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Biomedical subjects

P Mata

Publications and source records attributed to P Mata.

At least 19 recordsLinked to original sources
PubMed1998

Expression of inducible nitric oxide synthase after endothelial denudation of the rat carotid artery: role of platelets.

There is functional evidence suggesting that endothelial denudation stimulates inducible nitric oxide synthase (iNOS) activity in the vascular wall. In vitro studies have shown that iNOS expression in smooth muscle cells is reduced by endothelial cells. In the present study we have analyzed the time course of iNOS protein expression in the arterial wall after in vivo deendothelialization. Endothelial denudation was performed in the left carotid artery of Wistar rats, and the right carotid artery was used as control. Whereas iNOS protein was weakly expressed 6, 24, and 48 hours after endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after vascular damage. Because platelet adhesion and aggregation occur early after endothelial damage, we studied the role of activated platelets in the negative modulation of iNOS protein expression during the first 2 days after endothelial denudation. Early after in vivo endothelial injury, platelet-depleted rats showed a marked iNOS protein expression in the vascular wall. Similar results were obtained by blocking the platelet glycoprotein (GP) IIb/IIIa. Although iNOS protein is present in the arterial wall several days after endothelial denudation, early after arterial wall injury iNOS protein is weakly expressed. Platelets play a crucial role in preventing iNOS protein expression early after endothelial damage, an effect that can be avoided with GP IIb/IIIa blockers. Although iNOS protein was weakly expressed in vivo in the rat carotid artery wall 6, 24, and 48 hours after balloon endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after arterial damage. iNOS expression could be increased early after endothelial injury by removing circulating platelets and by an antibody against the GP IIb/IIIa. In conclusion, platelets prevent iNOS protein expression early after endothelial balloon damage, an effect that can be avoided with GP IIb/IIIa blocking agents.

Animals↗
PubMed1998

[Effects of dietary fat saturation on levels of plasma lipoprotein (a) and lipids].

BACKGROUND: Lipoprotein (a) (Lp[a]) is a known risk factor for coronary heart disease. Lp(a) plasma concentration mainly depends on genetic polymorphism. The aim of this study was evaluate the effect of dietary fat saturation on Lp(a) plasma concentration. SUBJECTS AND METHODS: Forty two subjects (eighteen women and twenty four men) were placed in four consecutive 5 weeks diet periods. Energy intake from proteins, carbohydrates and fats was constant during the study and there were only changes on fatty acids composition. First period was enriched in saturated fatty acids (SFA), second period in monounsaturated fatty acids (MUFA) and third and fourth periods were enriched in polyunsaturated fatty acids (PUFA). Fourth period was also enriched in PUFA n-3 (blue fish). RESULTS: Changes on dietary fat saturation had a significant effect on plasma lipids and lipoproteins. Lp(a) plasma concentration was minimum in SFA phase (6.8 [SD 7.3] mg/dl), increasing during MUFA phase (8.7 [8.5] mg/dl) and was maximum in PUFA n-6 and PUFA n-3 (11.5 [11.1] and 12.7 [11.9] mg/dl, respectively) (p < 0.0001). CONCLUSIONS: Changes on dietary fat saturation significantly modify Lp(a) plasma concentration. These variations went in opposite direction to LDL-cholesterol modifications and were clinically irrelevant.

Adult↗
PubMed1998

Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric oxide synthesis by human neutrophils.

Recent studies have suggested that the protective anti-ischemic effects of acetylsalicylic acid are stronger than the inhibition of platelet thromboxane A2 synthesis. Since ischemic events still occur in acetylsalicylic acid-treated patients, the development of new drugs with more powerful protective effects is needed. We compared the effects of a new platelet antiaggregating drug, 2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and of acetylsalicylic acid on the interaction between human neutrophils and platelets, examining the capability of neutrophils to generate nitric oxide (NO). Triflusal, in the presence of neutrophils, showed a greater antiplatelet potency than acetylsalicylic acid to inhibit thrombin-induced platelet activation. Significant stimulation of NO-mediated mechanisms in the presence of acetylsalicylic acid or triflusal was demonstrated by the following findings: (1) increased metabolism of arginine to citrulline, (2) increase of cGMP in the platelet/neutrophil system and (3) the inhibitory action of the L-arginine (L-Arg) competitive analogue, NG-nitro-L-arginine-methyl ester (L-NAME), which was reversed by L-Arg. Triflusal increased the stimulation of NO synthesis by neutrophils more than did of acetylsalicylic acid. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), alone or in combination with acetylsalicylic acid, did not modify NO production by neutrophils. Therefore, the whole molecule of triflusal is needed to stimulate NO production by neutrophils. Our results show that, in the presence of neutrophils, triflusal exerts an antiplatelet effect greater than that of acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP system. The present results indicate that it is possible to develop new and more potent acetylsalicylic acid-related antiplatelet drugs for the prevention of the myocardial ischemic/reperfusion processes.

Aspirin↗
PubMed1998

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Adult↗
PubMed1997

Effects of dietary fat saturation on eicosanoid production, platelet aggregation and blood pressure.

The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n-6 (PUFA n-6); and polyunsaturated n-6/n-3, (PUFA n-3)]. Each diet period lasted 5 weeks. There were no differences in 24-h 2,3-dinor-6- keto-prostaglandin F1 alpha excretion among dietary periods. A significant effect was noted regarding the excretion of 11-dehydro-thromboxane B2 (P < 0.0001). During the PUFA n-6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 mumolL-1) and collagen (2 mgL-1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Monounsaturated and polyunsaturated n-6 fatty acid-enriched diets modify LDL oxidation and decrease human coronary smooth muscle cell DNA synthesis.

Proliferation of smooth muscle cells (SMCs) plays an important role in atherosclerotic lesion progression. The purpose of this investigation was to examine the effect of diets differing in fatty acid composition on human coronary SMC entry in the cell proliferation cycle. Twenty-four healthy men and women were placed on four consecutive diets lasting 5 weeks each: (1) saturated fatty acid (SFA)-rich diet with palm oil; (2) monounsaturated fatty acid (MUFA)-rich diet with olive oil; (3) polyunsaturated fatty acid (PUFA) n-6-rich diet with sunflower oil; and (4) PUFA n-3-rich diet (3.8 g/d). All diets supplied 35% of calories as fat. Compared with the SFA diet, all unsaturated diets reduced LDL cholesterol. Resistance of LDL to oxidative modification was significantly increased during the MUFA period (P < .05). Human coronary SMCs were cultured and induced by sera derived from the different groups. 3H-Thymidine incorporation into doubling DNA was significantly (P < .01) reduced during the MUFA and PUFA n-6 periods but not during the PUFA n-3 diet with respect to the SFA diet. This effect was more pronounced in women than in men. In conclusion, the MUFA-enriched diet reduced SMC DNA synthesis and LDL levels and protected LDL from oxidation. Therefore, these combined effects suggest that an oleic acid-rich Mediterranean diet could be better than PUFA (n-6)- or PUFA (n-3)-rich diets in the prevention of atherosclerosis.

Cell Division↗
PubMed1997

[Pravastatin increases the activity pf the LDL receptors in lymphocytes of individuals with heterozygous familial hypercholesterolemia].

An investigation was conducted on the effects of pravastatin, an inhibitor of the HMG CoA reductase, on lipoproteins concentrations and degradation of LDL (low density lipoproteins) in 14 patients with familial hypercholesterolemia (FH). Therapy with pravastatin for twelve weeks, 20 mg every 12 hours, and a low fat (30% calories) and cholesterol (less than 300 mg/daily) diet decreased serum concentrations of LDL cholesterol and apolipoprotein B by 35.5% and 24%, respectively (p < 0.001 for both parameters). On the other hand, apolipoprotein A-1 concentrations increased by 15.1% (p < 0.05) and HDL cholesterol (high density lipoproteins) by 6.8%; concentrations of apolipoprotein A-II did not change. LDL degradation in peripheral lymphocytes increased by 41.3% (p < 0.05) and a correlation was observed (p < 0.05) between percentage of LDL degradation and percentage in the LDL cholesterol decrease. Likewise, a positive trend (p = 0.057) was observed between increases in LDL degradation and aging. These findings indicate that pravastatin favorably influences the lipoprotein profile and that this effect is mediated, at least partly, by an increase in cellular capacity of LDL degradation.

Adult↗
PubMed1996

Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro.

Forty-two healthy men and women were subjected to four consecutive dietary periods differing in the fat content of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (n-6) [PUFA(n-6)] and (n-3) [PUFA(n-3)]. Plasma lipids, vitamin E, and in vitro LDL oxidation were examined during each period. Adhesion of human monocytes to cultured human endothelial cells was used as a functional test to identify differences in the biological properties of LDL from each dietary period. Consumption of an SFA-rich diet resulted in higher LDL cholesterol (4.06 +/- 0.85 mmol/L, P < .05) than did consumption of MUFA- (3.59 +/- 0.75 mmol/L), PUFA(n-6)- (3.44 +/- 0.77 mmol/L), or PUFA(n-3)- (3.31 +/- 0.8 mmol/L) rich diets. HDL cholesterol was lower during both PUFA-rich diets (1.24 +/- 0.28 and 1.27 +/- 0.28 mmol/L for n-6 and n-3, respectively) than during the SFA-(1.32 +/- 0.36 mmol/L) and MUFA- (1.32 +/- 0.34 mmol/L) rich diets. LDL resistance to copper-induced oxidation, expressed as lag time, was highest during the MUFA-rich diet (55.1 +/- 7.3 minutes) and lowest during the PUFA(n-3)- (45.3 +/- 7 minutes) and SFA- (45.3 +/- 6.4 minutes) rich diets. LDL induction of monocyte adhesion to endothelial cells was lower during the MUFA-rich diet than the other periods. The highest monocyte adhesion was obtained during the PUFA(n-3) and SFA dietary periods. In conclusion, an MUFA-rich diet benefits plasma lipid levels compared with an SFA-rich diet. Furthermore, this diet results in an increased resistance of LDL to oxidation and a lower rate of monocyte adhesion to endothelial cells than the other dietary fats examined.

Adult↗
PubMed1995

Gene-diet interaction in determining plasma lipid response to dietary intervention.

It has long been known that there is an extremely high degree of variability in both human and nonhuman primates in terms of low density lipoprotein cholesterol (LDL-C) lowering in response to restriction of dietary saturated fat and cholesterol. In this regard we have reviewed the current knowledge regarding the gene-diet interaction in relation to plasma lipid response to dietary intervention. Several candidate gene loci have been examined in humans: apolipoprotein (apo) A-I, apo A-IV, apo B, apo C-III and apo E, as well as lipoprotein lipase (LPL). Several mutations at these loci have been found to be associated with responsiveness. We and others have documented that subjects carrying the apo E4 allele are more responsive with regard to LDL-C lowering in response to dietary fat and cholesterol restriction than subjects carrying the apo E3 or apo E2 alleles, whereas some studies report no association of apo E phenotypes with lipid response to some dietary interventions. Our own meta-analysis indicates that apo E genotype effects are modulated via alterations of amount and type of dietary fat. We have also documented that subjects carrying the common glutamine for histidine mutation at amino acid 360 of apo A-IV are significantly less responsive in terms of LDL-C lowering than subjects with the normal apo A-IV genotype is modulated via changes in dietary cholesterol. In addition, we have documented that the common G/A mutation within the promoter region of the apo A-I gene is associated with greater responsiveness of LDL-C to dietary fat alterations. The XbaI and insertion/deletion polymorphisms at the apo B gene locus and the HindIII restriction fragment length polymorphism (RFLP) at the LPL locus have also been associated with diet responsiveness. Therefore, in humans these gene loci account for a significant portion of the variability in plasma lipid response to dietary alterations.

Animals↗
PubMed1994

ApoA-IV phenotype affects diet-induced plasma LDL cholesterol lowering.

The National Cholesterol Education Program (NCEP) recommends that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/d, respectively (step 1 diet), in the general population to reduce plasma low-density lipoprotein cholesterol (LDL-C) levels and heart disease risk. We examined the LDL-C-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/d cholesterol) compared with an average American diet (39% fat, 15% saturated fat, and 435 mg cholesterol/d) in 153 subjects using diet periods of 4 through 24 weeks for each diet phase. The mean LDL-C reduction was 13% in men (n = 93) and 7% in postmenopausal women (n = 60). The effect of apolipoprotein (apo) A-IV phenotype on responsiveness was examined. LDL-C lowering in men was significantly (P < .005) less (7%) for 17 apoA-IV (1/2) subjects than for 76 apoA-IV (1/1) subjects (16%). In women, 7% lowering was observed in both 12 apoA-IV (1/2) subjects and 48 apoA-IV (1/1) subjects. ApoA-IV phenotype had a significant effect on plasma high-density lipoprotein cholesterol levels during both dietary periods; women carrying the apoA-IV-2 allele had higher levels than those homozygous for the apoA-IV-1 allele. The opposite was true for triglyceride levels, but only during the period when the subjects consumed the high-fat, high-cholesterol diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of apolipoprotein E phenotype on diet-induced lowering of plasma low density lipoprotein cholesterol.

The National Cholesterol Education Program (NCEP) has recommended that dietary total fat, saturated fat, and cholesterol intake be reduced to < or = 30% of calories, < 10% of calories, and < 300 mg/day, respectively (Step 1 diet) in the general population to reduce plasma low density lipoprotein (LDL) cholesterol levels and heart disease risk. We examined the LDL cholesterol-lowering response to such a diet (26% fat, 8% saturated fat, and 201 mg/day of cholesterol) as compared to an average American diet (39% fat, 15% saturated fat, and 435 mg/day of cholesterol) in 128 subjects using diet periods of 4-24 weeks for each diet phase. The mean LDL cholesterol reduction was 15% in males (n = 83) and 8% in post-menopausal females (n = 45). The effect of apolipoprotein (apo) E phenotype on responsiveness was examined. LDL cholesterol lowering in males was 14% for 60 apoE3/3 subjects, 23% for 10 apoE3/4 subjects, and 16% for 13 apoE3/2 subjects. Male apoE3/4 subjects had a significantly greater LDL cholesterol reduction (P = 0.006) and a greater decrease in the LDL/HDL ratio (P = 0.047) than apoE3/3 subjects. In females, 7% lowering in LDL cholesterol was observed in 34 apoE3/3 subjects and 11% lowering was observed in 7 apoE3/4 subjects (P = 0.12). A meta-analysis of data from published studies supports this conclusion. These data indicate that apoE phenotype modulates the LDL cholesterol-lowering response to a diet meeting NCEP Step 1 criteria, and that male subjects carrying the apoE4 allele are more responsive than other subjects.

Adult↗
PubMed1993

SPROUT: a program for structure generation.

SPROUT is a new computer program for constrained structure generation that is designed to generate molecules for a range of applications in molecular recognition. It uses artificial intelligence techniques to moderate the combinatorial explosion that is inherent in structure generation. The program is presented here for the design of enzyme inhibitors. Structure generation is divided into two phases: (i) primary structure generation to produce molecular graphs to fit the steric constraints; and (ii) secondary structure generation which is the process of introducing appropriate functionality to the graphs to produce molecules that satisfy the secondary constraints, e.g., electrostatics and hydrophobicity. Primary structure generation has been tested on two enzyme receptor sites; the p-amidino-phenyl-pyruvate binding site of trypsin and the acetyl pepstatin binding site of HIV-1 protease. The program successfully generates structures that resemble known substrates and, more importantly, the predictive power of the program has been demonstrated by its ability to suggest novel structures.

Artificial Intelligence↗
PubMed1993

Immunohistochemical study of intracranial cysts.

We present the immunohistochemical study of 11 cases of intracranial cysts: two extraventricular ependymal cysts, three colloid cysts of the third ventricle, four extraventricular choroidal cysts and two Rathke's cleft cysts. Antibodies against glial fibrillary acidic protein (GFAP), cytokeratins (AE1, CK5D, AE3), S-100 protein, epithelial membrane antigen (EMA), vimentin, neuron specific enolase (NSE), neurofilaments protein (NF) and prealbumin, were used. The epithelium of choroidal cysts, showed strong immunoreactivity for Prealbumin and cytokeratins, similar to the normal choroid plexus epithelium. The ependymal cysts showed epithelial immunoreactivity for GFAP and S-100, both glial markers expressed by the normal ependymal epithelium. On the contrary, the epithelial wall of colloid cysts and Rathke's cleft cyst, expressed epithelial markers (cytokeratins and EMA) but no neuroepithelial markers, with a immuno-phenotype similar to that of other cysts of endodermal nature. This finding supports the neuroepithelial origin for choroid and ependymal cysts, and an endodermal nature for colloid and Rathke's cleft cysts. We conclude that these immunohistochemical markers are useful in the differential diagnosis of intracranial cysts.

Brain Diseases↗
PubMed1993

[Effects of n-3 polyunsaturated fatty acids on the cardiovascular system. Should their use be recommended?].

The effects of n-3 polyunsaturated fatty acid (n-3 PFA) intake on lipoprotein metabolism, eicosanoid metabolism, coagulation and the fibrinolytic system, mediators of inflammation, and blood pressure are discussed. The possible role such effects may have on the process of atherogenesis is examined. Laboratory animal studies with n-3 PFA supplements are reviewed. Finally, a review of clinical and epidemiological studies in human subjects is made in order to evaluate whether the experimental findings have clinical relevance. The conclusion is that, at the present time, there is insufficient support for the use of n-3 PFA supplements either in prophylaxis or in treating ischemic cardiopathy.

Animals↗
PubMed1992

Effects of long-term monounsaturated- vs polyunsaturated-enriched diets on lipoproteins in healthy men and women.

The effect of dietary-fat saturation on plasma lipoprotein concentrations was assessed in 46 men and 32 women placed on a diet enriched in polyunsaturated fatty acids (sunflower oil) for 12 wk and, under isocaloric conditions, on a diet enriched in monounsaturated fatty acids (olive oil) for the next 16 wk in men and 28 wk in women. Fat comprised 37% of the total energy intake in men and 36% in women. At the end of the monounsaturated fatty acid diet no change occurred in total cholesterol (TC) in men but it increased by 9% in women. High-density-lipoprotein (HDL) cholesterol increased by 17% in men and by 30% in women. The atherogenic index (TC:HDL cholesterol) fell significantly in both sexes. No significant changes occurred in plasma low-density-lipoprotein cholesterol or in total triglycerides values. These data show that when compared with polyunsaturates, monounsaturates increased HDL cholesterol and reduced the atherogenic risk profile in both sexes.

Adolescent↗