Circumstances of substance use by street youth in Egypt support the case for intervening to prevent adverse childhood experiences

Background: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. Methods: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12–18 years, participated in open-ended, in-depth interviews. Results: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. Conclusions: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood.     

Characterization of a novel metabolite intermediate of ziprasidone in hepatic cytosolic fractions of rat, dog, and human by ESI-MS/MS, hydrogen/deuterium exchange, and chemical derivatization.

Ziprasidone (Geodone), a novel atypical antipsychotic agent, is recently approved for the treatment of schizophrenia. It undergoes extensive metabolism in preclinical species and humans after oral administration, and only a very small amount of administered dose is excreted as unchanged drug. In vitro studies using human liver microsomes have shown that the oxidative metabolism of ziprasidone is mediated primarily by CYP3A4. However, coadministration of ziprasidone with ketoconazole, a CYP3A4 inhibitor, showed only a modest increase in its exposure. Therefore, in vitro metabolism of ziprasidone was investigated in hepatic cytosolic fractions to further understand its clearance mechanisms in preclinical species and humans. The major metabolite from incubation of ziprasidone in cytosolic fractions of rat, dog, and human was characterized by liquid chromatography-tandem mass spectrometry and found to be the product of reductive cleavage. Derivatization and hydrogen/deuterium exchange were used to deduce that the addition of two hydrogen atoms had occurred at the benzisothiazole moiety. Further studies to determine the enzyme involved in the formation of this metabolite are currently in progress. The identification of this novel metabolite in cytosol has clarified the clearance mechanism of ziprasidone in humans and preclinical species.     

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.     

Burns during pregnancy: a gloomy outcome

The effect of burns on fetal and maternal survival is known to be detrimental. This prospective study describes the performance of pregnant burned patients who were managed and followed up for fetal and maternal outcomes at Ain Shams University's burn unit and Maternity Hospital during the period from October 1995 to September 1996. During the 12-month period, 27 pregnant burned patients were managed. Fetal and maternal mortality correlated with the total body surface area (TBSA) burned, the mortality rate being 63 per cent for both mothers and fetuses in the 25–50 per cent TBSA group. A fetal loss of 56 per cent with no maternal loss were recorded in the 15–25 per cent TBSA group. Experience in dealing with pregnant burned patients proves that early surgical excision and skin grafting, with timely termination of pregnancy are the best lines of treatment. Prevention or minimizing the effects of the burns may be achieved by proper education and guidance of the pregnant woman.     

Failure of in vitro-expanded hyperimmune cytotoxic T lymphocytes to affect survival of mouse embryos in vivo

This study was designed to address the question; does expression of paternal histocompatibility antigens by fetal cells make them susceptible to immune attack in vivo during normal pregnancy? The experimental design was based on the rationale that, if alloantigens are presented by trophoblasts or other fetal cells in a manner which allows accessibility, in vitro-generated immune effector cells of combined helper/cytotoxic phenotype should produce fetal rejection of abortion. Similarly generated effector cells are capable of accelerating skin graft rejection and, when combined with IL-2 in vivo, are capable of causing regression of antigenic, but operationally non-immunogenic, tumors. The alloimmune effector cells generated in vitro during the current study were highly cytotoxic against normal adult target cells, whereas placental cells were completely resistant to cytolysis and fetal cells were only slightly susceptible. Adoptive transfer of effector cells to mice at different stages of gestation had no apparent effect on pregnancy outcome. In vivo administration of IL-2 and/or indomethacin, which expand effector cell numbers in vivo and block PGE2-mediated immune suppression, respectively, failed to potentiate the cellular effect. The data provide additional evidence that paternal histocompatibility antigens are not expressed in a format which allows susceptibility to immune attack during pregnancy. The data are discussed with respect to the role of the trophoblast in protecting developing embryos.     

Radioimmunoassay method for the detection of IgE antibodies specific to alcuronium

A radio-immunoassay (RIA) was used to screen for specific IgE to myorelaxants. Alcuronium was coupled to epoxy-activated Sepharose. Sixteen patients with anaphylaxis to alcuronium (n = 2), gallamine (n = 2) or suxamethonium (n = 12) were studied. The diagnosis was established by intradermal tests (ID), passive cutaneous anaphylaxis tests and human basophil degranulation tests. The amount of non specific label retained by Sepharose-ethanolamine (with sera of patients) and Sepharose-alcuronium (with sera of 11 control subjects) was estimated. The RIA was positive 10/16 (8/14 patients having reacted to a muscle relaxant other than alcuronium). The RIA seemed to be useful in the diagnosis of anaphylaxis to muscle relaxants. Drug-reactive antibodies were specific of the quaternary ammonium radical, which was the common allergenic determinant of all molecules of muscle relaxants. This test accounted for in vitro cross-reactivity, but had no predictive value for the clinical risk of crossed-anaphylaxis. This risk was best assessed by ID; it was positive in three cases. Although it was not possible to compare ID and RIA, the interpretation of which was different, both tests should be recommended for the detection of sensitivity to muscle relaxants.