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1.
Pneumologie ; 73(1): 40-48, 2019 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-30508846

RESUMO

The chronic obstructive pulmonary disease (COPD) is characterised by mainly non-reversible bronchial obstruction with airflow limitation. Typically, it exhibits a progressive course. It is one of the leading causes of morbidity and mortality worldwide. In addition to dominating causative smoking and environmental exposures (especially biomass smoke from cooking with open fire stoves), about 15 % are due to occupational exposure. Relatively rare cases (ca. 6 %) do not show an external noxious influence. Occupational causes are frequently not recognised because a detailed occupational history has not been taken. This is especially evident by the discrepancy in the identified COPD prevalences and incidences shown in many studies on the one hand and relatively low numbers in the official statistics on reports, acknowledgements and compensations of the disorder on the other hand. Whether occupational exposures to inhalative noxae are - in addition to non-occupational factors (e. g. smoking) - causative according to legal definitions is frequently a challenging question. Respective decisions of social courts in litigations are presented.


Assuntos
Noxas/efeitos adversos , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Humanos , Doenças Profissionais/etiologia , Fatores de Risco , Fumar/efeitos adversos
2.
Curr Biol ; 27(4): R129-R133, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28222285

RESUMO

Nociception, the sensory mechanism that allows animals to sense and avoid potentially tissue-damaging stimuli, is critical for survival. This process relies on nociceptors, which are specialized neurons that detect and respond to potentially damaging forms of energy - heat, mechanical and chemical - in the environment. Nociceptors accomplish this task through the expression of molecules that function to detect and signal the presence of potential harm. Downstream of the nociceptive sensory input, the neural signals trigger protective (nocifensive) behaviors, and the sensory stimuli that reach the brain may be perceived as painful.


Assuntos
Temperatura Baixa/efeitos adversos , Temperatura Alta/efeitos adversos , Fenômenos Mecânicos , Nociceptividade/fisiologia , Nociceptores/fisiologia , Noxas/efeitos adversos , Animais
3.
J Dig Dis ; 17(11): 756-763, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27624611

RESUMO

OBJECTIVE: Although the intimate relationship between liver and gut has been previously reported under physiological and pathological conditions, intestinal involvement in the process of intrahepatic cholestasis of pregnancy remains unclear. The aim of this study was to investigate intestinal changes in 17α-ethynylestradiol (EE)-induced cholestatic rat model. METHODS: Liver injury was assessed by HE stain and serum biochemical parameters were measured. Intestinal transit was determined using ink marks. Neuronal protein expressions in the intestine were analyzed by Western blot. RESULTS: EE treatment induced liver damage, including severe bile duct hyperplasia, portal edema, portal infiltration, a loss of hepatic structure in periportal areas and increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. Large areas of inflammatory cell infiltration and increased myeloperoxidase activity were observed in the intestine of EE-induced cholestatic rats. The EE-treated group showed increased intestinal transit and malondialdehyde levels, while the glutathione content and superoxide dismutase activity were notably decreased, together with decreased protein gene product 9.5 and neuronal nitric oxide synthase expression in the ileum and colon. Furthermore, choline acetyltransferase expression was significantly decreased in the ileum, whereas no change was observed in the colon of EE-treated rats. CONCLUSION: EE-induced liver damage is associated with oxidative stress, inflammation and neural loss in the intestine, which may lead to altered intestinal motility.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Colestase Intra-Hepática/patologia , Etinilestradiol/farmacologia , Enteropatias/patologia , Fígado/patologia , Noxas/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/fisiopatologia , Modelos Animais de Doenças , Etinilestradiol/efeitos adversos , Trânsito Gastrointestinal/efeitos dos fármacos , Enteropatias/induzido quimicamente , Enteropatias/fisiopatologia , Intestinos/efeitos dos fármacos , Intestinos/inervação , Intestinos/patologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Masculino , Noxas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos
4.
Belo Horizonte; s.n; 2016. 126 p. ilus.
Tese em Inglês, Português | LILACS, BBO - Odontologia | ID: biblio-916403

RESUMO

Objetivos: Avaliar, em um estudo longitudinal de 5 anos, a associação entre o diagnóstico da doença peri-implantar (DPi) e a contagem de patógenos na presença e ausência de terapia de manutenção periodontal/peri-implantar (TMPP). Realizar uma revisão sistemática de estudos observacionais para avaliar se dados presentes na literatura indicam uma maior prevalência de peri-implantite (PI) em indivíduos com diagnóstico ou histórico de periodontite (PE). Métodos: O estudo longitudinal microbiológico foi realizado avaliando-se, através da técnica da reação em cadeia da polimerase em tempo real, as seguintes espécies bacterianas: T. forsythia, T. denticola, P. gingivalis, P. intermedia, F. nucleatum e A. naeslundii em 80 indivíduos com mucosite peri-implantar (MP) que realizavam consultas para manutenção periodontal/peri-implantar regular (GTP, n = 39) comparados aos que não realizavam (GNTP, n = 41). Para a revisão sistemática uma busca eletrônica foi conduzida até março de 2016. Foram encontrados 1330 estudos, 17 artigos foram incluídos na análise final (PROSPERO CRD42015009518). A meta-análise foi realizada para presença ou ausência de PI. Medidas de efeito sumário e taxas de razão de chances (OR) com 95% IC foram calculadas. Resultados: Os resultados do estudo longitudinal mostraram que, após 5 anos, houve uma diminuição da carga bacteriana total (CBT), na frequência das bactérias analisadas do complexo laranja (p = 0.013) e nas frequências isoladas de T. forsythia (p = 0.000), P. gingivalis (p = 0.003) e P. intermedia (p = 0.013) no GTP. Indivíduos com PI apresentaram maiores frequências de P. gingivalis (GNTP: p = 0,030; GTP: p = 0,000), T. denticola (GNTP: p = 0,017) e F. nucleatum (GTP e GNTP; p = 0.002) comparados aos com MP. Indivíduos que desenvolveram PI apresentaram um aumento na CBT (GTP: p = 0.047; GNTP: p = 0,055) e na frequência isolada de P. gingivalis (GNTP: p = 0,002) e F. nucleatum (GTP e GNTP; p = 0.000). Não houve diferenças estatisticamente significativas intergrupos em relação aos patógenos do complexo vermelho (p > 0,05). Tanto nos indivíduos com MP (T1 e T2: p = 0,000), quanto nos indivíduos com PI (T2: p = 0,000), a frequência do complexo laranja foi significativamente menor no GTP. A meta-análise dos estudos coorte mostrou que indivíduos (OR = 7.22), e implantes (OR = 5.63) apresentaram maior risco de desenvolver PI. Nos estudos transversais, em análises não ajustadas, indivíduos com PE apresentaram maior chance de ter PI (OR = 3.18). Quando a análise foi ajustada para tabagismo e diabetes não houve aumento estatisticamente significativo no risco para PI (OR = 1.73; IC 95% 0.86- 3.45). Conclusões: Pôde-se concluir que a ausência de consultas regulares para manutenção periodontal/peri-implantar foi associada com pior condição clínica periimplantar, maior incidência de PI e um aumento significativo na CBT. Adicionalmente, indivíduos com diagnóstico de PI apresentaram maiores frequências de P. gingivalis, T. denticola e F. nucleatum e maior CBT. A revisão sistemática permitiu concluir que indivíduos com diagnóstico ou histórico de PE podem apresentar um risco aumentado para PI. Mais estudos prospectivos são necessários para confirmar a evidência, principalmente os ensaios clínicos controlados randomizados


Aims: Evaluate, in a 5-year longitudinal study, the association between peri-implant disease's (DPi) diagnosis and the count of pathogens in the presence and absence of periodontal/peri-implant maintenance therapy. Conduct a systematic review of observational studies to evaluate whether data in the literature indicates a higher prevalence of peri-implantitis (PI) in subjects with diagnosis or history of periodontitis (PE). Methods: the microbiologic study was performed evaluating, through polymerase chain reaction in real time technique, the following bacterial species: T. forsythia, T. denticola, P. gingivalis, P. intermedia, F. nucleatum and A. naeslundii in 80 patients with peri-implant mucositis (PM) that were queries for periodontal/periimplant regular maintenance (GTP, n = 39) compared to those who were not (GNTP, n = 41). For the systematic review an electronic search was conducted until March 2016. It was found 1330 studies, 19 articles were included in the final analysis (PROSPERO CRD42015009518). The meta-analysis was performed for presence or absence of PI. Summary measures and odds ratio (OR) with 95% IC were calculated. Results: the results of the longitudinal study showed that, after 5 years, there was a decrease in the total bacterial load (TBL), the frequency of bacteria analyzed in the orange complex (p = 0.013) and in the frequencies of T. forsythia (p = 0.000), P. gingivalis (p = 0.003) and P. intermedia (p = 0.013) in the GTP. Individuals with PI had higher frequencies of P. gingivalis (GNTP: p = 0.030; GTP: p = 0.000), T. denticola (GNTP: p = 0.017) and T. nucleatum (GTP and GNTP; p = 0.002) compared to those with PM diagnosis. Individuals who have developed PI showed an increase in TBL (GTP: p = 0047; GNTP: p = 0.055) and in the isolated frequencies of P. gingivalis (GNTP: p = 0.002) and F. nucleatum (GTP and GNTP; p = 0.000). There were no statistically significant differences intergroups in relation to red complex pathogens (p > 0.05). Both in individuals with PM (T1 and T2: p = 0.000), as in individuals with PI (T2: p = 0.000), the frequency of orange complex was significantly lower in the GTP. The meta-analysis of cohort studies showed that individuals (OR = 7.22), and implants (OR = 5.63) presented a higher risk of developing PI. In the cross-sectional studies, in unadjusted analyses, individuals with PE presented a higher chance of having PI (OR = 3.18). When the analysis was adjusted for smoking and diabetes, there was no statistically significant increase in risk for PI (OR = 1.73; 95% CI 0.86-3.45). Conclusions: it might be concluded that the absence of regular periodontal/peri-implant maintenance was associated with worse peri-implant clinical condition, higher incidence of PI and a significant increase in TBL. Additionally, individuals diagnosed with PI showed greater frequencies of P. gingivalis, T. denticola and F. nucleatum and largest TBL. The systematic review showed that individuals diagnosed or with PE's history may have an increased risk for PI. More prospective studies are needed to confirm this evidence, especially the randomized controlled clinical trials


Assuntos
Humanos , Masculino , Feminino , Noxas/efeitos adversos , Peri-Implantite/diagnóstico , Peri-Implantite/epidemiologia , Periodontite/patologia , Periodontite/terapia , Reação em Cadeia da Polimerase em Tempo Real/estatística & dados numéricos , Estomatite/epidemiologia , Estudo Comparativo , Interpretação Estatística de Dados , Estudos Longitudinais , Meta-Análise em Rede , Fatores de Risco
5.
Int J Audiol ; 54 Suppl 1: S57-64, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25549170

RESUMO

OBJECTIVE: The purpose of this study is to determine the relationship between occupational exposures and hearing among elderly Latino Americans. DESIGN: A descriptive, correlational design used for this secondary analysis with the data from the Sacramento Area Latino Study of Aging (SALSA). STUDY SAMPLE: A total of 547 older adults were included. RESULTS: A majority of participants (58%) reported occupational exposures to loud noise and/or ototoxic chemicals. About 65% and over 90% showed hearing loss at low and high frequencies, respectively. Participants with occupational exposure to loud noise and/or ototoxic chemicals were, significantly, two times more likely to have hearing loss at high frequencies compared to those without exposure (OR = 2.29; 95% CI: 1.17 = 4.51, p = .016), after controlling for other risk factors of hearing loss such as age, gender, household income, current smoking, and diabetes. However, lifelong occupational exposure was not significantly associated with hearing loss at low frequencies (OR = 1.43; 95% CI: 0.94 = 2.18, p = .094). CONCLUSION: Lifelong occupational exposure to loud noise and/or ototoxic chemicals was significantly associated with hearing loss among elderly Latino Americans. Healthy work life through protection from harmful auditory effects of occupational exposures to noise and chemicals will have a positive impact on better hearing in later life.


Assuntos
Perda Auditiva/epidemiologia , Ruído/efeitos adversos , Noxas/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Idoso , California/epidemiologia , Estudos Transversais , Feminino , Perda Auditiva/etiologia , Humanos , Modelos Logísticos , Masculino , Prevalência
6.
Rev. bras. plantas med ; 16(4): 804-811, oct.-dic. 2014. graf, tab
Artigo em Inglês | LILACS | ID: lil-729887

RESUMO

This study sought to evaluate the chemical composition of the Allium sativum and Origanum vulgare essential oils and their effect on the growth inhibition of microorganisms, such as P. aeruginosa, S. Choleraesuis, A. flavus, A. niger and P. simplicissimum, important food contaminants. The main constituents of the oregano essential oil were 4-terpineol (27.03%), γ-terpinene (20.04%), and β-cymene (6.34%), and the main constituents of the garlic essential oil were diallyl trisulfide (38, 81%), diallyl disulfide (25.23%), and methyl allyl trisulfide (12.52%). Inhibition zones were formed in in vitro tests on the bacteria S. Choleraesuis and P. aeruginosa, except for A. sativum against P. aeruginosa. The inhibition of mycelial growth caused by the oregano essential oil occurred with the concentrations of 0.10, 0.03 and 0.05 mg mL-1 for the A. flavus, A. niger and P. simplicissimum fungi, respectively. The CMI for the garlic oil began at the 0.03 mg mL-1 concentration for all species of fungi. The oils presented an inhibitory effect against the microorganisms studied and constitute an alternative for microbiological control in food.


Objetivou-se avaliar a composição química e o efeito inibitório dos óleos essenciais de Allium sativum e Origanum vulgare frente ao crescimento dos micro-organismos Pseudomonas aeruginosa, Salmonella Choleraesuis, Aspergillus flavus, Aspergillus niger e Penicillium simplicissimum, importantes patógenos causadores de contaminações em alimentos. Para quantificação e identificação dos constituintes químicos dos óleos, utilizou-se cromatógrafo gasoso acoplado a espectrômetro de massas. Os principais constituintes do óleo essencial de orégano foram o 4-terpineol (27,03%), γ-terpineno (20,04%), β-cimeno (6,34%), e do alho, o dialil trissulfeto (38,81%), dialil dissulfeto (25,23%), metil alil trissulfeto (12,52%). Os resultados dos testes in vitro sobre as bactérias S. Choleraesuis e P. aeruginosa indicaram a formação de halo de inibição e revelaram o efeito inibitório para os referidos óleos, exceto para o óleo de A. sativum frente a P. aeruginosa. Para os fungos A. flavus, A. niger e P. simplicissimum a inibição do crescimento micelial provocada pelo óleo essencial de orégano ocorreu a partir das concentrações de 0,10, 0,03 e 0,05 µg mL-1, respectivamente, sendo que a CMI para o óleo de alho iniciou-se a partir da concentração 0,03 µg mL-1 para todas as espécies de fungos. Foi possível verificar que os óleos possuem efeito inibitório sobre os microrganismos estudados, sendo, portanto, uma alternativa no controle microbiológico de alimentos.


Assuntos
Química , Alho/metabolismo , Noxas/efeitos adversos , Óleos Voláteis/química , Origanum/farmacologia , Contaminantes Químicos em Alimentos
7.
Cir. plást. ibero-latinoam ; 40(3): 319-324, jul.-sept. 2014. ilus
Artigo em Espanhol | IBECS | ID: ibc-130019

RESUMO

La inyección de sustancias modelantes es un procedimiento usado desde el siglo XIX para mejorar el contorno corporal con fines estéticos. Durante la última década ha aumentado la demanda de técnicas quirúrgicas para la reconstrucción de los defectos originados tras la resección de unidades anatómicas afectadas por infiltración de estas sustancias modelantes, haciendo que en ocasiones tengamos que recurrir al empleo de expansores cutáneos, injertos, colgajos locales, colgajos regionales e incluso, a colgajos libres. Describimos el proceso de reconstrucción glútea en caso de infiltración de sustancias modelantes en el que tuvimos que emplear un colgajo de perforantes lumbares debido a su fiabilidad, a que preserva la musculatura, a su versatilidad de diseño sin comprometer otras posibles alternativas reconstructivas y por su baja morbilidad. Analizamos también la anatomía, diseño, técnica quirúrgica e indicaciones específicas de estos colgajos de perforantes de la región glútea (AU)


The injection of modeling substances is a process used with esthetic purposes since XIX century to improve body contour. In the past decade, there has been an increased demand on surgical techniques for reconstruction of defects arising after resection of anatomical units, such as: expanders, grafts, local flaps, regional flaps and free flaps. These resections are due to the infiltration of modeling substances. We describe a reconstruction process with a bilateral lumbar perforator flaps in a case of gluteal adyuvant disease. We analyze too the anatomy, design, surgical technique and specific indications for gluteal reconstruction (AU)


Assuntos
Humanos , Retalho Perfurante , Nádegas/cirurgia , Noxas/efeitos adversos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Materiais Biocompatíveis/efeitos adversos
8.
Blood ; 124(11): 1799-807, 2014 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-25051961

RESUMO

Rare missense mutations in the von Willebrand factor (VWF) A3 domain that disrupt collagen binding have been found in patients with a mild bleeding phenotype. However, the analysis of these aberrant VWF-collagen interactions has been limited. Here, we have developed mouse models of collagen-binding mutants and analyzed the function of the A3 domain using comprehensive in vitro and in vivo approaches. Five loss-of-function (p.S1731T, p.W1745C, p.S1783A, p.H1786D, A3 deletion) and 1 gain-of-function (p.L1757A) variants were generated in the mouse VWF complementary DNA. The results of these various assays were consistent, although the magnitude of the effects were different: the gain-of-function (p.L1757A) variant showed consistent enhanced collagen binding whereas the loss-of-function mutants showed variable degrees of functional deficit. We further analyzed the impact of direct platelet-collagen binding by blocking glycoprotein VI (GPVI) and integrin α2ß1 in our ferric chloride murine thrombosis model. The inhibition of GPVI demonstrated a comparable functional defect in thrombosis formation to the VWF(-/-) mice whereas α2ß1 inhibition demonstrated a milder bleeding phenotype. Furthermore, a delayed and markedly reduced thrombogenic response was still evident in VWF(-/-), GPVI, and α2ß1 blocked animals, suggesting that alternative primary hemostatic mechanisms can partially rescue the bleeding phenotype associated with these defects.


Assuntos
Colágeno/metabolismo , Integrina alfa2beta1/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Trombose/metabolismo , Fator de von Willebrand/metabolismo , Substituição de Aminoácidos , Animais , Cloretos/efeitos adversos , Cloretos/farmacologia , Colágeno/genética , Modelos Animais de Doenças , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacologia , Células HEK293 , Humanos , Integrina alfa2beta1/genética , Camundongos , Camundongos Knockout , Mutação de Sentido Incorreto , Noxas/efeitos adversos , Noxas/farmacologia , Glicoproteínas da Membrana de Plaquetas/genética , Estrutura Terciária de Proteína , Trombose/induzido quimicamente , Trombose/genética , Trombose/patologia , Fator de von Willebrand/genética
9.
G Ital Med Lav Ergon ; 36(4): 230-3, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-25558715

RESUMO

The restaurant and food preparation, cooking and distribution sector includes hotels, restaurants, catering, fast food, ecc. The restaurant and food preparation, cooking and distribution sector form a significant part of the Italian economy; they provide employment for a large number of people, both direct employees as well as part-time and contract staff. In this sector there are many hazards that can lead to a broad range of injuries and/or diseases to the workers. For the safety these hazards principally are slick floors, open flames, high temperature cooking surfaces, steam, knives and other cutting instruments and machineries. For the health: cleaning and disinfecting chemicals substances, cooking fumes and vapors, biological agents, heavy loads handling, thermal comfort, ecc. The paper presents an overview of the hazards in the sector and then make a focus on chemical risks identification and assessment to evaluate the workers' exposure (by skin adsorption and inhalation).


Assuntos
Culinária , Manipulação de Alimentos , Serviços de Alimentação , Doenças Profissionais/epidemiologia , Acidentes de Trabalho/prevenção & controle , Acidentes de Trabalho/estatística & dados numéricos , Fogo , Contaminação de Alimentos , Manipulação de Alimentos/métodos , Substâncias Perigosas/efeitos adversos , Humanos , Noxas/efeitos adversos , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional , Saúde do Trabalhador , Traumatismos Ocupacionais/epidemiologia , Traumatismos Ocupacionais/etiologia , Traumatismos Ocupacionais/prevenção & controle , Restaurantes , Medição de Risco , Local de Trabalho
10.
G Ital Med Lav Ergon ; 36(4): 382-91, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-25558740

RESUMO

Chemical, physical and biological risks among public safety and security forces. Law enforcement personnel, involved in routine tasks and in emergency situations, are exposed to numerous and several occupational hazards (chemical, physical and biological) whith likely health and security consequences. These risks are particularly high when the organization and preparation are inadequate, there is a lacking or insufficient coordination, information, education and communication and safety and personal protective equipment are inadequate or insufficient. Despite the objective difficulties, caused by the actual special needs related to the service performed or the organizational peculiarities, the risk identification and assessment is essential for worker health and safety of personnel, as provided for by Legislative Decree no. 81/2008. Chemical risks include airborne pollutants due to vehicular traffic (carbon monoxide, ultrafine particles, benzene, polycyclic aromatic hydrocarbons, aldehydes, nitrogen and sulfur oxides, lead), toxic gases generated by combustion process following fires (aromatic hydrocarbons, PAHs, dioxins and furans, biphenyls, formaldehyde, metals and cyanides), substances emitted in case of chemical accidents (solvents, pesticides, toxic gases, caustics), drugs (methylamphetamine), riot control agents and self-defence spray, lead at firing ranges, and several materials and reagents used in forensic laboratory. The physical hazards are often caused by activities that induce biomechanical overload aid the onset of musculoskeletal disorders, the use of visual display terminals and work environments that may expose to heat stress and discomfort, high and low pressure, noise, vibrations, ionizing and non-ionizing radiation. The main biological risks are blood-borne diseases (viral hepatitis, AIDS), airborne diseases (eg, tuberculosis, meningitis, SARS, anthrax), MRSA, and vector-borne diseases. Many of these risk factors are unavoidable or are not predictable; so a proper risk assessment is very important, especially in case of emergencies, and also the necessary preventive measures, a careful analysis of alternative options for action and decision-making, implementation of security measures due to the provision of appropriate PPE and effective management of risk communication have great importance. Another important aspect is the education and training of staff, as in emergency situations should be able to take protective measures as quickly as possible.


Assuntos
Doenças Transmissíveis/transmissão , Poluentes Ambientais/efeitos adversos , Substâncias Perigosas/efeitos adversos , Aplicação da Lei , Noxas/efeitos adversos , Doenças Profissionais/etiologia , Exposição Ocupacional , Fenômenos Físicos , Polícia , Patógenos Transmitidos pelo Sangue , Vazamento de Resíduos Químicos , Terminais de Computador , Armas de Fogo , Fogo , Humanos , Itália/epidemiologia , Ruído/efeitos adversos , Doenças Profissionais/epidemiologia , Doenças Profissionais/prevenção & controle , Saúde do Trabalhador/legislação & jurisprudência , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Medição de Risco , Gestão da Segurança , Vibração/efeitos adversos , Violência , Tempo (Meteorologia)
11.
Blood ; 122(25): 4094-106, 2013 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-24159172

RESUMO

The identity of vampire bat saliva anticoagulant remained elusive for almost a century. Sequencing the salivary gland genes from the vampire bat Desmodus rotundus identified Desmolaris as a novel 21.5-kDa naturally deleted (Kunitz 1-domainless) form of tissue factor pathway inhibitor. Recombinant Desmolaris was expressed in HEK293 cells and characterized as a slow, tight, and noncompetitive inhibitor of factor (F) XIa by a mechanism modulated by heparin. Desmolaris also inhibits FXa with lower affinity, independently of protein S. In addition, Desmolaris binds kallikrein and reduces bradykinin generation in plasma activated with kaolin. Truncated and mutated forms of Desmolaris determined that Arg32 in the Kunitz-1 domain is critical for protease inhibition. Moreover, Kunitz-2 and the carboxyl-terminus domains mediate interaction of Desmolaris with heparin and are required for optimal inhibition of FXIa and FXa. Notably, Desmolaris (100 µg/kg) inhibited FeCl3-induced carotid artery thrombus without impairing hemostasis. These results imply that FXIa is the primary in vivo target for Desmolaris at antithrombotic concentrations. Desmolaris also reduces the polyphosphate-induced increase in vascular permeability and collagen- and epinephrine-mediated thromboembolism in mice. Desmolaris emerges as a novel anticoagulant targeting FXIa under conditions in which the coagulation activation, particularly the contact pathway, plays a major pathological role.


Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Quirópteros , Inibidores do Fator Xa , Proteínas e Peptídeos Salivares/química , Proteínas e Peptídeos Salivares/farmacologia , Trombose/tratamento farmacológico , Animais , Bradicinina/química , Bradicinina/genética , Bradicinina/metabolismo , Cloretos/efeitos adversos , Cloretos/farmacologia , Modelos Animais de Doenças , Fator Xa/química , Fator Xa/genética , Fator Xa/metabolismo , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacologia , Células HEK293 , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Calicreínas/química , Calicreínas/genética , Calicreínas/metabolismo , Camundongos , Noxas/efeitos adversos , Noxas/farmacologia , Estrutura Terciária de Proteína , Proteínas e Peptídeos Salivares/genética , Trombose/induzido quimicamente , Trombose/genética , Trombose/metabolismo
12.
Joint Bone Spine ; 80(6): 621-5, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23566666

RESUMO

OBJECTIVES: To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHOD: The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control. RESULTS: Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS. CONCLUSION: Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Benzo(a)pireno/efeitos adversos , Membrana Sinovial/patologia , Fatores de Transcrição/biossíntese , Artrite Reumatoide/patologia , Células Cultivadas , Humanos , Noxas/efeitos adversos , Transdução de Sinais , Fumar/efeitos adversos , Fatores de Transcrição da Família Snail
13.
J Thromb Thrombolysis ; 34(2): 199-207, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22588534

RESUMO

A role for platelets in the pathogenesis of venous thrombosis was suggested by clinical and preclinical studies. However, examination of the platelet receptor, P2Y1, in this area has been limited. The goal of the current study was to examine effects of P2Y1 deletion, or selective antagonism with MRS2500, in oxidative venous thrombosis in mice. The P2Y12 antagonist, clopidogrel, was included as a reference agent. Anesthetized C57BL/6 or genetically modified mice underwent 3.5 or 5 % FeCl(3)-induced vena cava thrombosis. Pharmacokinetic properties of MRS2500 were defined for dose selection. Platelet aggregation and renal or tail bleeding times (BT) were measured to put antithrombotic effects into perspective. P2Y1 deletion significantly reduced (p < 0.001) venous thrombus weight by 74 % in 3.5 % FeCl(3) injury compared to P2Y1(+/+) littermates. MRS2500 (2 mg/kg, i.v.) significantly decreased (p < 0.001) thrombus weight 64 % in C57BL/6 mice. In the more severe 5 % FeCl(3)-induced injury model, thrombus weight significantly (p < 0.001) decreased 68 % in P2Y1(-/-) mice versus P2Y1(+/+) mice, and MRS2500 (2 mg/kg) was also beneficial (54 % decrease, p < 0.01). Renal BT doubled in P2Y1(-/-) versus P2Y1(+/+) mice, and increased threefold with MRS2500 compared to vehicle. Tail BT was markedly prolonged in P2Y1(-/-) mice (7.9X) and in C57BL/6 mice given MRS2500. The current study demonstrates that P2Y1 deletion or antagonism significantly reduced venous thrombosis in mice, suggesting that P2Y1 receptors play a role in the pathogenesis of venous thrombosis, at least in this species. However as with many antithrombotic agents the benefit comes at the potential price of an increase in provoked bleeding times.


Assuntos
Nucleotídeos de Desoxiadenina/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Receptores Purinérgicos P2Y1/metabolismo , Veias Cavas , Trombose Venosa/tratamento farmacológico , Animais , Plaquetas/metabolismo , Cloretos/efeitos adversos , Cloretos/farmacologia , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacologia , Deleção de Genes , Camundongos , Camundongos Knockout , Noxas/efeitos adversos , Noxas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/genética , Receptores Purinérgicos P2Y1/genética , Trombose Venosa/induzido quimicamente , Trombose Venosa/genética
14.
J Mol Neurosci ; 48(3): 482-92, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22528455

RESUMO

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.


Assuntos
Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Estresse Fisiológico/fisiologia , Animais , Doenças Autoimunes/fisiopatologia , Cardiomiopatias/fisiopatologia , Dermatite Alérgica de Contato/fisiopatologia , Suscetibilidade a Doenças , Homeostase/fisiologia , Inflamação/fisiopatologia , Isquemia/fisiopatologia , Nefropatias/fisiopatologia , Pneumopatias/fisiopatologia , Camundongos , Camundongos Knockout , Doenças do Sistema Nervoso/fisiopatologia , Neurotoxinas/toxicidade , Noxas/efeitos adversos , Pancreatopatias/fisiopatologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/deficiência , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Ferimentos e Lesões/fisiopatologia
15.
Toxicol Lett ; 213(1): 83-90, 2012 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-21501670

RESUMO

To understand environmental causes of disease, unbiased methods are needed to characterize the human exposome, which represents all toxicants to which people are exposed from both exogenous and endogenous sources. Because they directly modify DNA and important proteins, reactive electrophiles are probably the most important constituents of the exposome. Exposures to reactive electrophiles can be characterized by measuring adducts from reactions between circulating electrophiles and blood nucleophiles. We define an 'adductome' as the totality of such adducts with a given nucleophilic target. Because of their greater abundance and residence times in human blood, adducts of hemoglobin (Hb) and human serum albumin (HSA) are preferable to those of DNA and glutathione for characterizing adductomes. In fact, the nucleophilic hotspot represented by the only free sulfhydryl group in HSA (HSA-Cys(34)) offers particular advantages for adductomic experiments. Although targeted adducts of HSA-Cys(34) have been monitored for decades, an unbiased method has only recently been reported for visualizing the HSA-Cys(34) 'subadductome'. The method relies upon a novel mass spectrometry application, termed fixed-step selected reaction monitoring (FS-SRM), to profile Cys(34) adducts in tryptic digests of HSA. Here, we selectively review the literature regarding the potential of adductomics to partially elucidate the human exposome, with particular attention to the HSA-Cys(34) subadductome.


Assuntos
Exposição Ambiental/efeitos adversos , Noxas/efeitos adversos , Adutos de DNA/efeitos adversos , Exposição Ambiental/análise , Monitoramento Ambiental , Humanos , Noxas/análise , Noxas/metabolismo , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Compostos de Sulfidrila/efeitos adversos , Compostos de Sulfidrila/metabolismo , Toxicologia/métodos , Xenobióticos/efeitos adversos , Xenobióticos/metabolismo
16.
Rev Mal Respir ; 28(6): 809-22, 2011 Jun.
Artigo em Francês | MEDLINE | ID: mdl-21742242

RESUMO

Acute interstitial pneumonia (AIP) encompasses a spectrum of pulmonary disorders characterized by involvement of the lung interstitium and distal airways (bronchioles and alveoli). The onset of respiratory symptoms is acute, most often within two weeks. Most AIP take place de novo, but sometimes represent an acute exacerbation of chronic lung disease. The clinical presentation of AIP comprises rapidly progressive dyspnoea, associated sometimes with cough, fever, myalgia and asthenia. Chest radiography shows diffuse pulmonary opacities. The associated hypoxemia may be severe enough to cause acute respiratory failure. Underlying aetiologies are numerous and variable, particularly in relation to the underlying immune status of the host. Various histopathological entities may be responsible for AIP although diffuse alveolar damage is the predominant pattern. The diagnostic approach to a patient presenting with AIP is to try to determine the most likely underlying histopathological pattern and to search for a precise aetiology. It relies mainly on a meticulous clinical evaluation and accurate biological investigation, essentially guided by the results of bronchoalveolar lavage performed in an area identified by abnormalities on high resolution computed tomography of the lungs. Initial therapeutic management includes symptomatic measures, broad-spectrum antibiotic treatment adapted to the clinical context, frequently combined with systemic corticosteroid therapy.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doença Aguda , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Doença Antimembrana Basal Glomerular/complicações , Biomarcadores , Líquido da Lavagem Broncoalveolar , Broncoscopia , Terapia Combinada , Doenças do Tecido Conjuntivo/complicações , Diagnóstico por Imagem , Humanos , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/terapia , Noxas/efeitos adversos , Oxigenoterapia , Eosinofilia Pulmonar/complicações , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/etiologia , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Vasculite/complicações
18.
Otolaryngol Head Neck Surg ; 143(6): 837-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21109087

RESUMO

OBJECTIVE: It is not known how many olfactory receptor neurons should be intact to maintain olfaction in mouse models treated with 3-methylindole. The aim of this study is to investigate the relationship between a simple olfactory test outcome and the olfactory neuronal population. STUDY DESIGN: Mouse model. SETTING: Animal laboratory of the Seoul National University Bundang Hospital. SUBJECTS AND METHODS: Olfactory dysfunction was induced by intraperitoneal injection of 3-methylindole in 38 six-week-old female C57BL6 mice. Olfactory function was evaluated by a food-finding test following 72-hour starvation. The olfactory neuronal population was quantified by olfactory marker protein (OMP) expression. RESULTS: The average time for finding food was 8.1 seconds in control mice. It was 13.4, 84.4, 90.1, and 111.4 seconds for mice injected with 100, 200, 300, and 400 µg/g of 3-methylindole, respectively. Harvesting the whole olfactory neuroepithelium, densitometric analysis showed significant decrease of OMP in the 300- and 400-µg/g groups as compared with controls (18.8% and 17.5% of relative density, respectively). In the olfactory bulb, there was a significant decrease of OMP in the 200-, 300-, and 400-µg/g groups (44.5%, 37.0%, and 9.0% of relative density, respectively). The food-finding time had a significant reverse correlation with the relative density of OMP both in the olfactory bulb and in the olfactory neuroepithelium. CONCLUSION: Our study showed that olfactory impairment was correlated with olfactory neuronal population in mice treated with 3-methylindole. The food-finding test would be a useful tool that could be easily performed without special training in the 3-methylindole-treated C57BL6 anosmic mouse model.


Assuntos
Noxas/efeitos adversos , Transtornos do Olfato/induzido quimicamente , Neurônios Receptores Olfatórios/efeitos dos fármacos , Escatol/efeitos adversos , Olfato/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Noxas/administração & dosagem , Proteína de Marcador Olfatório/biossíntese , Escatol/administração & dosagem
20.
Clin Geriatr Med ; 26(1): 29-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20176291

RESUMO

Head injury has been recognized as an increasingly important determinant of late-life cognitive function. Despite a large number of research and clinical studies, no direct link has been established between minor head trauma with or without loss of consciousness and the development of dementia of the Alzheimer type. Similarly for alcohol, low doses have been found to be somewhat protective against dementia, whereas large doses increased the risk of late-life cognitive dysfunction. Among the many environmental toxins suspected of causing cognitive dysfunction, lead intoxication has the strongest evidence to support a link.


Assuntos
Envelhecimento/psicologia , Transtornos Relacionados ao Uso de Álcool/psicologia , Lesões Encefálicas/psicologia , Encéfalo/fisiopatologia , Demência/etiologia , Exposição Ambiental/efeitos adversos , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Transtornos Cognitivos/etiologia , Humanos , Noxas/efeitos adversos , Toxinas Biológicas/efeitos adversos
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