PubMed Health⌕ Search

Biomedical subjects

S Pinto

Publications and source records attributed to S Pinto.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Molecular pathobiology in heart failure].

Heart failure is a pathophysiological state resulting from disturbed cardiac function. It is based on complex molecular processes, many of which are not fully understood. During heart failure adaptive mechanisms, that reinstall altered cardiac function, are activated. The main mechanisms are: a) Alteration of the structure and composition of myocytes by myocardial hypertrophy, reexpression of fetal and neo-natal proteins and the expression of certain proto-oncogenes; b) Activation of the neuroendocrinal system, specifically the sympathetic nervous system, renin-angiotensin-aldosterone system and vasopressin release; c) Activation of autocrine and paracrine systems. However, when these systems are activated beyond a certain limit they contribute to heart failure aggravation. This can also be promoted by alteration of the calcium metabolism inherent in heart failure. The synthesis of the counterregulator atrial natriuretic factor is also increased.

Atrial Natriuretic Factor↗
PubMed1993

Increased thromboxane A2 production at primary tumor site in metastasizing squamous cell carcinoma of the larynx.

In order to evaluate the possible role of prostaglandins (PG) in invasion and metastasis of malignant cells in larynx carcinoma, arachidonic acid (AA) metabolite production by tumor tissue, peritumor tissue and node metastasis was investigated in comparison to that by healthy mucosa and unaffected lymph nodes. The study was performed by evaluating PGE2, 6ketoPGF1 alpha and thromboxane B2 (TXB2) production by radioimmunoassay in specimens from eight patients who underwent surgical treatment. The highest rate of AA metabolism was observed in peritumor tissue. PGE2 was the main metabolite produced in all tissues and its levels were significantly higher than those of 6ketoPGF1 alpha and TXB2 (p < 0.05). 6ketoPGF1 alpha production was higher (p < 0.01) than that of TXB2 and did not significantly change among the different tissues. TXB2 production was significantly increased (p < 0.05) by peritumor tissue as compared to healthy mucosa. The ratio between TXB2 and 6ketoPGF1 alpha production was found to be almost twofold higher in tumor tissue, peritumor tissue, metastatic and non-metastatic lymph nodes as compared to control tissue. The lowest AA metabolism was found in affected lymph nodes. These findings demonstrate a different AA metabolism at primary tumor sites in comparison to healthy mucosa suggesting a prometastatic role of TXB2 and supporting the hypothesis of the occurrence of an imbalance between TXB2 and 6ketoPGF1 alpha production in favouring metastatic spread.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Adjustable nylon ties for abdominal wall closure.

A study in 64 patients with a high risk of wound dehiscence or eviscerated wounds or in whom repeat laparotomies for peritoneal lavages due to sepsis were planned was accomplished using adjustable nylon ties for the closure of the abdominal wall, either as retention sutures or as one-layer sutures. The adjustable nylon ties are described, as well as the technique for placing and adjusting them. It is concluded that the adjustable nylon ties can substitute advantageously for the conventional retention sutures since the former are wider, easy to place, and can be readjusted to the point that they can be opened completely if it is necessary and then closed again. This is especially useful when repeat laparotomies for peritoneal lavages are required in patients with intra-abdominal sepsis.

Abdominal Muscles↗
PubMed1992

Monocyte tumor necrosis factor production in head and neck squamous cell carcinoma.

Changes in monocyte and macrophage function have been demonstrated in patients with head and neck squamous cell carcinoma. The purpose of this study was to evaluate tumor necrosis factor (TNF) production by activated monocytes from patients with head and neck squamous cell carcinoma and to evaluate its relation to cancer stage, weight loss, and performance status. Monocytes from patients (n = 10) and controls (n = 10) were isolated from peripheral blood mononuclear cells by plastic adherence and incubated with lipopolysaccharide (10 micrograms/mL). The TNF concentration of supernatants was assayed by TNF alpha-specific immunoassay. The TNF production by monocytes from head and neck squamous cell carcinoma patients was significantly higher (P less than .001) than those of controls. No significant relationship was found to cancer stage, weight loss, and performance status. These findings indicate that, in head and neck squamous cell carcinoma patients, an increased TNF production by activated monocytes takes place which does not correlate with cancer stage, cancer-related weight loss, and performance status.

Activities of Daily Living↗
PubMed1991

Changes in thromboxane A2 generation and plasma lipid pattern in pseudomenopause induced by gonadotropin releasing hormone (GnRH) analogue buserelin.

An increased risk of cardiovascular disease has been found in postmenopausal women in comparison to premenopausal women. The aim of this study was to investigate platelet function, blood clotting and plasma lipid levels in 12 women with a condition of hypoestrogenism, similar to the postmenopausal status induced by treatment with the GnRH analogue buserelin for uterine leiomyoma. Platelet aggregation in whole blood and platelet-rich plasma (PRP), serum thromboxane (TX) B2 production, fibrinopeptide A (FPA) plasma levels and plasma lipid pattern were measured before and after 13 weeks of buserelin treatment. No changes of platelet aggregability were found either in whole blood or PRP. Serum TXB2 generation increased significantly after 13 weeks of therapy (p less than 0.001). No signs of increased thrombin generation were found, as indicated by unchanged FPA plasma levels. Total cholesterol plasma levels were found increased after 13 weeks, LDL cholesterol levels showed a tendency to increase although not significantly. HDL cholesterol and triglyceride concentrations were unaffected. The changes of arachidonic acid metabolism and lipid pattern suggest that buserelin treatment may induce a condition of increased thrombotic risk even if the lack of enhanced thrombin generation and increased platelet aggregability indicates that no blood clotting activation occurs.

Adult↗
PubMed1990

Effects of long-term gestodene-containing oral contraceptive administration on hemostasis.

The purpose of this study was to evaluate the behavior of the hemostatic system during treatment with gestodene-containing oral contraceptives in monophasic (SHD 356, n = 15) and triphasic (SHD 415, n = 15) formulations. No changes in platelet (beta-thromboglobulin, platelet aggregate ratio, and megathrombocyte) and routine clotting assays were observed. Factor VIIc/factor VIIag ratio and fibrinopeptide A values showed a significant (p less than 0.005) increase after three cycles of both treatments. A slight, significant increase (p less than 0.01) in antithrombin III activity was observed during triphasic treatment. Protein C was unchanged. Fibrinolytic activity and plasminogen levels were significantly increased (p less than 0.05 and p less than 0.001). After 6 and 9 months, the factor VIIc/factor VIIag ratio was still significantly enhanced, whereas fibrinopeptide A values significantly (p less than 0.05) decreased, even if they were higher (p less than 0.05) than basal values. The persistence of factor VII activation without enhanced thrombin formation after long-term use of oral contraceptives suggests that at that time the activity of antithrombotic mechanisms counteracts the prothrombotic tendency, thus helping to minimize unwanted side effects on hemostasis during long-term drug administration.

Adolescent↗
PubMed1990

Cyclooxygenase and lipoxygenase metabolite synthesis by polymorphonuclear neutrophils: in vitro effect of dipyrone.

Functional activity of polymorphonuclear neutrophils (PMN) is associated with the metabolism of Arachidonic Acid (AA) released from membrane phospholipids. In this study the in vitro effect of dipyrone, a non steroidal anti-inflammatory drug, on the production of AA metabolites through cyclooxygenase (CO) and lipoxygenase (LO) pathways by stimulated PMN has been investigated. PMN isolated by counterflow centrifuge elutriator were greater than 98% pure and viable. Metabolite production was evaluated by RIA of Thromboxane A2 (TxA2), Prostaglandin E2 (PGE2), Leukotriene B2 (LTB4) and Leukotriene C4 (LTC4) after PMN stimulation with calcium ionophore A 23187 (20 microM). The levels of beta-thromboglobulin (RIA) lower than 5 ng/ml allowed us to rule out activation of residual contaminant platelets. In these experimental conditions, in the absence of dipyrone the products (ng/10(6) cells) of AA metabolism were LTB4 (3.51 +/- 0.22), LTC4 (0.81 +/- 0.08), TxB2 (0.144 +/- 0.025) and PGE2 (0.150 +/- 0.017). Incubation with dipyrone induced changes of PGE2 and TXB2 production in a dose dependent fashion (r = 0.83 and r = 0.87, p less than 0.001), obtaining already at the lowest drug concentration (5 micrograms/ml) a significant inhibition (33 and 40% for TxB2 and PGE2 p less than 0.005). No significant changes of LTB4 and LTC4 production have been observed. The results of this study indicate that dipyrone relevantly affects CO metabolite synthesis by stimulated PMN at concentrations comparable to those reached in therapeutic use. The inhibition of PGE2 synthesis which is present in inflamed tissues and actively participates in inflammatory reactions, could contribute to the therapeutic anti-inflammatory action of dipyrone.

Arachidonic Acids↗
PubMed1990

Sex related differences in platelet TxA2 generation.

Platelet lipid composition, c arachidonic acid (AA) metabolism by platelets (stimulated with thrombin), serum thromboxane (Tx)B2 production and plasma lipid composition were investigated in 53 healthy females (18-45 years) and 65 males (19-45 years) with similar dietary habits. In males, serum TxB2 production and cholesterol platelet membrane levels were found significantly higher (p less than 0.001 and p less than 0.05) than in females. No differences were observed between the two groups in the AA conversion through cyclo-oxygenase and lipoxygenase pathways or in the platelet phospholipid fatty acid composition. These findings indicate that in males the platelet proaggregatory capacity is greater than in females and the higher platelet TxB2 production does not depend on a larger AA availability or on enzyme activation for its conversion. The increased TxB2 production may be, at least in part, induced by functional differences such as a different membrane cholesterol content inducing, in its turn, an increased microviscosity and/or higher number of platelet receptors for thrombin.

8,11,14-Eicosatrienoic Acid↗
PubMed1990

Prostaglandins in squamous cell carcinoma of the larynx: tumor and peritumor synthesis.

Prostaglandin (PG) E2, 6ketoPGF1 alpha and Thromboxane B2 (TxB2) production by the tumor, peritumor and control tissue were investigated in specimens from patients (n = 11) with squamous cell carcinoma of the larynx, in relation to the extension and infiltration of the neoplasm and to the presence of inflammation, fibrosis and necrosis. In all specimens detectable amounts of 6ketoPGF1+ and TxB2 were found, but the predominant metabolite was PGE2. No differences in the levels of TxB2 and 6ketoPGF1 alpha were observed, but the only patient with lymphnodal involvement showed the lowest levels of 6ketoPGF1 alpha both in tumor and peritumor tissue. Higher amounts (p less than 0.05) of PGE2 were synthesized by peritumor tissues in comparison to control mucosa and tumor tissue independently of the occurrence of reactive infiltration. PGs synthesis did not correlate with inflammation, fibrosis, necrosis or staging of the neoplasm. However the two cases in stage T4 showed PGE2 generation at the highest levels both in neoplastic and perineoplastic tissue. These findings indicate that in squamous cell carcinoma of the larynx an increased production of PGE2 occurs, stemming not only from inflammatory cells but at least in part from neoplastic cells. This suggests that the study of arachidonic acid metabolism may contribute to characterization of the primary cancer and lead to better understanding of the mechanisms of tumor growth and diffusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Altered membrane fatty acid composition and increased thromboxane A2 generation in platelets from patients with diabetes.

Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in 42 diabetic patients (14 with macroangiopathic complications, 10 with microangiopathy and 18 without vascular complications) and in 42 clinically healthy subjects of similar age. All subjects were on a similar dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from all groups of diabetic patients produced increased amounts of TxA2 than platelets from controls (at least p less than 0.01) and patients with macroangiopathy (p less than 0.01). Platelet cholesterol and total platelet phospholipids were higher in patients with macroangiopathy, while the relative percentage of the different phospholipid fractions in platelet membrane and their saturated and unsaturated fatty acids were similar in the different groups. Arachidonic acid (AA) content in phosphatidylcholine (PC) was found to be significantly higher in diabetic patients than in controls (at least p less than 0.005). Moreover patients with macroangiopathy had higher AA (p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in PC (p less than 0.001) than the other groups of patients and controls.

Adult↗
PubMed1988

Platelet synthesis of cyclooxygenase and lipoxygenase products in type I and type II diabetes.

In 24 type I and 22 type II diabetic patients without vascular complications and in 25 controls platelet thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) production (by radioimmunoassay-RIA) and 1-14C arachidonic acid (AA) metabolism (by high pressure liquid chromatography-HPLC) after thrombin stimulation were studied. Platelets both from type I and type II diabetics generated larger amounts of TxB2 (p less than 0.001) and PGE2 (p less than 0.005) than controls, independently of the presence of retinopathy. No significant differences in platelet AA uptake or metabolism via the cyclooxygenase (CO) route, after thrombin stimulation (5 NIH U/ml), were observed in diabetic patients: lipoxygenase metabolites were found to be slightly, but significantly decreased. A positive linear relationship (r = 0.64, p less than 0.001) was found between HbA-1c and TxB2 production, but not with fasting plasma glucose. These results indicate that metabolic alterations can affect platelet function independently of vascular complications. The absence of alterations in intraplatelet 1-14C AA metabolism via CO, in the presence of increased TxB2 and PGE2 production from endogenous AA, suggests that the activation of CO is not the only possible mechanism of platelet activation and that probably an increased availability of platelet AA plays an important role in the enhanced platelet aggregation commonly found in diabetics.

Adult↗
PubMed1987

Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina.

Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase.

Acute Disease↗
PubMed1986

Platelet and coagulation functions during triphasic oestrogen-progestogen treatment.

The purpose of this investigation was the longitudinal evaluation of the hemostatic system before and after 1, 3, and 6 months of treatment with a triphasic oestrogen-progestogen combination. No changes of circulating platelet aggregates, as an index of in vivo platelet aggregability, and of megathrombocytes, an indirect evaluation of accelerated thrombocytopoiesis, were observed. A very slight, but significant, increase of Fibrinopeptide A (FPA), a reliable index of thrombin formation, was found only after 1 month of treatment; after 3 and 6 months, the increase of FPA was not homogeneous and not significant. Antithrombin III activity (AT III) showed no modifications after the first month; after 3 months AT III increased to a small extent, and after 6 months it was similar to basal values. Our findings indicate that the triphasic combination does not modify platelet functions and induces a low-degree activation of coagulation counteracted by an increased activity of the physiological inhibitors of blood clotting.

Adolescent↗