Efficacy of Fumonisin Esterase in Piglets as Animal Model for Fumonisin Detoxification in Humans: Pilot Study Comparing Intraoral to Intragastric Administration

Fumonisins, a group of highly prevalent and toxic mycotoxins, are suspected to be causal agents of several diseases in animals and humans. In the animal feed industry, fumonisin esterase is used as feed additive to prevent mycotoxicosis caused by fumonisins. In humans, a popular dosage form for dietary supplements, with high patient acceptance for oral intake, is capsule ingestion. Thus, fumonisin esterase provided in a capsule could be an effective strategy against fumonisin intoxication in humans. To determine the efficacy of fumonisin esterase through capsule ingestion, two modes of application were compared using piglets in a small-scale preliminary study. The enzyme was administered intraorally (in-feed analogue) or intragastrically (capsule analogue), in combination with fumonisin B1 (FB1). Biomarkers for FB1 exposure; namely FB1, hydrolysed FB1 (HFB1) and partially hydrolysed forms (pHFB1a and pHFB1b), were measured both in serum and faeces using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and toxicokinetic parameters were calculated. Additionally, the serum sphinganine/sphingosine (Sa/So) ratio, a biomarker of effect, was determined using LC-MS/MS. A significantly higher Sa/So ratio was shown in the placebo group compared to both esterase treatments, demonstrating the efficacy of the esterase. Moreover, a significant decrease in serum FB1 area under the concentration-time curve (AUC) and an increase of faecal HFB1 AUC were observed after intraoral esterase administration. However, these effects were not observed with statistical significance after intragastric esterase administration with the current sample size.     

Tissue Doppler imaging a new prognosticator for cardiovascular diseases

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is > or =15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score.     

Validation of fumonisin biomarkers in F344 rats

Fumonisins (FNs) are ubiquitous contaminants of cereal grains. Fumonisin B(1) (FB(1)) was linked to several animal and human diseases. To validate FB(1) biomarkers for studying human disease risks, F344 rats were administered by gavage with either a single dose of 0, 10 or 25 mg FB(1)/kg body weight (BW) or repeated doses of 0, 1.0, or 2.5 mg FB(1)/kg BW/day for 5 weeks. FB(1) excretion and FB(1)-induced metabolic alterations of sphingolipids in rat urine, feces and serum were assessed. Dose-dependent urinary and fecal excretion of free FB(1) were found in both single-dose- and repeat-dose-treated rats. In the single-dose study, urinary sphinganine (Sa) to sphingosine (So) ratio (Sa/So) reached a maximum at day 7 for the high-dose group and at day 5 for the low-dose group, whereas serum Sa/So showed only marginal changes. In the repeat-dose study, urinary Sa/So was persistently elevated at 2 weeks, while serum Sa/So was unchanged. Time course changes of sphinganine 1-phosphate (SaP) and sphingosine 1-phosphate (SoP) were also examined. Although serum Sa/So and SaP/SoP ratios showed no signs of time- or dose-dependent changes, a 10-fold increase in urinary SaP/SoP was observed, suggesting that urinary SaP/SoP is a more sensitive biomarker for FB(1) exposure. The accumulation of SaP and SoP was evident in the time course of SaP/Sa and SoP/So, which may reflect activity changes of enzymes closely related to the metabolism and catabolism of SaP and SoP. These results provide concrete evidence towards the practical use of excreted FB(1), Sa/So and SaP/SoP as biomarkers of exposure to FNs.     

Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice

Aging is an inevitable process associated with immune imbalance, which is characterized by a progressive functional decline in major organs, including lung. However, effects of altered Th1/Th2 commitment on lung senescence are largely unknown. To examine effects of altered Th1/Th2 balance on lung aging, we measured proportions of Th1 and Th2 cells and expression of cytokines, chemokines, collagen deposition and other relevant physiological and pathological parameters in 2- and 20-months-old (mo) CXCR3-deficient (CXCR3^−/−) C57BL/6J mice compared with wild-type (WT) mice. There was a significant weight-loss observed in 20-mo CXCR3^−/− mice compared with the same aged WT group. Although lung function and structure changed with age in both groups, central airway resistance (Rn), tissue elastance (H) and damping (G) were significantly lower in 20-mo CXCR3^−/− mice than those of WT mice. In contrast, the whole lung volume (V_L), the mean linear intercept length of alveolar (L_m), and the total lung collagen content were significantly elevated in 20-mo CXCR3^−/− mice. With aging, the lungs of WT mice had typical Th1-type status (increased population of Th1 cells and concentrations of cytokine IFN-γ and CXCR3 ligands) while CXCR3^−/− mice showed Th2-type polarization (decreased proportion of Th1 cells and concentrations of CXCR3 ligands but increased level of IL-4). Our data suggest that Immunosenescence is associated with lung aging, and that altered Th1/Th2 imbalance favors Th2 predominance in CXCR3^−/− mice, which contributes to the process of accelerated lung aging in this model.     

二尖瓣环收缩期峰值速度评价冠心病左室收缩功能的临床分析

目的分析脉冲多普勒组织成像技术(PW-DTI)所测二尖瓣环收缩期平均位移峰值速度(Sa)作为评价冠心病左心室收缩功能指标的临床价值。方法52例冠心病患者分为经皮冠状动脉介入术(PCI)组33例和未行PCI组19例,PCI组于PCI术前5 d及术后5 d、3个月、6个月随访,非PCI组于冠状动脉造影术后2 d及术后6个月随访;均行PW-DTI及常规超声检查,观察Sa的变化情况。PCI组据射血分数(EF)分成两个亚组:EF≥50%亚组和EF 30%～50%亚组;亚组间进行术前、术后比较;分别分析不同心脏功能患者Sa的变化情况。结果6个月后,PCI组平均Sa明显增高(P<0.001)。平均Sa与EF存在相关性(术前r=0.705,术后r=0.770,均P<0.0001)。结论Sa可作为评价冠心病左室收缩功能的指标。     

浅谈萨病治疗中心理疗法的重要性

萨病又称中风,现代医学称脑卒中。本文从病因和医学模式两方面讨论了蒙医治疗萨病中心理疗法的重要性。     

联合检测HLA-DR4、抗CCP抗体和抗Sa抗体在类风湿关节炎诊断中应用价值

目的 探讨联合检测HLA-DR4、抗CCP抗体和抗Sa抗体在类风湿关节炎诊断中应用价值.方法 在2014年10月至2017年1月期间,选取我院就诊的109例RA患者作为研究对象,选取同期我院收治的94例非RA患者和90例健康体检者作为对照组.比较三组患者血清HLA-DR4、抗CCP抗体和抗Sa抗体的阳性率、三项指标联合检测对RA诊断学指标.结果 RA组患者血清HLA-DR4、抗CCP抗体和抗Sa抗体阳性率显著高于非RA组和对照组(P<0.05).在HLA-DR4、抗CCP抗体和抗Sa抗体三个指标中,抗CCP抗体的灵敏度和特异性最高(P<0.05).在联合检测中,HLA-DR4、抗CCP抗体和抗Sa抗体联合检测的灵敏度和特异性最高(P<0.05).结论 HLA-DR4、抗CCP抗体和抗Sa抗体联合检测可以提高对类风湿关节炎的诊断准确率,可作为临床辅助诊断手段.     

早期类风湿关节炎患者自身抗体与放射学破坏的相关性研究

目的　探讨抗Sa抗体和抗角蛋白抗体 (AKA)对早期类风湿关节炎 (RA)放射学破坏的临床意义。方法　检测 4 2例早期RA患者的抗Sa抗体和AKA ,结合手、足X线片的病情分期和改进的Sharp评分分析。结果　初诊时及随诊 2年后抗Sa抗体、AKA阳性组X线分期较阴性组高。随诊 2年后抗Sa抗体、AKA阳性组Sharp评分较阴性组为高。随诊 2年后与初诊时相比较 ,抗Sa抗体、AKA阳性组X线分期、Sharp评分明显增高 ,抗Sa抗体阴性组增高。两种抗体同时阳性患者随诊 2年后Sharp评分明显增高。结论　抗Sa抗体、AKA可作为早期RA患者放射学破坏的预测指标。     

盐酸舍曲林联合中药伊木萨克治疗原发性早泄的临床研究

目的:探讨盐酸舍曲林联合中成药伊木萨克治疗原发性早泄的临床疗效。方法:2013年6月至2015年10月门诊收集无器质性疾病的原发性早泄患者192例,年龄22~48岁,平均(27.63±6.78)岁,随机分成两组:A组患者单用盐酸舍曲林50mg/d,性生活前4~6h服用;B组患者服用盐酸舍曲林50mg/d,同时给予中成药伊木萨克,3片/d,睡前口服;连续服用4周,比较两组之间治疗有效率、治疗前后平均阴道内射精潜伏时间(IELT)和配偶性交满意度以及治疗期间的不良反应。结果:两组患者IELT在治疗后均显著延长,配偶性交满意度显著提高,而B组较A组增加更显著,存在明显的统计学差异(P<0.05)。结论:盐酸舍曲林联合中成药伊木萨克治疗原发性早泄疗效显著优于单用盐酸舍曲林,但长期效果亟待进一步观察。