Biomedical subjects

A Estevez

Publications and source records attributed to A Estevez.

16 recordsLinked to original sources

PubMed2004

Biosynthesis and catabolism of prostaglandin F2alpha (PGF2alpha) are controlled by progesterone in the rat uterus during pregnancy.

Myometrial quiescence is a key factor in all species to accomplish a successful gestation. PGs play a crucial role in mediating parturition events, and their synthesis and metabolism are regulated by cyclooxygenases (COXs) and NAD(+)-dependent 15-hydroxy-PG dehydrogenase (PGDH), respectively. Progesterone (P(4)) is the hormone responsible for maintaining uterine smooth muscle quiescence during pregnancy. In this work, we have studied the effect of P(4) on the activity of COXs and PGDH, the uterine enzymes involved in the biosynthesis and metabolism of prostanoids in the rat. We found that during pregnancy PGF(2alpha) production and also protein levels of COX-1 and COX-2 were decreased. The exogenous administration of P(4) significantly inhibited the uterine production of PGF(2alpha) and also the protein level of COX-2. PGF(2alpha), metabolism was assessed by PGDH activity, which resulted high during pregnancy and increased as a result of P(4) administration. These results indicate that PGs levels were negatively modulated by P(4), which could be exerting its effect by increasing PGs metabolism through stimulation on PGDH activity and an inhibition on COX and that is a major mechanism for maintain uterine quiescence in pregnancy.

Abortifacient Agents, Nonsteroidal↗

PubMed2003

Relationship between endothelin 1 and nitric oxide system in the corpus luteum regression.

The present study was designed to investigate the relationship between the nitric oxide (NO) system and endothelin 1 (ET-1) in the mechanism of corpus luteum (CL) development and consequently regression in rats. We first evaluated basal ET-1 levels in ovarian tissue from rats with different stages of CL development. An increased ovarian ET-1 content was found during CL regression. In a dose-department response, ET-1 decreased progesterone (P4) and increased prostaglandin (PG) PGF2alpha production. By means of a competitive nitric oxide synthase (NOS) inhibitor: L-nitro arginine methyl ester (L-NAME) and a slow NO releasing: diethyl-aminetriamine (DETA-NONOate), we demonstrated that NO system could be the intermediary in the ET-1 diminishing P4 production. The Western blot analysis revealed an increase on iNOS while eNOS protein expression was diminished. We also found a diminution of total NOS activity after ET-1 treatment. These data suggest the existence of a functional relationship between ET-1 and NOS isoforms leading the regulation of CL functionally.

Animals↗

PubMed2003

Sequence of interleukin 1beta actions on corpus luteum regression: relationship with inducible cyclooxygenase and nitric oxide synthase expression.

Corpus luteum regression has been described in terms of: (i) functional luteolysis - a reversible decline in serum progesterone concentration; and (ii) structural luteolysis - irreversible morphological changes and tissue remodelling events within the cellular membrane. In rats, PGF(2alpha) and interleukin 1beta (IL-1beta) are involved in structural luteolysis, PGF(2alpha) by increasing ovarian lipid peroxidation, and IL-1beta by reducing progesterone and increasing PGF(2alpha) concentrations. The aim of the present report was to determine whether by an early action IL-1beta is able to regulate functional luteolysis. Thus, ovarian explants from rats at the mid-stage of corpus luteum development were incubated during short periods with either 15 or 25 ng IL-1beta ml(-1). At 15 ng ml(-1), IL-1beta inhibited progesterone after 4 and 8 h of culture without affecting PGF(2alpha) production, and a longer incubation (21 h) was needed to increase PGF(2alpha) production. In contrast, IL-1beta enhanced PGF(2alpha) concentrations at 8 h only at the higher dose (25 ng ml(-1)). The observed reduction in progesterone synthesis at the lower dose of IL-1beta before the increase in PGF(2alpha) concentrations led to the hypothesis that IL-1beta regulates functional luteolysis (progesterone diminution) before it affects structural luteolysis (PGF(2alpha) increase). The fact that the early IL-1beta action was described at 4 h but no effects on inducible nitric oxide synthase and inducible cyclooxygenase expression were found before this time led to the suggestion that these inductions were not necessary for the early IL-1beta action described.

Animals↗

PubMed2002

Interleukin-1beta in the functional and structural luteolysis. Relationship with the nitric oxide system.

The aim of the present report was to investigate the in vitro effect of interleukin-1beta(IL-1beta) on corpus luteum (CL) function and some aspects of this mechanism involved. Ovarian rat dispersates from mid-luteal phase were exposed to different doses of IL-1beta (1, 10, 20 ng/ml). Meanwhile 1, 10 and 20 ng/ml of IL-1beta decreased progesterone (P4) production, only the highest doses of IL-1beta increased prostaglandin F2alpha (PGF2alpha) levels. To investigate the possible relationship between PGs production and P4 synthesis, we incubated together IL-1beta (20 ng/ml) and indomethacin (0.1 mM) a potent inhibitor of cyclooxygenase pathway. We found that P4 inhibition induced by IL-1beta was completely prevented by addition of indomethacin. On the other hand, when ovarian rat tissue were exposed at 20 ng/ml of IL-1beta (doses that affected both PGF2alpha and P4 production) the nitric oxide synthase (NOS) activity was augmented. Moreover, IL-1beta effects on PGF2alpha and P4 levels were impaired when a NOS inhibitor N(W)-nitro- L -arginine methyl ester (L-NAME, 600 microM) was added to the incubation media. These data demonstrate that: (i) at the tested doses (1-20 ng/ml), IL-1beta is involved in CL function through the diminution of P4 production of whole ovarian dispersate culture; (ii) at the highest doses assayed (20 ng/ml) IL-1beta increased PGF2alpha production; (iii) at these doses, IL-1beta decreased P4 production by means of a cyclooxygenase pathway and (iv) the NO system would be a key intermediary second messenger in the IL-1beta actions.

Animals↗

PubMed2001

Nitric oxide synthase activity in the splanchnic vasculature of patients with cirrhosis: relationship with hemodynamic disturbances.

BACKGROUND/AIMS: It has been demonstrated that an overproduction of nitric oxide plays an important role in the pathogenesis of the hyperdynamic circulation exhibited by cirrhotic patients. Nevertheless, evidence is supported by studies performed in experimental models or by indirect measurements in humans. The purpose of this study has been to evaluate nitric oxide production in splanchnic vasculature of patients with cirrhosis and to investigate its possible relationship with systemic and splanchnic hemodynamics. METHODS: Nitric oxide synthase (NOS) activity was measured in hepatic artery and portal vein tissues of nine cirrhotic patients. Samples were obtained during liver transplantation. Control samples were obtained simultaneously from the corresponding tissues of the liver donors. Hemodynamic parameters were determined with Doppler ultrasonography. RESULTS: NOS activity was significantly higher in hepatic artery of cirrhotic patients than in controls (8.17 +/- 1.30 vs 4.57 +/- 0.61 pmoles/g of tissue/min, P < 0.05). Patients with ascites showed a higher hepatic artery NOS activity than patients without ascites. Highly significant correlation was observed between cardiac output and hepatic artery NOS activity as well as between portal blood flow and hepatic artery NOS activity. CONCLUSIONS: The present study demonstrates an enhanced production of nitric oxide in the splanchnic vasculature of patients with cirrhosis.

Adult↗

PubMed2001

Dual effects of nitric oxide in functional and regressing rat corpus luteum.

The present study investigated the effect of nitric oxide (NO) on the lifespan of the corpus luteum (CL). Using a competitive nitric oxide synthase (NOS) inhibitor, L-nitro arginine methyl ester (L-NAME, 600 micromol/l), and a long-life NO donor, diethyl-aminetriamine (DETA-NONOate, 10(-8), 10(-6) or 10(-4) mol/l), we found that in ovaries from rats at the mid stage of CL development, endogenous NO increased both glutathione (GSH) and progesterone production. However, during prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis NO acted as an intermediary molecule in the inhibitory effect of PGF(2 alpha), on GSH content. This was supported by the fact that in-vivo PGF(2 alpha) treatment enhanced nitric oxide synthase (NOS) activity. These results indicate that the NO could act with a dual action (protective or pro-oxidant) in CL development.

Animals↗

PubMed2001

Regulation of lipid peroxidation by nitric oxide and PGF2alpha during luteal regression in rats.

Corpus luteum regression is related to an increased generation of reactive oxygen species. Although several studies indicate that PGF(2alpha) is involved in regression of the corpus luteum in mammalian species through an increase in reactive oxygen species, the exact mechanism remains unknown. In the present study, the relationship between nitric oxide and PGF(2alpha) in regulation of lipid peroxidation was studied. Ovarian tissue from pseudopregnant rats at mid- (day 5) or late phase or at the time of regression (day 9 of pseudopregnancy) of corpus luteum development was used. Thiobarbituric acid reactants, used as a lipid peroxidation index, were higher on day 9 of pseudopregnancy than on day 5. In contrast, glutathione content (an antioxidant metabolite) was lower on day 9 than on day 5 of pseudopregnancy. These results indicate that there was an enhanced oxidative status in ovarian tissue during luteolysis. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME: 600 micromol l(-1)), a competitive nitric oxide synthase (NOS) inhibitor, led to a decrease in basal thiobarbituric acid reactant content in ovarian tissue from rats on day 9 of pseudopregnancy only, indicating that during regression of the corpus luteum, NO could act as intermediary in ovarian lipid peroxidation. Administration of a luteolytic dose (3 microg kg(-1) body weight i.p.) of a synthetic PGF(2alpha) increased thiobarbituric acid reactant content in ovaries from rats on day 9 of pseudopregnancy. As this effect was reversed partially by L-NAME, it is proposed that during regression of corpora lutea, PGF(2alpha) and NO are involved in regulation of lipid peroxidation. As this effect was only reversed partially, it is possible that there is another mechanism involving PGF(2alpha) (but not the NO-NOS pathway) in regulation of ovarian lipid peroxidation. Furthermore, the administration of PGF(2alpha) enhanced ovarian NOS activity, whereas cyclooxygenase inhibition (by indomethacin treatment in vivo) reduced it. As western blotting of ovarian homogenates obtained from PGF(2alpha)-injected rats increased inducible NOS (iNOS) content, it is concluded that PGF(2alpha) enhances both activity and synthesis of NO in rat ovarian tissues during luteolysis. Taken together, these results indicate that in ovaries with regressing corpora lutea, both NO and PGF(2alpha) are involved in part in regulation of lipid peroxidation.

Animals↗

PubMed2000

Working memory capacity and time course of predictive inferences.

A naming task assessed activation of inference concepts during reading. A predicting, or a control, context sentence was followed by a target word to be named, which represented the predicted event or an inconsistent event. The interval between the end of the context and the onset of the target word varied between 50 and 1050 msec. Individual differences in working memory capacity were assessed by the reading span task. As reflected by facilitation in naming latencies in the predicting condition, relative to the control condition, (a) inferences were not made within the first 50 msec after the context, regardless of reading span; (b) only the high-span participants drew inferences within a 550-msec interval; and, (c) both the high- and the low-span participants generated them within a 1050-msec interval. These results indicate that high working memory capacity accelerates the time course of predictive inferences, although they do not become automatic. We propose that this effect occurs because these inferences involve time-consuming elaborations that place demands on the effortful and limited resources of working memory. Deficiencies in word knowledge, speed of lexical access, or comprehension of explicit information do not account for low-span readers' difficulties in generating predictive inferences.

Adult↗

PubMed2000

Hypercapnia induces injury to alveolar epithelial cells via a nitric oxide-dependent pathway.

Ventilator strategies allowing for increases in carbon dioxide (CO(2)) tensions (hypercapnia) are being emphasized to ameliorate the consequences of inflammatory-mediated lung injury. Inflammatory responses lead to the generation of reactive species including superoxide (O(2)(-)), nitric oxide (.NO), and their product peroxynitrite (ONOO(-)). The reaction of CO(2) and ONOO(-) can yield the nitrosoperoxocarbonate adduct ONOOCO(2)(-), a more potent nitrating species than ONOO(-). Based on these premises, monolayers of fetal rat alveolar epithelial cells were utilized to investigate whether hypercapnia would modify pathways of.NO production and reactivity that impact pulmonary metabolism and function. Stimulated cells exposed to 15% CO(2) (hypercapnia) revealed a significant increase in.NO production and nitric oxide synthase (NOS) activity. Cell 3-nitrotyrosine content as measured by both HPLC and immunofluorescence staining also increased when exposed to these same conditions. Hypercapnia significantly enhanced cell injury as evidenced by impairment of monolayer barrier function and increased induction of apoptosis. These results were attenuated by the NOS inhibitor N-monomethyl-L-arginine. Our studies reveal that hypercapnia modifies.NO-dependent pathways to amplify cell injury. These results affirm the underlying role of.NO in tissue inflammatory reactions and reveal the impact of hypercapnia on inflammatory reactions and its potential detrimental influences.

Animals↗

PubMed2000

Ultrasonography evaluation of retrobulbar hematoma in bovine orbits

As the proptotic eye is pushed anteriorly against the canthis, pressure within the eye increases until there is inadequate perfusion of the eye due to the pressure effects. computed tomography (CT) scan of the orbit is the most common method of diagnosing a retrobulbar hematoma. In the trauma/emergency department setting, where the wait for a CT scan may present significant delay, bedside ultrasonography may aid in the rapid diagnosis and treatment of a retrobulbar hematoma. OBJECTIVE: To establish concordance between orbital CT scan and a bedside sonographic orbital evaluation of a retrobulbar hematoma. METHODS: Eighteen of 22 bovine orbits were injected with a 10-mL mixture of calcium-treated banked blood and contrast into the retro-orbital space thereby effecting a retrobulbar hematoma. Each orbit was studied with CT and evaluated by a neuroradiologist. Four orbits were left intact as controls. Each orbit underwent an ultrasonographic evaluation. The ultrasonographer was first allowed to study an orbit with a documented hematoma and a control. Thereafter, he was blinded to the orbits containing hematoma, did not physically examine each orbit, and completed each exam in a darkened room. The CT results were correlated with the ultrasound findings. RESULTS: 15 of 18 orbits (83%) were correctly identified as containing hematoma by ultrasound. All four intact orbits were correctly identified as being free of hematoma (kappa 0.6). CONCLUSIONS: Bedside ultrasonography may aid in the rapid diagnosis of a retrobulbar hematoma.

Journal Article↗

PubMed1999

Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling.

Concentrations of up to 1.5 milliunits/ml xanthine oxidase (XO) (1.1 micrograms/ml) are found circulating in plasma during diverse inflammatory events. The saturable, high affinity binding of extracellular XO to vascular endothelium and the effects of cell binding on both XO catalytic activity and differentiated vascular cell function are reported herein. Xanthine oxidase purified from bovine cream bound specifically and with high affinity (Kd = 6 nM) at 4 degreesC to bovine aortic endothelial cells, increasing cell XO specific activity up to 10-fold. Xanthine oxidase-cell binding was not inhibited by serum or albumin and was partially inhibited by the addition of heparin. Pretreatment of endothelial cells with chondroitinase, but not heparinase or heparitinase, diminished endothelial binding by approximately 50%, suggesting association with chondroitin sulfate proteoglycans. Analysis of rates of superoxide production by soluble and cell-bound XO revealed that endothelial binding did not alter the percentage of univalent reduction of oxygen to superoxide. Comparison of the extent of CuZn-SOD inhibition of native and succinoylated cytochrome c reduction by cell-bound XO indicated that XO-dependent superoxide production was occurring in a cell compartment inaccessible to CuZn-SOD. This was further supported by the observation of a shift of exogenously added XO from extracellular binding sites to intracellular compartments, as indicated by both protease-reversible cell binding and immunocytochemical localization studies. Endothelium-bound XO also inhibited nitric oxide-dependent cGMP production by smooth muscle cell co-cultures in an SOD-resistant manner. This data supports the concept that circulating XO can bind to vascular cells, impairing cell function via oxidative mechanisms, and explains how vascular XO activity diminishes vasodilatory responses to acetylcholine in hypercholesterolemic rabbits and atherosclerotic humans. The ubiquity of cell-XO binding and endocytosis as a fundamental mechanism of oxidative tissue injury is also affirmed by the significant extent of XO binding to human vascular endothelial cells, rat lung type 2 alveolar epthelial cells, and fibroblasts.

Animals↗

PubMed1999

The involvement of nitric oxide in corpus luteum regression in the rat: feedback mechanism between prostaglandin F(2alpha) and nitric oxide.

In the corpus luteum (CL), prostaglandin F(2alpha) (PGF(2alpha)) is a physiological agent with luteolytic actions. Nitric oxide (NO) is a messenger molecule capable of modulating diverse pathophysiological processes. The aim of the present study was to investigate the role of ovarian NO in PGE (a luteotrophic prostanoid) and PGF(2alpha) (a luteolytic prostanoid) production and in progesterone synthesis during CL regression in the rat. To obtain a longer functional CL, we used a pseudopregnant (PSP) rat model. By means of intrabursa ovarian sac treatment of two competitive nitric oxide synthase (NOS) inhibitors, N(G)-monomethyl-L-arginine (L-NMMA, 1 mg/kg) and N(W)-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg), and sodium nitroprusside (SNP, 0.05 mg/kg) as a NO generator, we found that NO, produced by the ovarian tissue during the last 2 days of CL development (days 8 and 9), increased PGF(2alpha) production in the ovary and diminished serum progesterone concentrations leading to CL involution. We also proposed a positive feedback mechanism between PGF(2alpha) and NO, to ensure luteal regression. Thus, we injected intraperitoneally a luteolytic dose (3 microg/kg) of a synthetic PGF(2alpha) during the mid and late phase of CL development. Ovarian NOS activity was evaluated. The results confirmed our hypothesis; we did not see any effect in the mid-stage of CL development, but increased ovarian NOS activity was found in PGF(2alpha)-injected late pseudopregnant rats.

Animals↗

PubMed1999

On-line predictive inferences in reading: processing time during versus after the priming context.

Prior research suggests that predictive inferences take time to construct on-line. The present study examines the relative contribution of time available during and after reading an inducing context. In six experiments, we manipulated the presentation rate of the context and the delay between the onset of the last word in the context and a target word. A predicting, or a control, sentence context was followed by a target word, which represented the predicted event or an unlikely event. The results indicated that increasing the time available during reading of the context improved comprehension of explicit information, but it did not affect construction of inferences. In contrast, increasing the delay at the end of the context did not affect explicit comprehension, but it enhanced the probability of inferences, as revealed by shorter latencies in naming the predictable target word after the inducing context, relative to the control context. These findings show that readers defer making predictive inferences until 1 sec after the sentence context has been read, regardless of the time available when they are processing the context.

Adult↗

PubMed1997

Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic activity produced by spinal astrocyte monolayers.

In the present study we have assessed whether riluzole stimulates the production of trophic activities for motoneurons by spinal astrocyte cultures. Astrocyte monolayers prepared from new-born rats were exposed to vehicle or riluzole (1-10 microM) for 30-36 h, then washed and further incubated without riluzole for 24 h in L15 medium to obtain the astrocyte conditioned media (ACM). Motoneuron-enriched cultures were used to test the ability of the ACM to support motoneuron viability. Astrocyte monolayers exposed to 1 microM riluzole did not show changes in morphology or in DNA or protein synthesis. However, the conditioned medium obtained from astrocyte monolayers after this treatment increased motoneuron survival compared to that from vehicle-treated cultures. A similar effect was found when astrocytes were exposed to a higher riluzole concentration (10 microM) but with greater dilutions of the conditioned medium. This trophic activity was abolished by boiling or after treatment with trypsin. These findings strongly suggest the existence of a new trophic mechanism, through which riluzole may exert motoneuron protection.

Animals↗

PubMed1994

Ventricular mass in hypertensive and normotensive obese subjects.

Two-dimensional echocardiography was performed in 29 normotensive obese subjects and 21 hypertensive obese subjects representative of the Chilean population. The left ventricular mass (LVM) did not correlate with height or body surface area (BSA) in these patients, but positively correlated with body mass index (BMI), tricipital skinfold thickness and blood pressure (BP). The LVM/BSA ratio was significantly higher in the hypertensive subjects and was correlated with BP only. Left ventricular hypertrophy (LVM/BSA > 120 or 150 g/m2 in women or men, respectively) was found in 28% of normotensive and 58% of hypertensive subjects (P = 0.036). No statistical differences were found in relative wall thickness (RWT) between both groups. Posterior wall thickness was independently associated with BP while interventricular septum thickness was positively associated with the waist/hip ratio. Systolic function, evaluated through fractional shortening and end systolic diameters, was negatively and independently associated with body fat area. Left ventricular hypertrophy is a prevalent condition in these obese subjects. Hypertension seems to exert an additive effect, mainly increasing posterior wall thickness. Fat accumulation was negatively related to systolic function in this sample, irrespective of blood pressure.

Adult↗

PubMed1987

Normal serum proteins in female breast carcinomas and fibroadenomas. An immunohistochemical study.

Several serum proteins were immunohistochemically studied in benign and malignant breast lesions in 13 patients. The majority of infiltrating duct and lobular carcinomas showed albumin and IgG abundant immune reactive cells. Fewer cells contained immune reactive alpha-1-antitrypsin and transferrin. Staining was diffuse and limited to the cell cytoplasm. Immune reactive cells alternated with non reactive ones in a characteristic heterogeneous pattern. The parenchymal cells in carcinomas were non reactive to ceruloplasmin, fibrinogen and alphafetoprotein. Myoepithelial and epithelial cells in fibroadenomas were also positive for albumin and IgG, but less frequently for alpha-1-antitrypsin and transferrin. Normal breast tissue surrounding fibroadenomas as well as a lactational adenoma showed no immune reactive cells. Mechanisms that may be involved with the presence of plasma proteins in the cytoplasm of parenchymal cells in breast lesions are discussed.

Adenofibroma↗