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PubMedDate not supplied

[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].

The combined birth prevalence of cleft palate [CP] and cleft lip with or without cleft palate [CL(P)] in Europe is approximately one in 700 with characteristic regional variations. Orofacial clefting (OC) is therefore now one of the most frequent congenital anomalies, with a higher birth prevalence that Down's Syndrome or Neural Tube defects, but still lower than cardiovascular malformation. Babies with OC require a multidisciplinary medical approach, surgery and rehabilitative treatments over time. This means an important effort in terms of social organization as well as economical costs for the health care system. In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex and heterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role of genetics in producing susceptibility to the environment. Four categories of genes for which there are results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of the embryo or in a particular period of the palatine arch development, such as the transforming growth factors alpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to the OC's pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), the methylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes or locus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Several environmental factors have been implicated in the OC etiology; among those, the folic acid supplementation during the periconceptional period that was found effective in the prevention of neural tube defects. In fact, folic acid deficiency may be responsible for different malformations through a common mechanism that interferes with the embryonic development, depending on the maternal or embryo genotype. Further investigation is required to study in depth how the genotype would modify the role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seem to be able to give worthwhile information. Studies carried out in Europe on these issues are a few, particularly those on gene-environment interaction. Recent results obtained in molecular biology and the availability of wealth of data can allow to perform ad hoc investigations, being important not only for the basic research but also for their public health implications. For this objective a specific scientific network at the European level has been set by the European Science Foundation (ESF), whose first step will be to establish consistent case ascertainment and data collection across Europe and to develop standardized protocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative research will enable combined analysis and lead to the identification of genetic susceptibility to certain environmental factors, including nutrition. Such studies would inform the current debate about the efficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo. Subsequent public health measures targeted according to risk might reduce the prevalence of disorders such as orofacial clefting.

Adult↗
PubMed2000

[Chemicals toxic to the olfactory system. Analysis and description].

AN IMPORTANT PROBLEM: Occupational exposure to chemical products can have toxic effects on the olfactory system. An important number of patients have experienced olfactory disorders subsequent to the development of the chemical industry and atmospheric pollution. EPIDEMIOLOGY DATA: Straightforward data are difficult to collect because several cofactors other than the toxic product are involved. Two lists of toxic products can be made. The first list includes products for which scientific data is available and the second products for which data is lacking. Olfactory tests also differ between authors and countries. TWO TYPES OF TOXICITY: Acute, accidental toxicity is evidenced by the lesions caused by inhalation of high-doses of strongly toxic agents. Chronic intoxication caused by lower concentrations of these inhaled agents does not produce a trigeminal reflex leading to a modified respiratory rate reducing the airborne aggression. APPROXIMATIONS: Clinical data describing the olfactory toxicity of certain industrial and chemical compounds are very significant but often cannot prove a cause and effect relationship. Data obtained with experimental models in rodents are difficult to extrapolate to humans.

Air Pollutants, Occupational↗
PubMed1997

Differentiation and breast cancer.

The mammary gland is an organ whose size, shape and function undergo fundamental changes during the various phases of a woman's growth. Although the development of the mammary gland begins during infancy, the most dramatic changes occur with the initiation of puberty. Pregnancy and lactation complete the functional development of the organ, which regresses during menopause. Epidemiological and experimental studies have demonstrated that certain hormonal influences, especially those related to reproduction, modify the risk of developing breast cancer. Thus, a full term pregnancy completed before the age of 24 years significantly reduces the lifetime incidence of breast cancer. Although the mechanism through which pregnancy protects the breast from breast cancer has not been clearly established, experimental models of mammary carcinogenesis have allowed researchers to determine that pregnancy inhibits the initiation of the neoplastic process through the induction of a complete differentiation of the mammary gland. This process activates specific genes, which in turn modify the response of the organ to ulterior hormonal changes. It is postulated that the same mechanism might be responsible for the protective effect of a woman's early first full term pregnancy. The greater incidence of breast cancer observed in nulliparous women correlates well with the greater susceptibility of the virgin rat to develop mammary carcinomas when exposed to chemical carcinogens. The successful induction of malignant transformation in the virgin animal mammary epithelium is due to the presence of undifferentiated structures with a high rate of cell proliferation. These structures are eliminated by pregnancy. The breast of nulliparous women retains those undifferentiated structures, which increase the predisposition of the organ to undergo malignant transformation, which will manifest itself clinically several years after its initiation. The correlation of human epidemiological, clinical and experimental data with those data obtained in rodent experimental models lends support to this hypothesis.

Animals↗
PubMed1993

Molecular epidemiology of lung cancer and the modulation of markers of chronic carcinogen exposure by chemopreventive agents.

Chronic inhalation exposure to environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs), cigarette smoke, 4-aminobiphenyl (4-ABP), ethylene oxide, and styrene is associated with elevations in biomarkers such as DNA adducts, protein adducts, sister chromatid exchanges (SCEs), chromosomal aberrations, gene mutation, and/or oncogene activation. These biomarkers indicate an increased cancer risk for the exposed population, although quantitative estimates cannot be made with certainty. There is convincing epidemiological evidence that the antioxidant and free radical-scavenging vitamins C and E and beta-carotene (beta-C) protect against cancer of the lung and other epithelial tissues, with somewhat weaker evidence for retinol. Experimental studies demonstrate that these micronutrients are capable of blocking or reducing tumor formation caused by diverse carcinogens. A variety of mechanisms appear to be involved, including suppression of carcinogen activation, enhancement of carcinogen detoxification, induction of cellular differentiation, inhibition of mutagenesis, enhancement of immunologic function, and/or reduction of the formation of carcinogen-DNA adducts, SCEs, micronuclei, and other markers of genotoxic damage. Therefore, we have recently investigated the possible modifying effect of serum vitamins C and E, beta-C, and retinol on a number of such biomarkers in a case-control study of lung cancer, and in a cross-sectional study of heavy smokers. Preliminary results indicate an inhibitory effect of certain vitamins on DNA adduct formation. A significant number of human intervention trials are ongoing involving these vitamins. It appears that biomarkers can provide useful intermediate endpoints for assessment of both the mechanisms and the efficacy of chemopreventive agents.

Animals↗
PubMed1998

Correlation between UVB irradiation and the proportion of cataract--an epidemiological study based on a nationwide patient survey in Japan.

Among the multiple factors affecting the human eye in work environment, ultraviolet B irradiation (UVB) has received much attention recently. To provide a clear information for the association between cataract and UVB irradiation, the prevalence data from the Patient Survey and UVB estimates in all the 47 prefectures in Japan were used to examine the relationship between cataract and UVB. In analyzing the relationship, we controlled possible effect modifiers; which were aged, that is 65 years old (yo.) or older, population per ophthalmologist, proportions of all the patients among the aged population and proportion of very elderly population (75 yo. or older) among the aged population. A sex-specific logistic regression analysis revealed that the adjusted odds ratio in women was 1.118 with a 95% confidence interval of 1.058-1.183. However, the adjusted odds ratio in men was not statistically significant (1.048 with 95% confidence interval 0.968-1.135). The unstable results of this study may be largely due to the non-definitive estimation of UVB exposure that this kind of study should be repeated when more valid UVB estimates is available.

Aged↗
PubMed1986

[Therapy and prevention of reflux esophagitis. Results of a multicenter study with cimetidine. I: Epidemiology and results of acute therapy].

In a sequential observational study efficacy and safety of two dosage regimens of cimetidine for the treatment of reflux-oesophagitis (RE) were examined. 22 office-based specialists took part in the trial. 187 patients received 1600 mg cimetidine (400 mg q.i.d.) daily and 136 patients received 800 mg cimetidine (400 mg b.i.d.) daily, over twelve weeks. The two dosages proved to be equally effective. In the group of patients with RE of stage I at the beginning of the trial, the healing rates were 82% under 1600 mg cimetidine/die and 86% under 800 mg cimetidine/die. In the group of those patients, who entered the study with RE of stage II, in both dosage groups the lesions of 87% of the patients were healed completely or had decreased to stage I. The severity of the mucosal lesions was judged endoscopically, based on a classification scheme modified according to Savary and Miller. The incidence of unwanted symptoms was not significantly different in both dosage groups (1600 mg: 5.3%, 800 mg: 3.4%); none of the symptoms which occurred was judged as definitely caused by cimetidine. The patient collective of the trial was characterized epidemiologically; out of the risk factors examined, only duration of RE history and number of previous RE episodes correlated with the severity of the disease, smoking and alcohol consumption showed no influence.

Adolescent↗
PubMed2003

Cross-cultural comparison of neurobehavioral performance in Asian workers.

Widely-used neurobehavioral tests have been developed and standardized on Western populations, but studies on subject factors for Asian populations have been very limited. For the effective application and interpretation of neurobehavioral tests in Asian populations, an evaluation of the effects of subject factors, including cultural background, is necessary. A cross-cultural study was conducted to evaluate the effects of cultural background and the interaction between cultural background and education on neurobehavioral tests in Asian populations. The Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Symbol Digit, and Finger Tapping Speed) and a pegboard test were administered to 537 workers who were not exposed to chemicals at work from Fareast (Korea and Chinese), Central (Uzbekistan and Tajikistan), and South Asia (Sri Lanka and Indonesia). The Fareast Asian group exhibited better performance in adjusted test scores than other Asian groups, achieving significance for Symbol Digit and Finger Tapping Speed in both genders. The magnitude of the effect of cultural background on Symbol Digit was comparable to the effect of about 10 years of education. Cultural background did not modify the relation between years of education and Symbol Digit in either males or females. This study may provide the first evidence that cultural background has a large impact on neurobehavioral test performance, even within Asian populations, and suggests that cultural background is a critical confounding factor that must be controlled in epidemiologic studies which include Asian populations in the sample.

Adolescent↗
PubMed2004

Psychopharmacological interactions between nicotine and ethanol.

Epidemiological, clinical, and laboratory evidence has shown a positive correlation between cigarette smoking and ethanol use, and previous studies suggest some commonality in the neural pathways mediating effects of nicotine and ethanol. In this study, the subjective and behavioral interactions among nicotine, ethanol, and the nicotinic antagonist mecamylamine were investigated. The main objectives were to determine how the rewarding effects of nicotine might be modified by ethanol, and to compare the effects of ethanol with those of a nicotinic antagonist (mecamylamine). A total of 48 smokers who regularly consumed alcoholic beverages participated in four laboratory sessions presenting a 2 (nicotine vs. denicotinized cigarette smoke)x2 (10 mg oral mecamylamine hydrochloride vs. placebo)x2 (ethanol.5 g/kg vs. placebo) design, with ethanol as a between-subjects factor. Dependent measures included blood alcohol concentration (BAC), as assessed by breath alcohol detector; subjective drug effects; and rate of ad lib smoking during a 2-hr period. Results showed that peak BAC averaged.03 g/dl in the ethanol condition. Ethanol potentiated some of the subjective rewarding effects of nicotine, including smoking satisfaction, stimulant as well as calming effects, and relief of craving for cigarettes. During the ad lib smoking period, mecamylamine decreased satisfaction associated with the nicotine-containing cigarettes; mecamylamine also induced smoking but only in the placebo ethanol condition. These results highlight the potent interaction between ethanol and nicotinic systems, and suggest that ethanol can potentiate the rewarding effects of nicotine as well as offset some of the effects of a nicotinic antagonist.

Adult↗
PubMed1996

[Actions of dehydroepiandrosterone: possible links with aging].

Dehydroepiandrosterone (DHEA) and its sulfo-conjugated derivative (SDHEA), secreted by the adrenal glands, are the most abundant circulating steroids in the human organism. The well-established fact that levels decrease progressively with age suggests a role in the aging process. They could also play a preventive role via an antitumoral action, stimulation of the immune system, an antiosteoporotic effect, a neuropsychologic action and cardiovascular protection. Nevertheless, it is not certain that evidence obtained from animal models can be transposed to man due to the specific nature of adrenal secretion of steroids in the human species. Epidemiological studies have often provided conflicting results. There have been few trials of administration in man, mostly aimed at studying the metabolic effects of DHEA. There is no evidence of secondary effects. Inversely, high-doses lead to transformation into active androgens with deleterious metabolic effects. Consequently, the current trend is to use low doses. Body weight, body composition, and sensitivity to insulin are not modified although variable effects on the lipid profile have been observed. Finally one study has produced much debate: a randomized trial demonstrating an improvement in wellbeing... Confirmation of this effect is certainly needed. In the absence of a satisfactory animal model, randomized prospective studies versus placebo are required to study the effect of substitution therapy in elderly subjects.

Aging↗
PubMed2005

A brief conceptual tutorial on multilevel analysis in social epidemiology: investigating contextual phenomena in different groups of people.

STUDY OBJECTIVE: (1) To provide a didactic and conceptual (rather than mathematical) link between multilevel regression analysis (MLRA) and social epidemiological concepts. (2) To develop an epidemiological vision of MLRA focused on measures of health variation and clustering of individual health status within areas, which is useful to operationalise the notion of "contextual phenomenon". The paper shows how to investigate (1) whether there is clustering within neighbourhoods, (2) to which extent neighbourhood level differences are explained by the individual composition of the neighbourhoods, (3) whether the contextual phenomenon differs in magnitude for different groups of people, and whether neighbourhood context modifies individual level associations, and (4) whether variations in health status are dependent on individual level characteristics. DESIGN AND PARTICIPANTS: Simulated data are used on systolic blood pressure (SBP), age, body mass index (BMI), and antihypertensive medication (AHM) ascribed to 25 000 subjects in 39 neighbourhoods of an imaginary city. Rather than assessing neighbourhood variables, the paper concentrated on SBP variance between individuals and neighbourhoods as a function of individual BMI. RESULTS: The variance partition coefficient (VPC) showed that clustering of SBP within neighbourhoods was greater for people with a higher BMI. The composition of the neighbourhoods with respect to age, AHM use, and BMI explained about one fourth of the neighbourhood differences in SBP. Neighbourhood context modified the individual level association between BMI and SBP. Individual level differences in SBP within neighbourhoods were larger for people with a higher BMI. CONCLUSIONS: Statistical measures of multilevel variations can effectively quantify contextual effects in different groups of people, which is a relevant issue for understanding health inequalities.

Adult↗
PubMed1999

Job strain and evolution of mental health among nurses.

The objective of this 2nd phase of a 2-year study among female nurses was to provide further empirical validation of the demands-control and social support model. The association of job strain with psychological problems and the potential modifying role of social support at work were examined. A questionnaire was sent at the workplace to 1,741 nurses. The same associations were found between psychological demands, decision latitude, and a combination of the 2 with psychological distress and emotional exhaustion for current exposure and for cumulative exposure. Social support had a direct effect on these psychological symptoms but did not modify their association with job strain. Longitudinal and prospective data are needed to study the occurrence and persistence of health problems when exposure is maintained or retrieved.

Adaptation, Psychological↗
PubMed2000

Placenta praevia and male sex at birth: results from a population-based study.

This study examined the relationship between male sex at birth and placenta praevia in 433031 mother/infant dyads (linked by a common institutional code and hospital admission number) in the Canadian province of Quebec, during the fiscal years of 1991/92-1995/96. The male-to-female ratio among pregnancies with and without placenta praevia was calculated and compared. The male-to-female ratio at birth was higher in pregnancies complicated by a placenta praevia (1.19) than in those without it (1.04; P < 0.02). This increased ratio persisted after accounting separately for the potential confounding and/or modifying effects of maternal age, infant birthweight and gestational age by stratified and multiple logistic regression analyses. We conclude that pregnant women with male babies carry a higher risk of placenta praevia.

Birth Weight↗
PubMed1995

Review of the biology of Quercetin and related bioflavonoids.

The French paradox is a dietary anomaly which has focused attention on the Mediterranean diet. Epidemiological studies revealed that this diet, replete in flavonoid-rich foods (Allium and Brassica vegetables, and red wine), correlated with the increased longevity and decreased incidence of cardiovascular disease seen in these populations. The most frequently studied flavonoid, quercetin, has been shown to have biological properties consistent with its sparing effect on the cardiovascular system. Quercetin and other flavonoids have been shown to modify eicosanoid biosynthesis (antiprostanoid and anti-inflammatory responses), protect low-density lipoprotein from oxidation (prevent atherosclerotic plaque formation), prevent platelet aggregation (antithrombic effects), and promote relaxation of cardiovascular smooth muscle (antihypertensive, antiarrhythmic effects). In addition, flavonoids have been shown to have antiviral and carcinostatic properties. However, flavonoids are poorly absorbed from the gut and are subject to degradation by intestinal micro-organisms. The amount of quercetin that remains biologically available may not be of sufficient concentration, theoretically, to explain the beneficial effects seen with the Mediterranean diet. The role of flavonoids may transcend their presence in food. The activity of flavonoids as inhibitors of reverse transcriptase suggests a place for these compounds in the control of retrovirus infections, such as acquired immunodeficiency syndrome (AIDS). In addition to specific effects, the broad-modulating effects of flavonoids as antioxidants, inhibitors of ubiquitous enzymes (ornithine carboxylase, protein kinase, calmodulin), and promoters of vasodilatation and platelet disaggregation can serve as starting material for drug development programmes.

Animals↗
PubMed2004

Fatty acids and the immune system: from basic science to clinical applications.

Over the last 25 years, the effects of fatty acids on the immune system have been characterized using in vitro, animal and human studies. Advances in fatty acid biochemistry and molecular techniques have recently suggested new mechanisms by which fatty acids could potentially modify immune responses, including modification of the organization of cellular lipids and interaction with nuclear receptors. Possibilities for the clinical applications of n-3 PUFA are now developing. The present review focuses on the hypothesis that the anti-inflammatory properties of n-3 PUFA in the arterial wall may contribute to the protective effects of n-3 PUFA in CVD, as suggested by epidemiological and secondary prevention studies. Studies are just beginning to show that dietary n-3 PUFA can be incorporated into plaque lipid in human subjects, where they may influence the morphology and stability of the atherosclerotic lesion.

Animals↗
PubMed2003

Catechin content of 18 teas and a green tea extract supplement correlates with the antioxidant capacity.

Our literature review of currently available data in the area of tea and cancer prevention demonstrated that there is more conclusive evidence for the chemopreventive effect of green tea compared with black tea. We suggest that this is due to a large variation of the flavanol content in tea, which is not taken into consideration in most of the epidemiological studies. It was the purpose of this study to determine the flavanol content of various teas and tea products and to correlate it with their radical scavenging activity. A modified oxygen radical absorbance capacity (ORAC) assay at pH 5.5 was utilized. The total flavavol content varied from 21.2 to 103.2 mg/g for regular teas and from 4.6 to 39.0 mg/g for decaffeinated teas. The ORAC value varied from 728 to 1686 trolox equivalents/g tea for regular teas and from 507 to 845 trolox equivalents/g for decaffeinated teas. There was a significant correlation of flavanol content to ORAC value (r = 0.79, P = 0.0001) for the teas and green tea extract. The large variation in flavanol content and ORAC value among various brands and types of tea provides critical information for investigators using tea in studies of nutrition and cancer prevention.

Antioxidants↗
PubMedDate not supplied

[Mechanisms of protective effects of moderate alcohol consumption on the cardiovascular system].

Consumption of alcoholic beverages has been known in many cultures since the ancient civilizations, so harmful consequences of excessive alcohol intake have been well explained. Many epidemiological studies confirmed lower morbidity and mortality rates of cardiovascular diseases in persons who drink alcohol "moderately" (1-2 drinks a day), independently of the kind of alcoholic beverage. This paper presents the review of molecular mechanisms that are believed to explain cardioprotective effect of moderate drinking--alcohol effects on lipoproteins, endothelial cells, blood clot formation and dissolution, as well as genetic and gender variances modifying the relation. A simple recommendation regarding the increase of alcohol consumption cannot be made on population level. The professionals must therefore concentrate on other preventive methods in order to reduce other significant risk factors of cardiovascular diseases.

Alcohol Drinking↗
PubMedDate not supplied

Modelling endemic onchocerciasis in man in the presence of vector controls.

A stochastic model for a parasitic disease is proposed which describes the acquisition of infectious material from an external source and the subsequent deterioration of the host reacting to the internally produced parasite. The model considers the endemic situation, where the disease is uncontrolled and the structure is both hierarchical and irreversible. The resulting compartmental model can be modified to incorporate piecewise-constant migration rates to respond to possible geographical and sociological fluctuations, which could affect the epidemiological dynamics. The model is illustrated using onchocerciasis prevalence data collected from nine West African village communities in 1975 and 1981, before and after the implementation of widespread larvacide controls as part of the O.C.P. in the Upper Volta region. Significance of the sex effects within onchocerciasis transmission is investigated and the effectiveness of controls is discussed.

Adolescent↗
PubMedDate not supplied

An epidemiologic assessment of genomic profiling for measuring susceptibility to common diseases and targeting interventions.

PURPOSE: The current clinical value of genomic profiling (testing for genotypes at multiple loci) for assessing susceptibility to common diseases and targeting behavioral and medical interventions is questionable. As common diseases result from many gene-environment interactions, epidemiologic studies should be used to examine the value of genomic profiling in terms of clinical validity (future disease positive and negative predictive value stratified by exposure), clinical utility (targeted interventions to reduce disease risk among persons with the profile) and public health utility (comparing reduction of disease burden in the population based on genomic profiling to population-wide interventions). METHODS: We investigate these parameters for a hypothetical common disease (5% lifetime risk), for which 3 genetic variants at different loci and one environmental exposure are risk factors. RESULTS: We show that even for modest effects of each variant alone (risk ratios from 1.5-3.0) and modest interactions between the exposure and the genes, the disease predictive value for people with 2 or more variants (especially 3) can be quite high (50-100%) in the presence of a modifiable exposure. Individual risks can then be reduced by targeted exposure intervention among persons with the genotype. However, the predictive value for multiple genotypes is much lower for rarer diseases (< 1 per 1000). Also, with increasing number of genes in a profile, the population impact of disease reduction for targeted intervention based on genotype will be smaller, especially for rare genotypes, weak associations, and weak interactions. CONCLUSION: To assess the value of genomic profiling, well-designed epidemiologic studies are needed to quantify disease risks, in addition to costs, benefits, and risks for testing and interventions.

DNA Fingerprinting↗