基质金属蛋白酶-13在骨性关节炎发病中的活性调控研究

目的 研究一氧化氮(NO)是否通过膜型基质金属蛋白酶-1(MT1-MMP)间接激活基质金属蛋白酶-13酶原(pro-MMP-13).方法 购买并传代人软骨肉瘤细胞(SW1353),用NO供体S-亚硝基-N-乙酰基青霉胺(SNAP),SNAP+NO清除荆氧合血红蛋白(OxyHb)和SNAP+组织金属蛋白酶抑制物-2(TI...     

哮喘患儿血清IL-4、IL-13及嗜酸性粒细胞意义的探讨

[目的]检测哮喘患儿血清中IL-4、IL-13及嗜酸性粒细胞(EOS)的水平并探讨其临床意义。[方法]取中-重度哮喘患儿28例为实验组1、缓解期哮喘患儿24例为实验组2、取正常儿童25例为对照组,分别取外周静脉血3mL,用ELISA方法检测IL-4、IL-13的含量,并进行外周血嗜酸性粒细胞计数。[结果]两实验组IL-4、IL-13、EOS计数水平均高于对照组,实验组1较实验组2明显增高;且哮喘患儿血清IL-4与IL-13水平呈正相关。[结论]IL-4、IL-13及EOS参与了哮喘的发病过程,其水平反映了病情的严重程度;且这些因子间存在着一定联系。     

国产13C-葡萄糖呼气试验检测糖尿病小鼠胰岛素抵抗的实验研究

目的 拟在糖尿病小鼠模型上建立一个无创的13C-葡萄糖呼气试验检测胰岛素抵抗(IR)的方法,并评估其与其他IR指数的相关性.方法 四氧嘧啶尾静脉注射法制作糖尿病小鼠模型.多时间点采集小鼠13C-葡萄糖(5 mg/kg)灌胃后呼出的气样.红外线同位素能谱仪测定气样,以90 min 13CO2丰度变化值(C90min)作为IR参数,评估糖尿病小鼠的IR情况及其在1U外源性胰岛素干预后的IR变化.测定糖尿病小鼠的空腹血糖及空腹胰岛素值,并以此来计算临床IR指数:稳态模型胰岛素抵抗评价指数(HOMA-IR)和定量胰岛素敏感性检测指数(QUICKI).分别分析C90min与HOMA-IR或QUICKI之间的相关性.结果 糖尿病小鼠的C90min值明显低于正常对照小鼠,分别为(0.79±0.18)％和(1.19±0.31)％(t=2.470,P＜0.05).1 U外源性胰岛素干预后,糖尿病小鼠的C90min值显著增加至(1.17±0.25)％(t=-2.522,P＜0.05).相关性分析显示,C90min与HOMA-IR(r=-0.64,P＜0.05)或QUICKI(r=0.88,P＜0.01)均有良好的相关性.结论 13C-葡萄糖呼气试验能够灵敏反映糖尿病小鼠的IR变化,其检测结果与目前临床IR指数有良好的相关性.     

~（13）C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

AIM: To find the most reproducible quantitative parameter of a standard ¹³C-methacetin breath test (¹³C-MBT).METHODS: Twenty healthy volunteers (10 female, 10 male) underwent the ¹³C-MBT after intake of 75 mg ¹³C-methacetin p.o. on three occasions. Short- and medium-term reproducibility was assessed with paired examinations taken at an interval of 2 and 18 d (medians), respectively.RESULTS: The reproducibility of the 1-h cumulative ¹³C recovery (AUC_0-60), characterized by a coefficient of variation of 10%, appeared to be considerably better than the reproducibility of the maximum momentary ¹³C recovery or the time of reaching it. Remarkably, as opposed to the short gap between consecutive examinations, the capacity of the liver to handle ¹³C-methacetin increased slightly but statistically significantly when a repeat dose was administered after two to three weeks. Regarding the AUC_0-60, the magnitude of this fixed bias amounted to 7.5%. Neither the time gap between the repeat examinations nor the gender of the subjects affected the ¹³C-MBT reproducibility.CONCLUSION: ¹³C-MBT is most reproducibly quantified by the cumulative ¹³C recovery, but the exactitude thereof may be modestly affected by persistent stimulation of CYP1A2 on repeat examinations.     

Switching from infliximab originator to a first biosimilar is safe and effective. Results of a case-control study with drug levels and antibodies evaluation

BackgroundInflammatory bowel disease is treated with anti-TNF agents such as infliximab and its biosimilars, but use of biosimilars is limited due to perceived risks of adverse events.AimTo explore safety and effectiveness of switching from the infliximab originator to a first biosimilar.Patients and methodsClinical and biological outcomes were compared between 53 patients who switched from the infliximab originator to the biosimilar CT-P13 (Switched group) and 13 patients treated with CT-P13 from the beginning (Naïve group). Infliximab trough levels and antidrug antibodies were measured.ResultsAt enrolment, patients in the Switched group had a longer median duration of infliximab treatment than Naïve (4.0 vs. 0.6 years, p < 0.0001) but similar proportions of patients were in remission (77% and 62%, respectively). Infliximab discontinuation due to adverse events or loss of efficacy was less common in the Switched (26%) than Naïve group (62%, p = 0.017). Variables independently associated with time to discontinuation were disease activity (p < 0.0001) and immunomodulating treatment (p = 0.019) at enrolment. Trough levels and antidrug antibodies were similar between groups during observation.ConclusionThis study confirms that switching from infliximab originator to a first biosimilar is safe and effective. Patients at highest risk of losing treatment efficacy are those with active disease, irrespective of the therapeutic switch.     

Applications of multi-nuclear magnetic resonance spectroscopy at 7T

AIM: To discuss the advantages of ultra-high field (7T) for 1H and 13C magnetic resonance spectroscopy (MRS) studies of metabolism.made at both 3 and 7T using 1H MRS. Measurements of glycogen and lipids in muscle were measured using 13C and 1H MRS respectively. RESULTS: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these me-tabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen (13C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) (1H) following exercise and refeeding. Glycogen levels were sig-nificantly decreased following exercise (-28% at 50% VO2 max; -58% at 75% VO2 max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study. CONCLUSION: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.     

Prader�CWilli syndrome and autism spectrum disorders: an evolving story

Prader-Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11-q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11-q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism.