Assessment of the pharmacokinetics,removal rate of hemodialysis,and safety of lactulose in hemodialysis patients

Lactulose is often used to treat hepatic encephalopathy or constipation, and also exhibits benefits to chronic renal insufficiency due to reduce nitrogen-related products in serum. The present study investigated the pharmacokinetics of lactulose, its removal rate through dialysis, and safety by administering lactulose 6.5 g (Lagnos Jelly Divided Pack 16.05 g) orally to six hemodialysis patients who resided in Taiwan. As a result, the means of maximum plasma concentrations (C_max) and Time to reach C_max (Tmax) were 3090 ± 970 ng/mL and 6.5 ± 2.3 hours, respectively. The mean plasma concentration was 2220 ± 986 ng/mL after administration for 24 hours. Sequentially, the mean plasma concentration reduced to 307 ± 117 ng/mL after the application of 4-hour dialysis. Area under the plasma concentration-time curve from zero to 24 h post-dose (AUC_0–24h) were 56,200 ± 21,300 ng h/mL and the AUC_0–28h was 61,200 ± 23,300 ng h/mL. The rate of lactulose removal by dialysis was 83.6 ± 8.9%. In addition, the multiple doses of lactulose using a simulated model suggested that no plasma accumulation would be expected while coordinating with dialysis. Good tolerability was confirmed, while the mild adverse effect of diarrhea was observed in one case during the study period. No death or serious adverse effect was reported. Based on the present study, we demonstrated the pharmacokinetic transition with respect to plasma levels of lactulose in patients with impaired renal excretion treated with hemodialysis.     

自制踝足矫形带对痉挛型偏瘫脑性瘫痪足下垂患儿下肢运动功能的疗效

目的观察自制自制踝足矫形带对痉挛型偏瘫脑瘫足下垂患儿下肢运动功能的疗效。方法 24例痉挛型偏瘫脑瘫足下垂患儿随机分为观察组和对照组各12例。两组患儿均行常规康复训练,对照组行步态训练,观察组佩戴自制踝足矫形带行步态训练,共12周。治疗前后分别采用腓肠肌改良Ashworth量表(MAS)、踝关节主动背屈活动度(ROM)和粗大运动功能测量(GMFM-88)D区(站立)、E区(走跑跳)进行评定。结果治疗后,两组MAS评分明显降低(P0.01),观察组低于对照组(P0.05);两组ROM、GMFM-88的D区和E区评分均明显高于治疗前(P0.01),观察组高于对照组(P0.05)。结论佩戴自制踝足矫形带行步态训练能进一步降低痉挛型偏瘫脑瘫患儿患侧的腓肠肌张力,增加踝关节活动度,提高下肢运动功能。     

Co-culture with periodontal ligament stem cells enhanced osteoblastic differentiation of MC3T3-E1 cells and osteoclastic differentiation of RAW264.7 cells

Objectives: Periodontal ligament stem cells (PDLSCs) are characterized by having multipotential differentiation and immunoregulatory properties, which are the main mechanisms of PDLSCs-mediated periodontal regeneration. Periodontal or bone regeneration requires coordination of osteoblast and osteoclast, however, very little is known about the interactions between PDLSCs and osteoblast-like cells or osteoclast precursors. In this study, the indirect co-culture approach was introduced to preliminarily elucidate the effects of PDLSCs on differentiation of osteoblast-like cells and osteoclast precursors in vitro. Materials and methods: Human PDLSCs were obtained from premolars extracted and their stemness was identified in terms of their colony-forming ability, proliferative capacity, cell surface epitopes and multi-lineage differentiation potentials. A noncontact co-culture system of PDLSCs and preosteoblastic cell line MC3T3-E1 or osteoclast precursor cell line RAW264.7 was established, and osteoblastic differentiation of MC3T3-E1 and osteoclastic differentiation of RAW264.7 were evaluated. Results: PDLSCs exhibited features of mesenchymal stem cells. Further investigation through indirect co-culture system showed that PDLSCs enhanced ALP activity, expressions of ALP, Runx2, BSP, OPN mRNA and BSP, OPN proteins and mineralization matrix deposition in MC3T3-E1. Meanwhile, they improved maturation of osteoclasts and expressions of TRAP, CSTK, TRAF6 mRNA and TRAP, TRAF6 proteins in RAW264.7. Conclusions: PDLSCs stimulates osteoblastic differentiation of osteoblast precursors and osteoclastic differentiation of osteoclast precursors, at least partially, in a paracrine fasion.     

Hypermethylation of TFPI2 correlates with cervical cancer incidence in the Uygur and Han populations of Xinjiang,China

Tissue factor pathway inhibitor 2 (TFPI2) is a Kunitz-type serine proteinase inhibitor, which plays an important role in the etiology of human malignancies. DNA methylation is a common epigenetic modification of the genome that is involved in regulating many cellular processes. In addition to human papilloma virus (HPV) infection, DNA methylation may play a role in the carcinogenesis of cervical cancer. Methylation of 22 CpG sites in the promoter region of the TFPI2 gene was detected by MassARRAY spectrometry and a gene mass spectrogram was drawn using MALDI-TOF MS. HPV16 was detected by PCR. We show that aberrant methylation of TFPI2 is present in a higher proportion of invasive cervical carcinoma (ICC) clinical samples as compared to normal cervical samples in Uygur and Han. Across the four pathologic lesions of the progression of cervical cancer, ICC showed the highest level of aberrant methylation, and with a stronger correlation between CpG site and lesion grade in Uygur than in Han. Moreover, a difference in TFPI2 methylation between Uygur patients positive and negative for HPV16 infection was observed at CpG_6 (P = 0.028) and CpG_15 (P = 0.007). Altogether, these results indicate that DNA methylation of TFPI2 may play an important role in the carcinogenesis of cervical cancer and that the differential methylation of TFPI2 may at least partially explain the disparity in cervical cancer incidence between Uygur and Han women.     

错误相关负电位在精神科临床上推广——附50例正常成人分析

目的:应用引进的德国仪器及新技术探讨并建立健康成人错误相关负电位(ERN)的正常值。方法:应用德国Brain Products公司的ERP记录与分析系统,对50例21~55岁健康成人右利手受试者,作了ERN检测。结果:(1)32个头皮记录点皆在约100~150ms处出现了一个负波,健康成人ERN波形较稳定。(2)在Cz、Fz、Pz、C3、C4 5个脑区,建立了健康成人ERN潜伏期和波幅均值。(3)左右侧比较及男女性别比较差异无统计学意义(P>0.05)。结论:健康成人ERN较稳定和可靠。ERN可作为一个有临床推广应用价值的ERP而用于神经精神科临床。     

Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment

Regulatory T (Treg) cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8⁺ Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8⁺ Treg cells in ovarian cancer (OC) patients. Here, we investigated CD8⁺ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8⁺ T cells and the forkhead box p3 (Foxp3)⁺ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8⁺ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8⁺ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including an increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8⁺ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8⁺ T cells cultured alone, the CD8⁺ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8⁺ Treg cells inhibited naïve CD4⁺ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8⁺ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.     

Amino acids 89–96 of Salmonella typhimurium flagellin represent the major domain responsible for TLR5-independent adjuvanticity in the humoral immune response

Toll-like receptor 5 (TLR5) signaling in response to flagellin is dispensable for inducing humoral immunity, but alterations of aa 89–96, the TLR5 binding site, significantly reduced the adjuvanticity of flagellin. These observations indicate that the underlying mechanism remains incompletely understood. Here, we found that the native form of Salmonella typhimurium aa 89–96-mutant flagellin extracted from flagella retains some TLR5 recognition activity, indicating that aa 89–96 is the primary, but not the only site that imparts TLR5 activity. Additionally, this mutation impaired the production of IL-1β and IL-18. Using TLR5KO mice, we found that aa 89–96 is critical for the humoral adjuvant effect, but this effect was independent of TLR5 activation triggered by this region of flagellin. In summary, our findings suggest that aa 89–96 of flagellin is not only the crucial site responsible for TLR5 recognition, but is also important for humoral immune adjuvanticity through a TLR5-independent pathway.     

Does parents' socio-economic status matter in intentions of vaccinating against human papillomavirus for adolescent daughters?

BackgroundThe Human Papilloma Virus (HPV) vaccination provides substantial protection, and it is best to be taken before the age of twelve. Taiwan approved HPV vaccines since 2006. However, very few female adolescent have been vaccinated until now.ObjectivesTo examine whether the parents'' socio-economic status matters in deciding to purchase HPV vaccination for their daughters based on the theory of planned behavior.MethodA structured questionnaire to collect 394 responses from parents of adolescent girls in Taiwan. Data was coded to categorize relevant socio-economic classes, and was analyzed with SPSS.ResultsThe behavior intentions of parents with low (mean= 5.28) and high (5.01) socio-economic status are significantly stronger than the moderate (4.56) in deciding to purchase the HPV vaccination. Socio-economic factor has a slightly negative impact (B= -0.08), and attitude (0.68), subjective norms (0.16), and behavior control (0.32) have positive impacts on the parents'' intention.ConclusionMajor impacts on the decision to purchase an HPV vaccination for their adolescent was not due to the parents'' socio-economic status but the parent''s attitude. As the major predictor of a less complicated decision, attitudes toward the HPV vaccination should be reinforced through continuous communications between service providers and patient-advocate groups.