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Biomedical subjects

A Pinto

Publications and source records attributed to A Pinto.

At least 325 records · Page 18Linked to original sources

Clinical evaluation of short-term defibrotide treatment of patients with atherosclerosis obliterans of the lower limbs.

Ten patients with atherosclerosis obliterans of the lower limbs (Fontaine stage IV) were studied under basal conditions during and after short-term administration of defibrotide (800 mg/day intravenously from day 1 to 10 and then 400 mg/day intramuscularly from day 11 to 30). The clinical effectiveness of defibrotide was evaluated not only clinically (subjective and objective symptomatology) but also by Doppler velocimetry (Windsor's Index (WI] and primary antiplasmin activity. Seven patients (70%) showed improvement in subjective and objective symptomatology. There were increases in WI at the end of intravenous treatment in 6 patients (60%). In the remaining 40%, WI did not change from basal values. All patients showed normalization of primary antiplasmin activity versus basal values (55.62%, 17.75 SD) at the end of both intravenous and intramuscular treatment (101.37%, 15.71 SD and 102.5%, 13.86 SD, respectively). Therefore, we think that defibrotide may be useful for therapy of atherosclerosis obliterans of the lower limbs.

Antithrombin III↗

Effects of ketanserin on blood pressure, peripheral circulation and haemocoagulative parameters in essential hypertensives with or without arteriosclerosis obliterans of the lower limbs.

Ketanserin is a new strong antiserotoninergic drug that, unlike the previous ones, is selective for 5-hydroxytryptamine receptors. This drug has been employed successfully in the treatment of arterial hypertension and of some peripheral vascular diseases. The authors are carrying out a trial on medium term treatment with ketanserin (K) or propranolol (P) in comparison with placebo, to evaluate their effects on blood pressure, haemocoagulative parameters and peripheral circulation. The trial is a double-blind cross-over random trial on subjects with mild or moderate hypertension. Until now 13 patients have ended the study; six of them are suffering from arteriosclerosis obliterans of the lower limbs at 1st or 2nd stage according to Fontaine. Both propranolol and ketanserin significantly reduced the blood pressure, although the decrease in systolic blood pressure was more evident after propranolol. Heart rate diminished significantly only after propranolol administration. The noninvasive, intermittent (every 30 min) monitoring of blood pressure showed a significant 24-hour reduction of blood pressure after administration of propranolol or ketanserin without significant changes of circadian behaviour of the blood pressure. After administration of ketanserin a slight improvement in peripheral circulation was demonstrated, evaluated by using strain-gauge plethysmography. As regards the results obtained for platelet function and other haemocoagulative parameters examined, adenosine diphosphate-induced platelet aggregation, adenosine diphosphate slope, collagen lag period, antithrombin III biological activity, and serum fibrinogen did not show noticeable modifications after treatment, while beta-thromboglobulin levels decreased slightly after ketanserin administration.

Adult↗

Cytochrome P450-dependent arachidonate metabolism in renomedullary cells: formation of Na+K+-ATPase inhibitor.

The medullary portion of the thick ascending limb of the loop of Henle (mTALH) has one of the highest concentrations of Na+K+-ATPase found in mammalian tissues, reflecting the importance of this nephron segment in the regulation of extracellular fluid volume, as active sodium transport is driven by Na+K+-ATPase. We have isolated cells derived primarily from the mTALH of the outer medulla of rabbit kidney and have identified a cytochrome P450-dependent mono-oxygenase system which metabolizes arachidonic acid to two biologically active oxygenated peaks, each containing two or more products. One of the peaks potently inhibits cardiac Na+K+-ATPase and the other relaxes blood vessels. We report that formation of these oxygenated arachidonate metabolites is stimulated by arginine vasopressin (AVP) and salmon calcitonin (SCT). In mTALH cells obtained from rabbits made hypertensive by aortic constriction there was a selective increase in P1 and P2 formation compared to other renomedullary cells.

Animals↗

Cytochrome P-450-dependent monooxygenase activity and endothelial-dependent relaxations induced by arachidonic acid.

The authors have recently identified a cytochrome P-450-dependent monooxygenase in vascular tissue, localized primarily to the endothelium. As this enzyme system can metabolize arachidonic acid (AA) to novel products, some of which produce vasodilation, the pathways involved in the vascular actions of AA (10(-8) to 5 X 10(-6) M) were examined on rings of rabbit pulmonary artery. In pulmonary rings with a low basal tension (1.5 g), AA produces a weak contraction which is prevented by removal of the endothelium or the addition of indomethacin (10(-6) M) but not SKF 525A (10(-5) M), suggesting the formation of an endothelial-dependent vasoconstrictor cyclooxygenase product. In contrast, rings precontracted to 3.5 to 4 g tension with phenylephrine (7 X 10(-7) M) exhibit a dose-related relaxation to AA, which is significantly greater (P less than .001, n = 32) in preparations with an intact endothelium. The endothelium-independent relaxation is suppressed by indomethacin whereas indomethacin fails to attenuate the endothelium-dependent response. In contrast, SKF 525A, an inhibitor of cytochrome P-450-dependent monooxygenase, markedly inhibits (P less than .001) AA-induced relaxations in intact rings in a dose-dependent manner while not affecting the response in rings denuded of endothelium. Intact vessels treated with SKF 525A (10(-6) M) appear to show diversion of the AA to vasodilator cyclooxygenase products, since the subsequent addition of indomethacin produces a further reduction of the AA-induced relaxations, whereas by itself indomethacin has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Antigenic population changes of Leptospira biflexa strains grown under the selective pressure of factorial antibodies.

Serovars jequitaia and tororò of Leptospira biflexa were cultured in the presence of homologous factor serum containing factorial antibodies (FcAbs) to their major antigens. After 39 serial passages they were then re-tested to determine whether their major antigens had remained unchanged. It was found that each parent strain had been replaced by an antigenic variant. The disappearance of each parent strain and its replacement by an antigenic variant was attributed to the selective conditions imposed by FcAbs. The antigenic variants behaved like true mutants. They lacked the major serovar antigens of the parent strains and had acquired some major antigens similar to those of two different serovars, one of which belonged to the same serogroup as the parent strain and the other to a different serogroup. A comparison of the major antigens of the parent strains with those of their antigenic variants indicated that factorial antibodies may be used selectively to obtain antigenic variants with a predefined pattern of major antigens.

Agglutination Tests↗

Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function.

The effects of nafazatrom on leukocyte function in vitro and in vivo were related to its ability to salvage ischemic myocardium in an occlusion-reperfusion model of myocardial injury in the anesthetized dog. Nafazatrom (0.4-75 microM) produced dose-related inhibition in vitro of neutrophil aggregation, superoxide anion generation, arachidonic acid metabolism, and, to a lesser extent, the release of beta-glucuronidase. In contrast, nafazatrom (0.4-37.5 microM) did not substantially influence platelet aggregation or the platelet metabolism of arachidonic acid. In vivo nafazatrom (10 mg/kg, po) reduced infarct size from 58 +/- 3% of the risk area (mean +/- SEM, n = 9) in control dogs to 23 +/- 2% of the risk area (n = 9, P less than 0.01). Nafazatrom also reduced the incidence of accompanying arrhythmias. Nafazatrom-induced myocardial salvage was not associated with any hemodynamic changes; moreover, it was independent of platelets, since thrombocytopenia did not prevent nafazatrom from exerting a protective effect. Measurements of the neutrophil-specific myeloperoxidase enzyme in ischemic myocardium indicate that the smaller infarct size in dogs treated with nafazatrom is accompanied by diminished leukocyte infiltration. Thus, the ability of nafazatrom to inhibit neutrophil function in vitro and cell infiltration in vivo may underly its myocardial-protective effects.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Calf blood flow and vascular resistance in middle-aged and elderly hypertensives.

Hypertension is associated with increased total peripheral vascular resistance. Calf blood flow and vascular resistance in two groups of hypertensives of different age has been evaluated: 85 middle-aged hypertensives (MH) and 25 elderly hypertensives (EH), and in two groups of 20 normotensive control subjects of similar age. Calf blood flow at rest (RF) and after ischaemia (PF) was determined by strain-gauge plethysmography. Basal (BVR) and minimal (MVR) vascular resistance were obtained by the mean blood pressure (MBP):RF and MBP:PF ratio. Blood flow at rest was reduced only in EH, while PF was significantly lower in MH and in EH in comparison with the respective controls. In parallel, BVR and MVR were higher in MH and in EH compared with controls. The increase of BVR and of MVR was more evident in EH. These results suggest that in EH there is an impairment of the calf maximal vasodilatation capacity, probably due to the long duration of hypertension.

Adolescent↗

Development of ovarian carcinoma in a cyclosporin A immunosuppressed patient.

This is the first report of an ovarian carcinoma developing in a patient immunosuppressed by Cyclosporin A. Thirteen months before the diagnosis of malignancy, the patient received a living related donor kidney transplant whose rejection was controlled by Cyclosporin A and prednisone. The tumor was rapidly fatal five weeks from diagnosis. The literature on malignant transformation in the immunosuppressed patient is reviewed with emphasis on a gynecologic perspective.

Adult↗

Nodular pulmonary amyloidosis.

An elderly man had a 10-year history of multiple pulmonary nodules that he had refused to have investigated. He died of a ruptured abdominal aortic aneurysm. At autopsy the nodules were shown to consist of amyloid. There was no evidence of systemic amyloidosis.

Aged↗