Mutational specificity of aflatoxin B1. Comparison of in vivo host-mediated assay with in vitro S9 metabolic activation

An intrasanguineous host-mediated assay was used to determinethe pattern of mutagenesis induced by the carcinogen aflatoxinBl in the lacl gene of Escherichia coli recovered from rat liver.To investigate the influence of different types of metabolicactivation, the mutation spectrum induced by AFB1 activatedin vitro by a commercially prepared S9 microsomal fraction fromAroclor 1254-treated rats was also obtained. A total of 281forward mutations affecting the N-terminal region of the laclgene were characterized by DNA sequencing analysis. AFB1 inducedsimilar type of mutations with similar site specificity whenactivated by the standard S9 fraction or by employing a rathost-mediated assay. These results indicate the ability of thein vitro S9 fraction to mimic the in vivo metabolism, suggestingthat the same active metabolite, presumably AFB1 8, 9-epoxide,is responsible for generating a similar pattern of DNA damage,as reflected in the similarity of mutational spectra. For bothactivation systems, most mutations (>90%) were base substitutionsthat occurred primarily at G: C pairs. Somewhat over one-halfof G: C targeted substitutions were GC>TA transversions,other mutations being evenly divided between G: C>AT transitionsand GC>CG trans-versions. The mutational specificity exhibitedby activated AFB1 can be explained by incorporation of differentbases opposite a single type of non-instructive lesion duringerror-prone DNA synthesis. To what extent the mutations aredue to the main adduct (AFB1-N7-Gua), its imidazole-ring-openedderivative or an apurinic site remains unknown.     

Spatial and Temporal Patterns of Neurogenesis in the Chick Retina

Chick embryo retinas were labelled in ovo by single injections of [3H]thymidine at selected times between days 2 and 12 of incubation. Embryos were later removed, at different stages of development, and the retinas processed for autoradiography of either serial sections or dissociated cell preparations. Analysis of unlabelled cells shows that neurogenesis starts, on day 2 of incubation, in a dorsotemporal area of the central retina, close to the posterior pole and to the optic nerve head. A gradient of neurogenesis spreads from this central area to the periphery, where neurogenesis ends, shortly after day 12, when the last few bipolar cells withdraw from the cell cycle. Additional dorsal-to-ventral and temporal-to-nasal gradients can be discerned in our autoradiographs. In all retinal sectors, ganglion cells start first to withdraw from the cell cycle, followed, with substantial overlapping, by amacrine, horizontal, photoreceptor plus Müller, and bipolar neuroblasts. Ganglion cells are also the first to reach the 50% level of unlabelled cells, followed this time by horizontal, photoreceptor, amacrine, Müller and bipolar cells. Finally, 100% levels of unlabelled cell populations are attained simultaneously by ganglion, horizontal and photoreceptor cells, followed by amacrine, then by Müller, and last by bipolar cells. Although all classes of neurons, in varying proportions, are being produced most of the time, our results also demonstrate that, in any given retinal area, the first cells leaving the cycle are determined to become ganglion cells, and the last ones bipolar cells, and not other types.     

Pseudomixoma peritoneal tipo adenomucinosis peritoneal diseminada con imágenes radiológicas atípicas

Pseudomyxoma peritonei is an unusual condition that has caused much confusion regarding its aetiology, clinical manifestations, treatment and prognosis. It is characterised by mucinous ascites and diffuse mucinous invasions of the peritoneum. Three histological subtypes have been defined: a) disseminated peritoneal adenomucinosis (peritoneal lesions composed of abundant extra-cellular mucin containing scant simple-to-focally-proliferating mucinous epithelium with little cytological atypia or mitotic activity); b) peritoneal mucinous carcinomatosis (peritoneal lesions composed of more abundant mucinous epithelium with the architectural and cytological features of carcinoma); and c) an intermediate group. The different histological subtypes have different prognoses. We report a case of disseminated peritoneal adenomatosis, and discuss its clinical management.     

Socioeconomic and contextual determinants of reproductive activity among adolescent women in Colombia]

OBJECTIVE: To contribute to a better understanding of the problems of pregnancy among adolescent women, including proximate and socioeconomic determining factors, in two large, culturally different cities in Colombia: Santa Fe de Bogotá and Cali. METHODS: This longitudinal study combined quantitative and qualitative research methods, using information generated by a survey of adolescents conducted in 2003. The survey included 550 adolescents in Bogotá and 550 adolescents in Cali, from all socioeconomic strata. To analyze the determinants, discrete-time proportional hazards models were used. For the qualitative study, 72 in-depth interviews and four focus groups were done. With the information organized by subjects and categories that were defined in relation to the purposes of the study, categories were identified that arose from the patterns and recurrences in the data, in order to see sociocultural trends by sex, stratum, and city. RESULTS: The patterns of sexual activity, union (married or unmarried relationship), and maternity differ considerably among the socioeconomic strata, in both of the cities. The adolescent women in the low stratum begin having sexual relations, form unions, and become mothers earlier in life and with greater frequency than do adolescent women in the medium or high strata. The main determinant of the reproductive behavior of adolescent women is the set of contextual and socioeconomic factors in the home, mainly the family context (environment and supervision) and the educational climate (the average number of years of formal education of the family members over the age of 15). CONCLUSIONS: Sex education has been provided in the schools in Colombia since 1993, but our results clearly indicate that it has had only a limited impact on the reproductive behavior of adolescent women.     

Promoting and sustaining health through increased vegetable and fruit consumption among European schoolchildren: The Pro Children Project

Aim The Pro Children consortium consists of the following partners: Knut-Inge Klepp (Coordinator), Department of Nutrition, University of Oslo, Norway; Carmen Perez Rodrigo, Unidad de Nutricion Comunitaria, Bilbao, Spain; Inga Thorsdottir, Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland; Pernille Due, Department of Social Medicine, University of Copenhagen, Denmark; Maria Daniel Vaz de Almeida, Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto, Portugal; Ibrahim Elmadfa and Alexandra Wolf, Institute of Nutrition, University of Vienna, Austria; Jóhanna Haraldsdóttir, Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark; Johannes Brug, Erasmus Medical Center Rotterdam, Department of Public Health, The Netherlands; Michael Sjöström and Agneta Yngve, Unit for Preventive Nutrition, Karolinska Institutet, Stockholm, Sweden; Ilse De Bourdeaudhuij, Department of Movement and Sport Sciences, Ghent University, Belgium.The Pro Children study is designed to assess vegetable and fruit consumption and determinants of the consumption patterns among European school children and their parents. A second objective is to develop and test strategies for promoting increased consumption of vegetables and fruits among school children and their parents.Subjects and methods Surveys of national, representative samples of 11-year-old school children and their parents were conducted in nine countries during October–November 2003, i.e. in Austria, Belgium, Denmark, Iceland, The Netherlands, Norway, Portugal, Spain and Sweden. Comprehensive school-based educational programmes were developed and tested in three settings, i.e. in the Bilbao region, Spain, in Rotterdam, The Netherlands, and in Buskerud county of Norway. A 24-h recall format and frequency items assessing regular intake were used to assess vegetable and fruit consumption. Determinants were assessed employing the theoretical framework of the ASE model (Attitudes, Social Influences and Self-Efficacy), including cognitive factors, normative influences, skills and environmental barriers related to vegetable and fruit consumption. The intervention programmes were tested employing a group-randomized trial design where schools were randomly allocated to an intervention arm and a delayed intervention arm. Surveys among all participating children and their parents were conducted prior to the initiation of the intervention (September 2003; month 0), immediately after the end of the intervention (at month 8) and at the end of the subsequent school year (month 20).Results Preliminary data from the project indicate that girls eat vegetables and fruit significantly more often than do boys across all participating countries. There are no sex differences, however, with respect to perceived availability of vegetables and fruit at home and outside the home setting. In all countries, perceived availability appears to be significantly associated with reported frequency of both vegetable and fruit consumption.Conclusion Experience so far indicates that the Pro Children Project will succeed in producing valid and reliable research instruments for assessing vegetable and fruit consumption among school children and their parents and that comparable, comprehensive intervention programmes can be implemented across geographic and cultural settings within Europe.     

Analysis of the toxic potential of venom from Loxosceles adelaida, a Brazilian brown spider from karstic areas.

Loxosceles adelaida spiders (Araneae, Sicariidae) are found near and inside the caves in the Parque Estadual Turistico do Alto Ribeira (PETAR), Sao Paulo, Brazil, which are visited by thousands of tourists every year. Several Loxosceles species are a public health problem in many regions of the world, by causing severe dermonecrosis and/or complement dependent haemolysis upon envenomation. The aim of this study was to characterize the biochemical and biological properties of L. adelaida venom and evaluate the toxic potential of envenomation by this non-synanthropic Loxosceles species. The biological activities of the L. adelaida venom was compared to that of Loxosceles gaucho, a synanthropic species of medical importance in Brazil. L. adelaida venom showed a similar potential to induce haemolysis, dermonecrosis and lethality as L. gaucho venom. L. adelaida crude venom was purified, yielding a 31 kDa component endowed with haemolytic and dermonecrotic activities. In conclusion, we show here that the troglophile Loxosceles species, L. adelaida, commonly found in the complex of caves from PETAR, is potentially able to cause envenomation with the same gravity of those produced by synanthropic species.     

Nerve growth factor and striatal glutathione metabolism in a rat model of Huntington's disease

Purpose: To test the influence of nerve growth factor (NGF) on striatal glutathione (GSH) content and the activities of GSH-related enzymes from quinolinic acid-lesioned rats. Methods: Rats were intrastriatally injected with QA and NGF. Enzymatic and GSH assays were performed one week later. Results: NGF prevented the QA-induced decline in glutathione reductase activity and GSH content. Conclusions: NGF is able to prevent some of the disturbances induced by the excitotoxic insult in the striatal GSH metabolism.     

Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.     

Addition of histamine to interleukin 2 treatment augments type 1 T-cell responses in patients with melanoma in vivo: immunologic results from a randomized clinical trial of interleukin 2 with or without histamine (MP 104).

PURPOSE: Preclinical investigations suggest that histamine dihydrochloride (HDC) protects T cells and natural killer cells from inhibition by monocyte-derived reactive oxygen metabolites and synergizes with interleukin (IL) 2 in inducing T-cell activation. Here, we investigate whether this mechanism is operational in patients with melanoma treated with HDC as an adjunct to IL-2. EXPERIMENTAL DESIGN: Melanoma patients having liver metastases were treated with IL-2 with or without HDC within a randomized, multicenter, phase III trial. The effect of HDC on type 1 and type 2 T-cell cytokine production was investigated in peripheral blood samples from 19 patients with the use of intracellular cytokine flow cytometry. Melanoma-specific T-cell responses were analyzed in eight HLA-A2-positive patients. RESULTS: Frequencies of CD3+ T cells producing IFN-gamma (type 1 T cells) in response to phorbol myristate acetate/ionomycin increased (median, 1.8-fold) in patients receiving IL-2 plus HDC but not in those receiving IL-2 alone (P < 0.01 for comparison between arms). In contrast, the number of IL-13-producing type 2 T cells that increased in patients after treatment with IL-2 was not modulated by HDC. Melanoma- and tyrosinase-specific IFN-gamma and IL-13-producing T cells were detected in two of four HLA-A2-positive patients with melanoma following treatment with HDC + IL-2. CONCLUSIONS: Treatment of patients with stage IV melanoma with HDC in combination with IL-2 increases type 1 T-cell responses and may promote induction of melanoma-specific T cells. These effects are of relevance for tumor immunotherapy and provide a potential mechanism for the clinical efficacy of HDC added to IL-2.     

Obesity, recreational physical activity, and risk of pancreatic cancer in a large U.S. Cohort.

BACKGROUND: Obesity and physical activity, in part through their effects on insulin sensitivity, may be modifiable risk factors for pancreatic cancer. METHODS: The authors analyzed data from the American Cancer Society Cancer Prevention Study II Nutrition Cohort to examine the association between measures of adiposity, recreational physical activity, and pancreatic cancer risk. Information on current weight and weight at age 18, location of weight gain, and recreational physical activity were obtained at baseline in 1992 via a self-administered questionnaire for 145,627 men and women who were cancer-free at enrollment. During the 7 years of follow-up, 242 incident pancreatic cancer cases were identified among these participants. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including personal history of diabetes and smoking. RESULTS: We observed an increased risk of pancreatic cancer among obese [body mass index (BMI) >/= 30] men and women compared with men and women of normal BMI [<25; RR, 2.08; 95% confidence interval (95% CI), 1.48-2.93, P(trend) = 0.0001]. After adjustment for between BMI, risk of pancreatic cancer was independently increased among men and women who reported a tendency for central weight gain compared with men and women reporting a tendency for peripheral weight gain (RR, 1.45; 95% CI, 1.02-2.07). We observed no difference in pancreatic cancer incidence rates between men and women who were most active (>31.5 metabolic equivalent hours per week) at baseline compared with men and women who reported no recreational physical activity (RR, 1.20; 95% CI, 0.63-2.27). CONCLUSION: This study, along with several recent studies, supports the hypothesis that obesity and central adiposity are associated with pancreatic cancer risk.