Risk factors for behavioral and emotional problems in childhood: a community study in Uruguay]

OBJECTIVES: To explore some of the demographic risk factors that are associated with the risk of behavioral or emotional problems in children, and to examine the possibility of an association between psychological stress in the parents and psychological problems in their children. METHODS: In this study, the presence of psychological stress in the parents and certain psychosocial characteristics that increase the risk of mental problems in childhood were examined in a sample of Uruguayan children from three communities, two urban and one rural. The study, which was carried out in Ciudad Vieja and Barrio Sur, in the city of Montevideo, and in Colonia de Sacramento, a rural town, comprised 115 children between the ages of 5 and 15. Mothers answered the Child Psychiatric Morbidity Questionnaire (QMPI), an instrument for the detection of behaviors pointing to the presence of emotional problems in children. Both parents also supplied the demographic information requested in the Psychiatric Epidemiology Research Interview Demoralization Scale; they answered the CAGE questionnaire, a screening tool for alcoholism; they responded to the Social Support Network Inventory; and they answered questions about their self-perceived mental health. RESULTS: Fifty-three percent of the children had scores greater than 6 on the QMPI, which indicates the possible presence of behavioral or emotional problems. Fathers' self-perception of emotional problems and mothers' feeling of being demoralized showed a statistically significant association with a greater risk of behavioral or emotional problems in their children. CONCLUSIONS: In light of our results, mental health in childhood is a social and public health problem that warrants further epidemiologic study in Uruguay.     

Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells

CDC25 phosphatases are important regulators of the cell cycle and represent promising targets for anticancer drug discovery. We recently identified NSC 119915 as a new quinonoid CDC25 inhibitor with potent anticancer activity. In order to discover more active analogs of NSC 119915, we performed a range of ligand-based chemoinformatic methods against the full ZINC drug-like subset and the NCI lead-like set. Nine compounds (3, 5–9, 21, 24, and 25) were identified with K_i values for CDC25A, -B and -C ranging from 0.01 to 4.4 μM. One of these analogs, 7, showed a high antiproliferative effect on human melanoma cell lines, A2058 and SAN. Compound 7 arrested melanoma cells in G2/M, causing a reduction of the protein levels of CDC25A and, more consistently, of CDC25C. Furthermore, an intrinsic apoptotic pathway was induced, which was mediated by ROS, because it was reverted in the presence of antioxidant N-acetyl-cysteine (NAC). Finally, 7 decreased the protein levels of phosphorylated Akt and increased those of p53, thus contributing to the regulation of chemosensitivity through the control of downstream Akt pathways in melanoma cells. Taken together, our data emphasize that CDC25 could be considered as a possible oncotarget in melanoma cells and that compound 7 is a small molecule CDC25 inhibitor that merits to be further evaluated as a chemotherapeutic agent for melanoma, likely in combination with other therapeutic compounds.     

2,7-Bis-(4-amidinobenzylidene)-cycloheptan-1-one dihydrochloride, tPA stop, prevents tPA-enhanced excitotoxicity both in vitro and in vivo.

Tissue-type plasminogen activator (tPA) is available for the treatment of thromboembolic stroke in humans. However, adverse effects of tPA have been observed in animal models of ischemic brain injuries. In the present study, we have used a synthetic tPA inhibitor, named 2,7-bis-(4-amidino-benzylidene)-cycloheptan-1-one dihydrochloride (tPA stop), to investigate the role of endogenous tPA in the cerebral parenchyma. In mouse cortical cell cultures, we observed that although tPA stop reduced N-methyl-D-aspartic acid (NMDA)-mediated excitotoxic neuronal death, it failed to modulate alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazole propanoic acid or kainate-mediated necrosis. In addition, we found that tPA stop could prevent the deleterious effects of both endogenous and exogenous tPA during NMDA exposure. At the functional level, tPA stop was found to prevent tPA-dependent potentiation of NMDA receptor-evoked calcium influx. The relevance of those findings was strengthened by the observation of a massive reduction of NMDA-induced excitotoxic lesion in rats when tPA stop was co-injected. Altogether, these data demonstrate that the blockade of the endogenous proteolytic activity of tPA in the cerebral parenchyma could be a powerful neuroprotective strategy raised against brain pathologies associated with excitotoxicity.     

BOOK REVIEWS

Malignant Melanoma . E. Holzle, P. Kind, G. Plewig, and W. Burgdorf .
Differential Diagnosis in Dermatology . 2nd Edition. Richard Ashton and Barbara Leppard .     

The origin of syphilis and the llama myth

The following is an extract from a presentation at the Seoul International Dermatology Symposium, Seoul, Korea, 8 May 1992     

BOOK REVIEWS

Book reviews in this article:
1993 Year Book of Dermatology . Arthur J. Sober and Thomas B. Fitzpatrick
Color Atlas of Cutaneous Disorders of the Lower Extremities . Joseph A. Witkowski and Harvey Lemont .     

Magnetic resonance imaging of estrogen-induced pituitary hypertrophy in rats

Estrogen-induced pituitary hypertrophy has been studied using magnetic resonance imaging in a group of 15 control and 30 experimental rats. Following the subcutaneous implantation of an estrogen pellet, differences in the anatomical appearance of the pituitary gland of the implanted rats can be detected in as little as 16 days, when compared to the control animals. The gland in the experimental animals appears diffusely enlarged with rounded margins, when viewed in sagittal T1-weighted magnetic resonance images. Additionally, a uniform signal intensity is not detected in the hypertrophic pituitary glands of estrogen-implanted rats, while in the control rats this is a common finding. A satellite study of 300 animals (treated in a manner identical to that in the imaging study) demonstrates that the weights of excised pituitaries in estrogen-treated rats increases to a statistically significant level in the interval 18 to 35 days. Changes in the appearance and volume of the pituitary gland observed with magnetic resonance imaging seem to have promise for the early detection of pituitary lesions in rats.     

The immunocompromised district in dermatology: A unifying pathogenic view of the regional immune dysregulation

Besides the systemic immune deficiency, a sectorial default in immune control may occur in immunocompetent subjects. This regional immune defect can appear and remain confined to differently damaged skin areas, lately labeled immunocompromised districts (ICDs).