RESUMO
BACKGROUND: In older adults, musculoskeletal pain is associated with increased concerns of falling, reduced balance and increased occurrence of falls. In younger adults, the intensity of neck pain and low back pain is associated with increased postural sway. It is not known if pain further impairs balance and concerns of falling in mobility-limited older adults, and if so, whether this is associated with different intensities of pain. OBJECTIVE: This study examined whether mobility-limited older adults with mild or intense neck pain and/or low back pain have significantly increased postural sway as measured by centre of pressure (COP) changes and concerns of falling compared to those without pain. METHODS: 48 older adults with a gait speed of < 0.9 m/s from Odense, Denmark were recruited through the public health service. Self-reported neck pain, low back pain, and concerns of falling were recorded on questionnaires. Sway range, velocity and area were recorded on a force plate in a comfortable standing stance. Pain intensity was rated on an 11 point numerical rating scale (0-10). Participants were sub-grouped into mild (0-4) and intense (> 5) neck pain or low back pain. RESULTS: Intense neck pain was associated with increased anterior-posterior sway range and area of sway. Intense low back pain was associated with increased concerns of falling. CONCLUSION: Intense neck pain in mobility-limited older adults is associated with significant changes in postural balance, and intense low back pain is associated with significantly higher concerns of falling.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Dor Lombar/epidemiologia , Dor Musculoesquelética/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Dinamarca , Feminino , Humanos , Vida Independente , Masculino , Equilíbrio Postural , Postura , Pressão , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Degenerative joint disease (DJD) in the lumbar spine is a common condition that is associated with chronic low back pain. Excessive loading of lumbar joints is a risk factor for DJD. Changes in lumbar lordosis significantly redistribute the forces of weight-bearing on the facet joints and the intervertebral discs. However, the relationship between lumbar lordosis and DJD has not been characterized in men and women. METHODS: We characterised the correlation between standing lumbar lordosis and DJD in standing radiographic images from 301 adult female and male chiropractic patients. DJD was rated using the Kellgren-Lawrence scale, and lordosis was measured using the Cobb angle. Linear and curvilinear correlations were investigated while controlling for age and sex. RESULTS: We found a highly significant curvilinear correlation between lordosis and DJD of the lower lumbar spine in both sexes, but especially in women, irrespective of the effects of age. We found the effect size of lordosis on lower lumbar DJD to be between 17.4 and 18.1% in women and 12.9% in older men. In addition, lordosis of 65 (95% CI 55.3-77.7) and 68 (98% CI 58.7-73.3) degrees were associated with minimal DJD in the lower lumbar spine of women and men respectively, and were therefore considered 'optimal'. This optimal lordotic angle was 73 (95% CI 58.8-87.2) degrees in older men. CONCLUSIONS: Both hypo- and hyper-lordosis correlate with DJD in the lumbar spine, particularly in women and in older men. These findings may well be of relevance to spinal pain management and spinal rehabilitation.
Assuntos
Lordose/complicações , Vértebras Lombares , Osteoartrite da Coluna Vertebral/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Lordose/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoartrite da Coluna Vertebral/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to evaluate the correlation between mild leg length discrepancy (LLD) and degenerative joint disease (DJD) or osteoarthritis. METHODS: We evaluated standard postural lumbopelvic radiographs from 255 adults (121 women and 134 men) who had presented with spinal pain for chiropractic care. Symmetry of femoral head diameters was used to exclude magnification errors. Pearson's partial correlation was used to control for age and derive effect sizes for LLD on DJD in the hip and lower lumbar motion segments. Krippendorff's α was used for intraobserver and interobserver reliability. RESULTS: A strong correlation was found between LLD and hip DJD in men (r = 0.532) and women (r = 0.246). We also found a strong correlation between LLD and DJD at the L5-S1 motion segment in men (r = 0.395) and women (r = 0.246). At the L4-5 spinal level this correlation was much attenuated in men (r = 0.229) and women (r = 0.166). CONCLUSIONS: These findings suggest an association between LLD and hip and lumbar DJD. Cause-effect relationships between mild LLD and DJD deserve to be properly evaluated in future longitudinal cohort studies.
Assuntos
Degeneração do Disco Intervertebral/complicações , Desigualdade de Membros Inferiores/complicações , Região Lombossacral/fisiopatologia , Osteoartrite do Quadril/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio PosturalRESUMO
AIMS: The aim of this study was to determine the associations between neck pain, concerns of falling and physical performance in older people. METHODS: Cross-sectional study of 423 community-dwelling Danes aged 75 years and older. Measures consisted of self-reported neck pain, physical performance (Short Physical Performance Battery), self-reported psychological concerns related to falling (Falls Efficacy Scale International), depression (Major Depression Inventory), cognitive function (Mini Mental State Examination), self-reported low-back pain and self-reported history of falls. Associations between neck pain and fear of falling were determined using multivariable logistic regression modelling. RESULTS: Bothersome neck pain that limits daily activities is significantly associated with concerns of falling (unadjusted odds ratio (OR) 3.29, 95% confidence interval (CI) 1.54-7.03) and impaired physical performance (unadjusted OR 2.26, 95% CI 1.09-4.69). However, these relationships became nonsignificant after adjusting for potential confounders. Bothersome neck pain and concerns of falling is attenuated by depression, and the relationship between bothersome neck pain and decreased physical performance is attenuated by concerns of falling, depression and previous history of falls. CONCLUSIONS: Bothersome neck pain in older people is associated with increased concerns of falling and decreased physical performance that are two known risk factors for falls in older people. However, these relationships are complicated by other variables, particularly depression.
RESUMO
Multiple sclerosis involves demyelination and axonal degeneration of the central nervous system. The molecular mechanisms of axonal degeneration are relatively unexplored in both multiple sclerosis and its mouse model, experimental autoimmune encephalomyelitis. We previously reported that targeting the axonal growth inhibitor, Nogo-A, may protect against neurodegeneration in experimental autoimmune encephalomyelitis; however, the mechanism by which this occurs is unclear. We now show that the collapsin response mediator protein 2 (CRMP-2), an important tubulin-associated protein that regulates axonal growth, is phosphorylated and hence inhibited during the progression of experimental autoimmune encephalomyelitis in degenerating axons. The phosphorylated form of CRMP-2 (pThr555CRMP-2) is localized to spinal cord neurons and axons in chronic-active multiple sclerosis lesions. Specifically, pThr555CRMP-2 is implicated to be Nogo-66 receptor 1 (NgR1)-dependent, since myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced NgR1 knock-out (ngr1(-)(/)(-)) mice display a reduced experimental autoimmune encephalomyelitis disease progression, without a deregulation of ngr1(-)(/)(-) MOG(35-55)-reactive lymphocytes and monocytes. The limitation of axonal degeneration/loss in experimental autoimmune encephalomyelitis-induced ngr1(-)(/)(-) mice is associated with lower levels of pThr555CRMP-2 in the spinal cord and optic nerve during experimental autoimmune encephalomyelitis. Furthermore, transduction of retinal ganglion cells with an adeno-associated viral vector encoding a site-specific mutant T555ACRMP-2 construct, limits optic nerve axonal degeneration occurring at peak stage of experimental autoimmune encephalomyelitis. Therapeutic administration of the anti-Nogo(623-640) antibody during the course of experimental autoimmune encephalomyelitis, associated with an improved clinical outcome, is demonstrated to abrogate the protein levels of pThr555CRMP-2 in the spinal cord and improve pathological outcome. We conclude that phosphorylation of CRMP-2 may be downstream of NgR1 activation and play a role in axonal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Blockade of Nogo-A/NgR1 interaction may serve as a viable therapeutic target in multiple sclerosis.
Assuntos
Axônios/metabolismo , Encefalomielite Autoimune Experimental/complicações , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Esclerose Múltipla/patologia , Degeneração Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Adulto , Análise de Variância , Animais , Anticorpos/uso terapêutico , Axônios/patologia , Axônios/ultraestrutura , Complexo CD3/metabolismo , Linhagem Celular Tumoral , Doenças Desmielinizantes/etiologia , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/imunologia , Feminino , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/deficiência , Proteínas Ligadas por GPI/imunologia , Regulação da Expressão Gênica/genética , Glicoproteínas/efeitos adversos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imunoprecipitação , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Mutação/genética , Proteínas da Mielina/antagonistas & inibidores , Proteínas da Mielina/deficiência , Proteínas da Mielina/imunologia , Glicoproteína Mielina-Oligodendrócito , Degeneração Neural/etiologia , Proteínas do Tecido Nervoso/genética , Neuroblastoma/patologia , Proteínas de Neurofilamentos/metabolismo , Receptor Nogo 1 , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Fragmentos de Peptídeos/efeitos adversos , Fosforilação , Receptores de Superfície Celular/antagonistas & inibidores , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/imunologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologiaRESUMO
Objective: The purpose of this article is to describe a protocol to examine the feasibility of combining podiatric orthotic treatment with multimodal chiropractic treatment to treat chronic low back pain (CLBP) in those with a functional short leg on the same side as a unilateral pronated foot. Methods: This is a protocol for a multicenter feasibility 2-arm parallel randomized controlled trial. One hundred and thirty-two adults with CLBP and a functional short leg on the same side as a unilateral pronated foot are to be recruited in Melbourne, Australia, and Madrid and Seville, Spain. Forty-four participants at each site are to be randomized to multimodal chiropractic treatment including spinal manipulation or to multimodal chiropractic treatment also involving spinal manipulation, together with podiatric custom-made orthoses. Chiropractic visits are to comprise 12 treatments over 4 weeks. Outcome measures will be recruitment, compliance, costs, CLBP-related disability, and perceived low back pain. Results: Feasibility results will be reported in text format and the clinical data reported using descriptive statistics focusing on any clinically significant results. Conclusion: This protocol describes a feasibility study for assessing the combination of podiatric orthotic treatment with multimodal chiropractic treatment to treat CLBP in those with a functional short leg on the same side as a unilateral pronated foot.
RESUMO
We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords of ngr1+/+ EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells of ngr1+/+ EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.
Assuntos
Fator Ativador de Células B/metabolismo , Linfócitos B/imunologia , Encefalomielite Autoimune Experimental/imunologia , Meninges/patologia , Esclerose Múltipla/imunologia , Animais , Linfócitos B/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Meninges/imunologia , Camundongos , Camundongos Knockout , Esclerose Múltipla/patologia , Proteínas Nogo/metabolismo , Receptor Nogo 1/genética , Receptor Nogo 1/metabolismo , Receptores Nogo/metabolismoRESUMO
Myelin is a dynamic membrane that is important for coordinating the fast propagation of action potentials along small or large caliber axons (0.1-10 µm) some of which extend the entire length of the spinal cord. Due to the heterogeneity of electrical and energy demands of the variable neuronal populations, the axo-myelinic and axo-glial interactions that regulate the biophysical properties of myelinated axons also vary in terms of molecular interactions at the membrane interfaces. An important topic of debate in neuroscience is how myelin is maintained and modified under neuronal control and how disruption of this control (due to disease or injury) can initiate and/or propagate neurodegeneration. One of the key molecular signaling cascades that have been investigated in the context of neural injury over the past two decades involves the myelin-associated inhibitory factors (MAIFs) that interact with Nogo receptor 1 (NgR1). Chief among the MAIF superfamily of molecules is a reticulon family protein, Nogo-A, that is established as a potent inhibitor of neurite sprouting and axon regeneration. However, an understated role for NgR1 is its ability to control axo-myelin interactions and Nogo-A specific ligand binding. These interactions may occur at axo-dendritic and axo-glial synapses regulating their functional and dynamic membrane domains. The current review provides a comprehensive analysis of how neuronal NgR1 can regulate myelin thickness and plasticity under normal and disease conditions. Specifically, we discuss how NgR1 plays an important role in regulating paranodal and juxtaparanodal domains through specific signal transduction cascades that are important for microdomain molecular architecture and action potential propagation. Potential therapeutics designed to target NgR1-dependent signaling during disease are being developed in animal models since interference with the involvement of the receptor may facilitate neurological recovery. Hence, the regulatory role played by NgR1 in the axo-myelinic interface is an important research field of clinical significance that requires comprehensive investigation.
RESUMO
INTRODUCTION: Chronic musculoskeletal pain is associated with reduced balance performance and falls risk. Manual therapies are commonly used interventions for musculoskeletal pain. There is emerging evidence that manual therapies may improve balance. The aim of this systematic review was to examine the effectiveness of manual therapies for musculoskeletal pain on measures of static and dynamic stability. METHODS: Six electronic databases were searched using pre-defined eligibility criteria and two independent reviewers assessed all identified records. Risk of bias was assessed using the 12-item Cochrane Risk of Bias assessment by two authors independently and any discrepancies resolved through consensus. Meta-analysis was conducted when three or more studies used the same outcome measures including gait speed, timed up and go test, step test and sit-to-stand test. RESULTS: Twenty-six studies were included in the analysis. Both spinal and extremity musculoskeletal pain conditions were represented. Manual therapies included manipulation, mobilisation and massage. The most common intervention compared to manual therapy was exercise. Outcome measures included both clinical and objective measures of stability. Overall the risk of bias was reported as generally low or unclear. CONCLUSION: Improvement in stability measures were reported in studies comparing manual therapy in the short term, but not long-term follow-up. There was no clear association between significant pain reduction and measures of stability. Further prospective studies are recommended to investigate whether manual therapies should be part of an integrative healthcare plan for risk of falls management and when a transition from manual therapy to more active interventions should occur for long term management.
Assuntos
Manipulações Musculoesqueléticas/métodos , Dor Musculoesquelética/fisiopatologia , Dor Musculoesquelética/terapia , Equilíbrio Postural , HumanosRESUMO
Background: Neck pain is a leading cause of individual and societal burden worldwide, affecting an estimated 1 in 5 people aged 70 years and older. The nature and outcomes of chiropractic care for older adults with neck pain, particularly those with co-morbid headaches, remains poorly understood. Therefore, we sought to ascertain: What proportion of Australian chiropractors' caseload comprises older adults with neck pain (with or without headache); How are these conditions treated; What are the reported outcomes? Methods: An online survey examining practitioner and practice characteristics, clinical patient presentations, chiropractic treatment methods and outcomes, and other health service use, was distributed to a random nationally representative sample of 800 Australian chiropractors. Quantitative methods were used to analyze the data. Results: Two hundred eighty-eight chiropractors (response rate = 36%) completed the survey between August and November 2017. Approximately one-third (M 28.5%, SD 14.2) of the chiropractors' patients were older adults (i.e. aged ≥65 years), of which 45.5% (SD 20.6) presented with neck pain and 31.3% (SD 20.3) had co-morbid headache. Chiropractors reported to combine a range of physical and manual therapy treatments, exercises and self-management practices in their care of these patients particularly: manipulation of the thoracic spine (82.0%); activator adjustment of the neck (77.3%); and massage of the neck (76.5%). The average number of visits required to resolve headache symptoms was reported to be highest among those with migraine (M 11.2, SD 8.8). The majority of chiropractors (57.3%) reported a moderate response to treatment in reported dizziness amongst older adults with neck pain. Approximately 82% of older adult patients were estimated to use at least one other health service concurrently to chiropractic care to manage their neck pain. Conclusion: This is the first known study to investigate chiropractic care of older adults living with neck pain. Chiropractors report using well-established conservative techniques to manage neck pain in older adults. Our findings also indicate that this target group of patients may frequently integrate chiropractic care with other health services in order to manage their neck pain. Further research should provide in-depth investigation of older patients' experience and other patient-reported outcomes of chiropractic treatment.
Assuntos
Quiroprática , Tontura/terapia , Cefaleia/terapia , Manipulação da Coluna , Cervicalgia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Background: Dizziness in older people is a risk factor for falls. Neck pain is associated with dizziness and responds favourably to neck manipulation. However, it is unknown if chiropractic intervention including instrument-assisted manipulation of the neck in older people with neck pain can also improve dizziness. Methods: This parallel two-arm pilot trial was conducted in Melbourne, Australia over nine months (October 2015 to June 2016). Participants aged 65-85 years, with self-reported chronic neck pain and dizziness, were recruited from the general public through advertisements in local community newspapers and via Facebook. Participants were randomised using a permuted block method to one of two groups: 1) Activator II™-instrument-assisted cervical and thoracic spine manipulation plus a combination of: light massage; mobilisation; range of motion exercises; and home advice about the application of heat, or 2) Sham-Activator II™-instrument-assisted manipulation (set to zero impulse) plus gentle touch of cervical and thoracic spinal regions. Participants were blinded to group allocation. The interventions were delivered weekly for four weeks. Assessments were conducted one week pre- and post-intervention. Clinical outcomes were assessed blindly and included: dizziness (dizziness handicap inventory [DHI]); neck pain (neck disability index [NDI]); self-reported concerns of falling; mood; physical function; and treatment satisfaction. Feasibility outcomes included recruitment rates, compliance with intervention and outcome assessment, study location, success of blinding, costs and harms. Results: Out of 162 enquiries, 24 participants were screened as eligible and randomised to either the chiropractic (n = 13) or sham (n = 11) intervention group. Compliance was satisfactory with only two participants lost to follow up; thus, post-intervention data for 12 chiropractic intervention and 10 sham intervention participants were analysed. Blinding was similar between groups. Mild harms of increased spinal pain or headaches were reported by 6 participants. Costs amounted to AUD$2635 per participant. The data showed a trend favouring the chiropractic group in terms of clinically-significant improvements in both NDI and DHI scores. Sample sizes of n = 150 or n = 222 for dizziness or neck pain disability as the primary outcome measure, respectively, would be needed for a fully powered trial. Conclusions: Recruitment of participants in this setting was difficult and expensive. However, a larger trial may be feasible at a specialised dizziness clinic within a rehabilitation setting. Compliance was acceptable and the outcome measures used were well accepted and responsive. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000653763. Registered 13 June 2013.Trial funding: Foundation for Chiropractic Research and Postgraduate Education (Denmark).
Assuntos
Acidentes por Quedas/prevenção & controle , Tontura/terapia , Manipulação Quiroprática/métodos , Manipulação da Coluna/métodos , Cervicalgia/terapia , Equilíbrio Postural/fisiologia , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Tontura/complicações , Tontura/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Manipulação Quiroprática/efeitos adversos , Manipulação Quiroprática/instrumentação , Manipulação da Coluna/efeitos adversos , Manipulação da Coluna/instrumentação , Cervicalgia/complicações , Cervicalgia/fisiopatologia , Satisfação do Paciente , Projetos Piloto , Resultado do TratamentoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Prior to the development of these characteristic pathological hallmarks of AD, anterograde axonal transport is impaired. However, the key proteins that initiate these intracellular impairments remain elusive. The collapsin response mediator protein-2 (CRMP-2) plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2 releases kinesin-1. Here, we tested the hypothesis that amyloid-beta (Aß)-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1 (an anterograde axonal motor transport protein) in AD. We found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 site. Additionally, in the transgenic Tg2576 mouse model of familial AD (FAD) that exhibits Aß accumulation in the brain with age, we found substantial co-localization of pT555CRMP-2 and dystrophic neurites. In SH-SY5Y differentiated neuronal cultures, Aß-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with kinesin-1. The overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon elongation. These data suggest that Aß-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function, leading to neuronal defects.
RESUMO
Although much research has been devoted to the characterization of the effects of whole-body vibration on seated occupants' comfort, drowsiness induced by vibration has received less attention to date. There are also little validated measurement methods available to quantify whole body vibration-induced drowsiness. Here, the effects of vibration on drowsiness were investigated. Twenty male volunteers were recruited for this experiment. Drowsiness was measured in a driving simulator, before and after 30-min exposure to vibration. Gaussian random vibration, with 1-15 Hz frequency bandwidth was used for excitation. During the driving session, volunteers were required to obey the speed limit of 100 kph and maintain a steady position on the left-hand lane. A deviation in lane position, steering angle variability, and speed deviation were recorded and analysed. Alternatively, volunteers rated their subjective drowsiness by Karolinska Sleepiness Scale (KSS) scores every 5-min. Following 30-min of exposure to vibration, a significant increase of lane deviation, steering angle variability, and KSS scores were observed in all volunteers suggesting the adverse effects of vibration on human alertness level.
Assuntos
Condução de Veículo , Fases do Sono , Vibração/efeitos adversos , Vigília , Adulto , Atenção , Simulação por Computador , Humanos , Masculino , Inquéritos e Questionários , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
Cell membrane thyroid hormone (TH) transport can be facilitated by the monocarboxylate transporter 8 (MCT8), encoded by the solute carrier family 16 member 2 (SLC16A2) gene. Human mutations of the gene, SLC16A2, result in the X-linked-inherited psychomotor retardation and hypomyelination disorder, Allan-Herndon-Dudley syndrome (AHDS). We posited that abrogating MCT8-dependent TH transport limits oligodendrogenesis and myelination. We show that human oligodendrocytes (OL), derived from the NKX2.1-GFP human embryonic stem cell (hESC) reporter line, express MCT8. Moreover, treatment of these cultures with DITPA (an MCT8-independent TH analog), up-regulates OL differentiation transcription factors and myelin gene expression. DITPA promotes hESC-derived OL myelination of retinal ganglion axons in co-culture. Pharmacological and genetic blockade of MCT8 induces significant OL apoptosis, impairing myelination. DITPA treatment limits OL apoptosis mediated by SLC16A2 down-regulation primarily signaling through AKT phosphorylation, driving myelination. Our results highlight the potential role of MCT8 in TH transport for human OL development and may implicate DITPA as a promising treatment for developmentally-regulated myelination in AHDS.
Assuntos
Diferenciação Celular/genética , Deficiência Intelectual Ligada ao Cromossomo X/genética , Transportadores de Ácidos Monocarboxílicos/genética , Hipotonia Muscular/genética , Atrofia Muscular/genética , Neurogênese/genética , Transporte Biológico/genética , Linhagem Celular , Di-Iodotironinas/administração & dosagem , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Humanos , Deficiência Intelectual Ligada ao Cromossomo X/tratamento farmacológico , Deficiência Intelectual Ligada ao Cromossomo X/patologia , Hipotonia Muscular/tratamento farmacológico , Hipotonia Muscular/patologia , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/patologia , Mutação , Bainha de Mielina/metabolismo , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Propionatos/administração & dosagem , Simportadores , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismoRESUMO
As a consequence of secondary pathophysiological mechanisms elicited after spinal cord injury (SCI), oligodendrocytes die by waves of apoptosis. This ultimately results in demyelination of intact axons leading to a loss of their conducting properties. Preservation of as few as 5% to 10% of myelinated axons in individual tracts can confer locomotor recovery. Thus, strategies aimed at rescuing mature oligodendrocytes ensheathing viable axons are likely to be of therapeutic significance. We report that leukemia inhibitory factor (LIF) can prevent oligodendrocyte apoptosis, notably contralateral to the spinal cord lesion, through the induction of the JAK/STAT and Akt signaling pathways as well as by potentiating the expression of the antiapoptotic molecule, cIAP2. Reduced oligodendrocyte apoptosis after SCI with LIF administration resulted in a substantial decrease in demyelination shown by the preservation of lamellated myelin surrounding viable axons and deposition of the degraded myelin basic protein. The data suggest that LIF signals survival in oligodendrocytes after SCI, prevents the secondary wave of demyelination, and thereby reduces inhibitory myelin deposits.
Assuntos
Doenças Desmielinizantes/tratamento farmacológico , Interleucina-6/administração & dosagem , Oligodendroglia/efeitos dos fármacos , Traumatismos da Medula Espinal , Animais , Axotomia/métodos , Proteína 3 com Repetições IAP de Baculovírus , Morte Celular/efeitos dos fármacos , Doenças Desmielinizantes/etiologia , Modelos Animais de Doenças , Feminino , Expressão Gênica/efeitos dos fármacos , Imunoprecipitação/métodos , Marcação In Situ das Extremidades Cortadas/métodos , Proteínas Inibidoras de Apoptose/metabolismo , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Camundongos , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina/metabolismo , Oligodendroglia/fisiologia , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF , Fatores de Transcrição STAT/metabolismo , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Ubiquitina-Proteína LigasesRESUMO
BACKGROUND: Nonpharmacological interventions have been shown to have some effectiveness in adults with dizziness; however, the effectiveness of these interventions in older people is unknown. PURPOSE: The aim of this study was to determine the effects of conservative nonpharmacological interventions for dizziness in older people. DATA SOURCES: The Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, CINAHL, AMED, Index to Chiropractic Literature, PsycINFO, and MANTIS were searched from inception to May 2014. STUDY SELECTION: Two investigators independently screened controlled trials with participants who were more than 60 years old and experienced dizziness. Studies of participants with dizziness from a specific diagnosis, such as Ménière disease and benign paroxysmal positional vertigo, were excluded. Outcome measures from the selected studies included self-reported dizziness and postural balance. DATA EXTRACTION: Two investigators independently extracted data on participants, interventions, comparison group, outcome measures, and results. The risk of bias of the included studies was assessed with Cochrane guidelines. DATA SYNTHESIS: Seven articles consisting of 7 controlled trials were included. All studies involved some form of exercise, including vestibular rehabilitation exercises, postural balance exercises, and tai chi exercise, as the main intervention. The studies had a high risk of bias because of the lack of adequate randomization and allocation concealment, the lack of reporting on cointerventions, the lack of reporting on reasons for dropouts, and the lack of reporting on participant adherence. LIMITATIONS: Heterogeneity among the included studies in interventions and outcome measures prohibited a meta-analysis. Only 2 studies reported a significant difference between the intervention group and the comparison group for self-reported dizziness. CONCLUSIONS: There is insufficient evidence to determine the effectiveness of nonpharmacological treatments for dizziness in older people. Current evidence is hampered by a high risk of bias, and well-designed trials with adequate masking, randomization, and adherence are needed.
Assuntos
Tontura/terapia , Terapia por Exercício , Equilíbrio Postural , Idoso , Idoso de 80 Anos ou mais , Tratamento Conservador , Terapia por Exercício/métodos , Humanos , Pessoa de Meia-Idade , Autorrelato , Resultado do TratamentoRESUMO
Although much is known about human body vibration discomfort, there is little research data on the effects of vibration on vehicle occupant drowsiness. A laboratory experimental setup has been developed. Vibration was applied to the volunteers sitting on the vehicle seat mounted on the vibration platform. Seated volunteers were exposed to a Gaussian random vibration, with 1-15 Hz frequency bandwidth at 0.2 ms(-2) r.m.s., for 20-minutes. Two drowsiness measurement methods were used, Psychomotor Vigilance Test (PVT) and Karolinska Sleepiness Scale (KSS). Significant changes in PVT (p<0.05) and KSS (p<0.05) were detected in all eighteen volunteers. Furthermore, a moderate correlation (r>0.4) was observed between objective measurement (PVT) and subjective measurement (KSS). The results suggest that exposure to vibration even for 20-minutes can cause significant drowsiness impairing psychomotor performance. This finding has important implications for road safety.
Assuntos
Fases do Sono/fisiologia , Vibração , Humanos , Masculino , Veículos Automotores , Postura , Desempenho Psicomotor/fisiologia , Vigília , Adulto JovemRESUMO
The mechanisms determining the fate of Schwann cells during disease and injury of the adult mammalian peripheral nervous system (PNS) are becoming defined by current advances in molecular neurobiology. It is now apparent that the molecular pathways which regulate the production of the mature myelinating Schwann cell during development may also apply to degenerative and regenerative mechanisms following PNS disease. This review outlines neurobiological responses of Schwann cells during development, injury and disease in order to define the molecular pathways which regulate these crucial events. These mechanisms have implications for our attempts to intervene pharmacologically during pathologies of the PNS.
Assuntos
Nervos Periféricos/crescimento & desenvolvimento , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Células de Schwann/fisiologia , Animais , Morte Celular/fisiologia , Sobrevivência Celular/fisiologia , Humanos , Traumatismos dos Nervos Periféricos , Nervos Periféricos/citologia , Células de Schwann/citologia , Células de Schwann/patologiaRESUMO
Osteoarthritis (OA) is an extremely common condition that creates substantial personal and health care costs. An important recognised risk factor for OA is excessive or abnormal mechanical joint loading. Leg length discrepancy (LLD) is a common condition that results in uneven and excessive loading of not only knee joints but also hip joints and lumbar motion segments. Accurate imaging methods of LLD have made it possible to study the biomechanical effects of mild LLD (LLD of 20mm or less). This review examines the accuracy of these methods compared to clinical LLD measurements. It then examines the association between LLD and OA of the joints of the lower extremity. More importantly, it addresses the largely neglected association between LLD and degeneration of lumbar motion segments and the patterns of biomechanical changes that accompany LLD. We propose that mild LLD may be an important instigator or contributor to OA of the hip and lumbar spine, and that it deserves to be rigorously studied in order to decrease OA's burden of disease.
L'arthrose est une pathologie extrêmement fréquente qui engendre des frais personnels et des coûts de soins de santé importants. Un facteur important de risque reconnu pour l'arthrose est la charge mécanique excessive ou anormale sur les articulations. L'inégalité de longueur des membres inférieurs (ILMI) est une affection fréquente qui se traduit par une charge inégale et excessive non seulement sur les articulations du genou, mais aussi sur les articulations de la hanche et les segments mobiles lombaires. Des méthodes d'imagerie précises de l'ILMI ont permis d'étudier les effets biomécaniques d'une ILMI légère (ILMI de 20 mm ou moins). Cette étude examine l'exactitude de ces méthodes par rapport aux mesures cliniques de l'ILMI. Elle se penche ensuite sur l'association entre l'ILMI et l'arthrose des articulations des membres inférieurs. Mais surtout, elle examine l'association peu étudiée entre l'ILMI et la dégénérescence de segments mobiles lombaires et les tendances des changements biomécaniques qui accompagnent l'ILMI. Nous suggérons que l'ILMI légère peut être un instigateur important ou un facteur de l'arthrose de la hanche et de la colonne lombaire, et qu'elle mérite d'être étudiée de plus près afin de diminuer la charge de morbidité de l'arthrose.
RESUMO
OBJECTIVE: The purpose of this case report is to describe chiropractic management of an elderly man with untreated bilateral hip joint dysplasia presenting with mild acute mechanical low back pain. CLINICAL FEATURES: A 75-year-old man presented with an insidious-onset intermittent low back pain of 3 days' duration. Physical examination findings supported a mechanical cause for mild acute low back pain. Plain radiography revealed dysplasia of hip joints with absence of femoral heads and necks and bilateral high dislocation. INTERVENTION AND OUTCOME: Chiropractic management included vibration, mobilization, light drop-piece adjustments of the lower lumbar and sacroiliac joints, and recommendation of the use of heat at home. Treatments were given 3 times over the course of 1 week. The low back pain intensity over this period dropped from 5 to 0 on an 11-point numerical rating scale, and the patient was discharged. CONCLUSION: This patient with substantial postural and gait abnormalities as a result of severe bilateral hip dysplasia associated with an unusual pattern of osteoarthritic change in the spine responded favorably to a short course of chiropractic care.