Biomedical subjects

J Pavia

Publications and source records attributed to J Pavia.

26 records · Page 2Linked to original sources

PubMed1991

M1 and M3 muscarinic receptor subtypes in rat forebrain.

At least three pharmacologically different muscarinic receptor subtypes (M1, M2 and M3) have been identified in rat brain. While M1 and M2 subtypes can be directly labelled by selective ligands (3H-pirenzepine and 3H-AF-DX 116, respectively), there are no truly selective ligands for the M3 subtype. In the present study, we have investigated a possible method of studying the pharmacological M3 subtype in rat forebrain using the non-selective labelled antagonist 3H-N-methyl-scopolamine (3H-NMS) in the presence of unlabelled pirenzepine to protect the M1 subtype. The results obtained in kinetic experiments using 3H-NMS in presence of 30.10(-9) M unlabelled pirenzepine (Kon 1.2.10(-8) M-1 m-1, Koff 4.7.10(-2) m-1 and Kd 0.4.10(-9) M) are compatible with the studies carried out in rat pancreatic islets and submaxillary gland which contain predominantly the M3 subtype. We have also performed inhibition experiments with the selective antagonist AF-DX 116. Due to the small proportion of M2 receptors present in rat forebrain, this drug is able to discriminate between M1 and non M1 non M2 receptor subtypes in competition experiments with 3H-NMS versus AF-DX 116 (Ki values 0.28.10(-6) M and 4.3.10(-6) M, respectively). When the competition experiments were performed using 3H-NMS in presence of 30.10(-9) M unlabelled pirenzepine, the Ki value obtained was 3.8.10(-6) M, very close to the value obtained for the non M1 non M2 receptor in competition experiments with 3H-NMS versus AF-DX 116 and in excellent agreement with the affinity of this drug for the glandular M3 subtype. All these data suggest that the approach using the non-selective antagonist 3H-N-methyl-scopolamine in presence of unlabelled pirenzepine allows the study of the pharmacological M3 subtype in rat forebrain.

Animals↗

PubMed1990

Circadian rhythm in muscarinic receptor subtypes in rat forebrain.

The binding of different ligands to muscarinic receptors in the central nervous system is regulated by several factors. Among these are the administration of drugs, disease, ontogeny or aging. Studies carried out in rat brains have demonstrated changes in the density of the muscarinic receptors at different times of the day. These changes might be related to variations in the circadian rhythms. In this work we have studied the binding of the [3H]-N-methyl-escopolamine, the agonist carbachol and the antagonist pirenzepine to muscarinic receptors in rat forebrains at 10.00, 14.00, 18.00, 22.00, 02.00 and 06.00 hr. We have observed changes in the density of muscarinic receptors but not changes in affinity to the radioligand. The Bmax values obtained by saturation studies were maximum at 14.00 hr and minimum at 02.00 hr (P less than 0.05 Mann-Whitney's test). Inhibition studies in the presence of the non-selective agonist carbachol and the selective antagonist pirenzepine, at the same time-points, did not show statistically significant changes in the Bmax values. These data indicate that changes in the Bmax values are only observed in the total population of muscarinic receptors and are not due to modifications in the subtypes of muscarinic receptors nor to the different affinity states of agonist binding.

Animals↗

PubMed1988

Effects of triflusal and acetylsalicylic acid on platelet aggregation in whole blood of diabetic patients.

A study was made on the inhibitory effect of triflusal (600 mg/d X 15) and acetylsalicylic acid (ASA, 400 mg/d X 15) on platelet aggregation in whole blood (WB) and platelet-rich plasma (PRP) induced by ADP (2.5 mumol/l), adrenaline (50 mumol/l), collagen (1 microgram/ml) and arachidonic acid (0.8 mmol/l), in 30 insulin-dependent diabetic patients without vascular complications. Determination was also made of the serum levels of thromboxane B2 (TxB2) and of the plasma levels of 6-keto-PGF1-alpha and of beta-thromboglobulin (B-TG). Both drugs exhibited higher inhibitory effects in WB than in PRP. In WB, a significant difference between triflusal and ASA was observed against ADP-induced aggregation (67% and 46% inhibition respectively, p less than 0.01). Both drugs strongly inhibit the formation of TxB2 in serum (85% and 99%, respectively). Triflusal does not significantly change the plasma levels of 6-keto-PGF1-alpha; ASA, by contrast, causes reduction of over 95% in those plasma levels. The plasma levels of B-TG were not modified by either of the drugs.

Adult↗

PubMed1988

Platelet antiaggregatory effect of triflusal in human whole blood.

An in vitro and ex vivo study has been made to determine the inhibition of platelet aggregation in human whole blood (WB) and platelet rich plasma by triflusal and its main metabolite HTB (2-hydroxy-4-trifluoromethylbenzoic acid). Triflusal was administered orally at 300 mg x 2/day, for 15 days, to 13 healthy volunteers (ex vivo tests). Triflusal and HTB, at concentrations lower than 1 mM, produced a significant inhibition of platelet aggregation induced by ADP (2.5 microM, final) and collagen (1 microgram/ml, final) in PRP, while about 50% inhibition was induced in WB samples at 0.12 mM. Ex vivo studies also revealed a stronger inhibitory effect of triflusal in WB samples against several inducers; differences were particularly pronounced against ADP (10.6 times more potent in WB). These results suggest an important role of red blood cells and/or leukocytes in the mechanism of action of triflusal. The antiplatelet effect of triflusal in WB was modified when incubated with HTB at therapeutic concentrations. The IC50 value against collagen increased from 82 to 140 microM with 37.5 microM HTB, but decreased in a dose-dependent manner when incubated with higher concentrations of HTB, suggesting that inhibition of platelet cyclooxygenase by HTB masks its negative interaction with triflusal.

Adenosine Diphosphate↗

PubMed1988

Effect of triflusal and acetylsalicylic acid on platelet aggregation in human whole blood: influence of red blood cells and leukocytes.

A study has been made on the in vitro effect of triflusal, acetylsalicylic acid (ASA and their major metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), and salicylic acid (SA), on platelet aggregation in human whole blood. SA exhibited no significant antiplatelet effects (IC50 greater than 2mM) against several inducers; the IC50 values for the other compounds were: triflusal, 140 microM against ADP and 63.2 microM against collagen; HTB, 100 microM against ADP and 260 microM against collagen; ASA 687 microM against ADP and 9.3 microM against collagen. Red blood cells potentiate the antiaggregant effect of HTB and of triflusal, and to a lesser extent, that of ASA; leukocytes primarily potentiate the effect of ASA and, to a lesser extent, that of triflusal.

Adult↗

PubMed1987

False-positive early indium-111 leukocyte scan.

An In-111 leukocyte scan was performed in a cirrhotic patient with ascitic fluid infection to rule out an abdominal abscess. Scintigraphy showed localized uptake in the area between the liver and right lung 30 minutes after reinjection of the labeled cells. The 24-hour study was negative. No purulent collection was demonstrated in any location.

False Positive Reactions↗

PubMed1985

Enterogastric reflux detection with technetium-99m IDA.

A Tc-99m IDA scan was performed in a patient with severe alkaline esophagitis subsequent to a Billroth I gastroenterostomy. The scan showed enterogastric reflux simultaneously with gastroesophageal reflux of bile. The study was recorded in a computer and the reflux quantitated.

Duodenogastric Reflux↗

PubMedDate not supplied

[Striatal dopamine transporter density decrease in first episode schizophrenic patients treated with risperidone].

UNLABELLED: Extrapyramidal symptoms and Parkinsonism (PS) are side effects commonly observed with antipsychotic treatment. However, about 24% of never-treated schizophrenic patients may suffer from PS, which contrast with that 1% observed from the general population. 123I-FP-CIT SPECT has probe useful to differentiate degenerative from non-degenerative PS, so it could be interesting using it for establishing the functional state of presynaptic dopamine neurons of these patients. AIM: To determine the dopamine transporter binding (DAT) in a homogeneous group of first-episode schizophrenic patients. METHODS: An open, transversal study. Thirty schizophrenic in-patients and 15 healthy subjects were recruited. Patients were treated with similar doses of risperidone and all subjects were scanned with 123I-FP-CIT. Extrapyramidal symptoms and psychopathological status was assessed by Simpson-Angus, CGI and PANSS. Semi-quantitative analyses of SPECT images were performed using ROIs placed in caudate nucleus, anterior, medium and posterior putamen and occipital cortex. RESULTS: Whole striatum 123I-FP-CIT binding ratio was significantly lower in patients than healthy subjects (t = 2.56, p < 0.014). This was observed in whole putamen (t = 2.66, p < 0.011), anterior (t = 2.35, p < 0.023), medium (t = 2.38, p < 0.022) and posterior putamen (t = 2.09, p < 0.042). No differences were observed in caudate nucleus (t = 1.81, p = 0.076). Females obtained higher binding ratios than males (t = -3.13, p < 0.003). No correlation was observed between 123I-FP-CIT binding ratios and clinical scales. CONCLUSION: In our series, first episode schizophrenic patients treated with risperidone have a decrease striatal DAT binding assessed with 123I-FP-CIT SPECT. This alteration could be related to their own schizophrenia disease or be secondary to the antipsychotic treatment.

Adult↗