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Agonist activity of N-desmethylclozapine at delta-opioid receptors of human frontal cortex
No full textThe clozapine metabolite N-desmethylclozapine (NDMC) has been recently shown to act at different neurotransmitter receptors and to display both antagonist and agonist activities. We have previously reported that in cells over-expressing the recombinant delta-opioid receptor NDMC behaved as partial agonist with high intrinsic activity, but its action at the receptors naturally expressed in human brain remained to be investigated. In the present study, we examined whether NDMC was able to bind to and activate delta-opioid receptors in membranes of post-mortem human frontal cortex. In radioligand binding assays, NDMC competition curves displayed high- (K(i)=26 nM) and low-affinity (K(i)=3 microM) components, whose proportion was regulated by guanine nucleotides in an agonist-like fashion. In functional assays, NDMC stimulated [(35)S]GTPgammaS binding (EC(50)=905 nM) and inhibited cyclic AMP formation (EC(50)=590 nM) as effectively as delta-opioid agonists, whereas clozapine was much less potent and efficacious and clozapine N-oxide was completely inactive. The NDMC agonist activity was potently antagonized by the delta-opioid antagonist naltrindole, but not by the micro-opioid receptor antagonist CTAP (D-phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) or the kappa-opioid antagonist nor-binaltorphimine. Moreover, blockade of either acetylcholine muscarinic, dopamine D(2) or serotonin 5HT(1A) receptors failed to affect NDMC agonist activity. These data demonstrate that at clinically relevant concentrations NDMC behaves as an efficacious agonist at delta-opioid receptors of human frontal corte
Hepatic injury to the newborn liver due to drugs
No full textThe result of the use of drugs in the newborn may be strongly influenced by the peculiar state of the neonate, characterized by the immaturity, at birth, of the processes controlling the absorption, distribution, metabolism and excretion of drugs. Additional important factors that may affect drugs' bioavailability and toxicity are gestational age, birth weight, intrauterine growth restriction, gender and, especially, liver function immaturity. Because of the high susceptibility to infections, antibiotics, in particular ampicillin and gentamicin, are the most widely used drugs in newborns. Erythromycin is often used for the therapy of gastrointestinal dismotility, while azithromycin has been proposed for the prevention of bronchopulmonary dysplasia. Prostaglandin synthesis inhibitors, like indomethacin, are administered on the first days of life to close the patent ductus arteriosus. All these drugs have been proved to can give rise to hepatotoxicity. The acute and chronic liver toxicity due to the most widely used drugs in the neonates will be here reviewed
Rectal perforation from endometriosis in pregnancy: case report and literature review
Full text linkThis case report describes a woman with spontaneous rectal perforation from decidualized endometriosis in pregnancy. A 37-year-old woman was admitted to our hospital at 30 wk of pregnancy with symptoms suggestive of pyelonephritis, which persisted until 33 wk of gestation when delivery of a premature male baby was performed through a cesarean section. On postoperative day 2, an abdominal computed tomography showed free air in the peritoneal cavity and a pelvic abscess. Explorative celiotomy revealed a diffuse severe fecaloid peritonitis that originated from a 3-cm wide rectal perforation. A Hartmann operation was then performed. Histopathological findings were consistent with decidualization of the rectal wall. Only 20 cases of intestinal perforation due to endometriosis have been reported in the literature. This report is believed to be the first case of spontaneous rectal perforation from endometriosis in pregnancy, and it shows the potential occurrence of serious and unexpected complications of the disease
Inflammatory pseudotumor of the liver. A report of two cases with unusual histologic picture
No full textTwo cases of inflammatory pseudotumor (IPT) of the liver are reported. Clinical presentation was vague and aspecific. Laboratory tests and data from imaging techniques provided no specific information on the actual nature of the lesions and were misleading, suggesting a malignant lesion in one patient and a complicated hydatid cyst in the other. On gross examination, the tumors appeared yellowish ore grey-yellow in color, with a firm cut surface and well circumscribed from the surrounding parenchyma, although a true capsule was not evident. Variability in the histological pattern was also observed, even though the major finding was in both cases an admixture of lymphocytes, plasmacells, granulocytes and monocytes. Lymphocytes were immunohistochemically heterogeneous; monocytes showed in one case large hyperchromic atypical nuclei, confirming the previously, reported possibility that some cases of IPT may be mistaken for sarcomas. Further evidence is added in support of the hypothesis that some liver IPT may result from the evolution of cholangitic abscesses
Tumore rabdoide del rene ad insorgenza neonatale: descrizione di un caso con osservazioni ultrastrutturali.
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