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R Testa

Publications and source records attributed to R Testa.

At least 73 records · Page 4Linked to original sources
PubMed1999

The rate of plasmin formation after in vitro clotting is inversely related to lipoprotein(a) plasma levels.

Lipoprotein(a) levels are largely genetically determined and are linked to increased risk of coronary artery disease. The hypothesis that elevated lipoprotein(a) levels lead to decreased fibrinolysis, due to the close structural homology with plasminogen, could in part explain the genesis of this risk, although contrasting results have been obtained in different studies. The aim of our study was to evaluate whether the rate of plasmin formation, enhanced in vitro by a fixed amount of human tissue plasminogen activator after clotting, was related to plasma lipoprotein(a) levels in 45 healthy subjects. Aliquots of human plasma were clotted with calcium chloride and thrombin followed by addition of tissue plasminogen activator. We then measured the time course of plasmin formation, determined as hydrolysis of H-D-valyl-L-leucyl-L-lysine-p-nitroanilide dihydrocortide (S-2251). The log of lipoprotein(a) level was negatively related to the rate of plasmin formation (r(s)=-0.46, P=0. 002), and multiple regression analysis indicated that this relationship was not influenced by the amount of plasminogen, fibrinogen, plasminogen activator inhibitor-1, tissue plasminogen activator, or by the size of apo(a) isoforms. These data support the concept that lipoprotein(a) can inhibit plasminogen activation and plasmin formation and can thereby play an important role in the genesis of atherosclerosis as an antifibrinolytic agent.

Adult↗
PubMed1999

Microchimerism and blocking activity in women with recurrent spontaneous abortion (RSA) after alloimmunization with the partner's lymphocytes.

Alloimmunization therapy using the partner's leukocytes has been reported to be effective in preventing the failure of pregnancy in patients who have suffered RSA of unknown cause. After alloimmunization, several investigators have reported the presence of blocking factors (BF) in women with successful pregnancies in in vitro assays of lymphocyte response. The recent discovery of small numbers of ubiquitous donor cells (microchimerism) in human transplants up to 29 years post-transplantation has raised questions about the migration of the chimeric cells and their role in the induction and perpetuation of tolerance. We have investigated the production of BF in the mixed lymphocyte reaction (MLR) before and in some patients after alloimmunization and its possible relation with the development of microchimerism (M). Before the treatment we studied 14 couples with three or more abortions who were evaluated clinically to rule-out genetic, structural, endocrine, infectious and autoimmune causes. The M study was done by nested PCR-SSP technique with HLA-DR alleles, before and after 30 days of the last immunization. Before the treatment only one patient was M positive and none were BF positive with inhibition effect (IE) > 50. Only eight underwent treatment. The patients had between three and nine alloimmunizations (x = 4.7). After treatment, all patients were M positive with IE > 50. Six months after the last immunization, four patients are M positive with IE > 50. In conclusion, the hypothesis proposes that alloimmunization establishes a state of microchimerism that would be the necessary allogeneic stimulus for T-cell activation, and the induction or maintenance of tolerance to the fetus during pregnancy. reserved.

Abortion, Habitual↗
PubMed1999

Progressive liver functional impairment is associated with an increase in AST/ALT ratio.

The ratio of serum aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio) has been proposed as a noninvasive method of assessing liver fibrosis and cirrhosis. Our aims were to confirm the usefulness of the AST/ALT ratio in diagnosing cirrhosis noninvasively as well as to verify the existence of a relationship between the ratio and liver functional impairment. In all, 348 patients (177 with chronic hepatitis, 171 with cirrhosis) were retrospectively evaluated and the AST/ALT ratio was related to monoethyl glycine xylidide (MEGX) formation. Moreover, in a subgroup of 54 patients we analyzed the relationships among the AST/ALT ratio and indocyanine green clearance and half-life. The AST/ALT ratio was able to separate patients with mild fibrosis from those with severe fibrosis and cirrhosis. The AST/ALT ratio, MEGX, prothrombin activity, and platelet count were selected by multivariate analysis as variables associated with cirrhosis. The AST/ALT ratio showed significant correlations both with MEGX formation and with indocyanine green clearance and half-life. The alterations of indocyanine green kinetics, which depend upon liver blood flow and uptake, were likely due to progressive fibrosis. These findings might partially explain the increase in the AST/ALT ratio as disease progresses.

Adult↗
PubMed1999

Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin.

AIMS: To assess the effects and safety of increasing sulphonylurea dosages or adding metformin in poorly controlled elderly Type 2 diabetic patients. METHODS: A 18-month multicentre clinical study was performed on sulphonylurea-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose > or = 200 mg/dl and HbA1c > or = 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic status and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. RESULTS: Similar improvements in glycaemic levels were observed with both treatments within the first month and a similar decrease in HbA1c within the third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/- 0.19 and HbAt1c(%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd treatment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.28, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA1c from 10.33 +/- 0.13 to 8.77+/-0.12 (for all P<0.0005). In this 2nd group, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-cholesterol levels (P < 0.02) were also observed. In the 1st group, anthrombin III activity increased significantly (P<0.01). In the 2nd group, significant reductions in markers of platelet function (FP4 and betaTG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P<0.01), and fibrinolysis inhibition (PAI-1 activity, PAI-1 antigen, P< 0.001) were observed. Increases in some fibrinolytic activation markers (t-PA activity, and AT-III activity, P<0.01) occurred. Fasting lactate concentrations were unchanged in the metformin-treated group. No serious adverse effects were observed in either group. CONCLUSIONS: These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effective and safe in an aged but healthy population. Metformin provides additional benefits counteracting several cardiovascular risk factors but must be administered with caution, bearing in mind the general contra-indications for the drug but not age alone.

Aged↗
PubMed1999

Determination of plasma metformin by a new cation-exchange HPLC technique.

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetic patients. This biguanide can induce dangerous complications such as lactic acidosis when its plasma concentration is too high. For this reason, the determination of plasma metformin should always be done during treatment. We developed a new HPLC method, for the routine determination of plasma metformin, with good reliability, rapid execution, and low costs. Sample preparation involved precipitation of the plasma proteins containing the internal standard buformin with a mixture of methanol, zinc sulfate, and ethylene glycol; the diluted supernatant was injected into a cation-exchange column. The mobile phase was potassium dihydrogenphosphate buffer-containing acetonitrile. The eluent was monitored at 236 nm. The calibration curve is linear within the range of 20-4000 ng/mL; the within-day coefficients of variation were less than 2.2% for metformin and 1.5% for buformin; the day-to-day coefficients of variation were less than 2.5% for metformin and 1.9% for buformin. The mean recoveries obtained from supplemented samples were included between 99.4 and 104.2% for metformin. Many characteristics make this method useful and easily accessible to all clinical laboratories equipped with HPLC instrumentation.

Administration, Oral↗
PubMed1999

Chronic liver disease related to hepatitis C virus: age of patients seems to be a determinant of severity independently of viral genotype.

BACKGROUND: Hepatitis C virus infection accounts for varying severity of chronic liver disease. Clinical manifestations of infection have been related to different virus genotypes, with conflicting results. DESIGN: We performed a cross-sectional study on a Northern-Italian group of patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma related to hepatitis C virus infection in order to verify the association of different viral strains and the outcomes of viral disease. METHODS: Two hundred and seventy-one patients referred to our unit for liver disease were studied and clinical, biochemical, histological, and functional parameters were investigated. RESULTS: Different viral genotypes were not associated with peculiar findings in any of the degrees of liver disease. However, a progressive age increase was associated with disease severity, although clinical and functional staging of cirrhotic patients with hepatocellular carcinoma was better compared to tumour-free cirrhotic patients. There was an increased prevalence of genotype 1b related to the age of the patients. In multivariate regression analysis the patients' age and apparent duration of infection were independently associated with the presence of cirrhosis and only the age of patients was associated to hepatocellular carcinoma. CONCLUSIONS: In the population we studied age of the patients seemed to be a determinant conditioning disease severity, likely reflecting older infections and long-standing liver disease. The prevalence of certain genotypes in varying degrees of liver disease could be an epiphenomenon which might also be explained by the changing prevalence of infecting strains over the past decades.

Adolescent↗
PubMed1999

Can the MEGX test and serum bile acids improve the prognostic ability of Child-Pugh's score in liver cirrhosis?

BACKGROUND: Liver transplantation is nowadays the therapeutic option for end-stage liver disease. Correct disease staging is the main step towards improving the timing of listing for liver transplantation so as to avoid premature or late entry. The need for correct prognostic evaluation is due to the limited number of donors and to the increasing number of patients awaiting transplantation. Our aim was to verify whether Child-Pugh's score might be improved by adding the monoethylglycinexylidide (MEGX) formation test and/or serum bile acid determination. METHODS: We evaluated 182 cirrhotic patients (44 Child-Pugh class A, 97 class B, and 41 class C) of mixed aetiology referring to a tertiary care centre for functional staging of liver disease. These patients were prospectively followed-up for 12-72 months. During this period, 45 patients died, 46 received a transplant, and 91 survived without transplantation. The end-point of analysis was either survival or liver disease-related death at the 6th, 12th, 18th and 24th months of follow-up. The 46 transplanted patients were excluded from the study upon transplantation. RESULTS: In our study, a cut-off for Child-Pugh's score < 8 confirmed its usefulness, especially in short-term prognostic prediction, while mid- and long-term prediction improved by almost 10% by using the combination of a Child- Pugh's score > 8 and an MEGX value < 15 mg/l. Cox's multi-variate regression analysis indicated that MEGX values either with Child-Pugh's score or with prothrombin activity and ascites were independent prognostic variables. CONCLUSIONS: Besides confirming that Child-Pugh's score as the basis of prognostic evaluation of cirrhotic patients, these results suggest that the MEGX test might be a complement to the original score when a patient is being evaluated for a liver transplantation programme.

Adult↗
PubMed1999

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients.

BACKGROUND/AIMS: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. METHODS: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. RESULTS: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. CONCLUSIONS: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence ofcholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.

Adult↗
PubMed1999

Vascular-selective effect of lercanidipine and other 1,4-dihydropyridines in isolated rabbit tissues.

The aim of this study was to characterize the in-vitro vasoselectivity of lercanidipine (in comparison with lacidipine, amlodipine, nitrendipine and felodipine) by evaluating its functional calcium antagonistic activity on rabbit vascular (aorta) and cardiac tissues (heart ventricle). Although incubation with all the compounds tested elicited a concentration-dependent relaxant effect on vascular tissue precontracted with KCl (80 mM), 50% relaxation was reached at different times for each concentration and drug tested. At 10 nM concentration 50% relaxation was reached after 210 min with lercanidipine, 278 min with amlodipine, 135 min with lacidipine, 75 min with nitrendipine and 70 min with felodipine. The onset of the effect was, therefore, similar for lercanidipine, amlodipine and lacidipine, but faster for nitrendipine and felodipine. Similarly, all the compounds tested concentration-dependently reduced the force of cardiac contraction (negative inotropic activity). In this model, the time needed to reach 50% reduction in contractile force was also concentration-dependent, and the ranking order of the speed of onset of the effect (evaluated as the ratio of the IC50 values (the concentrations inhibiting contraction by 50%) calculated after 1 and 4 h incubation) was lacidipine (3.8) > amlodipine (9.6) > felodipine (39) > lercanidipine (68) = nitrendipine (89). The vasoselectivity, expressed as the ratio of the IC50 values obtained on cardiac and vascular tissue, were (for 4 h incubation) 730, 193, 95, 6 and 3 for lercanidipine, lacidipine, amlodipine, felodipine and nitrendipine, respectively, showing that lercanidipine is the most vasoselective of the calcium-antagonists tested. The results show that lercanidipine reduces the inotropic force of the rabbit heart to a lesser extent than do other calcium antagonists, and that this drug had the best heart/vessel selectivity index among the compounds tested at all the times tested.

Animals↗
PubMed1999

Effect of several 5-hydroxytryptamine(1A) receptor ligands on the micturition reflex in rats: comparison with WAY 100635.

Several novel N-arylpiperazine derivatives were synthesized and tested for their 1) affinity and functional activity on 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in vitro; 2) activity in models predictive of antagonism at somatodendritic and postsynaptic 5-HT(1A) receptors; and 3) effects on the micturition reflex in anesthetized and conscious rats. These studies also included 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine hydrobromide (NAN 190), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione dihydrochloride (BMY 7378), and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-(2-pyridinyl)cyclohex anecarboxamide (WAY 100635). Almost all compounds were found to be potent and selective for the human recombinant 5-HT(1A) receptor, with K(i) values in the nanomolar range. [(35)S]GTPgammaS binding in HeLa cells expressing the recombinant human 5-HT(1A) receptor allowed classification of the compounds into neutral antagonists and partial agonists. Almost all neutral antagonists were active in blocking 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced forepaw treading in rats (postsynaptic model) and hypothermia in mice (somatodendritic model) with the same potency, whereas compounds showing partial agonistic activity were active in the postsynaptic model but were inactive, or poorly active, in the somatodendritic model. Neutral antagonists potently inhibited volume-induced bladder-voiding contractions in anesthetized rats. Contractions were completely blocked, and the disappearance of bladder contractions lasted 7 to 13 min after the highest doses tested. Furthermore, neutral antagonists increased bladder volume capacity in conscious rats during continuous transvesical cystometry, whereas micturition pressure was only slightly, and not dose-dependently, reduced. Partial agonists were inactive or poorly active, inducing a disappearance time of bladder contractions that did not exceed 6 min in anesthetized rats, and failing to increase bladder volume capacity in conscious rats. These findings indicate that only neutral 5-HT(1A) receptor antagonists are endowed with inhibitory effects on the bladder.

Animals↗
PubMed1999

A strong inverse relationship between PAI-1 and Lp(a) in hypertensive Type 2 diabetic patients.

Thrombophilia with a contemporary reduction of fibrinolytic activity has been observed both in diabetes mellitus and hypertension. Previously, we found a relationship between plasminogen activator inhibitor Type 1 (PAI-1) and lipoprotein(a) [Lp(a)] in Type 2 diabetes mellitus patients without complications. We hypothesised that this relationship could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis as found in Type 2 diabetes mellitus. The present work was aimed at investigating the influence of concurrent hypertension and diabetes mellitus on the plasma levels of these two fibrinolytic inhibitors. In addition, other risk factors, known to influence the fibrinolytic parameters, were taken into account. Forty-nine Type 2 nonhypertensive diabetic patients without complications, 47 Type 2 hypertensive diabetic patients without complications, 54 non-diabetic hypertensive subjects without complications as well as 87 control subjects were studied. Plasma concentrations of Lp(a), PAI-1 antigen and activity, and the main parameters of oxidative, lipo- and glycometabolic balance were determined. Significant statistical differences between diabetic and non-diabetic subjects were found concerning triglycerides and antioxidant defence (p<0.01). Analysis of variance showed the F test statistically significant in evaluating the Log PAI-1/Lp(a) (p = 0.02). Correlation analysis between Log PAI-1 antigen and Lp(a) was significant in non-hypertensive diabetic patients, as expected (r = -0.38, p<0.01), and even stronger in hypertensive diabetic patients (r = -O.72,p<0.01). These results allow to hypothesise that the relationship between PAI-1/Lp(a) could be determinant in avoiding vascular complications due to diabetes mellitus and hypertension.

Aged↗
PubMed1998

Which variable of stenosis severity best describes the significance of an isolated left anterior descending coronary artery lesion? Correlation between quantitative coronary angiography, intracoronary Doppler measurements and high dose dipyridamole echocardiography.

OBJECTIVES: This study sought to investigate the angiographic or intracoronary Doppler variables of stenosis severity that best correlate with the results of dipyridamole echocardiography. BACKGROUND: Quantitative coronary angiography and intracoronary Doppler flow velocity assessments are the commonly used techniques for the objective identification of significant coronary artery stenosis. METHODS: Thirty patients with an isolated lesion of the left anterior descending coronary artery (LAD) were studied by means of on-line quantitative coronary arteriography, intracoronary Doppler flow velocity measurements and dipyridamole echocardiography 6 months after percutaneous transluminal coronary angioplasty. The quantitative arteriographic analyses were performed on-line; post-stenotic Doppler flow velocities were measured at baseline and after adenosine infusion. Angiographic and Doppler measurements were compared with the corresponding dipyridamole echocardiographic data and analyzed by discriminant analysis. RESULTS: The dipyridamole echocardiographic response was positive in 11 patients (37%). The best cutoff values for predicting an abnormal echocardiographic response were 1) stenotic flow reserve of 2.8 (p = 0.0001); 2) 59% diameter stenosis (p = 0.0001); 3) minimal lumen diameter of 1.35 mm (p = 0.001); 4) coronary flow reserve of 2.0 (p = 0.0002); and 5) maximal peak velocity of 60 cm/s during hyperemia (p = 0.04). Multivariate analysis identified stenotic flow reserve as the only independent predictor of ischemia during dipyridamole echocardiography. CONCLUSIONS: Stenotic flow reserve is the variable that best describes the functional significance of an isolated LAD lesion, and a value of 2.8 is the best predictor of a positive dipyridamole echocardiographic response. Furthermore, angiographic variables of stenosis severity relate to echocardiographic test results better than intracoronary Doppler variables.

Adult↗
PubMed1998

A significant relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus without complications.

We previously found a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) in non-insulin-dependent diabetes mellitus and hypothesized that this could be due to a compensatory mechanism able to lower the risk of hypofibrinolysis found in type II diabetes mellitus. The aims of the present study were: (1) to confirm the association between plasminogen activator inhibitor type-1 and lipoprotein(a) in a different group of non-insulin-dependent diabetes mellitus patients and (2) to investigate whether the association could be related to diabetic complications. Other vascular risk factors able to influence fibrinolytic parameters such as glycemia, obesity, hypertension, dyslipidemia, and oxidative stress were also considered. Sixty-six non-insulin-dependent diabetes mellitus patients without diabetic complications (48 men, 18 women), 45 non-insulin-dependent diabetes mellitus patients with complications (21 men, 24 women), and 31 control subjects (17 men, 14 women) were studied. Plasma concentrations of lipoprotein(a), plasminogen activator inhibitor type-1 antigen and activity, and the main parameters of lipo- and glycometabolic balance were determined. Antioxidant defense was assayed as oxygen radical absorbance capacity of serum. Statistically significant differences among controls and the two diabetic groups were found for fasting glucose, cholesterol, triglycerides, and oxygen radical absorbance capacity of serum, while no statistically significant differences were evident for plasminogen activator inhibitor type-1 antigen and activity and lipoprotein(a). Regression analysis of log plasminogen activator inhibitor type-1/lipoprotein(a) showed a significant correlation only in diabetic patients without complications (r = -0.57, P < 0.001). These results show that a relationship between plasminogen activator inhibitor type-1 and lipoprotein(a) is characteristic of a diabetic population without complications, supporting the suggestion that this relationship could be a compensatory mechanism of the fibrinolytic system to limit the risks of hypofibrinolysis. A lack or a loss of capacity to balance lipoprotein(a) and plasminogen activator inhibitor type-1 could contribute to the pathogenesis of the diabetic complications.

Adult↗
PubMed1998

Super-normal 201Tl retention in hibernating myocardium: an ex-vivo study using the failing human heart.

OBJECTIVE: Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated. METHODS: In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis. RESULTS: Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion. CONCLUSIONS: This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.

Adult↗
PubMed1998

The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved?

Atherosclerosis results from multiple factors and involves several mechanisms, including endothelial monocyte and smooth muscle cell (SMC) changes, cholesterol accumulation, plaque rupture and thromboembolism. Calcium ions play a role in the initial and chronic development of atherosclerotic lesions. Several studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. In this study the antiatherogenic activity of lercanidipine, a new lipophilic, second-generation calcium antagonist, was investigated. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentrations ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC, with the (S)-enantiomer (69% inhibition) being 2.4-fold more active than the (R)-counterpart (29% inhibition). The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm, at least in vitro, the pharmacological potential of the compound to influence negatively the process of atherogenesis.

Animals↗
PubMed1998

Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats.

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/- 28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/- 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Acetylcysteine↗
PubMed1998

Wilson's disease with concomitant beta thalassaemia and factor V deficiency.

A case of late presentation of Wilson's disease in a female with a thalassaemic trait is reported in whom diagnosis of Factor V deficiency was made. Despite ignoring the disease for years the patient had compensated cirrhosis. She had a dramatic family history of Wilson's disease affecting at least two brothers and two sisters. Moreover, her haematologic problems were not clinically revealed until diagnosis had been made on the basis of suspicions arising from laboratory results. The therapy of choice for hepatolenticular degeneration was not feasible due to the patient's refusal. Zinc salts were, therefore, administered. To our knowledge the association of such rare genetic disorders has not been reported.

Factor V Deficiency↗