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2.
Mil Med Res ; 9(1): 48, 2022 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-36050805

RESUMEN

Because of its simplicity, reliability, and replicability, the Masquelet induced membrane technique (IMT) has become one of the preferred methods for critical bone defect reconstruction in extremities. Although it is now used worldwide, few studies have been published about IMT in military practice. Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury, early wound infection, and even delayed management in austere conditions. Based on our clinical expertise, recent research, and a literature analysis, this narrative review provides an overview of the IMT application to combat-related bone defects. It presents technical specificities and future developments aiming to optimize IMT outcomes, including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.


Asunto(s)
Personal Militar , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Infección de Heridas , Humanos , Procedimientos de Cirugía Plástica/métodos , Reproducibilidad de los Resultados , Traumatismos de los Tejidos Blandos/cirugía
3.
Biomedicines ; 10(2)2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35203694

RESUMEN

Bone is a very complex tissue that is constantly changing throughout the lifespan. The precise mechanism of bone regeneration remains poorly understood. Large bone defects can be caused by gunshot injury, trauma, accidents, congenital anomalies and tissue resection due to cancer. Therefore, understanding bone homeostasis and regeneration has considerable clinical and scientific importance in the development of bone therapy. Macrophages are well known innate immune cells secreting different combinations of cytokines and their role in bone regeneration during bone healing is essential. Here, we present a method to identify mRNA transcripts in cryosections of non-decalcified rat bone using in situ hybridization and hybridization chain reaction to explore gene expression in situ for better understanding the gene expression of the bone tissues.

4.
Clin Orthop Relat Res ; 479(12): 2737-2751, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34406150

RESUMEN

BACKGROUND: Usually, the two-stage Masquelet induced-membrane technique for extremity reconstruction begins with a polymethylmethacrylate (PMMA) cement spacer-driven membrane, followed by an autologous cancellous bone graft implanted into the membrane cavity to promote healing of large bone defects. In exceptional cases, spacers made of polypropylene disposable syringes were successfully used instead of the usual PMMA spacers because of a PMMA cement shortage caused by a lack of resources. However, this approach lacks clinical evidence and requires experimental validation before being recommended as an alternative to the conventional technique. QUESTIONS/PURPOSES: To (1) develop and (2) validate a critical-sized femoral defect model in rats for two stages of the Masquelet technique and to (3) compare the biological and bone healing properties of polypropylene-induced membranes and PMMA-induced membranes in this model. METHODS: Fifty male Sprague Dawley rats aged 8 weeks old received a 6-mm femur defect, which was stabilized with an external fixator that was converted into an internal device. In the development phase, the defect was filled with PMMA in 16 rats to determine the most favorable timing for bone grafting. Two rats were excluded since they died of anesthetic complications. The other 14 were successively euthanized after 2 weeks (n = 3), 4 weeks (n = 4), 6 weeks (n = 4), and 8 weeks (n = 3) for induced membrane analyses. In the validation phase, 12 rats underwent both stages of the procedure using a PMMA spacer and were randomly assigned to two groups, whether the induced membrane was preserved or removed before grafting. To address our final objective, we implanted either polypropylene or PMMA spacers into the defect (Masquelet technique Stage 1; n = 11 rats per group) for the period established by the development phase. In each group, 6 of 11 rats were euthanized to compare the biological properties of polypropylene-induced membranes and PMMA-induced membranes using histological qualitative analysis, semiquantitative assessment of the bone morphogenic protein-2 content by immunostaining, and qualitative assessment of the mesenchymal stromal cell (MSC; CD31-, CD45-, CD90+, and CD73+ phenotypes) content by flow cytometry. Quantitative measurements from serum bone turnover markers were also performed. The five remaining rats of each group were used for Masquelet technique Stage 2, in which rat bone allografts were implanted in the induced membrane cavity after the polypropylene or PMMA spacers were removed. These rats recovered for 10 weeks before being euthanized for microCT quantitative measurements and bone histology qualitative assessment to evaluate and compare the extent of bone regeneration between groups. RESULTS: Induced membrane analyses together with serum bone turnover measurements indicated that a 4-week interval time between stages was the most favorable. Removal of the induced membrane before grafting led to almost constant early implant failures with poor bone formation. Four-week-old rats with polypropylene-triggered induced membranes displayed similar histologic organization as rats with PMMA-driven induced membranes, without any difference in the cell density of the extracellular matrix (4933 ± 916 cells per mm2 for polypropylene versus 4923 ± 1284 cells per mm2 for PMMA; p = 0.98). Induced membrane-derived MSCs were found in both groups with no difference (4 of 5 with polypropylene versus 3 of 3 with PMMA; p > 0.99). Induced membrane bone morphogenic protein-2 immunolabeling and serum bone turnover marker levels were comparable between the polypropylene and PMMA groups. MicroCT analysis found that bone regeneration in the polypropylene group seemed comparable with that in the PMMA group (29 ± 26 mm3 for polypropylene versus 24 ± 18 mm3 for PMMA; p > 0.99). Finally, qualitative histological assessment revealed a satisfactory endochondral ossification maturation in both groups. CONCLUSION: Using a critical-sized femoral defect model in rats, we demonstrated that polypropylene spacers could induce membrane encapsulation with histologic characteristics and bone regenerative capacities that seem like those of PMMA spacers. CLINICAL RELEVANCE: In a same bone site, polymers with close physical properties seem to lead to similar foreign body reactions and induce encapsulating membranes with comparable bone healing properties. Polypropylene spacers made from disposable syringes could be a valuable alternative to PMMA. These results support the possibility of a cementless Masquelet technique in cases of PMMA shortage caused by a lack of resources.


Asunto(s)
Cementos para Huesos/efectos adversos , Trasplante Óseo/instrumentación , Equipos Desechables , Polimetil Metacrilato/administración & dosificación , Jeringas , Animales , Remodelación Ósea , Trasplante Óseo/métodos , Modelos Animales de Enfermedad , Diseño de Equipo , Masculino , Polipropilenos , Ratas , Ratas Sprague-Dawley
5.
Eur J Trauma Emerg Surg ; 47(5): 1373-1380, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33226484

RESUMEN

The reconstruction of long-bone segmental defects remains challenging, with the three common methods of treatment being bone transport, vascularized bone transfer, and the induced membrane technique (IMT). Because of its simplicity, replicability, and reliability, usage of IMT has spread all over the world in the last decade, with more than 300 papers published in the PubMed literature database on this subject so far. Most of the clinical studies have reported high rates of bone union, yet some also include more controversial results with frequent complications and revision surgeries. At the same time, various experimental research efforts have been designed to understand and improve the biological properties of the induced membrane. This literature review aims to provide an overview of IMT clinical results in terms of bone union and complications and to compare them with those of other reconstructive procedures. In light of our findings, we then propose an original classification scheme of IMT failures distinguishing between preventable and nonpreventable failures.


Asunto(s)
Trasplante Óseo , Humanos , Reproducibilidad de los Resultados
6.
Orthop Traumatol Surg Res ; 106(5): 797-801, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32376203

RESUMEN

BACKGROUND: The induced membrane technique (IMT) has been widely evaluated for reconstruction of post-traumatic bone defects. However, no specific evaluation was conducted in ballistic injuries. The objective of the present study was to compare IMT in conventional trauma (CT) versus ballistic trauma (BT) managed in a military trauma center. METHODS: A retrospective study was conducted between 2009 and 2018 in patients treated by IMT for post-traumatic bone defects, whatever the defect location. Endpoints comprised bone union, residual infection, additional bone grafting and lower-limb amputation. RESULTS: Thirty-six patients were included: 24 in the CT and 12 in the BT group. Demographics and injury pattern were similar in both groups, with open fracture and infected lesions predominating. The only significant difference was that tibial bone defects were larger in the BT group. Operative parameters and results were also similar. At a mean 24 months' follow-up, bone union rate was 83% in both groups, without significant differences in residual infection, complementary grafting or late amputation. CONCLUSION: IMT is appropriate to bone reconstruction in the aftermath of ballistic trauma, with similar results to those obtained in conventional trauma. LEVEL OF EVIDENCE: IV, retrospective study.


Asunto(s)
Fracturas Abiertas , Procedimientos de Cirugía Plástica , Trasplante Óseo , Fracturas Abiertas/cirugía , Humanos , Estudios Retrospectivos , Fracturas de la Tibia/cirugía , Resultado del Tratamiento
7.
J Clin Med ; 9(2)2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32041238

RESUMEN

The two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics.

8.
Eur J Trauma Emerg Surg ; 46(5): 1099-1105, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31451864

RESUMEN

PURPOSE: The induced membrane technique (IMT) is a two-stage procedure dedicated to reconstruction of bone defects of the limbs. The objective of this report was to evaluate employment of the IMT for the treatment of open tibia fractures managed in a military trauma center treating both wartime and peacetime injuries. METHODS: A retrospective study was performed among the patients treated via IMT for tibial bone defects related to open fractures between 2009 and 2018. The outcomes recorded included bone union, residual infection, amputation and lower limb function. RESULTS: During this period, 15 patients with a mean age of 39 years were included for the treatment of Gustilo II (2 cases) or Gustilo IIIB (13 cases) injuries. A mean number of 2.9 debridements were required before stage 1. Flap coverage was associated in 14 cases. The mean interval between stages was 22 weeks. Five patients were re-operated on after stage 1 due to persistent infection. The mean follow-up was 33 months. Bone union was achieved in 13 of the 15 cases (87%) at a mean time of 10.1 months. However, seven additional bone healing procedures were required, including six inter-tibiofibular grafting. Only one late septic recurrence was found. Most patients returned to work in sedentary jobs. CONCLUSIONS: This series is the first to report IMT use in a military setting. The prior eradication of infection constitutes a major challenge in tibial bone defects, especially in high-energy, multi-tissue injuries. An inter-tibiofibular bone reconstruction approach is required when external fixation is chosen.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Abiertas/cirugía , Personal Militar , Procedimientos de Cirugía Plástica/métodos , Fracturas de la Tibia/cirugía , Adulto , Trasplante Óseo , Desbridamiento , Femenino , Curación de Fractura , Fracturas Abiertas/clasificación , Humanos , Masculino , Membranas Artificiales , Persona de Mediana Edad , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/cirugía , Fracturas de la Tibia/clasificación
9.
Hypoxia (Auckl) ; 7: 41-52, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31440522

RESUMEN

PURPOSE: Bone marrow response to an organismal stress is made by orchestrating the interplay between hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Neither the cellular nor the molecular factors that regulate this process are fully understood, especially since this mechanism probably varies depending on the type of stress. Herein, we explored the differentiation and fate of MSCs and HSPCs in mice challenged with a hematopoietic stress or a mechanical stress applied separately or in combination. METHODS: Mice were subjected to 4 days of hypobaric hypoxia (hematopoietic challenge) and/or 7 days of hindlimb suspension (stromal challenge) and then sacrificed for blood and bone collection. Using hematological measurements, colony-forming unit assays, bone histomorphometry and array-based multiplex ELISA analysis, we evaluated challenge influences on both MSC and HSPC mobilization, differentiation (osteoblasts, osteoclasts, and mature blood cells) and fate. RESULTS: We found that hypoxia leads to HSPC mobilization and that an imbalance between bone formation and bone resorption accounts for this mobilization. Whilst suspension is also associated with an imbalance between bone formation and bone resorption, it does not induce HSPC mobilization. Then, we revealed cellular interactions by combining hematopoietic and stromal challenges together in mice. We showed that the hypoxia-driven HSPC mobilization is moderated by suspension. Moreover, when applied in a hypoxic environment, suspension offsets bone imbalance. We identified stroma cell-derived factors MIP-1α, HGF and SDF-1 as potent molecular key players sustaining interactions between hindlimb suspension and hypobaric hypoxia. CONCLUSION: Taken together, our data highlight the benefit of combining different types of stress to better understand the interplay between MSCs and HSPCs.

10.
Pain Med ; 20(7): 1294-1299, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30576555

RESUMEN

OBJECTIVE: Although anti-inflammatory drugs are commonly used in acute discogenic sciatica, data regarding their efficacy are scarce and controversial. We compared the efficacy and safety of intravenous ketoprofen and methylprednisolone with placebo in sciatica. DESIGN: Multicenter, double-blinded randomized controlled trial. SUBJECTS: Patients with confirmed discogenic acute sciatica, without neurologic deficit, were randomized into three arms. METHODS: Besides standard-of-care analgesic therapy, they received intravenous injections of methylprednisolone (60 mg/d) or ketoprofen (200 mg/d) or placebo for five days. The primary outcome was leg pain over five days. Secondary outcomes were clinical responses at days 3 and 5, lumbar pain, Straight Leg Raise Test and lumbar flexion index, analgesic consumption, realization of lumbar spine injections, and surgery during the study period. RESULTS: Fifty-four patients were randomized, and 50 completed the study. In patients admitted to the hospital for pain control with acute lumbar radicular pain due to intervertebral disc herniation and receiving an oral analgesic protocol including paracetamol, nefopam, tramadol, and morphine, there was no additional analgesic effect seen between groups. There was no significant difference in leg pain between the three groups over the study period. In the methylprednisolone group, however, we observed a higher rate of clinically relevant responses at day 3. No difference was observed on other secondary efficacy outcomes and safety. CONCLUSION: No significant difference in leg pain was observed between groups. However, there was a higher proportion of patients relieved with intravenous methylprednisolone at day 3, compared with ketoprofen or placebo.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Glucocorticoides/uso terapéutico , Cetoprofeno/uso terapéutico , Metilprednisolona/uso terapéutico , Ciática/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Ciática/etiología , Resultado del Tratamiento
11.
Biomaterials ; 159: 1-12, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29306094

RESUMEN

Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes. We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint, and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the in vivo performance of biomaterials for skeletal regeneration.


Asunto(s)
Medios de Contraste/química , Esqueleto/citología , Tomografía Computarizada por Rayos X/métodos , Compuestos de Tungsteno/química , Adipocitos/citología , Animales , Células de la Médula Ósea/citología , Hueso Esponjoso/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Espectrometría Raman
12.
Stem Cells Transl Med ; 3(8): 958-68, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24944208

RESUMEN

We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency.


Asunto(s)
Remodelación Ósea , Fracturas del Fémur/complicaciones , Fémur/fisiopatología , Curación de Fractura , Hipoxia/complicaciones , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/metabolismo , Fracturas del Fémur/fisiopatología , Fémur/diagnóstico por imagen , Fémur/metabolismo , Células Madre Hematopoyéticas/metabolismo , Suspensión Trasera , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteómica , Factores de Tiempo , Microtomografía por Rayos X
13.
Therapie ; 69(2): 163-8, 2014.
Artículo en Francés | MEDLINE | ID: mdl-24926635

RESUMEN

Gefitinib and erlotinib are selective epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor. They are approved for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations of EGFR-TK. We report the case of a hepatitis cytolytic during gefitinib treatment with a positive rechallenge. A relay by erlotinib has been initiated and doesn't give recurrence of hepatotoxicity. From a literature review and this observation, arguments have been provided to justify erlotinib as a safe and well-tolered alternative for patients who have to stop gefitinib after a severe hepatotoxicity.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/efectos adversos , Quinazolinas/uso terapéutico , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adulto , Anciano , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Sustitución de Medicamentos , Clorhidrato de Erlotinib , Gefitinib , Humanos , Neoplasias Pulmonares/patología , Masculino
14.
Mol Genet Genomics ; 289(5): 795-806, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24752400

RESUMEN

PTP1B is an important negative regulator of insulin and other signaling pathways in mammals. However, the role of PTP1B in the regulation of RAS-MAPK signaling remains open to deliberation, due to conflicting evidence from different experimental systems. The Drosophila orthologue of mammalian PTP1B, PTP61F, has until recently remained largely uncharacterized. To establish the potential role of PTP61F in the regulation of signaling pathways in Drosophila and particularly to help resolve its fundamental function in RAS-MAPK signaling, we generated a new allele of Ptp61F as well as employed both RNA interference and overexpression alleles. Our results validate recent data showing that the activity of insulin and Abl kinase signaling is increased in Ptp61F mutants and RNA interference lines. Importantly, we establish negative regulation of the RAS/MAPK pathway by Ptp61F activity in whole animals. Of particular interest, our results document the modulation of hyperactive MAP kinase activity by Ptp61F alleles, showing that the phosphatase intervenes to directly or indirectly regulate MAP kinase itself.


Asunto(s)
Proteínas de Drosophila/fisiología , Drosophila melanogaster/enzimología , Sistema de Señalización de MAP Quinasas , Proteína Tirosina Fosfatasa no Receptora Tipo 1/fisiología , Proteínas Tirosina Fosfatasas no Receptoras/fisiología , Animales , Ojo Compuesto de los Artrópodos/enzimología , Ojo Compuesto de los Artrópodos/crecimiento & desarrollo , Drosophila melanogaster/crecimiento & desarrollo , Epistasis Genética , Receptores ErbB/metabolismo , Femenino , Estudios de Asociación Genética , Masculino , Datos de Secuencia Molecular , Alas de Animales/enzimología , Alas de Animales/crecimiento & desarrollo
15.
Rheumatology (Oxford) ; 50(9): 1603-11, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21525139

RESUMEN

OBJECTIVES: The efficacy of pharmacological interventions in sciatica is limited and the use of systemic steroids is still controversial. We aimed at evaluating the efficacy and tolerance of systemic steroids in sciatica. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane databases until February 2010. Randomized placebo-controlled trials evaluating the efficacy and the tolerance of systemic steroids in sciatica were included. Efficacy and tolerance were assessed using the relative risk (RR) and 95% CI with the inverse variance method (RR > 1 means that the event is more likely to occur in the steroid group). We explored the heterogeneity between the studies using subgroup analysis. RESULTS: Seven studies (383 patients) were included. The difference in the rate of responders between both groups was not statistically significant (RR = 1.22, 95% CI 0.96, 1.56). The rate of adverse events was 13.3% for the patients in the steroid group and 6.6% for the placebo group (RR = 2.01, 95% CI 1.06, 3.80). The number needed to harm was 20 (95% CI 10, ∞). Twenty (15.3%) patients in the steroid group and seven (5.7%) patients in the placebo group underwent surgery. A trend towards a higher requirement for spinal surgery was observed in the steroid group (RR = 1.14, 95% CI 0.74, 1.75). The methodological quality slightly influenced the results. We did not find any publication bias. CONCLUSION: Steroid efficacy is not superior to the placebo in sciatica, but it has more side effects. The tolerance : efficacy ratio indicates against the use of systemic steroids in sciatica.


Asunto(s)
Glucocorticoides/uso terapéutico , Ciática/tratamiento farmacológico , Adulto , Dexametasona/uso terapéutico , Femenino , Humanos , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Placebos/uso terapéutico , Prednisolona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ciática/cirugía , Resultado del Tratamiento
16.
Virus Res ; 149(2): 217-23, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20144904

RESUMEN

All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (CPEs). We show here that a fragment of the early 3'end comprising four of the five CPE-like regions when inserted downstream of a reporter gene confers regulation of the gene expression. A key protein involved in cytoplasmic polyadenylation is CPEB. We show that the human CPEB1 can repress the activity of the reporter construct containing the HPV-16 early sequences. This repression can be counteracted by a human cytoplasmic poly(A) polymerase, hGLD-2 fused to CPEB1. The hGLD-2/CPEB1 fusion protein facilitates furthermore poly(A) elongation of early HPV transcripts.


Asunto(s)
Regulación Viral de la Expresión Génica , Interacciones Huésped-Patógeno , Papillomavirus Humano 16/fisiología , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Transcripción Genética , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Regiones no Traducidas 3' , Fusión Artificial Génica , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Polinucleotido Adenililtransferasa , Factores de Transcripción/metabolismo
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