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OBJECTIVES: The definition of work-related Asthma (WRA) has changed in recent years and new etiologies and agents have been identified. The aim of this study is to describe the main causal agents of WRA in France in the period 2001-2018 in the main work sectors. METHODS: Data were collected from the French national network of occupational health surveillance and prevention [Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)], Data between 2001 and 2018 with at least a probable or certain association with one occupational agent, were included. RESULTS: Work sectors with more cases OF WRA included personal service activities (10.6%), food industry (10.2%) and healthcare activities (7.6%). WRA cases were most frequently related to flour (10%), quaternary ammoniums compounds (5.3%), isocyanates (5.1%) and cleaning products (4.8%). CONCLUSION: Occupational exposure to specific agents capable of causing WRA is still present, and four agents represent more than 25% of the cases. Actions to prevent respiratory exposure are still relevant.
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Asma Ocupacional , Enfermedades Profesionales , Exposición Profesional , Humanos , Asma Ocupacional/epidemiología , Asma Ocupacional/prevención & control , Asma Ocupacional/etiología , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/prevención & control , Francia/epidemiología , HarinaRESUMEN
INTRODUCTION: In 2021, smoking was considered to be the leading cause of avoidable death in the world, causing numerous pathologies. The rate of smoking in French department of Finistère is high, and the ARS (regional health authority) has funded a prevention campaign for a tobacco-free hospital and campus in Brest. Some health students' smoke (17.8%) and/or vape (5.6%). The aim of this article was to study the middle-term impact of the Smokefree campus prevention campaign. MATERIAL AND METHOD: A descriptive cross-sectional study by self-administered questionnaire was carried out between 24/01/2022 and 21/02/2022, using Sphinx software. RESULTS: The participation rates were 29.9% (students) and 29.4% (professionals). Among students, 12.6% were smokers, as were 13.3% of professionals. Just over 75% of respondents were aware of Smokefree campus, and 75% knew that it concerned both vaping and smoking. Nearly 60% of respondents thought that the smoke-free campus program could improve coherence between (a) the care training function of the faculty and the IFPS and (b) its exemplarity on the issue of smoking. Among smokers, 44% thought that quitting smoking or vaping during working hours was possible, while and 44% thought that it was possible to quit, whatever the setting. For student smokers, this was contemplated by only 18.2%, and deemed possible by 24%. CONCLUSION: While the smoking rate has remained relatively high, the Smokefree campus campaign is widely known and understood. It is important to pursue this kind of prevention campaign insofar as it could have a positive impact on the health of future caregivers and their patients.
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Política para Fumadores , Humanos , Universidades , Estudios Transversales , Nicotiana , Actitud Frente a la Salud , Estudiantes , Hospitales , Prevención del Hábito de FumarRESUMEN
During the first months of the Sars-Cov-2 pandemic, French caregivers faced difficult situations, organizational changes, and rapidly changing recommendations. The occupational physicians of the hospital staff had to accompany the caregivers, both to answer their questions, both to better prevent the risks to their health in connection with the pandemic. Recommendations were quickly issued by the Société française de médecine du travail (French Society of Occupational Medicine). In our CHU, an evaluation of exposures was made by department. Occupational physicians advised agents and the institution to limit the risks to the health of agents. However, faced with the uncertainties linked to ignorance of the virus, how can we play both the role of protection of each agent, and that of a doctor registered in a health war? This article revisits from a distance the ethical tensions of the hospital occupational physician and the qualities necessary for the accomplishment of these missions.
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INTRODUCTION: In the framework of a "tobacco-free hospital and campus" campaign, we conducted a study on the prevalence of smoking and vaping among a university hospital (CHRU) staff. The study took place in late 2020 (from 1 September to 15 December), and involved self-assessment of the impact of the covid-19 pandemic on smoking. MATERIAL AND METHOD: A cross-sectional study was carried out using an online questionnaire, which was distributed by email and QR code posting and included socio-professional details as well as data on participants' smoking and vaping. RESULTS: There were 782 responses, representing a participation rate of 13.5%. The sample included 73.3% women and 22.7% men; 28.9% nurses, 24.9% medical staff, 3.6% nursing assistants and 42.6% other professional categories. The overall smoking rate was 13%. Sixty-two (7.9%) participants vaped; 37 (5%) vaped exclusively, 25 (3.2%) combined smoking and vaping. Men smoked more than women: 23.7% vs. 9.4% (P < 0.01). Medical staff smoked and vaped less than other categories; 6.2% vs 14.8% (P < 0.01) and 4.1% vs 9.1% respectively (P=0.02). Doctors were more often non-smokers: OR=2.71 (95% CI: 1.14-6.46). Among smokers, 25% said they had increased their cigarette consumption during the covid-19 pandemic, frequently as a means of combating stress or fatigue. CONCLUSION: This study showed a lower smoking rate than in the literature, possibly due to the high participation of physicians. Ours were the initial estimates of vaping among hospital staff.
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COVID-19 , Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , Femenino , Hospitales , Humanos , Masculino , Pandemias , Personal de Hospital , Fumar/epidemiología , Nicotiana , Vapeo/epidemiologíaRESUMEN
INTRODUCTION: Pulmonary siderosis or welder's lung is an occupational lung disease that is usually observed after chronic exposure to iron dust. OBSERVATION: A 55-years-old welder visited hospital with dyspnea linked to occupational exposure. Pulmonary function studies revealed lung function abnormalities with decerase of FEV1 and TPC. Based on the chest Tomography CT results, he was diagnosed with obliterans bronchiolitis. A chest biopsy was performed and the specimen is for a pulmonary siderosis aspect. DISCUSSION: This case of pulmonary siderosis is an unusual one by symptoms, CT images and short latency of exposure. An intense inhalation of iron particles could explain this case and inflammatory process and it highlights need of histological analysis of chest biopsy.
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Exposición Profesional , Siderosis , Soldadura , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Obreros Metalúrgicos , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Siderosis/diagnóstico , Siderosis/etiología , Siderosis/patologíaRESUMEN
INTRODUCTION: Smoking is one of the leading causes of preventable death worldwide. Data from the literature show that caregivers and health students have a high prevalence. The purpose of this article was to study the prevalence among health students (medicine, dentistry, physiotherapy, nursing) at a University and a Teaching Hospital in France. MATERIAL AND METHOD: This was a cross-sectional study using a self-administered questionnaire completed at the start of university meetings. This study was carried out as part of a campaign to combat smoking supported by the Brittany Regional Health Agency. RESULTS: The participation rate was 76.4%: 1349 respondents out of 1766 health students surveyed. The prevalence of smoking 17.8% and that of vaping 5.6%. Nursing students smoked and vaped more than students in other streams: respectively, for smoking, 21.8% (73/335) vs. 16.5% (167/1014) (P<0.001), for vaping, 10.4% (35/335) vs. 4.0% (39/980) (P<0.001). Students in 3rd year nursing smoked and vaped significantly more than those in the first 2 years (P=0.02 and P<0.001). CONCLUSION: The smoking rate was high, but comparable to the data for health students. Nursing students were significantly greater smokers, especially in the last year. Their vaping rate was higher than in other studies.
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Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Vapeo , Estudios Transversales , Francia , Humanos , Prevalencia , Encuestas y CuestionariosRESUMEN
INTRODUCTION: During the final part of their medical studies, residents are under a large amount of stress and work overload as reported by a literature review between 2004 and 2014 assessing 33.2% of burn out among them. Pregnancy and motherhood lead to major physical and psychological changes. The purpose of this study was to point out the female residents feeling about the consequences of motherhood and pregnancy during residency. METHODS: Semi-structured interviews were conducted for this qualitative study. It was based on the Grounded theory and analyzed by a continuous thematization. RESULTS: Ten interviews were conducted. Data saturation was obtained by the 8th interview. Diversity of medical specialty was sought. Residents expressed their feeling towards the consequences of pregnancy and motherhood during residency. The data analysis highlighted two major themes related to either work (training, industrial relations and job adaptation), or pregnancy and maternity. CONCLUSION: Becoming a mother during residency represents an additional challenge for residents. It implies adjustment from them and their work teams in order to reduce the negative effect on a professional and personal level.
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Internado y Residencia , Cuerpo Médico de Hospitales , Médicos Mujeres , Calidad de Vida , Trabajo , Femenino , Francia , Humanos , Entrevistas como Asunto , Embarazo , Investigación CualitativaRESUMEN
INTRODUCTION: Suffering at work among health professionals is a hot topic. Medical students, doctors of tomorrow, are far from being spared. Prevalence of anxiety and mood disorders range from 20.3 to 69 % for the former and from 12 to 30 % for the latter. The purpose of this article is to determine these factors by qualitative research, according to medical students' points of view. METHODS: It is a qualitative study using semistructured interviews. The analysis is done according to the Grounded Theory. RESULTS: 12 medical students are interviewed. They expressed difficulties at work and positive factors. Three major themes are identified in selective coding: occupational factors, " study " factors and individual factors. All themes are both a source of well-being and ill-being according to the situations specified in the results. CONCLUSION: Studying medicine includes positive and negative aspects. Abandonment issues, lack of recognition and insufficient coaching emerge from our study. Screening of suffering at work should be systematic for medical students.
INTRODUCTION: La souffrance au travail chez les professionnels de santé est un sujet d'actualité. Les étudiants en médecine, médecins de demain, sont loin d'être épargnés. Ils présentent notamment des troubles anxieux et de l'humeur dont les prévalences s'échelonnent de 20,3 à 69 % pour les premiers et de 12 à 30 % pour les seconds. Cette étude a pour objectif de déterminer ce qui est ressenti comme positif ou négatif au travail du point de vue des étudiants hospitaliers. Matériel et méthode : Il s'agit d'une étude qualitative par entretiens semi-dirigés. L'analyse se fait selon une thématisation progressive en suivant la Grounded Theory, ou théorisation ancrée, méthode issue des sciences sociales, visant à élaborer une théorie des représentations, non à partir d'hypothèses prédéterminées, mais à partir de données de terrain recueillies par entretiens. Résultats : La variation est maximale. La saturation des données a été atteinte avec 12 sujets. Ceux-ci ont exprimé des difficultés au travail mais aussi des facteurs de ressenti positif. Trois grands thèmes ont été définis en codage sélectif : les facteurs professionnels, les facteurs " étude " et les facteurs individuels. Quelle que soit la thématique abordée, les relations avec le ressenti du travail sont à la fois source d'épanouissement et de souffrance selon les situations précisées dans les résultats. CONCLUSION: Le vécu des études médicales comprend des aspects positifs et négatifs. Les problématiques de délaissement, de manque de reconnaissance ou encore d'accompagnement insuffisant ressortent de notre étude. Ceci ouvre des pistes de prévention. Le dépistage d'un malêtre au travail devrait être systématique chez ces étudiants.
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Estrés Laboral/epidemiología , Psiquiatría , Estrés Psicológico/epidemiología , Estudiantes de Medicina/psicología , Adulto , Estudios Transversales , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Internado y Residencia/estadística & datos numéricos , Entrevistas como Asunto/métodos , Masculino , Estrés Laboral/diagnóstico , Estrés Laboral/psicología , Psiquiatría/estadística & datos numéricos , Investigación Cualitativa , Estrés Psicológico/diagnóstico , Encuestas y Cuestionarios , Recursos Humanos , Adulto JovenRESUMEN
BACKGROUND: Protein contact dermatitis has frequently been reported in case studies (usually in cases involving contact with seafood products), but there are very few descriptive series. The objectives of this present study were firstly to determine the incidence of protein contact dermatitis among fishermen in France and compare it with data from onshore work involving seafood exposure. Second, to discover what factors could explain any differences. In order to answer these questions we analysed data from the French national occupational disease surveillance and prevention network (RNV3P) and occupational diseases declared to the French National Network for Monitoring and Prevention of Occupational Disease. This retrospective study was done for a 13 year period. CASE PRESENTATION: Between 2000 and 2012, we only found eight cases of protein contact dermatitis in the French network. There were no cases of protein contact dermatitis in the seafaring population. The eight cases from the French network are essentially allergies to different fish and chefs are the professionals most affected. Atopy is present in half of these cases. In the seafaring population we found several cases of allergic delayed-time contact dermatitis due to bryozoans and to gloves but no protein contact dermatitis. CONCLUSIONS: Chefs who have to cook seafood are more at risk of occupational protein contact dermatitis than fishermen. We think that skin protection (that is to say glove wearing) is better implemented in the fishing sector than in the catering profession on shore in France.
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UNLABELLED: Junior doctors are exposed to multiple occupational risks. The aim of this study was to assess the risk factors and protective factors for mood and anxiety disorders among junior doctors. MATERIALS AND METHODS: We conducted a cross-sectional study via an anonymous online questionnaire between October 2011 and June 2012. All the junior doctors in our faculty were included. The questionnaire inquired about demographic and health data. It contained four validated scales: the Center for Epidemiologic Studies Depression Scale (CES-D), the Spielberger anxiety questionnaire, the WHO quality of life (WHO - QOL) questionnaire and the Job Content Questionnaire. Finally, it sought to clarify the conditions of professional practice and the interactions between university programmes and junior doctorate students (change of specialty, pregnancy, leave of absence, etc.). RESULTS: 192 juniors doctors participated in the study, 68.2% of whom were women. Out of the group, 13.0% presented a depressive syndrome, while 28.7% presented an anxiety disorder, 32.8% were experiencing Job Strain and 29.7% Iso Strain. The risk factor for anxiety was competition between junior doctors: OR=4.23 (1.06 â 16.82). The protective factors for mood disorders were the help provided by senior physicians and the respect shown by patients: OR=0.21 (0.06-0.74) and 0.20 (0.06-0.75), respectively. CONCLUSION: This study demonstrated the impact of the relationships with senior physicians and patients on junior doctors' health at work. Consequently, prevention should not be focused uniquely on work organization, but should increase physicians' awareness of the importance of this relationship.
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Trastornos de Ansiedad/epidemiología , Cuerpo Médico de Hospitales , Trastornos del Humor/epidemiología , Enfermedades Profesionales/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Medición de Riesgo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
AIM: Dysbaric osteonecrosis (DON) continues to be a significant occupational hazard that has significant medical and social consequences for professional divers. This review aims to evaluate the prevalence and risk factors of DON among professional divers and to summarize the scientific knowledge regarding distribution of the lesions as well as disease prognosis and treatment. METHOD: A literature review using the Medline database. RESULTS: The prevalence of DON varies between 0 and 70.6% in professional divers, and its prevalence is highest in Turkey, Hawaii, Korea and Japan but is dependent on activity and medical monitoring. The risk of DON is very low for military divers who strictly obey the decompression rules and who undergo periodic medical examination. DON pre- dominately occurs in the proximal part of the femur and humerus. In a majority of cases, DON will progress despite the absence of further dysbaric exposure. CONCLUSION: The pathophysiology of the disease is incompletely understood and other etiological factors are perhaps being overlooked.
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Buceo/efectos adversos , Enfermedades Profesionales/etiología , Osteonecrosis/etiología , Estudios Transversales , Fémur , Humanos , Húmero , Estudios Observacionales como Asunto , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/terapia , Osteonecrosis/diagnóstico , Osteonecrosis/epidemiología , Osteonecrosis/terapia , Pronóstico , Factores de RiesgoRESUMEN
OBJECTIVE: Non-obese diabetic (NOD) mice develop an autoimmune exocrinopathy that shows similarities with Sjögren's syndrome. They provide an experimental model to study the pathoetiogenesis of this disease. MATERIALS AND METHODS: Salivary gland (SG) function and salivary sodium content were measured in 8-, 12-, 16- and 20-week-old NOD and age-matched CB6 mice. In NOD mice, SG expression of phenotypic cell markers, B cell-stimulating and costimulatory molecules were evaluated. Cytokine levels were measured in serum and SG homogenates. RESULTS: Microscopically evident SG inflammation in NOD mice was preceded by expression of intercellular adhesion molecule 1 on epithelial cells in the presence of macrophages and relatively high levels of cytokines. Next, an influx consisting of mainly T, B, natural killer, plasma and dendritic cells was seen. Most cytokines, except for interleukin (IL)12/IL23p40 and B cell-activating factor, decreased or remained stable over time, while glandular function deteriorated from 16 weeks of age onward compared with CB6 mice. CONCLUSION: Sjögren's syndrome-like disease in NOD mice occurs in multiple stages; immunological and physiological abnormalities can be detected before focal inflammation appears and salivary output declines. Extrapolating this knowledge to human subjects could help in understanding the pathogenesis and aid the identification of potential therapeutic targets.
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Modelos Animales de Enfermedad , Glándulas Salivales/fisiopatología , Sialadenitis/fisiopatología , Síndrome de Sjögren/etiología , Síndrome de Sjögren/inmunología , Animales , Factor Activador de Células B/biosíntesis , Antígenos CD40/biosíntesis , Citocinas/biosíntesis , Citocinas/sangre , Femenino , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Intercelular/sangre , Interleucinas/biosíntesis , Interleucinas/sangre , Linfocitos/inmunología , Macrófagos/inmunología , Ratones , Ratones Endogámicos NOD , Ratones Endogámicos , Saliva/química , Saliva/metabolismo , Glándulas Salivales/química , Glándulas Salivales/patología , Tasa de Secreción , Sialadenitis/patología , Sodio/análisis , Células TH1/inmunología , Células Th2/inmunología , Factores de TiempoRESUMEN
BACKGROUND: The aim of the study was to organise an assessment of the physical strains and environmental exposure to hydrocarbon derivatives in persons involved in shoreline clean-up of heavy oil products, in order to investigate the dangers of oil spill clean-up. MATERIAL AND METHODS: Forty-three healthy volunteers wearing protective equipment cleaning up an artificial shoreline underwent cardiac strain measurements, as well as a study of thermal stress (approximate WBGT index, water loss, measurement of internal body temperature before and after physical activity). A subjective assessment of perceived exertion was correlated to articular strain indicators recorded for the weight of loads lifted, movement frequency, and the range of movement. Environmental exposure was determined by using portable hydrocarbon detectors. RESULTS: For adult subjects in good physical condition, in neutral temperatures, oil spill clean-up is considered non-arduous. However, in sedentary, stressed subjects exposed to difficult climatic conditions, cleanup can be considered hard to extremely hard. In terms of environmental exposure, slight traces of toluene appeared once out of a total of 18 analysed samples. CONCLUSIONS: The sample studied was subject to physical articular strains and presented variable cardiac strain; environmental exposure was, on the other hand, slight when involving cleaning up heavy petroleum products. The subjects liable to carry out this activity are more tolerant to the efforts required when they are healthy, fit, young adults, in the non-arduous thermal conditions recorded in this study.
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Exposición a Riesgos Ambientales/efectos adversos , Exposición Profesional/efectos adversos , Contaminación por Petróleo/efectos adversos , Petróleo/toxicidad , Estrés Fisiológico , Adulto , Sistema Cardiovascular , Femenino , Francia , Indicadores de Salud , Frecuencia Cardíaca , Calor/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Sistema Musculoesquelético , Contaminación por Petróleo/estadística & datos numéricos , Esfuerzo Físico , Equipos de Seguridad/efectos adversosRESUMEN
BACKGROUND: The management of occupational dermatitis is often complex and relies on skills in both dermatology and occupational medicine. A bidisciplinary occupational dermatology consultation was set up in 2002 at Brest CHU. The aim of this study is to provide an assessment of 5 years of activity and to discuss the role of atopy. PATIENTS AND METHODS: From October 2002 to October 2007, 245 patients attended this consultation. 145 files concerning proven occupational dermatosis were studied (age, sex, occupation, dermatosis, allergens and history of atopy). One hundred and five patients completed a telephone questionnaire concerning their feelings about the consultation, the course of their dermatosis and the medicosocial outcome. RESULTS: The main forms of dermatosis were contact eczema (41%), irritant dermatitis (26%), exacerbation of atopic dermatitis (10%), associated eczema and irritant dermatitis (9%), and other (14%). DISCUSSION: The occupations of subjects (healthcare, building and civil engineering work, food and catering, agriculture, mechanics, hairdressing, cleaning, printing) and the allergens involved were similar to those described in the literature. The prognosis was poor (48% cure rate). Differential diagnosis between allergic eczema and irritant dermatitis was sometimes difficult and was based on clinical features and allergology tests. A history of atopy was found in 32% of patients and was particularly frequent among patients presenting allergic eczema associated with irritant dermatitis: this may be explained by the physiopathological mechanisms of atopic dermatitis (impairment of barrier function causing contact sensitization to potential allergens). CONCLUSION: Such a bidiscipinary occupational dermatology consultation has the advantage of optimizing management of these patients. Wider notification of occupational dermatosis would increase our knowledge of the causes of this condition and enable better prevention.
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Dermatitis Profesional/epidemiología , Hipersensibilidad Inmediata/epidemiología , Adolescente , Adulto , Alérgenos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ocupaciones/estadística & datos numéricos , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Occupational infectious respiratory diseases are underestimate pathology because of an asymptomatic infection or the general, unspecific symptoms. STATE OF THE ART: The most part of patients are among health care and agriculture or forestry workers (15% employee exposure of infectious risks in according with SUMMER study 2003). Biological risks interest two-third of health care workers, one-third of agriculture and food industry employees and one-forth of house-workers. Occupational diseases occur as flu-like illness, pneumonia, lung abscess or pleurisy. A possible classification for this pathology is by clinical manifestations: with respiratory predominance like tuberculosis, pasteurelosis, psittacosis or diseases like anthrax, brucellosis or tularemia with non respiratory predominance. PERSPECTIVES AND CONCLUSION: The authors remind the data of occupational respiratory infectious diseases, microbiological data and links between clinical symptoms and patients professions leading to diagnosis.
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Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/terapia , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/terapia , Humanos , Control de Infecciones , Enfermedades Profesionales/microbiología , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
OBJECTIVES: The non-obese diabetic (NOD) mouse is not only a widely used model for diabetes mellitus type I, but also for the chronic autoimmune disease Sjögren's syndrome (SS), mainly affecting salivary and lacrimal glands. We studied the efficacy of local recombinant serotype 2 adeno-associated viral (rAAV2) vector transfer of immunomodulatory transgenes to alter the SS-like disease in NOD mice. Data collected over a 2-year period indicated a changing SS phenotype in these mice and this phenomenon was investigated. METHODS: 10(10) particles rAAV2LacZ/gland were delivered to both submandibular glands (SMGs) of NOD/LtJ mice at 8 weeks (before sialadenitis onset) of age. Salivary flow rates were determined at 8 weeks and time of killing. Blood glucose levels and body weights were measured weekly. After killing, saliva and SMGs were harvested. Analyses of salivary output, inflammatory infiltrates (focus score), SMG cytokine profile, body weight, and diabetes mellitus status were performed. Data from six different experimental studies over 2 years were analyzed and compared. RESULTS: Salivary flow rate, focus score, and SMG cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12(p70), tumor necrosis factor-alpha and IFNgamma showed changes over time. There were no differences for body weight, diabetes mellitus prevalence, or blood glucose level of non-diabetic mice. CONCLUSION: This retrospective report is the first to describe longitudinal variability in the NOD mouse as a model for SS. We advise other investigators to continuously monitor the SS phenotype parameters and include appropriate controls when studying this disease in NOD mice.
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Modelos Animales de Enfermedad , Síndrome de Sjögren/fisiopatología , Análisis de Varianza , Animales , Femenino , Expresión Génica , Técnicas de Transferencia de Gen , Interferón gamma/metabolismo , Interleucinas/metabolismo , Operón Lac , Estudios Longitudinales , Ratones , Ratones Endogámicos NOD , Fenotipo , Saliva/metabolismo , Tasa de Secreción , Síndrome de Sjögren/genética , Glándula Submandibular/inmunología , Glándula Submandibular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Sjögren's syndrome is an autoimmune exocrinopathy, mainly affecting the lacrimal and salivary glands, and resulting in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown, and only palliative treatment is currently available. Data obtained from experimental animal and human studies using biological agents or gene therapeutics can offer insight into the disease process of Sjögren's syndrome. This article reviews the current literature on these approaches and assesses the lessons learnt about the pathogenesis of Sjögren's syndrome.
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Terapia Genética/métodos , Factores Inmunológicos/uso terapéutico , Síndrome de Sjögren/terapia , Animales , Modelos Animales de Enfermedad , Técnicas de Transferencia de Gen , Humanos , Síndrome de Sjögren/inmunologíaRESUMEN
BACKGROUND: Sjögren's syndrome (SS), an autoimmune exocrinopathy mainly affecting lachrymal and salivary glands, results in ocular and oral dryness (keratoconjunctivitis sicca and xerostomia). The aetiology and pathogenesis are largely unknown; currently, only palliative treatment is available. OBJECTIVE: To determine whether gene transfer of vasoactive intestinal peptide (VIP), based on its immunomodulatory properties, might be useful in the management of SS. METHODS: A recombinant serotype 2 adeno-associated virus encoding the human VIP transgene (rAAV2hVIP) was constructed and its efficacy tested in the female non-obese diabetic (NOD) mouse model for SS after retrograde instillation in submandibular glands (SMGs). 10(10) particles/gland of rAAV2hVIP or rAAV2LacZ (encoding beta-galactosidase; control vector) were administered at 8 weeks of age (before sialadenitis onset). Salivary flow rates were determined before vector delivery and at time of death (16 weeks). After death, saliva, serum, and SMGs were harvested. Salivary output, inflammatory infiltrates (focus scores), VIP protein expression, cytokine profile, and serum anti-VIP antibodies were analysed. RESULTS: rAAV2hVIP significantly improved the salivary flow, increased SMG and serum expression of VIP, and reduced SMG cytokines interleukin (IL) 2, IL10, IL12 (p70), and tumour necrosis factor alpha, and serum RANTES, compared with the control vector. No difference in focus scores or apoptotic rates was found; neutralising antibodies were not detected. CONCLUSIONS: Local delivery of rAAV2hVIP can have disease modifying and immunosuppressive effects in SMGs of the NOD mouse model of SS. The new strategy of employing VIP prophylactically may be useful for both understanding and managing the salivary component of SS.
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Terapia Genética/métodos , Síndrome de Sjögren/terapia , Transducción Genética/métodos , Péptido Intestinal Vasoactivo/genética , Adenoviridae/genética , Animales , Anticuerpos/sangre , Apoptosis , Citocinas/análisis , Citocinas/sangre , Células Epiteliales/patología , Femenino , Expresión Génica , Ingeniería Genética , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Operón Lac , Ratones , Ratones Endogámicos NOD , Modelos Animales , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/patología , Glándula Submandibular/inmunología , Glándula Submandibular/patología , Transgenes , Péptido Intestinal Vasoactivo/análisis , Péptido Intestinal Vasoactivo/sangreRESUMEN
OBJECTIVES: Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjögren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity. METHODS: Serum lipid levels [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides] and additional data regarding disease measures (clinical immunology parameters, focus score from labial salivary gland biopsy, salivary flow and ophthalmological measures) were available for 46 primary SS patients and 12 xerostomic controls. RESULTS: Significant differences between SS patients and controls means (s.d.) were seen for HDL (P = 0.04) and total cholesterol (P = 0.02). LDL (P = 0.12) and triglyceride (P = 0.08) levels were not different. In SS patients, but not in controls, total cholesterol (P = 0.003) and HDL cholesterol (P = 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies were related to a lower total cholesterol (P = 0.02) and anti-SSB antibodies to a lower HDL cholesterol level (P = 0.0497). CONCLUSIONS: Significant differences were seen in serum lipid levels of primary SS patients and these were associated with serological measures of inflammation. Our results are comparable to earlier findings in RA patients and raise questions related to adverse cardiovascular consequences in SS.
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Lípidos/sangre , Síndrome de Sjögren/sangre , Anticuerpos Antinucleares/sangre , Colesterol/sangre , Femenino , Humanos , Inmunoglobulina G/sangre , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Salivary glands (SGs) appear to be a useful target site for gene therapeutics. The ability to control transgene expression is essential for clinical application. Previously, in a proof-of-concept study, we have shown that the rapamycin-inducible transcriptional regulation system can regulate protein expression after adenoviral-mediated gene transfer to SGs. To evaluate the potential ability to utilize this regulatory system for long-term control of transgene expression in this tissue, we employed a 'third generation', single adenoassociated serotype 2 viral (AAV2) vector encoding human erythropoietin (hEPO) under the control of a rapamycin-inducible promoter. The vector, rAAV-TF2.3-hEPO (10(10) particles/animal), was delivered to mouse SGs. No detectable increase in serum hEPO or hematocrit levels was observed in the absence of rapamycin administration. However, rapamycin induced elevation of serum hEPO levels, as well as concomitant hematocrit changes, that were dose-dependent, completely reversible, and relatively stable over the course of this study (6 months), with no appreciable change in rapamycin responsiveness. Our results suggest that the rapamycin transcriptional regulation system delivered in a single AAV2 vector to SGs may be valuable for systemic protein replacement applications.