RESUMO
BACKGROUND: The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population. METHODS: A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified. RESULTS: Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a "U" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05). CONCLUSION: RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.
Assuntos
Traumatismos da Medula Espinal , Trombose Venosa , Humanos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/sangue , Estudos Retrospectivos , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Masculino , Feminino , Incidência , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Contagem de Eritrócitos , Idoso , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Anticoagulantes/uso terapêutico , Fatores de TempoRESUMO
Dyslipidemia is the most frequent cardiovascular (CV) risk factor in able-bodied athletes and is frequently undertreated, resulting in an underestimated risk of atherosclerosis-related diseases. Data on lipid profile in Paralympic athletes are lacking. Our study aimed to identify the prevalence of dyslipidemia and the influence of disability type and sporting discipline in Paralympic athletes. We evaluated 289 athletes who participated in the Paralympic Games from London 2012 to Beijing 2022. All athletes underwent clinical/physical evaluation, blood tests, and body composition analysis. They were divided into different groups based on sports disciplines and disability type (spinal cord injuries [SCIs] and non-SCIs [NSCIs]). Among the Paralympic athletes, 34.6% had a low-density lipoprotein (LDL) level ≥115 mg/100 ml. They were older (38.1 ± 9.2 vs 30.6 ± 9.6, p = 0.001) and had a higher CV risk. Athletes with SCI showed similar total cholesterol and triglycerides, higher LDL (110.9 ± 35.2 vs 102.7 ± 30.6 mg/100 ml, p = 0.03) and lower high-density lipoprotein (HDL) (53.6 ± 13.6 vs 60.5 ± 15.4 mg/100 ml, p = 0.001) than those with NSCI. Endurance athletes had lower LDL, the highest HDL, and the lowest triglycerides and LDL/HDL ratio compared with other sports disciplines. A mean follow-up of 61.5 ± 30.5 months was available in 47% athletes, and 72.7% of the athletes with dyslipidemia continued to present altered LDL values at follow-up. In conclusion, dyslipidemia is the most common CV risk factor in the Paralympics, affecting 35% of athletes, with only mild lipid changes over a medium-term time. The type of disability and sporting discipline has an impact on lipids, improving HDL and reducing LDL, with a better profile observed in NSCI and endurance athletes.
Assuntos
Dislipidemias , Paratletas , Humanos , Masculino , Adulto , Feminino , Itália/epidemiologia , Dislipidemias/epidemiologia , Dislipidemias/sangue , Lipídeos/sangue , Prevalência , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/epidemiologia , Fatores de Risco , Pessoa de Meia-Idade , Atletas , Triglicerídeos/sangue , Esportes para Pessoas com Deficiência , LDL-Colesterol/sangueRESUMO
STUDY DESIGN: Observational cohort. AIM: To show that Cystatin C is an accurate single marker to estimate GFR in motor complete persons with SCI. OBJECTIVES: To assess if Cystatin C is an accurate for estimating GFR in persons with SCI with no preserved motor power. To study if use of Serum creatinine for estimation of GFR in this population significantly overestimates GFR, thereby inaccurate. SETTING: Tertiary care hospital and Medical College, Vellore, South India. METHODS: 30 persons with SCI (ASIA A and B) fulfilling the inclusion criteria were recruited. Serum Creatinine and Serum Cystatin C values were obtained, and eGFR was calculated based on available formulae. 24-h urine for urine creatinine clearance-based eGFR was used as a reference value. RESULTS: Analysis with a Bland-Atman plot showed that eGFR estimated with Serum Cystatin C was more accurate than Serum Creatinine, using 24-h urine creatinine as a reference value. eGFR using Serum Creatinine significantly overestimated GFR by over 50.6%. Estimated GFR using Serum Cystatin C showed a meager mean difference of 0.5% from the reference 24-h urine creatinine clearance (mean difference of -2.56%). CONCLUSION: Serum Cystatin C is a much more accurate marker for estimating GFR in SCI, compared to serum Creatinine which overestimates GFR.
Assuntos
Biomarcadores , Creatinina , Cistatina C , Taxa de Filtração Glomerular , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/urina , Cistatina C/sangue , Masculino , Feminino , Creatinina/sangue , Creatinina/urina , Adulto , Taxa de Filtração Glomerular/fisiologia , Biomarcadores/sangue , Biomarcadores/urina , Pessoa de Meia-Idade , Estudos de Coortes , Adulto Jovem , Testes de Função Renal/métodosRESUMO
OBJECTIVE: Spinal cord injury (SCI) has become popular in recent years, and cognitive decline is a common complication. Adiponectin is a common protein hormone involved in the course of many diseases, but its relationship with SCI has not yet been elucidated. The purpose of our prospective study is to explore whether adiponectin can be used as a biomarker of cognitive decline in SCI. METHODS: A total of 64 healthy volunteers and 92 patients with acute SCI were recruited by us. Serum adiponectin levels, demographic data (age and gender), lifestyle (smoking and drinking), medical history (diabetes and hypertension), and clinical baseline data (low-density lipoprotein, high-density lipoprotein, and fasting blood glucose) were recorded. Three months after enrollment, we used the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function. Based on a quarter of the serum adiponectin levels, SCI patients were divided into 4 groups, and the differences in their MoCA scores were compared. In addition, we used multivariate linear regression to predict the risk factors of the MoCA score. RESULTS: The serum adiponectin level (6.1 ± 1.1 µg/ml) of SCI patients was significantly lower than that of the healthy control group (6.7 ± 0.9 µg/ml), and there was a significant difference between the two (p < 0.001). The group with higher serum adiponectin levels after 3 months of spinal cord injury had higher MoCA scores. Multivariate regression analysis showed that serum adiponectin level is a protective factor for cognitive function after SCI (ß = 0.210, p = 0.043). CONCLUSIONS: Serum adiponectin levels can be used as an independent predictor of cognitive function in patients with acute SCI.
Assuntos
Adiponectina/sangue , Disfunção Cognitiva/sangue , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Endogenous immune mediated reactions of inflammation and angiogenesis are components of the spinal cord injury in patients with degenerative cervical myelopathy (DCM). The aim of this study was to identify alteration of certain mediators participating in angiogenetic and inflammatory reactions in patients with DCM. A consecutive series of 42 patients with DCM and indication for surgical decompression were enrolled for the study. 28 DCM patients were included, as CSF samples were taken preoperatively. We enrolled 42 patients requiring surgery for a thoracic abdominal aortic aneurysm (TAAA) as neurologically healthy controls. In 38 TAAA patients, CSF samples were taken prior to surgery and thus included. We evaluated the neurological status of patients and controls prior to surgery including NDI and mJOA. Protein-concentrations of factors with a crucial role in inflammation and angiogenesis were measured in CSF via ELISA testing (pg/ml): Angiopoietin 2, VEGF-A and C, RANTES, IL 1 beta and IL 8. Additionally, evaluated the status of the blood-spinal cord barrier (BSCB) by Reibers´diagnostic in all participants. Groups evidently differed in their neurological status (mJOA: DCM 10.1 ± 3.3, TAAA 17.3 ± 1.2, p < .001; NDI: DCM 47.4 ± 19.7, TAAA 5.3 ± 8.6, p < .001). There were no particular differences in age and gender distribution. However, we detected statistically significant differences in concentrations of mediators between the groups: Angiopoietin 2 (DCM 267.1.4 ± 81.9, TAAA 408.6 ± 177.1, p < .001) and VEGF C (DCM 152.2 ± 96.1, TAAA 222.4 ± 140.3, p = .04). DCM patients presented a mild to moderate BSCB disruption, controls had no signs of impairment. In patients with DCM, we measured decreased concentrations of angiogenic mediators. These results correspond to findings of immune mediated secondary harm in acute spinal cord injury. Reduced angiogenic activity could be a relevant part of the pathogenesis of DCM and secondary harm to the spinal cord.
Assuntos
Aneurisma da Aorta Abdominal/sangue , Citocinas/sangue , Neovascularização Fisiológica , Traumatismos da Medula Espinal/sangue , Idoso , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Inflamação/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/cirurgiaRESUMO
OBJECTIVE: The purpose of this study was to uncover the role of microRNA-665 (miR-665) in protecting inflammatory response in microglia following spinal cord injury (SCI) and the underlying mechanism. PATIENTS AND METHODS: The serum levels of miR-665 and TREM2 (triggering receptor expressed on myeloid 2) in SCI patients (n=24) and healthy subjects (n=24) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). After lipopolysaccharide (LPS) induction in BV2 cells, the relative levels of miR-665 and TREM2 were detected by qRT-PCR, and relative levels of IL-6 and TNF-α in the culture medium were examined by ELISA. Next, TREM2, the target gene of miR-665, was determined by Dual-Luciferase reporter assay, and the relationship between the expression levels of TREM2 and miR-665 in SCI patients and BV2 cells was analyzed. Finally, the regulatory effects of miR-665 and TREM2 on IL-6 and TNF-α levels in the culture medium of LPS-induced BV2 cells were assessed. RESULTS: It was found that miR-665 was downregulated in serum of SCI patients and LPS-induced BV2 cells, while TREM2 was upregulated. Silenced miR-665 or overexpressed TREM2 was involved in protecting inflammatory response following SCI. Besides, rescue experiments showed that miR-665 participated in the regulation of inflammatory response following SCI by targeting TREM2. CONCLUSIONS: MiR-665 inhibits inflammatory response following SCI by targeting TREM2.
Assuntos
Inflamação/metabolismo , Glicoproteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Receptores Imunológicos/metabolismo , Traumatismos da Medula Espinal/metabolismo , Células Cultivadas , Humanos , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , MicroRNAs/sangue , MicroRNAs/genética , Microglia/efeitos dos fármacos , Microglia/metabolismo , Receptores Imunológicos/sangue , Receptores Imunológicos/genética , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/patologiaRESUMO
OBJECTIVE: Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI. METHODS: All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination. RESULTS: A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant (p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant (p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly (p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score (r = -0.327, p < 0.05). CONCLUSION: The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI.
Assuntos
Interleucina-1/sangue , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/metabolismo , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Medula Espinal/fisiopatologiaRESUMO
Spinal cord injury (SCI) involves nerve damage and often leads to motor, sensory and autonomic dysfunctions. In the present study, we have designed a clinical protocol to assess the feasibility of systemic delivery of allogenic canine bone marrow tissue-derived mesenchymal stem cell conditioned medium (BMMSC CM) to dogs with SCI. Four client-owned dogs with chronic SCI lasting more than six months underwent neurological and clinical evaluation, MRI imaging and blood tests before being enrolled in this study. All dogs received four intravenous infusions with canine allogenic BMMSC CM within one month. Between the infusions the dogs received comprehensive physiotherapy, which continued for three additional months. No adverse effects or complications were observed during the one, three and six months follow-up periods. Neither blood chemistry panel nor hematology profile showed any significant changes. All dogs were clinically improved as assessed using Olby locomotor scales after one, three and six months of BMMSC CM treatment. Furthermore, goniometric measurements revealed partial improvement in the range of joint motion. Bladder function improved in two disabled dogs. We conclude that multiple delivery of allogenic cell-derived conditioned medium to dogs with chronic SCI is feasible, and it might be clinically beneficial in combination with physiotherapy.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Doenças do Cão/terapia , Cães , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal/veterinária , Animais , Células Cultivadas , Meios de Cultivo Condicionados/química , Doenças do Cão/sangue , Doenças do Cão/fisiopatologia , Cães/sangue , Cães/fisiologia , Estudos de Viabilidade , Locomoção , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Projetos Piloto , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapiaRESUMO
BACKGROUND: The correlation between inflammatory responses caused by spinal cord injury (SCI) and the prognosis of patients with SCI still remains controversial. METHODS: In the present study, we preliminary investigated the serum levels of interleukin (IL)-4, IL-10, major histocompatibility complex (MHC)-I, and inducible nitric oxide synthase (iNOS) and compared the serum IL-4 and IL-10 expression in rats of high Basso-Beattie-Bresnahan (BBB) scores with these of low BBB scores. Besides, the infiltration of macrophage and the axonal regeneration of the injured spinal cord were observed from day 10 to day 30. RESULTS: We found that higher serum levels of IL-4 and IL-10 can reflect the restorability degree of SCI and could be potential biomarkers for the prognosis of SCI. The infiltration of the M2 subtype of macrophage and the axons regrowth might contribute to a better prognosis. CONCLUSIONS: The current study demonstrates that the serum levels of IL-4 and IL-10 are preliminarily adopted as serologic markers to forecast SCI, and high serum levels of IL-4 and IL-10 may indicate a better prognosis. Moreover, the way to promote macrophage polarization from M1 to M2 may contribute to better axonal regeneration.
Assuntos
Inflamação/sangue , Interleucina-10/sangue , Interleucina-4/sangue , Traumatismos da Medula Espinal/diagnóstico , Animais , Biomarcadores/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Inflamação/diagnóstico , Inflamação/patologia , Masculino , Prognóstico , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/patologia , Fatores de TempoRESUMO
The present study aimed to evaluate the effect of the CX3CR1 inhibitor AZD8797 in early recovery after acute SCI and elucidate its potential mechanism in blocking inflammation and apoptosis. Adult rats were sacrificed after 3, 7, 10, or 14 days of SCI. The injured spinal tissues were collected for assessing CX3C motif chemokine ligand 1(CX3CL1)/CX3C motif chemokine receptor 1 (CX3CR1) expression at each time point via western blotting (WB) and quantitative PCR. The cellular localization of the proteins was detected by immunofluorescence. Another batch of rats (subdivided into sham, injury model, AZD8797 and methylprednisolone groups) were used to evaluate locomotive recovery with a Basso Beattie Bresnahan score. Based on the expression level of CX3CR1, these rats were sacrificed at the most prominent stage of CX3CR1 expression (10 days after SCI), for assessing the serum levels of tumor necrosis factorα/interleukin (IL)6/IL1ß and the expression of CX3CL1/CX3CR1/caspase 3/Bcl2/Bax in the spinal cord tissues through WB and ELISA. Additionally, apoptosis and necrosis in the injured spinal cord were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling staining/fluorojade B staining. Expression levels of both CX3CR1 and CX3CL1 reached their peak 10 days after the injury, followed by a dramatic downward trend at 14 days. The enhanced expression of CX3CR1 was detected in astrocytes and microglia of the injured spinal cord. AZD8797 improved locomotive recovery after 10 days of SCI and was as effective as methylprednisolone. The effect of AZD8797 was mediated by suppressing apoptosis, necrosis and inflammatory responses, as assessed by WB/ELISA and morphological examinations. The current study has demonstrated that AZD8797 can effectively block overwhelming inflammation, apoptosis and necrosis after SCI and facilitate early recovery of locomotive function.
Assuntos
Apoptose/efeitos dos fármacos , Receptor 1 de Quimiocina CX3C/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pirimidinas/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Tiazóis/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Biomarcadores/sangue , Inflamação/sangue , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/sangueRESUMO
PURPOSE: Although men with spinal cord injury (SCI) exhibit a prostate volume significantly smaller compared to age-matched able-bodied men, the independent association of lower prostate volume with its putative determinants has never been analyzed in this population. This study was designed to identify variables independently associated with prostate volume in men with chronic SCI. METHODS: In this cross-sectional study, prostate volume of 138 men with chronic (> 1 years) SCI, aged 54.5 (25th-75th percentile: 36.0-66.0) years, was evaluated with trans-rectal ultrasonography. All patients underwent a complete neurological exam, as well as biochemical and hormonal assessment, including total testosterone (TT) levels. Free testosterone levels were calculated (cFT) by the Vermeulen formula. RESULTS: The median prostate volume was 23.4 mL. At the univariate analysis, a larger prostate volume was associated with higher TT (p = 0.00001) and cFT (p = 0.001), SCI level below T12 (p = 0.007), more advanced age (p = 0.04), lower body mass index (p = 0.04), higher functional independence score (p = 0.06), higher values of prostate-specific antigen (p = 0.12) and shorter duration of the injury (p = 0.21). However, at the multiple regression analyses, an independent and positive association only persisted between the prostate volume with either TT or cFT levels, and, to a lesser extent, with age and a level of spinal lesion below T12. A prostate volume below the median value was observed in 91.4% (32/35) of patients with both androgen deficiency (TT < 264 ng/dL) and spinal lesion level ≥ T12, but only in 16.5% (2/12) of patients with both normal androgen levels and spinal lesion level below T12 (p < 0.001). CONCLUSIONS: Our data indicate that lower testosterone levels and, to a lesser extent, a younger age and a spinal lesion level ≥ T12 represent the only variables exhibiting an independent association with a smaller prostate volume in men with SCI.
Assuntos
Próstata/patologia , Traumatismos da Medula Espinal , Coluna Vertebral/patologia , Testosterona/sangue , Adulto , Fatores Etários , Idade de Início , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Doença Crônica , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Próstata/diagnóstico por imagem , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/patologia , Coluna Vertebral/diagnóstico por imagem , UltrassonografiaRESUMO
Previous reports have warned about the influence of spinal cord injury (SCI) on the pharmacokinetics of various drugs. However, the role of SCI in the efficacy and safety of pharmacotherapy remains unknown. Thereby, our aim was to explore the role of SCI on pharmacokinetics and anti-inflammatory effect of naproxen in response to a local inflammatory challenge. Rats received a severe contusive SCI at T9 or sham injury. Pharmacokinetics of a single intravenous dose of naproxen (10 mg kg-1) was studied at days 1 and 15 post-surgery. For the anti-inflammatory assessment, carrageenan was subcutaneously injected in forelimb and hindlimb paws at the same post-surgery periods, and naproxen efficacy was evaluated measuring paw swelling. Plasma protein concentrations and body weight changes were also determined. Plasma naproxen levels and pharmacokinetic parameters were unchanged by acute injury, but subacute injury generated alterations in volume of distribution, clearance, and bioavailability, resulting in significantly reduced plasma naproxen concentrations, in the absence of changes in plasma proteins. Assessment of naproxen anti-inflammatory activity during the acute stage of injury could not be determined because of carrageenan failure to elicit swelling. During the subacute stage, naproxen anti-inflammatory effect on forelimbs (above injury) was similar to that observed in sham-injured animals, while it was almost absent in paralyzed hindlimbs. Under conditions of SCI and peripheral inflammation, pharmacokinetics and anti-inflammatory activity of naproxen vary according to post-injury timing and neurological status of the assessed region.
Assuntos
Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/uso terapêutico , Naproxeno/sangue , Naproxeno/uso terapêutico , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Feminino , Mediadores da Inflamação/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Vértebras Torácicas/lesões , Resultado do TratamentoRESUMO
STUDY DESIGN: A multicentre retrospective study. OBJECTIVE: A multicentre retrospective study was performed to observe the changes in serum cystatin C (CysC) levels in patients with acute spinal cord injury (SCI). SETTING: Four hospitals in China. METHODS: Over a 5-year study period, the CysC, creatinine (Cr), and blood urea nitrogen (BUN) levels of people who had incurred SCI in the preceding 7 days were collected and compared with those of people with limb fracture (LF) who were matched for injury time and gender. People with SCI also were grouped by injury duration, ASIA Impairment Scale (AIS) grade and the presence or absence of steroid therapy and compared each day. RESULTS: Three hundred and twenty-three samples from people with SCI were retrospectively collected; their mean serum CysC levels were significantly higher than those of people with LF (p < 0.001); No significant difference was observed in Cr or BUN levels between the two groups (p > 0.14). CysC levels increased on the second day, peaked on day 3, and returned to normal on day 5. The more severely injured individuals had higher CysC levels. Steroid therapy or not had no influence for CysC levels. CONCLUSION: CysC levels are increased in patients with acute SCI, possibly as a direct result of injury. Serum CysC is a potential biomarker of SCI.
Assuntos
Cistatina C/sangue , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/sangue , China , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ureia/sangueRESUMO
The transplantation of Wharton's jelly derived mesenchymal stromal cells (WJ-MSCs) possesses therapeutic potential for the treatment of a spinal cord injury (SCI). Generally, the main effect of MSCs is mediated by their paracrine potential. Therefore, application of WJ-MSC derived conditioned media (CM) is an acknowledged approach for how to bypass the limited survival of transplanted cells. In this study, we compared the effect of human WJ-MSCs and their CM in the treatment of SCI in rats. WJ-MSCs and their CM were intrathecally transplanted in the three consecutive weeks following the induction of a balloon compression lesion. Behavioral analyses were carried out up to 9 weeks after the SCI and revealed significant improvement after the treatment with WJ-MSCs and CM, compared to the saline control. Both WJ-MSCs and CM treatment resulted in a higher amount of spared gray and white matter and enhanced expression of genes related to axonal growth. However, only the CM treatment further improved axonal sprouting and reduced the number of reactive astrocytes in the lesion area. On the other hand, WJ-MSCs enhanced the expression of inflammatory and chemotactic markers in plasma, which indicates a systemic immunological response to xenogeneic cell transplantation. Our results confirmed that WJ-MSC derived CM offer an alternative to direct stem cell transplantation for the treatment of SCI.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Traumatismos da Medula Espinal/terapia , Geleia de Wharton/citologia , Animais , Células Cultivadas , Citocinas/sangue , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.
Assuntos
Ciclismo , Terapia por Estimulação Elétrica/métodos , Metabolismo Energético , Músculo Esquelético/inervação , Atrofia Muscular/terapia , Treinamento Resistido/métodos , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Insulina/sangue , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/sangue , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento Resistido/efeitos adversos , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Virginia , Adulto JovemRESUMO
Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.
Assuntos
Ácidos Nucleicos Livres/sangue , Biologia Computacional , MicroRNAs/sangue , Traumatismos da Medula Espinal/sangue , Adulto , Ácidos Nucleicos Livres/classificação , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Humanos , Masculino , MicroRNAs/classificação , Comportamento Sedentário , Traumatismos da Medula Espinal/patologia , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/genéticaRESUMO
BACKGROUND: Spinal cord injury (SCI) induces an acute alteration in bone metabolism. Although the aetiology of the bone disturbances is not precisely known, immobilisation reduces mechanical loading and the morphology of osteocytes, which are the primary mechanosensors. Periostin and sclerostin are secreted mostly by osteocytes and are involved in bone's mechanical response. OBJECTIVE: The present study was conducted to determine whether individuals with SCI present alterations in serum periostin and sclerostin and to assess their relationships with bone mineral density, bone turnover markers, fracture status, time since injury, densitometric osteoporosis and paraplegic vs. tetraplegic status. SUBJECTS AND METHODS: One hundred and thirty-one individuals with SCI (96 males and 35 females; 42.8⯱â¯13.7â¯yr old) with a mean 14.2⯱â¯12.1â¯years since the time of injury were evaluated and compared with 40 able-bodied controls in a cross-sectional study. Periostin and sclerostin were assayed by ELISA from Biomedica® (Vienna, Austria), and bone turnover markers and areal bone mineral density (aBMD) were concomitantly analysed. RESULTS: Compared with controls, individuals with SCI presented higher periostin (pâ¯<â¯0.01), lower sclerostin (pâ¯<â¯0.001), similar markers of bone turnover levels and lower aBMD at the hip. Compared with chronic individuals, bone turnover markers, sclerostin excepted, values were higher as well as aBMD at hip in individuals with acute SCI. Moreover, the aBMD differences were more marked in tetraplegic than paraplegic individuals. Bone mineral density, fracture status, densitometric osteoporosis and paraplegia vs. tetraplegia did not seem to substantially influence the values of biological markers, sclerostin excepted. CONCLUSION: This study showed for the first time that individuals with SCI presented higher periostin levels than healthy controls only during the acute phase. Conversely, sclerostin levels are lower whatever the post-injury time. Fractures and densitometric osteoporosis were not associated with differences in these two biological markers, whereas paraplegia vs. tetraplegia and fragility fracture status seemed to influence sclerostin levels only.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Remodelação Óssea , Osso e Ossos/patologia , Moléculas de Adesão Celular/sangue , Fraturas Ósseas/sangue , Osteoporose/sangue , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Densidade Óssea , Osso e Ossos/fisiopatologia , Feminino , Humanos , Masculino , Tamanho do Órgão , Osteoporose/complicações , Osteoporose/fisiopatologia , Paraplegia/sangue , Paraplegia/fisiopatologiaRESUMO
STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess the association between clinical and demographic factors, bisphosphonate use, and circulating total osteocalcin levels in men with chronic spinal cord injury. SETTING: Veteran Affairs Medical Center. METHODS: As part of an epidemiological study assessing SCI-related health conditions, 214 men with chronic spinal cord injury underwent a DXA scan and provided a blood sample and information regarding SCI, medication use, and fracture history. General linear models were used to assess clinical/demographic factors of osteocalcin, and if significant, were included in multivariate model. RESULTS: We found that total osteocalcin levels increased 1.0 ng/ml for every kilogram increase in lean mass (p = 0.05) and increased 4.53 ng/ml for every ng/ml increase in C-telopeptide level (p < 0.0001). Osteocalcin levels were greater in people reporting no alcohol consumption compared with drinkers (15.49 ng/ml versus 18.58 ng/ml, p < 0.0002), lower in diabetics compared with nondiabetics (15.23 ng/ml versus 18.92 ng/ml, p = 0.0001), and lower in bisphosphonate users compared with nonusers (15.50 ng/ml versus 18.58 ng/ml, p < 0.03). The association between age and osteocalcin was not significant (p = 0.06). This model explained 58% of the variation in ln osteocalcin levels (model p < 0.0001, r2 = 0.58). CONCLUSIONS: Total osteocalcin levels vary based on health habits, body composition, comorbid illnesses, and bisphosphonate use in men with chronic spinal cord injury.
Assuntos
Densidade Óssea/fisiologia , Fraturas Ósseas/sangue , Fraturas Ósseas/diagnóstico por imagem , Osteocalcina/sangue , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/diagnóstico por imagem , Absorciometria de Fóton/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Estudos de Coortes , Estudos Transversais , Fraturas Ósseas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos da Medula Espinal/tratamento farmacológico , Adulto JovemRESUMO
STUDY DESIGN: Prospective cohort study. OBJECTIVE: To study associations between specific bone turnover markers and fall-related fractures in individuals with spinal cord injury (SCI). SETTING: Rehabilitation Hospital. METHODS: Carboxy terminal collagen crosslinks (CTX), type-1 procollagen N-terminal (P1NP), albumin-corrected calcium (Ca2+), parathyroid hormone (PTH) and vitamin D were examined in a cohort of 106 participants with SCI at least 1 year post injury. The participants were followed for 1 year monitoring fall-related fractures. RESULTS: In total, 29 out of 106 reported having experienced a fall-related fracture post-injury at baseline, and 5 out of 100 had experienced a fall-related bone fracture during the 1 year follow-up. Our main findings were that high levels of serum CTX increased the odds of being in the fracture group, and that 25-hydroxy vitamin D (25 OHD) levels, Ca2+, PTH or P1NP were not associated with being in the fracture group. CONCLUSIONS: We here present an association between high-CTX plasma levels at baseline and fall-related fractures reported during a 1-year follow-up among individuals with established SCI. We recommend studies with larger SCI populations before further clinical implications can be drawn.
Assuntos
Acidentes por Quedas , Colágeno Tipo I/sangue , Fraturas Ósseas/sangue , Fraturas Ósseas/diagnóstico , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Traumatismos da Medula Espinal/complicaçõesRESUMO
Spinal cord injury (SCI) is an incurable disorder with an unmet need of an effective treatment. Recently, autologous human bone marrow-derived stem cells have shown to promote functional improvement, due to their anti-inflammatory and regenerative/apocrine properties. In this study, the primary objective was to test whether a single intrathecal injection with a 100⯵L suspension of 400,000 fresh human bone marrow-derived CD34+ and an equal number of CD105+ stem cells (Neuro-Cells (NC)), one day after balloon-compression of the spinal cord, improves motor function and reduces secondary damage in immunodeficient rats. During the first 5â¯weeks after this intervention, NC significantly improved locomotor recovery and induced less injury-associated adverse events compared to vehicle-treated rats. Histological analysis showed that NC reduced astrogliosis, and apoptosis early after administration (day 4), but not at a later stage (day 56) after SCI. Proteomic studies (at day 56) pointed to the release of paracrine factors and identified proteins involved in regenerative processes. As stem cells seem to reach their effects in acute lesions by mainly suppressing (secondary) inflammation, it is thus realistic to expect a lower magnitude of their eventual beneficial effect in T-cell deficient rats, a fact reinforcing the robustness of Neuro-Cells efficacy. Taken together, this study indicates that an intrathecal instillation of Neuro-Cells holds great promise as a neuro-regenerative intervention in a clinical setting with acute SCI patients.