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Biomedical subjects

V Gallardo

Publications and source records attributed to V Gallardo.

At least 37 records · Page 2Linked to original sources
PubMed1998

Plasma and platelet concentration and platelet uptake of serotonin in normal and pre-eclamptic pregnancies.

Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of pre-eclamptic hypertension. Platelets contain the largest storage of serotonin in peripheral blood and have the ability to take up this amine from surroundings, store and release it by several mechanisms. Plasma and platelet serotonin concentrations and platelet serotonin uptake have been measured in 8 non-pregnant women, 12 normal pregnant women and 8 women with severe pre-eclampsia. Plasma serotonin concentration was significantly higher in severely preeclamptic women, compared with age and gestation matched normal pregnant women. In addition, plasma serotonin concentration was directly related to systolic and diastolic blood pressure with severity of the syndrome. Furthermore, platelet serotonin concentration in women with pre-eclampsia was significantly higher than in non-pregnant controls, but it was not significantly different from the normal pregnant women. Moreover, serotonin is effectively taken up by platelets through a saturable transport process. The calculated apparent Km for serotonin uptake process did not differ significantly among non-pregnant women, normal pregnant women and women with pre-eclampsia. However, Vmax values were significantly higher in women with pre-eclampsia than in the normotensive pregnant women. As the actions of serotonin in the periphery could be terminated primarily by active uptake system by platelets and placenta, significant alterations in the rate of transport could result in physiologically significant changes in serotonin levels. These data raise the possibility that abnormal regulation of transporter function is involved in the etiology of pre-eclampsia.

Adult↗
PubMed1998

Mediation by 5-HT2 receptors of 5-hydroxytryptamine-induced contractions of human placental vein.

1. In isolated human placental chorionic vein segments, 5-hydroxytryptamine (5-HT; 10(-8) to 5 x 10(-5) M) elicited concentration-dependent contractions with EC50 = 5.5 (5.2-5.7) x 10(-8) M) and Emax = 93.1 +/- 7.3% of 75 mM KCl-induced contraction. 2. The agonist of 5-HT2 receptors, alpha-methyl-5-hydroxytryptamine, and the selective agonist of 5-HT1 receptors, N,N-dipropyl-5-carboxamidotryptamine and 5-carboxamidotryptamine, induced pronounced concentration-related contractions, which reached 71.1 +/- 6.0%, 53.0 +/- 5.0% and 75.0 +/- 7.8% at the highest dose tested, respectively. The agonist of 5-HT3 receptor, 2-methyl-5-hydroxytryptamine, reached a maximum averaging 36.7 +/- 5.1% of the maximal response to KCl. 3. The 5-HT1 and 5-HT3 receptor antagonists, methiothepin and metoclopramide (10(-7) to 10(-6) M) did not alter the response to 5-HT. However, ketanserin (10(-7) to 10(-6) M), a 5-HT2 receptor antagonist, induced significant inhibition of the concentration-response curve to 5-HT. 4. Contractile responses to 5-carboxamidotryptamine and 2-methyl-5-hydroxytryptamine were not affected by methiothepin and metoclopramide, respectively, whereas ketanserin significantly attenuated the contractile response to these agonists. 5. In conclusions, our study shows that 5-HT2 receptors mediate contraction of the human placental vein with no obvious role for 5-HT1-like, or 5-HT3 receptors.

Dose-Response Relationship, Drug↗
PubMed1997

Adsorption of a Corticoid on Colloidal Hematite Particles of Different Geometries

An electrokinetic study of the adsorption of a glucocorticoid drug, betamethasone disodium phosphate (BMP), on hematite (alpha-Fe2O3) particles is presented in this work. We analyze the electrophoretic mobility of both spherical and elongated hematite as a function of the concentration of BMP in the dispersion medium; it is found that, even for the lowest BMP concentration, the drug molecules adsorb onto the particles, changing their surface charge from positive to negative. When the drug concentration is increased between 10(-5) and 5 x 10(-3) M, the mobility of spherical hematite shows a monotonous increase from approximately -1.5 to approximately -3.5 &mgr;ms-1/Vcm-1; in the case of elongated particles, the mobility increases with BMP concentration up to 10(-4) M, larger concentrations of the corticoid having little effect on the electrokinetic properties of the particles. The effect of pH on the electrophoretic mobility of hematite is also investigated for two constant drug concentrations (0.05 and 0.5 mM); the isoelectric point of the particles is shifted to a pH below 3, another indication of adsorption of the negatively charged phosphate groups of BMP. These qualitative reasonings are confirmed by direct spectrophotometric determinations of the amount of BMP adsorbed on both hematite samples: spherical and ellipsoidal. The effect of pH on the adsorption density, Gamma, suggests that electrostatic interactions are not the only forces responsible for adsorption. In fact, although Gamma decreases with pH for both types of particles, it remains measurable up to pH 10, when strong electric repulsion is to be expected between hematite and phosphate groups. The effect of initial BMP concentration on Gamma is also studied. It is shown that a plateau region is reached in both samples, this indicating that their surfaces get saturated with BMP: the saturation begins when the coverage is of the order of approximately 1/8 (spherical particles) and approximately 1/40 (elongated particles) of a drug monolayer. Such difference might be due to the ellipsoidal hematite particles having a lower positive surface charge, since they are synthesized in a different dispersion medium.

Journal Article↗
PubMed1997

Relative potency of nitrovasodilators on human placental vessels from normal and preeclamptic pregnancies.

The relative potency of glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) was determined in human placental arteries and veins from normotensive gestants and preeclamptic women. This study demonstrates that the potency of the three nitrovasodilators is similar in normal and preeclamptic pregnancies. GTN and SNP behave as strong vasodilators and were significantly more potent as relaxant of venous than arterial segments. Meanwhile, SNAP was 1 order of magnitude less potent than GTN and SNP and is equally effective in reducing induced tone in arterial or venous segments. These observations suggest that the placental vessels obtained from normotensive and preeclamptic gestants resulted equally sensitive to the relaxant effect of each nitric oxide donor drug, and nitrovasodilators appear to be an interesting option for further clinical research on the prevention and management of preeclampsia.

Analysis of Variance↗
PubMed1996

Adsorption of betamethasone disodium phosphate on ethylcellulose latex: an electrokinetic study.

The use of polymer latexes as vehicles for drug transport and controlled delivery in the body is a very active research field in applied colloid science. In this work, the polymer chosen is a commercially available ethylcellulose-based material, Aquacoat. We report electrokinetic (electrophoresis) data on this polymer in the presence of the soluble glucocorticoid betamethasone disodium phosphate (BMP). The electrophoretic mobility of the particles becomes more negative as the concentration of BMP in the medium is increased between 10(-5) and 10(-3) M, this demonstrating that the negative species produced upon dissolution of BMP adsorb on the particles; this trend is reversed for higher concentrations due to the phenomenon of double layer thickness. When pH is increased at constant BMP concentration, the negative mobility increases in absolute value, but it reaches lower values than attained in the absence of BMP. This is interpreted as another consequence of adsorption, since the ionization constants of the phosphate and sulfate groups are different. Such adsorption is confirmed and measured by spectrophotometric analysis of the supernatants after centrifugation of the suspensions; it is found that the adsorption density increases with the initial concentration of BMP in the medium, an almost vertical isotherm being obtained for concentrations above 5 x 10(-3) M, possibly due to bidimensional aggregation of the adsorbed molecules and multilayer adsorption at higher concentrations. It is found that the adsorbed amount increases with the ionic strength of the medium as a consequence of screening of the particle and BMP charges, whereas these electrostatic contributions to adsorption manifest also in the pH dependence of adsorption. IR analysis of the particles after equilibration with BMP solutions of increasing concentration agrees well with adsorption data.

Adsorption↗
PubMed1996

Effect of amino acids on the stability properties of nitrofurantoin suspensions. Flocculation and redispersion compared with interaction energy curves.

The influence of the addition of amino acids, lysine, alanine and glutamic acid on the properties of nitrofurantoin suspensions was investigated. Flocculation and redispersability was investigated, taking into account the electrical properties of the nitrofurantoin/solution interface. We conclude that lysine and glutamic acid, but not alanine, would be suitable amino acids for control of the stability of nitrofurantoin suspensions.

Alanine↗
PubMed1995

Endothelial modulation of vascular tone and 5-hydroxytryptamine-induced responses in human chorionic arteries and veins.

1. In vitro studies were undertaken to evaluate the potential role of endothelium through release of vasodilators compounds on basal tension and on vasoconstrictor response induced by 5-hydroxytryptamine (5-HT) in chorionic arteries and veins rings from normotensive gestants. 2. N omega-nitro-L-arginine (100 microM) and methylene blue (10 microM) increased significantly the basal tension in chorionic arteries but not in veins. However, indomethacin (10 microM) inhibited the basal tension in both kinds of vessels. 3. The sensitivity to 5-HT was significantly lower in placental arteries than in veins. Removal of endothelium increased the sensitivity of placental arteries to 5-HT in 2.2-fold; however, in veins denudation had no significant effect. 4. N omega-nitro-L-arginine potentiated the 5-HT-induced tone in both types of vessels, but the increase of contraction was greater in chorionic arteries than in veins. However, indomethacin decreased the 5-HT-induced contractions in arteries and veins. 5. These results indicate that NO is more important than vasodilators prostanoids in the control of vascular tone and in 5-HT-induced placental contractile response.

Abortifacient Agents↗
PubMed1995

Nitric oxide and prostaglandin systems inhibition on the isolated perfused human placenta from normal and preeclamptic pregnancies.

Isolated human placental cotyledons from normal (NG) and preeclamptic gestants (PG) were perfused in vitro, and the effect of N omega-nitro-L-arginine (L-NA, 100 microM), methylene blue (MB, 50 microM), and indomethacin (INDO, 10 microM), on resting perfusion pressure and on the 5-hydroxytryptamine (5-HT)-induced vasoconstriction was established. In the HG, L-NA and MB increased resting perfusion pressure (p < 0.001) and INDO had no significant effect on resting pressure. In the PG, these agents did not significantly modify resting perfusion pressure. In the PG, 5-HT (10 microM-1 microM) caused greater maximal increases in perfusion pressure than in NG. In the NG, L-NA greatly enhanced the 5-HT-induced pressure, however INDO attenuated this effect. In the PG, L-NA did not modify significantly the 5-HT-induced response, but INDO reduced this response. These results suggest that basal release of nitric-oxide but not of vasodilator prostanoids may contribute to the low resting vascular tone in the NG and attenuates the strong vasoconstrictor effect induced by 5-HT. Impairment of action of nitric oxide could contribute to the enhanced pressor response to 5-HT observed in the PG.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Distribution of mast cells and the effect of their mediators on contractility in human myometrium.

OBJECTIVE: To examine the distribution of mast cells in human uterine tissue and to study the interactions between mast cell mediators (histamine and serotonin) and PGF2 alpha in human myometrium contractile activity. DESIGN: Distribution of mast cells were analysed in cryostat sections of myometrium samples stained with Toluidine blue. Contractile activity was evaluated in an isolated organ bath preparation on myometrial strips obtained from women whose pregnancies ended in elective caesarean section. SETTING: Biological Science Laboratories at the University of Concepción. SUBJECTS: Twenty women undergoing elective caesarean and 10 women undergoing hysterectomy at the G. Grant Hospital. MAIN OUTCOME MEASUREMENTS: Cumulative concentration-response curves for histamine and serotonin before and after the addition of subumbral concentrations of the PGF2 alpha or serotonin were performed. RESULTS: Serotonin was more active than histamine to evoke contractions (EC50:0.20 (SE 0.02) mumol/l vs 1.5 (SE 0.2) mumol/l, respectively). Furthermore, threshold concentrations of serotonin (0.05 mumol/l) potentiated the contractile effect of histamine (EC50:0.3 (SE 0.06) mumol/l and 50% increase in E(max)). PGF2 alpha had a poor contractile effect, but threshold concentrations (0.05 and 0.10 mumol/l) enhanced the contractile effect of both serotonin and histamine. A population of mast cells was found in close apposition to smooth muscle fibres. CONCLUSIONS: It is postulated that the simultaneous release of mast cell mediators (histamine and serotonin) in myometrium could be an important stimulus for evoking strong contractions in the human uterus. PGF2 alpha may have indirect effects in myometrium by amplifying the effects of histamine and serotonin.

Dinoprost↗
PubMed1993

Venous placental reactivity to serotonin in normal and preeclamptic gestants.

The effect of serotonin (5-HT) on the contractile activity of venous chorionic rings from normal and preeclamptic gestants was analyzed. The results indicate that the resting tension did not differ between the groups, but the spontaneous rhythmic contractions began earlier and were of higher amplitude in the preeclamptic group. Dose-response data indicate that venous segments from preeclamptic patients developed a 1.7-fold increase in sensitivity to 5-HT. These effects were accompanied by an increase in maximal isometric tension (Emax) and relaxation times. Decreased desensitization and lack of tachyphylaxis was observed in most of the vascular preparations from the preeclamptic group. These data suggest that 5-HT may have a role in the modulation of preeclampsia.

Chorionic Villi↗
PubMed1993

Serotonin-induced vasoconstriction in human placental chorionic veins: interaction with prostaglandin F2 alpha.

In vitro experiments using isolated rings and perfused segments of human chorionic veins, were designed to determine the effects of serotonin and their interaction with PGF2 alpha on vascular tension and perfusion pressure. These vessels responded vigorously with high sensitivity to the vasoconstrictor effects of serotonin in both experimental designs. Administration of PGF2 alpha also led to constriction of the veins, but this autacoid is at least 100 times less potent than serotonin. When adding PGF2 alpha previously to serotonin to the bathing fluid or to the perfusate, the serotonin response was significantly potentiated, increasing the maximal contractile response in 116 +/- 12% and the perfusion pressure in 180 +/- 25%. Both autacoids probably operate in this vascular bed interacting with each other and playing an important role in the regulation of placental blood flow in vivo.

Analysis of Variance↗
PubMed1991

Magnesium and potassium ions on tone and reactivity of human placental chorionic veins.

1. In vitro studies were undertaken to investigate the effects of external potassium [K+]0 2.4-7.1 mM and magnesium [Mg2+]0 0-4.8 mM concentration on human chorionic veins basal tone and on serotonin (5-HT)-induced contractions. 2. The higher the [Mg2+]0, the less the basal tension developed in isolated chorionic veins, irrespective of the [K+]0. 3. The EC50 value to 5-HT was enhanced by increases in [Mg2+]0, whereas the ability of 5-HT to induce a maximal contraction was attenuated. 4. The rightward shift of the concentration-response curves and reduced Emax response, observed when the concentration of [Mg2+]0 was raised, indicate a non-competitive antagonism of [Mg2+]0 with 5-HT. 5. The lack of an effect of [K+]0 on the EC50 and Emax values for 5-HT suggest that in this tissue the affinity of 5-HT for 5-HT receptors does not involve potassium. 6. These results suggest that basal tone and 5-HT-induced contractions of human chorionic vascular smooth muscle cells appear to be highly sensitive to alterations in extracellular Mg2+.

Chorionic Villi↗
PubMed1990

A study of the electrokinetic and stability properties of nitrofurantoin suspensions. I: Electrokinetics.

An experimental investigation is described of the electrokinetic properties of nitrofurantoin. The experiments are based on measurements of electrophoretic mobility in suspensions of this drug and the calculation of its zeta potential (zeta) following two different procedures. A simple mechanism is proposed for explaining the sign of the surface charge of nitrofurantoin and its increase with the pH of the medium. The effect on zeta of changes in the concentration of NaCl, CaCl2, or AlCl3 is studied for different pH values of the suspensions. The behavior of zeta in the presence of NaCl shows evidence of Cl- adsorption on the particles, especially at low electrolyte concentrations. The AlCl3 salt was capable of reversing the sign of the surface charge, changing it to positive when a given, pH-dependent concentration was added to the suspension. The effect of this salt on zeta for different pH values was probably due to the hydrolysis of the cation Al3+. A significant increase of the negative surface charge was observed when a small amount (0.1%) of a synthetic polymer, Carbopol 934, was present in NaCl or AlCl3 systems. This appears to indicate that the large polymer molecules adsorb on nitrofurantoin particles as part of their stabilizing mechanism.

Acrylic Resins↗
PubMed1990

A study of the electrokinetic and stability properties of nitrofurantoin suspensions. II: Flocculation and redispersion properties as compared with theoretical interaction energy curves.

The stability and redispersion properties of nitrofurantoin dispersions are experimentally studied using simple but reproducible techniques. Solutions of different electrolyte concentrations and pH values are employed as dispersing media. The pH appears to be a determinant factor in the properties studied. Thus, with all the electrolytes considered (NaCl, CaCl2, and AlCl3, almost optimum redispersion was achieved when the pH was maintained close to neutrality. However, the important effect of AlCl3 as compared with the other electrolytes is also clearly demonstrated. Especially interesting are the results obtained when 0.1% Carbopol is added to the suspensions. The important effect of this polymer on the surface charge of nitrofurantoin, mainly at pH 7, manifests in excellent redispersion of the suspensions with either of the electrolytes employed. Using simple expressions that approximate the equations proposed in the DLVO theory of interaction between colloidal particles, the variation of the total interaction energy between nitrofurantoin particles is calculated as a function of interparticle distance. The results are compared with the experimental determinations of the sedimentation and redispersion properties of nitrofurantoin. Although some discrepancies between theory and experiments are found, the results indicate a reasonable agreement between the general features of both.

Acrylic Resins↗
PubMed1990

Electrophoretic study of nitrofurantoin in aqueous suspensions. Effect of the addition of a polymeric thickener.

The electrophoretic mobility of nitrofurantoin (based on the microelectrophoresis method) has been studied in dilute dispersions of the drug. Specifically, the effect of NaCl, CaCl2 and AlCl3, pH, and a thickener, Carbopol 934, was determined. The electrophoretic mobility (mu) increases in absolute terms when the pH is raised between 3 and 9, although mu remains negative in this pH range. The variation of absolute mobility ([mu[) with NaCl concentration shows a pronounced maximum for a concentration of about 10(-4) M. However, when the concentration of CaCl2 in the medium is increased, [mu[ decreases steadily. The effect of AlCl3 concentration on the mobility is markedly influenced by the pH of the dispersing medium although a general trend is observed for mu to become more positive with increasing concentration of the salt. Finally, Carbopol 934 appears to impart an extra negative charge to the nitrofurantoin surface, since higher negative mobilities were measured in the presence of the polymer.

Acrylic Resins↗
PubMed1990

An improved topical formulation for urea.

The solubility of urea in different polar solvents was studied by means of determination of their dielectric constants. The most appropriate solvents turned out to be water and a water/propylene glycol (1:1 in volume) mixture. The best solvents were then used in the study of different semisolid vehicles for topical use (cetylic excipient, Beeler's base and Carbopol gel), which show different physicochemical characteristics. The final formulation contained a 40% (w/w) concentration in urea, since this value is most often used in Dermatology and, at the same time, it is the most problematic from a technological point of view. The stability of the different preparations was investigated by conductimetric and rheological determinations. The results are discussed in terms of both the solubility and stability of the active principles and the organoleptic and rheological characteristics of the final preparations.

Acrylic Resins↗
PubMed1985

Effects of ethanol ingestion on amino acid uptake in the dog liver in vivo.

The effect of ethanol ingestion on the uptake of labeled amino acids was studied in the in situ autoperfused dog liver. Ethanol was administered orally, as a 15% water solution, in a dose of 4 g/kg body weight/day as the only source of water for 2 days. Amino acid uptake was measured in anesthetized dogs by means of the single-passage, multiple-tracer dilution technique. In control animals, hepatic uptake of 14C-glycine, 3H-alpha-aminoisobutyric acid (3H-AIB) and 3H-L-leucine were 50, 15 and 66%, respectively. In the ethanol-treated dogs, glycine and AIB uptake was reduced by 70 and 63%, respectively. L-leucine uptake was reduced by only 23%. The plasma concentration of the naturally occurring amino acids was significantly increased after ethanol treatment, probably due to a reduced influx into hepatocytes. Simultaneous measurements of hemodynamic parameters showed a significant increase in the portal vein pressure of ethanol-treated animals, whereas the portal vein blood flow and hepatic extracellular volume were unaffected.

Amino Acids↗