Vitamin D Receptor (VDR) Genetic Polymorphisms Associated with Intervertebral Disc Degeneration

<正>Intervertebral disc degeneration(IDD)is characterized by disc dehydration and herniation,which is often associated with low back pain and lumbar radiculopathy due to nerve root compression or inflammation.The pathophysiology of IDD is not completely elucidated so far.Some researchers have indicated that disc degeneration begins as early as the second decade of life(Mayer et al.,2013).Common risk factors are     

氧化应激介导的NF-kB 信号转导通路在椎间盘退变中的作用

椎间盘位于两个椎体之间,在脊柱中发挥着连接、减震和固定作用,其发生退变可以引起一系列椎间盘退变性疾病,是多数 脊柱疾病发病的根本原因,探索椎间盘的退变机制是寻找其治疗措施的前提。椎间盘退变机制十分复杂,其最主要的病理基础是 椎间盘活性细胞减少以及其引起的细胞外基质合成减少和成分的改变,而NF-kB 作为一种普遍存在在真核细胞中的多向性转录 因子,通过多种途径在细胞增殖、分化及凋亡方面起着关键的作用,研究表明,抑制NF-kB信号通路可以有效的缓解椎间盘退变; 而引起NF-kB信号通路的异常激活的因素很多,其中氧化应激是一个重要的因素,同时研究证实在椎间盘退变中存在着氧化损 伤。因此,当年龄、营养、外伤等因素引起的椎间盘细胞中发生氧化应激,进而导致NF-资B信号通路的激活,从而使其转录活性增 高,触发凋亡信号,引起髓核细胞的大量凋亡,使其参与到椎间盘退变中。     

The Nucleus of the Intervertebral Disc from Development to Degeneration

The nucleus of the intervertebral disc in humans shows the mostdramatic changes with age of any cartilaginous tissue. It originatesfrom the notochord. In the foetus and infant, the nucleus containsactively dividing and biosynthetically active notochordal cells.The proteoglycans and other matrix components produced havea high osmotic pressure, imbibe water and maintain a hydratedstructure which, though it has little mechanical strength, hasa high swelling pressure which maintains disc turgor. In somespecies, the notochordal cells and the mucoid nucleus pulposuspersist throughout adult life. However by about 4 yr of agein humans, the notochordal cells have disappeared to be replacedby those of chondrocytic appearance but of unknown origin. Thesecells continue to produce proteoglycans but also synthesizesignificant amounts of collagen. The nucleus becomes firmerand less hydrated and loses its transparent appearance. Thecell density of the adult nucleus is very low with cells occupyingless than 0.5% of tissue volume; each cell thus has to turnover and maintain a large domain of extracellular matrix. Thedensity of living cells decreases with age, possibly becauseof problems with nutrient supply to this large avascular tissue.Proteoglycan concentration also falls, and nucleus hydrationdecreases markedly, the disc discolours and in many cases cleftsand fissures form. In most adults, the disc nucleus degenerateseventually to a stage where it can no longer fulfil its mechanicalrole.     

Tree Nuts Are Inversely Associated with Metabolic Syndrome and Obesity: The Adventist Health Study-2

Objective

To examine the relationships of nut consumption, metabolic syndrome (MetS), and obesity in the Adventist Health Study-2, a relatively healthy population with a wide range of nut intake.

Research Design and Methods

Cross-sectional analysis was conducted on clinical, dietary, anthropometric, and demographic data of 803 adults. MetS was defined according to the American Heart Association and the National Heart, Lung, and Blood Institute diagnostic criteria. We assessed intake of total nuts, tree nuts and peanuts, and also classified subjects into low tree nut/low peanut (LT/LP), low tree/high peanut (LT/HP), high tree nut/high peanut (HT/HP), and high tree/low peanut (HT/LP) consumers. Odds ratios were estimated using multivariable logistic regression.

Results

32% of subjects had MetS. Compared to LT/LP consumers, obesity was lower in LT/HP (OR = 0.89; 95% CI = 0.53, 1.48), HT/HP (OR = 0.63; 95% CI = 0.40, 0.99) and HT/LP (OR = 0.54; 95% CI = 0.34, 0.88) consumers, p for trend = 0.006. For MetS, odds ratios (95% CI) were 0.77 (0.47, 1.28), 0.65 (0.42, 1.00) and 0.68 (0.43, 1.07), respectively (p for trend = 0.056). Frequency of nut intake (once/week) had significant inverse associations with MetS (3% less for tree nuts and 2% less for total nuts) and obesity (7% less for tree nuts and 3% less for total nuts).

Conclusions

Tree nuts appear to have strong inverse association with obesity, and favorable though weaker association with MetS independent of demographic, lifestyle and dietary factors.     

Bright Liver and Alanine Aminotransferase Are Associated with Metabolic Syndrome in Adults

Objectives: The metabolic syndrome has become a significant health problem worldwide. In this study, we investigated the relationship between the metabolic syndrome, bright liver (BL) by ultrasonography (US), and plasma alanine aminotransferase (ALT) levels among apparently healthy adults. Research Methods and Procedures: A total of 15, 430 nonalcoholic healthy adults without hepatitis B or C were recruited from four nationwide MJ Health Screening Centers in Taiwan in 2000. Metabolic syndrome was defined using the National Cholesterol Education Panel (NCEP) metabolic syndrome criteria or modified NCEP criteria. Based on liver US, subjects were classified into either having BL or not. The relationship between the metabolic syndrome, BL, and ALT levels was examined using multivariate logistic regression analysis. Results: The crude OR of the metabolic syndrome was 13.92 (12.19 using modified NCEP criteria), and the age‐BMI‐sex—adjusted OR was 3.77 (3.71 using modified NCEP criteria) in subjects with BL vs. subjects without BL, respectively. The ORs of the metabolic syndrome were significantly higher in subjects with elevated ALT levels than in those with normal ALT levels. After adjustment for age, sex, and BMI, BL and elevated ALT level were independently associated with increased risk of the metabolic syndrome. Discussion: Presence of BL and elevated plasma ALT level was independently associated with increased risk of the metabolic syndrome in adults. These factors contribute to a list of well‐known risk factors, including obesity, aging, and male sex, and thus can be applied as an additional evaluation for the metabolic syndrome in a clinical setting.     

Work-Related Psychological Injury Is Associated with Metabolic Syndrome Components in Apparently Healthy Workers

Objective

The aim of this study was to evaluate the association between psychological damage caused by common occupational trauma and metabolic syndrome (MES).

Method

571 workers from 20 small Italian companies were invited to fill in the Psychological Injury Risk Indicator (PIRI) during their routine medical examination at the workplace.

Results

Compared to workers with no psychological injury, workers with a high PIRI score had a significantly increased risk of having at least one metabolic syndrome component (adjusted hazards ratio, 1.8; 95% confidence interval, 1.2 to 2.6). There was a significant increase in the risk of hypertriglyceridemia in male workers (OR 2.53 CI95% 1.03-6.22), and of hypertension in female workers (OR 2.45 CI95% 1.29-4.66).

Conclusion

Psychological injury related to common occupational trauma may be a modifiable risk factor for metabolic syndrome.     

Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking.     

几种椎间盘退变动物模型的建立和应用

椎间盘退变是一种年龄相关的退行性疾病,是引起下腰痛的主要因素,严重影响病人的生活质量,并显著增加家庭的经济负担。目前,缺少椎间盘退变的有效干预和治疗手段,部分原因是其发病机制尚未阐明。椎间盘退变动物模型的构建对于阐明该疾病的病理机制至关重要。椎间盘退变是一个复杂的过程,受机械应力、结构损伤、生物化学与基因表达等多种因素的影响。本文总结了应用异常机械应力、结构损伤、生物化学或化学诱导和基因敲除等方式构建的椎间盘退变动物模型。生物力学是维持椎间盘稳态的重要因素,异常的机械应力会导致椎间盘退变。同时,椎间盘退变常伴随结构性损伤,椎间盘结构破坏也会导致椎间盘发生退变。此外,生物化学或化学诱导和关键基因敲除也会导致椎间盘退变。本文按照造成异常机械应力的因素将机械应力模型分为加压模型和失稳模型;按照椎间盘结构将结构损伤模型分为髓核与纤维环损伤模型和软骨终板损伤模型。总结了生物化学或化学诱导模型以及新型的基因敲除模型。讨论了不同类型椎间盘退变动物模型的可能应用和局限性。     

Metabolic Syndrome,Alcohol Consumption and Genetic Factors Are Associated with Serum Uric Acid Concentration

Objective

Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals.

Methods

The cohort consisted of 589 healthy subjects aged 18–65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables.

Results

The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations.

Conclusion

Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.     

NF-κB信号通路参与高糖在椎间盘退行性变中影响及其作用的研究

目的:近来研究发现,椎间盘退变与代谢性疾病,尤其是与糖尿病具有明显的相关性,但具体机制尚未有深入研究。本实验拟探究高糖微环境诱导椎间盘退行性变及其对NF-κB信号通路的影响,为进一步揭示高糖诱导椎间盘髓核细胞退变的机制提供研究基础,为延缓、阻止糖尿病椎间盘退变和治疗糖尿病相关腰痛疾病带来新的策略和方法。方法:1、高糖微环境与IVDD的关系:使用5.5 mmol/L、15 mmol/L、30 mmol/L、100 mmol/L不同浓度葡萄糖培养基培养髓核细胞,RT-PCR检测髓核细胞MMP-3、MMP-13、Aggrecan、CollagenII的表达;2、NF-κB信号通路参与高糖微环境调控IVDD进展:Bay11-7082抑制NF-κB信号通路激活,再使用RT-PCR、Western Blot检测髓核细胞MMP-3、MMP-13、Aggrecan、CollagenII和NF-κB的表达。结果:RT-PCR检测显示,在不同葡萄糖浓度下,Aggrecan、CollagenII随浓度升高表达减少,MMP-3、MMP-13随浓度升高表达增加。RT-PCR、Western Blot检测显示,使用Bay11-7082可使高糖组中Aggrecan、CollagenII表达增加,MMP-3、MMP-13表达减少。结论:高糖微环境诱导椎间盘退行性变发病,且NF-κB信号通路参与高糖微环境诱导椎间盘退行性变发病。     

Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

PurposeTo measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans.MethodsParticipants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities.ResultsOne thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity.ConclusionsMeeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors.     

Higher Gravidity and Parity Are Associated with Increased Prevalence of Metabolic Syndrome among Rural Bangladeshi Women

Background

Parity increases the risk for coronary heart disease; however, its association with metabolic syndrome among women in low-income countries is still unknown.

Objective

This study investigates the association between parity or gravidity and metabolic syndrome in rural Bangladeshi women.

Methods

A cross-sectional study was conducted in 1,219 women aged 15–75 years from rural Bangladesh. Metabolic syndrome was defined according to the standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between parity and gravidity and metabolic syndrome, with adjustment of potential confounding variables.

Results

Subjects with the highest gravidity (> = 4) had 1.66 times higher odds of having metabolic syndrome compared to those in the lowest gravidity (0-1) (P _trend = 0.02). A similar association was found between parity and metabolic syndrome (P _trend = 0.04), i.e., subjects in the highest parity (> = 4) had 1.65 times higher odds of having metabolic syndrome compared to those in the lowest parity (0-1). This positive association of parity and gravidity with metabolic syndrome was confined to pre-menopausal women (P _trend <0.01). Among the components of metabolic syndrome only high blood pressure showed positive association with parity and gravidity (P _trend = 0.01 and <0.001). Neither Parity nor gravidity was appreciably associated with other components of metabolic syndrome.

Conclusions

Multi parity or gravidity may be a risk factor for metabolic syndrome.     

Low-Grade Albuminuria Is Associated with Metabolic Syndrome and Its Components in Middle-Aged and Elderly Chinese Population

Background

Micro-albuminuria has been well established as one of the risk factors of metabolic syndrome (MetS). However, the association of MetS and its components with low-grade albuminuria among those with normal urinary albumin excretion has not been clearly elucidated in Chinese population.

Methodology and Findings

A cross-sectional study was conducted among 9,579 participants with normal urinary albumin excretion, who were recruited from Jia Ding District, Shanghai, China. The single-void first morning urine sample was collected for urinary albumin and creatinine measurements, and urinary albumin-to-creatinine ratio (UACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as sex-specific upper UACR quartile in this population. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of MetS and its components increased across the UACR quartiles (all P _trend <0.01). A multivariable adjusted logistic regression analysis revealed that the prevalence of MetS was gradually elevated according to the UACR quartiles (adjusted odds ratios [ORs] were 1.14, 1.24 and 1.59 for UACR quartiles 2, 3 and 4, compared with the lowest quartile; P _trend<0.0001). In the further stratified logistic regression analyses, the associations between low-grade albuminuria and MetS were significant in both sex strata (male and female), both age strata (<60 and ≥60 years), both body mass index strata (<24 and ≥24 kg/m²), and both diabetes strata (yes and no). Compared to the lowest UACR quartile, the participants in the highest quartile of UACR had the highest prevalence of central obesity (OR = 1.43; 95%CI = 1.25–1.63), high blood pressure (OR = 1.64; 95%CI = 1.43–1.87), hyperglycemia (OR = 1.52; 95%CI = 1.30–1.78) and high triglycerides (OR = 1.19; 95%CI = 1.04–1.37).

Conclusions and Significance

Low-grade albuminuria was significantly associated with the increasing prevalence of MetS and its components in the middle-aged and elderly Chinese population with normal urinary albumin excretion.     

正常与退变椎间盘髓核和纤维环中生化成份的研究

本工作测定了椎间盘的髓核和纤维环中的生化成份,结果提示在退变的椎间盘中,糖醛酸,总己糖胺、半乳糖胺均明显下降,而羟脯氨酸的含量明显增加。在退变的纤维环中尚有组成硫酸角质素的主要成份葡萄糖胺量的明显下降。在退变的髓核和纤维环中,总蛋白质含量呈增加趋势,水的含量呈下降趋势。提示退变椎间盘中蛋白多糖含量降低,组成改变及胶原蛋白的增加可能是诱发椎间盘突出症的物质基础。     

MRI Assessment of Lumbar Intervertebral Disc Degeneration with Lumbar Degenerative Disease Using the Pfirrmann Grading Systems

Background

To evaluate by MRI intervertebral disc degeneration in patients with lumbar degenerative disease using the Pfirrmann grading system and to determine whether Modic changes correlated with the Pfirrmann grades and modified Pfirrmann grades of disc degeneration.

Methods

The clinical data of 108 surgical patients with lumbar degenerative disease were reviewed and their preoperative MR images were analyzed. Disc degeneration was evaluated using the Pfirrmann grading system. Patients were followed up and low back pain was evaluated using the visual analog scale (VAS) and the effect of back pain on the daily quality of life was assessed using Oswestry disability index (ODI).

Results

Forty-four cases had normal anatomical appearance (Modic type 0) and their Pfirrmann grades were 3.77±0.480 and their modified Pfirrmann grades were of 5.81±1.006. Twenty-seven cases had Modic type I changes and their Pfirrmann grades were 4.79±0.557 and their modified Pfirrmann grades were 7.00±0.832. Thirty-six cases exhibited Modic type II changes and their Pfirrmann grades and modified Pfirrmann grades were 4.11±0.398 and 6.64±0.867, respectively. One case had Modic type III changes. Kruskal-Wallis test revealed significant difference in modified Pfirrmann grade among Modic type 0, I and II changes (P<0.01) but no significant difference between Modic type I and II changes (P>0.05). Binary regression analysis showed that Modic changes correlated most strongly with disc degeneration. Follow up studies indicated that the VAS and ODI scores were markedly improved postoperatively. However, no difference was noted in VAS and ODI scores among patients with different Modic types.

Conclusion

Modic changes correlate with the Pfirrmann and modified Pfirrmann grades of disc degeneration in lumbar degenerative disease. There is no significant correlation between Modic types and surgical outcomes.     

Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study

Background

Age-related macular degeneration (AMD) is the main cause of blindness in the developed world. The etiology of AMD is multifactorial due to the interaction between genetic and environmental factors. IL-8 has a role in inflammation and angiogenesis; we report the genetic characterization of IL-8 allele architecture and evaluate the role of SNPs or haplotypes in the susceptibility to wet AMD, case-control study.

Methods

Case-control study including 721 AMD patients and 660 controls becoming from Italian population. Genotyping was carried out by Real Time-PCR. Differences in the frequencies were estimated by the chi-square test. Direct sequencing was carried out by capillary electrophoresis trough ABI3130xl.

Results

rs2227306 showed a p–value of 4.15*10⁻⁵ and an Odds Ratio (OR) for T allele of 1.39 [1.19–1.62]. After these positive results, we sequenced the entire IL-8 regulatory and coding regions of 60 patients and 30 controls stratified for their genotype at rs2227306. We defined two different haplotypes involving rs4073 (A/T), rs2227306 (C/T), rs2227346 (C/T) and rs1126647 (A/T): A-T-T-T (p-value: 2.08*10⁻⁹; OR: 1.68 [1.43–1.97]) and T-C-C-A (p-value: 7.07*10⁻¹¹; OR: 0.60 [0.51–0.70]). To further investigate a potential functional role of associated haplotypes, we performed an expression study on RNA extracted from whole blood of 75 donors to verify a possible direct correlation between haplotype and gene expression, failing to reveal significant differences.

Conclusions

These results suggest a possible secondary role of IL-8 gene in the development of the disease. This paper outlines the importance of association between inflammation and AMD. Moreover IL-8 is a new susceptibility genomic biomarker of AMD.     

Reduced Flexibility Associated with Metabolic Syndrome in Community-Dwelling Elders

Background

The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population.

Methods

A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force), lower extremity muscle endurance (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory endurance (2-minute step test). Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables.

Results

Metabolic syndrome was associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95% confidence interval (CI), 1.25–2.07) and decreased flexibility (OR, 0.97, 95% CI, 0.95–0.99) compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI.

Conclusion

Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength and cardiorespiratory fitness in the elderly were not observed. Furthermore, flexibility should be included in the complete evaluation for metabolic syndrome.     

Cardiorespiratory Fitness,Sedentary Behaviour and Physical Activity Are Independently Associated with the Metabolic Syndrome,Results from the SCAPIS Pilot Study

Background

Previous studies on the relation between lifestyle and the metabolic syndrome lack one or several aspects of the physical activity pattern in the analyses or cardiorespiratory fitness. Likewise, both uni- and triaxial accelerometry have been used, though, the predictive validity of these two modes has not been compared.

Objectives

The aims of the present study were firstly to investigate the independent relation between cardiorespiratory fitness and physical activity pattern to the metabolic syndrome (MetS) and secondly to examine the predictive validity of uni- and triaxial accelerometry, respectively.

Methods

Data was extracted from the SCAPIS pilot study (n=930, mean age 57.7 yrs). Physical activity pattern was assessed by accelerometry. Cardiorespiratory fitness was estimated using cycle ergometry. MetS was defined per the Adult Treatment Panel III from the National Cholesterol Education Program definition.

Results

Time spent sedentary (OR: 2.38, 95% CI: 1.54-4.24 for T3 vs T1), in light intensity (OR: 0.50, 95% CI: 0.28-0.90) and in moderate-to-vigorous activity (OR: 0.33, 95% CI: 0.18-0.61), as well as cardiorespiratory fitness (OR: 0.24, 95% CI:0.12-0.48), were all independently related to the prevalence of MetS after adjustment for potential confounders, fitness and/or the other aspects of the physical activity pattern. In addition, we found that triaxial analyses were more discriminant, with ORs farther away from the reference group and additional significant ORs.

Conclusion

The finding that several aspects of the physical activity pattern reveal independent relations to the MetS makes new possible targets for behaviour change of interest, focusing on both exercise and everyday life. When assessing the risk status of a patient, it is advised that triaxial accelerometry is used.     

Effects of Single Injection of Local Anesthetic Agents on Intervertebral Disc Degeneration: Ex Vivo and Long-Term In Vivo Experimental Study

Background

Analgesic discography (discoblock) can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD) cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model.

Methods

For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine). Nucleus pulposus (NP) cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI) and histological analysis.

Results

In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline- and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups.

Conclusions/Significance

In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents on degenerated IVDs.