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Biomedical subjects

M Bernardi

Publications and source records attributed to M Bernardi.

At least 235 records · Page 13Linked to original sources

Shaking behaviour induced by putrescine in naive rats: a pharmacological and histological study.

In untreated rats, the intraperitoneal injection of putrescine evoked a typical wet-dog shake response, that was maximal at a dose of 300 mg/kg and at room temperature (22 degrees) (number of shakes: 84.00 +/- 17.90/hr). In a hot environment (30 degrees) the number of shakes was markedly reduced (26.90 +/- 5.19/hr). The putrescine-induced shaking behaviour was unaffected by atropine, bicuculline, chlorpheniramine, cimetidine, methysergide, naloxone and noradrenaline, but was markedly antagonized by morphine. Naloxone pretreatment nullified the antagonistic activity of morphine. Histological studies showed marked alterations in brain vascular permeability, which was increased by putrescine. Morphine completely prevented this putrescine-induced vascular effect. These results suggest a correlation between WDS produced by putrescine and increase in brain vascular permeability. Furthermore they show that morphine can affect brain vascular permeability.

Animals↗

A psychosomatic outpatient clinic.

Current emphasis in clinical psychosomatic medicine is on psychiatric interventions in acute medical and surgical situations (consultation-liaison psychiatry and medical-psychiatric units). Little interest has been taken in psychosomatic interventions in chronic situations and outpatient settings. The functioning of a psychosomatic outpatient clinic (POC) is described. One-hundred consecutive referrals were analyzed. The most frequent diagnostic finding--according to DSM III criteria--was subsumed under the rubric of "psychological factors affecting physical condition," followed by affective illness, anxiety disturbances, and somatoform disorders. The results indicate that a POC may serve a specific and definable segment of patients, whose characteristics depart from the clinical populations in consultation-liaison psychiatry and medical-psychiatric units.

Adult↗

Putrescine has hypothermic and antipyretic activity, in rats.

Intraperitoneal injection of putrescine induced dose-related hypothermia in rats. The effect was more pronounced at room temperature (22 degrees C) than in a warm environment (30 degrees C), the maximum hypothermia (-2.64 +/- 0.29 degrees C, 30 min. after treatment) being obtained with the dose of 300 mg/Kg and remaining significant throughout 3 hr of observation. Putrescine also had antipyretic activity, as it significantly reduced pyrogen-induced fever at a dose level (100 mg/Kg i.p.) ineffective in causing hypothermia in normal rats. The hypothermic and antipyretic effects of putrescine were not associated with any obvious sign of toxicity.

Animals↗

Chronobiological study of factors affecting plasma aldosterone concentration in cirrhosis.

We studied the mechanisms leading to derangement of aldosterone secretion in cirrhosis. The circadian patterns of plasma renin activity (PRA), aldosterone, cortisol, sodium, and potassium were studied in 16 nonazotemic cirrhotics (group 1 without ascites, 7 cases; group 2 with ascites, 9 cases) and 7 healthy controls. Group 1 did not differ from controls in aldosterone, sodium, and potassium mean daily levels (mesors), but had reduced PRA mesor (p less than 0.05). Moreover, minor derangements in circadian patterns of PRA, aldosterone, and potassium were also found. Group 2 not only showed an increased mesor of PRA (p less than 0.05), aldosterone (p less than 0.001), and reduced sodium (p less than 0.005), but also achronia in daily fluctuations of PRA, aldosterone, and potassium. In all groups the mesors of PRA and aldosterone were correlated (r greater than or equal to 0.82; p less than 0.01 or less), but the regression line slopes of patients were steeper than those of controls (group 1, p less than 0.05; group 2, p less than 0.01). Moreover, although in controls and some group 1 patients aldosterone paralleled cortisol rhythmicity, most group 2 patients had aldosterone daily patterns correlated with those of PRA. Finally, no relationships between plasma potassium and aldosterone concentrations were found in patients, whereas they were strictly related in controls. These results suggest that the renin-angiotensin system is the prevalent determinant of aldosterone secretion in cirrhosis.

Adult↗

Effects on long-term sensitivity to pain and morphine of stress induced in the newborn rat by pain or manipulation.

Four times daily from postnatal day 1 to 15, rats were stressed either by being removed from the maternity cage (manipulation stress, MS) or by being placed on a hotplate at 55 degrees C (pain stress, PS). When 70 days old, they were examined for sensitivity to pain and to the analgesic effect of morphine, and for brain opiate receptors. Pain sensitivity of MS and PS rats was not significantly different from that of controls. The analgesic activity of morphine, assessed by the hotplate test at 49 degrees C, was significantly reduced in MS rats, while in PS rats it was similar to that in controls. 3H-dihydromorphine binding studies performed on whole brain synaptic membranes showed a reduction in the maximum number of binding sites in both MS and PS rats; on the other hand, the affinity constant was higher in PS rats, while in MS rats it was similar to that of controls. These data show that the repeated stress of removal from the mother during the first 15 days of life induce a reduction in the number of brain opiate receptors with reduced activity of morphine, while in rats exposed to repeated removal stress associated with painful stimuli the reduction in the number of brain opiate receptors seems to be counterbalanced by their higher affinity.

Animals↗

Behavioral activity and active avoidance learning and retention in rats neonatally exposed to painful stimuli.

Twice daily for the first 15 days after birth, rats from the same litters were either placed for 5 sec on a hot plate (55 degrees C) (treated group), or on a plate maintained at body temperature (38 degrees C) (manipulated group). Controls were left undisturbed. When 90 days old, they were studied for pain threshold, open-field behavior, and two-way active avoidance learning and retention. Weight gain, pain threshold, open-field behavior, and active avoidance retention were not significantly different in the three groups. On the other hand, the rate of two-way active avoidance learning was significantly greater in treated rats. These results suggest that repeated neonatal exposure to painful stimuli, in rats raised under otherwise normal conditions, improves later active avoidance performance. The most likely mechanisms are discussed.

Acoustic Stimulation↗

Effects of somatostatin on plasma ammonia and amino acid profile during fasting and after protein feeding in cirrhotic patients.

The effects of somatostatin on fasting and absorptive plasma ammonia and amino acids were studied in 12 cirrhotic patients. They received a 6 h intravenous infusion of somatostatin (500 micrograms/h) or saline, starting 90 min before protein feeding. During the fasting period somatostatin significantly reduced plasma ammonia (-18%) and total tryptophan (-39%), increased plasma leucine (+19%), isoleucine (+17%), glutamine (+22%), glycine (+13%), arginine (+14%) and lysine (+12%), and prevented the significant fall of phenylalanine (-8%), tyrosine (-6%), alanine (-8%) and threonine (-9%) seen with saline. The percent changes in ammonia and glutamine concentrations were inversely correlated (r = -80; p less than 0.001) After protein ingestion, somatostatin slowed the maximal plasma increase in ammonia and alpha-nitrogens by at least two hours, but their total 5 h plasma response was not reduced, and even, in some instances, significantly increased (valine, leucine, glutamine, alanine and serine) with respect to saline. The results suggest that in fasting cirrhotics somatostatin reduces plasma ammonia, probably through an impaired intestinal ammoniogenesis from circulating precursors, and inhibits the disposal of branched chain, aromatic (except tryptophan) and gluconeogenic amino acids. Furthermore, it delays, but does not reduce, the plasma increase in nitrogen after protein ingestion.

Adult↗

The renin-angiotensin-aldosterone system in human hepatic cirrhosis.

Changes in the renin-aldosterone axis have long been recognized as occurring in patients with liver cirrhosis; different patterns are encountered during the different stages of the disease. Patients in whom ascites has not yet developed usually show depressed plasma renin activity or concentration. The low levels may be due to effective extracellular fluid volume expansion, although this view is not accepted by all authors. According to the overflow theory of ascites formation, sodium retention should occur before the appearance of ascites and, hence, volume expansion should ensue. Since plasma aldosterone concentration is usually normal or even depressed at this stage, increased sodium retention can only be explained by an enhanced renal tubular sensitivity to mineral-corticoid hormone. Mounting evidence suggests that such an abnormality is present in nonascitic patients and progresses as the disease worsens. This abnormality also explains why greater than 50% of patients with ascites and avid renal sodium retention have plasma renin activity and aldosterone within the normal range. In the late stages of the disease, the development of massive compartmentalization of fluid as ascites, along with changes in cardiovascular homeostasis (reduced peripheral resistances, opening of arterovenous shunts, and reduced efficiency of the sympathetic nervous system), lead to striking activation of the renin-angiotensin-aldosterone system. The system is responsible for sodium retention and for the maintenance of arterial pressure, and can be involved, at least in part, in reducing renal perfusion.

Aldosterone↗

Convulsive syndrome induced by the intracerebroventricular injection of alpha-difluoromethylornithine in rats.

In adult rats, the intracerebroventricular injection of alpha-difluoromethylornithine (DFMO), a polyamine antimetabolite which specifically inhibits ornithine-decarboxylase, induces a typical convulsive syndrome (ED50 = 100 micrograms/rat) and death (LD50 = 300 micrograms/rat). Histological lesions are seen only with the highest doses and are essentially restricted to the Ammon's horn neurones. Since DFMO is currently undergoing clinical trials for use in cancer chemotherapy, including brain tumours, its CNS toxicity should be carefully considered.

Animals↗

Renal function impairment induced by change in posture in patients with cirrhosis and ascites.

The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline.

Adult↗

Importance of plasma aldosterone concentration on the natriuretic effect of spironolactone in patients with liver cirrhosis and ascites.

23 cirrhotics with ascites and sodium retention, whose aldosteronemia had been evaluated after an equilibration period at controlled sodium intake at the occasion of previous studies, were retrospectively investigated. The dosage of spironolactone needed to induce a negative sodium balance correlated significantly with plasma aldosterone concentration: r = 0.64; p less than 0.001. However, in cases with plasma albumin concentration less than 3 g/dl, glomerular filtration rate less than 80 ml/min, and plasma sodium concentration less than 136 mmol/l such a relationship was no longer significant. The diuretic response to spironolactone is mainly linked to plasma aldosterone concentration. Factors affecting the removal of ascites from the peritoneal cavity and renal sodium handling can influence the expected diuretic response to the drug.

Aldosterone↗

Comparative pharmacodynamics of furosemide and muzolimine in cirrhosis. Study on renal sodium and potassium handling and renin-aldosterone axis.

Ten male cirrhotic patients with ascites and reduced renal function were randomly given equivalent doses of furosemide and muzolimine by the oral route, through a single blind cross-over protocol. Renal function, electrolyte plasma concentrations and urinary excretions and renin-angiotensin-aldosterone system components were evaluated under basal conditions and after drug administration. The diuretic and saluretic effects being equal, the response to muzolimine was initially weaker but more prolonged than to furosemide, without rebound phenomena. The furosemide-induced natriuresis was in part related to the filtered sodium load, whereas muzolimine natriuresis was only correlated to the inhibition of tubular sodium reabsorption. No potassium wasting effect was seen after muzolimine administration. Transient plasma potassium concentration reduction observed during muzolimine suggests an ion shift within the intracellular compartment. Therefore, a possible interaction of the drug with cellular sodium active transport systems can be hypothesized. A significant increase of plasma renin activity was observed after furosemide. No significant changes were seen after muzolimine administration.

Angiotensin II↗

Depression and gastrointestinal illness: the joint use of biological and clinical criteria.

Occurrence and characteristics of depression were investigated in 37 consecutive patients suffering from gastrointestinal illness. More than 40% of patients with an organic digestive disease and about a quarter of those with functional gastroenterological complaints were found to suffer from a major depressive disorder according to DSM-III criteria. The dexamethasone suppression test--a laboratory marker of the endogenous depressive state--supported clinical diagnosis in several cases, yet its routine use to screen depression is not warranted because of its poor specificity. The results should alert the physician to include clinical and biological criteria for depression in the diagnostic work-up for gastrointestinal illness.

Adult↗

Effect of alpha-difluoromethylornithine (DFMO) on the behavioral syndrome induced by intracerebroventricular injection of ACTH 1-24, in rats.

Stretching-yawning syndrome (SYS) and penile erections (PE) are typical components of the behavioral picture induced by intracerebroventricular (i.c.v.) injection of ACTH 1-24. The present study shows that pretreatment with alpha-difluoromethylornithine (DFMO), and irreversible inhibitor of mammalian ornithine decarboxylase (ODC), antagonizes these behavioral effects in a dose-dependent way, in rats. These results suggest that ODC and polyamines may play a role in the transduction and transmission of receptor-mediated signals.

Adrenocorticotropic Hormone↗