Genetic susceptibility to autoimmune thyroid diseases in a Chinese Han population: Role of vitamin D receptor gene polymorphisms

Purpose

Previous studies have found that some immune-related genes were associated with autoimmune thyroid diseases (AITDs). A couple of studies have explored the association between vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR) gene polymorphisms and susceptibility to AITDs in different populations and found conflicting results. This case-control study was designed to evaluate the role of polymorphisms of VDR gene in the predisposition of AITDs in a Chinese Han population.

Methods

A total of 417 patients with Graves’ disease (GD), 250 patients with Hashimoto's thyroiditis (HT) and 301 healthy subjects were enrolled. The Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform was applied to detect four SNPs (rs1544410, rs2228570, rs731236 and rs7975232) in the VDR gene.

Results

In the rs7975232 allele A frequency showed a significant increase in GD patients (30.34% vs. 25.42% in controls; P = 0.041, OR = 1.278, 95%CI = 1.010–1.617). However, no relationship was found between clinical phenotypes and the four SNPs.

Conclusions

This result suggests that the VDR gene may be one susceptibility gene which contributes to the risk of GD.     

Serotonin increases the functional activity of capsaicin-sensitive rat trigeminal nociceptors via peripheral serotonin receptors

Peripheral serotonin (5HT) has been implicated in migraine and temporomandibular pain disorders in humans and animal models and yet the mechanism(s) by which 5HT evokes pain remains unclear. Trigeminal pain can be triggered by activation of the transient receptor potential V1 channel (TRPV1), expressed by a subset of nociceptive trigeminal ganglia (TG) neurons and gated by capsaicin, noxious heat, and other noxious stimuli. As 5HT is released in the periphery during inflammation and evokes thermal hyperalgesia, and TRPV1 is essential for thermal hyperalgesia, we hypothesized that 5HT increases the activity of capsaicin-sensitive trigeminal neurons and that this increase can be attenuated by pharmacologically targeting peripheral 5HT receptors. TG cultures were pretreated with 5HT (10 nM-100 μM), sumatriptan (5HT_1B/1D agonist), ketanserin (5HT_2A antagonist), granisetron (5HT₃ antagonist), or vehicle prior to capsaicin (30-50 nM). Single-cell accumulation of intracellular calcium was recorded or calcitonin gene-related peptide (CGRP) release was measured following each treatment. In addition, using in situ hybridization and immunohistochemistry, we detected the colocalization of 5HT_1B, 5HT_1D, 5HT_2A, and 5HT_3A, but not 5HT_2C mRNA with TRPV1 in TG cells. 5HT pretreatment evoked a significant increase in calcium accumulation in capsaicin-sensitive trigeminal neurons and enhanced capsaicin-evoked CGRP release, but had no significant effect when given alone. Sumatriptan, ketanserin, and granisetron treatment attenuated calcium accumulation and 5HT enhancement of capsaicin-evoked CGRP release. Together these results indicate that 5HT increases the activity of capsaicin-sensitive peripheral nociceptors, which can be attenuated by pharmacologically targeting peripheral 5HT receptors, thereby providing a mechanistic basis for peripheral craniofacial pain therapy.     

Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Rotavirus infection of cultured cells induces a progressive increase in plasma membrane permeability to Ca2+. The viral product responsible for this effect is not known. We have used tunicamycin and brefeldin A to prevent glycosylation and membrane traffic and study the involvement of viral glycoproteins, NSP4 and/or VP7, in rotavirus-infected HT29 and MA104 cells. In infected cells, we observed an increase of plasma membrane Ca2+ permeability and a progressive depletion of agonist-releasable ER pools measured with fura 2 and an enhancement of total Ca2+ content measured as 45Ca2+ uptake. Tunicamycin inhibited the increase in membrane Ca2+ permeability, induced a depletion of agonist-releasable and 45Ca2+-sequestered pools. Brefeldin A inhibited the increase of Ca2+ permeability and the increase in 45Ca2+ uptake induced by infection. We propose that the glycosylated viral product NSP4 (and/or VP7) travels to the plasma membrane to form a Ca2+ channel and hence elevate Ca2+ permeability.     

辨证分型为主治疗糖尿病性视网膜病变临床观察

观察以中医辨证论治结合降糖西药对糖尿病性视网膜病变的疗效。共治疗糖尿病性视网膜病变３８例５５只眼，其中单纯型３１只眼，增殖型２４只眼，并对治疗前后的视力、眼底病变的情况进行了比较。结果：显效１７只眼（３０．９％）有效２５只眼（４５．５％，无效１１只眼（２０．０％），恶化２只眼（３．６％），总有效率７６．４％。     

金属蛋白酶抑制剂对外源Rac1表达介导的细胞侵袭胶原屏障的影响

目的 体外研究金属蛋白酶(MMPs)抑制剂对外源Rac1基因表达介导的HT1080纤维肉瘤细胞侵袭胶原屏障的影响.方法 分别转染显性负调控突变体Rac1V12N17(HN)、持续活化型Rac1V12(HV)或空载体(HW)于纤维肉瘤HT1080细胞,G418筛选.蛋白印迹分析检测外源性Rac1基因表达,并在含胶原蛋白凝胶的3D基质中培养,用得克萨斯红结合的鬼笔环肽染色显示细胞肌动蛋白骨架构型.在含胶原蛋白凝胶覆盖滤膜的Transwell小室进行细胞侵袭胶原屏障实验,并观察MMPs抑制剂和抑肽酶对上述细胞侵袭实验的影响.结果 HV细胞伸出明显的突起,HN细胞形态紧凑,HV细胞侵袭胶原屏障的能力大于HW细胞,而后者又强于HN细胞,这种差别在应用广谱MMPs抑制剂后消失,而抑肽酶则无影响.结论 外源活化型Rac1基因在纤维肉瘤HT1080细胞内稳定表达可诱发肌动蛋白纤维聚集,并可增加HT1080纤维肉瘤细胞侵袭胶原屏障的能力,但这种细胞侵袭胶原蛋白能力的增强可被MMPs抑制剂阻断.     

健康体检中心存在的共性问题及对策

随着国民经济的发展,人们的健康意识逐渐增强,健康体检中心迅速兴起,但其发展过程中尚存在很多问题,如:缺乏准入标准;人员构成不合理;监督机制不到位;只重视经济利润,而忽视市场管理等。本文就健康体检中心存在的问题进行分析,并提出相应的对策。     

呕必宁对顺铂所致脑组织5-HT含量变化的影响

目的：探讨中药复方呕必宁防治化疗药诱发呕吐的中枢机制。方法：应用行为学与分子生物学的方法，比较对照组、NS组、中药组实验动物静脉注射DDP前后，动物呕吐反应，血、脑脊液中DDP浓度，脑脊液、脑组织中的5-HT、5-HIAA含量变化。结果：注射DDP后与NS组比较，中药组猫的呕吐率下降；与此同时脑脊液中DDP浓度明显低于NS组、脑脊液及脑组织中5-HT和5-HIAA浓度较NS组显著降低。结论：呕必宁对DDP所致呕吐反应具有防治作用，其机制可能与降低猫脑脊液中DDP的浓度，降低脑脊液、脑组织中5-HT、5-HIAA含量有关。     

No association between two polymorphisms at the 5HT2A gene and bipolar affective puerperal psychosis

OBJECTIVE: To examine whether variation at two common polymorphisms, T102C and -1438AG, of the serotonin 2A gene (5HT2A) are involved in the puerperal triggering mechanism of bipolar affective puerperal psychosis. METHOD: A total of 242 parous women diagnosed with bipolar disorder were genotyped for the two polymorphisms. Of these, 165 women had experienced a manic or psychotic episode, according to DSM-IV criteria, within 6 weeks of childbirth (the puerperal psychosis group). The comparison group comprised of 77 parous women who had not experienced psychiatric disturbance following childbirth. RESULTS: No significant differences between genotype or allelic frequencies were found between the two groups for either polymorphism. CONCLUSION: The results indicate that variation at two common polymorphisms of the 5HT2A gene does not appear to play a major role in the development of bipolar affective puerperal psychosis.     

Endogenous cannabinoid,anandamide, acts as a noncompetitive inhibitor on 5-HT3 receptor-mediated responses in Xenopus oocytes

The cloned 5-HT3 receptor from NCB-20 neuroblastoma cells was expressed in Xenopus oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5-HT3 receptors were voltage-clamped at -70 mV. Anandamide, at the concentration range of 0.1-100 microM, reversibly inhibited 1 microM 5-HT induced currents. The inhibition of 5-HT induced currents by anandamide was concentration-dependent with an EC50 of 3.7 microM and slope value of 0.94. This inhibitory effect was not dependent on the membrane potential and anandamide did not have an effect on the reversal potential of 5-HT-induced currents. In the presence of 10 microM anandamide, the maximum 5-HT-induced response was also inhibited and the respective EC50 values were 3.4 microM and 3.1 microM in the absence and presence of anandamide, indicating that anandamide acts as a noncompetitive antagonist on 5-HT3 receptors. CB1 receptor antagonist SR-141716A (1 microM) and pertussis toxin (5 microg/ml) did not cause a significant change on the inhibition of 5-HT responses by anandamide. The effect of anandamide was not changed by preincubating the oocytes with 0.2 mM 8-Br-cAMP, a membrane-permeable analog of cAMP, or Sp-cAMPS (0.1 mM), a membrane-permeable protein kinase A activator. These results suggest that the effect of anandamide is independent of the activation of cAMP pathway and not mediated by the activation of PTX sensitive G-proteins. In conclusion, we demonstrated that the endogenous cannabinoid anandamide inhibits the function of 5-HT3 receptors expressed in Xenopus oocytes in a cannabinoid-receptor independent and noncompetitive manner.     

5-HT(3) receptors and neurotransmitter release in the CNS: a nerve ending story?

Serotonin (5-HT) 5-HT₃ receptors are ligand-gated ion channels, which are generally thought to be involved in the presynaptic modulation of neurotransmitter release. However, analysis of published data reveals that most of the evidence for the alleged presynaptic role of 5-HT₃ receptors in modulating CNS neurotransmitter release is not compelling. Nevertheless, 5-HT₃ receptors are present in nerve terminals from some brain regions. The increased basic knowledge of the cellular physiology of central 5-HT₃ receptor ligand-gated ion channels provides opportunities for a detailed characterization of the specific presynaptic effects of 5-HT₃ receptors. Such reconsideration is required for the full appreciation of the functional role of 5-HT₃ receptors in the CNS.