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S Puig

Publications and source records attributed to S Puig.

102 records · Page 6Linked to original sources

Voltammetric study of 8-OH-DPAT effect on the raphe-trigeminal 5-HT system.

The effect of i.p. administration of the selective 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (100 micrograms kg-1) has been investigated by in vivo 5-hydroxyindole electrochemical (peak 3) detection in the nucleus raphe magnus (NRM) and medullary dorsal horn (MDH) of acute anaesthetized and unanaesthetized freely moving rats. 8-OH-DPAT induced a small but significant decrease in peak 3 in the NRM and MDH of anaesthetized rats. In freely moving animals, a similar small effect was observed at both NRM and MDH levels. With reference to similar in vivo studies demonstrating differential responsiveness of ascending serotonergic systems to 8-OH-DPAT, it is concluded that the serotonergic NRM-dorsal horn system is slightly affected by this 5-HT1A agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Neutrophilic pustulosis associated with chronic myeloid leukemia: a special form of Sweet's syndrome. Report of two cases.

Two subjects with Ph-positive chronic myeloid leukemia (CML) in whom pustular Sweet's syndrome was diagnosed are reported. The first patient was a 47-year-old woman who developed fever, painful ulcers of the oral mucosa and vagina and generalized pustulous skin lesions 2 years after the diagnosis of CML. Histologically, the skin lesions consisted of dense neutrophilic infiltrates with perifollicular disposition. The microbiologic studies were negative. The lesions showed a favorable response to corticosteroids, but fever recurred with every attempt of tapering prednisone; it finally disappeared with the addition of oral cyclophosphamide. The second patient was a 45-year-old man who developed fever and disseminated pustules with histologic features consistent with Sweet's syndrome and negative microbiologic studies at 2.5 years after diagnosis of CML. The picture showed a dramatic response to prednisone and did not recur after the drug was discontinued. In both patients, CML remained stable after resolution of Sweet's syndrome.

Cyclophosphamide↗

In vivo electrochemical evidence that the tricyclic antidepressant femoxetine potentiates the morphine-induced increase in 5-HT metabolism in the medullary dorsal horn of freely moving rats.

Acute administration of tricyclic antidepressants (TCAs) is known to potentiate morphine antinociception. At the medullary dorsal horn (MDH) level systemic morphine has been shown to increase serotonin (5-HT) metabolism as measured by in vivo electrochemistry in freely moving rats. Using similar electrochemical detection of 5-hydroxyindole (peak '3') within the MDH, the present study investigated the effect of the specific 5-HT uptake inhibitor femoxetine on peak 3 and the effects of this TCA on changes in 5-HT metabolism induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) (i) induced a small but significant increase in peak 3 and (ii) strongly potentiated the effect of morphine (10 mg/kg i.p.) on 5-HT metabolism, this potentiation being opiate specific since simultaneous injection of naloxone (1 mg/kg i.p.) abolished the effect of morphine. These findings provide an in vivo neurochemical basis for the potentiation of morphine antinociception by TCAs. They further emphasize the importance of 5-HT bulbospinal descending pathways in morphine antinociception.

Animals↗

Femoxetine blocks the morphine-induced increase in 5-HT metabolism, as measured by in vivo voltammetry in the nucleus raphe magnus of freely-moving rats.

Tricyclic antidepressants, when administered acutely, are known to potentiate morphine-induced antinociception. Systemic administration of morphine has been shown to increase the metabolism of serotonin (5-HT) at the level of the nucleus raphe magnus, as measured by in vivo electrochemistry, in freely-moving rats. Using a similar electrochemical detection of 5-hydroxyindole (peak "3") in the nucleus raphe magnus, the present study investigated the effect of the specific 5-HT uptake inhibitor, femoxetine, on peak 3 and on changes in the metabolism of 5-HT, induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) induced a significant decrease in peak 3 and completely abolished the effect of morphine (10 mg/kg i.p.) on the metabolism of 5-HT. These data do not support the contention that potentiation of morphine-induced analgesia, by tricyclic depressants results from an interaction between the tricyclic antidepressants and the morphine-induced increase in metabolism of 5-HT, at the level of the nucleus raphe magnus.

Animals↗

Comparative study of the multiple dose pharmacokinetics and the tolerance of a new NSAID (droxicam) versus piroxicam in healthy volunteers.

A controlled, randomized, double-blind, clinical trial has been performed in healthy volunteers in order to study the pharmacokinetics and tolerability of droxicam in comparison with piroxicam, when both drugs were administered at a dose of 20 mg/day for 20 days. Since transformation into piroxicam takes place in the gastrointestinal tract, unchanged droxicam was not detected in plasma. Steady state of plasma piroxicam concentrations was reached in all volunteers during the course of the study. Absorption kinetics of droxicam were delayed with respect to those of piroxicam (t1/2 a = 7.55 h for droxicam and 1.78 h for piroxicam). The remaining pharmacokinetical parameters studied showed no statistically significant differences. The bioavailability of both drugs was equal. Tolerability of droxicam and piroxicam was as usual for the NSAIDs, and no clinical or analytical side effects which could hinder its administration to wider populations were detected. Statistically significant differences in the number and type of side effects detected in the two treatment groups were not encountered.

Administration, Oral↗

[Progressive familial intrahepatic cholestasis (Byler disease): current genetics and therapy].

Progressive familial intrahepatic cholestasis (PFIC) is a congenital liver disease. First symptoms can frequently be seen shortly after birth. Quality and expectation of life are substantially reduced due to severe pruritus and the complications of progressive liver cirrhosis. PFIC is diagnosed on the basis of characteristic clinical and laboratory parameters and genetic analysis after exclusion of other liver diseases leading to intrahepatic cholestasis. Medical therapy is only effective in a proportion of children with PFIC. Partial biliary diversion (PBD) is nowadays considered the therapy of choice in patients with therapy-refractive pruritus. If performed in time, damage to the liver can be delayed or arrested, thus orthotopic liver transplantation (OLT) can be postponed or even avoided in at least some patients with PFIC. Besides providing a current overview of PFIC, we report on three patients who were successfully treated surgically. One patient was subjected to a new technique of PBD (cholecysto-appendicostomy), the other two had OLT.

Appendix↗

S-100beta and MIA in advanced melanoma in relation to prognostic factors.

We compared the sensitivity and specificity of S-100 and MIA in advanced melanoma, in 96 patients with no evidence of disease (NED) and 86 patients with metastatic melanoma. Abnormal S100 (>0.2 microg/l) and MIA (>14 ng/ml) results were found in 1.1% and 3.2% of NED patients and in 59.3% and 54.6% of the patients with active melanoma (p<0.001). Using both tumor markers simultaneously, the sensitivity increased up to 69.8% with the same specificity 96.8%. S100 serum levels were not related to growth patterns. By contrast, MIA levels seemed to be related to the growth pattern, with higher levels in nodular melanoma (60.6+/-87.1 ng/ml) compared with acral-lentigous melanoma (11.9+/-5.4 ng/ml) (p=0.02). Likewise, S100 was related to the metastases site with significantly higher sensitivity and mean concentrations in patients with brain metastases (p=0.01) with the lowest in those with lung MI. MIA was related to the same metastases locations but without statistical significance. In summary, both S100 and ML4 are useful markers related to prognostic factors, being more effective when used in combination.

Adult↗

Absorption, distribution and excretion of [14C]-Lesopitron after single and repeated administration in rats and dogs.

Disposition of [14C]-lesopitron was investigated in male rats and dogs after single and repeated oral administration. Radioactivity was rapidly and efficiently absorbed from gastrointestinal tract following oral administration. After 7 days, the radioactivity was mainly excreted into feces via bile. The cumulative urinary and fecal excretion was 99% and 75% of the administered dose in rats and dogs, respectively. [14C]-Lesopitron was widely distributed in rats, with the highest concentrations in liver and kidney, while the concentration in brain was similar to that in plasma. Radioactivity in most tissues decreased essentially in parallel with that in plasma. In rats, plasma levels of [14C]-lesopitron radioactivity achieved steady state on day 2 of repeated administration. The distribution pattern obtained after 7 consecutive daily oral doses was similar to that in the single-dose study. At 72 h after the last administration, tissue radioactivity was fully eliminated and no accumulation occurred. After i.v. administration in rats and dogs, plasma concentrations of lesopitron decreased biphasically with an apparent elimination half-life of 100 min. The absolute bioavailability of lesopitron was about 10%, suggesting an important first-pass effect. In rats, the lesopitron plasma concentrations were similar to those obtained for its metabolites (5-hydroxylesopitron and PmP), whereas in dogs, the PmP plasma concentrations were higher than those for lesopitron and 5-hydroxylesopitron.

Animals↗

Absorption, distribution and excretion of [14C]E-4716 after single-dose administration in rats and dogs.

The absorption, distribution and excretion of E-4716, a novel antihistamine, were studied in rats and dogs after single-dose oral or intravenous administration of [14C]E-4716. Radioactivity was rapidly and efficiently absorbed from the gastrointesanal tract after oral administration, and biphasic plasma concentration-time profiles were observed in both species. In rats, oral absorption was linear within the dose range studied, and no differences in administration route or doses were observed in elimination. Elimination was approximately twice as fast in dogs as in rats. No sex differences in elimination were observed in dogs. Radioactivity was widely distributed in rats, and levels in brain, eyes, fat and testes were lower than those in plasma. Excretion was mainly by feces in rats and by urine in dogs, showing species differences. After oral administration in rats, unchanged drug was rapidly absorbed and the absolute bioavailability was only 20%, suggesting an important first-pass effect.

Administration, Oral↗