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1.
Anticancer Res ; 40(10): 5735-5738, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988899

RESUMO

BACKGROUND/AIM: Surgical staging is paramount to treatment of primary bone sarcomas. Often, bone scintigraphy and/or positron emission tomography-computed tomography (PET-CT) are used to exclude skeletal metastases; however, skeletal metastases in chondrosarcoma are rare. The purpose of this study was to assess the utility of these staging methods in patients with chondrosarcoma. PATIENTS AND METHODS: We reviewed 138 (87 males, 51 female) patients, mean age 54±20 years, with a chondrosarcoma, who had completed a bone scintigraphy or PET/CT as part of surgical staging. Sensitivity, specificity, and positive/negative predictive value of the scans was calculated. RESULTS: Seventeen (12%) patients had a positive bone scintigraphy or PET-CT for skeletal metastases. In cases of bone scintigraphy (n=11), 6 were benign and 5 were skeletal metastases. In cases of PET-CT, 6 were skeletal metastases, 3 were positive and 3 benign. All positive cases regarded dedifferentiated chondrosarcoma. The overall sensitivity and specificity of a bone scan or PET-CT was 100% and 93.1%; with a positive and negative predictive value of 47.1% and 100%, respectively. CONCLUSION: Skeletal metastases at presentation of chondrosarcoma are rare and associated with dedifferentiated chondrosarcoma. Bone scintigraphy or PET-CT should only be performed in cases of high grade and dedifferentiated histology.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Condrossarcoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Cintilografia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Condrossarcoma/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tomografia Computadorizada por Raios X
2.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32953088

RESUMO

Obesity and osteoporosis are both common conditions with high rates of morbidity and mortality. There is a relationship between obesity and bone. There are multiple factors that influence the risk of fracture, including the quality of bone, the risk of falls, and the padding around the bone. These multiple factors partly explain the finding that obesity protects against fractures in some sites while increasing the risk in other parts of the body. While it is well known that increased weight builds bone, there are several mechanisms related to the obese state that make the bone more fragile. These include the increased production of bone marrow fat cells at the expense of bone-forming osteoblasts, an increase in inflammatory cytokines leading to the activation of bone-resorbing osteoclasts, mutations in the FTO gene, and obesity-induced increased osteoblast senescence. Surprisingly, the relationship between bone and obesity is not unidirectional; there is now evidence that osteocytes are able to regulate body weight by acting as weighing machines.


Assuntos
Osso e Ossos/patologia , Obesidade/fisiopatologia , Osteoblastos/citologia , Osteoclastos/citologia , Osteócitos/citologia , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Senescência Celular , Humanos
3.
Int J Nanomedicine ; 15: 5825-5838, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821104

RESUMO

Background and Purpose: The extracellular matrix (ECM) derived from bone marrow mesenchymal stem cells (BMSCs) has been used in regenerative medicine because of its good biological activity; however, its poor mechanical properties limit its application in bone regeneration. The purpose of this study is to construct a three dimensional-printed hydroxyapatite (3D-HA)/BMSC-ECM composite scaffold that not only has biological activity but also sufficient mechanical strength and reasonably distributed spatial structure. Methods: A BMSC-ECM was first extracted and formed into micron-sized particles, and then the ECM particles were modified onto the surface of 3D-HA scaffolds using an innovative linking method to generate composite 3D-HA/BMSC-ECM scaffolds. The 3D-HA scaffolds were used as the control group. The basic properties, biocompatibility and osteogenesis ability of both scaffolds were tested in vitro. Finally, a critical skull defect rat model was created and the osteogenesis effect of the scaffolds was evaluated in vivo. Results: The compressive modulus of the composite scaffolds reached 9.45±0.32 MPa, which was similar to that of the 3D-HA scaffolds (p>0.05). The pore size of the two scaffolds was 305±47 um and 315±34 um (p>0.05), respectively. A CCK-8 assay indicated that the scaffolds did not have cytotoxicity. The composite scaffolds had good cell adhesion ability, with a cell adhesion rate of up to 76.00±6.17% after culturing for 7 hours, while that of the 3D-HA scaffolds was 51.85±4.77% (p<0.01). In addition, the composite scaffold displayed higher alkaline phosphatase (ALP) activity, osteogenesis-related mRNA expression, and calcium nodule formation, thus confirming that the composite scaffolds had good osteogenic activity. The composite scaffolds exhibited good bone repair in vivo and were superior to the 3D-HA scaffolds. Conclusion: We conclude that BMSC-ECM is a good osteogenic material and that the composite scaffolds have good osteogenic ability, which provides a new method and concept for the repair of bone defects.


Assuntos
Durapatita/farmacologia , Matriz Extracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Adesão Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Hidrodinâmica , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteogênese/efeitos dos fármacos , Osteogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
4.
J Med Life ; 13(2): 265-268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742524

RESUMO

Bone metastases in cholangiocarcinoma are uncommon. We report the case of a patient with disseminated osteolytic lesions who was admitted to the Neurology Department for progressive paraparesis. On the computed tomography examination, specific features for cholangiocarcinoma were described, confirmed later by the histopathological aspect of the bone lesions.


Assuntos
Neoplasias dos Ductos Biliares/complicações , Colangiocarcinoma/complicações , Osteólise/complicações , Paraparesia/complicações , Neoplasias dos Ductos Biliares/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Colangiocarcinoma/patologia , Humanos , Masculino , Osteólise/diagnóstico por imagem , Paraparesia/diagnóstico por imagem , Tomografia Computadorizada por Raios X
5.
PLoS One ; 15(7): e0236105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726345

RESUMO

Ancient organic remains are essential for the reconstruction of past human lifeways and environments but are only preserved under particular conditions. Recent findings indicate that such conditions are becoming rarer and that archaeological sites with previously good preservation, are deteriorating. To investigate this, we returned to the well-known Swedish Mesolithic site Ageröd I. Here we present the result of the re-excavation and the osteological analyses of the bone remains from the 1940s, 1970s and 2019 excavation campaigns of the site, to document and quantify changes in bone preservation and relate them to variations in soil conditions and on-site topography. The results indicate that the bone material has suffered from accelerated deterioration during the last 75 years. This has led to heavily degraded remains in some areas and complete destruction in others. We conclude that while Ageröd can still be considered an important site, it has lost much of the properties that made it unique. If no actions are taken to secure its future preservation, the site will soon lose the organic remains that before modern encroachment and climate change had been preserved for 9000 years. Finally, because Ageröd has not been subjected to more or heavier encroachment than most other archaeological sites, our results also raise questions of the state of organic preservation in other areas and call for a broad examination of our most vulnerable hidden archaeological remains.


Assuntos
Arqueologia , Osso e Ossos/patologia , Mudança Climática , Atividades Humanas/estatística & dados numéricos , Preservação Biológica/métodos , Humanos
6.
PLoS One ; 15(7): e0236891, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730332

RESUMO

Signal Transducer and Activator of Transcription 3 (STAT3) has recently been shown to be involved in bone development and has been implicated in bone diseases, such as Job's Syndrome. Bone growth and changes have been known for many years to differ between sexes with male bones tending to have higher bone mass than female bones and older females tending to lose bone mass at faster rates than older males. Previous studies using conditional knock mice with Stat3 specifically deleted from the osteoblasts showed both sexes exhibited decreased bone mineral density (BMD) and strength. Using the Cre-Lox system with Cathepsin K promotor driving Cre to target the deletion of the Stat3 gene in mature osteoclasts (STAT3-cKO mice), we observed that 8-week old STAT3-cKO female femurs exhibited significantly lower BMD and bone mineral content (BMC) compared to littermate control (CN) females. There were no differences in BMD and BMC observed between male knock-out and male CN femurs. However, micro-computed tomography (µCT) analysis showed that both male and female STAT3-cKO mice had significant decreases in bone volume/tissue volume (BV/TV). Bone histomorphometry analysis of the distal femur, further revealed a decrease in bone formation rate and mineralizing surface/bone surface (MS/BS) with a significant decrease in osteoclast surface in female, but not male, STAT3-cKO mice. Profiling gene expression in an osteoclastic cell line with a knockdown of STAT3 showed an upregulation of a number of genes that are directly regulated by estrogen receptors. These data collectively suggest that regulation of STAT3 differs in male and female osteoclasts and that inactivation of STAT3 in osteoclasts affects bone turnover more in females than males, demonstrating the complicated nature of STAT3 signaling pathways in osteoclastogenesis. Drugs targeting the STAT3 pathway may be used for treatment of diseases such as Job's Syndrome and osteoporosis.


Assuntos
Reabsorção Óssea/patologia , Osso e Ossos/patologia , Osteoclastos/patologia , Osteogênese , Osteoporose/patologia , Fator de Transcrição STAT3/fisiologia , Animais , Densidade Óssea , Remodelação Óssea , Reabsorção Óssea/etiologia , Osso e Ossos/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/metabolismo , Osteoporose/etiologia
7.
Medicine (Baltimore) ; 99(27): e21102, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629743

RESUMO

RATIONALE: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease without standard treatments. Tripterygium wilfordii hook f (TwHF) is a traditional Chinese herb with anti-inflammatory effect, and 1.0 mg/(kg·d) dose of Tripterygium glycosides has been reported to significantly improve the disease activity of a SAPHO patient in a case report. However, the optimal dose of TwHF is still unclear. Here, we report the first case of SAPHO patient who achieved rapid remission in clinical symptoms after receiving 1.5 mg/(kg·d) dose of Tripterygium glycosides treatment. PATIENT CONCERNS: A 67-year-old woman noted palmoplantar pustulosis and pain in the anterior chest wall and waist. Bone scintigraphy demonstrated the typical tracer accumulation feature and magnetic resonance images showed bone marrow edema in lumbosacral vertebra. DIAGNOSES: The diagnosis was made by dermatological and osteoarticular manifestations and classical signs in bone scintigraphy in accordance with the diagnostic criteria proposed in 2012. INTERVENTIONS: Tripterygium glycosides was given with a primary dose of 1.5 mg/(kg·d) for 1 month and then reduced at a rate of 10 mg every 2 weeks until 1.0 mg/(kg·d) for a long-term maintenance. OUTCOMES: Fast-induced remission on clinical manifestations was achieved and magnetic resonance imaging abnormality was improved significantly. Additionally, no apparent side effects were observed. LESSONS: 1.5 mg/(kg·d) dose of Tripterygium glycosides seems to have fast-induced remission than 1.0 mg/(kg·d) with reliable safety. Besides, Tripterygium glycosides may also have a pharmacological effect of inhibiting osteolysis and enhancing bone strength.


Assuntos
Síndrome de Hiperostose Adquirida/tratamento farmacológico , Osso e Ossos/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Síndrome de Hiperostose Adquirida/patologia , Idoso , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Glicosídeos/administração & dosagem , Humanos , Região Lombossacral/diagnóstico por imagem , Região Lombossacral/patologia , Imagem por Ressonância Magnética/métodos , Osteólise/prevenção & controle , Psoríase/etiologia , Cintilografia/métodos , Indução de Remissão , Resultado do Tratamento , Tripterygium
8.
PLoS One ; 15(7): e0234927, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678818

RESUMO

Bone is one of the most common sites of metastasis from advanced solid tumors. Bone metastasis is a leading cause of pain and increases the risk of skeletal-related events (SREs) in cancer patients. In addition to affecting the quality of life, it also increases the medical costs and mortality risk. We aimed to examine the occurrence of bone metastasis and SREs in Korean cancer patients using a nationwide health database. Using claims data from the National Health Insurance Service-National Sample Cohort (2002-2013), we extracted the data of bone metastasis patients diagnosed with any of the seven major cancers in Korea from January 2002 to December 2010. Selected SREs included pathologic fracture, spinal cord compression, radiation therapy, and palliative bone surgery. We used time-to-event analysis to estimate patient survival after bone metastasis. A total of 21,562 newly diagnosed cancer patients were identified; bone metastases developed in 1,849 patients (breast cancer, 18.8%; prostate cancer, 17.5%; lung cancer, 13.7%). The median time from primary cancer diagnosis to bone metastasis was 18.9 months. The cumulative incidence of SREs was 45.1% in all bone metastasis patients. The most common cancer type was lung cancer (53.4%), followed by liver (50.9%), prostate (45.9%), breast (43.6%), and colorectal (40.2%) cancers. Almost all SREs developed 1 month after bone metastasis, except in patients with breast and prostate cancers (median: 5.9 months in breast cancer and 4.7 months in prostate cancer). Survival duration after the development of bone metastasis was < 6 months in stomach, liver, colorectal, and lung cancer patients. Breast and prostate cancer patients survived for > 1 year after the occurrence of SREs. This study reveals the epidemiology of bone metastasis and SREs in Korean cancer patients, and the findings can be used to assess the actual bone health status of cancer patients.


Assuntos
Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Neoplasias/epidemiologia , Adulto , Idoso , Osso e Ossos/patologia , Neoplasias da Mama/patologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Custos de Cuidados de Saúde , Humanos , Incidência , Seguro Saúde , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Neoplasias/patologia , Neoplasias da Próstata/patologia , Qualidade de Vida , República da Coreia/epidemiologia
10.
Cancer Immunol Immunother ; 69(9): 1905-1916, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32377818

RESUMO

Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results were correlated with clinicopathological characteristics. PD-L1 expression was observed in 13/46 (28.3%) GCTB (and in 1/24, 4.2%, control ABC, only) and associated with a shorter disease free interval according to univariate analysis. Moreover, in PD-L1-positive lesions, three genes (CD27, CD6 and IL10) were significantly upregulated (p < 0.01), while two were downregulated (LCK and TLR8, showing borderline significance, p = 0.06). Interestingly, these genes can be related to maturation and immune tolerance of bone tissue microenvironment, suggesting a more immature/anergic phenotype of giant cell tumors. Our findings suggest that PD-L1 immunoreactivity may help to select GCTB patients with a higher risk of recurrence who could potentially benefit from immune checkpoint blockade.


Assuntos
Antígeno B7-H1/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/imunologia , Tumores de Células Gigantes/genética , Tumores de Células Gigantes/imunologia , Transcriptoma/imunologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Regulação para Baixo/genética , Feminino , Tumores de Células Gigantes/patologia , Humanos , Tolerância Imunológica/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Regulação para Cima/genética , Adulto Jovem
11.
Proc Natl Acad Sci U S A ; 117(22): 12029-12040, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32404427

RESUMO

Hutchinson-Gilford progeria syndrome (HGPS) is a uniformly fatal condition that is especially prevalent in skin, cardiovascular, and musculoskeletal systems. A wide gap exists between our knowledge of the disease and a promising treatment or cure. The aim of this study was to first characterize the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and to determine the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. Microcomputed tomography and CT-based rigidity analyses were performed to assess cortical and trabecular bone structure, density, and rigidity. Bones were loaded to failure with three-point bending to assess strength. Contrast-enhanced µCT imaging of mouse femurs was performed to measure glycosaminoglycan content, thickness, and volume of the femoral head articular cartilage. Advanced glycation end products were assessed with a fluorometric assay. The changes demonstrated in the cortical bone structure, rigidity, stiffness, and modulus of the HGPS G608G mouse model may increase the risk for bending and deformation, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this HGPS model resemble changes observed in the age-matched WT controls, including early loss of glycosaminoglycans, and decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases in the elderly. Lonafarnib monotherapy did not improve bone or cartilage parameters, but treatment combinations with pravastatin and zoledronic acid significantly improved bone structure and mechanical properties and cartilage structural parameters, which ameliorate the musculoskeletal phenotype of the disease.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Modelos Animais de Doenças , Lamina Tipo A/genética , Progéria , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Glicosaminoglicanos/análise , Articulações/efeitos dos fármacos , Articulações/patologia , Lamina Tipo A/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Fenótipo , Piperidinas/uso terapêutico , Pravastatina/uso terapêutico , Progéria/tratamento farmacológico , Progéria/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Piridinas/uso terapêutico , Microtomografia por Raio-X , Ácido Zoledrônico/uso terapêutico
12.
J Bone Miner Metab ; 38(5): 607-619, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32415376

RESUMO

Diabetes mellitus (DM) is related to impaired bone healing and an increased risk of bone fractures. While it is recognized that osteogenic differentiation and the function of osteoblasts are suppressed in DM, the influence of DM on osteoclasts is still unclear. Hyperglycemia and inflammatory environment are the hallmark of DM that causes dysregulation of various pro-inflammatory cytokines and alternated gene expression in periodontal ligament cells, osteoblasts, osteocytes, osteoclasts, and osteoclast precursors. A methodological review on conceptual and practical implications of in vitro study models is used for DM simulation on bone cells. Several major databases were screened to find literature related to the study objective. Published literature within last 20 years that used in vitro DM-simulated models to study how DM affects the cellular behavior of bone cells were selected for this review. Studies utilizing high glucose and serum acquired from diabetic animals are the mainly used methods to simulate the diabetic condition. The combination with various simulating factors such as lipopolysaccharide (LPS), hydrogen peroxide (H2O2), and advanced glycation end products (AGEs) have been reported in diabetic situations in vitro, as well. Through screening procedure, it was evident DM-simulated conditions exerted negative impact on bone-related cells. However, inconsistent results were found among different reported studies, which could be due to variation in culture conditions, concentrations of the stimulating factors and cell lineage, etc. This manuscript has concisely reviewed currently existing DM-simulated in vitro models and provides valuable insights of detailed components in simulating DM conditions in vitro. Studies using DM-simulated microenvironment revealed that in vitro simulation negatively impacted periodontal ligament cells, osteoblasts, osteocytes, osteoclasts, and osteoclast precursors. Contrarily, studies also indicated beneficial influence on bone-related cells when such conditions are reversed.


Assuntos
Osso e Ossos/patologia , Diabetes Mellitus/patologia , Modelos Biológicos , Animais , Diabetes Mellitus/sangue , Humanos , Hiperglicemia/patologia , Osteoclastos/metabolismo , Osteócitos/patologia
13.
Clin Imaging ; 65: 5-7, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32344289

RESUMO

Osteochondromas, the most common benign bone tumor, are typically asymptomatic and discovered incidentally by imaging. Most frequently, osteochondromas occur at the metaphyses of long bones, and rarely involve the head and neck. We report the first case of a symptomatic osteochondroma of the temporal styloid process causing facial nerve paralysis.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Osteocondroma/diagnóstico por imagem , Osso Temporal/diagnóstico por imagem , Adulto , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Cabeça/patologia , Humanos , Masculino , Pescoço/patologia , Osteocondroma/patologia , Neoplasias de Tecidos Moles , Osso Temporal/patologia
14.
Clin Nucl Med ; 45(6): e294-e295, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32332310

RESUMO

Pancreatic disease can be associated with polyarthritis and panniculitis in a small number of patients, and this triad constitutes PPP syndrome. Early diagnosis is critical as it has high morbidity and mortality. Panniculitis can occur in fat present anywhere in the body. Involvement of fat in bone marrow is relatively uncommon, and radiologic imaging shows osteolytic lesions involving long bones. Here we present a case of acute pancreatitis, referred to our department for evaluation of severe joint pain and multiple bone pain. Tc-MDP scan with SPECT/CT has been done, which showed medullary expansion with heterogenous tracer uptake, that is, moth-eaten appearance.


Assuntos
Osso e Ossos/patologia , Necrose Gordurosa/complicações , Necrose Gordurosa/diagnóstico por imagem , Pancreatite/complicações , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Medronato de Tecnécio Tc 99m , Doença Aguda , Osso e Ossos/diagnóstico por imagem , Humanos , Masculino , Dor/complicações
15.
BMC Med Genet ; 21(1): 64, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228492

RESUMO

BACKGROUND: The calcium-selective channel TRPV6 (transient receptor potential cation channel subfamily V member 6) is crucial for maternal-fetal calcium transport across the placenta. TRPV6 mutations have recently been associated with an antenatally severe under-mineralising skeletal dysplasia accompanied by postnatal biochemical abnormalities. This is the first post-mortem report in a patient with TRPV6 skeletal dysplasia. CASE PRESENTATION: The female infant had severe antenatal and postnatal skeletal abnormalities by 20 weeks gestation and was ventilator-dependent from birth. These skeletal abnormalities were apparent at an earlier gestational age than in previous reported cases and a more severe clinical course ensued. Biochemical and skeletal abnormalities, including bone density, improved postnatally but cardiac arrest at 4 months of age led to withdrawal of intensive care. Compound heterozygous TRPV6 variants (c.1978G > C p.(Gly660Arg) and c.1528C > T p.(Arg510Ter)) were identified on exome sequencing. Post-mortem identified skeletal abnormalities but no specific abnormalities in other organ systems. No placental pathology was found, multi-organ histological features reflected prolonged intensive care only. Post-mortem macroscopic examination indicated reduced thoracic size and short, pale and pliable ribs. Histological examination identified reduced number of trabeculae in the diaphyses (away from the growth plates), whereas metaphyses showed adequate mineralisation and normal number of trabeculae, but with slightly enlarged reactive chondrocytes, indicating post-natal skeletal growth recovery. Post-mortem radiological findings demonstrated improved bone density, improved rib width, healed fractures, although ribs were still shorter than normal. Long bones (especially humerus and femur) had improved from initial poorly defined metaphyses and reduced bone density to sharply defined metaphyses, prominent growth restart lines in distal diaphyses and bone-in-bone appearance along diaphyses. CONCLUSIONS: This case provide bone histological confirmation that human skeletal development is compromised in the presence of TRPV6 pathogenic variants. Post-mortem findings were consistent with abnormal in utero skeletal mineralisation due to severe calcium deficit from compromised placental calcium transfer, followed by subsequent phenotypic improvement with adequate postnatal calcium availability. Significant skeletal recovery occurs in the early weeks of postnatal life in TRPV6 skeletal dysplasia.


Assuntos
Desenvolvimento Ósseo , Osso e Ossos/patologia , Canais de Cálcio/genética , Desenvolvimento Infantil/fisiologia , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Canais de Cátion TRPV/genética , Autopsia , Desenvolvimento Ósseo/genética , Osso e Ossos/anormalidades , Calcificação Fisiológica/genética , Cálcio/metabolismo , Canais de Cálcio/análise , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Osteocondrodisplasias/reabilitação , Parto/fisiologia , Canais de Cátion TRPV/análise
16.
Am J Surg Pathol ; 44(5): 633-640, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32294062

RESUMO

Abnormal accumulation of neutrophils in a subarticular bone usually raises the concern for osteomyelitis or septic arthritis, a disabling and potentially life-threatening medical condition. At the pathology department of a specialized orthopedic institute, we observed a distinct pattern of subarticular inflammation mimicking infection characterized by collections of neutrophils, macrophages, and fibrin in pseudocystic spaces of variable size and extent in the superficial subarticular bone not accompanied by granulation tissue or necrosis. We coined the term "inflammatory pseudoabscess" to describe these accumulations. From 1997-2015, we reported inflammatory pseudoabscesses in 157 primary arthroplasty/osteotomy specimens from 143 patients without penetrating trauma or hardware in the affected joint. The predominant gross and histologic features were those of destructive/inflammatory joint disease, including lymphoplasmacytic synovitis (95.3%), subchondral osseous chronic inflammation (80.3%), exudative synovitis (58.0%), synovial pannus (52.0%), and marginal erosions of articular cartilage and/or subarticular bone (43.3%). Clinical information was available in 137 (95.8%) patients, 107 (overall: 74.8%) of whom had preoperatively or postoperatively diagnosed inflammatory arthropathy, most commonly rheumatoid arthritis. The remaining 30 (overall: 21.0%) patients had no documented inflammatory disorders, but some had bilateral or multijoint arthropathy, hands/feet involvement, lymphoplasmacytic synovitis, ulcerative colitis, or family history of inflammatory arthropathy. There was no documented infection-associated implant failure. We believe that inflammatory pseudoabscess represents an intraosseous manifestation of noninfectious inflammatory disorders of joints. This feature should be recognized by pathologists and used to suggest further clinical evaluation for undiagnosed inflammatory joint diseases.


Assuntos
Abscesso/patologia , Osso e Ossos/patologia , Articulações/patologia , Neutrófilos/patologia , Sinovite/patologia , Abscesso/imunologia , Abscesso/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Artrite Reumatoide/cirurgia , Biópsia , Osso e Ossos/imunologia , Osso e Ossos/cirurgia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Articulações/imunologia , Articulações/cirurgia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sinovite/imunologia , Sinovite/cirurgia , Adulto Jovem
17.
Breast Cancer Res ; 22(1): 34, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272947

RESUMO

BACKGROUND: Osteoclast activation is a hallmark of breast cancer-induced bone disease while little is known about the role of osteoblasts in this process. Recently, we identified the homeodomain protein TG-interacting factor-1 (Tgif1) as a crucial regulator of osteoblast function. In this study, we demonstrate that lack of Tgif1 also restricts the progression of breast cancer bone metastases. METHODS: Transwell migration assays were used to investigate the osteoblast-breast cancer cell interaction in vitro. Molecular analyses included RNA sequencing, immunoblotting, and qRT-PCR. To determine the role of Tgif1 in metastatic bone disease, 4T1 breast cancer cells were injected intracardially into mice with a germ line deletion of Tgif1 (Tgif1-/-) or control littermates (Tgif1+/+). Progression of bone metastases and alterations in the bone microenvironment were assessed using bioluminescence imaging, immunofluorescence staining, confocal microscopy, and histomorphometry. RESULTS: Medium conditioned by osteoblasts stimulated breast cancer cell migration, indicating a potential role of osteoblasts during bone metastasis progression. Tgif1 expression was strongly increased in osteoblasts upon stimulation by breast cancer cells, demonstrating the implication of Tgif1 in the osteoblast-breast cancer cell interaction. Indeed, conditioned medium from osteoblasts of Tgif1-/- mice failed to induce breast cancer cell migration compared to control, suggesting that Tgif1 in osteoblasts augments cancer cell motility. Semaphorin 3E (Sema3E), which is abundantly secreted by Tgif1-/- osteoblasts, dose-dependently reduced breast cancer cell migration while silencing of Sema3E expression in Tgif1-/- osteoblasts partially restored the impaired migration. In vivo, we observed a decreased number of breast cancer bone metastases in Tgif1-/- mice compared to control littermates. Consistently, the presence of single breast cancer cells or micro-metastases in the tibiae was reduced in Tgif1-/- mice. Breast cancer cells localized in close proximity to Endomucin-positive vascular cells as well as to osteoblasts. Although Tgif1 deficiency did not affect the bone marrow vasculature, the number and activity of osteoblasts were reduced compared to control. This suggests that the protective effect on bone metastases might be mediated by osteoblasts rather than by the bone marrow vasculature. CONCLUSION: We propose that the lack of Tgif1 in osteoblasts increases Sema3E expression and attenuates breast cancer cell migration as well as metastases formation.


Assuntos
Neoplasias Ósseas/prevenção & controle , Osso e Ossos/patologia , Neoplasias da Mama/prevenção & controle , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/fisiologia , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/fisiologia , Semaforinas/genética , Microambiente Tumoral , Animais , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Osso e Ossos/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo , Osteoblastos/patologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
18.
Immunol Med ; 43(3): 103-106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32301686

RESUMO

Bone is one of the most common distant organs in which tumor cells tend to metastasize depending on complicated immune system and bone microenvironments. Clinical symptoms such as severe pain and bone fractures associated with bone metastases severely affect patients' quality of life. According to the pathological types of bone destruction caused by the biological characteristics of different primary cancer cells, bone metastases are classified as osteolytic, osteoblastic and mixed types. Herein, we discuss the molecular mechanisms of bone metastasis and the therapeutic strategy with focus on bone metabolism.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osso e Ossos/metabolismo , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Microambiente Tumoral , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Humanos , Terapia de Alvo Molecular , Osteoblastos/patologia , Osteólise , Qualidade de Vida
19.
Comput Methods Biomech Biomed Engin ; 23(9): 518-523, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32213103

RESUMO

Gradual screw loosening is a well-known failure mechanism in internal fixation. Loosening is primarily due to progressive bone loss caused by stress shielding, a phenomenon in which a medical device absorbs a disproportionate amount of load within the screw-bone construct. The proximity of elastic moduli of magnesium and bone presents the potential for alleviating screw loosening by allowing optimum stress to be transferred between screw and bone, and in turn, supporting bone remodeling around the screw. In this study, the effect of thread profile on stress transfer in a magnesium fixation was simulated using a 2-D finite element model. Modified stress parameters from a previous study were used to estimate stress transfer across three thread profiles. Results showed highest stress transfer in trapezoidal-shaped magnesium screw thread. In accordance, this study corroborates the potential for magnesium as an ultimate screw material to eliminate progressive screw loosening.


Assuntos
Parafusos Ósseos , Osso e Ossos/patologia , Análise de Elementos Finitos , Estresse Mecânico , Fenômenos Biomecânicos , Módulo de Elasticidade , Humanos
20.
J Bone Miner Metab ; 38(4): 501-510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140785

RESUMO

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Minerais/metabolismo , Ácido Risedrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nefrectomia , Fragmentos de Peptídeos/sangue , Fósforo/sangue , Pró-Colágeno/sangue , Ratos Sprague-Dawley , Ácido Risedrônico/farmacologia
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