Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
J Psychosom Obstet Gynaecol ; 44(1): 2243648, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37593941

RESUMO

A considerable number of pregnant women experience fear of childbirth (FOC), characterized by worries and fear of the unpredictable. Despite this, the psychological processes in FOC have received notably little attention. The aim of this study was to advance the understanding by exploring the applicability of the Intolerance of Uncertainty (IU) model on FOC. Anonymous data was collected in a sample of pregnant women (N = 357) with varying levels of FOC. Analyses supported the associations between FOC and all proposed psychological processes: IU, negative problem orientation, positive beliefs about worry and avoidance of inner experiences. The exploration of potential mediators of the relation between IU and FOC revealed that, of the three processes from the model, only positive beliefs about worry were a mediator, and more specifically, a partial mediator between IU and FOC. These findings add to the theoretical understanding of FOC, by indicating that the role of IU may be similar to other conditions inflicted by worry and anxiety, which may inform treatment development.


Assuntos
Transtornos Fóbicos , Gravidez , Feminino , Humanos , Incerteza , Ansiedade , Transtornos de Ansiedade , Medo
2.
Eur J Pain ; 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29635880

RESUMO

BACKGROUND: Recurring vulvovaginal pain is common, with evident effects on affected women's lives. Little is known about how affected women cope with painful sexual activities and how coping relates to pain intensity and psychosexual functioning over time. This prospective study explored the impact of avoidance and endurance on sexual function over time. Additionally, patterns of coping were studied on an individual level to increase knowledge about coping and its relation to psychosexual functioning. METHODS: One hundred and seventeen women, 18-35 years old, with recurring vulvovaginal pain answered questionnaires at two measurement points, five months apart, assessing avoidance and endurance coping, pain intensity and psychosexual functioning. A multiple regression model explored the predictive value of avoidance and endurance on sexual function over time. Cluster analyses investigated patterns of coping and stability within the clusters. These subgroups were compared on psychosexual outcomes. RESULTS: Avoidance at baseline was the only significant predictor of sexual function five months later. Distinct and stable subgroups with different patterns of coping were identified, where avoidance and endurance coping were used both separately and combined. Women who both avoided and endured had the most unfavourable outcomes in terms of psychosexual functioning. CONCLUSIONS: Avoidance of sexual activities was related to reduced sexual function over time, which calls for attention and clinical interventions targeting avoidance. Additionally, women who both avoid and endure sexual activities despite pain possibly need tailored interventions, as women with this coping pattern reported the lowest levels of psychosexual functioning. SIGNIFICANCE: In this prospective study, avoidance of sexual activities predicted sexual function over time, when controlling for pain intensity. Subgroups of women using distinct patterns of coping were identified. Those who both avoided and endured had the lowest levels of psychosexual functioning.

3.
Indoor Air ; 25(2): 168-75, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24920172

RESUMO

Particle mass and number concentrations were measured in a mechanically ventilated classroom as part of a study of ventilation strategies for energy conservation. The ventilation system was operated either continuously, intermittently, or shut down during nights while it was on during workdays. It appears that the nighttime ventilation scheme is not important for indoor particle concentrations the following day if fans are operated to give five air exchanges in advance of the workday. The highest concentrations of PM10 were found during and after workdays and were due to human activity in the classroom. The average workday PM10 concentration was 14 µg/m(3) , well below the WHO guideline values. The number concentration of particles with diameter <0.750 µm was typically between 0.5 × 10(3) and 3.5 × 10(3)  particle/cm(3) . These concentrations were largely independent of the occupants. Transient formation of small particles was observed when ventilation was shut down. Then remaining ozone reacted with terpenes emitted by indoor sources and gave up to 8 × 10(3)  particle/cm(3) before formation stopped due to lack of ozone. The intermittent ventilation regime was found least favorable for the indoor air quality in the classroom.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Material Particulado/análise , Instituições Acadêmicas , Ventilação/métodos , Conservação de Recursos Energéticos , Humanos , Tamanho da Partícula , Material Particulado/normas
4.
Indoor Air ; 20(6): 494-501, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21070375

RESUMO

UNLABELLED: The Dampness in Buildings and Health study (DBH) started in the year 2000 in Värmland, Sweden, with a baseline questionnaire sent to all children (n = 14,077) aged 1-6. Five years later, a follow-up questionnaire was sent to the children who were 1-3 years at baseline. A total of 4779 children participated in both the baseline and the follow-up studies and constitute the study population in this cohort study. The aim of this study was to examine the association between exposure to PVC-flooring in the child's and parent's bedroom in homes of children aged 1-3 and the incidence of asthma, rhinitis, and eczema during the following 5-year period. Adjusted analyses showed that the incidence of asthma among children was associated with PVC-flooring in the child's bedroom (AOR 1.52; 95% CI 0.99-2.35) and in the parent's bedroom (1.46; 0.96-2.23). The found risks were on borderline of significance and should therefore be interpreted with caution. There was further a positive relationship between the number of rooms with PVC-flooring and the cumulative incidence of asthma. PVC-flooring was found to be a stronger risk factor for incident asthma in multifamily homes when compared with single-family houses and in smoking families compared with non-smoking families and in women. PRACTICAL IMPLICATIONS: These longitudinal data from the DBH study found an association between the presence of PVC-flooring in the home and incident asthma in children. However, earlier results from the DBH study have shown that PVC-flooring is one important source for phthalates in indoor dust, and exposure to such phthalates was found to be associated with asthma and allergy among children. This emphasizes the need for prospective studies that focus on the importance of prenatal and neonatal exposure to phthalates in the development of asthma and allergy in children.


Assuntos
Asma/epidemiologia , Eczema/epidemiologia , Pisos e Cobertura de Pisos , Ácidos Ftálicos/toxicidade , Rinite Alérgica Perene/epidemiologia , Asma/etiologia , Pré-Escolar , Estudos de Coortes , Eczema/etiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Cloreto de Polivinila , Rinite Alérgica Perene/etiologia , Suécia/epidemiologia
5.
Indoor Air ; 20(4): 329-40, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20557376

RESUMO

UNLABELLED: In a nested case-control study with 198 children with asthmatic and allergic symptoms (cases) and 202 healthy controls in Värmland, Sweden, we have investigated the relationship between mold spore exposure (mean colony-forming unit) indoor and (i) different indexes of moldy odor indoor (observed by professional inspectors and reported by parents), (ii) visible signs of dampness in the homes of the children (observed and reported), and (iii) doctor-diagnosed asthma/allergy in children. No association was found between the spore concentration indoor and moldy odor and signs of visible dampness in the homes. When a semi-quantitative method in distinguishing between moldy houses or non-moldy houses was used, there were no significant differences between the observed indexes of moldy odor or visible signs of dampness (both observed and reported). No association could be found between the spore concentration in indoor air and asthma/allergy in the children. PRACTICAL IMPLICATIONS: Mold spore exposure indoor have been suggested as a possible explanation for airway problems such as asthma and allergy among people living in buildings with moisture-related problems. However, this investigation could not find any associations between the spore concentrations in indoor air and signs of dampness and moldy odor reported by parents or observed by professional inspectors. Neither was there any association between the indoor spore concentration and asthma/allergy among children. With these results, there is no reason for one-time air sampling of mold colony-forming unit (CFU) in indoor air of homes to identify risk factors for asthma/allergy in children living in Scandinavian countries.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Fungos/isolamento & purificação , Habitação , Hipersensibilidade/epidemiologia , Asma/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Fatores de Risco , Esporos Fúngicos/isolamento & purificação , Células-Tronco , Suécia/epidemiologia , Ventilação
6.
Indoor Air ; 19(3): 184-92, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19298228

RESUMO

UNLABELLED: There are consistent findings on associations between asthma and allergy symptoms and residential mold and moisture. However, definitions of 'dampness' in studies are diverse because of differences in climate and building construction. Few studies have estimated mold problems inside the building structure by odor assessments. In a nested case-control study of 400 Swedish children, observations and measurements were performed in their homes by inspectors, and the children were examined by physicians for diagnoses of asthma, eczema, and rhinitis. In conclusion, we found an association between moldy odor along the skirting board and allergic symptoms among children, mainly rhinitis. No associations with any of the allergic symptoms were found for discoloured stains, 'floor dampness' or a general mold odor in the room. A moldy odor along the skirting board can be a proxy for hidden moisture problem inside the outer wall construction or in the foundation construction. There are indications that such dampness problems increase the risk for sensitization but the interpretation of data in respect of sensitization is difficult as about 80% of the children with rhinitis were sensitized. Furthermore, low ventilation rate in combination with moldy odor along the skirting board further increased the risk for three out of four studied outcomes, indicating that the ventilation rate is an effect modifier for indoor pollutants. PRACTICAL IMPLICATIONS: This study showed that mold odor at the skirting board level is strongly associated with allergic symptoms among children. Such odor at that specific place can be seen as a proxy for some kind of hidden moisture or mold problem in the building structure, such as the foundation or wooden ground beam. In houses with odor along the skirting board, dismantling of the structure is required for an investigation of possible moisture damage, measurements, and choice of actions. In homes with low ventilation in combination with mold odor along the skirting board, there was even a higher risk of health effects. This emphasizes the need for the appropriate remediation as this is an ever increasing problem in poorly ventilated houses that are damp.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Hipersensibilidade/etiologia , Asma/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fungos , Habitação , Humanos , Umidade , Masculino , Odorantes , Fatores de Risco , Suécia , Ventilação
7.
Parasitology ; 136(1): 27-33, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18980703

RESUMO

Thioredoxin reductase (TrxR), a NADPH-dependent disulfide oxidoreductase, is vital in numerous cellular processes including defence against reactive oxygen species, cell proliferation and signal transduction. TrxRs occur in 2 forms, a high Mr enzyme characterized by those of mammals, the malaria parasite Plasmodium falciparum and some worms, and a low Mr form is present in bacteria, fungi, plants and some protozoan parasites. Our hypothesis is that the differences between the forms can be exploited in the development of selective inhibitors. In this study, cyclodextrin- and sulfonic acid-derived organotelluriums known to inhibit mammalian TrxR were investigated for their relative efficacy against P. falciparum TrxR (PfTrxR), a high Mr enzyme, and Trichomonas vaginalis TrxR (TvTrxR), a low Mr form of TrxR. The results suggest that selective inhibition of low Mr TrxRs is a feasible goal.


Assuntos
Antiprotozoários/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Tiorredoxina Dissulfeto Redutase/metabolismo , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/enzimologia , Animais , Ciclodextrinas/química , Humanos , Peso Molecular , Tiorredoxina Dissulfeto Redutase/química
8.
Acta Paediatr ; 97(9): 1210-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18624993

RESUMO

AIM: To estimate the incidence rates for asthma, rhinitis and eczema symptoms and to investigate the importance of different influential factors for the incidence of these symptoms. METHODS: The Dampness in Building and Health study commenced in the year 2000 in Värmland, Sweden with a parental questionnaire based on an ISAAC protocol to all children in the age of 1-6 years. Five years later a follow-up questionnaire was sent to the children that were 1-3 years at baseline. In total, 4779 children (response rate = 73%) participated in both surveys and constitute the study population in this cohort study. RESULTS: The 5-year incidence of doctor-diagnosed asthma was 4.9% (95% CI 4.3-5.3), rhinitis was 5.7% (5.0-6.4) and eczema was 13.4% (12.3-14.5). However, incidence rates strongly depend on the health status of the baseline population. Risk factors for incident asthma were male gender and short period of breast-feeding. Allergic symptoms in parents were also a strong risk factor for incident asthma, as well as for rhinitis and eczema. CONCLUSION: When comparing incident rates of asthma between different studies it is important to realize that different definitions of the healthy baseline population will give rise to different incident rates.


Assuntos
Asma/epidemiologia , Dermatite Atópica/epidemiologia , Rinite Alérgica Perene/epidemiologia , Asma/etiologia , Criança , Dermatite Atópica/etiologia , Características da Família , Feminino , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Rinite Alérgica Perene/etiologia , Fatores de Risco , Suécia/epidemiologia
9.
Allergy ; 61(4): 447-53, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16512807

RESUMO

BACKGROUND: The reported impact of day-care attendance on respiratory and atopic symptoms has varied between studies from different countries. Regarding to the 'hygiene-hypothesis', day-care attendance may lead to less sensitization later in life, but the question still is whether day-care attendance and subsequent exposure to more frequent early infections is a risk or a protection against future allergic disease or asthma (atopic and nonatopic). METHODS: A cross-sectional postal questionnaire was replied by parents of 10,851 children, aged 1-6 years, in the year 2000 in a Swedish region (DBH-phase 1). The questionnaire focused on respiratory and atopic symptoms, the home environment and information on day care of the children. RESULTS: Children in day care were reported to have more symptoms than children in home care: adjusted odds ratio (AOR) for wheezing last 12 months, AOR 1.33 (CI 95%: 1.12-1.58), cough at night apart from colds last 12 months AOR 1.56 (CI: 1.17-2.07), doctor diagnosed asthma AOR 1.23 (CI: 0.88-1.71), rhinitis last 12 months AOR 1.15 (CI: 0.92-1.44), doctor diagnosed hay fever AOR 1.75 (CI: 0.94-3.23), eczema last 12 months, AOR 1.49 (CI: 1.24-1.79), allergic reactions to foods, AOR 1.27 (CI: 1.07-1.52), >6 colds last 12 months of 2.57 (CI: 2.12-3.12) and ear infection ever AOR 2.14 (CI: 1.87-2.45). The increased risks were mainly seen and reached significance in the youngest group of children, aged 1-4 years. Adjusting and stratification for the number of airway infections last year did not change the risk associated with day-care attendance for allergic diseases. CONCLUSIONS: Attending day care was associated with an increased risk of symptoms related to airways infections as well with eczema and allergic reactions to food. No sign of protection from day-care attendance for allergic diseases was found up to 6 years of age. Multiple airway infections and day-care attendance were found to be independently associated with asthma and allergic symptoms.


Assuntos
Asma/etiologia , Creches , Hipersensibilidade/etiologia , Fatores Etários , Asma/epidemiologia , Criança , Pré-Escolar , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Lactente , Pais , Prevalência , Sons Respiratórios , Infecções Respiratórias/imunologia , Fatores de Risco
10.
Indoor Air ; 15(4): 275-80, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15982274

RESUMO

UNLABELLED: The aim of the study was to test the hypothesis that a low-ventilation rate in homes is associated with an increased prevalence of asthma and allergic symptoms among children. A total of 198 cases (with at least two of three symptoms: wheezing, rhinitis, eczema) and 202 healthy controls, living in 390 homes, were examined by physicians. Ventilation rates were measured by a passive tracer gas method, and inspections were carried out in the homes. About 60% of the multi-family houses and about 80% of the single-family houses did not fulfill the minimum requirement regarding ventilation rate in the Swedish building code (0.5 air changes per hour, ach). Cases had significantly lower ventilation rates than controls and a dose-response relationship was indicated. PRACTICAL IMPLICATIONS: A low-ventilation rate of homes may be a risk factor for allergies among children. Families with allergic children should be given the advice to have good ventilation in the home. In investigations, of associations between environmental factors and allergies, the air change rate in homes has to be considered.


Assuntos
Asma/epidemiologia , Asma/etiologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Ventilação , Estudos de Casos e Controles , Criança , Proteção da Criança , Pré-Escolar , Feminino , Habitação , Humanos , Lactente , Masculino , Prevalência , Suécia
11.
Indoor Air ; 15 Suppl 10: 48-55, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15926944

RESUMO

UNLABELLED: There is convincing epidemiological evidence that 'dampness' in buildings is associated with respiratory effects. In order to identify health-relevant exposures in buildings with 'dampness', the study 'Dampness in Buildings and Health' (DBH) was initiated. In the first step of the study, cross-sectional data on home characteristics including 'dampness' problems, and symptoms in airway, nose, and skin among 10,851 children (1-6 years), were collected by means of a questionnaire to the parents. The prevalence of wheezing during the last 12 months was 18.9% and doctor-diagnosed asthma 5.4%. Rhinitis during the last 12 months was reported for 11.1% of the children and eczema during the last 12 months 18.7%. Gender, allergic symptoms among parents, and age of the child were associated with symptoms. Water leakage was reported in 17.8% of the buildings, condensation on windows in 14.3%, and detached flooring materials in 8.3%. Visible mould or damp spots were reported in only 1.5% of the buildings. The four 'dampness' indices were associated to higher prevalence of symptoms in both crude and adjusted analysis. Furthermore, it was found that the combination of water leakage in the home and PVC as flooring material in the child's or parent's bedroom was associated to higher prevalence of symptoms among children. However, the interpretation of this finding is unclear. The combination of water leakage and PVC may be a proxy, for example, reconstruction because of water damages. PRACTICAL IMPLICATIONS: The study have showed that moisture-related problems in buildings are a risk factor for asthma and allergic symptoms among preschool children. The recommendation to the general public is to remediate damp buildings.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Exposição Ambiental , Doenças Respiratórias/etiologia , Água , Criança , Pré-Escolar , Estudos Transversais , Feminino , Pisos e Cobertura de Pisos , Nível de Saúde , Habitação , Humanos , Lactente , Masculino , Cloreto de Polivinila/efeitos adversos , Doenças Respiratórias/epidemiologia , Suécia/epidemiologia
12.
Org Lett ; 3(22): 3459-62, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11678682

RESUMO

[reaction: see text]. The influence of various Lewis acids in the radical cyclization of beta-allyloxyalkyl phenyl selenides was investigated. Whereas the unperturbed cyclization afforded trans-2,4-disubstituted tetrahydrofurans as the major products (cis/trans approximately 1/4.5), cyclization in the presence of trialkylaluminums (3 equiv) afforded predominantly (cis/trans approximately 7/1) the corresponding cis-isomers.

13.
J Org Chem ; 66(19): 6286-90, 2001 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-11559176

RESUMO

Treatment of 1-(benzylselenenyl)-5-butyl-5-nonanol (10) with oxalyl chloride followed by the sodium salt of N-hydroxypyridine-2-thione afforded the corresponding pyridine-2-thione-N-oxycarbonyl (PTOC) oxalate ester which was not isolated but immediately heated to provide 2,2-dibutylselenane (7). This transformation presumably involves a tertiary alkyl radical that undergoes intramolecular homolytic substitution at selenium with loss of the benzyl radical to provide the selenium-containing ring system (7). A similar protocol, when applied to 1-(2-benzylselenenyl-5-methoxyphenyl)-3-methyl-3-heptanol (18) and 1-(2-benzylselenenyl-5-methoxyphenyl)-3,7,11,15-tetramethyl-3-hexadecanol (19), followed by deprotection, afforded the selenium-containing alpha-tocopherol analogues 4 and 1f, respectively, in moderate yields. To the best of our knowledge, these transformations represent the first examples of tertiary radicals involved in homolytic substitution chemistry at selenium.


Assuntos
Compostos Heterocíclicos/química , Selênio/química , Vitamina E/análogos & derivados , Vitamina E/química
14.
Brain Res ; 911(1): 12-21, 2001 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-11489439

RESUMO

Antioxidant activities of 3-[4-(N,N-dimethylamino) benzenetellurenyl]propanesulfonic acid sodium salt (NDBT) were evaluated in solution, red blood cells, synaptosomal membranes, and cultured hippocampal neuronal cells after exposure to peroxynitrite (ONOO(-)) and hydroxyl radicals. The organotellurium compound NDBT possesses significant activity towards hydrogen peroxide and/or the hydroxyl radical in solution, demonstrated by inhibition of hydroxylation of terephthalic acid. In addition, the compound displayed great antioxidant abilities as shown by: reduction of ONOO(-)-induced 2,7-dichlorofluorescein (DCF) fluorescence in synaptosomes; complete prevention of lipid peroxidation in synaptosomes caused by OH radicals (TBARS), and significant prevention of protein oxidation caused by ONOO(-) and OH, indexed by the levels of protein carbonyls in synaptosomes and neuronal cells. The presence of the compound abolished neuronal cell death caused by ONOO(-). Further, the compound was effective in preventing the oxidative changes in synaptosomal membrane protein conformation and crosslinking (EPR spin labeling). Finally, the organotellurium molecule attenuated peroxynitrite-induced, luminol-dependent chemiluminescence in red blood cells--an index of cellular oxidation. These findings demonstrate the great potential of the antioxidant and are consistent with the notion that NDBT may have a role to play in modulating oxidative stress in neurodegenerative disorders, including Alzheimer's disease.


Assuntos
Ácidos Alcanossulfônicos/farmacologia , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Compostos Organometálicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Telúrio , Animais , Morte Celular/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/antagonistas & inibidores , Radicais Livres/metabolismo , Gerbillinae , Peroxidação de Lipídeos/efeitos dos fármacos , Medições Luminescentes , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nitratos/antagonistas & inibidores , Nitratos/farmacologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
15.
J Am Chem Soc ; 123(15): 3434-40, 2001 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-11472114

RESUMO

A novel synthesis of 2,3-dihydrobenzo[b]thiophene-5-ol based on intramolecular homolytic substitution on sulfur was reported. The "antioxidant profile" of the series of 2,3-dihydrobenzo[b]furan-5-ol (2a) its 1-thio (2b), 1-seleno (2c) and 1-telluro (2d) analogues was determined by studies of redox properties, the capacity to inhibit stimulated lipid peroxidation, the reactivity toward tert-butoxyl radicals, the ability to catalyze decomposition of hydrogen peroxide in the presence of glutathione, and the inhibiting effect on stimulated peroxidation in liver microsomes. The one-electron reduction potentials of the aroxyl radicals corresponding to compounds 2a-2d, E degrees (ArO(*)/ArO(-)) were 0.49, 0.49, 0.49, and 0.52 V vs NHE, respectively, as determined by pulse radiolysis. With increasing chalcogen substitution the compounds become slightly more acidic (pK(a) = 10.6, 10.0, 9.9, and 9.5, respectively, for compounds 2a-2d). By using Hess' law, the homolytic O-H bond dissociation enthalpies of compounds 2a-2d (340, 337, 336, and 337 kJ mol(-)(1), respectively) were calculated. The reduction potentials for the proton coupled oxidation of compounds 2a-2d (ArOH --> ArO(*) + H(+)) as determined by cyclic voltammetry in acetonitrile were 1.35 (irreversible), 1.35 (quasireversible) 1.13 (reversible), and 0.74 (reversible) V vs NHE, respectively. As judged by the inhibited rates of peroxidation, R(inh), in a water/chlorobenzene two-phase lipid peroxidation system containing N-acetylcysteine as a thiol-reducing agent in the aqueous phase, the antioxidant capacity increases (2d > 2c = 2b > 2a) as one traverses the group of chalcogens. Whereas the times of inhibition, T(inh), were slightly reduced for the oxygen (2a) and sulfur (2b) derivatives in the absence of the thiol-reducing agent, they were drastically reduced for the selenium (2c) and tellurium (2d) derivatives. This seems to indicate that the organochalcogen compounds are continuously regenerated at the lipid aqueous interphase and that regeneration is much more efficient for the selenium and tellurium compounds. The absolute rate constants for the oxidation of compounds 2a-2b by the tert-butoxyl radical in acetonitrile/di-tert-butyl peroxide (10/1) were the same-2 x 10(8) M(-)(1) s(-)(1). Whereas the oxygen, sulfur, and selenium derivatives 2a-2c were essentially void of any glutathione peroxidase-like activity, the organotellurium compound 2d accelerated the initial reduction of hydrogen peroxide, tert-butyl hydroperoxide, and cumene hydroperoxide in the presence of glutathione 100, 333, and 213 times, respectively, as compared to the spontaneous reaction. Compounds 2a-2d were assessed for their capacity to inhibit lipid peroxidation in liver microsomes stimulated by Fe(II)/ADP/ascorbate. Whereas the oxygen, sulfur, and selenium compounds showed weak inhibiting activity (IC(50) values of approximately 250, 25, and 13 microM, respectively), the organotellurium compound 2d was a potent inhibitor with an IC(50) value of 0.13 microM.


Assuntos
Antioxidantes/síntese química , Benzofuranos/síntese química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Radicais Livres/química , Peróxido de Hidrogênio/química , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
16.
Org Lett ; 2(11): 1589-92, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10841486

RESUMO

N-Allyl-beta-aminoalkyl phenyl selenides-precursors of 3-aza-5-hexenyl radicals-were prepared by ring opening of N-allylaziridines with benzeneselenol under acidic conditions or by sodium cyanoborohydride reduction of N-allylimines of alpha-phenylselenenyl ketones. The effect of various N-protective groups (acyl, sulfonyl, or phosphinoyl) on diastereoselectivity in thermally or photochemically initiated 3-aza-5-hexenyl reductive radical cyclization was studied. Whereas N-unprotected derivatives afforded trans-2,4-disubstituded pyrrolidines with good selectivity, the diphenylphosphinoyl group directed cyclization to occur in a highly cis-selective manner.

17.
J Org Chem ; 65(7): 2151-62, 2000 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-10774040

RESUMO

Acetalization, alpha-bromination, nucleophilic phenylselenenylation, oxidative elimination/hydrolysis was investigated as a novel protocol for the alpha,beta-dehydrogenation of aldehydes. Treatment of acetals with bromine in methylene chloride afforded the corresponding alpha-bromoacetals in 80-90% yields. Nucleophilic phenylselenenylation was then conveniently effected by treatment with benzeneselenolate generated in situ in dimethyl sulfoxide from diphenyl diselenide, hydrazine and potassium carbonate. Unbranched alpha-bromoacetals cleanly afforded substitution products whereas beta- and gamma-branched ones gave substantial amounts of alpha,beta-unsaturated acetals via formal loss of hydrogen bromide. Oxidative elimination/hydrolysis of these mixtures afforded alpha,beta-unsaturated aldehydes in 50-80% overall yields. In the case of tertiary alpha-bromoacetals, treatment with benzeneselenolate afforded only dehydrobromination products as mixtures of isomers. The presence of at least a catalytic amount of the organoselenium reagent was found to be crucial for olefin formation. A SET-mechanism, involving benzeneselenolate-induced electron transfer to the halide, loss of bromide ion, and hydrogen atom or proton/electron was proposed for the benzenselenolate-promoted elimination reaction. Experiments designed to trap carbon-centered radicals in intramolecular cyclization or ring-opening reactions failed to provide any evidence for free-radical intermediates.

18.
Mutat Res ; 464(2): 269-77, 2000 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-10648914

RESUMO

Previous literature reports have demonstrated that nucleated trout erythrocytes in conditions of oxidative stress are subjected to DNA and membrane damage, and inactivation of glutathione peroxidase. The present study was undertaken to evaluate the ability of three diaryl tellurides and the organoselenium compound ebselen to protect trout (Salmo irideus) erythrocytes against oxidative stress, induced thermally and by a variation of pH. The antioxidant ability of these molecules was evaluated through chemiluminescence. Impairment of DNA was assessed using the comet assay, a rapid and sensitive single cell gel electrophoresis technique, used to detect primary DNA damage in individual cells. At low concentrations (<10 microM), all the compounds used presented a protective effect on DNA damage without altering the hemolysis rate. In higher concentrations, they accelerated the hemolysis rate and two of the diaryl tellurides were strongly genotoxic.


Assuntos
Antioxidantes/toxicidade , Azóis/toxicidade , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Compostos Organometálicos/toxicidade , Compostos Organosselênicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eritrócitos/citologia , Hemólise/efeitos dos fármacos , Temperatura Alta/efeitos adversos , Concentração de Íons de Hidrogênio , Isoindóis , Medições Luminescentes , Testes de Mutagenicidade , Oncorhynchus mykiss , Compostos Organometálicos/química , Telúrio/química
19.
Chem Res Toxicol ; 13(1): 3-9, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10649960

RESUMO

The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc storage protein, metallothionein, by tert-butyl hydroperoxide is also catalyzed by the water-soluble organotellurium compounds. As compared to selenium-containing compounds (e.g., ebselen and selenocystamine), some of the tellurides that were tested ¿e.g., 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid, sodium salt¿ exhibit a significantly higher reactivity in these assays, making them some of the most effective compounds tested thus far. The catalysis of destruction of zinc-sulfur clusters by water-soluble organotellurium compounds could have implications for the bioavailability of zinc in vivo. These compounds might be lead compounds for the development of a new class of water-soluble, tellurium-based antioxidant and zinc-releasing drugs.


Assuntos
Metalotioneína/química , Nitratos/química , Compostos Organometálicos/química , Telúrio/química , Zinco/química , Benzoatos/química , Catálise , Hidroxilação , Nitritos/química , Oxidantes/química , Oxirredução , Fenilacetatos/química , Rodaminas/química , Solubilidade , Água/química , terc-Butil Hidroperóxido/química
20.
Anticancer Drug Des ; 15(5): 323-30, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11354308

RESUMO

The thioredoxin system (NADPH, thioredoxin reductase/ thioredoxin) is important for cancer cell growth and inhibition of apoptosis and presents an attractive target for anticancer drug development. Thioredoxin reductase is a selenocysteine-containing flavoenzyme that catalyzes the reduction of oxidized thioredoxin. This enzyme could therefore be used for regulating the activity of the thioredoxin system. Water-soluble organotellurium compounds of the diaryl telluride, alkyl aryl telluride and dialkyl telluride type, carrying sulfopropyl groups, were found to be the most efficient tellurium-based inhibitors of thioredoxin reductase ever tested. Some of the compounds inhibited the enzyme at submicromolar levels. The compounds also inhibited the growth of MCF-7 and HT-29 human cancer cells in culture at the 5-10 microM level but their hydrophilicity seemed to restrict cellular uptake.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Telúrio/química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Divisão Celular/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Células HT29 , Humanos , Solubilidade , Células Tumorais Cultivadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...