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1.
Transpl Int ; 37: 12202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38420268

RESUMEN

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT'AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation's impact (8:00 p.m.-8:00 a.m.) versus daytime (8:00 a.m.-8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors' rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Supervivencia de Injerto , Factores de Tiempo , Estudios Retrospectivos , Donantes de Tejidos , Complicaciones Posoperatorias/etiología
2.
Prog Urol ; 33(8-9): 412-420, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37328317

RESUMEN

INTRODUCTION: The COVID-19 pandemic disrupted all routine health care services in 2020. To date, data regarding adjustment and coverage of surgical backlog in the post-COVID era actually remains scarce. The aim of this study was to compare the number of urological procedures coded between 2019 and 2021 in public and private institutions to (i) quantify the variation in surgical activity linked to the shutdown in 2020 and (ii) study the adjustment of procedures over the year 2021. MATERIALS AND METHODS: This is a comprehensive retrospective analysis of all urological surgeries coded between January 1, 2019 and December 31, 2021 in France. Data were extracted from the open access dataset of the national Technical Agency for Information on Hospital Care (ATIH) website. In total, 453 urological procedures were retained and allocated in 8 categories. Primary outcome was the impact of COVID-19 analyzed by the 2020/2019 variation. The secondary outcome was the post-COVID catch-up analyzed by the 2021/2019 variation. RESULTS: Surgical activity in public hospitals dropped by 13.2% in 2020 compared to 7.6% in the private sector. The most impacted areas were functional urology, stones and BPH. Incontinence surgery did not recover at all in 2021. BPH and stone surgeries were far less impacted in the private sector, with even explosive activity in 2021, post-COVID period. Onco-urology procedures were roughly maintained with a compensation in 2021 in both sectors. CONCLUSION: The recovery of surgical backlog was much more efficient in the private sector in 2021. The pressure on the health system associated to the multiple COVID-19 waves may generate a gap between public and private surgical activity in the future.


Asunto(s)
COVID-19 , Hiperplasia Prostática , Masculino , Humanos , COVID-19/epidemiología , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , Francia/epidemiología
3.
Prog Urol ; 32(8-9): 593-600, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35314100

RESUMEN

BACKGROUND: With an increasing prevalence in industrialized countries, lithiasis represents a public health problem with significant economic cost. Ureteroscopy is nowadays the main treatment for kidney and ureteral stones with increasingly broad indications. While this treatment is relatively safe and effective, the complications can be severe. AIM: The aim of this study was to investigate the preoperative risk factors of complication in the 30 days following a rigid or flexible ureteroscopy in a large cohort of patients. METHODS: A retrospective multicenter study was conducted in 5 French centers between January 1st 2017 and 31st December 2018. All flexible and rigid ureteroscopies performed were included. All preoperative and per operative data were collected in an electronic database. Outcomes and complications within 30 days of the procedure were also collected. Univariate and multivariable analyses evaluated for potential predictors of postoperative complications. RESULTS: 1124 procedures were included. According to the occurrence of a postoperative complication, patients were divided into two groups, 109 in the group with complications. The majority of complications were minor, with only 13.7% classified as Clavien 3-4. In univariate analysis, ASA score>2 (odd ratio, OR=1.68, P=0.04), WHO performance status≥1 (OR=1.50, P=0.04) and neurologic disease (OR=2.78, P=0.005) were predictors of postoperative complications. In multivariable analysis, Charlson's score (OR=0.79, P=0.01) and ASA score>2 (OR=1.48, P=0.03) were independents risk factors of postoperative complication. Concerning major complications, in univariate analysis, cardiovascular disease (OR=3.71, P=0.032) and BMI (OR=0.87, P=0.02) were the only predictors of major complications after ureteroscopy. Only BMI was found In multivariable analysis (OR=0.86, P=0.01) CONCLUSION: Baseline characteristics and comorbidities of the patients, especially neurological diseases, were the main risk factors for short-term complications after ureteroscopy. Ureteroscopy remains a relatively safe and effective procedure. However, we advise surgeons to take precautions with fragile patients with multiple comorbidities or neurological disease.


Asunto(s)
Cálculos Renales , Enfermedades del Sistema Nervioso , Cálculos Ureterales , Humanos , Cálculos Renales/cirugía , Enfermedades del Sistema Nervioso/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Cálculos Ureterales/cirugía , Ureteroscopios/efectos adversos , Ureteroscopía/efectos adversos , Ureteroscopía/métodos
4.
Prog Urol ; 32(4): 284-290, 2022 Mar.
Artículo en Francés | MEDLINE | ID: mdl-35131167

RESUMEN

INTRODUCTION: Urinary incontinence after High Intensity Focused ultrasound (HIFU) is a poorly documented issue. To our knowledge, no study has evaluated the outcomes of artificial urinary sphincter (AUS) after HIFU. The aim of this study was to evaluate the functional outcomes of AUS for post-HIFU urinary incontinence. METHODS: The charts of all male patients who underwent an AUS implantation between 2004 and 2020 in 13 centers were reviewed retrospectively. Only men with a history of HIFU were included. The primary endpoint was social continence at 3 months defined as wearing 0 to 1 pad per day. RESULTS: Out of 1318 procedures, nine men were implanted with an AUS after HIFU including four men with an history of pelvic irradiation: 3 pelvic radiation therapy and 1 prostatic brachytherapy. The patients were divided into two groups, 5 in the HIFU group without a history of pelvic irradiation, 4 patients in the HIRX group with a history of pelvic irradiation. The median age was 74 years (IQR 71-76). There was no perioperative complication. The median follow-up was 47.5 (IQR 25-85.5) months. Social continence at 3 months was 75% in the total cohort: 80% in the HIFU group and 67% in the HIRX group. CONCLUSION: AUS implantation may provide satisfactory long-term functional outcomes in the treatment of stress urinary incontinence resulting from HIFU. Larger series are needed to confirm these findings. LEVEL OF EVIDENCE: 4.


Asunto(s)
Incontinencia Urinaria de Esfuerzo , Incontinencia Urinaria , Esfínter Urinario Artificial , Anciano , Humanos , Masculino , Implantación de Prótesis/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Incontinencia Urinaria/complicaciones , Incontinencia Urinaria/terapia , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/cirugía , Esfínter Urinario Artificial/efectos adversos
5.
Prog Urol ; 31(6): 324-331, 2021 May.
Artículo en Francés | MEDLINE | ID: mdl-33516609

RESUMEN

INTRODUCTION: BCG instillations are the gold-standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) with a decreased risk of tumor recurrence and muscle infiltration. From 2012 to 2014, a stock shortage of the Connaught strain has led to the cessation of supply for immucyst in France. The objective of this study was to evaluate the potential impact of BCG shortage on the management of patients with NMIBC. PATIENTS AND METHODS: We conducted a retrospective single-center study including patients followed from May 2005 to May 2015 with a high-risk NMIBC (primo-diagnosis). Patients were separated into two groups: not impacted by the shortage (NISG: 56 patients) and impacted by the shortage (ISG: 53 patients). Data on tumour recurrence (RFS), muscle progression (PFS) and overall and specific survival (OS and SS) were also analysed. RESULTS: The BCG induction schedule could not be carried out in 20.8% of cases in the ISG compared to only 5.3% of cases in NISG (P=0.02). Similarly, the maintenance treatment was incomplete for 56.6% of cases versus 37.5% in NISG (P=0.047). Nevertheless, it should be underlined that very high-risk NMIBC received a complete induction BCG schedule. The ISG seems to have benefited with the evolution of the guidelines with the use of diagnosis bladder fluorescence but without significant difference on the rate of second look bladder trans-uretral resection. The cystectomy rate was higher in ISG. No significant difference in RFS, PFS, OS, and SS between the two groups. CONCLUSION: In our experience, RFS, PFS, OS or SS were not impacted by the BCG shortage. These data may be explained by a better selection of very high-risk patients including the recommended BCG schedule and more frequently the use of diagnosis bladder fluorescence. LEVEL OF EVIDENCE: 3.


Asunto(s)
Adyuvantes Inmunológicos/provisión & distribución , Vacuna BCG/provisión & distribución , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Invasividad Neoplásica , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/patología
6.
Prog Urol ; 31(5): 293-302, 2021 Apr.
Artículo en Francés | MEDLINE | ID: mdl-33612443

RESUMEN

INTRODUCTION: Fertility preservation is essential before cancer treatment. When ejaculated sperm preservation is not possible, testicular tissue can be surgically collected by Onco-TESE technic (Oncological Testicular Sperm Extraction) to isolate sperm. We report on our experience with Onco-TESE in testicular cancer patients at the Rouen University Hospital. MATERIAL AND METHOD: Retrospective study including all pubescent men, treated for testicular cancer, uni- or bilateral, before any carcinological therapy, who have undergone Onco-TESE at the Rouen University Hospital. Fragment weight, detection of sperm or its precursors were analysed. A histological interpretation of the testicular tumor was carried out. For each positive sample, straws were kept at the French Sperm Bank. RESULTS: Twenty-four patients had an Onco-TESE: 58.34% severe sperm alteration (SSA) and 41.36% sperm collection failure (SCF), between 1996 and 2019. The mean age was 26.6 (±5.29) years. The mean procedure and length of stay were 71minutes (±30.7) and 3.75 days (±2.83), respectively. The rate of positive testicular biopsies (TB) was 58.33% overall and 66,67% in the case of TB on tumour testis. One patient had a Clavian-Dindo III complication. The mean number of straws preserved per patient was 14.28 (±15.34) for 7.14% use. CONCLUSION: Our results seem to confirm that Onco-TESE is an effective solution for preserving fertility in men with testicular cancer in cases of SSA or SCF. LEVEL OF EVIDENCE: III.


Asunto(s)
Preservación de la Fertilidad/métodos , Neoplasias Testiculares/cirugía , Testículo/cirugía , Recolección de Tejidos y Órganos , Adulto , Humanos , Masculino , Estudios Retrospectivos , Adulto Joven
7.
J Gynecol Obstet Hum Reprod ; 50(10): 102185, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34129991

RESUMEN

INTRODUCTION: Evaluation of fetal well-being during labor is based on fetal heart rate (FHR) analysis, which requires physiology expertise. The aim of the present study was to assess medical residents' fetal physiology training in terms of theoretical knowledge, FHR interpretation, and use of second-line examinations. METHODS: This single-center, prospective study of obstetrics and gynecology residents (N = 34) at CHU de Lille Hospital (Lille, France) was conducted from November 2017 to November 2018. Evaluation and training were conducted in three stages. First, residents' pre-training knowledge of FHR interpretation and use of fetal scalp blood sampling (FBS) was assessed using clinical cases. Second, a didactic training session on fetal physiology was delivered. Finally, post-training knowledge was evaluated using the same cases presented during pre-training. I: Pre-training, 3%, 11.8%, and 14.7% of residents considered their training on fetal physiology, FHR analysis, and second-line examinations, respectively, to be sufficient. Training significantly improved their theoretical knowledge, which was assessed using multiple-choice questions (median [interquartile range]: 1.5 [1.0-2.0] vs. 4.0 [3.0-4.5], p<0.001), and reduced the number of FBS requested (36.3% vs. 29.5%, p = 0.002). Krippendorff's alpha coefficient for the reproducibility of residents' responses improved significantly, reflecting greater homogenization of clinical practice decisions (alpha [95% confidence interval]: 0.60 [0.55-0.65] vs. 0.72 [0.67-0.76]). CONCLUSION: Improved fetal physiology knowledge promotes more accurate FHR interpretation, better indications for second-line examinations, and greater homogenization of clinical practice decisions. Future studies should evaluate the impact of fetal physiology training on clinical practice.


Asunto(s)
Frecuencia Cardíaca Fetal/fisiología , Pediatría/educación , Adulto , Competencia Clínica/normas , Competencia Clínica/estadística & datos numéricos , Femenino , Francia , Humanos , Internado y Residencia/métodos , Internado y Residencia/normas , Internado y Residencia/estadística & datos numéricos , Pediatría/normas , Pediatría/estadística & datos numéricos , Embarazo , Estudios Prospectivos , Reproducibilidad de los Resultados
8.
Disabil Rehabil ; 30(14): 999-1013, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18584376

RESUMEN

PURPOSE: The influence of vibration-induced white finger disease on the quality of life and possible social consequences is the subject of the study presented herein. METHOD: The data acquisition was carried out by means of a standardized questionnaire. Parameters such as quality of life, professional practice, prevention and social security were assessed among other things. RESULTS: Nearly three quarters of the interviewees (n = 115) did not consult a physician with the occurrence of the first complaints. Physicians frequently made the correct diagnosis only with delay. From the first occurrence of symptoms to the acknowledgment as an occupational disease 0.5-34.5 years had usually elapsed. The quality of life affected the patients and their families. Change of profession and unemployment were frequently associated with substantial problems. There is clear need for information regarding the clinical picture, protective possibilities in the workplace, recognition as an occupational disease and financial problems. The introduction of industrial safety measures was not substantially affected by the occurrence of the disease. CONCLUSIONS: A quick diagnosis and the recognition of this occupational disease are important in view of its potential reversibility upon discontinuation of the exposition to vibration. As a consequence, intensified preventive measures need to be called for.


Asunto(s)
Síndrome por Vibración de la Mano y el Brazo/epidemiología , Síndrome por Vibración de la Mano y el Brazo/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Alemania/epidemiología , Síndrome por Vibración de la Mano y el Brazo/economía , Humanos , Seguro , Masculino , Persona de Mediana Edad , Salud Laboral , Educación del Paciente como Asunto , Calidad de Vida , Encuestas y Cuestionarios , Desempleo
9.
Eur J Obstet Gynecol Reprod Biol ; 226: 54-58, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29843068

RESUMEN

OBJECTIVE: The aim of fetal heart rate monitoring during labour is to identify and prevent foetal distress, but its evaluation is not perfect. Fetal scalp blood sampling for pH measurement is one of the second-line methods of monitoring when fetal heart rate is classified as suspicious. This study aims to determine when pH testing should be performed after a prolonged deceleration. STUDY DESIGN: This was an experimental study in a fetal sheep model. A partial umbilical cord occlusion was performed for seven minutes followed by a recuperation period of 30 min. Hemodynamic parameters (heart rate, mean blood pressure and intra-amniotic pressure) and blood gases were recorded before occlusion (T0), during occlusion (T4), just after the end of occlusion (T7), and then 10, 20 and 30 min after occlusion (T17, T27 and T37 respectively). RESULTS: Ten experiments were carried out. During partial cord occlusion, the fetal pH decreased significantly to acidosis. After a prolonged deceleration with fetal acidosis, the pH recovered to a normal value, defined by a pH greater than or equal to 7.25, after 20 min of recuperation. CONCLUSION: After a prolonged deceleration, fetal pH normalizes between 20 and 30 min thereafter. Thus, if a foetal blood sample is indicated, this delay must be respected in order to avoid inducing an unnecessary intervention decision.


Asunto(s)
Acidosis/diagnóstico , Sufrimiento Fetal/diagnóstico , Frecuencia Cardíaca Fetal/fisiología , Trabajo de Parto , Acidosis/sangre , Acidosis/fisiopatología , Animales , Análisis de los Gases de la Sangre , Desaceleración , Femenino , Sufrimiento Fetal/sangre , Sufrimiento Fetal/fisiopatología , Concentración de Iones de Hidrógeno , Embarazo , Ovinos
10.
Scand J Work Environ Health ; 13(4): 352-5, 1987 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3433037

RESUMEN

A description was made of the development and application of infrared thermography and fingertip thermometry for the assessment of finger skin temperature during a cold provocation test. Three hundred and seventeen lumberjacks, grinders, metalworkers, stone cutters, and students were examined in laboratory and field investigations. Under laboratory conditions, the influence of water temperature and exposure duration was studied, and skin temperature measurements were made on the volar and dorsal side of the fingers. In the field occupational health examination, infrared thermography and fingertip thermometry were simultaneously applied during a cold provocation test. The following three types of temperature reaction could be recognized: normal rewarming and moderate delay and strong delay of rewarming. The temperature distribution along the finger length was analyzed. The following conclusions were drawn for practical application of the thermometric methods. Skin temperature must be measured on all 10 fingertips, either on the volar or on the dorsal surface. Fingertip thermometry may be used in occupational health examinations. Infrared thermography may yield more information on the development of disturbances in peripheral circulation along the finger length and may be used in special clinical work.


Asunto(s)
Dedos , Enfermedades Profesionales/diagnóstico , Enfermedad de Raynaud/diagnóstico , Termografía/métodos , Vibración/efectos adversos , Adulto , Frío , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Temperatura Cutánea
11.
Hastings Cent Rep ; 14(6): 23-4, 1984 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-6511374

RESUMEN

KIE: A Dutch ethicist offers a brief overview of bioethics activity in her country. Public attitudes toward medical controversies are marked by a willingness to debate the issues and widespread tolerance of others' opinions. The medical profession's involvement with bioethics is increasing as practitioners are faced with treatment dilemmas. Medical education is beginning to include ethics teaching, with four of the seven Dutch medical schools offering some ethics instruction, usually by a theologian. Lack of interest on the part of faculty and the small number of ethicists available to teach make it unlikely that a majority of health professionals will be exposed to ethics in the course of training. The only significant role of ethicists is as members of the Dutch Health Council, which advises the government on health issues.^ieng


Asunto(s)
Educación Médica , Ética , Discusiones Bioéticas , Diversidad Cultural , Análisis Ético , Eticistas , Humanos , Países Bajos
12.
Soz Praventivmed ; 25(6): 375-80, 1980 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-7245929

RESUMEN

The evaluation of different body postures during work needs considering the interactions of anthropometric, physiological, orthopaedic, angiologic and biomechanical criteria on one side and of working conditons on the other. Many professions in industry as well as many tasks of the housewife still have to be done in standing position. But standing for long periods leads to increased strain of the bone and muscle system and to increased complaints and illness of the feet and legs. A comprehending catalogue of the effects of dominating standing posture and a catalogue of preventive measures are presented.


Asunto(s)
Enfermedades Profesionales/etiología , Postura , Fenómenos Biomecánicos , Enfermedades Óseas/etiología , Enfermedades Cardiovasculares/etiología , Hemodinámica , Humanos , Pierna/irrigación sanguínea , Enfermedades Musculares/etiología , Esfuerzo Físico
13.
Cent Eur J Public Health ; 3 Suppl: 19-21, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-9150960

RESUMEN

In connection with medical appraisements of the occupational disease No. 2104 "Vibration-induced vasospastic disease" 240 patients could be examined a first time, 94 of them a second time, 42 patients a third time and 11 patients a forth time. The interval between examinations was 2, 4 or 6 years respectively. The standard procedure besides clinical whole body examination included anamnestic questionnaire, cold-provocation test with infrared thermography and vibrotactile perception test. The evaluation of the diagnoses in principle followed the Stockholm vascular V and sensorineural SN stages and was used to establish the grade of disability for compensation. The re-examinations after 2-6 years gave information on the development of the health status after cessation of vibration exposure. In only about 54% of all cases there was any improvement, in 39% the health status was unchanged, in 7% aggravated. It is obvious that the reversibility of the VWF if any needs many years abstaining from vibration exposure.


Asunto(s)
Evaluación de la Discapacidad , Dedos , Enfermedades Profesionales/diagnóstico , Enfermedades Vasculares Periféricas/diagnóstico , Vibración/efectos adversos , Estudios de Seguimiento , Alemania , Humanos , Enfermedades Profesionales/etiología , Enfermedades Profesionales/rehabilitación , Enfermedades Vasculares Periféricas/etiología , Enfermedades Vasculares Periféricas/rehabilitación , Pronóstico , Factores de Tiempo
14.
Cent Eur J Public Health ; 3 Suppl: 85-7, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-9150979

RESUMEN

The vibration sensitivity of the skin at the ten fingertips was tested with 72 chain saw operators examined due to VWF-disease and compared with controls. The vibrotactile perception threshold (frequency f = 125 Hz, load p = 1.3 N) proved to be 3 to 5 times as high for the exposed group compared to controls. There was no correlation between vibration sensitivity and peripheral circulation found in cold provocation test. Two different testing instruments (pallaesthesiometer = vibrotactometer) showed significant differences in results probably due to different technical details of the methods. It may be concluded that a standardization of the instrumentation and method is necessary for testing the vibrotactile perception threshold as a part of the nervous function in a comparable manner.


Asunto(s)
Dedos/fisiología , Agricultura Forestal , Síndromes de Compresión Nerviosa/diagnóstico , Enfermedades Profesionales/diagnóstico , Tacto , Vibración/efectos adversos , Adulto , Anciano , Estudios de Casos y Controles , Umbral Diferencial , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/etiología , Enfermedades Profesionales/etiología
15.
Tijdschr Diergeneeskd ; 108(19): 773-6, 1983 Oct 01.
Artículo en Holandés | MEDLINE | ID: mdl-6636105

RESUMEN

Among the many existing occupations, the so-called 'professions' occupy a special position. They are characterized, among other things, by a special intellectual component, special traditions and the fact that they serve the community in a particular fashion. With a profession goes a code including agreements concerning behaviour towards colleagues, clients and patients as well as the community. In the present paper, a number of critical questions are raised regarding the 'Code of Conduct for Veterinarians: Whose interests are served by this code and are given priority respectively? To what extent attention is paid to the rights of clients and patients? How are conflicts of loyalty settled or do they pass unnoticed? To what extent does monopolizing occur of a subject which others would also like to consider and have their say on, namely, the starting-points of a conscientious practice of veterinary medicine?


Asunto(s)
Ética Profesional , Responsabilidad Social , Medicina Veterinaria , Países Bajos
16.
Endocrinology ; 154(10): 3702-18, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23904355

RESUMEN

Glycogen synthase kinase 3 ß (GSK-3ß) is an essential negative regulator or "brake" on many anabolic-signaling pathways including Wnt and insulin. Global deletion of GSK-3ß results in perinatal lethality and various skeletal defects. The goal of our research was to determine GSK-3ß cell-autonomous effects and postnatal roles in the skeleton. We used the 3.6-kb Col1a1 promoter to inactivate the Gsk3b gene (Col1a1-Gsk3b knockout) in skeletal cells. Mutant mice exhibit decreased body fat and postnatal bone growth, as well as delayed development of several skeletal elements. Surprisingly, the mutant mice display decreased circulating glucose and insulin levels despite normal expression of GSK-3ß in metabolic tissues. We showed that these effects are due to an increase in global insulin sensitivity. Most of the male mutant mice died after weaning. Prior to death, blood glucose changed from low to high, suggesting a possible switch from insulin sensitivity to resistance. These male mice die with extremely large bladders that are preceded by damage to the urogenital tract, defects that are also seen type 2 diabetes. Our data suggest that skeletal-specific deletion of GSK-3ß affects global metabolism and sensitizes male mice to developing type 2 diabetes.


Asunto(s)
Desarrollo Óseo , Huesos/enzimología , Diabetes Mellitus Tipo 2/complicaciones , Metabolismo Energético , Glucógeno Sintasa Quinasa 3/metabolismo , Resistencia a la Insulina , Enfermedades Urogenitales Masculinas/complicaciones , Animales , Huesos/metabolismo , Huesos/patología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Cruzamientos Genéticos , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Susceptibilidad a Enfermedades , Femenino , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Masculino , Ratones , Ratones Noqueados , Ratones Mutantes , Ratones Transgénicos , Regiones Promotoras Genéticas , Caracteres Sexuales , Análisis de Supervivencia , Sistema Urogenital/patología , Destete
17.
Endocrinology ; 152(5): 1755-66, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21325041

RESUMEN

The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/ß-catenin. The two GSK-3 proteins, GSK-3α and GSK-3ß, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase inhibition in this system, in agreement with the antagonistic role of these two kinases in response to signals such as IGF. However, cartilage-specific deletion of the Gsk3b gene in mice has minimal effects on skeletal growth or development. Molecular analyses demonstrated that compensatory up-regulation of GSK-3α protein levels in cartilage is the likely cause for this lack of effect. To our knowledge, this is the first tissue in which such a compensatory mechanism is described. Thus, our study provides important new insights into both skeletal development and the biology of GSK-3 proteins.


Asunto(s)
Cartílago/enzimología , Glucógeno Sintasa Quinasa 3/metabolismo , Tibia/enzimología , Aminofenoles/farmacología , Animales , Western Blotting , Cartílago/metabolismo , Proliferación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Femenino , Eliminación de Gen , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Placa de Crecimiento/efectos de los fármacos , Placa de Crecimiento/crecimiento & desarrollo , Placa de Crecimiento/metabolismo , Inmunohistoquímica , Masculino , Maleimidas/farmacología , Ratones , Ratones Noqueados , Técnicas de Cultivo de Órganos , Fosfatidilinositol 3-Quinasas/metabolismo , Tibia/efectos de los fármacos , Tibia/crecimiento & desarrollo , Regulación hacia Arriba , beta Catenina/metabolismo
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