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Biomedical subjects

R Franco

Publications and source records attributed to R Franco.

At least 181 records · Page 10Linked to original sources
PubMed1989

Bradykinin antagonism and prostaglandins in blood pressure regulation.

These experiments were designed to analyze the interaction of a bradykinin antagonist with prostaglandins in blood pressure regulation of normotensive rats. Male Wistar rats, divided into three groups, received a 5-minute intra-arterial infusion of the bradykinin antagonist [( DArgo-Hyp3-Thi5,8-DPhe7]BK-TFA) at 250 micrograms/min. Groups were either intact rats (group I, n = 5), pretreated with indomethacin (group II, n = 10), or pretreated with both indomethacin and prazosin (group III, n = 8). The bradykinin antagonist infusion, which was shown to inhibit exogenous bradykinin by greater than 76% in intact animals, did not alter mean arterial pressure in group I rats despite a twofold increase in norepinephrine and a threefold increase in epinephrine. Group II rats presented a progressive increase in mean arterial pressure during the bradykinin antagonist infusion (14 +/- 3 mm Hg), with no statistically significant change in plasma catecholamines. Group III, with lower baseline mean arterial pressure due to alpha 1-adrenergic blockade, had an increase in mean arterial pressure comparable with group II during bradykinin antagonist infusion (22 +/- 5 mm Hg), confirming that this response was not sympathetically mediated. We conclude that in normotensive rats bradykinin plays a role in blood pressure regulation that is closely linked to that of prostaglandins and that points to a balance between these systems.

Adrenergic alpha-Antagonists↗
PubMed1989

Theoretical study of the protonation and tautomerization of adenosine, formycin, and their 2-NH2 and 2-F derivatives: functional implications in the mechanism of reaction of adenosine deaminase.

A quantum chemical study of adenosine, formycin, and their 2-NH2 and 2-F derivatives is performed. The tautomerism of neutral and protonated species as well as the protonation of adenosine, formycin, and their derivatives are theoretically studied using semiempirical MNDO and AM1, as well as ab initio STO-3G methods. Calculations have been performed on a reduced model, in which the ribose moiety has been substituted by a hydroxy-methyl group. Results indicate that adenosine is mainly protonated at the N1 atom, whereas formycin can be protonated on N1 or N3, depending on the tautomeric form (N8-H or N7-H). The quantum chemical study of the N1-protonated molecules shows that a second protonation of adenosine is mainly on the N3 atom, whereas formycin can be protonated on N8 or N3, depending on the tautomeric form. On the other hand, results indicate that the protonation of formycin and its derivatives at the N1 atom leads to a change in their tautomeric preference from N7-H to N8-H. The importance of both tautomerism and protonation reactions in the mechanism of action of adenosine deaminase is studied by means of a quantitative structure activity relationships strategy. Significant correlations were found between several electronic parameters and the logarithm of the maximum rate of deamination (log Vm) of the studied compounds. For formycin and its derivatives, it was necessary to consider their N8-H tautomeric forms. The electronic parameters giving good correlations were as follows: energy of the minimum of the ab initio molecular electrostatic potential on N1, net charge over purine (pyrazolo-pyrimidine) and pyrimidine rings, and the N1 protonation energy. It must be noted that all these parameters are informative in relation to a proton attack. Adenosine and purine ribosides have been studied largely because of their high biological relevance. They are constituents of nucleic acids, intermediates in secondary metabolism, neuromodulators, and neurohormones. Their analogues have been extensively used because of their wide range of pharmacological effects (1). Formycin A (Fig. 1) is one of the most studied analogues of adenosine. It is a natural product extracted from Nocardia interforma (2) with proven antiviral (3-5), antibiotic (2), immunodepressant (6), antitumor (6), and antimetabolic (5) activities.

Adenosine↗
PubMed1988

Purification and partial characterization of brain adenosine deaminase: inhibition by purine compounds and by drugs.

Rat brain adenosine deaminase (E.C. 3.5.4.4.) was purified 667-fold from the supernatant fraction by the following techniques: heat treatment (60 degrees C), fractionation with ammonium sulfate, column chromatography on DEAE-Sepharose, and preparative gel electrophoresis. The purified enzyme was homogeneous by the criterion of polyacrylamide disc gel electrophoresis and isoelectric focusing. Amino acid composition is given. The isoelectric point of the enzyme (5.2) was determined by isoelectric focusing on agarose. The apparent molecular weight was estimated to be 39,000 (Stokes Radius [Rs] = 27.3 A) using a calibrated Sephacryl S-300 column. The study of the influence of the temperature on the initial reaction rates allowed calculation of Ea (8.9 Kcal/mole) and delta H (5.0 Kcal/mole) values. The variation of V and Km with pH suggests the existence of a sulfhydryl group and an imidazole group in the enzyme-substrate complex. The enzyme had a Km (adenosine) of 4.5 X 10(-5) M and was inhibited by inosine, guanosine, adenine, and hypoxanthine but not by other intermediates of purine metabolism. None of the inhibitors were active as substrates. The enzyme was also inhibited by dimethyl sulfoxide and ethanol. Inhibition by ethanol can account partially for the CNS depressant effects of levels 3 and 4 of alcohol intoxication. A number of drugs having therapeutic uses such as sedative, anxiolytic, analgesic, and relaxant are modulators of the enzyme. Among these, lidoflazine, phenylbutazone, and chlordiazepoxide are the most potent as inhibitors (Ki 30, 54, and 83 microM, respectively), whereas medazepam is the most potent as activator (Ka 0.32 mM). Thus, it is concluded that some drugs that inhibit adenosine uptake also modulate adenosine deaminase activity. Besides, since the enzyme is located extracellularly [Franco et al, 1986], these drugs can modulate the physiological effects exerted by extracellular adenosine.

Adenosine Deaminase↗
PubMed1988

Identification and rejection of outliers in enzyme kinetics.

A program (AICOUT) for the correct choice of the experimental value and weight for replicate enzyme kinetic determinations is given. It is based on the method of identification of outliers proposed by Kitagawa (Technometrics, 21 (1979) 193-199). The program is written in BASIC and FORTRAN77. The FORTRAN77 version of AICOUT program coupled to a FORTRAN77 version of the non-linear regression program previously published by Canela (Int J Biomed Comput, 15 (1984) 121-130) is given. This joint program leads to an improvement of precision and confidence in the estimated parameters when the suitable strategy is used. This strategy is as follows: (i) the experimental points are selected, (ii) several replicates of each point are performed, (iii) data are analyzed and outliers are rejected, (iv) normal or biweighted regression is carried out.

Algorithms↗
PubMed1988

Degradation of adenosine by extracellular adenosine deaminase in the rat duodenum.

1. Extracellular degradation of adenosine by adenosine deaminase was studied in the rat duodenum using high performance liquid chromatography (HPLC) and pharmacological techniques. 2. Relaxant responses to adenosine (1-10 microM) were potentiated in a concentration-dependent manner by erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and deoxycoformycin, both of which are inhibitors of adenosine deaminase. 3. Breakdown of adenosine, determined by HPLC, due to incubation with segments of rat duodenum was inhibited by both EHNA and deoxycoformycin. Cytosolic sources of adenosine deaminase were excluded. 4. Relaxant responses to adenosine were also potentiated by the adenosine transport inhibitor dilazep, which did not inhibit adenosine deaminase activity. 5. The extracellular adenosine deaminase activity (4 units/g tissue) was high compared with activity previously determined in other organs.

Adenosine↗
PubMed1988

Determination of the characteristics, properties and homogeneity of rat brain microsomes. Binding of lactate dehydrogenase, malate dehydrogenase and 5' nucleotidase to microsomal membranes.

Quantitatively, the amount of microsomes obtained using dimethyl sulfoxide is larger than that obtained from sucrose solutions (Centelles, Franco & Bozal (1986) Biol. Chem. Hoppe Seyler 367, 461-475). In this paper it is demonstrated that from a qualitative point of view they appeared to be indistinguishable with respect to molecular characteristics. Thus, both types of microsomes had the same behaviour in experiments of isopicnic ultracentrifugation with Percoll, isoelectric focusing and gel permeation. In these experiments, the 5'-nucleotidase, lactate dehydrogenase and malate dehydrogenase activities bound to the microsomal fraction were also studied. Lactate and malate dehydrogenase activities were always found in free and membrane-bound form. In contrast, 5'-nucleotidase activity was always encountered bound to microsomal membranes.

5'-Nucleotidase↗
PubMed1987

Subpopulations of T cells in lung biopsies from patients with pigeon breeder's disease.

Monoclonal antibodies were used to determine surface phenotypes of T cells in tissue obtained by open lung biopsies from patients with chronic hypersensitivity pneumonitis (pigeon breeder's disease). The results indicate that an increased number of suppressor/cytotoxic cells is present in these patients when compared with the number of helper/inducer cells. These findings, which were present within the interstitium, are consistent with those found in bronchoalveolar lavage of patients with this disease. In addition, in two-thirds of the patients there was a greater total number of helper and suppressor cells than the total count for Pan T cells. A possible interpretation of these findings might be the presence of both markers in the same cell.

Adult↗
PubMed1987

Simulation of the purine nucleotide cycle as an anaplerotic process in skeletal muscle.

A computer model of purine nucleotide and citric acid cycles joined through fumarate is given. Steady-state equations corresponding to metabolic enzymes are written based on the information from the literature about their kinetic behavior. Numerical integration of this set of equations is performed and in order to maintain an overall stabilization between the two cycles, enzymatic activities, in the form of V, have been calculated. Sensitivity coefficients for enzymes indicate that the control is exerted, depending upon the intermediate concentrations, and furthermore, it is demonstrated that AMP concentration in muscle should be very low. From stabilization, simulation of exercise conditions has been performed by diminishing [ATP] and increasing accordingly [ADP] and [AMP]. In such conditions the operation of purine nucleotide cycle leads to a considerable increase in the level of citric acid cycle intermediates. Disruption of purine nucleotide cycle by altering some of the three enzymatic steps leads to a lesser increase of these intermediates. The set of results presented seems to confirm the hypothesis that purine nucleotide cycle acts as an anaplerotic process in muscle, as the experimental results of Aragon and Lowenstein (Aragon, J.J., and Lowenstein, J.M. (1980) Eur. J. Biochem. 110, 371-377) suggest.

AMP Deaminase↗
PubMed1987

Distribution of adenosine deaminase in some rat tissues. Inhibition by ethanol and dimethyl sulfoxide.

The level of adenosine deaminase in various rat tissues has been tested. The enzyme activity of cytosolic fractions decreased in the following order: lung greater than spleen greater than small intestine greater than stomach greater than kidney greater than heart greater than liver greater than skeletal muscle greater than forebrain greater than cerebellum. The enzyme had identical patterns from tissue to tissue with respect to Km, V, and Ki values for ethanol and for dimethyl sulfoxide, with respect to electrophoretic behaviour and to inhibition by antibodies anti-rat brain adenosine deaminase.

Adenosine Deaminase↗
PubMed1987

Sympathoadrenal and other responses to hypoglycaemia in the young foal.

The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than in the neonates. No significant changes in glucose or catecholamines were seen after fasting alone. The adrenocortical response to hypoglycaemia was poor after birth, but significant changes occurred in the older foals with a 3-fold increase in plasma cortisol at 60 min after 0.5 i.u. insulin/kg. There were significant increases in plasma FFA after hypoglycaemia in both groups of animals, but the rise was less pronounced in the neonates. A significant positive correlation was found between plasma adrenaline and FFA values. Hypoglycaemia also resulted in a significant rise in plasma lactate and a slow fall in alpha-amino nitrogen. These findings show that hypoglycaemia in the foal is followed by stimulation of the adrenal medullary component of the sympathetic system and by activation of the adrenal cortex with a number of consequent metabolic changes. The hypoglycaemic effects of insulin were more intense and the response more rapid in the older foals than in the neonates, which exhibited some degree of insulin resistance.

Animals↗