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Biomedical subjects

M Carmignani

Publications and source records attributed to M Carmignani.

At least 19 recordsLinked to original sources

Vanadate as factor of cardiovascular regulation by interactions with the catecholamine and nitric oxide systems.

The effects of 1 microgram/mL of vanadium, given for 12 mo as sodium metavanadate in drinking water, on cardiovascular and biochemical indices of male rabbits were investigated. At the end of the exposure period, vanadium was more accumulated in bones and kidneys than in spleen and liver; the cardiac ventricles and the aorta contained similar amounts of this element. Blood pressure and heart rate were unchanged in the vanadate-exposed animals since the observed decrease of both cardiac inotropism and stroke volume was counteracted by an increase of peripheral vascular resistance, with reduction of arterial blood flow. The arterial levels of sodium, potassium and aldosterone were unmodified by vanadate which, however, strongly raised those of noradrenaline, adrenaline, L-DOPA, and dopamine. Vanadate caused a marked increase of the activity of monoamine oxidase in renal tubules and liver (probably in relation to the increased plasma catecholamine levels) and a reduction of that of glucose-6-phosphate dehydrogenase in the kidney. There was also evidence that vanadium reduces synthesis and/or release of nitric oxide, the endothelium-derived vasodilating factor, likely through a reduced formation from bradykinin. It was concluded that vanadium may represent an environmental factor of altered cardiovascular homeostasis.

Animals

Trypanosoma cruzi meningoencephalitis in AIDS mimicking cerebral metastases: case report.

A case of Chagas' meningoencephalitis in a 47 year-old patient with AIDS is presented. The diagnosis was established by examination of the cerebrospinal fluid which showed the presence of Trypanosoma cruzi. CT-scan revealed multiple cerebral lesions which only became evident by contrast administration. A second CT after 13 days showed a severe evolution with displacement of the midline structures leading to the patient's death. This case, as well as other case reports published, has shown the fulminant evolution of Chagas' meningoencephalitis in AIDS patients and the importance of cerebrospinal fluid examination for the diagnosis.

AIDS-Related Opportunistic Infections

[Linear accelerator radiosurgery].

Radiosurgery is the precise radiation of a known intracranial target with a high dose of energy, sparing the adjacent nervous tissue. Technological advances in the construction of linear accelerators, stereotactic instruments and in computer sciences made this technique easier to perform and affordable. The main indications for radiosurgery are inoperable cerebral vascular malformations, vestibular and other cranial schwannomas, skull base meningiomas, deep seated gliomas and cerebral metastases. More recently, the development of fraccionated stereotactic radiotherapy increased the spectrum of indications to bigger lesions and to those adjacent to critical nervous structures. We present our initial experience in the treatment of 31 patients. An adequate control of the neoplastic lesions was obtained and the adequate time of observation is still needed to evaluate the results in arteriovenous malformations.

Adolescent

Renal toxicity and arterial hypertension in rats chronically exposed to vanadate.

The effects of 1, 10, or 40 micrograms/ml of vanadium, given for six or seven months as sodium metavanadate in drinking water on cardiovascular and biochemical variables and the electrolyte metabolism of male Sprague-Dawley rats were investigated. At the end of the exposure period, all animals exposed to vanadate had increased systolic and diastolic blood pressure. This effect was not dose dependent and heart rate and cardiac inotropism were not affected. The role of defective renal function and electrolyte metabolism in such effects was supported, in the rats exposed to 10 and 40 ppm of vanadium, by the following changes: (a) decreased Na, + K(+)-ATPase activity in the distal tubules of nephrons; (b) increased urinary excretion of potassium; (c) increase in plasma renin activity and urinary kallikrein, kininase I, and kininase II activities; (d) increased plasma aldosterone (only in the rats treated with 10 ppm of vanadium). The alterations in the rats exposed to 1 ppm of vanadium were: (a) reduced urinary calcium excretion; (b) reduced urinary kallikrein activity; (c) reduced plasma aldosterone. These results suggest that blood hypertension in rats exposed to vanadate depends on specific mechanisms of renal toxicity related to the levels of exposure.

Animals

Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide.

Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-1b forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4- [(3-methyl-2-butenyl)-guanidino]butane. The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by i.v. route in anesthetized rats at doses ranging from 50 to 1600 micrograms/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta 1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.

Acylation

Specific increase of L-dopa levels in plasma upon infusion of tyrosinase containing liposomes.

1. The present paper reports the effects of liposome-entrapped tyrosinase (EC 1.14.18.1. L-Tyrosine, L-3,4-dihydroxyphenylalanine: oxygen oxidoreductase) infusion on the catecholamine contents of rat plasma. The actions of liposomes and free tyrosinase have also been investigated. 2. From the experiments, evidence has been obtained that liposome-entrapped tyrosinase is able to affect specifically L-3,4-dihydroxyphenylalanine (L-DOPA) levels which increase dramatically. 3. The possible use of liposome-entrapped tyrosinase to raise L-DOPA levels in catecholamine related disorders is discussed. 4. Liposomes without tyrosinase provoke no significant changes of catecholamine or L-DOPA levels while free tyrosinase does induce a change but in a less constant fashion than the liposome-entrapped enzyme.

Animals

Zinc and copper in tissues of rats with blood hypertension induced by long-term lead exposure.

Male Sprague-Dawley rats received for 14 months 0, 15, 30 and 60 micrograms/ml of lead in drinking water. Both blood pressure and tissue lead were augmented with a dose-response effect, while cardiac inotropism was increased only in the rats treated with 60 ppm of lead. In the exposed animals, zinc and copper were unchanged in kidneys and testicles and augmented in the brain, while copper, but not zinc, was reduced in the heart. These data suggest a possible relation between the modifications of copper and zinc metabolism and the effects of lead on cardiovascular homeostasis.

Administration, Oral

Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats.

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.

Animals

Kallikrein-kinin,enkephalin, renin-aldosterone and catecholamine systems in the vanadate (as vanadyl)-induced arterial hypertension.

Exposure to vanadate was found to induce arterial hypertension through effects on renin-angiotensin-aldosterone, renal peptidergic, and central and peripheral catecholaminergic systems. Vanadate increased, mainly in vascular myocells, both receptor-operated Ca2+ channel- and cyclic-AMP-dependent availability of Ca2+ for contractile processes. Vanadate was selectively accumulated by tissues in the +4 oxidation state (vanadyl).

Aldosterone

Physiologic role of the peripheral enkephalinergic system in regulating cardiovascular homeostasis: evidence of interactions with the renin-angiotensin and kallikrein-kinin systems.

On isolated heart preparation, it was found that Leu5-Enkephalin (Leu5-ENK) did not influence the cardiac function. On the other hand, Leu5-ENK induced a specific dose-related inhibition, in the cardiac perfusate, of the activities of kininase II (KII) and angiotensin converting enzyme (ACE) (but not of kininase I-KI). Instead no detectable alterations of the above enzymatic activities with the used concentrations of Leu5-ENK were observed in vitro. This opioid also increased specifically the effects induced by some of the autacoids, related to both renin-angiotensin and kallikrein-kinin systems, on the KII and ACE activities. A specific correlation between these Leu5-ENK-induced modifications and the functional responses of the heart to the same autacoids was observed. Naloxone (NAL) and more significantly ICI 174864 (ICI) opposed or reversed the inhibitory effect of the used opioid whereas they had neither inhibitory nor synergic effect on both KII and ACE activity by themselves. The possible physiologic role of the enkephalins in regulating cardiovascular function by acting peripherally on some humoral systems through modulatory mechanism was discussed.

Animals

A human monoclonal autoantibody isolated from a patient with infectious mononucleosis reactive with both self antigens and Epstein-Barr virus nuclear antigen (EBNA).

In order to investigate the mechanism(s) by which Epstein-Barr virus (EBV) induces the outcome of autoantibodies during infectious mononucleosis (IM), a human IgM (k) monoclonal antibody to cytoskeletal filaments of epithelial cells has been prepared by EBV transformation of peripheral blood B lymphocytes obtained from a patient with IM. The antibody was also found to react with smooth muscle of frozen sections of human stomach tissue by immunofluorescence, and with the Epstein-Barr nuclear antigen (EBNA) by an enzyme-linked immunosorbent assay. These findings demonstrate at the clonal level the epitope homology between host's cell antigens and EBV-encoded nuclear antigen, which might have relevance in EBV-induced autoimmunity.

Antibodies, Monoclonal

Ultrastructure of the testis in rats with blood hypertension induced by long-term lead exposure.

Male Sprague-Dawley rats received 60 micrograms/ml of lead (as acetate) in drinking water for 18 months. Their blood pressure and cardiac inotropism were increased. Lead was augmented in blood, kidney and brain, but not in testis. Examination by light microscopy of the organs did not reveal alterations. Ultrastructural examination of the testis with both transmission and scanning electron microscopy (EM) did not evidence modifications in the external part of the seminiferous tubules, in the spermatogenetic cells and in the connective tissue including the Leydig cells; only Sertoli cells presented increased size of lysosomes.

Animals