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Biomedical subjects

J Duarte

Publications and source records attributed to J Duarte.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cardiovascular effects of captopril and enalapril in obese Zucker rats.

The effects of two weeks of oral administration of the angiotensin-converting enzyme inhibitors captopril (a sulphydryl-containing drug) and enalapril (which lacks the sulphydryl group) on skeletal muscle glucose uptake, arterial blood pressure, cardiac hypertrophy, proteinuria and aortic vascular reactivity in obese Zucker rats were evaluated. Captopril (50 mg kg(-1) once daily) and enalapril (10 mg kg(-1) did not modify body weight gain or food or water intake. Both drugs decreased systolic blood pressure (157+/-6, 133+/-4 and 136+/-3 mm Hg, in vehicle-, captopril- and enalapril-treated rats, respectively), blood glucose (172+/-8 vs. 151+/-7 and 158+/-5 mg dl(-1), respectively), proteinuria (46+/-10 vs. 17+/-2 and 18+/-2.5 mg dl(-1), respectively) and heart weight (2.17+/-0.03, 1.98+/-0.02 and 1.99+/-0.04 mg g(-1)of body weight, respectively). Plasma insulin concentration was significantly increased by enalapril (17+/-2 ng ml(-1) vs. 9+/-2) but not by captopril (12+/-1). In the absence of insulin, the diaphragms from captopril- or enalapril-treated rats showed a significantly higher glucose uptake than that of controls (31% and 30% vs. control group, respectively). The presence of insulin in the incubation medium did not stimulate peripheral glucose uptake in the control group but significantly increased glucose uptake in diaphragms from captopril- or enalapril-treated rats (enhancement of glucose uptake vs. control: 52% and 43%, respectively). Endothelium-intact aortic rings from control Zucker rats showed a poor relaxant response to acetylcholine (maximal relaxation of 38.4+/-4.7%). Captopril significantly improved the endothelium-dependent vascular relaxation responses to acetylcholine and the endothelium-independent relaxation to the nitric oxide donor sodium nitroprusside whereas enalapril did not modify these relaxant responses. Neither captopril nor enalapril significantly affected the vascular contractile responses to the vasoconstrictors noradrenaline or KCl. In conclusion, the angiotensin-converting enzyme inhibitors captopril and enalapril reversed insulin resistance and the associated cardiovascular complications (cardiac hypertrophy, hypertension and proteinuria) in the obese Zucker rat, an animal model of non-insulin-dependent (type II) diabetes mellitus. However, only captopril, but not enalapril, improved the impaired endothelium-dependent and independent relaxant responses in the isolated rat aorta.

Acetylcholine↗
PubMed1999

Effects of visnagin on cyclic nucleotide phosphodiesterases and their role in its inhibitory effects on vascular smooth muscle contraction.

1. Visnagin relaxed aortae previously contracted by noradrenaline. This effect was unalterated by endothelium removal and potentiated, at high concentrations, by the previous incubation with sodium nitroprusside. 2. Visnagin weakly inhibited the hydrolytic activity of the cyclic nucleotide phosphodiesterase (PDE) isozymes (PDE5, PDE4, PDE3, cyclic GMP activated PDE2 and PDE1). 3. The present results indicate an involvement of PDE inhibition in the relaxant effect of visnagin at high concentration (>5x10(-5) M).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta.

1. The present study was undertaken to analyse the mechanism of the contractile response induced by the bioflavonoid myricetin in isolated rat aortic rings. 2. Myricetin induced endothelium-dependent contractile responses (maximal value=21+/-2% of the response induced by 80 mM KCl and pD2=5.12+/-0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively. 3. Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 microM), the cyclo-oxygenase inhibitor, indomethacin (10 microM), the thromboxane synthase inhibitor, dazoxiben (100 microM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 microM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 microM). 4. In cultured bovine endothelial cells (BAEC), myricetin (50 microM) produced an increase in cytosolic free calcium ([Ca2+]i) which peaked within 1 min and remained sustained for 6 min, as determined by the fluorescent probe fura 2. This rise in [Ca2+]i was abolished after removal of extracellular Ca2+ in the medium. 5. Myricetin (50 microM) significantly increased TXB2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca2+-free media and by indomethacin. 6. Taken together, these results suggests that myricetin stimulates Ca2+ influx and subsequently triggers the activation of the PLA2 and cyclo-oxygenase pathways releasing TXA2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of Tp receptors on vascular smooth muscle cells.

Animals↗
PubMed1998

Etiopathogenesis of transient ischemic attacks and minor ischemic strokes: a community-based study in Segovia, Spain.

BACKGROUND AND PURPOSE: We sought to analyze the etiology and underlying vascular risk factors of transient ischemic attacks (TIAs) and minor ischemic strokes (MISs). METHODS: We prospectively studied the vascular risk factors and etiologic categories in 235 patients with TIAs and MISs from a community-based register in a rural area of Spain. Five etiologic categories were considered: (1) cardioembolism, (2) large-artery atherosclerosis, (3) small-artery disease, (4) other etiologies, and (5) undetermined etiology. Systematic investigations included neuroimaging (CT/MRI) and vascular studies (duplex scan/MR angiography and angiography in selected cases). RESULTS: The two most frequent etiologic categories were small-artery disease (31%) and cardioembolism (26%). Large-artery atherosclerosis was detected in 11% of the patients. Significant carotid stenosis (> or =50%) was present in 13% of patients with carotid territory events. No cause could be found or it was uncertain in almost one third of the patients. The distribution of etiologic categories was similar in TIAs and MISs. The most prevalent vascular risk factors were as follows: arterial hypertension (50%), smoking (26%), atrial fibrillation (20%), hypercholesterolemia (17%), diabetes (15%), ischemic heart disease (12%), and peripheral vascular disease (3%). Carotid bruits were detected in 3% of the patients. CONCLUSIONS: An etiologic classification of TIAs and MISs is feasible. The two most frequent pathogenetic mechanisms in our study were small-artery disease and cardioembolism. The prevalence of large-artery atherosclerosis was low.

Aged↗
PubMed1998

Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease.

OBJECTIVE: To determine the frequency and the linkage distribution of seven mutations at the polymorphic gene coding for the arylamine N-acetyl transferase (NAT2; EC 2.3.1.5) in 121 unrelated patients with sporadic PD and in 121 unrelated healthy volunteers. METHODS: The study was performed with mutation-specific PCR using genomic DNA obtained from blood of the probands. RESULTS: Comparison of the NAT2 genotypes of the overall PD patients and control subjects did not indicate statistically significant differences. However, patients with early-onset PD (onset before the age of 50 years, n=37) showed a higher frequency of slow-acetylation genotypes (78.4% patients) compared with both healthy control subjects (55.4%) and with late-onset (onset after 51 years of age, n=84) PD patients (54.8%). Such a difference was statistically significant (p < 0.015) and was the result of a homogeneous increase in the frequency of slow-acetylation alleles. All subgroups analyzed in the study were in Hardy-Weinberg equilibrium for mutations at the NAT2 gene. CONCLUSIONS: Slow-acetylation-mutated alleles may be considered low-penetrance genes in early-onset PD pathogenesis, with a relative risk ratio for individuals with slow-acetylation genotype of 2.92 (95% CI, 1.26 to 6.78). This study provides evidence for the interaction of genetic and environmental factors in the etiology of sporadic PD.

Adult↗
PubMed1998

[Abciximab (ReoPro) in primary angioplasty].

UNLABELLED: The aim of the study was to evaluate the efficacy and safety of abciximab (ReoPro) in primary percutaneous transluminal coronary angioplasty (P.T.C.A.) in patients with myocardial infarction (M.I.). From June 96 to October 97, 16 patients with a mean age of 58 +/- 12 years, 86% males, with myocardial infarction (less than 12 hours of pain) were treated with ReoPro during P.T.C.A. The infarction was anterior in seven patients (44%), inferior in eight patients (50%) and non-Q wave in one patient (6%). Nine patients (47%) had a previous history of angina or myocardial infarction. The mean time from onset of symptoms to hospital arrival was 306 +/- 370 min and the mean time between hospital admission and the beginning of the procedure was 79 +/- 86 min. P.T.C.A. was performed on the anterior descending artery and right coronary in 44% and 56%, respectively. The success rate was 94%. Stents were used in 31%. In patients with angiographic success, we obtained TIMI III flow in 14 patients and TIMI II in one patient. No complications arose during P.C.T.A; no significant changes in platelets or hemoglobin were observed after the procedure. In this group of patients, one case of hematoma was found at the site of puncture with no need for transfusion. During hospitalization, no major coronary events were found. During the follow-up of 10.5 +/- 4.9 months, one patient died after non cardiac surgery and one patient was submitted to coronary artery bypass graft; there was no reinfarction nor new P.T.C.A. CONCLUSIONS: In our experience with ReoPro during direct angioplasty, we obtained good immediate and long term results, with no significant bleeding complications.

Abciximab↗
PubMed1997

Effect of tyrosine kinase and tyrosine phosphatase inhibitors on aortic contraction and induction of nitric oxide synthase.

We studied the effects of the tyrosine kinase inhibitors genistein and tyrphostin and the tyrosine phosphatase inhibitors sodium orthovanadate and phenylarsine oxide on endotoxin-mediated induction of nitric oxide (NO) synthase in rat aorta and its effects on vascular contractility. Genistein (i.p. 10 mg/kg) inhibited the ex vivo vascular hyporesponsiveness to noradrenaline and the aminoguanidine-sensitive nitrite accumulation induced by endotoxin (i.p. 5 mg/kg) in aortic rings. Low concentrations of genistein (10(-6) M) and tyrphostin (3 x 10(-6) M) inhibited both endotoxin-induced hyporesponsiveness and nitrite and NOx accumulation in vitro in rat aorta without affecting control nitrite or NOx accumulation or contraction. Higher concentrations of genistein (10(-5) and 5.5 x 10(-5) M), sodium orthovanadate (10(-4) M) and phenylarsine oxide (10(-6) M) produced an irreversible depression of noradrenaline-induced contractions. In the presence of these drugs, endotoxin did not induce further depression of vascular contractility and did not increase nitrite or NOx production. In conclusion, there is a dissociation between the effects of these drugs on vascular smooth muscle contraction and NO synthase induction, the latter being more sensitive to inhibition by these drugs. Surprisingly, tyrosine phosphatase inhibitors produced similar effects to those of tyrosine kinase inhibitors, suggesting that there is a complex relationship between tyrosine kinases and phosphatases in the signalling pathway of agonist-induced vascular smooth muscle contraction and NO synthase induction.

Animals↗
PubMed1997

[Intravenous leiomyomatosis with cardiac extension].

Intravenous leiomyomatosis is a very rare uterine neoplasm, characterized by histological benignity. In some cases, it could extend through the ovaric or iliac veins up to the vena cava and the right chambers of the heart. We report a patient with symptoms of right heart failure, who was diagnosed by transesophagic echocardiography of intravenous leiomyomatosis with extension to the right ventricle. Complete excision was achieved employing simultaneous sternotomy and laparotomy with echocardiographic intraoperative monitorization.

Echocardiography↗
PubMed1997

Involvement of protein kinase C in reduced relaxant responses to the NO/cyclic GMP pathway in piglet pulmonary arteries contracted by the thromboxane A2-mimetic U46619.

1. Impairment of nitric oxide (NO)/cyclic GMP production and/or increased activities of thromboxane A2 (TXA2) and endothelin-1 (ET-1) have been associated with pulmonary hypertension. We have analysed the interactions of noradrenaline (NA), the TXA2-mimetic U46619 and ET-1 with the relaxation induced via cyclic GMP in isolated piglet intrapulmonary arteries. 2. The contractions induced by NA were augmented by endothelium removal or by methylene blue and pre-contracted rings were fully relaxed by acetylcholine, sodium nitroprusside (SNP), atrial natriuretic peptide and 8-bromo-cyclic GMP. In contrast, U46619- and ET-1 induced contractions were endothelium-independent and only partially relaxed by the latter vasodilators. Whereas the reduced responses to SNP in arteries contracted by U46619 were independent of the U46619-induced tone, a higher concentration of ET-1 (tone higher than that induced by NA) was required to reduce the vasodilator responses to SNP. NA, U46619 and ET-1 had no effect on the SNP-induced increases in cyclic GMP. 3. The reduced relaxant responses to SNP in arteries pre-contracted by U46619 were specific for piglet pulmonary arteries since they were not observed in piglet mesenteric or coronary arteries or in rat pulmonary arteries. Furthermore, there were no differences in the relaxant response to the adenylate cyclase activator forskolin in piglet pulmonary arteries pre-contracted by either NA, U46619 or ET-1. 4. SNP-induced relaxation was inhibited by thapsigargin (but not by inhibition of the membrane Na+/ K+ ATPase nor K+ channels) indicating a role for Ca2+ sequestration by the Ca2+ ATPase in the effects of SNP. 5. The phorbol ester 12-myristate, 13-acetate inhibited the relaxant response to SNP. The inhibitory effect of U46619 on SNP-induced relaxation was abolished by the protein kinase C inhibitor (PKC) staurosporine suggesting that PKC may be a part of the signal transduction mechanism. 6. In summary, piglet pulmonary arteries when activated by a TXA2-mimetic show abnormally reduced relaxant responses to the NO/cyclicGMP pathway. This effect appears to be mediated by activation of PKC.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

CYP2D6 polymorphism is not associated with essential tremor.

Recent reports have shown an association between cytochrome P450IID6 (CYP2D6) polymorphism and Parkinson's disease. We investigated the association between this polymorphism and the risk for developing essential tremor (ET). Leukocytic DNA from 91 unrelated ET patients and a control group of 258 unrelated healthy individuals was studied for the occurrence of eight different CYP2D6 allelic variants by using allele-specific PCR amplification Xbal and EcoRI-RFLP's analyses. The prevalence for these allelic variants in the ET and control groups were, respectively: CYP2D6*1 76.9 and 78.7%, CYP2D6*2 0.5 and 0.2%, CYP2D6*3 0 and 1%, CYP2D6*4 12.1 and 12.2%, CYP2D6*5 1.6 and 1.7%, CYP2D6*9 4.4 and 2.9%, CYP2D6*2x2 4.4 and 3.2%. The prevalence of subjects with absent CYP2D6 activity (those carrying two defect genes) was 1.1 and 3.1% in ET and control groups, respectively. Both groups studied were in Hardy-Weinberg equilibrium. These results indicate that mutations at the CYP2D6 gene do not seem to be a major factor in determining susceptibility to ET, and reinforces the view that ET and parkinsonism are distinct conditions.

Adolescent↗
PubMed1996

Effects of flavonoids on rat aortic smooth muscle contractility: structure-activity relationships.

1. Flavonoids produced a concentration-dependent relaxation of the contractile responses induced by noradrenaline, KCl, or phorbol 12-myristate-13-acetate in rat aortic rings. Only the flavonoid with three contiguous hydroxyls in B rings (myricetin), at low concentrations, potentiates the contractions evoked by these agonists. 2. The relaxant effects of flavanone on the noradrenaline-induced contractions were potentiated by isoprenaline and those of morin, chrysin, flavanone, and naringenin by sodium nitroprusside. 3. Several mechanisms are implicated in the vasodilatory effects of flavonoids: inhibition of protein kinase C; inhibition of cyclic nucleotide phosphodiesterases; and/or decreased Ca2+ uptake.

Animals↗
PubMed1996

Postural myoclonus induced by phenytoin.

Involuntary movements are an infrequent complication of treatment with phenytoin and include tremor, asterixis, myoclonus, parkinsonism, and dyskinesias. The mechanism by which phenytoin exerts its actions is unclear. Phenytoin has been observed to exert variable effects on dopamine metabolites and also may induce changes in serotonergic activity. In this report, we discuss the available experimental evidence concerning the possible mechanisms of involuntary movements induced by phenytoin. We describe a case of postural myoclonus during treatment with phenytoin.

Aged↗
PubMed1996

Tubular vacuum-powered blood-pumping device with active valves.

We propose a new vacuum-driven blood pump having a tubular shape with active valves. This design avoids any possible problems caused by membrane breakage, thereby minimizing the risk of gas embolic events and stagnation regions. By using active valves, it is possible to ensure better flow control and minimize pressure gradients inside and outside the pump. The low cost of the pump's disposable parts enables it to be used for such applications as a ventricular assist device, a pulsatile pump device in extracorporeal circulation, a pump in hemodialysis and apheresis circuits, and a pump in extracorporeal membrane oxygenator systems.

Equipment Design↗
PubMed1996

Headache of recent onset in adults: a prospective population-based study.

One hundred consecutive adult patients with headache of recent onset were prospectively studied. Every patient was examined by craneal CT scan. Their mean age was 46 years (range 17-82). Neurological examination was normal in 80 patients. Organic headache represented 39% of the entire group, and 26% of them had a normal neurological examination. The yield of CT scan in patients with headaches and a normal neurological examination was 22.5% (95% IC: 14%-33%); of which we encountered the following pathologies: intracranial tumors (13), hydrocephalus (2), arachnoid cyst (1), toxoplasmic abscess (1) and parenchymal hemorrhage (1). The clinical characteristics of the headache on their own was insufficient to rule out the possibility of an intracranial tumor. Neuroimaging studies should be performed in all adult patients with non-vascular headache of recent onset, and previously headache-free individuals.

Adolescent↗