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Biomedical subjects

A Ferro

Publications and source records attributed to A Ferro.

At least 55 records · Page 3Linked to original sources
PubMed2000

beta(2)-adrenoceptors activate nitric oxide synthase in human platelets.

Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L-citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to 0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively (P<0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca(2+). In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2% respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through beta(2)ARs, as determined by coincubation with betaAR subtype-selective antagonists. We conclude that beta(2)ARs activate platelet NOS by increasing cAMP, and that this activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the L-arginine/NO system mediates the effects of beta(2)ARs on adhesion but not aggregation.

Blood Platelets↗
PubMed2000

A novel family of S-nitrosothiols: chemical synthesis and biological actions.

S-Nitrosothiols are a class of chemical compounds that decompose to release nitric oxide and show promise in the treatment of a variety of cardiovascular diseases. Some of these are present in vivo and others have been synthesized in vitro. However, those discovered or synthesized to date have very little tissue selectivity or specificity. We synthesized a number of novel S-nitrosated dipeptides of high purity and examined their effects on vasorelaxation using rat mesenteric arteries and on inhibition of platelet aggregation using platelets from healthyhuman subjects. For comparison, we also tested the effects of S-nitroso-l-glutathione (GSNO, an S-nitrosothiol present in vivo) and S-nitroso-N-acetyl-d-beta,beta-dimethylcysteine (SNAP(D), the d-isomer of SNAP, a commonly used S-nitrosothiol previously synthesized in vitro) in these biological systems. Satisfactory elemental analyses were obtained for all compounds synthesized (less than +/- 0.3%), and all accurate mass measurements were within 1-5 ppm of the expected mass. The novel S-nitrosated dipeptides all elicited vasorelaxation with significantly higher potency, of the order of one log molar unit, than either GSNO or SNAP(D). However, all compounds inhibited U46619-induced platelet aggregation with similar potency to GSNO and SNAP(D). These findings indicate a degree of tissue selectivity which may prove to be of therapeutic usefulness.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Nitric oxide-dependent vasodilatation of rabbit femoral artery by beta(2)-adrenergic stimulation or cyclic AMP elevation in vivo.

Some studies suggest that beta-adrenoceptor-mediated vasorelaxation is in part mediated through nitric oxide (NO) release. We wished to determine the contribution of the L-arginine / NO system to vasodilatation in response to beta-adrenoceptor stimulation with isoprenaline or cyclic adenosine-3',5'-monophosphate (cyclic AMP) elevation with forskolin and dibutyryl cyclic AMP in vivo, using a rabbit femoral artery constant perfusion model. Baseline femoral artery pressure was similar in rabbits receiving isoprenaline, forskolin or dibutyryl cyclic AMP. Isoprenaline, forskolin and dibutyryl cyclic AMP each decreased femoral artery pressure in a dose-dependent manner. The doses (mol kg(-1)) of isoprenaline, forskolin and dibutyryl cyclic AMP which decreased pressure by 10% from baseline, expressed as a negative logarithm (-log ED(10)) were: 10.0+/-0.2, 9.5+/-0.1 and 4.9+/-0.1 respectively (P<0.0001 for each). Use of beta-adrenoceptor subtype-selective antagonists showed that the vascular response to isoprenaline was purely due to stimulation of the beta(2)-adrenoceptor subtype. Injection of 1 micromol kg(-1) N(G)-nitro-L-arginine methyl ester (L-NAME) did not alter baseline pressure. However, it abolished the pressure response to isoprenaline (P<0.0001), and significantly attenuated the pressure responses to forskolin and dibutyryl cyclic AMP: -log ED(10) values for forskolin and dibutyryl cyclic AMP, in the presence of L-NAME, were 7.9+/-0.1 and 3.5+/-0.3 respectively (P<0.0001 for each, as compared with values in the absence of L-NAME). These results indicate that beta(2)-adrenergic stimulation and cylic AMP elevation activate the L-arginine/NO system in rabbit femoral artery in vivo, and that NO generation contributes importantly to the changes in vascular tone induced by agents which modulate beta-adrenoceptors or cyclic AMP.

Adrenergic beta-2 Receptor Agonists↗
PubMed2000

S-Nitrosothiols: a class of nitric oxide-donor drugs.

Nitric oxide (NO) was originally described as the principal endothelium-derived relaxing factor, but it is now known to subserve a variety of functions throughout the body, both physiological and pathophysiological. NO-donor drugs decompose in the body, by a variety of mechanisms, to generate NO. Such drugs have been used for many years in cardiovascular therapeutics, in particular the organic nitrates for the prevention and treatment of angina pectoris and sodium nitroprusside for the treatment of hypertensive emergencies. However, patients taking long-term nitrates often develop tolerance, and prolonged nitroprusside administration can give rise to cyanide accumulation in the body. Newer NO-donor drugs, in particular the S-nitrosothiols, offer advantages over the existing drugs, since they do not share these drawbacks, and initial small clinical studies suggest that they may be of benefit in a variety of cardiovascular disorders. Here we briefly review the chemistry and physiology of NO, and discuss the chemistry and clinical possibilities of the S-nitrosothiols.

Cardiovascular Diseases↗
PubMed2000

[Cardiac tomography with 99mTc-tetrofosmin after nitrate administration in patients with ischemic cardiopathy and left ventricular dysfunction].

PURPOSE: To investigate the role of technetium-99m (99mTc) tetrofosmin single-photon emission Computed Tomography (SPECT) associated with nitrate administration in the detection of hypoperfused but still viable myocardium in patients with chronic coronary artery disease and left ventricular (LV) dysfunction. MATERIAL AND METHODS: Twenty-two patients (mean age 54 +/- 11 years) with coronary artery disease, previous myocardial infarction and LV dysfunction (LV ejection fraction 38 +/- 13%) were examined. On different days all patients underwent 99mTc tetrofosmin (740 MBq) SPECT under control conditions at rest and after sublingual nitroglycerin administration (10 mg). Regional tetrofosmin activity was quantitatively measured in 22 myocardial segments per patient. In each segment, tracer uptake was expressed as a percentage of the region with the peak activity. RESULTS: Under control conditions, 267 myocardial segments (55%) showed normal tetrofosmin uptake (> 70% of peak activity), 107 segments (22%) showed a moderate reduction (51-70%) and 110 segments (23%) a severe reduction (< or = 50%) in tracer uptake. Among the 110 segments with a severe reduction in tetrofosmin uptake, 20 (18%) showed increased tracer uptake > or = 10% of after nitrate administration (from 44 +/- 5% to 58 +/- 3%, p < 0.0001). The remaining 90 (82%) segments with a severe reduction in tetrofosmin uptake did not show any change after nitroglycerin administration (from 38 +/- 9% to 39 +/- 8%, p = ns). CONCLUSIONS: In patients with chronic coronary artery disease and LV dysfunction, tetrofosmin cardiac SPECT associated with sublingual nitrate administration allows the detection of severely hypoperfused but still viable myocardium.

Adult↗
PubMed2000

[Hemodynamic and coronary angiographic performance at a center with medium-low activity: organization model, activity indicators, and costs].

BACKGROUND: In order to evaluate the cost-effectiveness of coronary angiography performed in a low volume Center, we examined our 1-year activity. METHODS: The organizational model of the multipurpose cardiac catheterization laboratory is described. In this type of facility both coronary angiographic and electrophysiological studies are performed. To evaluate the laboratory performance we examined the utilization level, the appropriateness of the studies, the complication rates and the number of studies that had to be repeated because of inadequate data or image quality. The costs were calculated for the in-house laboratory setting (the actual scenario) and for the 25 km distant laboratory setting (the historical scenario). RESULTS: The laboratory caseload of coronary angiography was 342 studies, 46% of the overall laboratory activity; 175 patients (51%) underwent non-pharmacological therapy, 129 patients (38%) were treated with medical therapy; the percentage of patients with normal coronary arteries was 11%. Two patients (0.58%) had vascular complications, 1 patient (0.29%) developed an acute myocardial infarction 2 hours after coronary angiography without any evidence of angiographic modifications at the repeated study. In no patient the study had to be repeated because of inadequate data or image quality. The mean cost of a coronary angiography was Lit. 512,000 (265 Euro) for the actual scenario; it would have been Lit. 694,000 (359 Euro) for the historical scenario, with Lit. 182,000 (94 Euro) saved. CONCLUSIONS: These findings are consistent with the accepted criteria of good laboratory performance and cost-effectiveness. Thus coronary angiography can be performed effectively and efficiently in a low volume Center.

Cardiac Care Facilities↗
PubMed1999

Activation of nitric oxide synthase by beta 2-adrenoceptors in human umbilical vein endothelium in vitro.

1. Some animal studies suggest that beta-adrenoceptor-mediated vasorelaxation is in part mediated through nitric oxide (NO) release. Furthermore, in humans, we have recently shown that forearm blood flow is increased by infusion of beta2-adrenergic agonists into the brachial artery, and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) inhibits this response. 2. The purpose of the present study was to determine whether stimulation of human umbilical vein endothelial beta-adrenoceptors causes vasorelaxation and nitric oxide generation, and whether this might be mediated by cyclic adenosine-3',5'-monophosphate (cyclic AMP). 3. Vasorelaxant responses were determined in umbilical vein rings to the nonselective beta-adrenergic agonist isoprenaline and to the cyclic AMP analogue dibutyryl cyclic AMP, following precontraction with prostaglandin F2alpha. 4. NOS activity was measured in cultured human umbilical vein endothelial cells (HUVEC) by the conversion of [3H]-L-arginine to [3H]-L-citrulline, and adenylyl cyclase activity by the conversion of [alpha-32P]-ATP to [32P]-cyclic AMP. 5. Isoprenaline relaxed umbilical vein rings, and this vasorelaxation was abolished by beta2- (but not beta1-) adrenergic blockage, and by endothelium removal or 1 mM L-NMMA. In addition, vasorelaxant responses to dibutyryl cyclic AMP were inhibited by 1 mM L-NMMA, with a reduction in Emax from 90.0+/-9.3% to 50.5+/-9.9% (P<0.05). 6. Isoprenaline 1 microM increased NOS activity in HUVEC (34.0+/-5.9% above basal, P<0.001). Furthermore, isoprenaline increased adenylyl cyclase activity in a concentration-dependent manner; this response was inhibited by beta2 (but not beta1-) adrenergic blockade. Forskolin 1 microM and dibutyryl cyclic AMP 1 mM each increased NOS activity in HUVEC, to a degree similar to isoprenaline 1 microM. The increase in L-arginine to L-citrulline conversion observed with each agent was abolished by coincubation with NOS inhibitors. 7. These results indicate that endothelial beta2-adrenergic stimulation and cyclic AMP elevation activate the L-arginine/NO system, and give rise to vasorelaxation, in human umbilical vein.

Adenylyl Cyclase Inhibitors↗
PubMed1999

Circadianicity of hemostatic function and coronary vasomotion.

Acute myocardial infarction, sudden cardiac death and ischemic stroke show a circadian periodicity, occurring more frequently in the morning. Because arterial thrombosis is common to these disorders, a circadianicity of prothrombotic and antithrombotic processes may contribute to explain the 24 h rhythms of these acute events. Available data indeed indicate that coronary vasomotor tone, platelet aggregability, plasma inhibition of fibrinolysis, coagulant activity and blood viscosity are all greater in the morning than at other times of day, producting a relative prothrombotic state in the early morning.

Blood Coagulation↗
PubMed1999

Evaluation of polycyclic aromatic hydrocarbon-DNA adducts in exfoliated oral cells by an immunohistochemical assay.

Polycyclic aromatic hydrocarbon-DNA adducts were evaluated in oral cells from 98 healthy volunteers by an immunohistochemical method using a specific antiserum against benzo(a)pyrene-DNA adducts revealed by the immunoperoxidase reaction. Mean adduct content, determined as relative staining intensity by absorbance image analyzer, was significantly higher in the cells from tobacco smokers compared with nonsmokers (330 +/- 98, n = 33 versus 286 +/- 83, n = 64, respectively) with a P = 0.013 obtained by two-sample t test with equal variances. We found that in the smoker group, the PAH-DNA adduct content increases with the number of cigarettes. Thus, the relative staining intensity was 305 +/- 105 in the group smoking 1-10 cigarettes/day (n = 16), 347 +/- 77 in the 11-20 group (n = 14), and 386 +/- 112 in the group smoking more than 20 cigarettes/day (n = 3; P = 0.03 by nonparametric test for trend). No significant association was detected between PAH-DNA adducts in oral cells and variables such as residential area, oral infections, alcohol or vitamin intake, grilled food consumption, and professional activity. This work confirms and extends previous data suggesting that this immunohistochemical method might be used as a valuable dosimeter of genotoxic damage in a carcinogen-exposed population, although further studies are needed to verify the applicability of the test in high-risk populations other than smokers.

Adolescent↗
PubMed1998

Distribution of hepatitis B virus genotypes in two different pediatric populations from Argentina.

Differences in pathogenesis and the probability of becoming a chronic carrier depend on the age at which hepatitis B virus (HBV) infection is acquired, ranging from 82% in infants less than 6 months of age to 15 to 30% in older children. HBV genotypes from 22 pediatric patients from two areas that differ in prevalence have been determined. Phylogenetic analysis shows a clear difference between the genotype distribution in Buenos Aires, a low-prevalence area, and that found in Gualeguay, Entre Ríos, a high-prevalence area. While the analysis allocated the sequences in the Buenos Aires group to genotypes A (36%), D (9%), and F (55%), the Gualeguay group presented exclusively genotype A isolates with very low nucleotide divergence, which suggests a strong founder viral population. The high prevalence of genotype F in the Buenos Aires group and its high intragroup heterogeneity agree with the American origin of this genotype.

Argentina↗
PubMed1998

[Complicated liver hydatid: experience at one center].

The object of the present paper is to show four patients treated at the "Ricardo Gutiérrez" Children's Hospital, with diagnosis of complicated liver hydatid disease, since april 1977 until january 1997. The four patients were previously healthy, and were admitted with acute symptomatology, which varied depending on the kind of complication. They were all studied before surgery, except for one patient, with simple x-ray, abdominal ultrasonography, and in some cases with computerized tomography; in addition blood serologic analysis were performed, which allowed us 100% effectiveness in the diagnosis. The observed complications were two intrabiliary rupture of the hydatid cyst, one infection of the cyst, and one intra abdominal rupture. All patients underwent surgery, which confirmed the diagnosis, and an uneventful follow up of 20 years in the first child. In spite of the infrequent presentation of the complicated hydatid disease, in an endemic region it is not impossible for it to be seen. In this case it will require a well trained team of specialists, to solve not only the problems that the diagnosis and treatment mean, but also the possibility of a correct follow-up, with the resolution of the possible obstacle that might show-up for the disease itself, and from the changes that the surgery produces.

Adolescent↗
PubMed1998

Genomic and phylogenetic analysis of hepatitis C virus strains from Argentina.

HCV genomic characterization was performed by nucleotide sequence analysis (n=50) combined with restriction fragment length polymorphism (RFLP) of the 5' UTR region in 82 isolates corresponding to different Argentine groups. Genotype 1 was detected in 70.7% of the samples (58 out of 82), genotype 2 in 21.9% (18 of 82) and genotype 3 in the remaining 6 sera (7.3%). HCV 1b subtype contributed with 35.3% to the whole population studied (29 to 82) and was detected in 6 out of 21 sporadic cases. Besides their epidemiological significance, these results should be taken into account when future vaccines are considered on the basis of geographical HCV genotypic prevalence.

Adolescent↗
PubMed1997

A prospective study of the effects of prolonged timolol therapy on alpha- and beta-adrenoceptor and angiotensin II receptor mediated responses in normal subjects.

AIMS: Long-term treatment with beta 1-selective adrenergic antagonists gives rise to cross-sensitisation of cardiac beta 2-adrenoceptor responses, with no corresponding alteration in beta 1-adrenoceptor responses. We performed a prospective randomised double-blind placebo-controlled cross-over study of the effects of nonselective beta-blockade with timolol on alpha-adrenergic and angiotensin II receptor mediated responses in normal subjects. We also wished to study the time course of beta 1- and beta 2-adrenergic responses after withdrawal of timolol. METHODS: Six healthy males received timolol 10 mg twice daily or placebo for 14 days. On day 11 of treatment, vascular alpha 1-, alpha 2- and angiotensin II receptor responses were assessed by measuring the blood pressure increases in response to intravenous phenylephrine, alpha-methylnoradrenaline and angiotensin amide respectively, following one dose of timolol 10 mg (to block the beta-adrenergic effects of phenylephrine and alpha-methylnoradrenaline). Both systolic and diastolic blood pressure increased in response to each of these drugs, but these increases were not different on timolol treatment or placebo. Following cessation of treatment with timolol or placebo, beta 1- and beta 2-adrenoceptor mediated responses were assessed by measuring the heart rate responses to treadmill exercise and intravenous salbutamol infusion respectively. Half each of the subjects underwent this 2 days and 3 days respectively, after the end of treatment. RESULTS: Both exercise-induced and salbutamol-induced tachycardia were not different following placebo or 3 days following the end of timolol treatment. However, 2 days following timolol treatment, both were attenuated; the reduction in salbutamol-induced tachycardia was significant, whilst the reduction in exercise tachycardia did not reach statistical significance. We also measured metabolic responses to exercise and to salbutamol infusion. Exercise induced a rise in plasma potassium and noradrenaline. Salbutamol produced a fall in plasma potassium, a rise in plasma glucose and insulin and also a rise in plasma noradrenaline. All of these changes were not different following placebo or 3 days after the end of timolol treatment; by contrast, 2 days following timolol treatment, all were significantly attenuated, with the exception of the rise in plasma glucose. In addition, the rise in both plasma glucose and insulin in response to an oral load of 75 g glucose were not different post-placebo, 2 or 3 days post-timolol. CONCLUSIONS: These results show that, following 14 days of nonselective beta-adrenoceptor blockade with timolol, there is evidence of residual beta-adrenoceptor blockade 2 days after drug withdrawal; this finding is in contrast with the known plasma profile of timolol (half-life 3-6 hours), but is consistent with our previous observations of the slow speeds of association and dissociation of timolol with beta-adrenoceptors in vitro. There is no evidence, in this study, of beta-adrenergic sensitisation following timolol withdrawal, nor of cross-regulation of vascular alpha 1-, alpha 2- or angiotensin II receptors in response to nonselective beta-adrenoceptor blockade.

Adrenergic alpha-Agonists↗
PubMed1997

Sneddon's syndrome: a vascular systemic disease with kidney involvement?

Sneddon's syndrome is a systemic disease characterized by livedo reticularis and cerebrovascular disease. Other organs may be involved as well. Typical vascular lesions in the skin biopsy and/or digital arteries biopsy can be found. Arterial hypertension, cardiac pathology (ischemic disease, myocardial infarction, valvulopathy), venous thrombosis and even fetal death are also found sometimes. We present a case of Sneddon's syndrome in which typical vascular lesions in the kidney were demonstrated for the first time unequivocally confirming the systemic nature of this syndrome.

Adult↗