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2.
J Dual Diagn ; 20(2): 122-131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38408374

RESUMO

OBJECTIVE: Evidence suggests that pain intensity may be indirectly linked to hazardous drinking and PTSD symptom severity via pain-related anxiety. The goal of this analysis was to test the hypotheses in a population with PTSD symptoms that pain intensity would be positively and indirectly associated with hazardous drinking, alcohol dependence, alcohol-related problems, and PTSD symptom severity via pain-related anxiety. METHODS: Heavy drinkers with probable PTSD were recruited via Qualtrics panels (N = 371, 53% Female, Mage = 39.68, SD = 10.86). Linear regression and conditional process models were conducted to examine indirect associations between pain intensity and primary outcomes via pain-related anxiety. RESULTS: Pain intensity was found to be indirectly associated with hazardous drinking, alcohol dependence, alcohol-related problems, and PTSD symptom severity via greater pain-related anxiety. CONCLUSION: These initial findings suggest that pain-related anxiety may play an important role in relations between the experience of pain and hazardous patterns of alcohol consumption among individuals with probable PTSD. Future research is needed to determine the temporal nature of these associations and to examine the potential utility of treatments that address pain-related anxiety in the context of comorbid pain, PTSD, and hazardous drinking.


Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Adulto , Masculino , Alcoolismo/complicações , Alcoolismo/epidemiologia , Medição da Dor , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Ansiedade/complicações , Ansiedade/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Dor/complicações , Dor/epidemiologia , Transtornos Relacionados ao Uso de Álcool/complicações
3.
J Cancer Res Clin Oncol ; 149(19): 17511-17527, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37906352

RESUMO

PURPOSE: Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. METHODS: A prospective case-control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. RESULTS: Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP. CONCLUSION: Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined.


Assuntos
Neoplasias , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Caquexia/diagnóstico , Caquexia/etiologia , Força da Mão , Neoplasias/patologia , Biomarcadores , Músculo Esquelético/patologia , Proteína C-Reativa/análise , Hemoglobinas
4.
Spine Deform ; 11(3): 545-558, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36454530

RESUMO

PURPOSE: To create an updated and comprehensive overview of the modeling studies that have been done to understand the mechanics underlying deformities of adolescent idiopathic scoliosis (AIS), to predict the risk of curve progression and thereby substantiate etiopathogenetic theories. METHODS: In this systematic review, an online search in Scopus and PubMed together with an analysis in secondary references was done, which yielded 86 studies. The modeling types were extracted and the studies were categorized accordingly. RESULTS: Animal modeling, together with machine learning modeling, forms the category of black box models. This category is perceived as the most clinically relevant. While animal models provide a tangible idea of the biomechanical effects in scoliotic deformities, machine learning modeling was found to be the best curve-progression predictor. The second category, that of artificial models, has, just as animal modeling, a tangible model as a result, but focusses more on the biomechanical process of the scoliotic deformity. The third category is formed by computational models, which are very popular in etiopathogenetic parameter-based studies. They are also the best in calculating stresses and strains on vertebrae, intervertebral discs, and other surrounding tissues. CONCLUSION: This study presents a comprehensive overview of the current modeling techniques to understand the mechanics of the scoliotic deformities, predict the risk of curve progression in AIS and thereby substantiate etiopathogenetic theories. Although AIS remains to be seen as a complex and multifactorial problem, the progression of its deformity can be predicted with good accuracy. Modeling of AIS develops rapidly and may lead to the identification of risk factors and mitigation strategies in the near future. The overview presented provides a basis to follow this development.


Assuntos
Disco Intervertebral , Cifose , Escoliose , Humanos , Escoliose/patologia , Vértebras Torácicas/patologia , Disco Intervertebral/patologia
6.
Eur Cell Mater ; 40: 21-37, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32672345

RESUMO

Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration. Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression. Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1ß, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.


Assuntos
Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Técnicas de Cultura de Tecidos , Animais , Fenômenos Biomecânicos , Condroitinases e Condroitina Liases/metabolismo , Colagenases/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Cabras , Disco Intervertebral/fisiopatologia , Degeneração do Disco Intervertebral/fisiopatologia , Fatores de Tempo
7.
HIV Med ; 20(10): 704-708, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31454139

RESUMO

OBJECTIVES: The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home-based HIV counselling and testing (HBHCT) and telephone-facilitated support for linkage in rural South Africa. METHODS: A population-based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public-sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan-Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART. RESULTS: Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART. CONCLUSIONS: Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Aconselhamento/métodos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta/estatística & dados numéricos , População Rural/estatística & dados numéricos , África do Sul , Adulto Jovem
8.
Osteoarthritis Cartilage ; 26(10): 1400-1408, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29935308

RESUMO

OBJECTIVE: Mechanical overloading induces a degenerative cell response in the intervertebral disc. However, early changes in the extracellular matrix (ECM) are challenging to assess with conventional techniques. Fourier Transform Infrared (FTIR) imaging allows visualization and quantification of the ECM. We aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity. DESIGN: Three experiments were conducted; Exp 1.: In vivo, lumbar spines of seven goats were operated: one disc was injected with chondroitinase ABC [cABC (mild degeneration)] and compared to the adjacent disc (control) after 24 weeks. Exp 2a: Ex vivo, caprine discs received physiological loading (n = 10) or overloading (n = 10) in a bioreactor. Exp 2b: Cell activity was diminished prior to testing by freeze-thaw cycles, 18 discs were then tested as in Exp 2a. In all experiments, FTIR images (spectral region: 1000-1300 cm-1) of mid-sagittal slices were analyzed using multivariate curve resolution. RESULTS: In vivo, FTIR was more sensitive than biochemical and histological analysis in identifying reduced proteoglycan content (P = 0.046) and increased collagen content in degenerated discs (P < 0.01). Notably, FTIR analysis additionally showed disorganization of the ECM, indicated by increased collagen entropy (P = 0.011). Ex vivo, the proteoglycan/collagen ratio decreased due to overloading (P = 0.047) and collagen entropy increased (P = 0.047). Cell activity affected collagen content only (P = 0.044). CONCLUSION: FTIR imaging allows a more detailed investigation of early disc degeneration than traditional measures. Changes due to mild overloading could be assessed and quantified. Matrix remodeling is the first detectable step towards intervertebral disc degeneration.


Assuntos
Colágeno/metabolismo , Matriz Extracelular/metabolismo , Degeneração do Disco Intervertebral/diagnóstico , Disco Intervertebral/metabolismo , Vértebras Lombares/diagnóstico por imagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Modelos Animais de Doenças , Cabras , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo
9.
J Periodontal Res ; 52(6): 965-974, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28635007

RESUMO

The periodontal ligament (PDL) connects the tooth root and alveolar bone. It is an aligned fibrous network that is interposed between, and anchored to, both mineralized surfaces. Periodontal disease is common and reduces the ability of the PDL to act as a shock absorber, a barrier for pathogens and a sensor of mastication. Although disease progression can be stopped, current therapies do not primarily focus on tissue regeneration. Functional regeneration of PDL may be achieved using innovative techniques, such as tissue engineering. However, the complex fibrillar architecture of the PDL, essential to withstand high forces, makes PDL tissue engineering very challenging. This challenge may be met by studying PDL anatomy and development. Understanding PDL anatomy, development and maintenance provides clues regarding the specific events that need to be mimicked for the formation of this intricate tissue. Owing to the specific composition of the PDL, which develops by self-organization, a different approach than the typical combination of biomaterials, growth factors and regenerative cells is necessary for functional PDL engineering. Most specifically, the architecture of the new PDL to be formed does not need to be dictated by textured biomaterials but can emerge from the local mechanical loading conditions. Elastic hydrogels are optimal to fill the space properly between tooth and bone, may house cells and growth factors to enhance regeneration and allow self-optimization by the alignment to local stresses. We suggest that cells and materials should be placed in a proper mechanical environment to initiate a process of self-organization resulting in a functional architecture of the PDL.


Assuntos
Regeneração Tecidual Guiada Periodontal , Ligamento Periodontal/anatomia & histologia , Processo Alveolar/anatomia & histologia , Animais , Regeneração Tecidual Guiada Periodontal/métodos , Humanos , Odontogênese , Ligamento Periodontal/crescimento & desenvolvimento , Ligamento Periodontal/ultraestrutura , Raiz Dentária/anatomia & histologia
10.
Ann Oncol ; 28(6): 1268-1273, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28327932

RESUMO

BACKGROUND: Rolapitant, a long-acting neurokinin (NK)1 receptor antagonist (RA), has demonstrated efficacy in prevention of chemotherapy-induced nausea and vomiting in patients administered moderately or highly emetogenic chemotherapy. Unlike other NK1 RAs, rolapitant does not inhibit or induce cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined adverse events (AEs) by use versus non-use of drug substrates of CYP2D6 or BCRP. PATIENTS AND METHODS: Patients were randomized to receive either 180 mg oral rolapitant or placebo ∼1-2 h before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data for treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. RESULTS: In the integrated safety population, 828 of 1294 patients (64%) in the rolapitant group and 840 of 1301 patients (65%) in the control group experienced at least one TEAE. Frequencies of common TEAEs were similar in the rolapitant and control populations. Overall, 53% of patients received CYP2D6 substrate drugs, none of which had a narrow therapeutic index (like thioridazine or pimozide), and 63% received BCRP substrate drugs. When grouped by concomitant use versus non-use of CYP2D6 or BCRP substrate drugs, TEAEs and TESAEs occurred with similar frequency in the rolapitant and control populations. CONCLUSIONS: The results of this study support the safety of rolapitant as part of an antiemetic triple-drug regimen in patients receiving emetogenic chemotherapy, including those administered concomitant medications that are substrates of CYP2D6 or BCRP, such as ondansetron, docetaxel, or irinotecan.


Assuntos
Citocromo P-450 CYP2D6/efeitos dos fármacos , Compostos de Espiro/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Vet J ; 220: 17-23, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28190488

RESUMO

Degenerative lumbosacral stenosis is a common disease in dogs characterised by intervertebral disc herniation, loss of disc height and stenosis. Decompressive dorsal laminectomy and partial discectomy can cause spinal instability and worsen foraminal stenosis. Pedicle screw and rod fixation (PSRF) with an intervertebral body cage allows for distraction and restoration of disc height and restores foraminal apertures. The aim of this study was to evaluate the ex vivo biomechanical properties of a titanium intervertebral cage alone and in combination with PSRF in the lumbosacral spine of dogs. The range of motion, neutral zone, neutral zone stiffness and elastic zone stiffness of the lumbosacral joint (L7-S1) of nine canine cadavers were determined in flexion/extension, lateral bending and axial rotation for four conditions: (1) native (unmodified) spine; (2) dorsal laminectomy and discectomy; (3) stand-alone cage; and (4) cage in combination with PSRF. The intervertebral disc height decreased after dorsal laminectomy, but increased after insertion of the cage. Insertion of the stand-alone cage decreased the range of motion and neutral zone compared to the laminectomy-discectomy and increased neutral zone stiffness in all directions. The range of motion further decreased after PSRF. From a biomechanical point of view, the use of a stand-alone intervertebral cage is a potential alternative to dorsal fixation of the lumbosacral junction, since it increases spinal stability and restores disc height.


Assuntos
Discotomia/veterinária , Cães/fisiologia , Cães/cirurgia , Laminectomia/veterinária , Região Lombossacral/cirurgia , Parafusos Pediculares/veterinária , Titânio/uso terapêutico , Animais , Fenômenos Biomecânicos , Cadáver , Disco Intervertebral/cirurgia , Amplitude de Movimento Articular
12.
Osteoarthritis Cartilage ; 24(7): 1292-301, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26828357

RESUMO

OBJECTIVE: The Temporomandibular Joint (TMJ) disc is a fibrocartilaginous structure located between the mandibular condyle and the temporal bone, facilitating smooth movements of the jaw. The load-bearing properties of its anisotropic collagenous network have been well characterized under tensile loading conditions. However, recently it has also been speculated that the collagen fibers may contribute dominantly in reinforcing the disc under compression. Therefore, in this study, the structural-functional role of collagen fibers in mechanical compressive properties of TMJ disc was investigated. DESIGN: Intact porcine TMJ discs were enzymatically digested with collagenase to disrupt the collagenous network of the cartilage. The digested and non-digested articular discs were analyzed mechanically, biochemically and histologically in five various regions. These tests included: (1) cyclic compression tests, (2) biochemical quantification of collagen and glycosaminoglycan (GAG) content and (3) visualization of collagen fibers' alignment by polarized light microscopy (PLM). RESULTS: The instantaneous compressive moduli of the articular discs were reduced by as much as 50-90% depending on the region after the collagenase treatment. The energy dissipation properties of the digested discs showed a similar tendency. Biochemical analysis of the digested samples demonstrated an average of 14% and 35% loss in collagen and GAG, respectively. Despite the low reduction of collagen content the PLM images showed considerable perturbation of the collagenous network of the TMJ disc. CONCLUSIONS: The results indicated that even mild disruption of collagen fibers can lead to substantial mechanical softening of TMJ disc undermining its reinforcement and mechanical stability under compression.


Assuntos
Estresse Mecânico , Disco da Articulação Temporomandibular , Animais , Colágeno , Glicosaminoglicanos , Suínos , Articulação Temporomandibular , Suporte de Carga
13.
J Biomater Appl ; 30(7): 983-94, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26494611

RESUMO

Nucleus pulposus replacement therapy could offer a less invasive alternative to restore the function of moderately degenerated intervertebral discs than current potentially destructive surgical procedures. Numerous nucleus pulposus substitutes have already been investigated, to assess their applicability for intradiscal use. Still, the current choice of testing methods often does not lead to efficient translation into clinical application. In this paper, we present the evaluation of a novel nucleus pulposus substitute, consisting of a hydromed core and an electrospun envelope. We performed three mechanical evaluations and an in vivo pilot experiment. Initially, the swelling pressure of the implant was assessed in confined compression. Next, we incorporated the implant into mechanically damaged caprine lumbar intervertebral discs to determine biomechanical segment behaviour in bending and torsion. Subsequently, segments were serially tested in native, damaged and repaired conditions under dynamic axial compressive loading regimes in a loaded disc culture system. Finally, nucleus pulposus substitutes were implanted in a live goat spine using a transpedicular approach. In confined compression, nucleus pulposus samples as well as implants showed some load-bearing capacity, but the implant exhibited a much lower absolute pressure. In bending and torsion, we found that the nucleus pulposus substitute could partly restore the mechanical response of the disc. During dynamic axial compression in the loaded disc culture system, on the other hand, the implant was not able to recover axial compressive behaviour towards the healthy situation. Moreover, the nucleus pulposus substitutes did not remain in place in the in vivo situation but migrated out of the disc area. From these results, we conclude that implants may mimic native disc behaviour in simple mechanical tests, yet fail in other, more realistic set-ups. Therefore, we recommend that biomaterials for nucleus pulposus replacement be tested in testing modalities of increasing complexity and in their relevant anatomical surroundings, for a more reliable prediction of clinical potential.


Assuntos
Materiais Biocompatíveis/química , Disco Intervertebral/fisiologia , Núcleo Pulposo/fisiologia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Animais , Fenômenos Biomecânicos , Força Compressiva , Feminino , Cabras , Vértebras Lombares/fisiologia , Teste de Materiais , Movimento , Próteses e Implantes , Estresse Mecânico , Pesquisa Translacional Biomédica , Suporte de Carga
14.
Eur Cell Mater ; 29: 330-40; discussion 340-1, 2015 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-26091731

RESUMO

The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS). For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49), and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53). These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP) ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.


Assuntos
Degeneração do Disco Intervertebral/fisiopatologia , Disco Intervertebral/fisiopatologia , Vértebras Lombares/fisiopatologia , Suporte de Carga/fisiologia , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/fisiologia , Cadáver , Elasticidade , Glicosaminoglicanos/metabolismo , Humanos , Hidroxiprolina/metabolismo , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/metabolismo , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Porosidade , Radiografia , Fatores de Tempo
15.
Osteoarthritis Cartilage ; 23(7): 1057-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25827971

RESUMO

Intervertebral disc degeneration is a major cause of low back pain. Despite its long history and large socio-economical impact in western societies, the initiation and progress of disc degeneration is not well understood and a generic disease model is lacking. In literature, mechanics and biology have both been implicated as the predominant inductive cause; here we argue that they are interconnected and amplify each other. This view is supported by the growing awareness that cellular physiology is strongly affected by mechanical loading. We propose a vicious circle of mechanical overloading, catabolic cell response, and degeneration of the water-binding extracellular matrix. Rather than simplifying the disease, the model illustrates the complexity of disc degeneration, because all factors are interrelated. It may however solve some of the controversy in the field, because the vicious circle can be entered at any point, eventually leading to the same pathology. The proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level.


Assuntos
Degeneração do Disco Intervertebral/fisiopatologia , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Matriz Extracelular/patologia , Matriz Extracelular/fisiologia , Humanos , Disco Intervertebral/anatomia & histologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Mecanotransdução Celular/fisiologia , Estresse Mecânico
16.
Eur Cell Mater ; 30: 210-31, 2015 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-27227695

RESUMO

Intervertebral disc (IVD) degeneration is associated with most cases of cervical and lumbar spine pathologies, amongst which chronic low back pain has become the number one cause of loss of quality-adjusted life years. In search of alternatives to the current less than optimal and usually highly invasive treatments, regenerative strategies are being devised, none of which has reached clinical practice as yet. Strategies include the use of stem cells, gene therapy, growth factors and biomaterial carriers. Biomaterial carriers are an important component in musculoskeletal regenerative medicine techniques. Several biomaterials, both from natural and synthetic origin, have been used for regeneration of the IVD in vitro and in vivo. Aspects such as ease of use, mechanical properties, regenerative capacity, and their applicability as carriers for regenerative and anti-degenerative factors determine their suitability for IVD regeneration. The current review provides an overview of the biomaterials used with respect to these properties, including their drawbacks. In addition, as biomaterial application until now appears to have been based on a mix of mere availability and intuition, a more rational design is proposed for future use of biomaterials for IVD regeneration. Ideally, high-throughput screening is used to identify optimally effective materials, or alternatively medium content comparative studies should be carried out to determine an appropriate reference material for future studies on novel materials.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Degeneração do Disco Intervertebral/cirurgia , Dor Lombar/cirurgia , Animais , Humanos
17.
Artigo em Inglês | MEDLINE | ID: mdl-25485264

RESUMO

The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery periods.

18.
Vaccine ; 32(29): 3611-6, 2014 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-24814557

RESUMO

African horse sickness (AHS) is typically a highly fatal disease in susceptible horses and vaccination is currently used to prevent the occurrence of disease in endemic areas. Similarly, vaccination has been central to the control of incursions of African horse sickness virus (AHSV) into previously unaffected areas and will likely play a significant role in any future incursions. Horses in the AHSV-infected area in South Africa are vaccinated annually with a live-attenuated (modified-live virus [MLV]) vaccine, which includes a cocktail of serotypes 1, 3, 4 (bottle 1) and 2, 6-8 (bottle 2) delivered in two separate doses at least 21 days apart. In this study, the neutralising antibody response of foals immunized with this polyvalent MLV AHSV vaccine was evaluated and compared to the response elicited to monovalent MLV AHSV serotypes. Naïve foals were immunized with either the polyvalent MLV AHSV vaccine, or a combination of monovalent MLV vaccines containing individual AHSV serotypes 1, 4, 7 or 8. There was a marked and consistent difference in the immunogenicity of individual virus serotypes contained in the MLV vaccines. Specifically, foals most consistently seroconverted to AHSV-1 and responses to other serotypes were highly variable, and often weak or not detected. The serotype-specific responses of foals given the monovalent MLV vaccines were similar to those of foals given the polyvalent MLV preparation suggesting that there is no obvious enhanced immune response through the administration of a monovalent vaccine as opposed to the polyvalent vaccine.


Assuntos
Doença Equina Africana/prevenção & controle , Anticorpos Antivirais/sangue , Cavalos/imunologia , Vacinas Virais/uso terapêutico , Vírus da Doença Equina Africana/classificação , Animais , Anticorpos Neutralizantes/sangue , Imunidade Humoral , Testes de Neutralização , Distribuição Aleatória , Sorotipagem , África do Sul , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/imunologia
19.
Eur Spine J ; 22(12): 2731-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24043338

RESUMO

PURPOSE: To relate the progress of vertebral segmental stability after interbody fusion surgery with radiological assessment of spinal fusion. METHODS: Twenty goats received double-level interbody fusion and were followed for a period of 3, 6 and 12 months. After killing, interbody fusion was assessed radiographically by two independent observers. Subsequently, the lumbar spines were subjected to four-point bending and rotational deformation, assessed with an optoelectronic 3D movement registration system. In addition, four caprine lumbar spines were analysed in both the native situation and after the insertion of a cage device, as to mimic the direct post-surgical situation. The range of motion (ROM) in flexion/extension, lateral bending and axial rotation was analysed ex vivo using a multi-segment testing system. RESULTS: Significant reduction in ROM in the operated segments was already achieved with moderate bone ingrowth in flexion/extension (71 % reduction in ROM) and with only limited bone ingrowth in lateral bending (71 % reduction in ROM) compared to the post-surgical situation. The presence of a sentinel sign always resulted in a stable vertebral segment in both flexion/extension and lateral bending. For axial rotation, the ROM was already limited in both native and cage inserted situations, resulting in non-significant differences for all radiographic scores. DISCUSSION: In vivo vertebral segment stability, defined as a significant reduction in ROM, is achieved in an early stage of spinal fusion, well before a radiological bony fusion between the vertebrae can be observed. Therefore, plain radiography underestimates vertebral segment stability.


Assuntos
Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Modelos Animais , Fusão Vertebral/métodos , Animais , Fenômenos Biomecânicos , Feminino , Seguimentos , Cabras , Vértebras Lombares/fisiopatologia , Movimento , Radiografia , Amplitude de Movimento Articular , Rotação , Fusão Vertebral/instrumentação , Suporte de Carga/fisiologia
20.
J Hum Nutr Diet ; 26(1): 24-31, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23279362

RESUMO

BACKGROUND: Mid-upper arm circumference (MUAC) is used as an alternative measure for body mass index to determine thinness in older persons. However, there are limited data on the reproducibility of this measurement in an older population. The present study examined the reproducibility of MUAC measurements in older persons, as well as the influence of different body positions and clothing. METHODS: A cross-sectional reproducibility study was performed in a nursing home (n = 43; age 65-96 years) and swimming pool facilities (n = 107; age 65-88 years). A different pair of observers independently measured the MUAC of each participant in the upright position on two occasions within 1 week. In the nursing home, measurements were also performed for each participant in the laying position and with clothes covering the upper arm. RESULTS: Mean differences and the 95% limit of agreement for inter-observer reproducibility of MUAC were 0.0 cm (-2.6 to 2.5 cm) for the swimming pool facilities and 0.3 cm (-0.6 to 1.3 cm) for the nursing home. Intra-class correlation coefficients (ICCs) were 0.89 and 0.92, respectively. Mean differences between laying and upright positions were 0.1 cm (-2.0 to 2.2 cm) and 0.0 cm (-1.9 to 2.0 cm) for each observer, respectively (ICC 0.96-0.97). Mean differences between clothes versus bare upper arm were -2.7 cm (-6.2 to 0.7) and -2.4 (-5.6 to 0.9 cm) (ICC 0.75 and 0.78). CONCLUSIONS: The reproducibility of the MUAC measurement in older persons is acceptable for group comparisons and, although borderline for the swimming pool facilities, remains acceptable for clinical purposes. The measurement can also be performed in the laying position but not with clothes covering the upper arm.


Assuntos
Antropometria/métodos , Braço , Composição Corporal , Avaliação Geriátrica/métodos , Magreza , Idoso , Idoso de 80 Anos ou mais , Vestuário , Estudos Transversais , Feminino , Humanos , Masculino , Casas de Saúde , Variações Dependentes do Observador , Postura , Reprodutibilidade dos Testes , Natação
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