[Changes caused by uridine amphetamine induced hyperthermia in mice and rats].
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Amphetamine↗
Biomedical subjects
R Testa
Publications and source records attributed to R Testa.
Physiology of growth and sporulation in Bacillus cereus. I. Effect of glutamic and other amino acids.
Buono, F. (Syracuse University, Syracuse, N.Y.), R. Testa, and D. G. Lundgren. Physiology of growth and sporulation in Bacillus cereus. I. Effect of glutamic and other amino acids. J. Bacteriol. 91:2291-2299. 1966.-Growth and sporulation were studied in Bacillus cereus by use of an active culture technique and a synthetic medium. A high level of glutamic acid (70 mm) was required for optimal growth and glucose oxidation followed by sporulation even though relatively little glutamic acid was consumed (14 mm). Optimal growth occurred with a combination of 14 mm glutamic acid and 56 mm (NH(4))(2)SO(4), aspartic acid, or alanine. Ornithine or arginine at 70 mm could replace glutamic acid in the synthetic medium without affecting the normal growth cycle. Glutamic acid was not replaced by any other amino acid, by (NH(4))(2)SO(4), or by a combination of either alpha-ketoglutarate or pyruvate plus (NH(4))(2)SO(4). Enzyme assays of cell-free extracts prepared from cells harvested at different times were used to study the metabolism of glutamic acid. Glutamic-oxaloacetic and glutamic-pyruvate transaminases were completely activated (or derepressed) during early stages of sporulation (period of 6 to 8 hr). Alanine dehydrogenase responded in a similar manner, but the levels of this enzyme were much higher throughout the culture cycle. Neither glutamic dehydrogenase nor alpha-ketoglutarate dehydrogenase was detected. Sporulation in a replacement salts medium was studied with cells harvested at different times from the synthetic medium. Cultures 2 to 6 hr old were unable to sporulate in the replacement salts medium unless glutamic acid (7.0 mm) was present. By the 6th hr, cells were in the early stages of sporulation, showing spore septa development. Cultures 8 hr old sporulated in the replacement salts medium. Other metabolic intermediates able to replace glutamic acid in the replacement salts medium were alanine, aspartic acid, and glutamine at equimolar concentrations. Also, ammonium ions in combination with pyruvic, oxaloacetic, alpha-ketoglutaric, or fumaric acid replaced glutamic acid. The likely role of these metabolites is discussed.
Alanine↗
Effects of drugs used in the therapy of detrusor hyperactivity on the volume-induced contractions of the rat urinary bladder.
In this study we examined the effects of the drugs most commonly utilized in the therapy of overactive detrusor, on the volume-induced contractions of rat urinary bladder. Anticholinergics such as propantheline bromide and emepronium bromide, as well as oxybutynin decreased the amplitude of the voiding contractions after intravenous (i.v.) administration in a dose-dependent way. These anticholinergics, on the other hand, generally increased the frequency of the contractions. Nifedipine dose-dependently reduced the amplitude of the contractions. Flavoxate induced a dose-related decrease in the frequency without effects on the amplitude of the peaks. Its main metabolite 3-methylflavone-8-carboxylic acid (MFCA) was inactive after i.v. administration. Terodiline was active on the amplitude and apparently on the frequency of the voiding contractions. The alpha-adrenoceptor antagonist prazosin, as well as indomethacin, inhibited only the frequency of the voiding contractions. All the drugs active in reducing the frequency of the voiding contractions after i.v. administration, proved effective also after intracerebroventricular (i.c.v.) injection. The model of the volume-induced contractions of rat urinary bladder, seems to be a useful tool to evaluate in vivo the effects of a compound on the bladder, allowing the possibility of distinguishing among antimuscarinics and calcium antagonists, which peripherally decrease bladder contractility, and other drugs inducing a decrease in the frequency of the voiding reflex acting on the micturition centre(s) in the central nervous system (CNS).
Animals↗
Usefulness and safety of pirenzepine in double-contrast study of upper gastrointestinal tract: comparison with scopolamine methylbromide.
To evaluate usefulness of pirenzepine, a selective M1 antimuscarinic drug, for diagnostic double-contrast study of the upper gastrointestinal tract, pirenzepine and scopolamine methylbromide (SMB) were compared in a single blind randomized trial. Seventy consecutive patients were enrolled in the study. Artifacts, bowel distention, painting of stomach and duodenal bulb, and global quality of the images were blindly evaluated by four independent observers by means of a numerical score (1-4). Under SMB slightly but significantly better results for stomach were scored (3.1 +/- .7 vs. 2.7 +/- 7, p < 0.01). No differences were found in the study of the duodenal bulb. Heart rate and rhythm during the study were recorded by electrocardiogram (ECG). SMB induced tachycardia in all patients (from 77 +/- 20 to 117 +/- 28 beats/min, p < 0.01) while pirenzepine did not (from 77 +/- 16 to 81 +/- 23, p = NS). After SMB, two patients exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Thus, pirenzepine provides good results in double-contrast studies (equal to SMB), while presenting no adverse effects. It could be proposed as a first choice hypotonic agent in upper gastrointestinal examination.
Adult↗
Pirenzepine versus scopolamine methyl bromide in double-contrast barium enema study of large bowel.
To evaluate the usefulness of pirenzepine for diagnostic double-contrast barium enema study of the large bowel, pirenzepine and scopolamine methyl bromide (SMB) were compared in a single, blind, randomized trial. Sixty consecutive patients were enrolled in the study. Quantitative analysis of bowel distention was done by measuring the maximum diameter of the transverse colon before and after drug administration. Four independent observers blindly evaluated distention and mucosal coating of the large bowel and global quality of the images. No differences were found in the diagnostic performance between the two drugs. However, pirenzepine induced a slight but significantly larger distention of the large bowel (68 +/- 12 vs. 65 +/- 8 mm, p = 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients (from 72 +/- 15 to 98 +/- 24 beats/min, p < 0.01), whereas pirenzepine did not (from 76 +/- 13 to 78 +/- 20, p = NS). After SMB, one-patient exhibited faintness, and some patients complained of visual accommodation defects, dryness of the mouth, and dizziness. Pirenzepine had a diagnostic performance similar to SMB in avoiding adverse effects elicited by SMB.
Adult↗
Effects of some antidepressants on the volume-induced reflex contractions of the rat urinary bladder: lack of correlation with muscarinic receptors affinity.
It has been suggested that tricyclic antidepressants such as imipramine, might exert their anti-enuretic action by a blockade of muscarinic receptors in the detrusor muscle of the urinary bladder. We have therefore investigated the effects of two tricyclic (imipramine and nortriptyline) and three atypical (citalopram, amineptine and mianserin) antidepressants on the micturition reflex and muscarinic receptors in rats. The micturition reflex pathway was monitored indirectly by recording the rhythmic intravesical pressure waves which occurred when the bladder was distended and maintained under constant saline-volume. The activity of the antidepressants was correlated to their potencies as antagonists of [3H]QNB binding to rat brain (mainly M1 receptors) and bladder (mainly M2 receptors) membranes, as well as antagonists of carbachol-induced contractions of rat bladder strips. Only imipramine and citalopram dose dependently inhibited the voiding contractions, whereas nortriptyline, imipramine and mianserin (in order of potency) were active both in binding studies and as competitive antagonists of carbachol-induced bladder contractions, but were inactive in inhibiting the micturition reflex. The present data seem to suggest that affinities for muscarinic receptors are unrelated to the inhibition of micturition reflex.
Animals↗
Influence of pump compliance (peristaltic vs. infusion) on urodynamic measurement during cystometry in conscious rats.
Cystometry, employing natural or pump-induced bladder filling, is the most widely used method for studying bladder reflexes and micturition in conscious rats. However, discrepancies in basal values of urodynamic parameters are often reported, especially for micturition pressure. The aim of this study was to establish whether the type of pump used (peristaltic or infusion) might yield different urodynamic parameters. Differences between natural filling (evaluated in water-loaded animals and considered "physiological micturition") and pump-evoked cystometrograms, as well as the compliance of these systems, and the effects of pharmacologically diverse drugs (prazosin, oxybutynin, and naproxen) acting on the bladder voiding were evaluated. Micturition pressure recorded from pump-evoked cystometrograms showed differences from natural micturition that were related to the total compliance of the system (pump + tube) and not only to the nature of the pump used. Drug-induced changes of micturition pressure during natural micturition resembled those recorded during bladder infusion with a peristaltic pump more than those with an infusion pump. Other basal values and drug-induced changes of bladder capacity were the same during natural and pump-evoked micturition. The present findings indicate that cystometrographic parameters obtained during pump-evoked micturition with a system at high compliance (peristaltic pump) are equivalent to those observed during physiological micturition.
Animals↗
Correlation between extent of myocardial dysfunction and markers of irreversible damage in failing hearts.
BACKGROUND: The structural correlates of 201Tl uptake in patients with advanced postischemic pump dysfunction are unclear. There are no good experimental models adequately reflecting the mixture of normal, dysfunctional but viable, and necrotic regions characteristic of chronic ischemic heart disease in human beings. METHODS AND RESULTS: Four heart transplant candidates with idiopathic dilated cardiomyopathy and seven with ischemic heart disease underwent rest-injection 4-hour redistribution 201Tl single-photon emission computed tomography before surgery. Delayed tracer uptake was categorized into severely reduced (<50%), mildly or moderately reduced (50% to 74%), and normal (> or =75%) and related to echocardiographic wall motion and histologic findings in the hearts excised at transplantation. In idiopathic dilated cardiomyopathy, despite severe wall motion impairment, minimal or mild myocardial damage and homogeneously high 201Tl uptake were found. In ischemic heart disease, wall motion did not discriminate extensive from mild structural damage. 201Tl activity was inversely related to myocardial fibrosis (r = -0.50, p = 0.0001). Severe defects in 201Tl uptake (<50%) predicted extensive (>30%) fibrosis with 83% sensitivity and 63% specificity. Segmental akinesis and apical location resulted in loss of sensitivity (74% and 58%, respectively). No histologic or wall motion abnormality accounted for poor specificity. In the individual patient, more than nine segments determined viable by imaging criteria predicted left ventricular fibrosis of less than 15% with 86% accuracy. CONCLUSIONS: This histopathologic-clinical correlative study supports current evidence of good sensitivity but limited specificity of 201Tl rest-redistribution tomographic imaging in the evaluation of viable myocardium. In the individual patient, more than nine viable segments reliably predicted a limited extension of fibrosis.
Adult↗
Age-dependent changes of serum oxygen radical scavenger capacity and haemoglobin glycosylation in non-insulin-dependent diabetic patients.
BACKGROUND: Contradictory results have been reported in the literature concerning the correlation between glycosylated haemoglobin (HbA1c) and peroxidation level in serum of diabetic patients. OBJECTIVE: To evaluate this correlation in type 2 diabetic patients by comparing the level of HbA1c with the oxygen radical absorbance capacity (ORAC(OH)) of serum. METHODS: One hundred and five type 2 diabetic patients were enrolled for the study. After having obtained informed consent, venous blood samples were drawn after overnight fast at the time of routine diabetic check-ups. The blood was collected in plain and EDTA (1 mg/ml) tubes. Glycosylated haemoglobin (HbA1c) was determined by cation-exchange chromatography (HPLC), and spectrophotometric detection (Diamat Analyzer, BioRad). Serum was used for biochemical determinations performed by standard laboratory procedures and for ORAC(OH) analysis. This last parameter was determined measuring the loss of beta-phycoerytrin fluorescence due to oxidation by hydroxyl radicals generated by Cu(2+) and H(2)O(2), in the presence and absence of serum. Seventy-eight control age-matched subjects were obtained from the personnel staff of our Research Department and old healthy subjects, selected on the basis of Senieur Protocol, were relatives of the above mentioned personnel. RESULTS: When the population of diabetic patients was taken as a whole, a decrease of ORAC(OH) has been observed compared to the controls. Moreover, negative correlations were found comparing ORAC(OH) either with HbA1c (r = -0.213; p = 0.029) and with the age of patients (r = -0.27; p = 0.005). To better understand the effect of age, the data were re-examined dividing the diabetics into two populations, i.e. under and over 65 years of age. An age-dependent decrease of ORAC(OH) and an increase in HbA1c levels has been observed comparing these two populations; however, the correlation between the two parameters remained statistically significant only in the oldest group (r = -0.31; p = 0.026). CONCLUSIONS: Present data point to an involvement of oxidative stress in the glycation of haemoglobin especially in old diabetic patients, and provide support for the potential use of an antioxidant therapy in these patients, irrespective of their glycaemic control.
Adult↗
Modifications in the serum concentrations of prolyl hydroxylase in patients with chronic hepatitis B during and after interferon therapy.
A total of eight patients with chronic active HBsAg-positive hepatitis was treated with recombinant interferon-alpha 2b for 12 months and serum aspartate aminotransferase, alanine aminotransferase, gamma-globulin and prolyl hydroxylase concentrations were determined every 3 months. Liver biopsies after 12 months' treatment revealed a significant (P less than 0.05) reduction in the histological activity score. After 6 months, alanine aminotransferase (P less than 0.01) and aspartate aminotransferase (P less than 0.05) concentrations fell significantly compared with baseline concentrations. Serum prolyl hydroxylase concentrations declined significantly (P less than 0.05) after 15 months and remained depressed. It is concluded that interferon-alpha 2b therapy reduced fibrogenetic activity in chronic active hepatitis B.
Adult↗
Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis.
BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test. RESULTS: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels. CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.
Adult↗
Probability of non-response during interferon therapy in patients with chronic hepatitis C.
BACKGROUND/AIMS: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters. METHODOLOGY: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders. RESULTS: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%. CONCLUSIONS: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.
Adult↗
Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C.
BACKGROUND/AIMS: Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. METHODOLOGY: We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. RESULTS: We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). CONCLUSIONS: The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.
Adult↗
13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis.
BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.
Adult↗
Tauroursodeoxycholic acid administration as adjuvant therapy in cirrhotic patients on transplantation waiting lists.
BACKGROUND/AIMS: The lack of organ availability and an increased number of end-stage cirrhotic patients has led to the lengthening of liver transplantation waiting lists. The progressive worsening of clinical and functional performance in patients awaiting the graft is one of the factors implicated in the increased mortality during the wait and in poor transplantation outcome. In this work our aim was to evaluate the effects of tauroursodeoxycholic acid administration on biochemical, clinical and functional parameters in a group of cirrhotic patients consecutively placed onto our liver transplantation waiting list. METHODOLOGY: Ten cirrhotic patients underwent biochemical, clinical and functional evaluation at the time of entering on our liver transplantation waiting list, then tauroursodeoxycholic acid was administered until liver transplantation. Complete evaluation was repeated every 2 months. The results were compared to those of a comparable historical control group that had undergone liver transplantation the year before the study. RESULTS: All patients were transplanted within 6 months from insertion on the waiting list. Longitudinal analysis of the treated group showed that cholestasis and cytolisis parameters constantly decreased and that gamma-glutamyl transpeptidase was significantly lower compared to baseline values at the 4th month of therapy. Clinical and functional parameters remained stable during follow-up. Comparison with the control group showed that gamma-glutamyl transpeptidase, alkaline phosphatase and both aminotransferases were reduced at the 4th month of therapy. Fewer days of hospital stay and less intensive care were required in the treated group. CONCLUSIONS: Treatment of end-stage cirrhotic patients awaiting liver transplantation with tauroursodeoxycholic acid improves biochemical parameters of cytolisis and cholestasis, and furthermore helps to maintain clinical and functional stability during the wait. Improved biochemical conditions and steady clinical-functional performance may promote better short-term transplant outcome.
Case-Control Studies↗
Does surveillance for hepatocellular carcinoma in HCV cirrhotic patients improve treatment outcome mainly due to better clinical status at diagnosis?
BACKGROUND/AIMS: Cirrhotic patients with hepatitis C virus infection are a group at higher risk for hepatocellular carcinoma. Conventional screening programs detect only few early hepatocellular carcinomas that are eligible for radical treatment. Our aim was to compare characteristics of patients, modality of treatment, and outcome in anti-HCV positive cirrhotics with hepatocellular carcinoma diagnosed during follow-up, or incidentally. METHODOLOGY: Sixty-one hepatocellular carcinomas were consecutively diagnosed in cirrhotic anti-HCV patients from 1993-1998 among which 34 during biannual ultrasonographic-biochemical follow-up and the others incidentally. Child-Pugh's score, alpha-fetoprotein levels, uni- or multifocality of the tumor, and treatment and survival of the patients were then analyzed on the basis of modality of diagnosis. RESULTS: Surgical treatment was feasible only in a minority of patients. Radical and palliative treatment was more frequent among patients with HCC diagnosed during follow-up. Child-Pugh's score was lower in these patients, moreover their survival rate was better. Analysis of survival of patients treated with the same procedure and grouped by modality of diagnosis did not demonstrate any differences. Regression analysis showed that patients with a lower Child-Pugh's score, one nodule, with a tumor diagnosed during follow-up and who were treated had a better survival rate. CONCLUSIONS: In our population surveillance did not detect a higher percentage of curable HCC. Nevertheless the results of palliative treatment and of curative treatment overlapped. Overall better outcome was observed in patients with preserved liver function whatever the treatment. Surveillance allowed us to diagnose HCC in patients with these characteristics thus leading to an improved survival rate.
Aged↗
[Patient rights in clinical experimentation and medical practice].
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Clinical Trials as Topic↗
The heart transplant as a clinical model to assess viable myocardium by radioactive tracers.
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Coronary Circulation↗