Mechanistic Approaches To The Prevention Of Mutation And Cancer

Cancer and other mutation-related diseases can be prevented at three levels: primary prevention, which is addressed to healthy individuals in order to prevent occurrence of the disease; secondary prevention, which is addressed to early stage patients in order to prevent progression of the disease; and tertiary prevention, which is addressed to patients after therapy in order to prevent relapses of the disease. Although the most obvious approach to prevention is to minimize exposures to recognized risk factors, a complementary strategy is represented by chemoprevention, using dietary and pharmacological agents that reinforce the host defence machinery. Since 1988, I proposed detailed classifications of mechanisms of inhibitors of mutagenesis and carcinogenesis. They may apply not only to cancer but also to other degenerative diseases that have replaced infectious diseases as the leading causes of death in the population. In fact, certain mechanisms, such as damage to nuclear DNA and mtDNA, oxidative stress, chronic inflammation, signal transduction alterations and epigenetic changes may be involved in the pathogenesis of different diseases. Studies performed in our laboratory have shown that certain genomic alterations that are usually investigated in cancer research may also be detected in other chronic diseases, such as atherosclerosis, degenerative heart diseases, chronic obstructive pulmonary diseases, neurological disorders, eye diseases, skin ageing, and alopecia. Similar alterations were investigated in critical periods of life, such as birth and ageing. The nucleotide alterations occurring at birth in the lung render the newborn particularly vulnerable to the action of environmental agents. In fact, we demonstrated that cigarette smoke becomes a potent carcinogen in mice when exposure starts at birth and continues early in life. We investigated a number of chemopreventive agents by evaluating modulation of intermediate biomarkers and carcinogenicity. An optimal agent should not excessively alter the physiological patterns of gene expression, microRNA and proteome profiles, but at the same time it should be effective in inhibiting alterations induced by mutagens and carcinogens. It should be noted that most chemopreventive agents possess pleiotropic properties. The knowledge of mechanisms can be exploited to combine different agents working with complementary mechanisms. Like the therapy of important diseases, such as cancer, cardiovascular diseases, AIDS, etc., uses combinations of drugs, combined chemoprevention is a quite promising strategy. Although a large number of agents are potentially able to prevent cancer, we are in search of tools to predict, hopefully in the single individual, their efficacy and safety in humans

Los concejos municipales pluripartidarios : elementos para conocer esta nueva experiencia de gestión municipal

El estudio abarcó quince municipios de El Salvador, y aunque el mismo no pretende hacer generalizaciones sobre el funcionamiento de los Concejos Municipales Plurales (CMP), ofrece información sobre algunos aspectos que están relacionados con la forma en que pueden estar funcionando los gobiernos municipales plurales. El documento dividido en cuatro grandes apartados presenta un breve resumen de la metodología utilizada; una sucinta contextualización de los mismos a partir de los resultados electorales para gobiernos locales; el siguiente apartado aborda cómo ha sido el funcionamiento de los Concejos Municipales Plurales, lo cual se hace a partir de la sistematización de entrevistas y encuestas realizadas para esta investigación; adicionalmente se presentan algunos elementos a considerar como lecciones, dificultades y desafíos que enfrentan los CMP, y que han sido retomados de las entrevistas hechas a diferentes actores. En el último apartado de este estudio, se presenta un conjunto de propuestas que pretenden contribuir a un mejor funcionamiento de dichos Concejos

Evaluación de financiamiento para un bar de cerveza artesanal en el distrito de Barranco

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Mechanisms Of Inhibition Of Cigarette Smoke Genotoxicity And Carcinogenicity

Epidemiological studies have demonstrated that it is possible to prevent lung cancer and other smoke-related diseases by avoiding exposures to tobacco smoke. A complementary strategy is chemoprevention, which is based on the administration of dietary and pharmacological agents, which is addressed to (a) addicted active smokers, who are unable to quit smoking, (b) ex-smokers, who are still at risk for several years, and (c) involuntary smokers, including passively exposed individuals as well as transplacentally exposed individuals. The biological effects of cigarette smoke (CS) as a complex mixture, either mainstream (MCS) or sidestream (SCS) or environmental (ECS), have been poorly explored. We showed that MCS and ECS induce a broad variety of alterations of intermediate biomarkers in animal models, including adducts to nuclear DNA and mtDNA, oxidatively generated DNA damage, proliferation, apoptosis, alterations of oncogenes and tumor suppressor genes, multigene expression, microRNA and proteome profiles as well as cytogenetic damage in the respiratory tract, bone marrow and peripheral blood. CS-altered end-points were variously modulated by chemopreventive agents of natural or pharmacological origin, such as N-acetyl-L-cysteine (NAC), 1,2-dithiole-3-thione, oltipraz, 5,6-benzoflavone, phenethyl isothiocyanate (PEITC), indole-3-carbinol, sulindac, and budesonide. Combinations of agents were also assayed. Since it is difficult to assess the efficacy of chemopreventives in clinical trials, it is essential to understand the mechanisms by which certain agents are expected to prevent smoke-related cancer. Preclinical studies are also useful to demonstrate the potential efficacy of chemopreventive agents. Unfortunately, until recently a suitable animal model for evaluating CS carcinogenicity and its chemoprevention was not available. We demonstrated that ECS and especially MCS become potently carcinogenic when exposure of mice starts at birth, as shown by very short latency times, high incidence and multiplicity of benign lung tumors, early occurrence of malignant lung tumors, and lesions in other organs. This mouse model was successfully used to demonstrate the ability of NAC, PEITC, and budesonide to prevent smoke-induced lung cancer, according to protocols mimicking the situation either in current smokers or in ex-smokers. Other dietary or pharmacological agents, including curcumin, anthocyanins, myo-inositol, SAHA, bexarotene and pioglitazone, are now under study. NAC was even successful to prevent lung cancer induced by MCS after birth when it was administered during the prenatal life. Therefore, it is now possible to investigate in vivo not only alterations of intermediate biomarkers but also the modulation of CS carcinogenesis by chemopreventive agents working with different mechanisms

Proinsulin: From Hormonal Precursor to Neuroprotective Factor

In the last decade, non-canonical functions have been described for several molecules with hormone-like activities in different stages of vertebrate development. Since its purification in the 1960s, proinsulin has been one of the best described hormonal precursors, though it has been overwhelmingly studied in the context of insulin, the mature protein secreted by the pancreas. Beginning with our discovery of the presence and precise regulation of proinsulin mRNA in early neurulation and neurogenesis, we uncovered a role for proinsulin in cell survival in the developing nervous system. We subsequently demonstrated the ability of proinsulin to prevent pathological cell death and delay photoreceptor degeneration in a mouse model of retinitis pigmentosa. In this review, we focus on the evolution of proinsulin/insulin, beginning with insulin-like peptides expressed in mainly the neurosecretory cells of some invertebrates. We summarize findings related to the regulation of proinsulin expression during development and discuss the possible effects of proinsulin in neural cells or tissue, and its potential as a neuroprotective molecule

Epidemiology of cancers of infectious origin and prevention strategies

Infectious and parasitic diseases represent the third cause of cancer worldwide. A number of infectious and parasitic agents have been suspected or recognized to be associated with human cancers, including DNA viruses, such as papillomaviruses (several HPV types), herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), and hepadnaviruses (HBV); RNA viruses, such as flaviviruses (HCV), defective viruses (HDV), and retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2,HERV-K, and XMRV); bacteria, such as H. pylori, S. typhi, S. bovis, Bartonella, and C. pneumoniae; protozoa, such as P. falciparum; trematodes, such as S. haematobium, S. japonicum, S. mansoni, O. viverrini, O. felineus, and C. sinensis. Each one of the chronic infections with H. pylori, HPV, and HBV/HCV is responsible for approximately the 5% of all human cancers. The primary prevention of infection-related cancers is addressed both to avoidance and eradication of chronic infections and to protection of the host organism. Vaccines provide fundamental tools for the prevention of infectious diseases and related cancers. The large-scale application of the HBV vaccine has already shown to favorably affect the epidemiological burden of primary hepatocellular carcinoma, and HPV vaccines have specifically been designed in order to prevent cervical cancer and other HPV-related cancers. The secondary prevention of infection-associated cancers has already found broad applications in the control of cervical cancer. Detection of early gastric cancer by endoscopy has been applied in Asian countries. Avoidance of local relapses, invasion, and metastasis may be achieved by applying tertiary prevention, which targets specific mechanisms, such as angiogenesis

The Analysis of Implementation of Integrated Village Program-Establishing the Era of Independent Society for the Development in Pobaim Village, Nimboran District, Jayapura Regency

Policy and development are associated concepts. To improve the quality of life, policy must be made within the context of development. Policy so made becomes the manual for implementing development goals into various programs and projects. Nowadays, the failure of development which has been aimed at the growth of the economy, and which has the characteristics of being centralized and top-down, has increased the awareness of the need for development agents to include the dimension of empowerment in the national development strategy. Empowerment development strategy has already been implemented in Jayapura regency. This basic strategy is aimed at inspiring the people in the districts and villages to take initiative in independent development. The popular participation of the society has made the implementation of common goals in the district achieved so effectively that the development of Pobaim village, Nimboran district, and Jayapura regency can be done maximally and the society can achieve independence in the implementation of development. The limitation of this research is that it is only done in one location. Research done in different locations may produce different result

La excelencia científica en pareja: Tanto monta-monta tanto

La presencia de las mujeres en la ciencia y la tecnología, especialmente en los niveles más altos, es escasa y no refleja, incluso en nuestros días, la masiva incorporación de las mujeres al mundo académico y profesional. El peso de los estereotipos sociales sitúa a menudo a las mujeres ante la disyuntiva "familia/carrera", dilema especialmente relevante en una profesión vocacional y muy absorbente como la investigación. Este dilema hace que la elección del compañero de vida sea crucial para el desarrollo de la mujer. Hemos escogido aquí el ejemplo de seis parejas de científicos, tres españolas y tres extranjeras, en las que ellas, todas excepcionales, han sido incondicionalmente apoyadas por sus parejas científicas y vitale