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1.
Rev Epidemiol Sante Publique ; 61(2): 172-9, 2013 Apr.
Artigo em Francês | MEDLINE | ID: mdl-23477883

RESUMO

BACKGROUND: Continued employment of people with health problems that reduce their ability to work is a major social issue. The French measures to optimize job retention are characterized by a multiplicity of participants, and their efficacy depends largely on the capacity of these different participants to work together. The objective of this study was to document the perceived role, attitudes and practices of participants involved in these job retention measures and of general practitioners, as well as their difficulties in this domain. METHODS: In 2009, 15 semi-directive interviews were conducted in the region of Provence-Alpes-Côte d'Azur (PACA) of occupational physicians, general practitioners, and other participants involved in the occupational reclassification of workers no longer completely fit for their job. The data collected were analyzed from a thematic perspective. RESULTS: The different groups of professionals questioned agreed on the primacy of the role of the occupational physician, on the importance of early consideration of each worker's case, and on the need to work together as partners to optimize the prospects of job retention. This study nonetheless showed numerous communication difficulties between the various professionals: although informal exchanges have developed over time, the efficacy of the system seems to be limited by a lack of clarity about the role of each institution, divergences of opinions on some key points including the role of the physicians caring for the patient, and, more largely, lack of information about the tools for job retention. CONCLUSION: The distribution of homogeneous knowledge, the development of multidisciplinary collaborative practices and the pooling of the lessons of experience between the different groups of participants are essential for the success of job retention procedures.


Assuntos
Atitude do Pessoal de Saúde , Doença Crônica , Emprego/psicologia , Médicos/psicologia , Padrões de Prática Médica , Comunicação , França , Clínicos Gerais/psicologia , Humanos , Saúde Ocupacional , Medicina do Trabalho , Equipe de Assistência ao Paciente , Papel do Médico
2.
Int Arch Occup Environ Health ; 83(3): 251-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19730876

RESUMO

PURPOSE: Physicians can play an important role in the reporting of occupational diseases (ODs), which are still under-reported in many countries. We aimed to identify physicians' difficulties in recognizing and reporting ODs and to study the characteristics of the physicians that do report ODs. METHODS: We conducted a telephone study in 2006-2007 among general practitioners (GPs), pulmonologists and rheumatologists in south-eastern France, concerning their knowledge, attitudes and practice in occupational health. Simple and multiple logistic regressions were performed to study factors associated with the issue of medical certificates for the claim process. RESULTS: Three hundred and ninety-one GPs, 95 pulmonologists and 96 rheumatologists participated. GPs reported significantly less often than specialists that they questioned their patients on past occupational exposure. They more frequently reported difficulties in identifying the occupational origin of diseases, and lack of knowledge on the OD reporting system. Issue of medical certificates for OD reporting was significantly more frequent among specialists than among GPs, among physicians considering that ODs are a public health problem, among those acquainted with the forms required to establish certificates, using internet to obtain information, having trade union activities, or having contact with occupational physicians (OPs). CONCLUSION: Initial and continuing training should be developed to encourage physicians, in particular GPs, to question patients on their working conditions and to become better acquainted with claim procedures. Physicians should also be provided with tools for identification of ODs that are suited to their practices, and collaboration with OPs should be fostered.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Notificação de Abuso , Doenças Profissionais/diagnóstico , Médicos de Família , Pneumologia , Reumatologia , Análise de Variância , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Entrevistas como Assunto , Masculino , Doenças Profissionais/epidemiologia , Inquéritos e Questionários
3.
J Occup Rehabil ; 19(3): 256-63, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19462158

RESUMO

INTRODUCTION: Identifying patients with psychological stress at work (PSW) and managing them are complex tasks. We studied the frequency of PSW as perceived by general practitioners (GPs), their practices in such situations, and the factors associated with these perceptions and practices, especially drug prescription. METHODS: Cross-sectional telephone study of GPs in southeastern France with a questionnaire about knowledge, attitudes, behavior, and practices in occupational health. We explored the management of PSW with a case-vignette of a 45-year-old supermarket cashier consulting for psychological stress that he or she attributes to the job. RESULTS: In all, 391 GPs participated; 87.2% reported that they encountered PSW often in their practice. GPs reported that they would treat the case-vignette patient by prescribing anxiolytics (66.5%) or sick leaves (65.7%) or referral to an occupational physician (80.3%) or a mental health specialist (44.8%). A multiple logistic regression showed that GPs reported prescribing an anxiolytic most frequently for the vignette-patient when they saw a high number of patients daily, asked patients about working conditions, suggested a sick leave or a referral to a specialist to the case-vignette patient and perceived more obstacles to reporting an occupational disease. CONCLUSION: Our study suggests that PSW is perceived by GPs as one of the principal work-related health problems and that in such situations, most GPs say they would prescribe drugs and sick leave and refer the patient to an occupational physician. Initial and continuing education programs and good practice guidelines would be useful to help them deal with these problems.


Assuntos
Exposição Ocupacional/efeitos adversos , Saúde Ocupacional/estatística & dados numéricos , Relações Médico-Paciente , Médicos de Família/estatística & dados numéricos , Estresse Psicológico/tratamento farmacológico , Adaptação Psicológica , Ansiolíticos/uso terapêutico , Estudos Transversais , Feminino , França , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Psicometria , Inquéritos e Questionários
4.
Rev Epidemiol Sante Publique ; 57(6): 456-65, 2009 Dec.
Artigo em Francês | MEDLINE | ID: mdl-19914017

RESUMO

BACKGROUND: A qualitative study was conducted in 2008 of occupational physicians (OPs) in south-eastern France to document their attitudes, opinions and practices on prevention and screening of occupational cancers. This was done to provide elements to prepare the questionnaire of a quantitative study in 2009. METHODS: Semi-structured interviews were conducted using a structured interview guide with 20 OPs. The data collected were subjected to an analysis of thematic content type. RESULTS: The analysis revealed that OPs face many difficulties when preventing occupational cancers. For most of OPs, these difficulties appeared related to "external factors": lack of involvement of employers and minimization of risks by employers and employees. Lack of time, overload and, for some OPs, perceived lack of independence towards employers, were also mentioned as barriers to cancer prevention. This study also suggested hypotheses related to OPs themselves (internal factors): perceived lack of effectiveness and, trend to minimize the risks of occupational cancer in their geographical area. Finally, the results suggest a significant heterogeneity of OPs' practices regarding occupational cancer screening. CONCLUSION: These results raise several hypotheses that will be addressed further in the quantitative survey. They warn about the difficulties of a profession that seems to encounter a demographic and identity crisis.


Assuntos
Atitude do Pessoal de Saúde , Neoplasias/prevenção & controle , Doenças Profissionais/prevenção & controle , Medicina do Trabalho , Feminino , França , Humanos , Masculino , Papel do Médico , Padrões de Prática Médica
5.
Occup Environ Med ; 65(6): 392-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17928383

RESUMO

OBJECTIVES: To study physician barriers to workers' compensation claims for asbestos-related cancers, focusing on smokers' stigma and physicians' speciality and role perception. METHODS: Cross-sectional telephone study of 486 randomly-selected general practitioners (GPs) and pulmonologists in south-eastern France. Standardised questionnaires explored their behaviour, attitudes and practices in the field of occupational health and their responses to a case vignette of a lung cancer patient with long-term occupational asbestos exposure. Randomised subgroups of GPs and pulmonologists heard alternative versions varying only as regards the worker's smoking status. We studied factors associated with the recommendation that the case vignette patient file a compensation claim with simple and multiple logistic regressions. RESULTS: The response rate was 64.4% among GPs and 62.5% among pulmonologists. Recommending the filing of an occupational disease claim was significantly associated in multiple logistic regressions with speciality (OR 4.46; 95% CI 2.38 to 8.37, for pulmonologists vs GPs), patient's smoking status (OR 3.15; 95% CI 2.11 to 4.70, for non-smokers vs smokers), physician's workload (OR 1.83; 95% CI 1.17 to 2.88, for 25) and role perception (OR 2.00; 95% CI 1.22 to 3.27, for those who considered completing occupational disease medical certificates to be part of their role vs those who did not). CONCLUSIONS: The results of this French study appear applicable to various countries and contexts. To make physicians and especially GPs more aware of occupational health and smoking stigma, officials and educators must give these topics higher priority during initial training and continuing medical education. Tools and equipment that take time constraints into account should be developed and disseminated to help physicians manage occupational diseases.


Assuntos
Amianto/toxicidade , Atitude do Pessoal de Saúde , Neoplasias Pulmonares/etiologia , Doenças Profissionais/etiologia , Fumar/psicologia , Indenização aos Trabalhadores , Estudos Transversais , Feminino , França , Humanos , Masculino , Medicina , Papel do Médico , Médicos de Família/psicologia , Fumar/efeitos adversos , Especialização , Carga de Trabalho
6.
Rev Epidemiol Sante Publique ; 55(5): 376-81, 2007 Oct.
Artigo em Francês | MEDLINE | ID: mdl-17766072

RESUMO

BACKGROUND: Occupational health is a major public health problem in France. However, the level of investment of general practitioners and specialist physicians in this field is not well documented. We aimed at studying elements moving closer or differentiating groups of professionals (notably physicians) in the field of occupational health in terms of conceptions of their roles (prevention and care) and of practices (in particular detection and notification of occupational diseases and perceived barriers). METHODS: We conducted a qualitative study in south-eastern France which consisted of in-depth interviews of physicians and actors involved in the prevention of occupational hazards or in their indemnification. Then discourse analysis was carried out on the corpus collected. Content analysis grouped the data into themes. RESULTS: Several reasons could explain the low investment of physicians in the field of occupational health: insufficient detection of occupational causes of diseases, complexity of administrative procedures of declaration and bias of causal interpretation for the patients exposed to other risk factors such as smoking. The fear that notifying an occupational disease might have repercussions on patients' socio-professional situations places physicians in a situation of ethical dilemma: inducing a social risk on one side, ignoring his rights on the other. Physicians are not sufficiently prepared to deal with these situations, because they lack appropriate knowledge and support from specialists in the field, due to an important bulk-heading of actors and their practices. CONCLUSION: To sensitize and train physicians to occupational health and to support multi-field practices are essential.


Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Saúde Ocupacional , Médicos , Educação Médica , Ética Médica , Medicina de Família e Comunidade , França , Humanos , Medicina , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Medicina do Trabalho/educação , Direitos do Paciente , Papel do Médico , Fatores de Risco , Fumar , Meio Social , Especialização
7.
Disabil Rehabil ; 27(10): 553-9, 2005 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-16019864

RESUMO

PURPOSE: The objective was to estimate the psychometric properties of the Modified-Modified Schober Test (MMST). DESIGN: This study compared range of motion measurements of lumbar flexion in low back pain (LBP) patients using the MMST with measurements calculated on X-rays as the gold standard, and compared the measurements taken by two independent examiners. METHOD: This study was conducted at the main hospital in the Outaouais area, Quebéc, Canada. Thirty-one subjects with LBP from private and public clinics participated in the study. After a warm-up session, measurements with the MMST were taken in neutral position and an X-ray technician took an exposure in the same position. RESULTS: Pearson's correlation test (r) between measurements made with the MMST and the gold standard, intra-class correlation coefficient (ICC), minimum metrically detectable change (MMDC) and confidence interval (CI) were used to analyze the data. The MMST demonstrated moderate validity (r=0.67; 95%CI 0.44-0.84), excellent reliability (intra: ICC=0.95; 95%CI 0.89-0.97; inter: ICC=0.91; 95%CI 0.83-0.96) and a MMDC of 1 cm. CONCLUSIONS: In our sample of LBP patients, the MMST showed moderate validity but excellent reliability and MMDC.


Assuntos
Avaliação da Deficiência , Dor Lombar/diagnóstico , Região Lombossacral/fisiopatologia , Modalidades de Fisioterapia , Amplitude de Movimento Articular , Adulto , Feminino , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/fisiopatologia , Masculino , Variações Dependentes do Observador , Radiografia , Reprodutibilidade dos Testes
8.
Neurology ; 26(7): 664-6, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-180456

RESUMO

Levels of cyclic adenosine monophosphate (AMP) in the basilar artery and in circulating blood of cats were determined after the production of spasm by topical application of blood to the vessel and following treatment with agents known to alter cyclic AMP. Isoproterenol, known to stimulate adenyl cyclase, and aminophylline, a phosphodiesterase inhibitor, were studied alone and in combination. Cyclic AMP of the basilar artery fell from a mean control value of 43 to 26 pmoles per milligram of protein following the production of vasospasm. Intravenous administration of isoproterenol alone and in combination with aminophylline produced dilatation of the basilar artery, which was associated with a marked rise in the cyclic AMP concentration in the vessel. The finding that cerebral vasospasm is associated with a fall and vasodilation with a rise in cyclic AMP concentration supports the hypothesis of an active role for cyclic nucleotides in the regulation of cerebrovascular smooth muscle tone.


Assuntos
Artéria Basilar/metabolismo , AMP Cíclico/metabolismo , Aminofilina/farmacologia , Animais , Artéria Basilar/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Gatos , AMP Cíclico/sangue , Frequência Cardíaca/efeitos dos fármacos , Ataque Isquêmico Transitório/metabolismo , Isoproterenol/farmacologia
9.
J Toxicol Environ Health A ; 53(7): 507-30, 1998 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-9561966

RESUMO

Groups of 4 male Wistar rats were dosed intravenously with 14C-labeled benzo[a]pyrene dissolved in an Emulphor/water vehicle at 3 different dose levels and killed at 1 of 15 specific time intervals from 5 min to 32 h after dosing. 14C-Radiolabel concentration-time data were obtained for blood, brain, adipose, heart, kidney, liver, lung, spleen, and testes. Benzo[a]pyrene concentration-time data were obtained for blood, adipose, kidney, liver, and lung. Appropriate mathematical models were fitted to these data and to the data for metabolites derived as the residuals from 14C-radiolabel minus benzo[a]pyrene difference, where applicable. Nonlinear kinetics were found for 14C-radiolabel in liver, while the data from lung for both 14C-radiolabel and for benzo[a]pyrene per se supported the binding of benzo[a]pyrene in that tissue.


Assuntos
Benzo(a)pireno/farmacocinética , Carcinógenos Ambientais/farmacocinética , Tecido Adiposo/química , Tecido Adiposo/metabolismo , Animais , Área Sob a Curva , Benzo(a)pireno/isolamento & purificação , Carcinógenos Ambientais/isolamento & purificação , Meia-Vida , Injeções Intravenosas , Masculino , Modelos Biológicos , Ratos , Ratos Wistar , Distribuição Tecidual
10.
Am J Vet Res ; 47(6): 1398-401, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3729142

RESUMO

A conjugate of asparaginase and monomethoxypolyethylene glycol was evaluated in acute, subacute, and subchronic toxicologic studies in mice, rats, and dogs. The drug induced low-grade toxicosis. The appearance and behavior of rats and dogs were not affected by the treatment. Only large doses produced inactivity, loss of appetite, and loss of weight. The LD50 could not be established. The drug retarded slightly body weight gains in dogs and female rats and produced mild anemia in 30% of the female rats. Urinalysis and blood chemical determinations in rats and dogs were generally not affected by the treatment. Monomethoxypolyethylene glycol-asparaginase was detectable in the plasma of mice 13 days after IV, intraperitoneal, or IM administration, and in dogs for 3 to 4 weeks.


Assuntos
Asparaginase/toxicidade , Polietilenoglicóis/toxicidade , Animais , Asparaginase/administração & dosagem , Cães , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C3H , Polietilenoglicóis/administração & dosagem , Ratos , Ratos Endogâmicos , Especificidade da Espécie
13.
Arch Phys Med Rehabil ; 61(9): 402-5, 1980 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6774694

RESUMO

Concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in serum and 17-ketosteroids (17-KS) in urine of 10 paraplegic and 10 quadriplegic subjects were measured from onset of injury and followed once a week for 4 months. Compared with age-matched normal controls, paraplegic subjects showed significantly lower serum levels of LH and FSH for 2 weeks and of testosterone for 6 weeks after spinal cord trauma, following which periods of time these hormones attained normal levels. By contrast, in quadriplegic subjects, serum testosterone concentrations remained significantly lower than those of the controls during the entire 4-month testing period. Furthermore, in another group of 10 chronic (1 to 6 years after onset of injury) paraplegic and 10 chronic quadriplegic subjects, serum testosterone and FSH concentrations were comparable to those of the normal controls. Serum LH concentrations were at control levels in chronic paraplegic but significantly depressed in chronic quadriplegic subjects. The concentrations of urinary 17-KS exhibited sharp fluctuations over the 4-month period and were below control levels in paraplegic but within control limits in quadriplegic subjects. The results indicate that the function of the hypothalamic-pituitary-gonadal axis is disturbed for at least 4 months in quadriplegic subjects.


Assuntos
17-Cetosteroides/urina , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Traumatismos da Medula Espinal/metabolismo , Testosterona/sangue , Adulto , Doença Crônica , Humanos , Masculino , Paraplegia/metabolismo , Quadriplegia/metabolismo
14.
Arch Phys Med Rehabil ; 61(3): 139-42, 1980 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7369852

RESUMO

In 10 paraplegic and 10 quadroplegic subjects, bone resorption was investigated by determining urinary excretion of hydroxyproline, calcium, and phosphorus. Measurements were performed weekly from the onset to 4 months after injury. During the first 7 weeks following injury, urinary excretion of calcium in paraplegic and quadriplegic subjects reached the highest level (380 +/- 180 mg/24hr). From 7 to 16 weeks after injury average urinary excretion of calcium (245 +/- 72 mg/24hr) remained significantly greater than that in controls (100 +/- 25 mg/24hr; p less than 0.05). Urinary hydroxyproline was elevated in paraplegic subjects (80 +/- 18 mg/24hr) for 8 weeks and in quadriplegic subjects (102 +/- 37 mg/24hr) for the entire 16 weeks following injury compared with that in controls (48 +/- 12 mg/24hr; p less than 0.05). Both paraplegic and quadriplegic subjects excreted more phosphorus (1.6 +/- 0.4 gm/24hr) than controls (0.85 +/- 0.2 gm/24hr; p less than 0.05) only during the first 2 weeks following spinal cord injury. During the acute phase of the injury (0-3 months), urinary excretion of calcium and magnesium was significantly higher (p less than 0.05) in subjects with complete compared with incomplete spinal cord lesions.


Assuntos
Reabsorção Óssea , Osso e Ossos/metabolismo , Minerais/urina , Traumatismos da Medula Espinal/urina , Adulto , Cálcio/urina , Humanos , Hidroxiprolina/urina , Magnésio/urina , Masculino , Osteoporose/prevenção & controle , Paraplegia/urina , Fósforo/urina , Quadriplegia/urina , Fatores de Tempo
15.
J Toxicol Environ Health ; 15(5): 603-7, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4046067

RESUMO

[14C(U)]-Labeled 1,2,3,4-tetrachlorobenzene was administered orally to squirrel monkeys. Urine was collected from these animals, pooled and analyzed for metabolites by thin-layer chromatography, high-performance liquid chromatography, and gas chromatography-mass spectroscopy. N-Acetyl-s-(2,3,4,5-tetrachlorophenyl) cysteine was shown to be the major metabolite and accounted for 85% of the radioactivity found in urine. A minor metabolite was identified as 2,3,4,5-tetrachlorophenol. This study demonstrates for the first time that an N-acetyl cysteine conjugate has been isolated and identified as metabolite of a chlorinated benzene. This pattern of chlorobenzene metabolism is significantly different from the one obtained with the rat and rabbit, where tetrachlorophenols constitute the major metabolites.


Assuntos
Clorobenzenos/urina , Acetilcisteína/metabolismo , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Cromatografia Gasosa-Espectrometria de Massas , Saimiri
16.
J Environ Sci Health B ; 22(4): 439-53, 1987 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3655190

RESUMO

The tissue distribution and excretion of three trichlorobenzene isomers (TCB) were investigated in the rat. Single doses of TCBs were administered orally to groups of 5 fasted rats at 10 mg/kg body weight. Serial sacrifices were carried out and the radioactivity contents were determined in tissues and blood. For all three TCB isomers, radioactivity appeared in the blood and tissues at 0.5 h, and peaked around 2-4 h after dosing. Fat, skin, and liver had high concentrations of the parent compound while kidney and muscle had high levels of metabolites. Elimination of TCB from tissues and blood can best be described by a two-compartmental open pharmacokinetic model. The terminal half-lives were 145, 93 and 68 h for 1,2,3-, 1,2,4 and 1,3,5-TCB isomer respectively. Ninety-five percent of the administered 1,2,3- and 89% of the 1,3,5-isomers were eliminated within 48 h in the urine and feces with the former being the major route.


Assuntos
Clorobenzenos/farmacologia , Animais , Radioisótopos de Carbono , Clorobenzenos/urina , Fezes/análise , Isomerismo , Masculino , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade , Distribuição Tecidual
17.
Cancer ; 59(12): 2011-5, 1987 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-3567863

RESUMO

Thirty-seven dogs with malignant lymphoma were treated with either polyethylene glycol conjugated (PEG) asparaginase alone (10-30 IU/kg intraperitoneally [IP] weekly--20 dogs) or PEG-asparaginase combined with one cycle of chemotherapy (vincristine, cyclophosphamide, methotrexate, and prednisone), followed by maintenance PEG-asparaginase (30 IU/kg, IP weekly--17 dogs). In the 20 dogs (eight were chemotherapy resistant) treated with PEG-asparaginase alone, seven had a complete response (CR), seven had a partial response (PR), five had no response (NR), and one was not evaluable (NE). The duration of response (CR + PR) ranged from 14 to 102 days (median, 48 days). In the eight chemotherapy-resistant dogs (seven were previously resistant to L-asparaginase) four had responses (one CR and three PR). In the 17 dogs treated with combined PEG-asparaginase and chemotherapy, 13 had a CR, two had a PR, and two had NR. None of the dogs had had prior chemotherapy, and the duration of response (CR + PR) ranged from 7 to 840+ days, with a median of 126+ days. Four dogs are still on maintenance PEG-asparaginase at 16+, 21+, 26+, and 28+ months. Toxicity consisted of death due to massive tumor breakdown (two dogs), disseminated intravascular coagulation (DIC--one dog), hypersensitivity reaction (one dog), vomiting (three dogs) and soft stools (three dogs). Four normal dogs were given very high doses of PEG-asparaginase (200 IU/kg and 1200 IU/kg) once weekly for two treatments without any significant toxicity. These results indicate that PEG-asparaginase has antitumor activity in dog with spontaneously occurring malignant lymphoma.


Assuntos
Asparaginase/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma/tratamento farmacológico , Animais , Asparaginase/administração & dosagem , Asparaginase/sangue , Asparaginase/toxicidade , Cães , Polietilenoglicóis
18.
J Free Radic Biol Med ; 2(4): 283-8, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3584850

RESUMO

Treatment with catalase and SOD (superoxide dismutase) could diminish the damage due to oxygen free radical formation, but these enzymes are rapidly removed from circulation. The covalent attachment of monomethoxypolyethylene glycol (PEG) to catalase and SOD extended their plasma half-lives. Toxicity of PEG-catalase and PEG-SOD was evaluated in mice and rats prior to their use as free radical scavengers. Rodents used in acute, subacute, and subchronic toxicologic studies could tolerate large doses of PEG-catalase and PEG-SOD without developing toxic signs. The conjugates did not affect survival rate, appearance, behavior, food intake, blood chemistry, hematology, or urinalysis. In general, body weight gains, organ weights, and histomorphology were also unaffected. Massive doses of PEG-catalase caused slight weight loss, splenic hypertrophy, and generalized splenic stimulation in mice. Massive doses of PEG-SOD resulted in vacuolation in splenic macrophages in rats. PEG-catalase and PEG-SOD circulated for 3 days and 8 days, respectively, in mice following i.v. or i.m. administration.


Assuntos
Catalase/toxicidade , Oxigênio/metabolismo , Polietilenoglicóis/toxicidade , Superóxido Dismutase/toxicidade , Animais , Células Sanguíneas , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Catalase/sangue , Catalase/urina , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Radicais Livres , Meia-Vida , Masculino , Camundongos , Polietilenoglicóis/sangue , Polietilenoglicóis/urina , Ratos , Superóxido Dismutase/sangue , Superóxido Dismutase/urina , Urina
19.
Toxicol Ind Health ; 12(1): 105-21, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8713718

RESUMO

The tissue distribution, metabolism, and excretion of 14C-labeled 2,4,4'-trichlorobiphenyl (CB-28) were studied in the rat. Following intravenous administration, radioactivity was removed from the blood rapidly and distributed to tissues. The time-courses of varying concentrations of CB-28 in tissues and blood were described mathematically using nonlinear regression analysis. The highest concentrations of radioactivity were found in the adipose and skin, which showed distinct uptake phases. High levels were seen at 30 minutes in liver and brain, but quickly declined. Fifty-two percent of the given dose was excreted in feces within 14 days. Intraperitoneal administration to three female rats for five consecutive days provided tissues which were analyzed for metabolites.


Assuntos
Bifenilos Policlorados/farmacocinética , Animais , Radioisótopos de Carbono , Feminino , Injeções Intraperitoneais , Injeções Intravenosas , Masculino , Bifenilos Policlorados/metabolismo , Bifenilos Policlorados/urina , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
20.
Artigo em Inglês | MEDLINE | ID: mdl-198395

RESUMO

The role of the adrenergic receptor in mediating pulmonary vascular responses to gaseous and humoral agents was investigated by use of epinephrine injections in the perfused feline pulmonary circulation. Alteration of the balance between alpha- and beta-adrenergic activity was quantified by measurement of decreasing vasoconstrictor activity to epinephrine and rising lobar tissue 3',5'-adenosine cyclic monophosphate (cAMP) levels. The increased beta-adrenergic activity thus generated was associated with marked reductions in the pulmonary vasoconstrictor responses to hypoxia, hypercapnic acidosis, and histamine, but not to serotonin. Repeated pulmonary vasodilations or increases in blood, but not pulmonary tissue, levels of cAMP induced by theophylline doses, which would not necessarily affect the beta-adrenergic activity, did not alter the pulmonary vasoconstrictor responses to hypoxia, hypercapnia, or histamine. These data support the significant role which the adrenergic system plays in mediating pulmonary vasoconstrictor responses to certain specific gaseous and humoral agents, and the specificity with which this mediation occurs serves to link hypoxia and histamine together so that the latter could serve as a mediator of the former.


Assuntos
Epinefrina/farmacologia , Histamina/farmacologia , Hipóxia/fisiopatologia , Circulação Pulmonar/efeitos dos fármacos , Receptores Adrenérgicos beta/fisiologia , Receptores Adrenérgicos/fisiologia , Serotonina/farmacologia , Acidose/fisiopatologia , Animais , Gatos , AMP Cíclico/sangue , Hipercapnia/fisiopatologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Teofilina/farmacologia , Vasoconstrição/efeitos dos fármacos
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