多囊卵巢综合征患者对ACTH反应的差异及其机制探讨

目的 观察多囊卵巢综合征(PCOS)患者ACTH兴奋试验后17羟孕酮(17OHP)的不同反应,及其与21羟化酶(CYP21)启动子区单核苷酸多态性的关系,初步探讨PCOS患者肾上腺源性高雄激素的产生机制.方法 对30名正常女性和101例PCOS患者进行ACTH兴奋试验,将PCOS患者分为高反应组(HR-PCOS)和正常反应组(NR-PCOS).比较两亚组基本情况、激素水平.对其中87例PCOS患者和30名正常女性进行CYP21启动子区-710 bp-1 bp测序,了解其单核苷酸多态性与ACTH兴奋后17OHP水平之间的关系.结果 在101例PCOS患者中,21例(20.8%)ACTH兴奋试验后17OHP水平高于正常,为HR-PCOS组;其余80例(79.2%)反应正常,为NR-PCOS组.HR-PCOS组血清总睾酮水平高于NR-PCOS组(P<0.05),NR-PCOS组高于对照组(P<0.01).HR-PCOS组基础17OHP、硫酸脱氢表雄酮(DHEAS)和兴奋后17OHP、DHEAS均显著高于NR-PCOS组和对照组(均P<0.05),NR-PCOS组与对照组之间没有差异.CYP21启动子区-535 C>T与17OHP高反应有关,-535位点的基因型与兴奋后170HP水平存在较好的相关性(r=0.20,P=0.03).其少见基因型(T/T型)和等位基因型T在高反应组中多见(P<0.05或P<0.01).该位点等位基因存在T者,发生17OHP高反应的相对危险度为3.69(95%CI 1.69～8.06).结论 约有20%PCOS患者ACTH兴奋试验后17OHP反应增高,并伴有血清总睾酮、肾上腺源性雄激素增高,提示PCOS患者17OHP对ACTH兴奋试验的高反应可能是肾上腺源性高雄激素产生的机制之一.CYP21A2启动子区-535位点的基因变异与17OHP对ACTH兴奋试验的反应性有关.     

2型糖尿病60例下丘脑-垂体-肾上腺轴功能的变化

目的探讨2型糖尿病患者下丘脑-垂体-肾上腺（HPA）轴功能的变化及其相关因素。方法测定60例2型糖尿病患者（糖尿病组）和30例健康体检者（对照组）的血浆皮质醇（F）、促肾上腺皮质激素（ACTH）、空腹胰岛素（FINS）、空腹血糖（FPG）、血脂、糖化血红蛋白（HbA。c）的水平以及血压、体重、腰围、臀围,计算体质量指数（BMI）、腰臀比（WHR）、胰岛素抵抗指数（HOMA-IR）。结果糖尿病组皮质醇昼夜节律紊乱发生率高于对照组（53．33％vs26．67％,P〈0．05）;糖尿病组高皮质醇发生率高于对照组（46．67％v820％,P〈0．05）;糖尿病组0时皮质醇、8时皮质醇及日平均皮质醇高于正常对照组（P〈0．01）。糖尿病组ACTH昼夜节律紊乱发生率高于对照组（60．00％vs36．67％,P〈0．05）;糖尿病组0时ACTH及日平均ACTH高于对照组（P〈0．01）。直线相关分析显示糖尿病组日平均皮质醇水平与WHR、FPG、HbA1c、HOMA-IR、甘油三酯（TG）呈正相关,与高密度脂蛋白-胆固醇（HDL-C）呈负相关。糖尿病组日平均ACTH与WHR、FPG、HbA。C、HOMA—IR呈正相关。结论2型糖尿病患者存在HPA轴功能紊乱,以皮质醇和ACTH昼夜节律紊乱、皮质醇活性亢进为主。     

多囊卵巢综合征患者血清对氧磷酯酶1活性、氧化应激与胰岛素抵抗的关系

目的探讨对氧磷酯酶1（PON-1）活性、氧化应激在多囊卵巢综合征（PCOS）患者发生胰岛素抵抗（IR）中的作用。方法41例PCOS患者分为肥胖组17例和非肥胖组24例,另有20名健康女性纳入正常对照组。所有研究对象均行口服糖耐量试验（OGTT）和胰岛素释放试验,使用稳态模型评价IR及胰岛B细胞分泌功能,空腹静脉取血检测丙二醛（MDA）、超氧化物歧化酶（SOD）活性及PON-1活性。结果（1）PCOS非肥胖组和PCOS肥胖组的空腹胰岛素、餐后2小时血糖及胰岛素、HOMA—IR及HOMA-β均高于正常组（P〈0．05）,且PCOS肥胖组的空腹胰岛素、餐后2小时血糖及胰岛素、HOMA—IR均高于PCOS非肥胖组（P％0．05）。（2）PCOS非肥胖组和PCOS肥胖组的MDA、SOD及PON-1与正常组比较差异有统计学意义（P〈0．05）;PCOS肥胖组的SOD显著低于PCOS非肥胖组（P％0．01）,而MDA及PON-1两组之间差异无统计学意义（P〉0．05）。（3）相关分析显示：在PCOS非肥胖组,SOD与PON—1正相关（r=0．417,P〈0．05）,SOD与IR负相关（r=0．492,P〈0．05）。结论PCOS患者无论肥胖与否,均存在餐后血糖升高、PON-1活性降低、氧化应激、IR,且肥胖患者更为严重;PCOS患者的氧化应激与IR相关。     

内皮功能障碍与胰岛素抵抗和肥胖关系研究的7年随诊观察

目的观察血管内皮功能、胰岛素抵抗（IR）和肥胖之间的动态关系。方法对583例单纯性肥胖者进行7年随访,共计431例纳入随访分析。按照初访时内皮依赖性血管舒张功能（EDD）、胰岛素抵抗指数（HOMA-IR）以及随访时减重与否分组,对各组随访前后EDD、HOMA-IR和体脂进行比较分析。结果（1）与初访时比较内皮功能异常组7年后腰臀比和HOMA—IR明显升高（P〈0．05）,EDD显著降低（P〈O．05）,内皮功能正常组体重指数较前降低（P〈O．05）,HOMA—IR和EDD无显著变化。（2）无论初访或随访IR组腰围和HOMA—IR均明显高于非IR组（P〈0．05或P〈0．01）,但EDD在初访时两组无显著差异,随访时前者明显低于后者以及本组初访时（均P〈0．05）。（3）初访时,未减重组HOMA_IR高于减重组（P〈0．05）,EDD低于减重组（P〈0．01）。7年后未减重组体重指数、腰围和HO-MA—IR均明显高于减重组（P〈0．05或P〈0．01）,EDD明显低于减重组（P〈0．01）。且与初访时比较,随访时未减重组HOMA-IR显著升高（P〈O．05）,EDD显著降低（P〈0．05）。减重组HOMA-IR、EDD无明显变化。结论内皮功能障碍可能是导致超重和肥胖相关的IR的病因,两者也是影响减重效果的原因之一,但前者可能与减重关系更密切。     

在汉族雄激素过多症女性中筛查非经典型21-羟化酶缺乏症

目的初步了解中国汉族雄激素过多症女性中非经典型21-羟化酶缺乏症(NC-21OHD)的患病情况.方法对85例汉族雄激素过多症患者及14名健康女性进行卵泡期ACTH兴奋试验.结果雄激素过多组睾酮(T)、LH均显著高于正常对照组[(2.86±1.26 vs 1.11±0.48)nmol/L,(9.19±6.15 vs 2.71±1.89)U/L,均P＜0.01];雄激素过多组中具有多囊卵巢综合征(PCOS)临床表现的有60例,占70.6%.根据ACTH兴奋试验结果诊断NC-21OHD 3例,占雄激素过多组的3.5%(3/85).除3例NC-21 OHD外,雄激素过多组(n=82)0 min血皮质醇(F0)显著高于正常对照组[(127.0±40.7 vs 106.2±14.8)μg/L,P＜0.01];0 min和60 min 17-OH孕酮(17-OHP0及17-OHP60)也显著高于对照组 [(1.67±0.85 vs 0.66±0.29)μg/L, (3.98±1.32 vs 2.03±0.68)μg/L,均P＜0.01],而60 min血皮质醇(F60)没有明显差异[(252.6±28.9 vs 245.9±28.9)μg/L,P＞0.05].比较Δ17-OHP及Δ17-OHP/ΔF,雄激素过多组也均显著高于正常对照组[(2.30±1.07 vs 1.37±0.61)μg/L,(0.20±0.10 vs 0.10±0.05),均P ＜0.01]. 结论85例雄激素过多症妇女中NC-21OHD为3例,占3.5%.ACTH兴奋试验对鉴别NC-21OHD与其它原因导致女性高雄激素血症有重要意义.     

血糖控制达标2型糖尿病患者血清炎症指标与相关代谢指标关系分析

回顾性分析血糖控制达标的139例2型糖尿病患者一般临床资料及相关炎症指标;血清FKN采用双抗体夹心酶联免疫方法（ELISA）测定。根据体重指数（BMI）分为体重正常组（50例）、超重组（44例）及肥胖组（45例）,对相关指标进行统计分析。结果（1）三组血糖、糖化血红蛋白比较无差异（均P〉0．05）;与正常体重组比较,超重组及肥胖组FKN、hs—CRP水平显著升高,而HDL—C水平显著降低（均P〈0．05）。肥胖组收缩压和舒张压水平均高于正常体重组,肥胖组血清FKN、hs-CRP、ALT、TG水平显著高于超重组（均P〈0．05）。（2）Pearson相关性分析显示,血清FKN水平与BMI、腰围、TG呈正相关（P〈0．05）;血清hs—CRP与BMI、腰围、TG呈正相关（P〈0．01）,而与HDL—C呈负相关（P〈0．05）。（3）多元逐步回归分析显示,血清FKN与BMI具有显著相关性（β=0．32,P〈0．01,R2=0．40）;血清hs—CRP与BMI独立相关（β=0．30,P〈0．01,R2=0．37）。结论单纯血糖控制达标不能完全纠正2型糖尿病患者慢性炎症状态。     

2型糖尿病双下肢动脉粥样硬化与BMI和腰围的关系

收集17名正常人，20名单纯肥胖患者，42名2型糖尿病患者的临床资料，以彩色血管多普勒超声探测受试者的双下肢股动脉、胭动脉、胫前动脉、胫后动脉及足背动脉，并测量内中膜最厚处厚度及斑块数目、管腔狭窄程度。结果①在2型糖尿病组动脉粥样硬化斑的阳性率显著高于正常组及单纯肥胖组（P值分别〈0．05及〈0．01），且内中膜厚度显著大于后二者（P值分别〈0．05及〈0．01）。2型糖尿病组较正常对照组及单纯肥胖组动脉损伤发生率高、程度重（P值分别〈0．05及〈0．01）。②2型糖尿病患者中，下肢动脉硬化与体重指数、腰围呈显著正相关（P〈0．01）。结论在本资料的2型糖尿病患者中，90％已有动脉粥样硬化，中心性肥胖对2型糖尿病患者动脉硬化有显著影响。     

多囊卵巢综合征肾上腺起源学说研究进展

有研究表明，20％～33％的多囊卵巢综合征（PCOS）患者存在脱氢表雄酮（DHEA）及脱氢表雄酮硫酸盐（DHEAS）升高，可能与PCOS患者。肾上腺中合成类固醇激素的关键酶活性增加、肾上腺对促肾上腺皮质激素（ACTH）刺激的敏感性增加及功能亢进有关。肾上腺皮质机能初现提前（PA）的女性也存在肾上腺皮质P450c17a酶活性亢进，进而导致肾上腺分泌雄激素显著增多。PA的主要特征与PCOS相似，如多毛、肥胖、黑棘皮症、高胰岛素血症和胰岛素抵抗等。对黑种和白种人的多项研究表明，PA患者的胰岛素／胰岛素样生长因子（IGF）系统失调，表现为高胰岛素血症和胰岛素样生长因子结合蛋白-1（IGFBP-1）水平下降，     

合并阻塞性睡眠呼吸暂停的高血压患者血压变异性和靶器官损害的研究

目的阻塞性睡眠呼吸暂停（OSA）引发睡眠期间血流动力学变化,增加夜间血压变异性,加重靶器官损害,但这种影响可能受年龄的干扰。方法143例多导睡眠诊断的OSA患者分为3组：〈60岁高血压组（62例）、〈60岁正常血压组（38例）和〉60岁正常血压组（43例）,全部进行24h动态血压监测,分析白天和夜间血压变化的标准差（SD）和变异系数（CV）,在排除年龄干扰因素外,判断OSA对血压变异性的影响及靶器官的损害情况。结果与〈60岁正常血压组相比,高血压组白天和夜间血压变化SD明显增加,白天收缩压18．5和10．6mmHg（P〈O．05）;白天舒张压13．8和10．6mmHg（P〈0．05）;夜间收缩压20．5和12．6mmHg（P〈0．01）;夜间舒张压17．8和12．6mmHg（P〈O．01）。血压CV也明显增加,白天收缩压0．119和0．078（P〈0．01）;白天舒张压0．139和0．118（P〈0．05）;夜间收缩压0．137和0．111（P〈0．01）;夜间舒张压0．195和0．177（P〈O．01）。与〉60岁正常血压组相比,高血压组白天和夜间血压变化SD明显增加,白天收缩压18．5和13．3mmHg（P〈O．05）;白天舒张压13．8和10．2mmHg（P〈O．05）;夜间收缩压20．5和15．2mmHg（P〈0．01）;夜间舒张压17．8和14．2mmHg（P〈0．01）。白天收缩压CV增加（0．119和0．093;P〈O．05）;夜间收缩压和舒张压CV增加（O．137和0．123;P〈0．01;0．195和0．179;P〈0．05）。与〈60岁正常血压组相比,〉60岁正常血压组白天收缩压CV增加（0．093和0．078;P〈O．05）。与〈60或〉60岁正常血压组相比,高血压组靶器官损害增加（P〈0．01）。与〈60岁正常血压组相比,〉60岁正常血压组靶器官损害也增加（P〈0．05）。结论尽管年龄可能影响血压变异性,但是OSA对血压变异性的影响明显超过年龄的作用,并加重靶器官损害。因此,对于合并OSA的老年高血压患者更应给予足够重视。     

温州地区汉族人群G蛋白β3亚基C825T基因多态性与肥胖的相关性研究

目的研究温州地区汉族人群G蛋白β3亚基（GNB3）C825T等位基因多态性与超重及单纯性肥胖的相关性。方法超重及单纯性肥胖组为肥胖专科门诊中随机选取161例超重或单纯性肥胖患者，并于温州市中心血站随机选取313名体重正常健康献血者为对照组，PCR-RFLP检测基因型。结果（1）温州地区汉族人群GNB3 825T等位基因频率为0．428，与其他人种的基因频率显著不同。（2）超重及单纯性肥胖组的TT基因型携带者显著增加（P〈0．01），TT／CT导致肥胖的比数比（OR值）为2．9（95％可信区间1．8-4．7，P〈0．01）；TT／CC致肥胖的OR值为2．7（95％CI 1．5—4．7，P〈0．01）；TT基因型分布按体重指数（BMI，kg／m^2）分组后，正常体重（18≤BMI〈23）、超重（23≤BMI〈25）、Ⅰ度肥胖（25≤BMI〈30）和Ⅱ度肥胖（BMI≥30）4组均显著高于低体重（BMI〈18组，P〈0．05或P〈0．01）；Ⅰ度肥胖、Ⅱ度肥胖组高于正常体重组（均P〈0．05）；Ⅱ度肥胖组高于超重组（P〈0．01）。（3）同组男女间比较GNB3 C825T基因型和T等位基因频率分布差别无统计学意义。结论GNB3 C825T等位基因频率分布存在种族差异，温州地区汉族人群GNB3 825T等位基因频率为0．428，GNB3 825T等位基因与超重及单纯性肥胖呈正相关。GNB3 825T基因型可作为早期预测单纯性肥胖的遗传学指标之一。     

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.