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Biomedical subjects

G Coata

Publications and source records attributed to G Coata.

14 recordsLinked to original sources
PubMed1999

Nitric oxide-releasing NSAIDs inhibit interleukin-1beta converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFalpha.

BACKGROUND: Nitric oxide (NO)-releasing NSAIDs are a new class of NSAID derivatives with markedly reduced gastrointestinal toxicity. Although it has been demonstrated that NO-NSAIDs spare gastric mucosal blood flow, molecular determinants involved in this effect are unknown. AIM: To investigate the effect of aspirin, naproxen and flurbiprofen, and their NO-derivatives, on gastric apoptosis and endothelial cell damage induced by tumour necrosis factor-alpha (TNFalpha). In other systems, TNFalpha-induced apoptosis is mediated by caspases, a growing family of cysteine proteases similar to the IL-1beta converting enzyme (ICE), and so we have investigated whether NO-NSAIDs modulate ICE-like endopeptidases. METHODS: Rats were treated orally with aspirin, naproxen and flurbiprofen, or their NO-releasing derivatives in equimolar doses, and were killed 3 h later to assess mucosal damage and caspase activity. Endothelial cells (HUVECs) were obtained from human umbilical cord by enzymatic digestion. Caspase 1 and 3 activities were measured by a fluorimetric assay using selective peptides as substrates and inhibitors. Apoptosis was quantified by ELISA specific for histone-associated DNA fragments and by the terminal transferase nick-end translation method (TUNEL). RESULTS: In vivo NSAID administration caused a time-dependent increase in gastric mucosal damage and caspase activity. NCX-4016, NO-naproxen and NO-flurbiprofen did not cause any mucosal damage and prevented cysteine protease activation. NSAIDs and NO-NSAIDs stimulated TNFalpha release. Exposure to TNFalpha resulted in a time- and concentration-dependent HUVEC apoptosis, an effect that was prevented by pretreating the cells with NCX-4016, NO-naproxen, NO-flurbiprofen, SNP or Z-VAD.FMK, a pan-caspase inhibitor. The activation of ICE-like cysteine proteases was required to mediate TNFalpha-induced apoptosis of HUVECs. Exogenous NO donors inhibited TNFalpha-induced cysteine protease activation. Inhibition of caspase activity was due to S-nitrosylation of ICE/CPP32-like proteases. NO-NSAIDs prevented IL-1beta release from endotoxin-stimulated macrophages. CONCLUSIONS: NO-releasing NSAIDs are a new class of non-peptide caspase inhibitors. Inhibition of ICE-like cysteine proteases prevents endothelial cell damage induced by pro-inflammatory agents and might contribute to the gastro-protective effects of NO-NSAIDs.

Animals↗
PubMed1996

Doppler velocimetry of different sections of the fetal middle cerebral artery in relation to perinatal outcome.

To assess the standard curves of pulsatility index (PI) in different segments of middle cerebral artery (MCA): initial segment (MI) and subcortical segment (M2); to determine the variation of the flow velocity waveforms (FVW) of the M1 and M2 segments of MCA in presence of fetal distress and to establish the possible correlation between the two segments of MCA. 50 normal pregnancies from 25 weeks of gestation to term and 20 pregnancy with alteration of fetal growth rate were investigated with serial records of the FVW of the M1 and M2 segments of the MCA and of the umbilical artery (UA) with a colour Doppler system. Severe fetal distress was associated to cerebral-placental ratio below 1 (C/P < 1). The perinatal outcome was established on the basis: 1) abnormal intrapartum CTG, 2) emergency cesarean section, 3) Apgar score at 1st and 5th minute after birth and 4) birth eight centiles. In normal pregnancy P1 of M2 was always higher than that of M1: therefore M2/M2 resulted below 1, with a maximum peak near 32 weeks of gestation. In presence of moderate fetal distress only P1 of M2 was reduced (M1/M2 > 1). It exists a significant difference of PI in M1 and M2 segments of fetal MCA during gestation: thus MCA so it is important to identify the tract of fetal MCA when recording its FVW. Moreover we suppose that an initial "cerebral sparing" effect exists in order to protect the cortex by the initial hypoxic injury: this is shown by a M1/M2 > 1. The progression of fetal distress results in a greater haemodynamic modification, the so called "brain sparing" which is usually present when C/P < 1.

Apgar Score↗
PubMed1995

Effect of low-dose oral triphasic contraceptives on blood viscosity, coagulation and lipid metabolism.

The purpose of the study was to determine the relationship between hemorheological profile, i.e. blood viscosity, and other risk factors for cardiovascular and thrombotic diseases in women taking oral contraceptives and if blood viscosity may be considered a marker of cardiovascular risk in OC users. Plasma levels of coagulation parameters, serum lipids, blood viscosity and RBC deformability were determined in a group of 10 women taking OC vs. 10 controls. The blood parameters were evaluated before OC use and thereafter at 3 and 6 months. A significant change in the partial thromboplastin time, fibrinogen, HDL and apolipoprotein A-I was observed, while the other parameters remained unchanged. Plasma viscosity was significantly increased during OC treatment; whole blood viscosity and RBC deformability remained unchanged. However, although some parameters were significantly modified during OC treatment, all alterations remained within the normal range of laboratory values. The data confirm that low-dose triphasic OC therapy does not affect significantly the coagulation system, serum lipid metabolism and blood viscosity. Plasma viscosity measurement may be considered as a marker for monitoring women using OC because it is apparently the most sensitive parameter.

Adolescent↗
PubMed1994

Management of postmenopausal osteoporosis.

More than 25% of postmenopausal women are at risk of osteoporosis. In order to avoid its consequences, it is necessary to find an appropriate prevention and/or treatment. We studied: (1) 15 postmenopausal women treated with percutaneous estradiol (50 micrograms/24 h) plus MPA (10 mg/10 days/month); (2) 15 postmenopausal women treated with synthetic calcitonin nasal spray at the daily dose of 100 IU; (3) 10 postmenopausal women treated with nandrolone decanoate (50 mg every 3 weeks); (4) 10 postmenopausal women treated with ipriflavone (600 mg/day); and (5) 10 postmenopausal women treated with sodium fluoride (20 mg) plus calcium (600 mg). Clinical examination, bone mass measurement (total BMD), hematochemical and urinary parameters of bone metabolism (calcium, urinary hydroxyproline, PTH) and growth factors (as IGF-I and TNF-beta) were evaluated. After 6 months of therapy, a complete prevention of bone resorption was achieved. In agreement with current literature, we observed that the various therapeutic approaches have all some positive effect on BMD, with different results on pain, blood biochemical parameters and growth factors' concentrations.

Aged↗
PubMed1992

Serum and salivary magnesium levels in migraine and tension-type headache. Results in a group of adult patients.

It has been suggested that magnesium plays a central role in different etiopathogenetic conditions involved in the onset of migraine. We measured, by atomic absorption spectrophotometry, serum and salivary magnesium levels in drug-free migraine patients with and without aura and in tension-type headache patients. Migraine sufferers with and without aura and tension-type headache had significantly lower levels of serum and salivary magnesium concentrations in the interical periods than a group of healthy young individuals. Serum magnesium levels tended to be further reduced during attacks in all patient groups studied. A statistically significant decrease in salivary magnesium levels was evident only for migraine patients with aura. Serum magnesium levels and to a lesser extent salivary magnesium levels might express indirectly the lowering of brain extracellular magnesium concentration which occurs in migraine patients both in the intererictal periods and ictally.

Adult↗
PubMed1992

Erythrocyte membrane composition in pregnancy-induced hypertension: evidence for an altered lipid profile.

OBJECTIVE: To investigate whether the increased membrane fluidity postulated as a possible contributing factor to the hypertensive states of pregnancy is related to the lipid composition of the erythrocyte membrane. DESIGN: An observational case control study. SUBJECTS: 30 women with pregnancy induced hypertension, 26 normotensive pregnant women matched for gestational age, and 10 normotensive non pregnant nulliparous women. INTERVENTIONS: Erythrocyte membranes were prepared from venous blood samples obtained from all the women. MAIN OUTCOMES MEASURES: Lipid analysis, including cholesterol to phospholipids ratio, distribution of phospholipid classes and fatty acid composition of total phospholipids in erythrocyte ghosts. RESULTS: The cholesterol/phospholipid ratio was significantly higher in the women with pregnancy induced hypertension compared with the normotensive pregnant women (mean 1.24, SD 0.31, 95% CI 1.12 to 1.35 vs mean 0.90, SD 0.09, 95% CI 0.86 to 0.94; P less than 0.01). Normotensive non-pregnant erythrocyte membrane cholesterol/phospholipid ratio was 0.88 (SD 0.11, 95% CI 0.79 to 0.96). The percentage distribution of different phospholipid classes and fatty acid composition was similar in all the four groups. CONCLUSIONS: The increased cholesterol/phospholipid ratio of the erythrocyte membrane found in pregnancy-induced hypertension represents one factor involved in the pathophysiology of this condition and a possible biochemical marker of the disease.

Adult↗
PubMed1992

Serum and salivary magnesium levels in migraine. Results in a group of juvenile patients.

In the last few years a fundamental role for magnesium in establishing the threshold for migraine attacks and involvement in the pathophysiologic mechanisms related to its onset has become evident. We measured serum and salivary magnesium levels in juvenile migraine patients (with and without aura) and in a group of healthy young individuals by atomic absorption spectrophotometry. Migraineurs were studied in migraine-free (interictal) periods and during attacks. In comparison with normal subjects, migraine patients had lower levels of serum and salivary magnesium interictally. Serum magnesium levels tended to be further reduced during attacks. With respect to the values of interictal periods we observed a reduction, not statistically significant, of salivary magnesium levels for both migraine groups. Serum, and to a lesser extent salivary magnesium level reduction, could be an expression, at the peripheral level, of reduced cerebral magnesium levels which would contribute, at least in part, to defining the threshold for migraine attacks.

Adolescent↗
PubMed1992

Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache.

Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.

Adult↗
PubMed1992

Abnormal platelet lipid membrane composition in pregnancy induced hypertension.

The cholesterol:phospholipid ratio (C/PL) was measured in platelet plasma membrane in patients with pregnancy-induced hypertension [with proteinuria (PE), and without proteinuria (PIH)] and in matched normotensive gestational controls (NT). The C/PL was raised in the platelet membrane from PE (1.52 +/- 0.50, 95% CI 1.13 to 1.90) and PIH (1.38 +/- 0.34, 95% CI 1.08 to 1.67) compared with that from NT controls (0.88 +/- 0.13, 95% CI 0.80 to 0.95) (p less than 0.01, ANOVA test). No correlation was found when C/PL was regressed against total serum cholesterol levels. The abnormality of lipid composition of the platelet plasma membrane could account for some of the changes in platelet function that have been described in PIH.

Blood Platelets↗
PubMed1990

A comparative chemometric study of QSAR descriptors.

Traditional descriptors for Qsar models are compared with two alternative blocks obtained by computer chemistry tools: electronic densities and principal properties. All three sets show similar prediction abilities by PLS modelling.

Models, Chemical↗
PubMedDate not supplied

Platelet thromboxane A2 receptor number and function in normal and hypertensive pregnancy.

PROBLEM: Our study evaluated the number and function of platelets for thromboxane A2/prostaglandin H2 (TxA2/PGH2) and the platelet response to TxA2 receptor agonists in normal and hypertensive pregnancy. In addition, correlations between platelet membrane lipid composition and TxA2 receptor number and function were evaluated. METHODS: Ten normotensive healthy pregnant women (GC), 10 hypertensive pregnant women (PIH), and 10 normotensive nonpregnant healthy women (C) were examined. Radioligand binding and aggregation studies were performed. Lipid composition of platelet membrane was assessed as cholesterol to phospholipids ratio (CH/PL) and normalized to protein content. RESULTS: TxA2/PGH2 receptor binding sites and affinity did not differ among the groups. An enhanced response to TxA2 receptor agonist U46619 in GC and in PIH compared to C was observed, while platelet response to thrombin was not different among the groups. CH/PL was altered in PIH respect to GC and C. No significant correlation was found between CH/PL and number and function of platelet TxA2 receptors in PIH. CONCLUSIONS: In PIH there is no alteration of number or function of TxA2 receptors on platelet membrane. However, the enhanced TxA2 production associated with the increased sensitivity of platelet to TxA2 in pregnancy may contribute to the microcirculatory thrombotic changes of PIH.

Blood Platelets↗
PubMedDate not supplied

Spermatozoa fertilization capability: multivariate data analysis.

The Hamster egg fertilization rate with human spermatozoa is one of the methods to estimate male fertility capability. The authors describe the statistical-mathematical method, PLS (Partial Least Square) to evaluate a cause-effect relationship between the Hamster egg fertilization level and the number and motile level of the spermatozoa.

Female↗