Addictiveness and sttractiveness of tobacco additives

SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks): et al.The Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) has been asked to evaluate the role of tobacco additives in the addictiveness and attractiveness of tobacco products. The criteria for dependence established in humans indicate that tobacco has a high addictive potential, but it remains difficult to assess the addictiveness of individualadditives. In animal studies the addictive potency of the final tobacco product cannot be assessed. The reinforcing potency of drugs is measured after intravenous injections and suggests that the abuse liability of pure nicotine is weaker than the addictive potential of tobacco products in humans. The currently used methods to define addictiveness of nicotine and additives are thus not considered adequate. In humans, the positive correlation between tobacco consumption and dependence suggests that individuals with high nicotine levels in their blood are more dependent. In animal studies using self-administration, an inverted U-shaped dose-response curve has generally been revealed suggesting that the addictiveness of nicotine is not directly linearwith the dose. There is however substantial variation in the response to nicotine in both animals and humans, and genetic factors probably play an important role. No tobacco additives which are addictive by themselves have so far been identified. However, sugars, polysaccharides and cellulose fibres which are naturally present in tobacco, or sugars added in high quantities to most tobacco products, give rise to numerous aldehydes, such as acetaldehyde, in tobacco smoke. Acetaldehyde given intravenously is self-administered and enhances the addictiveness of nicotine in experimental animals. Additives that facilitate deeper inhalation (e.g. menthol) or inhibit the metabolism of nicotine may enhance the addictiveness of nicotine indirectly. Substances such as ammonia that increase the pH of the tobacco and the smoke, result in higher amounts of uncharged nicotine. However, it is uncertain if more nicotine isabsorbed with higher smoke pH. For smokeless tobacco it seems that an increased pH enhances nicotine absorption in the mouth.The methods used to quantify the addictive potency of additives have limitations because of technical challenges in experimentally manipulating the presence or absence of anadditive in a tobacco product. Such experiments require large technical and financial resources. In addition, there are ethical issues if testing in humans is considered. Due to these limitations, the available methodologies are not considered adequate. A number of technical characteristics of cigarettes (paper, filter, packing, geometry) influence the content of different substances in the smoke and the size of smoke particles. Many smokers compensate for a lower dose of nicotine by increasing puff volume and frequency, and by deeper inhalation. The particle size of the smoke aerosol does not seem to substantially influence the exposure to nicotine. The technical characteristics of cigarettes may thus modulate smoking behaviour but it is uncertain if this leads to a higher risk of addiction. Attractiveness is defined as the stimulation to use a product. The attractiveness of tobacco products may be increased by a number of additives but is also influenced by external factors such as marketing, price etc. Animal models do not currently exist for the assessment of attractiveness. In humans, the attractiveness of individual tobaccoproducts may be compared in panel studies, surveys, and by experimental measures. Another method is to experimentally adjust tobacco products to exclude or include individual additives and test responses to them. However, this type of research is difficult due to ethical considerations that will usually preclude human testing of tobacco products, particularly among non-users or children. The use of fruit and candy flavours seems to favour smoking initiation in young people. Menthol also attracts a number of smokers, in particular African Americans. Some additives decrease the harshness and increase the smoothness of the smoke. Certain additives yield a full and white smoke and other additives reduce the lingering odour of the smoke in order to favour the acceptability of smoking to people around. Additives considered attractive may in principle lead to brand preference or a higher consumption of tobacco products. However, it remains difficult to distinguish the direct effects of these additives from indirect effects such as the marketing towards specific groups.Peer Reviewe

Spatial distribution of Parkinson's disease mortality in Spain, 1989-1998, as a guide for focused aetiological research or health-care intervention

<p>Abstract</p> <p>Background</p> <p>Aetiologically, genetic and environmental factors having an uneven spatial distribution may underlie Parkinson's disease (PD). Undiagnosis of PD in selected regions might have limited access to treatment with levodopa and simultaneously, if present at death, determined PD underreporting at the death record. The purpose of this study was to describe and analyse municipal mortality due to PD in Spain in aetiological and interventional perspective.</p> <p>Methods</p> <p>PD mortality at a municipal level was modelled using the Besag-York- Molliè autoregressive spatial model, combining demographic information with cause-of-death diagnostic data (International Classification of Diseases 9^thRevision (ICD-9) code 332.0). Municipal relative risks (RRs) were independently estimated for women, men and both sexes, and plotted on maps depicting smoothed RR estimates and the distribution of the posterior probability of RR>1.</p> <p>Results</p> <p>A south-north gradient, with large geographical areas suggesting clustered towns with high mortality, was seen in Asturias, the Basque Country, Balearic Islands and, particularly, in the Lower Ebro valley around Tarragona. Similarly, there was a suggestion that lowest mortality was clustered in the south-east and south-west. We identified some isolated or clustered municipalities with high mortality that were situated near industrial plants reported to be associated with environmental xenobiotic emissions. However, the same pattern was also observed for some cities with low mortality.</p> <p>Conclusion</p> <p>Municipal PD mortality in Spain was unevenly distributed. Patterns were roughly similar to reported provincial PD mortality and use of levodopa. While the overall pattern appears to result from spatially selective PD undiagnosis, and can not be ascribed to industrial emissions, it can not be excluded that selected "hot spots" reflect genetic factors and/or environmental exposures inducing parkinsonism. A few municipal populations, located in low-mortality-risk areas in the vicinity of polluting plants or registering high excess PD mortality, might constitute a priority for conducting direct etiological studies. Additionally, interventions aimed to reduce potential PD undiagnosis might be most appropriate in the South.</p

Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement

Resveratrol is a natural compound that mimics the antioxidant and antiaging effects of caloric restriction, mainly mediated through SIRT1, a deacetylase that induces longevity and neuroprotection. We aimed to analyze the effects of resveratrol on the brain status of control non-transgenic (NoTg) and AD transgenic (3xTg-AD) mice to discern the mechanisms involved in a potential inducement of resilience against age-related neurodegeneration and Alzheimer's disease (AD). Mice were fed with a diet supplemented with 100 mg/kg of resveratrol from 2 months of age during 10 months. Resveratrol administration induced complete protection against memory loss and brain pathology in 3xTg-AD mice, and also induced cognitive enhancement in healthy NoTg mice. Resveratrol improved exploration and reduced anxiety in both mouse strains, indicative of well-being. Resveratrol reduced the presence of Aβ and p-tau pathology in the hippocampus of the 3xTg-AD mouse. Proteostasis analysis showed the following in both NoTg and 3xTg-AD mice: (i) increased levels of the amyloid-degrading enzyme neprilysin, (ii) reduction of the amyloidogenic secretase BACE1, and (iii) increase of proteasome protein levels and enhancement of proteasome activity. Resveratrol also increased AMPK protein levels, then upregulating the SIRT1 pathway, as shown by the activation of PGC-1α and CREB in both mice, resulting in further beneficial changes. Our data demonstrated that resveratrol induces cognitive enhancement and neuroprotection against amyloid and tau pathologies. Improvement of proteostasis by resveratrol, in both healthy and AD mice, suggests that it is a mechanism of brain resilience and defense against neurodegeneration caused by the accumulation of aberrant proteins

Las nuevas enfermedades y la contaminación química.

Hace varios años, un grupo de prestigiosos científicos, entre los que se contaban varios galardonados con el Premio Nobel, suscribieron el Llamamiento de París, en el que advertían de que la contaminación química está produciendo una pandemia silenciosa, que contribuye, entre otras cosas, al crecimiento del cáncer, de la infertilidad y de problemas en el sistema hormonal o en el aparato respiratorio o nervioso. En el mismo sentido se han expresado otros manifiestos científicos como la Declaración de Praga, esta última centrada en las alteraciones endocrinas. El hombre ha creado más de 100.000 sustancias químicas sintéticas que no estaban presentes en la naturaleza, y sólo una mínima parte de ellas ha sido debidamente evaluada en cuanto a sus posibles riesgos para la salud humana y el medio ambiente.Peer Reviewe

La investigación biomédica en España (II). Evaluación del Fondo de Investigación Sanitaria (FIS) a través de los proyectos de investigación financiados en el período 1988-1995 a centros de investigación, facultades y escuelas

En un trabajo previo, publicado en esta misma revista, los autores han estudiado los resultados generados por los proyectos de investigación financiados por el Fondo de Investigación Sanitaria (FIS) a las Instituciones Sanitarias Asistenciales (hospitales) y los procedentes de los cuestionarios de encuestas remitidos a los investigadores responsables de tales proyectos y a los directores gerentes de los hospitales en los que se realizaron los mismos. En el presente trabajo, se continúa el proceso de evaluación del FIS, centrándose la atención en la distribución de los proyectos de investigación concedidos a los centros de investigación, facultades y escuelas, y en los resultados obtenidos a través de los cuestionarios de encuesta cumplimentados por los investigadores principales pertenecientes a estas instituciones o entidades.La realización de este trabajo ha sido posible gracias a la financiación otorgada por el FIS al proyecto de investigación 96/1803.Peer reviewe

Differential Estrogenic Effects of the Persistent Organochlorine Pesticides Dieldrin, Endosulfan, and Lindane in Primary Neuronal Cultures

The organochlorine chemicals endosulfan, dieldrin, and ghexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the g-aminobutyric acid-A (GABAA) receptor makes them convulsants. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER). Here, we study the effects of dieldrin, endosulfan, and lindane on ERs in primary cultures of cortical neurons (CN) and cerebellar granule cells (CGC). All the compounds tested inhibited the binding of [3H]-estradiol to the ER in both CN and CGC, with dieldrin in CGC showing the highest affinity.We also determined the effects of the pesticides on protein kinase B (Akt) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Dieldrin and endosulfan increased Akt phosphorylation in CN, which was inhibited by the ERb antagonist 4-[2-phenyl-5,7- bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl]phenol. Instead, Akt and ERK1/2 phosphorylation induced by dieldrin in CGC was mediated by multiple activation of ERa, ERb, and G protein– coupled receptor 30. Lindane did not activate these pathways, but it inhibited estradiol-mediated Akt and ERK1/2 activation. In CN, all the chemicals activated ERK1/2 through a mechanism involving GABAA and glutamate receptors. Long-term exposure to these pesticides reduced the levels of ERa, but not of ERb. Moreover, extracts of CN treated with endosulfan, dieldrin, or lindane induced cell proliferation in MCF-7 human breast cancer–derived cells, whereas only extracts of CGC treated with dieldrin induced MCF-7 cell proliferation. Overall, the observed alterations on ER-mediated signaling and ER levels in neurons might contribute to the neurotoxicity of these organochlorine pesticides.Ministry of Health(FIS 061212, FIS 10/0453); CIBERESP (AA08-001); Generalitat de Catalunya (2009/SGR/214); Consejerı ´a de Innovacio´n, Ciencia y Empresa de la Junta de Andalucı´a (P09-CTS-5488).Peer reviewe

Peripheral maintenance of the axis SIRT1-SIRT3 at youth level may contribute to brain resilience in middle-aged amateur rugby players

Physical exercise performed regularly is known to improve health and to reduce the risk of age-related diseases. Furthermore, there is some evidence of cognitive improvement in physically active middle-aged and older adults. We hypothesized that long-term physically active middle-aged men may have developed brain resilience that can be detected with the analysis of peripheral blood markers. We aimed to analyze the activation of pathways potentially modulated by physical activity in a cohort of healthy amateur rugby players (n = 24) and control subjects with low physical activity (n = 25) aged 45-65 years. We had previously reported neuropsychological improvement in immediate memory responses in the player group compared to the controls. Here, we tested the expression of selected genes of longevity, inflammation, redox homeostasis, and trophic signaling in whole blood mRNA. Analyses were also performed on blood samples of young (aged 15-25 years) control subjects with low physical activity (n = 21). Physical activity and other lifestyle factors were thoroughly recorded with standardized questionnaires. Interestingly, middle-aged control subjects showed lower levels of expression of SIRT1, SIRT3, CAT, and SOD1 than the young controls, although rugby players maintained the expression levels of these genes at a young-like level. Middle-aged players showed lower levels of IL1B than the non-physically active groups. However, there was a tendency towards a decrease in trophic and transduction factors in middle-aged groups as compared to the young controls. A statistical study of Spearman's correlations supported a positive effect of sporting activity on memory and executive functions, and on peripheral gene expression of SIRT1, SIRT3 and downstream genes, in the middle-aged rugby players. Our results indicate that the SIRT1-SIRT3 axis, and associated neuroprotective signaling, may contribute to the anti-aging resilience of the brain mediated by physical exercise

SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks) Opinion on The safety of the use of bisphenol A in medical devices

SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks), Safety of the use of bisphenol A in medical devices, 18 February 2015Testai, Emanuela; Hartemann, Philippe; Rodríguez-Farré, Eduard; Rastogi, Suresh Chandra; de Jong, Wim; Bustos, Juana; Castle, Laurence; Gundert-Remy, Ursula; Hensten, Arne; Kopperud, Hilde Molvig; Olea, Nicolás; Piersma, Aldert; SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks). The Safety of the use of Bisphenol A in medical devices. [S.l.]: European Commission, 2015. 166 p. ISSN 1831-4783 . ISBN 978-92-79-30133-9 . DOI Doi: 10.2772/75546This opinion assesses whether the use of bisphenol A in medical devices such as implants, catheters, and dental devices could give reasons for safety concerns, to provide indications on limit values for BPA release from medical devices and to identify any patient group, e.g. infants, pregnant and breastfeeding women who would be particularly at risk. Several exposure scenarios have been evaluated taking into account the material used, information related to BPA leaching, the duration of a single treatment and the frequency of treatments, giving rise to toxicologically relevant acute, short and long term exposure. The SCENIHR concludes that risk for adverse effects of BPA may exist when the BPA is directly available for systemic exposure after non-oral exposure routes, especially for neonates in intensive care units, infants undergoing prolonged medical procedures and for dialysis patients. Although the benefit of medical devices has also to be considered, the SCENIHR recommends that, where practicable, medical devices that do not leach BPA should be used. The possibility of replacing BPA in these products should be considered against their efficiency in the treatment, as well as the toxicological profile of the alternative materials. However, better data on exposure would be beneficial for the refinement of the present risk assessment, to be carried out when new data on exposure via medical devices will be available.Peer Reviewe

Jardins per a la salut

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia. Assignatura: Botànica farmacèutica. Curs: 2014-2015. Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són el recull de les fitxes botàniques de 128 espècies presents en el Jardí Ferran Soldevila de l’Edifici Històric de la UB. Els treballs han estat realitzats manera individual per part dels estudiants dels grups M-3 i T-1 de l’assignatura Botànica Farmacèutica durant els mesos de febrer a maig del curs 2014-15 com a resultat final del Projecte d’Innovació Docent «Jardins per a la salut: aprenentatge servei a Botànica farmacèutica» (codi 2014PID-UB/054). Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pels professors de l’assignatura. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica. També s’ha pretès motivar els estudiants a través del retorn de part del seu esforç a la societat a través d’una experiència d’Aprenentatge-Servei, deixant disponible finalment el treball dels estudiants per a poder ser consultable a través d’una Web pública amb la possibilitat de poder-ho fer in-situ en el propi jardí mitjançant codis QR amb un smartphone