椎间盘内注射医用臭氧对椎间盘退变模型自身免疫反应的影响

目的:观察椎间盘内注射医用臭氧对椎间盘退变(intervertebral disc degeneration,IDD)动物模型自身免疫反应的影响,探讨其作用机理.方法:50只新西兰兔随机分为A、B、C、D、E共5组,其中A组为正常组,不作处理;B组为假手术组,仅暴露纤维环而不穿刺;C、D、E组采用后外侧纤维环穿刺的方法建立腰椎间盘退变模型(L6/7),在造模后14dD组模拟临床手术椎间盘内注射臭氧干预,E组椎间盘内注射医用纯氧,于造模后14d、21d对5组动物进行自由行走疼痛行为学评分,并于21d获取各组动物外周血,L6、L7神经根及L6/7髓核,运用透射比浊法测定各组动物血清中免疫球蛋白IgG和IgM水平,ELISA法测定血清中TNF-α、IL-1、IL-6的含量;免疫组化染色观察髓核中抗原抗体复合物沉积情况,应用图像分析系统记录染色阳性细胞的累积光密度值(integrated optical density,IOD);BCA蛋白定量法检测腰神经根中PLA2的活性.结果:造模后1周左右(平均7.4d)C、D、E组动物手术侧后肢活动减少,并在爬行前进时明显偏离手术侧,行走疼痛学评分分别为2.81±0.13分、2.69±0.11分、2.64±0.31分,组间比较差异无统计学意义(P＞0.05);D组注射臭氧后上述异常行为逐渐减轻,处死前行走疼痛学评分为0.54±0.12分,低于C组(2.75±0.17分)及E组(2.52±0.96分)(P＜0.05);D组动物血清中IgG、IgM水平(6.05±0.49g/L,1.98±0.28g/L)低于C组(8.98±0.77g/L,2.40±0.25g/L)及E组(8.52±0.63g/L,2.91±0.3 1g/L) (P＜0.05),与A组(5.43±0.29g/L,1.72±0.15g/L)及B组(4.97±0.35g/L,1.66±0.27g/L)比较差异无统计学意义(P＞0.05);D组炎性细胞因子TNF-α、IL-1、IL-6的含量(98±11pg/ml,247±21pg/ml,149±23.4pg/ml)亦低于C组(256±39pg/ml,404±19pg/ml,231±41.3pg/ml)及E组(244±45pg/ml,410±15pg/ml,249±21.7pg/ml) (P＜0.05),与A组(70±6pg/ml,223±17pg/ml,141±12.6pg/ml)及B组(79±1 1pg/ml,238±32pg/ml,138±17.4pg/ml)比较差异无统计学意义(P＞0.05);D组髓核中抗原抗体复合物阳性沉积光密度值(7.40±3.56)小于C组(27.49±12.84)及E组(29.55±10.38)(P＜0.05),其相应节段腰神经根PLA2活性(0.0189±0.0072μmol/min·L)较C组(0.1685±0.0103μmol/min·L)及E组(0.1994 ±0.080μmol/min·L)明显下降(P＜0.01),与A组(0.0036±0.0081μmol/min·L和B组(0.0098±0.0043 μmoL/min·L)比较差异无统计学意义(P＞0.05).结论:医用臭氧能够在一定程度上抑制腰椎间盘退变模型中异常的自身免疫反应,这可能是臭氧治疗椎问盘退变引起的腰痛的作用机制之一.     

经皮椎间盘摘出联合医用臭氧治疗腰椎间盘突出症

目的探讨经皮髓核摘除术(PLD)联合医用臭氧注射治疗腰椎间盘突出症的临床效果及可行性。方法临床与影像检查确诊为腰椎间盘突出25例,先行PLD,后行椎间盘内及椎旁注射臭氧。结果25例病人治疗后经一年随访,治愈21例,有效24例,无效1例,无一例并发症。结论PLD联合医用臭氧治疗腰椎间盘突出症,安全可靠,可改善治疗效果,减少不良反应,值得推广应用。     

中药封包外敷联合臭氧局部注射治疗脊神经后支综合征56例

目的 评估中药封包联合臭氧治疗脊神经后支综合征的临床疗效。 方法 将112例脊神经后支综合征患者随机分为观察组和对照组,每组56例,在中药封包外敷腰背部痛区的基础上,观察组予局部臭氧注射,对照组予局部神经阻滞,连续治疗3周。观察治疗后疼痛缓解情况,并评估治疗3周后及治疗后3个月临床疗效。 结果 治疗3周后和治疗后3个月,两组VAS评分均较治疗前明显下降（P<0.05）,且观察组显著低于对照组（P<0.05）;治疗3周后和治疗后3个月,两组临床疗效的分布比较,差异均具有统计学意义（P<0.05）,观察组明显优于对照组。 结论 中药封包联合臭氧局部注射可有效治疗脊神经后支综合征,且远期疗效显著。     

臭氧自血疗法联合药物治疗带状疱疹后神经痛的疗效评价

 目的探讨臭氧自血疗法联合药物治疗带状疱疹后神经痛（PHN）的效果。方法纳入118例PHN患者并随机分为对照组和观察组,每组59例。对照组采用双氯芬酸、普瑞巴林和甲钴胺药物口服治疗,观察组在此基础上联合臭氧自血疗法,均治疗1个月。使用VAS评分、SF-MPQ评分及WHOQOL-BREF量表评估治疗前、治疗后1周、2周和1个月时所有PHN患者的症状改善情况,同时检测血浆β-内啡肽、P物质、IL-1β和TNF-α的水平。结果完成研究103例,其中对照组52例,治疗组51例。与对照组相比,观察组患者治疗后1个月时VAS评分(t=2.38）、SF MPQ评分(t=2.72)和WHOQOL BREF评分(t=2.54)均有统计学差异(均P<0.05),观察组血浆β-内啡肽水平(t=2.61)明显提高,P物质水平(t=2.48)、IL-1β(t=2.32)和TNF-α(t=2.40)水平明显下降(均P<0.05)。结论臭氧自血疗法联合药物治疗优于单纯药物治疗PHN。     

Skin cancer and ultraviolet-B radiation under the Antarctic ozone hole: southern Chile, 1987-2000

BACKGROUND: Punta Arenas, Chile, the southernmost city in the world (53 degrees S), with a population of 154,000, is located near the Antarctic ozone hole (AOH) and has been regularly affected by high levels of ultraviolet-B (UV-B) radiation each spring for the last 20 years. Large increases in UV-B associated with the AOH have been measured with increases in UV-B at 297 nm of up to 38 times those of similar days with normal ozone. Recently we reported significant increases in sunburns during the spring of 1999 on days with low ozone because of the AOH. METHODS: A surveillance of skin cancers occurring from 1987 to 2000 was performed. Age, sex, location, type of skin cancer and skin phototype were recorded. A Brewer Spectrophotometer was used in order to obtain in situ measurements of ozone and UV-B. Total Ozone Mapping Spectrometer (TOMS) data from National Aeronautics and Space Administration (NASA) was used in order to establish pre-ozone hole climatology. RESULTS: Ozone levels as low as 145 DU (Dobson Units) were recorded, a 56% decrease in ozone, and UV-B levels up to 4.947 J/m2. These levels are close to summertime levels at mid latitudes. For the 14-year period--from 1987 to 2000--173 cases of skin cancer were diagnosed, 65 during the first 7 years, 108 during the second, an increase of 66%. Cutaneous malignant melanoma (CMM), 19% of the cases, increased by 56%, raising the rate from 1.22 to 1.91 per 100,000. Non-melanoma skin cancer (NMSC), 81% of the total, increased the rate from 5.43 to 7.94 per 100 000 (P < 0.05), a 46% increase. Patients with CMM and NMSC had skin phototypes I-II in 59% and 54% of cases, respectively. Days with more than 25% ozone loss occurred in 143 days during the last 20 springs. Significant increases of UV-B were observed under ozone hole conditions, especially around 300 nm, the most carcinogenic wavelengths. CONCLUSIONS: Highly unusual ozone loss and UV-B increases have occurred in the Punta Arenas area over the past two decades resulting in the non-photoadapted population being repeatedly exposed to an altered solar UV spectrum with a greater effectiveness for erythema and photocarcinogenesis. This phenomenon has not previously been reported over other populated areas and an additional increase in the skin cancer rate attributable to the AOH may be occurring. Research on the clinical and subclinical impact of these abnormalities is urgently needed.     

Alveolar permeability to protein in rats differentially susceptible to ozone

Sprague-Dawley rats susceptible (DS) to NaCl-induced hypertension suffer higher mortality when exposed daily to 2.0 ppm ozone than do hypertension-resistant (DR) rats, independent of salt in the diet or systemic blood pressure. To investigate one possible contribution to this differential sensitivity to ozone, alveolar permeabilities to serum albumin were measured both in ozone-exposed and in control DS and DR rats. Female rats aged 5-7 weeks maintained on a low-salt (0.4% NaCl) diet were injected intravenously with 125I-bovine serum albumin and were then exposed to either 2.0 ppm ozone or air for 5 h. After pentobarbital anesthesia, the rats were exsanguinated and their lungs were lavaged in situ with saline. Lavage fluids and blood samples were measured for radioactivity using a NaI-well gamma counter. The results indicated that while DS and DR control rats have similar pulmonary permeabilities to 125I-albumin, the lungs of the ozone-exposed DS animals were 63% (p less than 0.02) more permeable than those of DR rats exposed to ozone. Sloughing of epithelial tissue, mucous formation and an accumulation of macrophages in the end-airways were more pronounced among ozone-exposed DS animals than in DR-ozone-exposed rats. This increased damage among DS rats correlated well with the increased protein permeability levels. In similar studies, Sprague-Dawley (D) rats were more variable in their response to ozone than either inbred strain. However, the results appeared generally more like those of the DS animals, suggesting that the trait selected by inbreeding may have been resistance rather than sensitivity to ozone-induced lung injury.     

The investigation of non‐invasive techniques for treating early approximal carious lesions: an in vivo study

Objectives: The aim of this study was to examine non‐cavitated approximal caries using non‐invasive treatment methods. Materials and methods : Molar and premolar teeth with approximal caries were used in this in vivo study. Approximal caries lesions were evaluated with visual and radiographic inspection and with the DIAGNOdent device. Five groups were formed to study non‐invasive treatment, and each had at least 25 early approximal carious lesions. Patients in the control group were not treated. After the separation, either ozone application, acidulated phosphate fluoride gel, CPP‐ACP‐containing material (Tooth Mousse), or an antibacterial bonding agent (Clearfil Protect Bond) was used. For 18 months after the non‐invasive treatment, radiological controls were used to observe the progress of the initial and approximal caries in the 1st, 3rd, 6th and 12th months of follow‐up. A Mann–Whitney U‐test was used to perform the statistical analysis; in‐group comparisons were made with the Wilcoxon signed‐rank test, and a quantitative assessment was performed using a chi‐squared test. Results: At the end of 18 months, the caries lesions in the control group were observed to progress (P < 0.01). The lesions that were scored as 1a during a visual inspection recovered by using non‐invasive treatments. Conclusion: Approximal caries lesions that were detected at the early stages remained stationary when using antibacterial agents and materials that promoted remineralisation. Clinical relevance: Antibacterial agents and remineralisation materials can be used in treatment of early approximal caries lesions.     

臭氧髓核消融联合小针刀治疗腰椎间盘突出症的临床分析

目的：观察臭氧髓核消融联合小针刀治疗腰椎间盘突出症的临床疗效。方法：150例腰椎间盘突出症患者采用臭氧髓核消融联合小针刀治疗,从后侧方穿刺至病变椎间盘中央,椎间盘外注入臭氧,椎间隙及患椎棘突旁进行针刀松解,观察效果。结果：穿刺成功率100％,总有效率92％。结论：臭氧髓核消融联合小针刀治疗腰椎间盘突症出安全有效,值得临床推广。     

Protective Role of Interleukin-10 in Ozone-Induced Pulmonary Inflammation

Background

The mechanisms underlying ozone (O₃)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.

Objectives

We investigated the molecular mechanisms underlying interleuken-10 (IL-10)–mediated attenuation of O₃-induced pulmonary inflammation in mice.

Methods

Il10-deficient (Il10^−/−) and wild-type (Il10^+/+) mice were exposed to 0.3 ppm O₃ or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O₃-induced inflammation.

Results

Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10^−/− mice than in Il10^+/+ mice after exposure to O₃ at all time points tested. O₃-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10^−/− compared with Il10^+/+ mice. Gene expression analyses revealed several IL-10–dependent and O₃-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.

Conclusions

Results indicate that IL-10 protects against O₃-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O₃-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.     

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0?ppm ozone for 4?h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.