亚硫酸盐和雌激素及炎症因子在老年女性膝骨关节炎血清与关节液中的水平及意义

目的探讨亚硫酸盐和雌激素及炎症因子在老年女性骨关节炎患者血清及关节液中的含量变化及其抗炎效应。方法选择住院老年女性患者26例,年龄55～75岁,中位年龄67岁;病史1.8～25.6年,平均10年。均为我科初诊患者,根据骨性关节炎诊断标准确诊为膝骨关节炎,留取治疗前常规关节腔减压治疗时抽吸的关节液,及治疗后复查时的关节液。测定血清雌二醇水平、血清及关节液中的亚硫酸盐及白介素(IL-1、IL-6、IL-8)的含量变化。结果老年女性膝骨关节炎患者的血清雌激素(雌二醇)水平显著低于对照组(P<0.01);急性期血清关节液中亚硫酸盐和炎性因子(IL-1、IL-6和IL-8)均较高,经治疗后恢复期时各值均显著下降(P<0.01)。再根据不同年龄段分组,测定不同年龄段的膝骨关节炎患者急性期血清及关节液中亚硫酸盐和炎症因子(IL-1、IL-6和IL-8)的变化,各炎症因子变化差异无统计学意义(P>0.05);而血清雌二醇水平随年龄增加而减低,差异有统计学意义(P<0.01);急性期骨关节液中亚硫酸盐水平随年龄增加而减低,差异有统计学意义(P<0.01)。随着年龄的增长,骨关节炎患者血清雌二醇水平与关节液中亚硫酸盐含量之间有相关性(R2=-0.991,P<0.05)。结论亚硫酸盐和雌激素及炎症因子共同参与老年女性骨关节炎的发病过程,可能是一种生物活性分子在炎症局部发挥一定的病理生理学作用。     

Changes of the levels of sulfite,estrogen and inflammatory factors in serum and synovial fluids in elderly women with knee osteoarthritis

目的 探讨亚硫酸盐和雌激素及炎症因子在老年女性骨关节炎患者血清及关节液中的含量变化及其抗炎效应.方法 选择住院老年女性患者26例,年龄55 ～ 75岁,中位年龄67岁;病史1.8 ～25.6年,平均10年.均为我科初诊患者,根据骨性关节炎诊断标准确诊为膝骨关节炎,留取治疗前常规关节腔减压治疗时抽吸的关节液,及治疗后复查时的关节液.测定血清雌二醇水平、血清及关节液中的亚硫酸盐及白介素(IL-1、IL-6、IL-8)的含量变化.结果 老年女性膝骨关节炎患者的血清雌激素(雌二醇)水平显著低于对照组(P＜0.01);急性期血清关节液中亚硫酸盐和炎性因子(IL-1、IL-6和IL-8)均较高,经治疗后恢复期时各值均显著下降(P＜0.01).再根据不同年龄段分组,测定不同年龄段的膝骨关节炎患者急性期血清及关节液中亚硫酸盐和炎症因子(IL-1、IL-6和IL-8)的变化,各炎症因子变化差异无统计学意义(P＞0.05);而血清雌二醇水平随年龄增加而减低,差异有统计学意义(P＜0.01);急性期骨关节液中亚硫酸盐水平随年龄增加而减低,差异有统计学意义(P＜0.01).随着年龄的增长,骨关节炎患者血清雌二醇水平与关节液中亚硫酸盐含量之间有相关性(R2=-0.991,P＜0.05).结论 亚硫酸盐和雌激素及炎症因子共同参与老年女性骨关节炎的发病过程,可能是一种生物活性分子在炎症局部发挥一定的病理生理学作用.     

支原体肺炎合并心肌炎患儿促炎与抑炎因子表达的变化观察

目的观察支原体肺炎合并心肌炎患儿促炎与抑炎因子表达的变化情况。方法选取2016年2月至2017年8月期间的35例支原体肺炎患儿为A组,同期的35例心肌炎患儿为B组,35例支原体肺炎合并心肌炎患儿为C组,检测与比较三组患儿的血清促炎因子(TNF-α、IL-1β及IL-6)及抑炎因子(IL-10及IL-13)水平。结果 C组的血清促炎与抑炎因子表达均高于A组及B组,而B组则高于A组,差异有统计学意义(P <0.05)。结论支原体肺炎合并心肌炎患儿促炎与抑炎因子均呈现显著升高的状态,应重视对此类患儿进行炎性反应的监控与调节。     

膝骨性关节炎患者血清和关节液FGF-21与IL-1及TNF-a水平的变化及意义

目的 探讨膝骨关节炎(Knee osteoarthritis,KOA)患者血清、关节液中成纤维细胞生长因子-21(Fibroblast growth factor 21,FGF-21)、白介素-1(interleukin-1,IL-1)、肿瘤坏死因子-a(tumor necrosis factor-a,TNF-a)的水平变化情况,阐述其在膝骨关节炎发病过程中的作用.方法 采用酶联免疫吸附测定法(Enzyme-linked immunosorbent assay,ELISA)检测2013年3月至2015年12月本院门诊及住院部诊治的97例膝骨关节炎患者血清、关节液中FGF-21、IL-1、TNF-a的含量.其中,97例KOA患者依据膝关节X线的Kellgren& Lawrence(K-L)分级,分为对照组(KOA 0级,n=18)和实验组(KOA 1,n=20;KOA 2,n=20;KOA 3,n=19;KOA 4,n=20).结果 与对照组血清FGF-21水平[(323.15±97.63)pg/ml]相比较,实验组各组血清FGF-21水平变化不大,差异无统计学意义(均P＞0.05).实验组各组间血清IL-1、TNF-a水平随着膝骨关节炎疾病进程,浓度逐渐增大,差异有统计学意义(均P＜0.05).与对照组关节液FGF-21水平[(198.23±65.41) pg/ml]、IL-1水平[(36.17±6.89) pg/ml]、TNF-a水平[(18.94±5.81) pg/ml]相比较,实验组各组关节液FGF-21、IL-1、TNF-a水平随着膝骨关节炎疾病进程,浓度逐渐增大,差异有统计学意义(均P＜ 0.05).相关性分析结果表明,血清IL-1、TNF-a水平与K-L分级呈现正相关(相关系数r=0.899、0.942,P＜0.05),而血清FGF-21与K-L分级呈现负相关(相关系数r=-0.121,P＞ 0.05).关节液FGF-21、IL-1、TNF-a水平与K-L分级均呈现正相关(相关系数r=0.876、0.941、0.916,P＜ 0.05).结论 膝骨关节炎血清及关节液FGF-21、IL-1与TNF-a因子参与膝骨关节炎疾病进程,有一定的参考意义.     

阿奇霉素序贯疗法对小儿支原体肺炎患者炎性因子及体液免疫功能调节的影响研究

目的:研究阿奇霉素序贯疗法对小儿支原体肺炎患者炎性因子及体液免疫功能调节的影响。方法:选取2013年1月—2014年12月间诊治的小儿支原体肺炎患者100例作为研究对象;将其随机分为观察组和对照组,每组50例;对照组患者均给予阿奇霉素常规治疗,观察组患者均给予阿奇霉素序贯疗法治疗,治疗后检测两组患儿体内炎性因子(IL-10)、促炎因子(包括TNF-α、IFN-γ)以及体液免疫功能指标(包括免疫球蛋白Ig G、Ig A、Ig M和外周血中的补体C_3、C_4。结果:治疗前两组患儿血清中炎性因子均较高,经两组间比较其差异无统计学意义(P>0.05);治疗7和12 d时两组患儿血清中抗炎因子和促炎因子低于对照组(P<0.05);治疗前两组患儿外周血中Ig A水平处于较低水平,补体C_3、C_4以及Ig M、Ig G处于较高水平,经两组间比较其差异无统计学意义(P>0.05);治疗后两组患儿的Ig A水平上升,Ig M、Ig G下降,与治疗前比较其差异有统计学意义(P<0.05),且观察组患儿改善更加显著;观察组患儿补体C_3、C_4均显著下降;对照组患儿补体C3仍低于观察组(P<0.05),对照组患儿补体C_4与治疗前比较其差异无统计学意义(P>0.05)。结论:采用阿奇霉素序贯疗法治疗小儿支原体肺炎患儿,可显著改善其血清中炎性因子及体液免疫功能,其疗效优于阿奇霉素的常规治疗。     

血清炎性因子水平和稳定期慢性阻塞性肺疾病的相关性研究

目的探讨及研究血清炎性因子水平和稳定期慢性阻塞性肺疾病的关系。方法选取2012年12月至2014年5月于本院进行诊治的75例稳定期慢性阻塞性肺疾病患者为观察组,并以同期的75名健康吸烟者为对照组,然后将两组的血清TNF-α、MCP-1、BNP及CRP水平进行比较,然后将观察组中不同BODE指数分级及SGRQ评分者的检测水平,并以Logistic分析上述检测指标与稳定期慢性阻塞性肺疾病的关系。结果观察组的血清TNF-α、MCP-1、BNP及CRP水平均高于对照组,BODE指数分级较高及SGRQ评分较高者检测水平高于BODE指数分级较低及SGRQ评分较低者,经Logistic分析显示上述检测指标与稳定期慢性阻塞性肺疾病均有密切的关系,P均<0.05。结论稳定期慢性阻塞性肺疾病患者的血清炎性因子水平呈现明显升高的趋势,其与疾病有密切的关系。     

类风湿关节炎与巨噬细胞炎性蛋白-1α的相关性研究

目的探讨巨噬细胞炎性蛋白-1α（MIP-1α）在类风湿关节炎（RA）患者外周血、关节液的mRNA表达水平及其在RA发病机制中的作用。方法采用实时荧光定量PCR技术检测19例RA、6例骨关节炎患者的关节液和外周血单个核细胞（SFMC和PBMC）中MIP-1αmRNA表达水平。同时采用ELISA法测定MIP-1α的浓度。并与15例健康对照者比较。结果 MIP-1αmRNA在RA组外周血和关节液中均有表达,差异有统计学意义（P〈0.01）。RA组MIP-1α的血清及关节液含量明显高于其他组;关节液中MIP-1α的浓度高于血清（P〈0.01）。结论 MIP-1α介导的炎性反应是RA发病机制中重要因素。     

聚蛋白多糖酶与膝骨关节炎相关性研究

目的 观测并探讨膝骨关节炎关节液及血清中聚蛋白多糖酶(ADAMTSs)水平与病变程度的关系.方法 单侧膝骨关节炎87例中,早期为45例,中晚期为42例.检测其患侧膝关节液和血清中ADAMTSs水平.以健康志愿者30例为正常对照组.结果 膝骨关节炎患者关节液及血清中ADAMTSs水平均高于正常对照组,随着病变程度加重,膝关节液及血清中ADAMTSs水平显著增加,关节液与血清中ADAMTSs水平存在线性相关关系.结论 ADAMTSs水平在骨关节炎患者膝关节液和血清中均升高,与病变程度密切相关,检测关节液及血液该种指标有助于病情早期诊断.     

剖宫产产妇围手术期炎症因子变化

目的观察比较剖宫产和阴道自然分娩产妇围手术期炎症因子的表达水平。方法选取剖宫产产妇52例作为观察组、自然分娩产妇53例作为对照组,均记录临床资料并检测产前、产后12、24及72h血清中各促炎因子、抗炎因子及其他炎症因子的表达水平。结果术前两组间各炎症因子水平无差异,两组术后各炎症因子水平对比术前均有明显升高,但相比对照组,观察组的变化更为显著(P<0.05);观察组术后12、24h各炎症因子表达水平达到高峰,72h时有明显下降。结论剖宫产产妇围手术期短程预防性用药有积极意义,值得继续推广使用。     

血清炎症相关因子在急性胰腺炎患者的表达及临床意义

目的 探讨血清炎症相关因子在急性胰腺炎(AP)患者的表达及临床意义.方法 选取145例A P患者分为轻症组(M A P组,46例)、中重症组(M S A P组,51例)和重症组(S A P组,48例),另选取健康体检者50例为对照组.采用ELISA法检测各组外周血促炎因子(IL-1β、IL-6、TNF-α)和抑炎因子[细胞因子信号传导抑制蛋白3(SOCS3)、IL-10].检测并比较四组血生化指标WBC、C反应蛋白(CRP)、淀粉酶(AMY)、脂肪酶(LIP)、降钙素原(PCT)、ALT、AST、BUN和Cr水平.结果 与对照组比较,MAP组、MSAP组和SAP组WBC、CRP、AMY、LIP、PCT、ALT、AST、BUN、Cr等血清生化指标和IL-1β、IL-6、TNF-α促炎因子水平均升高,且随着疾病严重程度而增加(P<0.05).与对照组比较,MAP组、MSAP组和SAP组SOCS3、IL-10表达均升高(P<0.05),且随疾病严重程度增加而表达上调,MSAP组表达最高(P<0.05);SAP组SOCS3和IL-10表达较MSAP组下调(P<0.05).结论 AP患者促炎及抑炎因子均显著升高,血清炎症相关指标参与了AP发病过程,检测其变化对病情判断有重要参考价值.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Arsenic induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture

Arsenic at a nonlethal level in drinking water consumed over a period of time has been reported to produce chronic toxicity and various types of health problems ranging from skin cancer to disturbance in memory. Neurotoxic effects have been reported in clinical cases with chronic exposure to arsenic. Physiological detoxication of arsenic occurs partially through methylation. Arsenic and its methylated derivatives are distributed in different organs and systems. The present study examined the possible interference in the neuronal development and differentiation due to the exposure to arsenic during gestation. The experiments were carried out to examine short and long term effects of arsenic on brain explants and cells grown and maintained in tissue culture system. The effects of arsenic exposure showed changes in brain cell membrane function indicated by generation and release of reactive oxygen-nitrogen intermediates. On the morphological aspect the explants' growth was reduced, ground matrix was lost and neural networking was inhibited. Cells showed signs of apoptotic changes. Arsenic toxicity may induce damage to brain cells prior to more visible clinical conditions. The deleterious effects also pass from the maternal to fetal tissue across the transplacental barrier.     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85–100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Circulating nucleic acids in plasma and serum: roles in diagnosis and prognosis in diabetes and cancer

The presence of DNA and RNA circulating in human plasma and serum is described. The possible sources of the DNA/RNA in blood, their ability to enter other cells and to express in the recipient cells are discussed and the relationship with metastases considered. The possible role(s) of the DNA/RNA in clinical diagnosis, in monitoring treatment and in prognosis are considered for diabetes and oncology.     

SalB stimulates neurogenesis and angiogenesis in vitro and in vivo

Aims： Previous studies suggested that Salvianolic acid B （SalB） has strong protective effect against cerebral ischemia. Recently, Sal B has been reported to enhance angiogenesis in vitro. Based on the information above, in this study we are interested in the effect of SalB on neurogenesis and angiogenesis. Methods：In vitro study, we used embryonic mouse （El6） primary cortical neural cultures. Neuron was recognized by anti-MAP2 with immunocytochemistry. Neurogenesis was tested with BrdU incorporation by ELSA method. SalB（ 10 -6 -10 -8M） or vehicle was added to the culture medium 24 hrs before BrdU addition. In vivo, middle cerebral artery occlusion （MCAO） rats were used as focal cerebral ischemia model.     

Metabolic interaction between imipramine and carbamazepine in vivo and in vitro in rats

Summary The pharmacokinetic consequences of the combination of carbamazepine with imipramine in male Wistar rats have been investigated. It was found that a 2-week treatment with the combination resulted in the increase of the concentrations of the parent compounds and a simultaneous decrease in their metabolites in blood plasma i.e. carbamazepine inhibited imipramine demethylation in the side chain while imipramine inhibited carbamazepine 10,11-epoxidation. The velocity of imipramine 2-hydroxylation and 10,11-epoxy-carbamazepine hydration did not seem to be changed by the combination. On the basis of studies in vitro it is concluded that the observed metabolic interaction between carbamazepine and imipramine is due to the competition of the drugs for the active centre of cytochrome P 450 and to a certain qualitative alteration of the enzyme by imipramine as can be deducted from the decrease of carbamazepine binding to the cytochrome. Send offprint requests to K. J. Netter     

Nicotine metabolism and urinary elimination in mouse: in vitro and in vivo

This study aimed at elucidating the in vivo metabolism of nicotine both with and without inhibitors of nicotine metabolism. Second, the role of mouse CYP2A5 in nicotine oxidation in vitro was studied as such information is needed to assess whether the mouse is a suitable model for studying chemical inhibitors of the human CYP2A6. The oxidation of nicotine to cotinine was measured and the ability of various inhibitors to modify this reaction was determined. Nicotine and various inhibitors were co-administered to CD2F1 mice, and nicotine and urinary levels of nicotine and four metabolites were determined. In mouse liver microsomes anti-CYP2A5 antibody and known chemical inhibitors of the CYP2A5 enzyme blocked cotinine formation by 85-100%, depending on the pre-treatment of the mice. The amount of trans-3-hydroxycotine was five times higher than cotinine N-oxide, and ten times higher than nicotine N-1-oxide and cotinine. Methoxsalen, an irreversible inhibitor of CYP2A5, significantly reduced the metabolic elimination of nicotine in vivo, but the reversible inhibitors had no effect. It is concluded that the metabolism of nicotine in mouse is very similar to that in man and, therefore, that the mouse is a suitable model for testing novel chemical inhibitors of human CYP2A6.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Consistency in catecholamine and cortisol excretion in males and females

Data from a series of experiments performed on 24 female and 24 male subjects were used to evaluate the consistency in urinary catecholamine and cortisol excretion. Data were available from 8 laboratory situations of varying activity level and content, spaced at intervals of maximum 3 months. Correlational analyses showed that for cortisol, interindividual consistency was higher for measures obtained on the same day than for measures obtained on different days. Interindividual consistency was generally high in catecholamine and cortisol excretion during non-stressful situations in both sexes. During experimental stress, however, consistency was as high as during nonstress for males, while it was lower for females. Analysis of variance components confirmed these results and showed that in males variation due to interindividual differences was high during both baseline and experimental-stress situations, while in females it was high during baseline situations only. During experimental stress, variation for females was due primarily to interaction. It is suggested that the males showed a more generalized stress response over situations than the females.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.