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Biomedical subjects

M Bernardi

Publications and source records attributed to M Bernardi.

At least 109 records · Page 6Linked to original sources

Chemiluminescent real time imaging of post-ischemic oxygen free radicals formation in livers isolated from young and old rats.

Oxygen free radicals generation is a major cause of liver injury during reperfusion. Luminescence analysis has been recently proposed to measure free radical generation by isolated cells or organs, but it allows only global tissue luminescence. Using a special Saticon videocamera with image intensifier we aimed to visualize and localize oxygen free radical generation in isolated perfused livers exposed to an oxydative stress. Livers isolated from rats aged 4 and 30 months were exposed to ischemia/reperfusion; photons emission by the organs was continuously recorded. Lucigenin was utilized as a chemiluminigenic probe to assess superoxide anion generation. In both groups, chemiluminescence was not detectable during ischemia, while it was observed after reperfusion. Photons emission started after few minutes of reperfusion, was maximal after 15-20 min and disappeared within 50-60 min. Chemiluminescence emitted by livers from younger rats however, was significantly higher when compared to chemiluminescence emitted by organs isolated from old rats (0.8 +/- 0.1 vs 0.44 +/- 0.08 photons x 10(5)/s, respectively, after 15 min; p < .01). The superimposition of chemiluminescent and live image permitted to determine the regional production rate and distribution of photons. In conclusion, the age of the rats influences significantly the amount of oxyradicals produced in the liver during post-ischemic reperfusion. The method described, allowing the visualization in real time of oxygen free radicals generation on the surface of isolated intact organs, represents a novel and potent tool for the study of oxidative stress.

Acridines↗

Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors.

Prolonged Q-T interval predicts severe arrhythmias and sudden death, and has been shown to occur in alcoholic liver disease and cirrhotic patients who are candidates for liver transplantation. This study first evaluated the prevalence of prolonged Q-T interval in a large population of unselected patients with cirrhosis, and assessed the relationship between abnormal Q-T, etiology, and severity of liver disease and mortality of patients. Possible causes of Q-T abnormality were also explored. Ninety-four patients with cirrhosis without overt heart disease and 37 control subjects with mild chronic active hepatitis were enrolled. Rate-corrected Q-T interval (Q-Tc) was assessed along with routine liver tests, Child-Pugh score, serum bile salts, electrolytes and creatinine, plasma renin activity, aldosterone, norepinephrine, atrial natriuretic factor and, gonadal hormones. Q-Tc was longer in patients with cirrhosis than in controls (440.3 +/- 3.2 vs. 393.6 +/- 3.7 ms; P < .001) and prolonged (> 440 ms) in 44 patients (46.8%) and 2 controls (5.4%; P < .001). Q-Tc length was not influenced by the etiology of cirrhosis and correlated with Child-Pugh score (r = .53; P < .001), liver tests such as prothrombin activity, and serum concentrations of albumin and bilirubin, plasma bile salts, and plasma norepinephrine. Multivariate analysis showed that only Child-Pugh score and plasma norepinephrine were independently correlated with Q-Tc duration. Over a median follow-up period of 19 months (range, 2-33 months), patients with Q-Tc longer than 440 ms had a significantly lower survival rate than those with normal Q-Tc. Q-T interval is frequently prolonged in patients with cirrhosis, regardless the etiology of the disease, worsens in parallel with the severity of the disease, and may have an important prognostic meaning. In addition to other undefined factors related to the severity of cirrhosis, sympathoadrenergic hyperactivity may play a pathogenetic role.

Electrocardiography↗

Mono-oligoclonal immunoglobulin abnormalities in diabetic patients after kidney transplantation: influence of simultaneous pancreas graft.

Monoclonal components (MC) are detected in as high as 30% of renal transplant recipients. Our aim was to evaluate the incidence, relevance and consequence of monoclonal components in patients with Type I (insulin-dependent) diabetes who received kidney (n = 22), kidney and whole pancreas (n = 41), kidney and segmental pancreas (n = 24) and kidney and islets (n = 12) transplants. Immuno-suppression was based on prophylactic anti-lymphocyte globulins, corticosteroids, azathioprine and cyclosporin in all patients; acute rejection was treated with steroids or anti-lymphocyte monoclonal immunoglobulin therapy (OKT3) or both. Serum immunofixation was carried out in all patients before transplantation and then after at 6 months and then yearly. Monoclonal components were detected in 81 of 99 patients (82%); 52 patients (52%) developed them within 6 months of transplantation, 15 (15%) between 6 and 12 months, with a peak prevalence at 1 year post-transplant (58%) and a decrease thereafter (10% at 9 years). Kidney recipients showed a lower incidence of monoclonal components when compared with those who received kidneys and segmental pancreases and those who received kidneys and whole pancreases. Monoclonal components were more often detected in patients who had previously experienced an acute renal rejection. Cytomegalovirus infection and acute rejection occurring in the same patient further increased the risk of developing monoclonal components, the development of which did not correlate with OKT3 treatment. A Post-transplant lymphoproliferative disorder was developed by two patients (2%), one with 5 and the other with 6 monoclonal components. In conclusion, diabetic patients receiving kidney and/or Pancreas transplantation, experiencing both cytomegalovirus infection and acute rejection, are at greatest risk of developing monoclonal components but they appear to be benign and transient; multiple band detection is a marker for the subsequent development of post-transplant lymphoproliferative disorder.

Adult↗

Determinants of maximal instantaneous muscle power in women aged 50-75 years.

The present study aimed at analysing the age-related decline in maximal muscle power (W) in 52 sedentary healthy women aged between 50 and 75 years to determine whether force or velocity is the major determinant. Maximal muscle power was estimated from two types of vertical jumps, squatting (SJ) and countermovement (CmJ), performed on a force platform. It was obtained by measuring the vertical force (F(opt)) applied to the body centre of gravity and calculating the corresponding vertical velocity (v(opt)). An age-related decline in absolute W was statistically significant in all the conditions examined and in both peak W and average power (W) values. The decrease in v(opt) was also statistically significant. Also F(opt) declined but this reduction was not statistically significant with the exception of the average value in CmJ. Not surprisingly the highest W were obtained in CmJ, and the difference in power production between the two types of jump showed an age-related decrement only in W. The main finding of the study was the demonstration that v(opt) was the critical determinant of the age-related decline in W in healthy elderly women.

Aged↗

Lamivudine treatment for acute hepatitis B after liver transplantation.

BACKGROUND/AIMS: Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. METHOD: Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. RESULTS: Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. CONCLUSIONS: These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.

Acute Disease↗

Effect of ischemia--reperfusion on heat shock protein 70 and 90 gene expression in rat liver: relation to nutritional status.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

Adenosine Triphosphate↗

Spectral analysis of intercycle heart fluctuations in the diethyl-ether-anaesthetized or pithed rat treated with prazosin, dl-propranolol, endothelin-1, alpha-r atriopeptin and ACE-inhibitors.

1. Frequency-domain spectral analysis of stationary ECG R-R intervals was made by fast Fourier transformation (FFT) in conditions of monitored arterial blood pressure and respiratory activity in diethyl-ether-anaesthetized and pithed adult rats. This technique yields a number of parameters which allow quantitative evaluation of the non-random distribution of the mean values obtained in time-domain studies. The frequency-analysis method enables the overall heart rate variability to be broken down into its various constituents, which are differently affected by physiological loading and capable of selective reactivity to pharmacological agents. 2. The low-frequency spectral component obtained by breaking down the total spectral density power, i.e. the appropriate variability signal (band width < 0.15 Hz) and a higher-frequency band corresponding to spontaneous (0.80-1.60 Hz) or artificially imposed (0.75 Hz) respiratory activity were estimated and their integrated areas evaluated as absolute powers or normalized fractional values. 3. The power of the high-frequency spectral component increased in all animal preparations under treatment with prazosin, dl-propranolol, endothelin-1 and the angiotensin converting enzyme (ACE) inhibitors captopril, lisinopril, quinapril and ramipril. The power of the low-frequency band increased under alpha-r atriopeptin and ACE inhibitors in the pithed preparations only, and decreased in the anaesthetized animals. 4. The new power spectrum features and trends detected indicate that these time-independent, model-dependent cardiovascular and respiratory markers are subject to some form of complex peptidergic control. 5. The relative roles of the various factors operating in the genesis of these short-term changes in spectral power in the low- and high-frequency bands cannot be interpreted as indicating a reciprocal push-pull relationship between sympathetic and parasympathetic control. 6. The study findings, however, can be interpreted as providing evidence of a different and to some extent alternative form of integrative cardiovascular control persisting in the pithed rats (i.e. in the 'peripheral', CNS-destroyed preparations). 7. New areas of theoretical and applied research are being developed in the (auto)classification of (iso)receptors and drug analogues through exploration of multiple physiological and pharmacokinetic parameters in the frequency-domain. Furthermore, model-independent frequency-domain methods not requiring stationary data will afford scope for even more significant developments by separating the overlapping dynamic processes from a whole series of correlated effects.

Animals↗

Ageing affects anoxia/reoxygenation injury in rat hepatocytes.

BACKGROUND: The reoxygenation phase after a period of anoxia leads to oxyradical formation, responsible for damage to cell membranes. Ageing is associated with functional and structural changes in liver cells, which modify their sensitivity to reoxygenation injury. The aim of this study was to determine the effects of ageing on the sensitivity of hepatocytes to anoxia/reoxygenation. METHODS: Oxyradical formation and cell injury were evaluated in hepatocytes isolated from rats of different ages exposed to 2 h of anoxia and 1 h of reoxygenation. Anion superoxide was measured by lucigenin-enhanced chemiluminescence, hydrogen peroxide by luminol-enhanced chemiluminescence, and cell damage by lactate dehydrogenase (LDH) release. RESULTS: During anoxia, oxyradical production dropped to background levels in both groups. LDH release was significantly greater in ageing hepatocytes. During reoxygenation, a massive generation of anion superoxide and hydrogen peroxide, followed by a sharp increase in LDH release, was observed in both groups. However, both oxyradicals and cell injury were significantly greater in liver cells obtained from ageing rats. CONCLUSIONS: The data confirm that hepatocytes produce high levels of free radicals during post-ischemic reoxygenation and suggest that ageing cells are more sensitive to reperfusion injury.

Aging↗

[Actinomycosis of the tongue. Report of two cases and review of the literature].

Actinomycosis of the tongue is a rare form of infection whose initial clinical manifestation is a submucosal swelling that may mimic both benign and malignant neoplasias. Two cases are, presented and their clinical features and diagnostic criteria are discussed in the light of twelve cases drawn from the literature. Infection in the tongue is rare, though perhaps underestimated. It is generally located on the anterior two thirds laterally to the median sulcus, and presents as a moderately painful nodule set deep in the extrinsic and intrinsic muscles and poorly mobile on the adjacent planes. In a few weeks the lesion increases in size and painfulness with consequent loss of function in the absence of diagnosis and appropriate antibiotic management. Both our patients, in fact, presented with deep lesions and no apparent involvement of the mucosa, and were investigated by means of fine-needle aspiration biopsy (FNAB). The aspirated material was used to prepare both routine smears and cell blocks embedded in paraffin. The pathological material provided by this combination of methods proved quantitatively and qualitatively sufficient for the definitive diagnosis of actinomycosis in both cases.

Actinomycosis↗

Investigation into the use of alcohol at thermal spas: can a spa represent a place for primary prevention?

Primary prevention is one of the most effective means used nowadays to make the general population aware of most of the problems connected with health, but information campaigns have not yet shown results of alcohol-related problems at thermal spas. The aim of this study was to assess the mean daily alcohol intake (grams/day) in a thermal spa population. The sample was conducted over a 6 month period and consisted of 290 subjects. The mean age was 59.01 years (range 23-89, SD +/-14.20) (150 males and 140 females). All of the subjects underwent a medical examination free of charge and an alcohol case history report. The medical staff working at the spa included two doctors, a biologist, a cardiologist, and a dietician. In the final 176 subjects studied, the mean daily alcohol intake was 32.33 g/day, significantly higher in the males than the females (p < 0.001). The 176 subjects were subsequently divided into three subgroups according to their daily alcohol intake: group A, <40 g/day; group B, 40 to 79 g/day; group C, > or =80 g/day. The number of subjects in group A was significantly greater than in group B and group C (p < 0.001). It is important to emphasize that 33.5% of the subjects studied presented a mean daily alcohol intake of > or =40 g/day and therefore were more exposed to the risk of the onset of alcohol-related problems. In view of these results, thermal spas should thus be considered an additional place in which to identify subjects at risk for problematic use of alcohol and represent an environment in which primary prevention campaigns could be started.

Adult↗

[Emergency coronary surgery after failed angioplasty: 11 years of experience (1987-1997)].

METHODS: From January 1987 to December 1997, thirty patients underwent emergent or urgent coronary artery bypass grafting after failed elective percutaneous transluminal coronary angioplasty. Dissection/occlusion of the target artery was the commonest complication, but we also had two cases of stent dislocation and one case of coronary artery wall perforation. Two-thirds of the patients experienced extreme preoperatory hemodynamic instability (i.e., cardiac arrest or cardiogenic shock) and half had to be intubated in the Catheterization Laboratory. An average of 1.73 grafts/patient was performed. Complete coronary revascularization was achieved in 93% of the cases; the internal mammary artery could be employed in one-third only. RESULTS: In-hospital mortality was 10%, and perioperatory myocardial infarction or persistent ischemia could be detected in half of the patients. The need for aortic counterpulsation, and the use of inotropic and antiarrhythmic drugs were higher than average in this group of patients; while intensive care unit and hospital stay were longer. Patients with deteriorated preoperative hemodynamics fared significantly worse. Late results were encouraging: seventy-five per cent of all patients (and 84% of hospital survivors) were still alive an average of 52 months after surgery. Two-thirds of all patients (and 72% of hospital survivors) were alive and angina-free. CONCLUSIONS: Even in the current era, revascularization surgery after failed coronary angioplasty still carries an increased risk for postoperative complications and death, especially for patients with deteriorated preoperative hemodynamic conditions. On the other hand, postoperative middle- and long-term results are encouraging, as hospital survivors were similar to elective bypass patients regarding survival and freedom from return of angina.

Adult↗

Rat hepatocytes isolated from alcohol-induced fatty liver have an increased sensitivity to anoxic injury.

The aim of this study was to determine whether rat hepatocytes isolated from steatotic or nonsteatotic livers have different thresholds for injury due to anoxia-reoxygenation. Rats were fed ethanol or control diets for 8 weeks. Histology showed that more than 75% of the hepatocytes in alcohol-fed and less than 3% in control animals contained fatty vacuoles. The glycogen content was significantly reduced in steatotic livers. Isolated hepatocytes were cast in agarose gel threads and perfused with Krebs-Henseleit bicarbonate buffer. Cell viability was determined by Trypan Blue (TB) exclusion; cell injury was determined by lactate dehydrogenase (LDH) release; and superoxide anion (O2.-) was determined by lucigenin-enhanced chemiluminescence (LCL). During the pre-anoxic basal perfusion the following occurred: viability was 86% +/- 1% and 85% +/- 1%; LDH release was 16 +/- 3 and 15 +/- 3 mU/min; and LCL was 4 +/- 1 and 5 +/- 1 nA in steatotic and nonsteatotic hepatocytes, respectively. Cell viability decreased slightly under 4 hours of aerobic perfusion without differences between the two groups. In contrast, fatty hepatocytes died much faster than did control hepatocytes during anoxia; after 3 hours viability was 17% +/- 8% vs. 60% +/- 2% (P < .001), respectively. With reoxygenation following 2 hours of anoxia, the changes in viability, in LDH release, and in LCL were similar in both groups. These results indicate that in hepatocytes isolated from alcohol-fed rats when compared with control hepatocytes: 1) cell viability under aerobic conditions is not influenced; 2) anoxic injury is significantly increased; 3) a reduction in the hepatic glycogen stores, which may contribute to the enhanced sensitivity to anoxia, can be demonstrated; and 4) O2.- generation and cell injury occurring immediately after reoxygenation do not appear to be affected.

Animals↗

(ECTO) nucleotidase kinetics observed by 31P-NMR spectroscopy: resolution of signals.

We used 31P-NMR to study the action of the drug ouabain, a digitalis glycoside, on the ecto-nucleotidase catalysed reaction pathway: [formula: see text] Even under conditions where it was impossible to resolve all resonances from the individual species, the rate constants for the individual steps may be evaluated by a chi 2 fit of equations describing the global kinetics to the NMR data. The fitted values of the reaction rate constants show no inhibition of any step in the reaction pathway, confirming previous results. This improved kinetic method can be used to evaluate the effect of different substrates, ions and drugs, both in intact or pathologically altered organs and in tissue subcellular fractions.

Adenosine Triphosphatases↗

Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.

BACKGROUND/AIMS: Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis. METHODS: Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period. RESULTS: Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups. CONCLUSIONS: Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.

Adult↗