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Biomedical subjects

S Pinto

Publications and source records attributed to S Pinto.

At least 19 recordsLinked to original sources
PubMed2005

Is Hyperhomocyst(e)inemia a humoral predictor of coronary heart disease?

Elevated plasma homocyst(e)ine levels have prothrombotic and proatherosclerotic effects. Data from prospective studies indicated that plasma homocyst(e)ine acts as a modest independent predictor of coronary heart disease. At present, no conclusive data are available on the possible interaction between hyperhomocyst(e)inemia and hypertension and the occurrence of cardiovascular events. Recent longitudinal studies in high risk patients indicated that hyperhomocyst(e)inemia is strongly associated with recurrent cardiovascular events. However, this finding is not in line with the few available data from prospective studies, which failed to observe a protective role of homocyst(e)ine-lowering therapy in secondary prevention of cardiovascular events. Future results from ongoing larger trials are expected to provide more definitive answers concerning the need to support the routine use of folic acid in patients with CHD. Since the definitive impact of mild hyperhomocyst(e)inemia on coronary heart disease is still to be established, widespread determination of homocyst(e)ine levels is not needed in a general population at the present time. In contrast, knowledge of homocyst(e)inemia may be important for specific groups of individuals, such as high risk patients, and for those patients in whom traditional risk factors do not appear to account for an increased incidence of cardiovascular events.

Clinical Trials as Topic↗
PubMed2004

PET and SPECT functional imaging studies in Parkinsonian syndromes: from the lesion to its consequences.

Functional imaging techniques provide major insights into understanding the pathophysiology, progression, complications, and differential diagnosis of Parkinson's disease (PD). The dopaminergic system has been particularly studied allowing now early, presymptomatic diagnoses, which is of interest for future neuroprotective strategies. The existence of a compensatory hyperactivity of dopa-decarboxylase at disease onset has been recently demonstrated in the nigrostriatal and also extrastriatal dopaminergic pathways. Modification of dopamine receptors expression is observed during PD, but the respective contribution of dopaminergic drugs and the disease process towards these changes is still debated. Abnormalities of cerebral activation are seen and are clearly task-dependent, but the coexistence of hypoactivation in some areas and hyperactivation in others is also now well established. Such hyperactivation may be compensatory but could also reflect an inability to select appropriate motor circuits and inhibit inappropriate ones by PD patients. Interestingly, dopaminergic medications or surgical therapy reverse such abnormalities of brain activation.

Corpus Striatum↗
PubMed2003

Neovascularisation is a prognostic factor of early recurrence in T1/G2 urothelial bladder tumours.

BACKGROUND: Of patients with superficial bladder cancer, a group are still at risk of disease recurrence, progression and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial cell carcinoma (UCC), and is a potential therapeutic target. However, the selection of the appropriate patients remains a dilemma. PATIENTS AND METHODS: Vascular endothelial growth factor (VEGF) expression and the presence of angiogenesis and occurrence of CD31, CD34, endoglin and factor VIII immunoexpression, were evaluated in 66 superficial papillary UCCs of the bladder and were correlated with classical histopathological factors and disease outcome. RESULTS: VEGF immunoreactivity was observed in 100% of cases, and more intensely in the luminal surface. The presence of microvessel clusters independently of a fibrovascular core was observed in 22.7% of cases. Of these, the T1/G2 subgroup had an independent and significantly lower recurrence-free survival (P = 0.0002). CONCLUSIONS: These results indicate that the presence of angiogenesis in tumour urothelium is a potential prognostic factor in superficial UCC, particularly in T1/G2 tumours, and may be used to select patients for anti-angiogenic treatments.

Antigens, CD↗
PubMed2001

Duplex ultrasonographic study of the renal arteries before and after renal artery stenting.

The aim of our study was to evaluate feasibility and accuracy of colour-coded duplex US in the detection of renal artery stenosis before and after stenting. Eighty-four patients (23 women, 61 men; mean age 64 years) with significant renal artery stenosis were studied with Doppler US, before and after stenting. A combined anterior and translumbar approach was used to visualise the renal arteries. Renal artery stenosis and in-stent restenosis were proved by the increase of renal peak systolic velocity (PSV) and reno-aortic ratio (RAR). Laboratory-specific threshold values of PSV and RAR were used to assess sensitivity and specificity of Doppler US. The renal arteries were visualised in all patients (feasibility 100%). A statistically significant difference of PSV and RAR was demonstrated between patent and stenotic renal arteries, before stenting, and between stenotic and stented renal arteries. No difference was demonstrated in cases of in-stent restenosis ( n=21). Before stenting, sensitivity of PSV and RAR was 93%, whereas specificity rates were 92 and 96%, respectively. After stenting sensitivity and specificity rates were, respectively, 90 and 93% for PSV, and 95 and 95% for RAR. Doppler US represents a feasible and reliable technique in the detection of renal artery stenosis and in-stent restenosis, although laboratory-specific threshold values are required to improve its accuracy.

Feasibility Studies↗
PubMed2001

Renal artery stenting in patients with a solitary functioning kidney.

PURPOSE: To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney. METHODS: Palmaz stents were placed in 16 patients with a solitary functioning kidney, renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%), arterial dissection after PTRA (13%) and primary stenting (25%). Immediate results were evaluated by DSA. On follow-up (6-36 months), patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound. RESULTS: Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean +/- SD 104 +/- 6 vs 92 +/- 3; p < 0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean +/- SD 200 +/- 142 micromol/l vs 197 +/- 182 micromol/l; p > 0.05). CONCLUSION: Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.

Adult↗
PubMed2001

Effect of bilateral stimulation of the subthalamic nucleus on parkinsonian voice.

The purpose of this study was to assess several acoustic features of the voices of 26 parkinsonian patients under two conditions, with and without bilateral chronic stimulation of the subthalamic nucleus (STN) to estimate the effectiveness of this procedure on parkinsonian speech. When compared to unstimulated patients, stimulated patients showed longer duration of sustained vowels, shorter duration of sentences, nonsense words, and pauses, more variable fundamental frequency (f0) in sentences, and more stable f0 during sustained vowels. Relative intensity was unchanged in both conditions. Further acoustic analyses are warranted to clarify the role of STN stimulation on parkinsonian speech.

Dysarthria↗
PubMed2000

Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women.

BACKGROUND: The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the L-arginine-nitric oxide (NO) pathway and oxidative stress. Methods and Results-In 26 healthy women (age, 45.7+/-5.4 years) and 18 fertile women with leiomyoma (age, 44.5+/-5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0. 15, 0.45, 1.5, 4.5, or 15 microgram. 100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, or 4 microgram. 100 mL(-1). min(-1)), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during L-arginine (200 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or N(G)-monomethyl-L-arginine (L-NMMA; 100 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 microgram. 100 mL(-1). min(-1); 13 control subjects and 9 patients) or vitamin C (8 mg. 100 mL(-1). min(-1); 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 beta-estradiol TTS, 50 microgram/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by L-arginine and L-NMMA, respectively (P<0.05), but was unaffected by indomethacin or vitamin C. After ovariectomy, the modulating effect of L-arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine (P<0.05). ERT restored L-arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT. CONCLUSIONS: Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.

Acetylcholine↗
PubMed1999

latheo encodes a subunit of the origin recognition complex and disrupts neuronal proliferation and adult olfactory memory when mutant.

The Drosophila latheo (lat) gene was identified in a behavioral screen for olfactory memory mutants. The original hypomorphic latP1 mutant (Boynton and Tully, 1992) shows a structural defect in adult brain. Homozygous lethal lat mutants lack imaginal discs, show little cell proliferation in the CNS of third instar larvae, and die as early pupae. latP1 was cloned, and all of the above mentioned defects of hypomorphic or homozygous lethal lat mutants were rescued with a lat+ transgene. lat encodes a novel protein with homology to a subunit of the origin recognition complex (ORC). Human and Drosophila LAT both associate with ORC2 and are related to yeast ORC3, suggesting that LAT functions in DNA replication during cell proliferation.

Amino Acid Sequence↗
PubMed1999

latheo, a Drosophila gene involved in learning, regulates functional synaptic plasticity.

Mutations in the latheo (lat) gene disrupt associative learning in Drosophila , but a role for LAT in regulating neuronal function has not been demonstrated. Here, we report that LAT plays a central role in regulating Ca2(+)- and activity-dependent synaptic plasticity. Immunological localization of the LAT protein indicates it is present at synaptic connections of the larval neuromuscular junction (NMJ) and is enriched in presynaptic boutons. Basal synaptic transmission amplitude at the lat mutant NMJ is elevated 3- to 4-fold, and Ca2+ dependence of transmission is significantly reduced. Multiple forms of synaptic facilitation and posttetanic potentiation (PTP) are strongly depressed or absent at the mutant synapse. Our results suggest that LAT is a novel presynaptic protein with a role in the Ca2(+)-dependent synaptic modulation mechanisms necessary for behavioral plasticity.

Animals↗
PubMed1999

Noninvasive assessment of renal artery stenosis: current imaging protocols and future directions in ultrasonography.

Doppler ultrasound is one of many modalities that have been evaluated for the detection of renal artery stenosis. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories have, however, prevented universal acceptance of this technique as a reliable screening test for renal artery stenosis. The recent introduction of ultrasound contrast agents has substantially expanded the potential of color Doppler ultrasound. The use of microbubble echoenhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. Moreover, contrast-enhanced Doppler ultrasound can provide functional information through analysis of renal time-intensity wash in/wash out curves. State-of-the-art contrast-enhanced Doppler ultrasound seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension.

Blood Flow Velocity↗
PubMed1997

Effects of estrogen replacement therapy on thrombin generation.

The aim of this study was to investigate the hemostatic system in menopausal women before and after three months of treatment with transdermal estradiol (TTS 50, 50 micrograms/die, n = 13) or coniugated equine estrogen (CEE, 0.625 mg/die, n = 9) by evaluating : beta-thromboglobulin, platelet factor 4, factor VIIag, factor VIIc, fibrinopeptide A-FPA-, thrombin-antithrombin-TAT-complexes, antithrombin-AT-activity, protein C, plasma fibrinolytic activity (euglobulin clot lysis time), plasminogen and antiplasmin activity. FPA levels significantly increased during TTS 50 treatment (p < 0.001) while protein C showed a slight but significant decrease in both treatments (TTS 50 p < 0.001, CEE p < 0.05). TAT complexes and AT were found unaltered. Platelet function and fibrinolytic activity did not significantly change. A significant relationship between FPA and estradiol levels, which were significantly increased during. TTS 50 therapy, was found (r = 0.40, p < 0.05). These findings indicate that unopposed estradiol given by transdermal route induces a slight but significant blood clotting activation, which seems strictly related to its biological activity.

Administration, Cutaneous↗
PubMed1997

Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps.

A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗
PubMed1996

The long-term treatment of social phobia with moclobemide.

Patients meeting the social phobia criteria of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) on the DSM-III-R Structured Clinical Interview (n = 101) entered a long-term moclobemide treatment study. These patients were treated for 2 years with moclobemide (phase I) followed by drug withdrawal, in most cases abruptly (phase II). Those who relapsed entered phase III for a further period of 2 years of treatment. During phase I 40 patients (39.6%) withdrew due to inefficacy or relapse. Two patients were removed from the study because of other diagnoses (borderline or schizophreniform). At the end of phase I the remaining patients (58.4%) were rated as not ill (45.5%) or minimally ill (11.9%). Effort was taken to achieve the maximum dose of moclobemide (750 mg/day) and the mean (+/-SD) dose was 723.3 +/- 67.7 mg/day (month 21). A marked decrease in symptoms in the patients who responded was recorded on the Liebowitz Scale for Social Phobia, Clinical Global Impressions. Hamilton Anxiety Scale and Hamilton Depression Scale. Non-response was mainly associated with co-morbidity, especially alcohol abuse, axis II disorders, and a history of major depression or secondary dysthymia. The drug was well tolerated; the more frequent side effects were mild and occurred mainly in the first 2 months of phase I, including nausea, headaches or insomnia. In phase II there was a relapse rate of 88% and 51 patients entered phase III; these patients are still being treated.

Adolescent↗
PubMed1996

Menopause is associated with endothelial dysfunction in women.

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.

Acetylcholine↗