters correlated significantly with advancing age in the whole population (p < 0.01), however the values of the correlation coefficients were very low. On the other hand, examining the different age-groups we found that these parameters did not consequently correlate with age, in fact hematocrit, red blood cell aggregation and whole blood viscosity values were negatively correlated with age in old males (p < 0.05). In the selected population these parameters did not correlate with advancing age. CONCLUSIONS: In the whole population the correlation of hemorheological parameters and advancing age may be just of statistical, but not clinical significance because of the high number of subjects. In the selected population these parameters did not correlate with advancing age. Our results suggest that these parameters are mostly independent of aging, increased values are not associated with older age but the more frequently occurring diseases.

Adult↗
PubMed2006

The effect of blood glucose levels on hemorheological parameters, platelet activation and aggregation in oral glucose tolerance tests.

Rheological factors and increased platelet aggregation are convincingly implicated in the development of micro- and macrovascular disease associated with diabetes mellitus. The present examination has been designed to describe the effects of a standard oral glucose load on hemorheological parameters, platelet activation and aggregation in patients with normal and pathologic glucose tolerance. Oral glucose tolerance test (OGTT) was performed in 30 patients suspected to have diabetes mellitus. Hematocrit, erythrocyte aggregation, red blood cell filterability, plasma and whole blood viscosity, soluble P-selectin levels and platelet aggregation were tested paralelly with blood glucose measurements 1, 2, and 3 hours after glucose consumption. Patients were divided into two groups based on glucose tolerance. Patients with abnormal glucose tolerance (IGT/DM) showed significant elevation in red blood cell aggregability (Myrenne indices M and M1) at the 2- and 3-hour samplings (p<0.01 and p<0.001, respectively). Patients with normal glucose tolerance (NGT) showed significant elevation only in M1 index (p=0.01). Plasma viscosity decreased significantly compared to fasting values in IGT/DM patients in all samples, but remained unchanged in NGT patients. Hematocrit decreased in IGT/DM patients significantly from the 2-hour samplings on (p<0.05), in normoglycaemic patients its decrease reached a borderline significance at 3-hour measurements. No significant changes were detected in whole blood viscosity, red blood cell filterability and sP-selectin levels during OGTT in either examined groups. No examined parameters were significantly correlated to blood glucose levels at any sampling. Erythrocyte aggregation showed significant correlation with BMI (p<0.01). Our results demonstrate that after the intake of a standard amount of glucose the development of rheological alterations is not simultaneous with the elevation of blood glucose levels, and our data suggest that the observed elevation in erythrocyte aggregation during OGTT might be associated with hyperinsulinemia.

Aged↗
PubMed2005

Pulmonary embolization as primary manifestation of hepatocellular carcinoma with intracardiac penetration: a case report.

Intracardiac manifestation of hepatocellular carcinoma (HCC) is a rare condition and an uncommon finding even at autopsy. Pulmonary tumor embolism as a presenting feature of HCC has been published only twice previously. In our case report, a 63-year-old man presented with high fever and six episodes of recurrent pneumonias during the last half year. Echocardiography was performed, a solid mass was found in the right atrium. Transesophageal echocardiography proved a tumor mass in the inferior vena cava (IVC) extending into the right atrium, abdominal ultrasound revealed tumor mass in the IVC and a solid tumor in the liver. Combined liver and heart surgery was attempted in order to remove the tumor mass from both the liver and the right atrium. Acute cor pulmonale occurred during tumor removal from the right atrium and the patient expired. In addition to local factors the possibility of embolization should arise in the background of recurrent pneumonia. Occult carcinoma must be included in possible causes of recurrent pulmonary embolism. Searching for primary malignancy should include HCC as frequent cause of hypercoagulability. In case of HCC, echocardiography is suggested because of the possibility of expansion in IVC or right atrium and tumor-embolization.

Carcinoma, Hepatocellular↗
PubMed2005

Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS). OBJECTIVE: To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance. METHODS: The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events. RESULTS: PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin. CONCLUSIONS: Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.

Adult↗
PubMed2005

Prevention of doxorubicin-induced acute cardiotoxicity by an experimental antioxidant compound.

Doxorubicin is a widely used anticancer agent, but its application is restricted by its cardiotoxic side effects. The current theory of its cardiotoxicity is based on free radical formation. The compound H-2545, having a 3-carboxamido-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole moiety, was reported to exhibit antioxidant properties and accumulate in cell membranes, scavenging free radicals at the site of formation. Therefore, we hypothesized that H-2545 could reduce the doxorubicin-induced acute deterioration of cardiac function. Langendorff-perfused rat hearts were treated with doxorubicin and/or H-2545, its metabolite H-2954, or dihydrolipoamide. High-energy phosphate levels, contractile function, lipid peroxidation, protein oxidation, and Akt phosphorylation were investigated. We also determined whether the antioxidants influenced doxorubicin toxicity on malignant cells. During perfusion with doxorubicin, the energetic and functional parameters of the myocardium were improved by adding H-2545. H-2545 significantly diminished doxorubicin-induced lipid and protein damage. On H-2545 treatment, the doxorubicin-triggered Akt phosphorylation was markedly reduced, whereas dihydrolipoamide had such an effect only at higher concentrations. H-2545 did not alter the anticancer effect of doxorubicin on malignant cell lines. We propose that the coadministration of the antioxidant H-2545 attenuates doxorubicin-induced acute cardiotoxicity without interfering with its anticancer effects. Prevention of the acute adverse effects of doxorubicin on myocardium may hinder the later development of cardiomyopathy.

Animals↗
PubMed2005

Measurement of whole blood viscosity profiles via an automated viscometer: technical details and clinical relevance.

Recent basic science and large-scale clinical studies involving blood rheological factors have led to a similar conclusion: the mechanics of blood flow play an important role in the development and progression of various cardiovascular diseases (e.g., coronary artery disease, stroke). Several viscometer systems to measure whole blood viscosity have been developed, yet blood viscosity measurements are not routinely employed in clinical practice, primarily due to the complexity of currently available methods. Herein we provide a description of a new, computer-controlled capillary viscometer that offers a convenient approach to the measurement of blood viscosity over a wide range of shear rates. The new viscometer uses a disposable test section, requires small volumes of blood, provides viscosity data that compare well with those from other viscometers, and completes all testing and data analysis within five minutes.

Blood Viscosity↗
PubMed2004

Postural control in athletes participating in an ironman triathlon.

We studied the degree of dependence on vision of static postural control among ten male adult ironmen and ten healthy subjects (firemen, control group) who took part in regular physical activity, and the perturbations of equilibrium after prolonged exercise in ironmen. Static postural stability was measured during standing on a single-force platform alternating between eyes open and eyes closed. First, body sway was analysed on a force plate in both groups, and the athletes then took part in an ironman triathlon. The measurement was repeated after the race. The sway in both directions was subjected to spectral analysis. The frequency spectrum of the platform oscillations was calculated by fast Fourier transformation in the intervals 0-0.3, 0.3-1 and 1-3 Hz. The sway path in both directions and the total path were significantly lower in the ironmen than in the control group without vision, and the absence of visual control caused a significant increase in sway in both directions in the control group, but not in the ironmen. The frequency analysis revealed a higher level of stability in the medio-lateral direction with closed eyes. The endurance race caused increases in both the total sway path only with closed eyes, and these changes were significant at higher frequency bands. These results indicate that ironmen are more stable and less dependent on vision for postural control than the control subjects, and the prolonged stimulation of the proprioceptive, vestibular and visual inputs in the endurance race causes a significant disturbance in postural control.

Adult↗
PubMed2004

Inhibition of ADP-evoked platelet aggregation by selected poly(ADP-ribose) polymerase inhibitors.

Pathologic platelet activation has been implicated in the pathogenesis of ischemic heart disease. Since cardiomyocytes can be protected from ischemia-reoxygenation injury by poly(ADP-ribose) polymerase (PARP) inhibitors mimicking the adenine/ADP part of NAD, their structural resemblance to ADP may also enable the blockade of platelet aggregation via binding to ADP receptors. Blood samples drawn from healthy volunteers were pre-incubated with different concentrations of PARP inhibitors: 4-hydroxyquinazoline, 2-mercapto-4(3 H)-quinazolinone, or HO-3089. ADP-, collagen- and epinephrine-induced platelet aggregation was evaluated according to the method described by Born. The effect of PARP inhibitors on thrombocyte aggregation was also examined when platelets were sensitized by heparin and in the presence of incremental concentrations of ADP. All examined PARP inhibitors reduced the ADP-induced platelet aggregation in a dose-dependent manner (significant inhibition at 20 microM for HO-3089 and at 500 microM for the other agents; P < 0.05), even if platelets were sensitized with heparin. However, their hindrance on platelet aggregation waned as the concentration of ADP rose (no effect at 40 microM ADP). PARP inhibitors had minimal effect on both collagen- and epinephrine-induced platelet aggregation. Our study first demonstrates the feasibility of a design for PARP inhibitors that does not only protect against ischemia-reperfusion-induced cardiac damage but may also prevent thrombotic events.

Blood Platelets↗
PubMed2004

Short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial function in patients with cerebrovascular disease and hyperlipidaemia.

INTRODUCTION AND OBJECTIVE: Haemorrheological parameters and endothelial function are known to be altered in vascular diseases, including stroke. Treatment with HMG-CoA reductase inhibitors ('statins') improves cerebrovascular (and cardiovascular) morbidity and mortality in patients with atherosclerosis; the beneficial effects may involve lipid-independent mechanisms. The aim of this study was to assess the short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial dysfunction in patients with chronic cerebrovascular disease and hyperlipidaemia. PATIENTS AND METHODS: Twenty-seven patients (mean age 61 +/- 8 years) with chronic cerebrovascular disease and hyperlipidaemia were included in the study. Serum lipid levels, haemorrheological parameters (haematocrit, plasma fibrinogen levels, plasma and whole blood viscosity [WBV] and red blood cell [RBC] aggregation and deformability) and platelet aggregation were assessed at baseline and after 1 and 3 months of treatment with atorvastatin (Sortis) 10 mg/day. von Willebrand factor (vWF) activity (a measure of endothelial function) was measured at baseline and after 1 month of treatment. Adverse events were recorded at each visit. Physical examinations, haematological assessments and serum and urine chemistry assays were performed during the study. RESULTS: Plasma total cholesterol levels were reduced by a mean of 27% compared with baseline after both 1 and 3 months of treatment (p < 0.001). Low density lipoprotein-cholesterol levels were reduced by a mean of 40% and 38% (p < 0.001), respectively, after 1 and 3 months of treatment, compared with baseline values. Triglyceride levels decreased by 20% at 1 month and by 10% after 3 months (p < 0.001). Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment. CONCLUSIONS: Our findings show that the beneficial effects of atorvastatin are complex. Besides lipid lowering, atorvastatin can improve haemorrheological parameters, platelet aggregation and endothelial dysfunction after short-term and low-dose therapy. Whether such early laboratory changes translate into clinical utility for secondary stroke prevention awaits the results of endpoint trials.

Aged↗
PubMed2004

Hemorheological methods in drug research.

Development of new drugs is a sophisticated process that requires several, different methods. In our experiments we have applied two rheological models to study experimental and clinically used drugs. The antioxidant properties of several agents were estimated by erythrocyte filtration technique. The known antioxidant compound vitamin E was used to validate our measurements. An experimental cardioprotective agent, H-2545 provided significant protection against oxidative changes in red blood cell filterability (p<0.001). Although some of the examined, known cardiovascular drugs also showed significant antioxidant effect, they were less efficient than H-2545 and the scavenger effect of this novel agent exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring improved significantly its antioxidant capacity suggesting this molecular segment to be responsible for the antioxidant effect. In our second model the antiplatelet effect of experimental poly(ADP-ribose) polymerase (PARP) inhibitors was evaluated. Two widely used antiplatelet agents: acetyl salicylic acid and eptifibatide served as controls in the validation of the measurements. PARP inhibitors reduced ADP-induced platelet aggregation in a dose-dependent manner (p<0.05). However, their hindrance on platelet aggregation waned as the concentration of ADP rose. Regarding the platelets' role in the development of ischemic vascular diseases, the antiaggregating property of PARP inhibitors may exert additional beneficial effects on tissue blood supply under conditions of compromised vascular flow.

Adenosine Diphosphate↗
PubMed2003

Impact of a novel cardioprotective agent on the ischaemia-reperfusion-induced Akt kinase activation.

Cardioprotective effect of a free radical-scavenging compound (HO-3073) was examined during ischaemia-reperfusion (IR) in isolated heart perfusion system and its influence on the pro-survival Akt signalling pathway was addressed. Rat hearts were perfused according to the Langendorff method and subjected to a global 25-min ischaemia and 15, 45 and 90-min reperfusion either untreated or treated with HO-3073 (2, 5 and 10 microM) and/or wortmannin (100 nM, inhibitor of phosphatidylinositol-3-kinase). HO-3073 facilitated the recovery of myocardial energy metabolism as assessed by 31P NMR spectroscopy (creatine phosphate recovery in reperfusion was 76+/-5%, while in untreated hearts 32+/-4%). Functional performance of the hearts followed by a left ventricular balloon manometer was also markedly improved by HO-3073 administration (recovery of rate-pressure product related to normoxia was 47+/-3%, while in untreated hearts 12+/-3%). HO-3073 diminished the infarct size measured by TTC staining (29+/-6% as opposed to 64+/-7% in untreated ischaemia-reperfusion). HO-3073 also significantly attenuated lipid peroxidation (thiobarbituric acid reactive substances) and protein oxidation (protein carbonyl content) compared to untreated hearts. HO-3073 enhanced the ischaemia-reperfusion-triggered phosphorylation of Akt-1 (activation) and glycogen synthase kinase-3 beta (inactivation) as evidenced by Western blot analysis. Wortmannin co-administration neutralised the beneficial effects of HO-3073 on cardiac energetics, contractile function, infarct size, as well as Akt signalling. Our results first display that a radical-scavenging molecule possesses the ability to intensify the pro-survival functioning of phosphatidylinositol-3-kinase/Akt pathway, which is presumed to play an additive role in the cardioprotective properties of HO-3073.

Animals↗
PubMed2003

Akt activation induced by an antioxidant compound during ischemia-reperfusion.

Molecular mechanisms of cardioprotection afforded by modified mexiletine compounds were investigated during ischemia-reperfusion (IR) in Langendorff perfused hearts. Rat hearts were subjected to a global 25 min ischemia followed by reperfusion, either untreated or treated with mexiletine, or three substituted mexiletine derivates (5 muM). A modified mexiletine derivative (H-2693) promoted best the recovery of myocardial energy metabolism (assessed by (31)P NMR spectroscopy) compared to untreated and mexiletine-treated hearts. H-2693 also preserved cardiac contractile function and attenuated the IR-induced lipid peroxidation (TBARS formation) and protein oxidation (carbonyl content). Western blot revealed that H-2693 propagated the phosphorylation of Akt (activation) and its downstream substrate glycogen synthase kinase-3beta (GSK-3beta, inactivation) compared to untreated IR. Parallel treatment with the phosphatidylinositol-3-kinase (upstream activator of Akt) inhibitor wortmannin (100 nM) abolished the beneficial effects of H-2693 on energetics and function, and reduced Akt and GSK-3beta phosphorylation. As a result of the antiapoptotic impacts of Akt activation, H-2693 decreased caspase-3 activity, which was neutralized by wortmannin. Here we first demonstrated that a free radical-entrapping compound could activate the prosurvival Akt pathway beyond its proven ability to scavenge reactive oxygen species. In conclusion, the favorable influence of H-2693 on signaling events during IR may have considerably contributed to its cardioprotective effect.

Androstadienes↗
PubMed2003

The significance of intrathecal catheter location in rats.

Although chronic intrathecal catheterization is a widely used method in rats, few calibration experiments have been performed. In this study, we investigated the correlation between the side position of the catheter tip and the side differences observed in the motor and sensory disturbances after intrathecal administration of lidocaine to a large number of rats. The existence of a sensory block was determined by the paw withdrawal test. The motor impairment was assessed by observing the complete clubbing of the hindpaw and measuring the hindpaw grip strength. After experimental use, we established the position of the catheter tip. The catheter tips were variously located in all directions of the transverse plane in the rat spinal subarachnoid space. Lidocaine administration (100 or 500 microg/5 microL; n = 264 and 112, respectively) led to dose-dependent motor and sensory disturbances. The effect of 100 microg of lidocaine exhibited side differences; i.e., the extents of both motor (r = 0.77) and sensory (r = 0.60 and r = 0.67 for the right and the left side, respectively) disturbances correlated significantly with the location of the catheter tip. Our data have shown that detection of the paralytic and/or antinociceptive effect of small-dose lidocaine before planned experiments is a simple and reliable method for prediction of the location of the catheter tip. We suggest that the position of the catheter might cause side differences in the drug effect, especially if small doses of drugs are administered and their effects are investigated on both sides.

Anesthetics, Dissociative↗