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R Testa

Publications and source records attributed to R Testa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of different 5-hydroxytryptamine receptor subtype antagonists on the micturition reflex in rats.

OBJECTIVE: To evaluate the effects of antagonists of different subfamilies of 5-hydroxytryptamine (5-HT) receptors on bladder function in anaesthetized and conscious rats. MATEERIALS AND METHODS: The urinary bladder of female anaesthetized rats was catheterized urethrally and filled with physiological saline until spontaneous bladder contractions occurred. Infravesical pressure was measured by a pressure transducer and displayed continuously on a chart recorder. The time of bladder quiescence (to the disappearance of rhythmic contractions) after injection with different compounds tested was recorded. Conscious rats underwent cystometry with chronically (infravesical) implanted catheters to continuously record bladder capacity (evaluated as amount of saline infused between voiding cycles) and maximal voiding pressure. The affinity for the human recombinant serotoninergic 5-HT1A subtype (inhibition of specific binding of [3H]8-hydroxy-2-(di-n-propylamino) tetralin) and the effects on the [35S]guanosine 5'-(gamma-thio) triphosphate (GTPgammaS) binding in HeLa cells was also evaluated. RESULTS: Among the compounds tested, only 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl-piperazine (p-MPPI) and methiothepin showed nanomolar affinity for the 5-HT1A receptors, the former being a neutral antagonist and the latter an inverse agonist in the [35S]GTPgammaS binding model. Intravenous injection of low doses of p-MPPI and methiothepin induced a dose-dependent disappearance of isovolumic bladder contractions in anaesthetized rats (> 10 min). At the highest doses, the dose-response curves were bell-shaped. The amplitude of bladder contractions was not markedly altered. The tested antagonists of 5-HT2, 5-HT3, 5-HT4, and 5-HT6 serotoninergic subtypes were poorly active or inactive in the model. Similarly, these compounds were inactive on cystometry in conscious rats, whereas p-MPPI and methiothepin induced a consistent increase in bladder capacity. Methiothepin also decreased the voiding pressure, whereas p-MPPI did not affect this variable. CONCLUSIONS: These findings confirm that only selective 5-HT1A receptor antagonists have favourable effects on the bladder, inducing an increase in bladder capacity with no derangement of bladder contractility.

Action Potentials↗
PubMed2001

Serum pro-collagen III peptide levels are related to lobular necrosis in untreated patients with chronic hepatitis C.

OBJECTIVE: Liver biopsy is mandatory for correctly grading and staging chronic hepatitis activity. Nevertheless, serum markers of fibrogenesis may be useful to help us understand the mechanisms of the fibrogenic process, to follow-up patients, and to establish the efficacy of therapy. In this study, our aim was to identify the relationships between pro-collagen III peptide (PIIIP) serum levels and detailed liver histology in a group of untreated patients with chronic hepatitis C (CHC). METHODS: We studied 147 CHC patients. Correlation analysis of PIIIP serum levels was performed in 109 patients, after having excluded those with alcohol abuse or concomitant hepatitis B virus infection. PIIIP serum levels were assessed using an assay that measures both Col 1-3 peptide (reflecting collagen synthesis) and Col 1 peptide (reflecting collagen degradation). Relationships of serum PIIIP with histology was carried out by evaluating grading and staging separately. Moreover, each component of the necro-inflammatory score was also taken into consideration. RESULTS: PIIIP levels were abnormal in 101 patients (93%). Moreover, PIIIP levels were no different between patients with (12.1 +/- 6.3 ng/ml) or without (13 +/- 5.8 ng/ml) fibrosis. In univariate analysis, no relationship was observed with fibrosis (rs = 0.033, not significant), while PIIIP levels were significantly correlated with lobular necrosis only (rs = 0.295, P = 0.0020). Multivariate analysis confirmed this latter finding (P = 0.0150). Among biochemical parameters, PIIIP showed relationships with aminotransferase (AST, rS = 0.294, P = 0.0022; ALT, rs = 0.236, P = 0.0142) and alkaline phosphatase (rs = 0.146, P = 0.0223). CONCLUSIONS: In patients with CHC, serum PIIIP levels reflect histological parameters strictly related to fibrogenesis. Therefore, PIIIP is a useful tool to evaluate ongoing fibrogenic activity of CHC. A complete histological score is needed in order to understand the relationships between biochemical markers of fibrogenesis and histology.

Adult↗
PubMed2001

Liver iron accumulation in chronic hepatitis C patients without HFE mutations: relationships with histological damage, viral load and genotype and alpha-glutathione S-transferase levels.

BACKGROUND: Host and viral factors have been suggested as possible causative factors for the presence of liver iron accumulation in chronic hepatitis C. However, there is no agreement regarding the influence of liver iron accumulation on the biochemical and histological severity of chronic hepatitis C. Moreover, data concerning the relationships between both viral load and genotype and liver iron accumulation are scanty. AIMS: To evaluate the biochemical, histological and virological assessment of a group of chronic hepatitis C patients without risk factors for iron overload, on the basis of the presence, degree and distribution of liver iron accumulation. METHODS: Fifty-three chronic hepatitis C patients (34 men, 19 women; age 44 +/- 11 years) with no risk factors for liver iron accumulation and showing no HFE mutations were chosen from a broader cohort of chronic hepatitis C patients. The presence, degree and distribution of liver iron accumulation were assessed using Deugnier's score. Relationships between the presence of liver iron accumulation and grading and staging were carried out separately. Hepatitis C virus RNA serum levels and viral genotype were compared in patients with or without liver iron accumulation. Alpha glutathione S-transferase serum levels were assessed in all patients. RESULTS: Overall, liver iron accumulation was mild and was present in 19 patients (36%). It was associated with male gender (P = 0.0358), and was reflected by high serum iron levels (P = 0.001) and high ferritin levels (P < 0.0001). Hepatitis C virus RNA levels and genotype were not associated with the presence of liver iron accumulation. In multivariate analysis, ferritin was the only variable significantly associated with liver iron accumulation (P < 0.0001). Grading was higher in patients with liver iron accumulation regardless of the site of iron deposition. Fibrosis was present in all patients with iron overload; these patients were more frequently cirrhotic. Moreover, patients with mesenchymal or mixed deposition had higher staging than patients with hepatocytic or no iron deposition. This feature was reflected by higher alpha-glutathione S-transferase levels. CONCLUSIONS: Liver iron accumulation is mild in chronic hepatitis C patients without HFE mutations and is mainly reflected by serum ferritin levels. Viral characteristics do not seem to play a role in iron deposition. Liver iron accumulation is associated with higher grading, advanced fibrosis and cirrhosis. Moreover, higher staging is associated with mesenchymal or mixed iron deposition. In these patients, higher alpha-glutathione S-transferase levels seem to reflect more complex damage.

Adult↗
PubMed2001

Vitamin E intake reduces plasminogen activator inhibitor type 1 in T2DM patients.

Previous studies hypothesised that vitamin E could protect against coronary heart disease and vascular complications in diabetes, but no studies have been performed regarding its eventual effects on fibrinolysis. Nevertheless, in Type 2 diabetes mellitus (T2DM) a profound reduction in the fibrinolytic activity has been demonstrated to be involved in vascular complications, probably due to plasminogen activator inhibitor type 1 (PAI-1) overproduction. On this basis we aimed to verify whether an antioxidant treatment with vitamin E is able to lower PAI-1 plasma levels in T2DM. Thirteen T2DM patients (9 males and 4 females; mean age+/-SD, 64.4+/-3.3 yr) were selected through strict admission criteria. These patients were treated with vitamin E (500 IU/die) for 10 weeks. Glyco-lipometabolic, oxidative and haemocoagulative parameters were evaluated at baseline and after 5, 10, 30 and 60 weeks. Vitamin E levels at different times were [median (interquartile range)] 6.1 (5.3-7.7), 8.5 (7.3-9.9), 9.7 (8.9-12.9), 5.6 (4.4-6.8), 5.7 (4.5-7.1) microg/ml, respectively. Significant differences were found for PAI-1 antigen (p=0.006), PAI-1 activity (p=0.028), apolipoprotein B (p=0.015) and antioxidant defence, evaluated as ferric reducing ability of plasma (FRAP) values (p=0.005). Particularly, decrements were detected for PAI-1 antigen between baseline and the 10th week (p<0.05), followed by an increase back to basal at the 30th week. Similar behaviour was found for PAI-1 activity. Regarding the antioxidant defence, FRAP values increased until the 30th week (p<0.05) with a decrease at the 60th week. These results demonstrate that vitamin E is able to lower PAI-1 levels in diabetic patients but this effect does not seem related to improvements of glycometabolic data or to the increase in FRAP values, suggesting that PAI-1 overproduction can be decreased by other effects of vitamin E on endothelial cells.

Aged↗
PubMed2001

Effects of the nuclear factor-kappaB inhibitors 2-hydroxy-4-trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and inflamed bladder.

PURPOSE: We examined the effects of intravenous administration of the 2 nuclear factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) on bladder filling and voiding in anesthetized and conscious rats. MATERIALS AND METHODS: Disappearance of isovolumic bladder contractions after intravenous administration of different doses of aspirin and HTB in anesthetized, transurethrally catheterized rats was evaluated. Cystometry was performed in conscious rats during bladder infusion with saline or diluted acetic acid as well as in those with cyclophosphamide induced cystitis. Changes in bladder capacity and voiding pressure were evaluated after intravenous administration of test compounds. RESULTS: Aspirin induced a dose dependent disappearance of isovolumic bladder contractions in anesthetized rats with an extrapolated dose of 2.1 mg./kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive, inducing a dose independent block of 3 to 4 minutes after intravenous administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60 minutes after intravenous administration of 30 and 100 mg./kg. In rats with a bladder infused with acetic acid aspirin was much more active when injected at the initiation of inflammation and after 1 hour of irritant infusion. In this latter situation aspirin increased bladder capacity up to 60% after intravenous administration of 30 and 100 mg./kg. Similar results were obtained in rats with cyclophosphamide induced cystitis in which the bladder was infused with saline. In these cystometrography models 30 mg./kg. HTB intravenously was completely inactive. CONCLUSIONS: The results show that HTB is devoid of significant effects on the micturition reflex in the absence or presence of bladder inflammation, suggesting that acute inhibition of nuclear factor-kappaB does not influence bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and nuclear factor-kappaB inhibitor, was always effective, indicating the important role of cyclooxygenase enzymes.

Animals↗
PubMed2001

N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide: a novel pre- and postsynaptic 5-hydroxytryptamine(1A) receptor antagonist active on the lower urinary tract.

N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-nitrophenyl) cyclohexanecarboxamide (Rec 15/3079) was synthesized with the aim of obtaining a novel compound with 5-hydroxytryptamine (5-HT)(1A) antagonistic properties and activity in controlling bladder function at the level of the central nervous system. Rec 15/3079 showed a selective high affinity for the 5-HT(1A) receptor (K(i) = 0.2 nM). At the human recombinant 5-HT(1A) receptor, Rec 15/3079 acted as a competitive, neutral antagonist in that it did not modify basal [(35)S]guanosine-5'-O-(3-thio)triphosphate binding to HeLa cell membranes but shifted the activation isotherm to 5-HT to the right, in a parallel manner, with a pK(b) value of 10.5. Accordingly, Rec 15/3079 (i.v.) potently antagonized 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT)-induced hypothermia in mice (ID(50) = 20 microg/kg) and 8-OH-DPAT-induced forepaw treading in rats (ID(50) = 36 microg/kg). In vitro Rec 15/3079 was poorly active in antagonizing carbachol-induced bladder (pD'(2) = 5.03) and norepinephrine-induced urethral (apparent pK(b) = 6) contractions. However, in anesthetized rats, Rec 15/3079 (10-100 microg/kg i.v.) blocked isovolumic bladder contractions with no effect on their amplitude. In conscious rats and guinea pigs with bladders filled with saline, Rec 15/3079 (300-1000 microg/kg i.v.) increased bladder volume capacity (BVC) without affecting bladder contractility. In conscious rats with bladders filled with dilute acetic acid, Rec 15/3079 (300 microg/kg i.v.) reversed the decrease of BVC induced by the acid. To evaluate apparent selective effect on lower urinary tract reflexes, Rec 15/3079 was tested in experimental models for sedative, analgesic, anxiolytic, and antidepressant activity. Rec 15/3079 showed only a slight decrease in the duration of immobility in the behavioral despair test (antidepressant activity) at 1 mg/kg i.v. No anxiolytic activity was observed at 10 mg/kg i.v. No effect was observed in the hot plate test, but Rec 15/3079 increased tail-flick latencies after 3 to 10 mg/kg i.v. In conclusion, these studies demonstrate that Rec 15/3079 is endowed with favorable effects on bladder function, and it is devoid of unwanted side effects at the level of central nervous system at doses at least 10-fold higher than those active on the bladder.

Analgesics↗
PubMed2000

Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction.

BACKGROUND: The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI. METHODS AND RESULTS: Fifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline (P<0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients (P=0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients (P=0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group and 36% in the saline group (P=0. 001). Function worsened in 2% of dysynergic segments in the adenosine group and in 20% in the saline group (P=0.0001). Adverse cardiac events occurred in 5 patients in the adenosine group and in 13 patients in the saline group (P=0.03). CONCLUSIONS: Intracoronary adenosine administration is feasible and well tolerated in AMI. Adenosine adjunct to primary PTCA ameliorates flow, prevents the no-reflow phenomenon, improves ventricular function, and is associated with a more favorable clinical course.

Adenosine↗
PubMed2000

Utility of alpha-glutathione S-transferase assessment in chronic hepatitis C patients with near normal alanine aminotransferase levels.

OBJECTIVES: To study whether determining alpha-glutathione S-transferase (alpha-GST) might improve the assessment of chronic hepatitis C (CHC) patients with near normal alanine aminotransferase levels (NNA). DESIGN AND METHODS: We studied 119 viraemic CHC patients. They were subdivided into two groups according to the pattern of alanine aminotransferase (ALT) alteration, i.e. consistently above (HA) or below (NNA) twice the upper normal value. In these patients we assessed alpha-GST and correlated its levels to clinical, histological, and virological findings, further evaluating whether alpha-GST might improve the assessment of CHC patients with NNA. RESULTS: alpha-GST showed a significant correlation with aminotransferases, though not with histological necroinflammatory activity and fibrosis or with hepatitis C virus RNA levels. Twenty-seven patients had NNA (23%), and within this subgroup of patients alpha-GST identified a subset of patients with a higher viral load. CONCLUSIONS: alpha-GST in CHC patients is related to hepatocellular necrosis parameters, but unrelated both to histology and to viraemia. However, in patients with NNA, alpha-GST identified a subgroup of patients with a higher viral load. In this subgroup of patients alpha-GST alteration likely represents the expression of a more severe damage. Because this injury is not detectable by the usual biochemical or histological work-up, we suggest that alpha-GST could a useful tool for monitoring liver damage over time.

Adult↗
PubMed2000

Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis.

BACKGROUND/AIM: Serum levels of leptin, the adipocyte-derived hormone regulating food intake and energy expenditure in mammals, have been found to be increased in cirrhotic patients. The aim of the present study was to investigate leptin serum level in relation to anthropometric features and liver function in patients with viral chronic hepatitis or liver cirrhosis. METHODS: Serum leptin levels were determined by radioimmunoassay in 30 male and 10 female patients with chronic hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four respective control groups. Liver function was evaluated by the monoethylglycinexylidide formation test. Body mass index and body fat mass were estimated by weight, height and skinfold thickness measurements. RESULTS: Compared with controls, absolute serum leptin levels were significantly (p<0.01) lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin serum levels were significantly (p<0.05) higher in cirrhotic than in chronic hepatitis patients. When expressed in relation to body fat mass, the above differences persisted; however, cirrhotic females showed significantly (p<0.05) higher serum leptin values than controls. Serum leptin values correlated negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of patients. CONCLUSIONS: In patients with chronic viral liver disease, serum leptin levels tend to increase as liver function worsens. This may reflect a decline in the ability to downregulate energy expenditure as an adaptation to anorexia and/or to defective substrate utilisation due to liver disease and may negatively influence body weight homeostasis in these patients.

Adipose Tissue↗
PubMed2000

Plasma glycohydrolase levels in patients with type 1 diabetes at onset and in subjects undergoing an intravenous glucose tolerance test.

The effect of hyperglycemia and insulin deficiency on the plasma level of lysosomal glycohydrolases, namely N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, and alpha-D-glucosidase, was investigated. Two patient groups were assessed: (1) 28 children with type 1 diabetes at onset (fasting blood glucose, 444+/-154 mg/100 mL; hemoglobin A1c, 11.9%+/-2.4%; symptom duration, 15.9+/-8 days; and absence of complications), (2) 14 adult subjects undergoing an intravenous glucose tolerance test (IVGTT), consisting of 8 non-obese subjects (body mass index, 26+/-0.04 kg/m2; fasting blood glucose, 82+/-13 mg/100 mL; blood insulin, 6+/-0.04 mU/L) and 6 obese subjects (fasting blood glucose, 97+/-3.5 mg/100 mL; blood insulin, 27+/-6 mU/L, with normal oral glucose tolerance test). Enzyme activity was determined with the fluorimetric method. The mean level of all evaluated enzymes was significantly increased in patients with type 1 diabetes at diagnosis compared with normal controls. Increased enzyme levels were also detected in the group of adults undergoing an IVGTT in whom hyperglycemia was accompanied by insulin resistance (ie, obese subjects). Glycohydrolase abnormalities appear to be related to insulin deficiency rather than hyperglycemia. Lysosomal apparatus abnormalities seem to be an inherent feature of diabetes that is present at disease onset. The possible role of insulin in the regulation of plasma glycohydrolase levels is discussed.

Adolescent↗
PubMed2000

The monoethylglycinexylidide test does not impair psychometric performance in patients with chronic hepatitis or cirrhosis.

Lidocaine (LID) is an aminoethylamide used in hepatology to perform the monoethylglycinexylidide (MEGX) test for the evaluation of liver function in patients with cirrhosis (CIR) or chronic hepatitis (CH). The authors evaluated whether the MEGX test changes psychometric performance in patients with chronic liver disease and, in particular, whether it might trigger subclinical portosystemic encephalopathy in patients with CIR. Thirty patients with CIR and 20 patients with CH were studied. They underwent a standard-dose MEGX test, before and after which a psychometric test was administered and blood pressure, heart rate, and adverse effects were recorded. The MEGX test did not modify psychometric performance. Mean arterial blood pressure and heart rate did not change at the end of the MEGX test in either patients with CH or CIR. Adverse effects were present in 66% of all patients during lidocaine injection and lasted up to 3 minutes afterwards. They were more frequent in patients with CH than in patients with CIR (85% vs 53%). No relationship was found between adverse effects and lidocaine dosage, nor between adverse effects and MEGX or lidocaine concentration at 15 minutes. Standard-dose MEGX test does not worsen or trigger portosystemic encephalopathy in CIR. Adverse effects were frequent but mild.

Adult↗
PubMed2000

Histologic determinants of monoethylglycinexylidide formation in patients with chronic hepatitis C.

Patients affected by chronic hepatitis C (CHC) display a peculiar histologic picture characterized by the presence of steatosis and bile duct damage in addition to evidence of inflammation, necrosis, and fibrosis. In the staging of these patients, functional evaluation may be considered a complementary tool. The monoethylglycinexylidide (MEGX) test has been used in diagnostic and prognostic assessment of chronic liver disease as a quantitative liver function test. In this study the authors evaluated whether different sampling times for the test could reflect different histologic patterns. The authors studied 82 patients with biopsy-proven CHC who underwent functional evaluation by means of MEGX test. The authors found that MEGX15 better reflected the histologic findings of necrosis and inflammation, and MEGX60 the presence of fibrosis. Neither steatosis nor bile duct damage showed a strong correlation with either sampling time. Moreover, MEGX levels showed a progressive decrease as histologic grading of chronic hepatitis progressively increased. Stepwise regression analysis identified necrosis and inflammation as histologic variables associated with both MEGX15 and MEGX30, and fibrosis as a variable associated with MEGX60. These results suggest that a decline in liver metabolic function corresponds to a progressive increase in liver damage, and that this circumstance should be taken into account when prescribing drugs to patients with CHC.

Adult↗