老年人亚甲基四氢叶酸还原酶、蛋氨酸合成酶基因多态性及同型半胱氨酸水平与冠心病的关系

目的探讨老年人同型半胱氨酸(Hcy)水平与冠心病的关系,并对亚甲基四氢叶酸还原酶(MTHFR)A1298C基因多态性、蛋氨酸合成酶(MS)A2756G基因多态性与Hcy水平及冠心病的关系进行探讨. 方法 177例老年人为研究对象,其中129例冠状动脉造影证实为冠心病患者(冠心病组),48例冠状动脉造影完全正常(对照组).荧光偏振免疫分析法测定Hcy水平,聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析MTHFR A1298C、MS A2756G基因多态性. 结果冠心病组血Hcy水平显著高于对照组[(16.2±8.6)对(12.7±5.0)μmol/L,P<0.01].MTHFR A1298C基因多态性CC纯合子和AC杂合子血Hcy水平均显著低于AA野生型[(9.1±2.5)、(13.5±6.6)对(16.0±8.3)μmol/L,P<0.01],CC纯合子和AC杂合子间血Hcy水平差异无显著性(P>0.05);MTHFR 1298CC纯合子在冠心病组的分布频率显著低于对照组(3.1%对14.6%,P<0.05).MS A2756G基因多态性GG+AG基因型血Hcy水平显著低于AA野生型[(12.8±6.5)对(15.6±8.1)μmol/L,P<0.05],MS 2756GG+AG基因型在冠心病组的分布频率显著低于对照组(9.3%对20.8%,P<0.05). 结论本研究入选的老年人群中,冠心病患者血Hcy水平升高.MTHFR 1298CC基因型及MS 2756 GG +AG基因型与低血Hcy水平相关,它们可能会通过降低血Hcy水平而减少老年人冠心病的发生.     

同型半胱氨酸代谢异常与冠心病的关系

目的：探讨同型半胱氨酸代谢异常与冠心病的关系。方法：选择245例健康对照者和入住我院冠心病房的439例经冠状动脉造影证实为冠心病者作为研究对象，监测其血浆同型半胱氨酸（Hcy）、叶酸和VitB12水平，分析亚甲基四氢叶酸还原酶（MTHFR）基因多态性，并根据冠状动脉造影结果，分成单支、双支和三支病变组，分析病变支数与MTHFR基因多态性的关系。结果：冠心病患者血浆Hcy水平（17．61＋11．62）显著高于对照组（12．92＋8．23）（P〈0．001），叶酸和VitBl2水平低于对照组（P〈0．05）。冠心病组TT基因型明显高于对照组（P〈0．05），冠心病组中三支血管病变组的TT基因频率比单支和双支血管病变组高（P〈0．005），TT型纯合子的血浆Hcy含量与CC型纯合子和CT杂合子比较具统计学差异（P〈0．001），而叶酸和VitB12含量低于后两者（P〈0．05）。结论：血浆Hcy含量和MTHFR基因突变相关，其TT纯合子血浆Hcy水平最高，而在三支血管病变组的TT基因频率最高，提示MTHFR基因突变可导致Hcy水平升高，是冠心病的危险因素。     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N^5,N^10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与冠心病的关系。方法应用聚合酶链反应（PCR）技术和限制性酶切片段长度多态性（RFLP）分析技术检测50例冠心病患者（冠心病组）和50例正常人（对照组）的MTHFR基因C677T多态性,应用高效液相色谱法测定血浆同型半胱氨酸（Hcy）水平,采用125I标记放免法测定血清叶酸浓度。结果1.冠心病组与对照组MTHFR基因频率分布不同（P〈0.05）,对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%,冠心病组分别为26.0%,44.0%,30.0%。冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异（P〈0.05）。2.两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者（P〈0.05）,而后两者间无显著性差异（P〉0.05）。3.冠心病组Hcy浓度高于照组（P〈0.05）,两组叶酸水平无显著性差异（P〉0.05）,血浆Hcy浓度与叶酸水平呈显著负相关（r分别为-0.617和-0.588,P〈0.05）。结论MTHFR基因C677T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素。     

肝硬化高同型半胱氨酸血症与MTHFR基因C667T多态性的关系

目的研究肝硬化血浆同型半胱氨酸(HCY)水平及其与N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性的关系.方法采用柱前衍生化-HPLC方法检测112例健康对照者、87例肝硬化患者血浆同型半胱氨酸的水平,用多聚酶链反应-限制性内切酶片断长度多态性技术(PCR-RFLP)检测其MTHFR基因C667T多态性.结果健康对照组平均血浆HCY浓度为(8.34±3.59)μmol/L,肝硬化组平均血浆HCY浓度为(21.71±4.85)μmol/L.与健康对照组相比,肝硬化组血浆HCY水平显著升高,差异有统计学意义(P＜0.01).PCR-RFLP检测结果发现MTHFR基因型有3种,即纯合子突变TT(+/+)型,杂合子突变TC(+/)型,正常CC(-/-)型.肝硬化组中+/+型、+/型和/-型频率分别为29.9%、52.9%、17.2%;健康对照组分别为19.6%、33.9%、46.4%,两组差异有统计学意义.肝硬化组MTHFR基因突变无论是纯合子还是杂合子突变基因型,其血浆HCY水平均明显高于正常基因型.结论高同型半胱氨酸血症可能是肝硬化的一个危险因素,血浆HCY水平可作为肝硬化的一个辅助诊断指标,MTHFR基因C667T多态性可能是肝硬化高同型半胱氨酸血症的易感基因之一.     

血浆同型半胱氨酸水平亚甲基四氢叶酸还原酶基因多态性与强直性脊柱炎的相关性研究

目的 探讨血浆同型半胱氨酸(Hcy)水平与强直性脊柱炎(AS)间的联系,分析AS患者MTHFR基因C677T突变的多态性,并探讨MTHFR基因多态性与AS的相关性.方法 运用酶联免疫吸附试验(ELISA)测定100例AS患者及60名健康志愿者血浆Hcy浓度,应用多聚酶链反应-限制性内切酶片段长度多态性(PCR-RELP)分析MTHFR基因的多态性.结果 AS患者血浆Hcy浓度明显高于对照组,两组间差异有统计学意义(P＜0.01);AS组T/T型、C/T型、C/C型基因频率分布及T、C等位基因频率与对照组比较差异无统计学意义(P＞0.05);AS组T/T基因型突变的比例与对照组比较差异有统计学意义(P＜0.05);AS组和对照组T/T型的血浆Hcy水平明显高于C/T型和C/C型(P＜0.01).Logistic回归分析显示高Hcy血症是AS发病的独立危险凶素(P＜0.01,OR=4.582,95%CI=1.984～10.585).结论 AS患者血浆Hcy浓度明显高于健康志愿者,高Hcy血症是AS发病的独立危险因素.MTHFR基因T/T型突变是血浆Hcy浓度升高的一个重要影响机制,MTHFR基因T/T型突变可能与AS的发生有相关性.     

左旋多巴治疗帕金森病所致高同型半胱氨酸血症的研究

目的 探讨血浆同型半胱氨酸（Hcy）水平与左旋多巴（L-dopa）治疗帕金森病（PD）的相关性。方法 依据英国脑库PD诊断标准，从2011年5月至2013年3月来北京大学第五临床医学院神经内科住院及门诊就诊的患者中入选，一共收集PD组161例，其中男性88例，女性73例，年龄（64.36±11.06）岁，病程范围：0.5～22（6.3±5.4）年。比较PD组和正常对照组Hcy，维生素B12、叶酸水平与L-dopa治疗时间、剂量，运动并发症、焦虑、抑郁和痴呆发生率的相关性，并对PD伴高同型半胱氨酸血症（HHcy）的原因进行分析，同时还对PD组（161例）和正常对照组（240例）MTHFR基因和COMT基因多态性进行分析。结果 161例PD患者平均血浆Hcy水平（17.65±9.36）μmol/L，明显高于正常对照组（10.12±3.20）μmol/L（P＜0.001）。纳入分析的6个因素（包括性别、年龄、L-dopa治疗时间、剂量、叶酸和维生素B12浓度）单因素分析发现，L-dopa治疗对影响HHcy有统计学意义（P＜0.01）。导致PD患者HHcy的原因分析结果以正常叶酸和维生素B12水平为主，＞84%，间接提示HHcy可能与Hcy代谢途径中的相关酶的基因突变有关。本研究PD组与正常对照组COMT和MTHFR基因多态性的分布无统计学差异（P＞0.05），但对PD组按Hcy水平进行分层分析结果显示，C677T基因型及等位基因在HHcy患者（＞15μmol/L）和Hcy正常患者（＜15μmol/L）的频率分布差异有统计学意义（P＜0.05）。另外，161例PD患者中有77例伴有HHcy，剔除未治疗组22例外，余55例中有运动波动症者35例（63.6%），有异动症者3例（5.5%），有焦虑和抑郁30例（54.5%），有痴呆者12例（21.8%）。结论 L-dopa治疗的PD患者容易产生HHcy，HHcy可以使L-dopa治疗后运动并发症、焦虑、抑郁和痴呆的发生率增加或病情加重。     

亚甲基四氢叶酸还原酶G1793A基因多态性及高同型半胱氨酸血症与溃疡性结肠炎的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)G1793A基因多态性、血浆同型半胱氨酸(Hey)、叶酸及维生素B12浓度与溃疡性结肠炎(UC)的关系.方法 在299例UC患者和764例正常对照者中,采用聚合酶链反应-限制性片段长度多态性(PCR-RELP)检测MTHFR G1793A基因多态性,循环酶法检测血浆Hey水平,微粒子免疫化学发光法检测血浆叶酸和维牛素B12浓度.结果 UC组MTHFR 1793(A)等位基因和(GA+AA)基因型频率明显比正常对照组增高(22.24%比14.20%,P<0.001;42.81%比26.97%,P<0.001);血浆Hey水平亦明显高于正常对照组[(20.67±6.42)mmol/L比(13.21±5.11)mmol/L,P<0.001],而叶酸和维生素B12浓度明显降低[(11.37±6.34)nmol/L比(14.89±7.21)nmol/L,P<0.001;(324.15±127.53)pmol/L比(421.54±128.45)pmol/L,P<0.001].另外,UC组中高同型半胱氨酸血症(Hhcy)(Hcy≥15 mmol/L)及叶酸缺乏(叶酸≤7 nmol/L)的发生率显著高于正常对照组(32.44%比25.78%,P=0.029;23.41%比17.01%,P=0.016).结论 MTHFR G1793A基因多态性、Hhcy、叶酸缺乏及低维生素B12水平与湖北汉族UC明显相关.Hcy代谢酶基因可能涉及UC的发病机制.     

叶酸缺乏对大鼠同型半胱氨酸水平及动脉损伤的影响

目的观察叶酸缺乏饮食对大鼠血浆同型半胱氨酸(Hcy)水平及动脉组织的影响.方法雄性Wistar大鼠20只均分成2组,分别给予叶酸缺乏(叶酸缺乏组)和叶酸正常(对照组)饲料,饲养3个月后检测血清叶酸和血浆Hcy浓度及红细胞超氧化歧化酶(SOD)和谷胱甘肽过氧化物酶(GPX)活力,实验后光镜检查主动脉组织学变化.结果叶酸缺乏组实验后血清叶酸浓度[(6.08±1.84)μg/L]明显低于实验前[(13.32±2.02)μg/L]和对照组[(12.17±1.67)μg/L],而血浆Hcy浓度[(28.66±6.07)μmol/L]明显高于实验前[(9.75±1.86)μmol/L]和对照组[(9.49±1.77)μmol/L,P＜0.01];红细胞SOD[(37389.5±5158.4)NU/g*Hb]高于对照组[(30355.7±6349.2)NU/g*Hb],GPX活力[(10.94±3.05)U/L]低于对照组[(17.93±3.05)U/L,P＜0.05];主动脉组织出现内皮细胞肿胀、变性、脱落,裸露的内膜附有血栓和胶原纤维,内皮下组织疏松并出现平滑肌细胞,内弹力膜断裂,中膜明显增厚.结论叶酸缺乏饮食可引发高Hcy血症和动脉损伤,高Hcy血症诱导体内高氧化应激可能是动脉损伤机制之一.     

亚甲基四氢叶酸还原酶基因多态性对老年冠状动脉粥样硬化性心脏病患者血浆同型半胱氨酸水平的影响

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性对老年冠状动脉粥样硬化性心脏病(冠心病)患者血浆同型半胱氨酸(Hcy)水平的影响。方法老年冠心病患者200例作为健康冠心病组,老年健康体检者200例作为对照组,冠心病组患者随机分为叶酸治疗组和常规治疗组。测定所有入选者MTHFR基因型和血浆Hcy水平。结果 MTHFR存在三种基因型:TT、CT、CC。冠心病组T等位基因和C等位基因分布和健康对照组比较差异有统计学意义(P0.05);冠心病组TT、CT和CC基因型和健康对照组比较差异有统计学意义(P0.05),冠心病组TT基因型比例高于对照组。冠心病组血浆Hcy水平高于健康对照组(P0.05)。冠心病组中男性血浆Hcy水平高于女性(P0.05),高血压患者血浆Hcy水平高于非高血压患者(P0.05);冠心病组不同MTHFR基因型患者血浆Hcy水平比较差异有统计学意义(P0.05),其中TT基因型血浆Hcy水平高于CT和CC基因型(P0.05),CT基因型血浆Hcy水平高于CC基因型(P0.05)。叶酸治疗组治疗后TT基因型血浆Hcy水平和治疗前比较差异有统计学意义(P0.05),其余冠心病各亚组治疗后血浆Hcy水平和治疗前比较差异无统计学意义(P0.05)。结论 MTHFR基因多态性和冠心病及其血浆Hcy水平有关,叶酸治疗可以改善冠心病患者血浆Hcy水平,以TT基因型效果显著。     

血浆同型半胱氨酸及其相关酶基因多态性与Alzheimer病的关系

目的探讨同型半胱氨酸（homocysteine,Hey）及其相关酶5,10亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）的基因多态性与阿尔茨海默病（Alzheimer$disease,AD）的关系。方法对68例AD患者和68例健康对照组采用循环酶法测定血浆Hcy水平;多聚酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测MTHFR基因C677T的多态性。结果AD患者血浆Hcy水平13．92&#177;5．513μmoL／L显著高于健康对照组10．83&#177;3．800μmol／L;MTHFRC677T各基因型总体分布在两组之间差异有显著性,其中C／T基因型在AD组中所占比例（64．71％）显著高于对照组（42．65％）。结论血浆高Hcy水平可能参与AD的发生发展;MTHFR基因C677T突变导致的基因多态性可能参与了AD的遗传机制;山西汉族人血浆高Hcy水平在很大程度上与遗传有一定关系。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.