Can estrogenic radicals, generated by lactoperoxidase, be involved in the molecular mechanism of breast carcinogenesis?

Mutations of regulatory genes, which perturb the mechanism of cell replication resulting in abnormal cell proliferation, are the main cause of cancer. Many endogenous and exogenous chemicals (including estrogenic hormones) are known to represent a major carcinogenic risk for humans. 2-OH- and 4-OH-derivatives of estrogenic molecules have been shown to form stable adducts with purine DNA bases and act as 'depurinating' agents, thus altering gene transcription (Cavalieri EL, Stack DE, Devanesan PD et al. Proc Natl Acad Sci USA 1997; 94: 10937-10942). Lactoperoxidase (LPO), which is produced by mammary glands, is likely to be involved in breast carcinogenesis, because of its ability to interact with estrogenic hormones and oxidise them through two one-electron reaction steps. We investigated the reactivity of LPO towards five molecules: 17-beta-estradiol (a natural hormone), diethylstilbestrol (a synthetic drug, supplied to pregnant women for preventing spontaneous abortion), exestrol (a synthetic antigonadotropic estrogen), 2-OH- and 4-OH-estradiol (catabolic products of estradiol). Enzymatically generated radical derivatives of such molecules were stabilized by spin-trapping or by chelation of a diamagnetic metal ion and characterized with EPR spectroscopy. A kinetic study of the oxidation process was carried out using EPR and UV-visible spectroscopy

Death and its epidemiological investigation: considerations about some relevant aspects

O artigo aborda questões relativas ao óbito e sua investigação como elementos importantes para a Epidemiologia e a Saúde Pública. Ressalta aspectos ligados à melhoria da sua qualidade e da vigilância, bem como da pesquisa científica/epidemiológica nessa área, vistos sob a óptica da legislação e das normas éticas existentes no Brasil. Discute o problema relativo, a saber, "a quem pertence a informação em saúde e quais os limites de sua utilização", tratando, inclusive, da possibilidade do uso de bancos de dados identificados. Conclui sugerindo meios hábeis, como "Termo de Responsabilidade e Confidencialidade" por parte do pesquisador, para que a pesquisa científica/epidemiológica possa ter continuidade no país, com agilidade e oportunidade.This article addresses death and issues related to its investigation, as important components for Epidemiology/Public Health. It highlights aspects linked to the improvement of quality of investigation and surveillance of death, as well as the advance of scientific/epidemiological research in this area, analyzed in view of current legislation and ethical principles in Brazil. We discuss the problem related to knowing "whom the health information belongs to and which are the limits of its utilization", considering also the possibility of using identified databases. At the end, we suggest competent ways, as a "Term of Responsibility/Confidentiality" signed by the researcher in order to enable scientific/epidemiological research to continue in the country, in a more opportune and agile manner

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.FAPESPCNP

Epidemiology of intensive care unit-acquired sepsis in Italy: results of the SPIN-UTI network

BACKGROUND: Sepsis is the major cause of mortality from any infectious disease worldwide. Sepsis may be the result of a healthcare associated infection (HAI): the most frequent adverse events during care delivery especially in Intensive Care Units (ICUs). The main aim of the present study was to describe the epidemiology of ICU-acquired sepsis and related outcomes among patients enrolled in the framework of the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project. STUDY DESIGN: Prospective multicenter study. METHODS: The SPIN-UTI network adopted the European protocols for patient-based HAI surveillance. RESULTS: During the five editions of the SPIN-UTI project, from 2008 to 2017, 47.0% of HAIs has led to sepsis in 832 patients. Overall, 57.0% episodes were classified as sepsis, 20.5% as severe sepsis and 22.5% as septic shock. The most common isolated microorganisms from sepsis episodes were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The case fatality rate increased with the severity of sepsis and the mean length of ICU-stay was significantly higher in patients with ICU-acquired sepsis than in patients without. CONCLUSION: Our study provides evidence that ICU-acquired sepsis occurs frequently in Italian ICU patients and is associated with a high case fatality rate and increased length of stay. However, in order to explain these findings further analyses are needed in this population of ICU patient

The AMS-02 Time of Flight System. Final Design

The AMS-02 detector is a superconducting magnetic spectrometer that will operate on the International Space Station. The time of flight (TOF) system of AMS-02 is composed by four scintillator planes with 8, 8, 10, 8 counters each, read at both ends by a total of 144 phototubes. This paper describes the new design, the expected performances, and shows preliminary results of the ion beam test carried on at CERN on October 2002.Comment: 4 pages, 6 EPS figures. Proc. of the 28th ICRC (2003

Comparative study of the biological behaviour in hamster of two isolates of leishmania characterized respectively as L. major-like and L. donovani

Hamster inoculated intraperitoneally with 1 x 10(7) parasites of L. donovani and L. major-like of the New World were studied in groups of 15, 30, 60 and 90 days of infection. The parasite load and density showed progressive increase with the evolution of the infection and was higher in the L. donovani groups than in the L. major-like groups. The L. major-like groups showed parasite density higher in the spleen than in the liver and was similar in both organs in L. donovani groups. The histopathology showed a diffuse marked hyperplasia and hypertrophy of the reticuloendothelial system with high parasitism in the L. donovani groups while there was focal involvement of these organs in L. major-like groups, forming nodules of macrophages that were scantly parasitised. The biological behaviour could be useful in the preliminary studies of Leishmania strain in regional laboratories and understanding the histopathology of lesions caused by different leishmania species.Experimentos utilizando-se hamsters inoculados intraperitonealmente com 1 x 10(7) parasitas de 2 cepas, L. donovani (MHOM/BR/72/LD 46) e L. major-like (MCAN/BR/73/LD 70) isoladas no Novo Mundo foram realizados e estudados em grupos de 15, 30, 60 e 90 dias de infecção. A carga e a densidade parasitária mostraram progressivo aumento com a evolução da infecção e foi maior nos grupos inoculados com L. donovani do que nos grupos inoculados com L. major-like. Os grupos inoculados com L. major-like mostraram densidade parasitária maior no baço que no fígado e foram semelhantes em ambos os órgãos nos grupos inoculados com L. donovani. A histopatologia mostrou intensa e difusa hyperplasia e hipertrofia do sistema reticuloendotelial com alto parasitismo nos grupos inoculados com L. donovani, enquanto foi encontrado envolvimento focai nestes órgãos nos grupos inoculados com L. major-like, formando nódulos de macrófagos discretamente parasitados. O comportamento biológico seria útil em estudos preliminares de identificação de cepas de Leishmania em laboratórios regionais e na compreensão da histopatologia das lesões causadas por diferentes espécimes de leishmanias

Glutamine parenteral supplementation in stem cell transplant

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THE IMPORTANCE OF CONGENITAL MALFORMATIONS AT BIRTH

Introduction: Countries that have overcome high infant mortality rates show, nowadays, concentration of deaths in the neonatal period and, within it, mainly in the first week of life (early neonatal deaths). Regarding causes of death, as some diseases have started to be controlled, a significant proportional increase in the participation of congenital malformations has been verified. Objective: To describe the prevalence of congenital malformations (CM) at birth in conceptuses (stillbirths and live births) of women hospitalized in institutions located in the city of São Paulo, Brazil. Methods: Descriptive, cross-sectional study carried out at 4 hospitals in the city of São Paulo during 3 months in the 2 and semester of 2011. Data were collected by means of interviews with the women and examinations of hospital records. The CM were studied according to variables of epidemiological and socio-demographic interest. The deaths were analyzed according to underlying and associated causes. Results: The results showed the occurrence of 9.1% of CM registered among stillbirths and 4.3% among live births. Among the latter – 238 newborns – 284 CM were registered, totaling 1.2 CM per live birth with CM registered. Among the 238 newborns that had a CM register, there were 10 deaths by CM (4.2%). This value differs from the one verified among the live births without CM register that died (19 out of 5,341 or 0.4%). Aiming to identify possible  occurrences of death after hospital discharge, a linkage was performed between the official mortality database of the city of São Paulo and the study’s database. The occurrence of 18 deaths was found in this way, 4 of which were caused by CM. Thus, the total of deaths in the 1 st year of life was 47, and 14 of them had CM as the underlying cause, which leads to a proportional infant mortality by CM equal to 29.8% and an infant mortality coefficient by CM of 2.5%o live births. The data show a high undercount of CM in the registers of the official information systems (regarding SINASC, the prevalence of CM in the study was three times the prevalence for the city of São Paulo and 5.4 times the prevalence for Brazil). Conclusion: It is necessary to implement measures to improve the register of CM in the information systems, such as: raising doctors’ awareness concerning the importance of diagnosing CM and registering it in the newborn’s hospital records, creating a specific space to register the CM in the newborn’s hospital records, and qualifying and monitoring the personnel in charge of filling in the Certificate of Live Birth and transcribing it to the information systems