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Biomedical subjects

D Valente

Publications and source records attributed to D Valente.

At least 19 recordsLinked to original sources
PubMed1998

Bromocriptine modulates P-glycoprotein function.

The multidrug resistance (MDR)-associated P-glycoprotein (P-gp) is a membrane transporter which carries, at the expense of MgATP hydrolysis, many amphiphilic molecules, such as the MDR-related cytotoxic drugs vincristine and vinblastine, and the MDR-reversing agents verapamil and progesterone. We have tested the effects on P-gp function of bromocriptine (BCT), an ergot alkaloid known as a D2 dopaminergic receptor agonist. BCT (at 4 microM) partially reverses the P-gp-mediated vincristine resistance of the Chinese hamster lung fibroblasts DC-3F/ADX, a MDR cell line. P-gp containing membrane vesicles prepared from the DC-3F/ADX cells exhibit, in the absence of any added drug, a basal MgATPase activity due to P-gp. BCT inhibits this basal ATPase activity, with a half-inhibiting concentration of 0.30 +/- 0.15 microM. BCT also inhibits the verapamil-induced P-gp ATPase stimulation competitively (Ki approximately 0.2 microM), and the progesterone-induced P-gp ATPase stimulation non-competitively (Ki approximately 0.07-0.10 microM). BCT also non-competitively inhibits the vinblastine-dependent P-gp ATPase activity within the same concentration range. Hydroxylated metabolites of BCT have different effects on P-gp ATPase, only the monohydroxylated being able to modulate both the basal and the drug-stimulated ATPase activities. In conclusion, these effects of BCT on P-gp function can be linked to a specific interaction with P-gp, probably involving inhibition of P-gp-mediated drug transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effect of variability of plasma interferences on the accuracy of drug immunoassays.

Most immunoassays applied to drugs in human plasma do not use an extraction of analyte. To compensate for interferences due to plasma proteins or salts, standards are prepared in drug-free plasma. Because the concentration of plasma components varies from one subject to another, it is likely that the drug-free plasma is not representative of the potential interference in each plasma. Using two immunoassays, for a steroid (nomegestrol acetate) and a heptapeptide (BN 52080), the authors have shown that tracer binding to the antibody may vary significantly between plasma from different subjects. Intersubject variability of tracer-antibody binding was 21.6% (coefficient of variation for 25 subjects) for nomegestrol acetate. When the same plasma were spiked with the steroid at a concentration corresponding to the central part of the standard curve, the recovery was between 39 and 215%. Intersubject variability in tracer binding was lower (7.7%) for the peptide immunoassay, but still affected accuracy. The authors show that this problem is common to direct immunoassays for other drugs and must be solved in assay development.

Drug Monitoring↗
PubMed1997

Metabolite involvement in bromocriptine-induced prolactin inhibition in rats.

Bromocriptine (BCT) is a dopamine D2 receptor agonist used for the treatment of Parkinson's disease and hyperprolactinemic disorders. After oral administration, BCT is metabolized into mono- or dihydroxylated metabolites. To study how these metabolites influence parent drug pharmacodynamics, we administered BCT to rats intravenously (1 mg/kg i.v.) and orally (10 mg/kg p.o.) and measured the inhibition of prolactin secretion. Despite similar areas under the curve for BCT, the duration of the effect was 36 h after oral and only 18 h after intravenous administration. Pharmacokinetic/pharmacodynamic models were used to correlate the concentration of BCT in the effect compartment with the lowering of prolactin. One of these models (effect compartment model) showed that the effective concentration (EC50) at the site of action was much lower after oral (0.56 nM) than after intravenous administration (3.68 nM). In contrast, the EC50 values based on BCT metabolite data were in the same range for both administrations. These observations suggested the activity of one or more BCT metabolites. To confirm this hypothesis, hydroxylated metabolites of BCT (produced in vitro by rat liver microsomes) were administered i.v. (100 microg/kg) in rats. We found that monohydroxylated BCT was able to lower prolactin secretion like BCT. Dihydroxylated metabolites, as well as monohydroxylated metabolites, were effective in reducing in vitro prolactin secretion. Because we demonstrated that the concentration of hydroxylated metabolites after oral administration is 55-fold that of BCT, it can be concluded that BCT activity in the pituitary after oral administration is mediated by its metabolites.

Animals↗
PubMed1996

Enzyme immunoassays for bromocriptine and its metabolites.

We have developed two bromocriptine enzyme immunoassays with different specificities for applications in human and animal pharmacokinetic studies. The first assay uses antibodies directed against the cyclopeptide structure of bromocriptine, and is specific for untransformed bromocriptine. The second assay uses antibodies directed against the bromolysergic part of the molecule and allows the measurement of both bromocriptine and its metabolites. Enzymatic tracers were obtained by covalent coupling of bromocriptine analogs to acetylcholinesterase from the electric eel Electrophorus electricus. Both assays have a limit of detection of 10 pg/ml and a limit of quantification of 50 pg/ml. The specificity of the assays was determined following fractionation by high-performance liquid chromatography of rat samples obtained after administration of bromocriptine.

Administration, Oral↗
PubMed1987

[Radiation-induced intestinal injuries].

Postoperative radiation after the removal of radiosensitive tumours may cause acute or chronic intestinal lesions. In some cases severe complications requiring one or more operations may arise even years later and unfortunately the morbidity and mortality rates are high. The paper presents a discussion of the clinical onset of these pictures as well as diagnostic and therapeutic possibilities in the light of personal experience and information obtained from the literature.

Humans↗
PubMed1987

Study of mediators of anaphylaxis in nasal wash fluids after aspirin and sodium metabisulfite nasal provocation in intolerant rhinitic patients.

Nasal histamine (H), leukotriene C4 (I-LTC4) and SRS-A activity were studied in seven aspirin-(ASA)-intolerant patients (AIR) with rhinitis and in five ASA-tolerant control patients with chronic rhinitis after nasal provocation (NP) with a lysine acetylsalicylate solution. The same parameters were also studied after metabisulfite (MBS) NP in four sulfite-intolerant patients with rhinitis and in six control patients with chronic rhinitis. In six ASA-intolerant subjects and in four controls, we studied the PGD2 levels in nasal washes after ASA NP 0.2 mL of lysine acetylsalicylate solution (10 mg/mL) was sprayed intranasally in ASA-intolerant patients and controls and a 25-mg/mL MBS solution in sulfite intolerant patients and controls. Nasal wash fluids were obtained using 5 mL of 0.15 M saline before and 7 1/2, 15, 30, and 60 minutes after nasal provocation. The nasal provocation with ASA induced itching and sneezing in four out of seven intolerant subjects. In this subgroup histamine values in nasal wash fluids were significantly higher versus the remaining ASA-intolerant patients at 30 and 60 minutes (P less than .05 and P less than .01, respectively) and versus controls at 60 minutes (P less than .01). We found significantly higher I-LTC4 (P less than .01) and SRS-A levels in nasal washes collected from ASA-intolerant subjects versus controls at 60 minutes after nasal provocation. There was no significant increase in the mean PGD2 values in either the ASA-intolerant or control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗
PubMed1986

A tetrodotoxin-like substance found in the Brazilian frog Brachycephalus ephippium.

A tetrodotoxin-like substance, denoted ephippiotoxin, was obtained from the tissue of Brachycephalus ephippium, a small pumpkin-coloured frog collected in the Atlantic Forest of the southeast region of Brazil. Ephippiotoxin is a dialyzable substance soluble in water, methanol and ethanol, but insoluble in organic solvents such as chloroform and other apolar solvents. After treatment with active charcoal (Norit-A) and purification with ion-exchange Amberlite IRC-50 resin (NH4 + form), a freeze-dried residue was obtained, with a toxicity of c. 117 micrograms/kg (mice, i.p.). Ephippiotoxin showed the same mobility as crystalline tetrodotoxin (Sankyo) when submitted to thin-layer chromatography (silica gel G) using seven different solvent systems. White mice (20 +/- 1 g) injected i.p. with either B. ephippium tissue extracts or semi-purified toxin showed partial paralysis of the hind limbs, lethargy, altered breathing rhythm and clonic convulsions. Death occurred within 1.5-30 min after injection, depending on the dose. Ephippiotoxin induced atrioventricular diastolic blockade in the toad heart. It also inhibited the response of toad striated muscle to direct and indirect electric stimulation and blocked the compound action potential of isolated frog sciatic nerve.

Action Potentials↗
PubMed1985

Early detection of pregnancy by new beta-hCG monoclonal urine test.

1,066 urine samples were assayed by beta-human chorionic gonadotrophin (beta-hCG) monoclonal pregnancy test with a sensitivity of 150 IU hCG/l. Tests were performed in 5 independent laboratories and results were compared with those of pregnancy tests which were used routinely. Urine samples which showed discordant results under evaluation were reassayed for beta-hCG using radioimmunoassay. 569 urine samples were from nonpregnant women, and a consistent result with comparison pregnancy tests was achieved in 97.19% of urine samples. The trial test from 389 urine samples of pregnant women was 99.49% in accordance with routine pregnancy tests. Results from 108 urine samples of women over 40 years of age indicate the high specificity of the new beta-hCG monoclonal pregnancy test. Titration experiments showed 63% positive tests at 150 IU beta-hCG/l. Data presented combine to suggest that this new monoclonal pregnancy test is a valuable aid in diagnosing early pregnancy. It may also be used in the diagnosis of tubal pregnancy and in other ectopic processes.

Adult↗
PubMed1984

A study on melanophore receptors of Papiliochromis ramirezi (Teleostei, Cichlidae).

Melanophores of Papiliochromis ramirezi aggregate their melanosomes in the presence of catecholamines. Their order of potency are: at 10(-4) M, norepinephrine greater than isoproterenol = epinephrine; at 10(-6) and 10(-8) M, norepinephrine = isoproterenol greater than epinephrine. These effects are antagonized not only by phentolamine but also by propranolol. The catecholamines are unable to induce pigment dispersion. Melanosome dispersion is obtained with cholinergic drugs and the order of potency is nicotine greater than acetylcholine = pilocarpine. Their effects are inhibited by atropine and also by d-tubocurarine and potentiated by physostigmine. The evidences suggest the presence of undifferentiated adrenoceptors, related to the melanosome aggregation and undifferentiated cholinoceptors related to the melanosome dispersion.

Acetylcholine↗
PubMed1983

Detection of morphine in urine by hemagglutination inhibition, with use of lyophilized reagents.

We describe a modified test of hemagglutination inhibition for the detection of morphine in urine, similar to the well-known test for pregnancy. The reaction takes place in test tubes or ampoules containing carefully matched amounts of lyophilized morphine antiserum and tanned human erythrocytes coated with morphine conjugated to rat serum albumin. The reagents are reconstituted by adding 100 microL of urine and 400 microL of water, and the result is read after 60 min. The detection limit, tested with the method of Gorodetzky (Clin Chem 19:753, 1973), was about 200 ng of total morphine per milliliter of urine. For more than 2000 samples, results by our test agreed satisfactorily with those obtained by an accepted RIA method. The test is suitable for rapid screening in field work, monitoring subjects during detoxication, and use in nonspecialized laboratories. Confirmatory analysis is needed for quantitative measurements, forensic purposes, and discrimination between morphine and cross-reacting opiates.

Cross Reactions↗
PubMed1979

[The role of renin after betablocking diuretic and vasodilator treatment in essential hypertension (author's transl)].

Ten patients affected by essential moderate or severe hypertension were given five sequential treatments, each for three weeks: 1) placebo, 2) chlorthalidone (Cl) 100 mg daily, 3) Cl 50 mg + oxprenolol slow release (Ox) 160 mg daily, 4) Ox 160 mg and 5) Ox 320 mg daily. Four subjects poor responders (DPB greater than or equal to 110 mmHg) received a later administration of Ox 160 + Cl 50 + hydrallazine (Hydr) 25-100 mg daily. Both groups of patients showed the greatest antihypertensive action with Ox 160 + Cl 50 mg daily. Oxprenolol induced a similar hypotensive effectiveness at 160, as well as 320 mg/day. Relationship between plasma renin activity (PRA) values and antihypertensive response to each treatment takes the following conclusions: 1) Basal PRA levels cannot be a guide for preferential choice of diuretic or betablocking therapy. 2) It is likely that renin activated by Cl and Hydr partially blunts their hypotensive activity. On the contrary, essential hypertension with normal or low PRA does not seem depending on angiogensinogenic factors. 3) Oxprenolol remarkably inhibits the overreninism induced by chlorthalidone and hydrallazine, in such way increasing their antihypertensive action. 4) In the management of essential moderate or severe hypertension is preferable to employ a mild dosage of betablockers and diuretics, rather than use higher doses of a single agent.

Adrenergic beta-Antagonists↗