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BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Neumología , Biopsia , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/terapia , Pulmón/patologíaRESUMEN
BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.
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Fibrosis Pulmonar Idiopática , Trasplante de Pulmón , Neumología , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/terapia , Pulmón/patología , NeumólogosRESUMEN
A class of cobalt-based oxides exhibits a peculiar type of transition, entangling valence and spin state degrees of freedom of 4f and 3d elements. It constitutes one of the most spectacular illustrations of the interplay between charge, spin and lattice degrees of freedom in strongly correlated materials. In this work, we present a thermodynamic model capable to reproduce the main features of this transition. Our approach is based on the minimization of a free energy combining the contributions of two sublattices and the interaction between them. The coupling energies introduced in the model are related to well-known chemical pressure effects in the perovskite structure. The results of this model are compared to experimental data derived from x-ray absorption spectroscopy.
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INTRODUCTION AND OBJECTIVE: Dyspnoea is a major symptom in COPD patients, but the determinants that could be associated with a higher dyspnoea mMRC score in COPD patients remain unclear. Our research aimed to study the determinants of dyspnoea at the threshold of 1, 2, 3 and 4 mMRC. PATIENTS AND METHODS: Diagnosis of COPD was made using spirometry with post-bronchodilator FEV1FVC<70%. An online questionnaire has been employed by pulmonologists to recruit COPD patients. The following variables were collected: age, gender, BMI, FEV1, RV, IC, TLC, FRC, mMRC, frequency of exacerbations and comorbidities. The LASSO was used to select the variables associated with the mMRC dyspnoea scale in a subgroup (who had no missing IC, RV and FRC values) of 421 COPD patients defined by the previously mentioned variables. RESULTS: One thousand nine hundred and sevety-three patients (65.3% males, average age=66±10, 38% current smokers) were included. Dyspnoea was correlated with a low FEV1 and with the number of exacerbations in the past 12 months. Multivariate analysis showed that the determinants of dyspnoea(mMRC≥2) are: FEV1: OR=3.71[2.86-4.82]; anxiety: OR=2.52[1.82-3.47]; cough: OR=1.94[1.57-2.40]; bronchiectasis: OR=1.84[1.03-3.29]; age: OR=1.80[1.45-2.24]; hyperinflation (RV/TLC): OR=1.68[1.34-2.11]; ischemic cardiopathy: OR=1.63[1.22-2.18]; hypertension: OR=1.52[1.21-1.91]; exacerbations (≥2): OR=1.41[1.10-1.81]; women: OR=1.39[1.10-1.74] and overweight: OR=1.33[1.06-1.67]. The subgroup analysis showed that: FEV1: OR=3.47[1.96-6.12]; exacerbations (≥2) OR=2.31[1.33-4.17] and hyperinflation (IC/TLC) OR=0.57[0.35-0.85] were associated with higher dyspnoea (mMRC≥2). CONCLUSION: Our results showed that dyspnoea is related to the severity of airflow limitation, gender, exacerbations, comorbidities and hyperinflation.
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Enfermedad Pulmonar Obstructiva Crónica , Anciano , Disnea/diagnóstico , Disnea/epidemiología , Disnea/etiología , Femenino , Volumen Espiratorio Forzado , Humanos , Pulmón , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , EspirometríaRESUMEN
BACKGROUND: Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD). However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice. The aim of this study is to evaluate the impact of COPD on patient's sexuality and the explanatory variables of sexual dissatisfaction. METHODS: Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website. Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected. RESULTS: Seven hundred and fifty one subjects were included and were characterized as follows: women-51%, mean age-61 years, in a couple-62% and 70%-retired. Every grade of COPD was represented. Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity. From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position). Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs). ASEX questionnaire confirmed patients' dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue. Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8). Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation. CONCLUSION: Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected. Sexual guidance should be a part of patient's consultations improve quality of sexual life.
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Costo de Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/psicología , Conducta Sexual/psicología , Disfunciones Sexuales Fisiológicas/etiología , Disfunciones Sexuales Fisiológicas/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida/psicología , Conducta Sexual/fisiología , Disfunciones Sexuales Fisiológicas/fisiopatología , Encuestas y CuestionariosRESUMEN
INTRODUCTION: In patients suffering from chronic obstructive pulmonary disease (COPD), the acceptance of the illness is probably a major factor in the improvement of quality of life. The aim of this study is to identify the criteria associated with a good or bad acceptance of the disease and to identify means of improving it. METHODS: We have undertaken a telephone enquiry among patients with COPD with the aid of a standardized questionnaire established by several health experts. RESULTS: Of the 1040 patients who have been contacted, 356 (34 %) replied to the questionnaire. Ninety-nine patients reported unacceptance of their disease (28 %). The patients who did not accept their disease were significantly more severe, with more difficulty in performing daily life activities, particularly exercising. These patients had significantly greater difficulty in understanding their disease and also reported more frequently a moralizing attitude among their family. CONCLUSION: The greater the handicap of the disease, the greater is the difficulty in accepting the disease by the patient. The doctor could have an impact in improving the therapeutic education and involving the family in the patient's care.
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Conducta , Aceptación de la Atención de Salud , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/psicología , Anciano , Actitud Frente a la Salud , Estudios de Cohortes , Ejercicio Físico/fisiología , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Educación del Paciente como Asunto/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
First-order magnetic transitions (FOMTs) with a large discontinuity in magnetization are highly sought in the development of advanced functional magnetic materials. Isosymmetric magnetoelastic FOMTs that do not perturb crystal symmetry are especially rare, and only a handful of material families, almost exclusively transition metal-based, are known to exhibit them. Yet, here we report a surprising isosymmetric FOMT in a rare-earth intermetallic, Eu2In. What makes this transition in Eu2In even more remarkable is that it is associated with a large latent heat and an exceptionally high magnetocaloric effect in low magnetic fields, but with tiny lattice discontinuities and negligible hysteresis. An active role of the Eu-5d and In-4p states and a rather unique electronic structure borne by In to Eu charge transfer, altogether result in an unusual exchange mechanism that both sets the transition in motion and unveils an approach toward developing specific magnetic functionalities ad libitum.
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Experimental investigations of crystal structure, magnetism and heat capacity of compounds in the pseudoternary GdScGe-GdScSb system combined with density functional theory projections have been employed to clarify the interplay between the crystal structure and magnetism in this series of RTX materials (R = rare-earth, [Formula: see text] = transition metal and X = p-block element). We demonstrate that the CeScSi-type structure adopted by GdScGe and CeFeSi-type structure adopted by GdScSb coexist over a limited range of compositions [Formula: see text]. Antimony for Ge substitutions in GdScGe result in an anisotropic expansion of the unit cell of the parent that is most pronounced along the c axis. We believe that such expansion acts as the driving force for the instability of the double layer CeScSi-type structure of the parent germanide. Extensive, yet limited Sb substitutions [Formula: see text] lead to a strong reduction of the Curie temperature compared to the GdScGe parent, but without affecting the saturation magnetization. With a further increase in Sb content, the first compositions showing the presence of the CeFeSi-type structure of the antimonide, [Formula: see text], coincide with the appearance of an antiferromagnetic phase. The application of a finite magnetic field reveals a jump in magnetization toward a fully saturated ferromagnetic state. This antiferro-ferromagnetic transformation is not associated with a sizeable latent heat, as confirmed by heat capacity measurements. The electronic structure calculations for [Formula: see text] indicate that the key factor in the conversion from the ferromagnetic CeScSi-type to the antiferromagnetic CeFeSi-type structure is the disappearance of the induced magnetic moments on Sc. For the parent antimonide, heat capacity measurements indicate an additional transition below the main antiferromagnetic transition.
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Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.
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Enfermedad Pulmonar Obstructiva Crónica/terapia , Reacción de Fase Aguda , Progresión de la Enfermedad , Francia , Humanos , Lenguaje , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Calidad de Vida , Índice de Severidad de la Enfermedad , Sociedades Médicas/normas , Análisis de SupervivenciaRESUMEN
Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.(AU)
La bronchopneumopathie chronique obstructive (BPCO) est la maladie respiratoire chronique dont le poids sur la santé publique est le plus grand par sa morbidité, sa mortalité et les dépenses de santé qu'elle induit. Pour les individus atteints, la BPCO est une source majeure de handicap du fait de la dyspnée, de la limitation d'activité, des exacerbations, du risque d'insuffisance respiratoire chronique et des manifestations extra-respiratoires qu'elle entraîne. Les précédentes recommandations de la Société de pneumologie de langue française (SPLF) sur la prise en charge des exacerbations BPCO date de 2003. Se fondant sur une méthodologie adaptée de GRADE, le présent document propose une actualisation de la question des exacerbations de BPCO en développant un argumentaire couvrant quatre champs d'investigation : (1) épidémiologie, (2) évaluation clinique, (3) prise en charge thérapeutique et (4) prévention. Les modalités spécifiques de la prise en charge hospitalière et ambulatoire y sont discutées, particulièrement les aspects relevant de l'évaluation de la sévérité de l'exacerbation et de la prise en charge pharmacologique.(AU)
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Humanos , Broncodilatadores/uso terapéutico , Corticoesteroides/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Índice de Severidad de la Enfermedad , Reacción de Fase Aguda , Enfermedad Pulmonar Obstructiva Crónica/prevención & controlRESUMEN
The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sertoli cell (SC)-specific Rb knockout mouse line (SC-RbKO) was generated using the Cre/loxP recombination system. SC-RbKO mice exhibited an age-dependent testicular atrophy, impaired fertility, severe SC dysfunction, and spermatogenic defects. Removal of Rb in SC induced aberrant SC cycling, dedifferentiation, and apoptosis. Here we show that E2F3 is the only E2F expressed in mouse SCs and that RB interacts with E2F3 during mouse testicular development. In the absence of RB, the other retinoblastoma family members p107 and p130 began interacting with E2F3 in the adult testes. In vivo silencing of E2F3 partially restored the SC maturation and survival as well as spermatogenesis in the SC-RbKO mice. These results point to RB as a key regulator of SC function in adult mice and that the RB/E2F3 pathway directs SC maturation, cell cycle quiescence, and RB protects SC from apoptosis.
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Diferenciación Celular/fisiología , Factor de Transcripción E2F3/metabolismo , Proteína de Retinoblastoma/metabolismo , Células de Sertoli/metabolismo , Animales , Apoptosis/genética , Factor de Transcripción E2F3/genética , Silenciador del Gen , Masculino , Ratones , Ratones Noqueados , Proteína de Retinoblastoma/genética , Células de Sertoli/citologíaRESUMEN
A wide family of cobalt oxides of formulation (Pr(1-y)Ln(y))(1-x)Ca(x)CoO3 (Ln being a lanthanide) exhibits a coupled valence and spin-state transition (VSST) at a temperature T*, which involves two concomitant modifications: (i) a change in the spin state of Co(3+) from low-spin (T < T*) to a higher spin state (T > T*) and (ii) a change in the valence state of Pr, from a mixed Pr(4+)/Pr(3+) state (T < T*) to a purely trivalent state (T > T*), accompanied by an ~ 90 K is investigated by magnetization and heat capacity measurements.First, we quantitatively characterized the jumps in magnetic susceptibility (χ) and entropy (S) around T*. Then, these values were compared to those calculated as a function of the variations in the population of the different cationic species involved in the VSST. X-ray absorption spectroscopy experiments recently showed that the higher spin state above T* should be regarded as an inhomogeneous mixture between low-spin (LS) and high-spin (HS) states. In the frame of this description, we demonstrate that the jumps in both χ and S can be associated with the same change in the Co(3+) HS content around T*. This result lends further support to the relevance of the LS/HS picture for the VSST, challenging the currently dominant interpretation based on the occurrence of an intermediate-spin (IS) state of Co(3+) above T*.
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Magnetic properties of a series of (La(0.7)Sr(0.3)MnO(3)/SrRuO(3)) superlattices, where the SrRuO(3) layer thickness is varying, are examined. A room-temperature magnetocaloric effect is obtained owing to the finite size effect which reduces the T(C) of La(0.7)Sr(0.3)MnO(3) layers. While the working temperature ranges are enlarged, - ΔS(M)(max) values remain similar to the values in polycrystalline La(0.7)Sr(0.3)MnO(3). Consequently, the relative cooling powers are significantly improved, the microscopic mechanism of which is related to the effect of the interfaces at La(0.7)Sr(0.3)MnO(3)/SrRuO(3) and higher nanostructural disorder. This study indicates that artificial oxide superlattices/multilayers might provide an alternative pathway in searching for efficient room-temperature magnetic refrigerator for (nano) micro-scale systems.
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Genomics has brought with it a true biological revolution and can be applied to all areas of life sciences. The advent of genomics is thus linked to the development of high-throughput techniques which allows the genome of organisms as a whole to be studied. The first high-throughput techniques to be developed were sequencing methods. These advances will allow new approaches to a variety of problems in biology. For instance, the emerging fields of genomic medicine in humans and genomic selection in livestock are promising. After the sequencing of genomes, genomics has shifted to the study of gene expression and function. This is called the "post-genomic area" by some authors or "functional genomics" by others. The most recent "omics" to be developed are associated with the study of the metabolism (e.g. metabolomics). Integrative "omics" approaches (e.g. nutrigenomics) are based on the association of the omics tools at different levels (DNA, RNA, proteins, metabolites) for a specific objective (here nutrition). In terms of perspectives, it is likely that methods for collecting data will outstrip our capacity to adequately analyse these data. So scientists must develop bioinformatic tools and methods to overcome this difficulty. In addition, high-throughput techniques need to be developed in physiology in order to match the increasing amount of genomic information with true biological data. Finally, there is no doubt that all these new approaches will allow important new genes and novel biological mechanisms to be discovered. Physiological models with invalidated or over-expressed genes will be precious tools to check these new biological discoveries.
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Regulación de la Expresión Génica/fisiología , Genómica/métodos , Metabolómica/métodos , Nutrigenómica/métodos , Minería de Datos/métodos , Humanos , Fenotipo , Fenómenos Fisiológicos , Análisis de Secuencia/métodosRESUMEN
BACKGROUND/AIMS: Bisphosphonates have been reported to decrease fractures related to osteogenesis imperfecta (OI). We assessed the efficacy and long-term safety of pamidronate therapy in patients with moderate-to-severe OI. METHODS: We conducted an open-label uncontrolled study in 14 boys and 13 girls whose mean age was 6.8 years at baseline. Intravenous pamidronate, 1 mg/kg/day, was given for 3 consecutive days every 4 months for 2-6 years, with physical therapy and orthopedic surgery as appropriate. Mobility score, fracture rate, height, bone mineral density (BMD) and bone healing were evaluated throughout follow-up. RESULTS: In 24 (89%) patients, the fracture rate decreased to
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Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Osteogénesis Imperfecta/tratamiento farmacológico , Absorciometría de Fotón , Aminoácidos/orina , Densidad Ósea , Conservadores de la Densidad Ósea/efectos adversos , Niño , Preescolar , Difosfonatos/efectos adversos , Femenino , Curación de Fractura/efectos de los fármacos , Fracturas Óseas/diagnóstico por imagen , Humanos , Infusiones Intravenosas , Masculino , Osteocalcina/sangre , Osteogénesis Imperfecta/sangre , Osteogénesis Imperfecta/diagnóstico por imagen , Osteogénesis Imperfecta/orina , Pamidronato , Hormona Paratiroidea/sangre , Estudios ProspectivosRESUMEN
Spermatogenesis in the adult male depends on the action of FSH and androgen. Ablation of either hormone has deleterious effects on Sertoli cell function and the progression of germ cells through spermatogenesis. In this study we generated mice lacking both FSH receptors (FSHRKO) and androgen receptors on the Sertoli cell (SCARKO) to examine how FSH and androgen combine to regulate Sertoli cell function and spermatogenesis. Sertoli cell number in FSHRKO-SCARKO mice was reduced by about 50% but was not significantly different from FSHRKO mice. In contrast, total germ cell number in FSHRKO-SCARKO mice was reduced to 2% of control mice (and 20% of SCARKO mice) due to a failure to progress beyond early meiosis. Measurement of Sertoli cell-specific transcript levels showed that about a third were independent of hormonal action on the Sertoli cell, whereas others were predominantly androgen dependent or showed redundant control by FSH and androgen. Results show that FSH and androgen act through redundant, additive, and synergistic regulation of spermatogenesis and Sertoli cell activity. In addition, the Sertoli cell retains a significant capacity for activity, which is independent of direct hormonal regulation.
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Receptores Androgénicos/fisiología , Receptores de HFE/fisiología , Células de Sertoli/metabolismo , Espermatogénesis/fisiología , Andrógenos/farmacología , Animales , Femenino , Hormona Folículo Estimulante/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Genotipo , Masculino , Ratones , Ratones Noqueados , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Androgénicos/genética , Receptores de HFE/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células de Sertoli/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatogénesis/genéticaAsunto(s)
Regulación de la Expresión Génica/fisiología , Receptores de Transferrina/biosíntesis , Túbulos Seminíferos/crecimiento & desarrollo , Animales , Barrera Hematotesticular/crecimiento & desarrollo , Inmunohistoquímica/métodos , Masculino , Ratas , Ratas Wistar , Túbulos Seminíferos/citología , Células de Sertoli/fisiología , Espermatogénesis/fisiologíaRESUMEN
Many studies have shown a correlation between transferrin (Tf) concentration and sperm yield in several mammalian species. We have used transgenic mice expressing human Tf (hTf) to investigate if overexpression of Tf increases the efficiency of mouse spermatogenesis. We demonstrated that a 36% increase of Tf does not ameliorate the efficiency of mouse spermatogenesis but on the contrary resulted in a 36% decrease of testis sperm reserves. Tf overexpression had no effect on testicular determination and development, however testicular function of these transgenic mice was affected in an age-dependent manner. At 16 months of age, testicular and epididymal weights were significantly reduced. While spermatogenesis was qualitatively normal, testicular functions were perturbed. In fact, testosterone rate after human chorionic gonadotropin (hCG) stimulation was lower in Tf overexpressing mice. Intratesticular concentration of estradiol-17beta was increased and fluid accumulation after ligation of rete testis was more abundant in these transgenic mice. Surprisingly, we found that endogenous Tf levels were also increased in Tf overexpressing mice and we demonstrated for the first time that Tf may serve to upregulate its own expression in testis. Collectively, our data show that Tf overexpression has negative effects on testicular function and that Tf levels require strict regulation in the testis.
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Testículo/fisiología , Transferrina/genética , Animales , Cruzamientos Genéticos , Femenino , Hormona Folículo Estimulante/metabolismo , Regulación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Humanos , Hormona Luteinizante/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Hipófisis/metabolismo , Reproducción/fisiología , Espermatogénesis/fisiología , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrollo , Testosterona/metabolismo , Transferrina/farmacología , Transferrina/fisiologíaRESUMEN
INTRODUCTION: The aim of the study was to compare the characteristics of occupational asthma (OA) resulting from sensitisation to allergens of high (HMW) or low (LMW) molecular weight. METHODS: All new cases of allergic OA seen in an occupational health department between January 2001 and March 2004 were included. The patients underwent a standardised assessment including a questionnaire, skin tests, spirometry and measurement of non-specific bronchial reactivity. They were divided into 2 groups depending on the molecular weight of the causal agent (groups HMW and LMW). RESULTS: 77 patients were included, 30 in the HMW group and 47 in the LMW group. No significant difference in severity at the time of diagnosis was found between the two groups (symptoms, spirometry, PD20 methacholine) but the time between the first symptoms and diagnosis was longer in the HMW group (7.1 +/- 7.8 years against 3.2 +/- 4.1 years, p = 0.01). Atopy was more common in the HMW group (57% vs. 27%, p = 0.01). CONCLUSION: The severity of OA at the time of diagnosis does not appear to be influenced by the molecular weight of the causal agent.