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Biomedical subjects

A Guerrero

Publications and source records attributed to A Guerrero.

At least 37 records · Page 2Linked to original sources
PubMed2004

Antioxidant effects of a single dose of acetylsalicylic acid and salicylic acid in rat brain slices subjected to oxygen-glucose deprivation in relation with its antiplatelet effect.

The aim of the present study was to analyze the relative participation of the antiplatelet and the antioxidant effects of acetylsalicylic acid (ASA) and salicylic acid (SA) after a single dose (1 or 10 mg/kg i.p.) in an in vitro model of anoxia in slices of rat brain. After 20 min of drug administration, blood and brain were obtained (n=6 rats per group). We measured: lipid peroxidation, glutathione levels and lactate dehydrogenase efflux (LDH), ASA and SA concentrations and platelet aggregation in whole blood. An increase in lipid peroxidation (80%) and in LDH efflux (520%) and a decrease in glutathione levels (35%) were observed after 120 min anoxia in saline-treated rats. SA reduced this oxidative stress and LDH efflux, but it did not modify platelet aggregation. ASA strongly inhibited platelet aggregation but exerted a poor antioxidant effect. ASA was not detectable in brain tissue. We conclude that repeated doses of ASA are necessary to obtain a tissular antioxidant effect, probably when liver generates enough SA.

Animals↗
PubMed2004

Antioxidant effect of acetylsalicylic and salicylic acid in rat brain slices subjected to hypoxia.

Acetylsalicylic acid (ASA) reduces the incidence of ischemic stroke mainly through its antithrombotic action; however, it also has a direct neuroprotective effect. The present study was designed to evaluate the effect of ASA on oxidative stress and the activity of nitric oxide synthase (NOS) in an in vitro model of hypoxia in rat brain slices. Rat brain slices were perfused with nitrogen (hypoxia) for a maximum of 120 min, after which we measured lipid peroxidation, glutathione levels, glutathione-related enzyme activities, and constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) activities. In brain tissue subjected to hypoxia, ASA reduced oxidative stress and iNOS activity (all increased by hypoxia), but only when used at higher concentrations. The effects of salicylic acid (SA) were similar but more intense than were those of ASA. After oral administration, the effect of SA was much greater than that of ASA, and the decrease in cell death with SA was seen much more clearly. In view of the greater effect of SA compared to ASA on changes in oxidative stress parameters in a model of hypoxia, and higher brain concentrations of SA when it is administered alone than when ASA is given (undetectable levels), we conclude that SA plays an important role in the cytoprotective effect in brain tissue after ASA administration.

Animals↗
PubMed2004

Formation of cartilage in aortic valves of Syrian hamsters.

The formation of cartilage in aortic valves of Syrian hamsters was studied using histological, histochemical and immunohistochemical techniques. The sample consisted of 281 specimens aged 0-363 days, all of which had a normal (tricuspid) aortic valve. The first sign of valvular chondrogenesis is the presence of small groups of cells embedded in a type II collagen-positive matrix. These groups of cells, which can appear as early as one day after birth, increase in size and differentiate into hyaline cartilage or fibrocartilage. From the fourth day of life, all hamsters examined displayed cartilaginous foci in the aortic valve. They were located along the fibrous attachments of the valve leaflets to their respective sinuses, including the valve commissures. A considerable proportion (76%) of cartilages formed within the first 40 days of life, that is during the period of time in which the histogenesis of the valve takes place. The present observations are consistent with the assumption that in mammals, the precursors of the aortic valve chondrocytes are neural crest-derived cells. Results of a statistical analysis substantiate that the incidence is significantly higher in (1) the territory that comprises the collagenous condensation of the ventral commissure and the ventro-lateral and proximal fibrous attachments of the right leaflet to its sinus, and (2) the proximal fibrous attachment of dorsal leaflet to its sinus. These findings together with data in the literature concerning the distribution of stress in each leaflet-sinus assembly of the valve during the cardiac cycle, suggest that mechanical action might play an inductive role in the formation of the cartilaginous tissue in the aortic valve of mammals. In addition, they point to the possibility that locally intense mechanical stimulation is responsible for the differentiation of the anticipated cartilaginous tissue into hyaline cartilage.

Aging↗
PubMed2004

Isolation and characterization of a lipoxygenase from Pseudomonas 42A2 responsible for the biotransformation of oleic acid into ( S )-( E )-10-hydroxy-8-octadecenoic acid.

The isolation of a new lipoxygenase-like (LOX-like) enzyme from Pseudomonas 42A2 and its characterization is described. The enzyme, located in the periplasm of the cell, which contained 0.55 mol of Fe2+ per mol of protein, is monomeric and has a molecular mass of 45 kDa. In the presence of oxygen, the enzyme converts oleic acid into (E)-10-hydroperoxy-8-octadecenoic acid (HPOD), which decomposes to the corresponding (E)-10-hydroxy-8-octadecenoic acid (HOD). The absolute configuration of this acid was determined as S on the basis of exciton-coupled CD data, and specific rotation and NMR analysis of the corresponding p -bromobenzoate derivative. The reaction in vivo leads to the dihydroxy derivative (E)-7,10-dihydroxy-8-octadecenoic acid (DHOD), so that the three hydroxy-fatty acids can be isolated from the culture medium. The activity of the enzyme was optimal between 25 and 30 degrees C and 44% of its activity still remained at 55 degrees C. Its optimal pH is 8.5-9; and the presence of magnesium ions increased LOX activity by 1.5. The activity of the LOX is highest in unsaturated fatty acids containing double bonds in position 9 (oleic, linoleic and linolenic acids), linoleic acid being preferred (100% activity) over linolenic (60.4%) and oleic acids (46%). However, kinetic studies showed that the affinity of the enzyme is similar for the three substrates.

Biotransformation↗
PubMed2004

Formation of cartilaginous foci in the central fibrous body of the heart in Syrian hamsters (Mesocricetus auratus).

The formation of cartilage in the mammalian heart has been studied in the aortic and pulmonary valves. The chondrogenetic process that takes place in the cardiac skeleton is still unknown. The present study was designed to illustrate the ontogeny of cartilaginous foci occurring in the central fibrous body of the Syrian hamster (Mesocricetus auratus) heart. Hearts from 472 animals aged 0-708 days were examined using histological, histochemical and immunohistochemical techniques. Cartilage was present in the central fibrous body of 118 (25%) specimens. A further 104 hamsters were used for the detection of calcific deposits in the central fibrous body. Six (5.8%) showed calcified cartilage. The first sign related to chondrogenesis was the presence of small groups of cells embedded in a type II collagen-positive extracellular matrix. These cellular groups, which can appear as early as 2 days after birth, differentiate into hyaline cartilage or, less frequently, into fibrocartilage. The highest production of cartilaginous foci takes place between days 40 and 80. Thereafter, formation of new foci is uncommon. This indicates that appearance of cartilage in the central fibrous body of the heart is not a consequence of cardiac aging. The cartilaginous foci seem to act as pivots resisting mechanical tensions generated during the cardiac cycle. Deposition of calcium in the extracellular matrix of the foci can be regarded as a reinforcement of the cartilaginous tissue.

Aging↗
PubMed2004

Vigabatrin-induced modification of Ki-67 expression in gingival epithelium: immunohistochemical study of a short series.

OBJECTIVE: To study the expression and role in vigabatrin (VGB)-induced gingival enlargement of Ki-67 antigen and p27KIP1, p21WAF1, and p53, proteins that activate or inhibit cell-cycle progression. MATERIALS AND METHODS: Six patients treated with VGB for partial epileptic seizures refractory to classic anticonvulsant treatment were studied. Gingival biopsies were taken from four of these patients for immunohistochemical studies; 10 control biopsies from individuals with healthy gingiva and 10 from patients with periodontal disease were also evaluated. RESULTS: Four of the six patients presented some degree of gingival enlargement (mild or moderate). Nuclear expression of Ki-67 was elevated (mean of 894 positive cells/mm2 in VGB-induced gingival enlargement vs. 391 cells/mm2 in controls with healthy gingiva and 425 cells/mm2 in controls with periodontal disease) (p < 0.01, analysis of variance: anova), and nuclear expression of cyclin-dependent kinase (cdk) inhibitors p27KIP1 and p21WAF1 was reduced. The patients with gingival enlargement presented inflammatory infiltrate in lamina propria, mainly composed of T lymphocytes (CD3+) and plasma cells (CD38+), which was even more intense than in the biopsies of patients with periodontal disease. CONCLUSION: The overexpression of antigen Ki-67 and slight underexpression of cdk-inhibitors p27KIP1 and p21WAF1 suggest that VGB induced an increase in cell proliferation and contributed, together with concomitant periodontal disease, to the gingival enlargement.

Adolescent↗
PubMed2004

Lethal toxicity after 5-fluorouracil chemotherapy and its possible relationship to dihydropyrimidine dehydrogenase deficiency: a case report and review of the literature.

5-fluorouracil (5-FU) is a chemotherapeutic agent widely used in the treatment of solid malignancies, especially in colorectal cancer. A characteristic note seen with its use is the considerable interindividual variation in the incidence and severity of the toxicities seen among patients. We report the case of a 55-year old woman who presented with severe, lethal toxicity to standard doses of 5-fluorouracil (5-FU) and folinic acid. We discuss the known clinical determinants of toxicity. We also discuss the possible molecular factors implicated in the variable toxicity seen to 5-FU, especially in regards to dihiyropyrimidine dehydrogenase, a pivotal enzyme in the metabolism of 5-FU.

Antimetabolites, Antineoplastic↗
PubMed2004

[Treatment of hyperphosphatemia with sevelamer in patients with chronic renal failure].

UNLABELLED: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate. RESULTS: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins. CONCLUSIONS: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.

Acid-Base Equilibrium↗
PubMed2003

Role of aluminous component of fly ash on the durability of Portland cement-fly ash pastes in marine environment.

The durability, of mixtures of two kinds of Spanish fly ashes from coal combustion (ASTM class F) with 0, 15 and 35% replacement of Portland cement by fly ash, in a simulated marine environment (Na(2)SO(4)+NaCl solution of equivalent concentration to that of sea water: 0.03 and 0.45 M for sulphate and chloride, respectively), has been studied for a period of 90 days. The resistance of the different mixtures to the attack was evaluated by means of the Koch-Steinegger test. The results showed that all the mixtures were resistant, in spite of the great amount of Al(2)O(3) content of the fly ash. The diffusion of SO(4)(2-), Na+ and Cl- ions through the pore solution activated the pozzolanic reactivity of the fly ashes causing the corresponding microstructure changes, which were characterized by X-ray diffraction (XRD), mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). As a result, the flexural strength of the mixtures increased, principally for the fly ash of a lower particle size and 35% of addition.

Coal↗
PubMed2003

Occurrence and densities of bacteriophages proposed as indicators and bacterial indicators in river waters from Europe and South America.

AIMS: To evaluate the feasibility of bacteriophages as a complementary tool for water quality assessment in surface waters from different parts of the globe. METHODS AND RESULTS: Faecal coliform bacteria, enterococci, spores of sulphite-reducing clostridia, somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis were determined by standardized methods in raw sewage and in 392 samples of river water from 22 sampling sites in 10 rivers in Argentina, Colombia, France and Spain, which represent very different climatic and socio-economic conditions. The results showed that the indicators studied maintained the same relative densities in the raw sewage from the different areas. Classifying the river water samples according to the content of faecal coliform bacteria, it can be observed that the relative densities of the different bacterial indicators and bacteriophages changed according to the concentration of faecal coliform bacteria. There was a relative increase in the densities of all groups of bacteriophages and sulphite-reducing clostridia with respect to faecal coliforms and enterococci in the samples with low counts of faecal coliform bacteria. CONCLUSIONS: The numbers of bacterial indicators and bacteriophages were similar in the different geographical areas studied. Once released in rivers, the persistence of the different micro-organisms differed significantly. Bacteriophages and spores of sulphite-reducing clostridia persisted longer than faecal coliforms and enterococci. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacteriophages in river water samples provide additional information to that provided by bacteria about the fate of faecal micro-organisms in river water. The easy, fast and cheap methods for phage determination are feasible both in industrialized and developing countries.

Bacteriophages↗
PubMed2003

The conus valves of the adult gilthead seabream (Sparus auratus).

The conus (bulbo-ventricular) valves of teleosts perform a key function in the control of blood backflow during ventricular diastole. However, the structural characteristics of these valves are almost unknown. This paper presents a systematic anatomical, histological and structural study of the conus valves of the adult gilthead seabream (Sparus auratus). S. auratus shows two major left and right valves consisting of the leaflet and the supporting sinus. Each valvar leaflet can be divided into a stout proximal body and a flap-like distal region. The proximal body is structured into three layers: a luminal fibrosa, a dense cellular core and a parietal fibrosa. The luminal fibrosa is a collagenous structure extending the entire length of the leaflet, while the parietal fibrosa is restricted to the most proximal area. The dense cellular core consists of fibroblastic cells and a matrix rich in glycoconjugates, collagen and elastin. The histochemical and structural data suggest that the luminal fibrosa bears most of the force associated with valvar closure, while the cellular core acts as a cushion dampening vibrations and absorbing the elastic recoil. The sinus wall is a fibrous layer which shows proximal-distal differences in thickness. It also shows compositional differences that can be related to mechanical function. We describe the presence of a fibrous cylinder formed by the sinus wall, the fibrous interleaflet triangles and the fibrous layer that covers the inner surface of the conus myocardium. This fibrous cylinder constitutes the structural nexus between the ventricle, the conus and the bulbus arteriosus, provides support for the conus valves and separates the valvar complex from the surrounding tissues. The structure of the conus valves in S. auratus is different from that found in other vertebrates. Anatomical similarities between the conus valves and the mammalian arterial valves are emphasized. Each phyletic group appears to have developed specific structures in order to perform similar functions.

Animals↗
PubMed2003

Differences in the effects of extended-release aspirin and plain-formulated aspirin on prostanoids and nitric oxide in healthy volunteers.

This study was designed to evaluate the effects of extended-release aspirin on platelet aggregation and the production of prostanoids and nitric oxide. The participants in this double blind, randomized and crossover study were 20 healthy volunteers. Interventions were 150 mg of plain-formulated aspirin (PFASA) and 150 mg of extended-release aspirin (ERASA). Blood samples were collected before and 10, 20, 60, 120, 240, 480 and 1440 min after the first dose; 3, 7 and 14 days after daily administration and 24 h after the last dose. The main measures were platelet aggregometry, thromboxane B2, 6-keto-prostaglandin (PG) F1alpha and nitric oxide in each control. Platelet aggregation was inhibited by 50% with ERASA, and by 77% with PFASA. No differences were found in chronic treatment. Thromboxane B2 was inhibited more by the latter (51-67%), but 90% inhibition was observed in both groups after 3 days. The levels of 6-keto-PGF1alpha was reduced by 20% with ERASA and by 58% with PFASA. Nitric oxide production increased in both groups, but after 24 h, and 7-14 days, elevated concentrations of nitric oxide were found only in the ERASA. The antiplatelet effects of ERASA provide pharmacological advantages (greater prostacyclin synthesis and prolonged increase in nitric oxide production) over those provided by the plain formulation.

Adult↗
PubMed2003

Effects of camonagrel, a selective inhibitor of platelet thromboxane synthase, on the platelet-subendothelium interaction.

The aim of this study was to compare the effects of a new thromboxane synthase inhibitor, camonagrel, on platelet aggregation and platelet-subendothelium interaction under flow conditions, in comparison with a standard thromboxane synthase inhibitor (dazoxiben) and a cyclooxygenase inhibitor (acetylsalicylic acid). With respect to platelet aggregation in whole blood, the 50% inhibitory concentrations (IC(50)) of camonagrel were between 318 and 797 micromol/l after induction with collagen and adenosine 5'-diphosphate, respectively. For inhibition of thromboxane B(2) synthesis, the IC(50) values were 868 +/- 68 micromol/l; prostaglandin E(2) was inhibited only by acetylsalicylic acid (IC(50) for camonagrel >2,000 micromol/l), and the leukocyte 6-keto-PGF(1alpha) level was increased by camonagrel. The greatest reduction in percentage subendothelial surface occupied by platelets (mainly in the thrombi) after blood perfusion was seen after incubation with camonagrel in the range of concentrations that inhibited collagen-induced platelet aggregation. In conclusion, camonagrel reduced platelet-subendothelium interaction under flow conditions, showing this effect in a range of concentrations lower than in inhibition of platelet aggregation.

Adolescent↗
PubMed2003

The effect of propofol on the interaction of platelets with leukocytes and erythrocytes in surgical patients.

UNLABELLED: We tested the antiplatelet effect described for propofol in vitro in surgical patients. Platelet aggregation induced by adenosine diphosphate, collagen, and arachidonic acid was tested in samples of whole blood, platelet-rich plasma (PRP), PRP with red blood cells, and PRP with leukocytes. Also measured were platelet production of thromboxane (Tx)B(2) and leukocyte production of 6-keto-prostaglandin F(1 alpha) (a stable metabolite of prostacyclin) and plasma levels of nitrites + nitrates (indicator of nitric oxide production). Anesthesia was induced with a bolus IV injection of sodium thiopental 4 mg/kg (n = 10), with a bolus dose of 2.5 mg/kg of propofol (n = 20), or with propofol total IV anesthesia (n = 20). Sodium thiopental did not modify any of the analytical values. In patients who received a bolus injection of propofol, platelet aggregation was significantly reduced in whole blood and in PRP + leukocytes. Platelet production of TxB(2) was reduced by 35%; the inhibition of 6-keto-prostaglandin F(1 alpha) was not statistically significant. Plasma levels of nitrites + nitrates increased by 37%; this change correlated significantly with the decrease in systolic and diastolic blood pressure (both P < 0.05). Similar changes, albeit of larger magnitude, were seen in patients who were given total IV anesthesia with propofol. In conclusion, propofol inhibited platelet aggregation in surgical patients mainly as a result of the inhibition of Tx synthesis and the increase in nitric oxide production. These effects are thought to be related to the hypotensive effect of this anesthetic. IMPLICATIONS: In vitro experiments have shown that propofol inhibits platelet aggregation and increases nitric oxide production. This study shows that doses habitually used to induce or maintain anesthesia also have these effects. These findings have potential applications for patients at increased risk for bleeding and may partly explain the hypotensive effect of propofol.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

Inmunoferon, an immunomodulator of natural origin, does not affect the rat liver cytochrome P-450 and phase II conjugation enzymes.

Inmunoferon is a glycoconjugate of natural origin with immunomodulatory properties. It has recently been shown to regulate TNF-alpha expression induced by lipopolysaccharide (LPS) challenge through a hypothalamo-pituitary-adrenal (HPA)-dependent mechanism. Inmunoferon is orally administered to immunocompromised patients as an adjuvant during immune therapy such as vaccination or infectious diseases treatment. Due to its mainly adjuvant nature, it is necessary to determine if coadministration of Inmunoferon affects the activity of other drugs. In this study we analyzed the possible modification of the hepatic drug biotransformation system by using Inmunoferon in a rat model, which may result in changes in the biological activity of other drugs administered simultaneously. Inmunoferon-treated animals showed no differences to control littermates in antipyrine metabolism. No differences were found in either cytochrome P-450 and b5 levels or cytochrome P-450-dependent activities and phase II conjugation enzymes in lysates from Inmunoferon-treated rat hepatic cells. The same treatment reduced levels of serum TNF-alpha in LPS-challenged animals. In summary, Inmunoferon is unable to affect the hepatic bioconjugation system during administration and thus seems unlikely to interact with, or modify the effect of, coadministered drugs.

Adjuvants, Immunologic↗
PubMed2002

Effects of S-adenosyl-L-methionine on lipid peroxidation and glutathione levels in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation.

We analyzed the effects of S-adenosyl-L-methionine (AdoMet) on tissue oxidative stress in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation. The thiobarbituric acid reactive substances (TBARS), total and oxidized glutathione, and lactate-dehydrogenase efflux (LDH) from tissue to the incubation medium, were measured. Brain slices were incubated without glucose and with N2, then glucose was added and O2 was perfused. After the anoxic-reoxygenation period, increase in TBARS, oxidized glutathione and LDH efflux, and decrease in total glutathione levels, were observed. The incubation with AdoMet before the anoxic period reduced TBARS (31-1000 micromol/l), glutathione production was increased (31-1000 micromol/l), LDH efflux decreased 6.41% with 15 micromol/l and 61.5% with 500 micromol/l). In the ex vivo experiments, we administered 50 mg/kg per day p.o., AdoMet for 3 days, then brain slices were collected and the anoxia-reoxygenation experiment was carried out. AdoMet led to the inhibition of brain lipid peroxidation and increased total glutathione production, after 3 h-reoxygenation. The increase of LDH efflux in non-treated rats was reduced by 77%. We conclude that AdoMet exerts citoprotective effects in an experimental model of brain slices reoxygenation after oxygen-glucose deprivation.

Animals↗
PubMed2002

Effects of two preparations of 75-mg extended-release aspirin on platelet aggregation, prostanoids and nitric oxide production in humans.

OBJECTIVE: The lowest dose of aspirin shown to be effective in the secondary prevention of thrombotic accidents is 75 mg/day. Presystemic acetylation of cyclooxygenase and the formation of salicylic acid in the liver are fundamental to ensure optimum antithrombotic effects of aspirin. This study was designed to compare the effects of two forms of extended-release aspirin (at 75 mg/day) on prostanoid and nitric oxide synthesis in healthy volunteers. METHODS: The participants in this single-blind cross-over study (n = 6) were randomly assigned to receive one of three different formulations: plain-formulated aspirin (PF), extended-release aspirin that released acetylsalicylic acid steadily over 5 h (EX5) or an extended-release formulation that released 49% of the drug during the first 2 h after intake (EX2) and the rest of the dose during the subsequent 5 h. Laboratory analyses were done for platelet aggregation and thromboxane B2 (in whole blood), 6-keto-prostaglandin F1alpha (in leucocytes), neutrophil nitric oxide production and plasma nitrite/ nitrate levels. RESULTS: The PF and EX2 formulations inhibited platelet aggregation by 97% with no significant difference in effect between the two. In contrast, maximum inhibition of aggregation by the EX5 formulation was only 30%. Similar effects were found for platelet thromboxane production: PF and EX2 led to 99% inhibition, whereas EX5 led to 76% inhibition (P < 0.05). The inhibition of prostacyclin production differed in all three treatments (63% for PF, 40% for EX2 and 24% for EX5). The increase in leucocyte nitric oxide production also differed in all three treatments (1.01-fold the basal value with PF, 1.4-fold with EX5 and 3.6-fold with EX2). Both extended-release formulations maintained high levels of nitric oxide production 24 h after the last dose, whereas in the PF period nitric oxide concentration had returned to basal values after this time. The changes in plasma nitrite concentrations in each period of treatment were similar to those seen for leucocyte nitric oxide. CONCLUSION: The pharmacodynamic profile of the extended-release formulations was better than that of plain-formulated aspirin in terms of thromboxane/prostacyclin balance and nitric oxide production. However, the EX2 formulation inhibited platelet function more effectively than did the EX5 formulation.

6-Ketoprostaglandin F1 alpha↗