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M Abreu

Publications and source records attributed to M Abreu.

27 records · Page 2Linked to original sources

Synthesis of some 3-(1-azabicyclo[2.2.2]octyl) 3-amino-2-hydroxy-2-phenylpropionates: profile of antimuscarinic efficacy and selectivity.

A series of 3-quinuclidinyl atrolactate [3-(1-azabicyclo[2.2.2]octyl) 2-hydroxy-2-phenylpropionate, QNA] derivatives in which the methyl group of the parent is substituted with a tertiary amino substituent was prepared and tested for antimuscarinic activity. In general, potency was markedly decreased, although the morpholinyl and thiomorpholinyl derivatives retained significant activity. These compounds were also examined for muscarinic receptor subtype selectivity. Their subtype selectivities were comparable to that of (R,R)-QNA. The results of this investigation suggest possible differences in the accessory binding sites of the proteinaceous receptor subtypes.

Animals↗

The effect of wheat bran on the excretion of cadmium in rats.

The influence of wheat bran as a source of dietary fibre on the excretion of ingested cadmium from diet was studied. The cadmium contents in the diets, faeces, urine, liver, kidney and spleen were determined, as well as the weight gains, the relative weights of the cited organs, and the levels of alkaline phosphatase in serum. No evidence is provided that an increasing portion of wheat bran in the diets induced an increase in cadmium excretion. Changes in the studied toxicity parameters were not found.

Alkaline Phosphatase↗

Characterization of adenosine receptors in the PC12 pheochromocytoma cell line using radioligand binding: evidence for A-2 selectivity.

Examination of the binding characteristics of the adenosine agonist radioligands [3H]N6-cyclohexyladenosine [( 3H]CHA), [3H]cyclopentyladenosine [( 3H]CPA), and [3H]5'-N-ethylcarboxamido adenosine [( 3H]NECA) to membranes prepared from PC12 cells showed that the A-1-selective ligands (CHA and CPA) had minimal binding, which was not amenable to analysis using curve-fitting programs. However, [3H]NECA, a nonselective A-1/A-2 agonist, gave reproducible binding, which was enhanced by removal of endogenous adenosine, using the catabolic enzyme adenosine deaminase. This binding was of high affinity (KD = 4.7 nM) with limited capacity (263 fmol/mg of protein). Specific binding of [3H]NECA was unaffected by the presence of either CPA (50 nM) or MgCl2 (10 mM) but was sensitive to guanylylimidodiphosphate (100 microM), a finding suggesting involvement of an N-protein mechanism in the coupling of the adenosine receptor labeled by [3H]NECA to other components of the receptor complex. Binding of [3H]NECA to PC12 cell membranes was stereo-selective, with the R isomer of N6-phenylisopropyladenosine (PIA) being approximately 12 times more active than S-PIA. The A-1-selective agonist CPA was a weak inhibitor of [3H]NECA binding (Ki = 251 nM). The rank order of activity of adenosine agonists in displacing specific [3H]NECA binding was NECA greater than or equal to 2-chloroadenosine greater than CHA greater than or equal to 5'-N-methylcarboxamido adenosine greater than or equal to R-PIA greater than CPA greater than S-PIA. Binding was also displaced by the marine adenosine agonist 1-methylisoguanosine and by a series of xanthine antagonists with the activity order being 1,3-dipropyl-8-(2-amino-4-chloro)phenylxanthine greater than 8-phenyltheophylline greater than 8-p-sulfophenyltheophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Cardiac effects of lead.

Symptoms consistent with cardiac disease have been noted as part of the syndrome of lead (Pb) intoxication. All types of cardiotoxicity noted in patients have been reproduced in experimental animals exposed acutely to high concentrations of Pb, or chronically exposed to lower levels. Types of cardiac effects observed include negative inotropism and electrocardiogram abnormalities, particularly conduction defects. Neonatal rats exposed to Pb via the milk of dams provided a drinking solution of lead acetate exhibit approximately four times the sensitivity to the arrhythmogenic effect of norepinephrine as adults compared with controls. Cardiotoxicity occurs after exposure as short as the first 10 postnatal days, but is not expressed until the rats are adult. Increased sensitivity to the arrhythmogenic effect of norepinephrine was seen in Pb-exposed animals in vivo and in isolated hearts from Pb-exposed animals in vitro. Norepinephrine arrhythmogenesis in vivo was attenuated by atropine or vagotomy, which indicates vagal nerve involvement. Possible mechanisms including interference with central gamma-aminobutyric acid systems, alteration of adrenergic nerve development, and Pb-Ca interaction are discussed.

Animals↗

[Radioimmunolocalization of head and neck tumors with a new monoclonal antibody against the EGF receptor. Preliminary results].

OBJECTIVE: To show the results of Radioimmunodetection (RID) using Cuban monoclonal antibody (MoA) anti-egf-ior-egf-r3 labeled with 99mTc for the detection of primary tumors and/or metastases of head and neck epithelial malignant tumors. MATERIAL AND METHODS: Thirteen patients aged from 16-62 years (mean: 54.8 years) with primary tumors and metastases in the regional cervical lymph nodes were retrospectively evaluated. The labelling dose was 1480-2220 MBq (40-60 mCi). Planar images were performed after 10 minutes and together with SPECT images after 18-24 hours following MoA administration. The matrix was 128 x 128. SPECT images were reconstructed using the Butterworth 4/16 filter. A positive result was defined when the lesions were visualized. RESULTS: RID localized 11 of the known primary tumors in the 13 patients studied. In the two other patients, in whom the primary tumor site was unknown, cervical lymph node metastases were found. The results of 3 of the RID were false negative but in the other 10, RID was able to localize the primary tumor and cervical lymph node metastases. Sensitivity was 77 % and the predictive positive value was 100 %. CONCLUSIONS: The results of this study show that the Cuban MoA ior-egf-r3 can be employed for RID of primary head and neck tumors and their metastases. The radiation dose is adequate for RID.

Adolescent↗