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Objective: The cytochrome P450 (CYP450) superfamily is implicated in important life processes, including metabolism of many molecules. CYP3A account for the largest portion of CYP450 proteins in human, including CYP3A4, CYP3A5 and CYP3A7. The purpose of this study was to investigate the immunohistochemical expression of CYP3A4 and CYP3A7 in human liver at different post-conceptional (PC) ages.Methods: Human liver samples from 30 fetuses and newborns were, clustered according with the PC age, routinely processed for immunohistochemical analysis of CYP3A4 and CYP3A7.Results: CYP3A4 was positive in all but two cases, CYP3A7 was positive in all but one case, which was negative also for CYP3A4.Conclusions: Our data on immunohistochemical detection of CYP3A4 and CYP3A7 during development show that CYP3A4 expression is not restricted to the post-natal age, being the immunostaining for both CYP3A4 and CYP3A7 identical after 25 weeks of PC age, thus the relationship between these CYP450 isoforms should be considered much more complex than previous thought. A high interindividual variability was observed among subjects at all gestational age. The variable CYP3A expression suggests the existence of a marked interindividual variability in drug metabolism during the intrauterine life and in perinatal period. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the effects of different allosteric modulators on the functional activity of γ-aminobutyric acid (GABA)B receptors in membranes of post-mortem human frontal cortex were examined. Western blot analysis indicated that the tissue preparations expressed both GABAB1 and GABAB2 subunits of the GABAB receptor heterodimer. In [35S]-GTPγS binding assays, Ca2+ ion (1mM) enhanced the potency of the agonists GABA and 3-aminopropylphosphinic acid (3-APA) and that of the antagonist CGP55845, but not that of the GABAB receptor agonist (−)-baclofen. CGP7930 (2,6-di-t-Bu-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol), a positive allosteric modulator of GABAB receptors, potentiated both GABAB receptor-mediated stimulation of [35S]-GTPγS binding and inhibition of forskolin (FSK)-stimulated adenylyl cyclase activity. Chelation of Ca2+ ion by EGTA reduced the CGP7930 enhancement of GABA potency in stimulating [35S]-GTPγS binding by two-fold. Fendiline, also reported to act as a positive allosteric modulator of GABAB receptors, failed to enhance GABA stimulation of [35S]-GTPγS binding but inhibited the potentiating effect of CGP7930. The inhibitory effect was mimicked by the phenothiazine antipsychotic trifluoperazine (TFP), but not by other compounds, such as verapamil or diphenydramine (DPN). These data demonstrate that the function of GABAB receptors of human frontal cortex is positively modulated by Ca2+ ion and CGP7930, which interact synergistically. Conversely, fendiline and trifluoperazine negatively affect the allosteric regulation by CGP7930. [Copyright &y& Elsevier]

In this study, we examined the immunohistochemical occurrence and distribution of glial cell line-derived neurotrophic factor (GDNF) in autoptic specimens of normal human hippocampus at different ages, from 22 weeks of gestation (w.g.) to adult life. Two different anti-GDNF polyclonal antibodies were used. Western blot analysis on homogenates of human and rat brain and recombinant human GDNF resulted in differential detection of monomeric and dimeric forms of the proteins. The ABC immunohistochemical technique revealed that in the Ammon’s horn, numerous positive cell bodies occurred in the pyramidal layer, the majority of them being present in the proximal CA1 and in CA2. Sparse positive neurons could be observed in the stratum oriens and moleculare. In the fascia dentata many granule cells showed a light punctate staining, whereas more heavily labelled neurons occurred in the polymorphic layer and, occasionally, in the molecular layer. The distribution pattern of GDNF-like immunoreactivity appeared consistently similar throughout life stages from 29 w.g. to adult age. However, intensity of labelling and frequency of neuronal cell bodies was highest in the neonate and decreased in adulthood. The present data provide a comprehensive map of the localization of GDNF-like immunoreactive neurons in the human archicortex at developmental ages and in the mature tissue and represent a first step towards the identification of hippocampal neurons which express the protein and/or are responsive to it. They further suggest that GDNF may play a role in the development of intrahippocampal circuitry and in neuronal function and maintenance throughout life. [Copyright &y& Elsevier]

Endometriosis involving the rectus abdominis muscle is very rare; until now, only 19 such cases have been reported in the medical literature since it was first described in 1984 by Amato and Levitt; almost all were associated with previous abdominal surgery such as cesarean section or other operations. We report two additional cases of this very rare condition presenting with an abdominal mass which was surgically excised with an accompanying margin of normal tissue. Both patients are well and without recurrence. Endometriosis pain has generally been described as cyclical and this condition usually develops in an old surgical scar. Endometriosis has no pathognomonic imaging findings on CT, MRI or sonography, as its appearance depends on the phase of the menstrual cycle, the proportion of stromal and glandular elements, the amount of bleeding and the degree of surrounding inflammatory and fibrotic response. Surgery is the treatment of choice including 5-10 mm of surrounding healthy tissue as surgical margin, to prevent recurrence. Our experience is in agreement with the data of the literature. We suggest that endometriosis must be included in the differential diagnosis of a symptomatic mass in the abdominal wall in women with and without a surgical history.

This 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.

As only a minority of low-grade dysplastic lesions of the cervix uteri will eventually progress to carcinoma, predicting the behavior of these lesions could be of high value in clinical practice. The aim of the study was to evaluate p16 ink4a and L1 as immunohistochemical markers of the biologic potentiality of low-grade dysplasia of the uterine cervix. The study included 38 conization specimens with coexisting cervical intraepithelial neoplasia grade 1 (CIN1) and 3 (CIN3) (group A) and 28 punch biopsies from women with CIN1 and proven spontaneous regression in the follow-up (group B). In group A, all CIN3 were p16 ink4a positive (p16+) and L1 negative (L1-). The CIN1 of this group were p16+L1- and p16+L1+ in 68.42% and 31.57%, respectively. No other expression pattern was found in this group. In group B, the p16+L1-, p16+L1+, p16-L1+, and p16-L1- patterns were found in 3.57%, 25%, 14.29%, and 57.14%, respectively. Overall, 96.29% p16+L1- CIN1 were found in group A, whereas all the p16-L1+ and p16-L1- CIN1 were found in group B. A significant difference between staining pattern distributions of group A and B was observed (P<0.0001). The results of the study show that p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions. Particularly in cases in which the grade of the lesion is morphologically difficult to assess, the p16/L1 expression pattern could be useful for planning the clinical management of these women.

The gallbladder is an unusual location of pancreatic heterotopia, defined as the presence of pancreatic tissue lacking anatomical and vascular continuity with the main body of the gland. A 28-year-old man presented with anorexia, nausea and pain in the right upper abdomen. On physical examination, the abdomen was tender to palpation and Murphy sign was positive. The patient underwent a cholecystecomy. This case, in our opinion, is very interesting since it permits to consider a controversial issue in the pathology of the gallbladder. The histological appearance of ductal structure in pancreatic heterotopia resembles the histological picture of both Aschoff-Rokitansky (AR) sinuses and adenomyomas. This finding suggests that these lesions are linked by a common histogenetic origin. We suggest that the finding of an adenomyoma in the gallbladder should prompt an extensive sampling of the organ in order to verify the coexistence of pancreatic rests.

The present report refers to a case of "primitive" endometriosis of the umbilical scar in a 50-years-old woman who complained of the appearance at the umbilicus of two nodules measuring 7 and 2 mm in diameter. These nodules, which were brownish in colour, were responsible for prickly pain and itching unrelated to the menstrual cycle. Both nodules were excised after a preoperative non-specific diagnosis of granuloma. Pathology findings revealed "cutaneous endometriosis". The authors believe that the appearance of a nodular swelling at the umbilicus of a woman of child-bearing age should lead to a suspicion of endometriosis among the possible diagnoses.