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2.
Artigo em Inglês | MEDLINE | ID: mdl-36740269

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have increased the rate of presenteeism among front-line physicians. Presenteeism is the term used to describe attendance at work despite ill health that would normally prompt rest or absence from work. This study aimed to examine the associations between COVID-19 clinical practice and presenteeism among physicians. METHODS: A cross-sectional study was conducted from December 2021 to January 2022. The questionnaires were distributed to 21,737 employed physicians who were members of the Japan Medical Association. Presenteeism was measured by the Work Functioning Impairment Scale. Multiple logistic regression analysis was used to evaluate the association between COVID-19 clinical practice and presenteeism. RESULTS: Overall, 3,968 participants were included in the analysis, and presenteeism was observed in 13.9% of them. The rate of presenteeism significantly increased with both the number of COVID-19 patients treated and the percentage of work time spent treating these patients (both P values for trend < 0.001). In comparison to those not currently engaged in the treatment of COVID-19 patients, presenteeism was significantly higher among front-line (adjusted odds ratio [aOR] = 1.71, 95% confidence interval [CI]: 1.16-2.53) and second-line physicians supporting those in the front-line (aOR = 1.45, 95% CI: 1.17-1.78). There was no association between involvement in COVID-19 vaccination services and presenteeism. CONCLUSIONS: The burden on front-line and second-line physicians in COVID-19 clinical practice must be minimized. Employed physicians also need to recognize the importance of communicating with their workplaces about presenteeism.


Assuntos
COVID-19 , Médicos , Humanos , COVID-19/epidemiologia , Presenteísmo , Japão/epidemiologia , Estudos Transversais , Vacinas contra COVID-19 , Inquéritos e Questionários
3.
J Occup Health ; 64(1): e12377, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36459419

RESUMO

OBJECTIVES: Long working hours in Japan is a social concern. This is also true for the working hours of physicians, who often do side work in addition to working at their main hospital. New physician work regulations to be implemented in Japan require work-hour management, including side work. This study examined the association between physicians' overtime and side work hours and their health outcomes. METHODS: We conducted a cross-sectional study using data from a survey of working physicians conducted by the Japan Medical Association from 2021 to 2022. Questionnaires completed by 2906 full-time working physicians aged 24-69, excluding junior resident doctors, were analyzed. Depressive symptoms and the presence of thoughts of death or suicide using the Quick Inventory of Depressive Symptomatology - Japanese version was used to assess health outcomes. Logistic regression analysis was performed using overtime at the main place of employment and side work hours as exposure factors. RESULTS: Both depressive symptoms and thoughts of death or suicide increased in the group with longer overtime hours at the main place of work. A similar tendency was observed for side work but adjusting for overtime hours eliminated the association. In other words, total working hours had an impact on health, regardless of whether overtime work at the main place of employment or side work. CONCLUSIONS: Despite the existence of multiple hurdles to managing working hours, including side work, the working environment for physicians needs to be improved to protect their health and quality of medical care.


Assuntos
Depressão , Médicos , Humanos , Estudos Transversais , Japão/epidemiologia , Depressão/epidemiologia , Emprego , Capsaicina , Mentol
4.
Sangyo Eiseigaku Zasshi ; 62(3): 115-126, 2020 May 25.
Artigo em Japonês | MEDLINE | ID: mdl-31656235

RESUMO

OBJECTIVES: The objectives of this study were to analyze current trends in occupational health activities by classifying reports from medical facilities in Japan. METHODS: Reports of current workplace-level occupational health activities from medical activities that were collected by the Japan Medical Association Occupational Health Committee were used for the study. Of 5,000 questionnaire forms sent to medical facilities, 1,920 responses were returned. The freely described reports on ongoing occupational health activities contained in these responses were classified according to each of the following aspects of reported activities: 1) details of occupational health activities including main actors in workplace-level actions; and 2) approaches taken for occupational safety and health. The classification of the reports was implemented by a working group comprising selected occupational health practitioners and researchers. RESULTS: Among 1,920 survey responses, 581 valid texts were analyzed. Altogether, 1,044 occupational health activities currently undertaken by the facilities were extracted. The reported activities that were classified according to details of occupational health activities mainly comprised "Measures for preventing overwork, labor management, and work-style reform" (35.7%), "Measures for improving mental health" (21.0%), and "Review of occupational safety and health management systems" (19.3%). Medical facilities implementing "Measures for mental health" alongside "Measures for preventing overwork, labor management, and work-style reform" were reported in 13.2% of the responding medical facilities. "Occupational health professionals or safety and health management staff" (71.7%) were the most frequent main actors of these activities, followed by "Members of the workplace" (18.4%) and "Outsourced experts" (2.4%). "Comprehensive safety and health management" (42.0%) was the most common approach taken for occupational safety and health, followed by "Management focusing on topics" (23.8%) and "Case management" (16.5%). Most of these activities focused on primary prevention aimed at labor management including prevention of overwork, work-style reform, and mental health promotion. Another key trend could be "Teamwork among occupational safety and health staff, workers, and employers at respective workplaces as well as outsourced experts." DISCUSSION: Several key trends were extracted from current occupational health activities at medical facilities. In most cases, these measures were implemented simultaneously. This suggests the importance of combining primary prevention measures for mental health with measures for labor management including prevention of overwork. These activities reflect emerging trends that incorporate teamwork between experts, workers, and employers, and provide new perspectives on workplace-level occupational safety and health activities.


Assuntos
Instalações de Saúde , Promoção da Saúde , Doenças Profissionais/prevenção & controle , Saúde Ocupacional , Humanos , Japão , Saúde Mental , Segurança , Inquéritos e Questionários , Tolerância ao Trabalho Programado , Carga de Trabalho , Local de Trabalho
5.
Intern Med ; 56(11): 1421-1424, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28566609

RESUMO

We herein report a 65-year-old man demonstrating dementia with Lewy bodies who first presented with Bálint's syndrome. Two years later, a mild cognitive impairment was noted. From three years after onset, he developed progressive parkinsonism, visual hallucination, and autonomic dysfunction, in line with the deterioration of the cognitive function. Single photon emission computed tomography with a 99mTc-ethylcysteinate dimer performed two years after onset revealed hypoperfusion in the restricted area of the bilateral superior parietal lobule, which extended to the lateral occipital cortices within two years. It is suggested that the pathological process can extend from the parietal to occipital lobes.


Assuntos
Doença por Corpos de Lewy/complicações , Doenças do Sistema Nervoso/complicações , Idoso , Cognição , Progressão da Doença , Humanos , Masculino , Síndrome , Tomografia Computadorizada de Emissão de Fóton Único
6.
Seishin Shinkeigaku Zasshi ; 119(2): 98-104, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-30620844

RESUMO

The certified psychologist is a cross-disciplinary profession ; thus, the qualification test and curriculum should cover not only medical but also non-medical areas. The number of men- tal health professionals working in medical areas is high. Knowledge and skills in the health care area are necessary for certified psychologists and candidates. Knowledge covers laws and systems of medical services, including medical safety and infection control, and medical knowledge at the non-professional/patient level. In the general medical area, skills of: 1) having multilevel perspectives, 2) understanding dynamics and collaborating, and 3) facilitating com- munication with difficulties, are necessary. When going down the clinical river, holding an OAR [Open, Available, Responsible] is significant, not only for those who working in the medical area but for everyone, because every certified psychologist is obligated to cooperate.


Assuntos
Psicologia/educação , Atitude Frente a Saúde , Hospitais Gerais , Humanos
7.
Seishin Shinkeigaku Zasshi ; 113(4): 397-404, 2011.
Artigo em Japonês | MEDLINE | ID: mdl-21702131

RESUMO

Physicians in hospitals are so exhausted that mental healthcare providers other than physicians, such as psychologists, might be necessary. A clinical education program for psychologists in general hospitals has been developed. Applicants should be at Level 2 of Stoltenberg & McNeil's IDM (Integrated Development Model) model. Seven domains of objectives are introduced. Core competencies are multi-dimensional knowledge, understanding dynamics and collaborating, and communication skills with challenging patients. Sustainable education strategies and evaluation methods are discussed. A TV-based education program is useful for the purpose of acquiring general medical knowledge.


Assuntos
Psicologia Clínica/educação , Objetivos , Hospitais Gerais , Japão , Modelos Psicológicos
8.
Int J Behav Med ; 18(4): 384-90, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21125365

RESUMO

BACKGROUND: Physicians' mental health can be affected by unreasonable demands and complaints made by patients. PURPOSE: The purpose of this study is to determine the association between depressive symptoms and suicidal ideation among physicians working in hospitals in Japan and unreasonable patient demands and complaints. METHODS: We sent an anonymous questionnaire to 10,000 randomly selected physicians working at hospitals who were members of the Japan Medical Association. The anonymous self-report questionnaire sought to determine the number of unreasonable demands and complaints made by patients or their family members reported by physicians in the previous 6 months. Depressive symptoms and suicidal ideation were measured using the Japanese version of the Quick Inventory of Depressive Symptomatology (QIDS). Logistic regression analysis was used to explore the associations of depressive symptoms and suicidal ideation with reported unreasonable demands and complaints. RESULTS: Among the 3,864 respondents, men (46.3%) reported experiencing unreasonable patient demands and complaints more frequently than women (40.4%). Depressive symptoms were indicated in 8.3% of men and 10.5% of women, and 5.7% of men and 5.8% women were determined to exhibit suicidal ideation. The number of unreasonable demands and complaints in the previous 6 months was significantly associated with depressive symptoms and suicidal ideation for both men and women (P for trend <0.01). CONCLUSIONS: Physicians should recognize the health risks of unreasonable demands and complaints, and hospitals should provide support for physicians dealing with these stressors.


Assuntos
Transtorno Depressivo/etiologia , Relações Médico-Paciente , Médicos/psicologia , Estresse Psicológico/etiologia , Ideação Suicida , Adulto , Idoso , Atitude do Pessoal de Saúde , Estudos Transversais , Transtorno Depressivo/psicologia , Feminino , Hospitais , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
9.
Int J Med Sci ; 7(3): 101-9, 2010 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-20567610

RESUMO

BACKGROUND: To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions containing lipid. METHODS: The pH value of a TPN solution containing lipid (pH 6.0, containing 20 ppm of NaHSO(3)) was adjusted by the addition of HCl to 5.7, 5.4, or 4.9. The pH value of another TPN solution (pH5.5, containing 400 ppm of NaHSO(3)) was adjusted by the addition of NaOH to 5.9, 6.3, or 6.8. A specific number of each microorganism was added to 10 mL of each test solution and incubated at room temperature. The number of microorganisms was counted as colony forming units at 0, 24, and 48 hrs later. RESULTS: C albicans increased similarly at any pH values in the TPN solution. The bacterial species also increased rapidly at pH6.0 in the solution containing 20 ppm of NaHSO(3), but growth was suppressed as the pH value was reduced, with growth halted at pH4.9. However, these bacterial species did not increase, even at pH5.9, in the other solution containing 400 ppm of NaHSO(3). CONCLUSIONS: These results suggest that Candida species can grow rapidly in almost all TPN solutions regardless of the acidity, lipid, and NaHSO(3); also, some bacterial species may grow in TPN solutions containing lipid unless the pH value is 5.0 or less. Therefore, each TPN solution should be examined whether or not the bacterial species can proliferate.


Assuntos
Nutrição Parenteral Total , Bacillus cereus/efeitos dos fármacos , Bacillus cereus/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Sulfitos/farmacologia
10.
BMC Public Health ; 10: 127, 2010 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-20222990

RESUMO

BACKGROUND: Physicians' mental health may be adversely affected by the number of days of work and time spent on-call, and improved by sleep and days-off. The aim of this study was to determine the associations of depressive symptoms with taking days of off duty, hours of sleep, and the number of days of on-call and overnight work among physicians working in Japanese hospitals. METHODS: A cross-sectional study as a national survey was conducted by mail. The study population was 10,000 randomly selected physicians working in hospitals who were also members of the Japan Medical Association (response rate 40.5%). Self-reported anonymous questionnaire was sent to assess the number of days off-duty, overnight work, and on-calls, and the average number of sleep hours on days not working overnight in the previous one month. Depressive state was determined by the Japanese version of the Quick Inventory of Depressive Symptomatology. Logistic regression analysis was used to explore the associations between depressive symptoms and the studied variables. RESULTS: Among the respondents, 8.3% of men and 10.5% of women were determined to be depressed. For both men and women, depressive state was associated with having no off-duty days and averaging less than 5 hours of sleep on days not doing overnight work. Depressive state was positively associated with being on-call more than 5 days per month for men, and more than 8 days per month for women, and was negatively associated with being off-duty more than 8 days per month for men. CONCLUSION: Some physicians need some support to maintain their mental health. Physicians who do not take enough days-off, who reduced sleep hours, and who have certain number of days on-calls may develop depressive symptoms.


Assuntos
Plantão Médico , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Hospitais/estatística & dados numéricos , Médicos/psicologia , Sono/fisiologia , Tolerância ao Trabalho Programado/psicologia , Adulto , Plantão Médico/estatística & dados numéricos , Idoso , Atitude do Pessoal de Saúde , Estudos Transversais , Depressão/etiologia , Transtorno Depressivo/etiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Médicos/estatística & dados numéricos , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
11.
J Toxicol Sci ; 31(3): 229-34, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16960433

RESUMO

Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia.


Assuntos
Ácido Cítrico/toxicidade , Hipocalcemia/induzido quimicamente , Animais , Cálcio/sangue , Ácido Cítrico/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Tempo de Coagulação do Sangue Total
12.
Clin Nutr ; 25(6): 984-93, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16698131

RESUMO

BACKGROUND & AIMS: The possible clinical significance of the toxic effects of citrate has not yet been fully clarified. This study was therefore conducted to confirm the toxicity and determine the tolerable infusion rate of citrate administered by rapid intravenous infusion to conscious dogs. METHODS: Citrate solutions were infused via the cephalic vein of 4 conscious dogs at 0.33, 0.67, or 1.33mmol/kg/h up to 1.33mmol/kg. Clinical signs and the electrocardiogram were observed during and after infusion. Serum citrate and ionized calcium levels were also measured. RESULTS: Although the mean citrate level increased in accordance with the infusion rate, the calcium level decreased. No significant changes in clinical signs or the electrocardiogram were observed during infusion at 0.33mmol/kg/h despite an increase in the serum citrate level to 1.22+/-0.11mmol/l (pre-infusion value: 0.38+/-0.01mmol/l) and a decrease in the serum calcium level to 1.28+/-0.03mmol/l (pre-infusion value: 1.50+/-0.05mmol/l). Vomiting and QTc prolongation were observed at 0.67mmol/kg/h or higher. Salivation and tachycardia were observed at 1.33mmol/kg/h. CONCLUSIONS: Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33mmol/kg/h.


Assuntos
Anticoagulantes/farmacocinética , Cálcio/sangue , Ácido Cítrico/farmacocinética , Hipocalcemia/induzido quimicamente , Animais , Anticoagulantes/toxicidade , Área Sob a Curva , Ácido Cítrico/toxicidade , Cães , Relação Dose-Resposta a Droga , Eletrocardiografia , Infusões Intravenosas , Síndrome do QT Longo/induzido quimicamente , Magnésio/sangue , Masculino , Distribuição Aleatória , Salivação , Taquicardia/induzido quimicamente , Fatores de Tempo , Vômito/induzido quimicamente
13.
Clin Nutr ; 25(4): 653-60, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16698135

RESUMO

BACKGROUND & AIMS: Citrate is a useful chemical as a stabilizer for infusion solutions. However, cardiovascular depression associated with ionized hypocalcemia has been observed during massive transfusion of citrated blood products. The goal of the present study was to determine the maximum acceptable infusion rate of citrate and safe blood ionized calcium (Ca(2+)) levels. METHODS: Citrate was administered intravenously to anesthetized rats at infusion rates between 0.5 and 2.0 mmol/kg/h for 4 h. Changes in heart rate (HR), arterial blood pressure, and the concentrations of plasma citrate and blood Ca(2+) were measured. RESULTS: Infusion of citrate caused decreases in arterial blood pressure and HR, but no severe cardiovascular depression was observed at infusion rates up to 1.0 mmol/kg/h. Plasma citrate levels reached a steady state within 1 h after the start of infusion at up to 1.0 mmol/kg/h. The concentrations of plasma citrate and blood Ca(2+) were 1.35 and 0.89 mmol/l, respectively, 4h after the start of infusion at 1.0 mmol/kg/h. CONCLUSIONS: The maximum acceptable infusion rate of citrate was 1.0 mmol/kg/h in anesthetized rats, and no severe cardiovascular effects were observed when the blood Ca(2+) level was 0.89 mmol/l or above.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cálcio/sangue , Quelantes/farmacocinética , Ácido Cítrico/farmacocinética , Frequência Cardíaca/efeitos dos fármacos , Animais , Área Sob a Curva , Quelantes/metabolismo , Ácido Cítrico/sangue , Relação Dose-Resposta a Droga , Humanos , Hipocalcemia/induzido quimicamente , Infusões Intravenosas , Masculino , Distribuição Aleatória , Ratos
14.
Psychiatry Clin Neurosci ; 59(5): 527-32, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16194253

RESUMO

Recent neuropsychological studies have found deficits in the verbal memory of patients with obsessive-compulsive disorder. Difficulties in using organizational strategies were presumed to be the cause. Preceding studies did not look closely at their ability of feature detection of stimuli. Efficiency in feature detection is crucial to use the attributes or feature of stimuli as a clue in memory tasks. We examined verbal memory deficit and the ability of feature detection in Japanese patients with obsessive-compulsive disorder. We administered Iddon et al.'s verbal strategy task to 16 patients with obsessive-compulsive disorder and 16 healthy controls. The feature of Iddon et al.'s task was to include a phase that showed subjects the semantic structure of the task and timed each subject's analysis of the organization. Patients with obsessive-compulsive disorder were slower to classify stimuli words into semantic categories than were healthy controls. They recalled and recognized significantly fewer words than did healthy controls. In recall tasks, they used less organizational strategy than did healthy controls. Patients with obsessive-compulsive disorder were slower to analyze features of stimuli words than were healthy controls. This slowness possibly contributes to impaired memory performances that patients showed during the encoding process, since the efficient use of organizational strategies in limited time is difficult for them.


Assuntos
Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Memória de Curto Prazo , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/psicologia , Fatores Etários , Atenção/fisiologia , Progressão da Doença , Feminino , Humanos , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Reconhecimento Psicológico , Análise de Regressão , Aprendizagem Verbal/fisiologia
15.
Seishin Shinkeigaku Zasshi ; 107(6): 570-5, 2005.
Artigo em Japonês | MEDLINE | ID: mdl-16048105

RESUMO

Senior psychiatrists at general hospital without psychiatric ward are usually so short of both manpower and time that they should easily lose incentives to collaborate with residents who would come at least one month under 2004 reform of residency. In this article, the author argue that the handicaps where residents should serve outpatient clinic and consultation-liaison-service at the hospital and experience other hospitals or institutions for relatively short term (mainly only one month at most) are not handicaps at all but features. Supervision during overall period of residency which concerns residents' career development and mental health, peer-supervision using live cameras or video recording, qualitative approach which utilizing weekly problem solution tasks were introduced to maintain incentives to collaboration.


Assuntos
Educação de Pós-Graduação em Medicina , Hospitais Gerais , Internato e Residência , Psiquiatria/educação , Encaminhamento e Consulta , Educação de Pós-Graduação em Medicina/métodos , Humanos , Relações Interinstitucionais , Internato e Residência/métodos , Japão , Ambulatório Hospitalar , Unidade Hospitalar de Psiquiatria
16.
Congenit Anom (Kyoto) ; 43(3): 168-76, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14684966

RESUMO

We previously reported infertility in female rats that received N-acetyl-L-cysteine (NAC) intravenously at a dosage of 1000 mg/kg/day. Unfertilized oocytes and gestation day 1 and 2 embryos were assessed morphologically, and the results suggested that absence or thinning of the zona pellucida (ZP) is related to infertility. However, the morphological characteristics of oocytes before ovulation and recovery from the effects of NAC were not clarified. In the present study, the ovarian follicles were histopathologically examined and the recovery of reproductive function was evaluated to investigate the effects of NAC. Female Sprague-Dawley rats at 10 weeks of age received NAC intravenously at 1000 mg/kg/day for more than 1 week. Thinning of the ZP was observed in the ovarian follicles in all stages of growth by light microscopy. Outflow of the components of the ZP between the corona radiata and disarrangement of the corona radiata were more pronounced in growing follicles than in large secondary follicles. Similar findings were observed by electron microscopy, and the effects of NAC were limited to the ZP. Infertility and thinning of the ZP were observed in the no-recovery NAC group, but not in the recovery NAC group, in which animals recovered within four estrous cycles after NAC administration. It has been reported that the ZP is expressed by oocytes or by both oocytes and granulosa cells, but no changes were noted in these cells. The present findings suggest that NAC affects the ZP directly and that reproductive function may recover from the effects of NAC.


Assuntos
Acetilcisteína/toxicidade , Fertilidade/efeitos dos fármacos , Sequestradores de Radicais Livres/toxicidade , Infertilidade Feminina/induzido quimicamente , Oócitos/patologia , Folículo Ovariano/patologia , Zona Pelúcida/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Células da Granulosa/efeitos dos fármacos , Infertilidade Feminina/fisiopatologia , Masculino , Oócitos/ultraestrutura , Folículo Ovariano/ultraestrutura , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Zona Pelúcida/patologia
17.
J Toxicol Sci ; 28(2): 95-107, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12820541

RESUMO

A 4-week intravenous repeated dose toxicity study of L-cysteine (L-Cys) was conducted in male Sprague-Dawley rats to investigate in detail the toxic effects of this compound and to determine the dose level at which these toxic effects are observed following repeated intravenous administration. Male rats were randomly allocated to 4 groups to receive L-Cys by intravenous administration at dosages of 0, 100, 300, and 1,000 mg/kg body weight/day. Body weight gain was significantly suppressed throughout the study period in the 1,000-mg/kg group, although food consumption was reduced only on study day 3. A decrease in spontaneous activity, salivation, stereotypy, ptosis, and tremor were observed in the 1,000-mg/kg group. Mild anemia characterized by decreases in hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and an increase in the reticulocyte count was also noted in the 1,000-mg/kg group. Histopathological examination showed sperm granulomas in the epididymis and necrosis of the Purkinje cells and granular layer in the cerebellum in the 1,000-mg/kg group. Slight tubular basophilia with blood or hyaline casts was observed in the kidney in the 300-mg/kg and 1,000-mg/kg groups, associated with proteinuria or occult blood in urinalysis. Additional studies are needed to clarify the causes for these toxicological findings by excess of L-Cys.


Assuntos
Cisteína/toxicidade , Animais , Contagem de Células Sanguíneas , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Cisteína/administração & dosagem , Cisteína/urina , Ingestão de Alimentos/efeitos dos fármacos , Injeções Intravenosas , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
18.
Biol Reprod ; 69(1): 242-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12620935

RESUMO

The toxic effects of i.v. administration of N-acetyl-l-cysteine (NAC), a component of parenteral nutrition solutions, on fertility and embryonic development were investigated in SD male and female rats at doses of 100, 300, and 1000 mg kg-1 day-1. Infertility was observed in females in the 1000-mg/kg group throughout the period from before mating to embryogenesis. No effect of NAC on the reproductive ability of the male rats was seen. The oocytes and embryos were assessed morphologically to clarify the cause of the effects of NAC. The unfertilized oocytes (UO) recovered from the ampullae of the uterine tubes and Gestational Day (GD) 1 and 2 embryos recovered from the oviducts or uterus of the rats that received NAC i.v. at a dosage of 1000 mg kg-1 day-1 for more than 1 wk before mating were assessed morphologically by stereomicroscopy. In addition, the thickness of the zona pellucida (ZP) was calculated by morphometric evaluation of the UO. Fewer UO were collected in the NAC group than in the control (nontreatment) group. Interestingly, ZP-lacking or partially ZP-lacking oocytes were observed in the NAC group, and the morphometric evaluation of the UO showed thinning of the ZP. The number of embryos in each animal was markedly decreased on GD1, and no embryos were recovered on GD2 in the NAC group. The oocytes that had ZP affected by NAC treatment were abnormal or nonviable. The findings of the present study suggest that changes in the ZP are related to the infertility associated with NAC.


Assuntos
Acetilcisteína/toxicidade , Infertilidade Feminina/induzido quimicamente , Reprodução/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Animais , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Feminino , Masculino , Oócitos/efeitos dos fármacos , Oócitos/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Zona Pelúcida/efeitos dos fármacos , Zona Pelúcida/patologia
19.
Synapse ; 46(1): 32-7, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12211096

RESUMO

In the present study, we attempted to predict the risk of extrapyramidal side effects of a selective monoaminergic antagonist, risperidone, by analyzing the correlation between the dopamine D(2) receptor occupancy and the degree of extrapyramidal side effects of the drug. The occupancies of D(2) and 5-HT(2) receptors at various doses of risperidone were calculated by means of a receptor occupancy theory. The extrapyramidal side effects after administration of risperidone were attempted to predict by theoretical analysis of the correlation between the calculated occupancies and the evidence of extrapyramidal symptoms using a ternary complex model. The pharmacokinetic/pharmacodynamic analysis utilized the data concerning the pharmacokinetics of risperidone and 9-hydroxyrisperidone (active metabolite), their binding affinities with D(2) and 5-HT(2) receptors, and the clinical evidence of extrapyramidal symptoms (Extrapyramidal Symptom Rating Scale: ESRS), gathered from the literature. The mean occupancy of 5-HT(2) receptors after the administration of regular doses of risperidone was suggested to be more than 90%, whereas the mean occupancy of D(2) receptors varied between 50-80%, depending on the dose. The correlation between the occupancy of D(2) receptors and the extrapyramidal symptoms could be successfully analyzed with a ternary complex model, showing the predictability of the model for the extrapyramidal side effects of risperidone. Since the estimated risk of the extrapyramidal side effects varied with the dose, the present method of predicting the extrapyramidal side effects of risperidone may provide a basis for developing a rational dosing regimen for the drug.


Assuntos
Doenças dos Gânglios da Base/induzido quimicamente , Antagonistas de Dopamina/efeitos adversos , Modelos Biológicos , Receptores de Dopamina D2/metabolismo , Risperidona/efeitos adversos , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Antagonistas de Dopamina/sangue , Antagonistas de Dopamina/farmacocinética , Humanos , Isoxazóis/efeitos adversos , Isoxazóis/farmacocinética , Palmitato de Paliperidona , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Risperidona/sangue , Risperidona/farmacocinética
20.
Arch Gen Psychiatry ; 59(1): 25-30, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11779278

RESUMO

BACKGROUND: The clinical efficacy of dopamine D2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D2 receptors of patients with schizophrenia. METHODS: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Region-of-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D2 receptor binding. RESULTS: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. CONCLUSIONS: The lower BP values indicate fewer D2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia.


Assuntos
Giro do Cíngulo/fisiopatologia , Receptores de Dopamina D2/fisiologia , Esquizofrenia/fisiopatologia , Adulto , Mapeamento Encefálico , Antagonistas de Dopamina/farmacocinética , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Pirrolidinas/farmacocinética , Valores de Referência , Salicilamidas/farmacocinética , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico , Tomografia Computadorizada de Emissão
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