吡格列酮对2型糖尿病患者胰岛素抵抗的影响

观察吡格列酮对2型糖尿病患者胰岛素抵抗的治疗作用,对30例2型糖尿患者予吡格列酮30mg／d口服,12周后发现餐后2小时血糖（PC2hPG）、糖化血红蛋白（GHbA1c）、空腹血糖（FPG）、胰岛素抵抗指数（Homa—IR）与用药前比较明显降低（P〈0．01）。提示吡格列酮可降低FPG、PC2hPG、GHbA1c及血浆胰岛素水平,明显减轻胰岛素抵抗。     

吡格列酮对胰岛素抵抗HepG2细胞胰岛素受体底物表达的影响

目的探讨毗格列酮对胰岛索抵抗（IR）HepG2细胞胰岛素受体底物（IRS）蛋白表达的影响。方法胰岛素抵抗HepG2细胞模型建立后,培养液中加入吡格列酮共同孵育,观察吡格列酮对模型细胞葡萄糖掺入率的影响;应用免疫细胞化学染色法观察吡格列酮对IR HepG2细胞IRS-1、IRS-2表达的影响。结果与模型细胞组比较,1×10^-5mol／L吡格列酮显著提高了HepG2细胞的葡萄糖掺入率（P〈0．01）,使IRHepG2细胞IRS-1、IRS-2蛋白的表达显著增加（P〈0．05）。结论吡格列酮的胰岛素增敏作用可能与胰岛素信号转导分子IRS-1、IRS-2蛋白的表达增强有关。     

吡格列酮对高脂大鼠非酒精性脂肪肝与胰岛素抵抗的影响

目的探讨环境因素引起的非酒精性脂肪肝与胰岛素抵抗的关系,并观察吡格列酮对其的影响。方法应用59％高脂饮食喂养大鼠4周制成胰岛素抵抗的动物模型后,给予药物吡格列酮干预4周,观察非酒精性脂肪肝对大鼠胰岛素敏感性的影响以及吡格列酮对其的干预。结果经59％高脂饮食喂养8周后,模型对照组较正常对照组大鼠空腹血糖及胰岛素均明显增高,血脂、血清游离脂肪酸（FFA）亦明显增高。而给予吡格列酮干预后药物干预组较模型对照组大鼠空腹血糖及胰岛素均明显减低,血脂、血清FFA亦明显减低。结论高脂饮食可诱导非酒精性脂肪肝并导致胰岛素抵抗,而吡格列酮可干预此过程。     

盐酸吡格列酮联用诺和灵胰岛素治疗老年糖尿病

盐酸吡格列酮(简称吡格列酮)为胰岛素增敏剂，与胰岛素联用可减少胰岛素用量，降糖、降脂、减轻胰岛素抵抗(IR)。本文观察了吡格列酮联用诺和灵胰岛素(30R)对磺脲类失效，用胰岛素仍效果不佳的老年2型糖尿病的疗效，报道如下。     

吡格列酮改善胰岛素抵抗和脂代谢异常并降低血清视黄醇结合蛋白4的浓度

目的探讨吡格列酮（Pio）改善胰岛素抵抗（IR）的可能机制和对血脂的影响。方法30只Wistar雄性大鼠分为阴性对照（Nc）、高脂饮食（HF）、吡格列酮（Pio）3组。采用高脂饮食对HF组及Pio组大鼠制作IR模型,成功后Pio组给予Pio20mg·kg^-1·d^-1灌胃。8周后检测相应指标。结果与HF组相比,Pio组HOMA-IR、TG、LDL-C、视黄醇结合蛋白4水平及磷酸烯醇式丙酮酸羧激酶（PEPCK）酶比活性均明显降低（P均〈0．05）,HDL-C明显升高（P〈0．05）。结论吡格列酮能降低血清视黄醇结合蛋白4水平,抑制肝脏PEPCK酶活性,改善IR和糖、脂代谢。     

吡格列酮联合二甲双胍治疗糖耐量受损疗效观察

将糖耐量受损（IGT）患者分成两组，分别给予吡格列酮（对照组）和吡格列酮＋二甲双胍（观察组）治疗3个月后，观察两组血糖、胰岛素、稳态模型胰岛素抵抗指数（HOMA-IR）的变化情况。结果两组血糖、胰岛素、HOMA-IR均显著降低，观察组上述指标改善程度明显优于对照组。认为吡格列酮能改善IGT和胰岛素抵抗，同时服用二甲双胍则效果更佳。     

2型糖尿病合并非酒精性脂肪肝患者经吡格列酮治疗后核苷酸结合寡聚化结构域样受体蛋白3的变化

目的 探讨吡格列酮治疗2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFLD）患者血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)水平的改变。方法 收集上海健康医学院附属周浦医院内分泌科2021年1月到2022年10月就诊的T2DM合并NAFLD患者80例，随机分为对照组及吡格列酮治疗组，随访4周。分析两组研究对象基线及随访时血糖、血脂、肌酐、谷丙转氨酶等生化指标；运用ELISA双抗体夹心法检测外周血NLRP3水平。结果 最终吡格列酮组35例、对照组36例完成全部试验。吡格列酮组基线血清NLRP3为（5.4±1.1）μg/L，随访时为（4.8±0.8）μg/L，有明显下降；而对照组基线血清NLRP3为（5.2±1.0）μg/L，随访时为（5.2±0.8）μg/L，无明显改变，并且随访时吡格列酮组血清NLRP3水平低于对照组。除随访时吡格列酮组TC水平高于对照组外，两组间血糖、血脂、肝肾功能均无明显差异。结论 T2DM合并NAFLD患者使用吡格列酮治疗后在改善糖脂代谢的同时，也可以降低血清NLRP3水平。     

吡格列酮对非酒精性脂肪性肝病患者的氧化应激参数和炎症因子的影响

目的:观察吡格列酮对非糖尿病非酒精性脂肪性肝病(NAFLD)患者肝脏脂肪含量及氧化应激参数和炎症因子水平的影响,探讨吡格列酮防治NAFLD的可能作用机制。方法:采用随机、单盲、对照组的研究。106例非糖尿病NAFLD患者随机分为吡格列酮组52例和对照组54例,对照组予以常规生活方式干预,吡格列酮组在常规生活方式干预的基础上予吡格列酮30 mg,1次/d,疗程均为24周。检测2组患者干预前后的肝/脾CT比值、血清丙氨酸转氨酶(ALT)、γ-谷氨酰转肽酶(GGT)、游离脂肪酸(FFA)、丙二醛(MDA)、4-羟壬烯醛(4-HNE)、白介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α,用稳态模型评估胰岛素抵抗指数(HOMA-IR)。结果:治疗前2组各项指标均无显著差异(P>0.05)。对照组干预前后上述指标均无明显变化(均P>0.05)。吡格列酮组治疗后肝/脾CT比值明显升高(P<0.05),血清ALT、GGT、FFA、MDA、4-HNE、IL-1β、IL-6、TNF-α、HOMA-IR均明显下降(均P<0.05)。结论:吡格列酮治疗可以明显减轻NAFLD患者肝脏脂肪含量,降低NAFLD患者的氧化应激参数和炎症因子水平。     

预防性应用吡格列酮改善胰岛素抵抗的脂肪内分泌机制

目的探讨吡格列酮改善胰岛素抵抗过程中脂肪内分泌功能的改变。方法45只W istar雄性大鼠随机分为对照组、胰岛素抵抗组和吡格列酮组。胰岛素抵抗动物模型成功建立后,分析各组抵抗素、脂联素和脂联素受体的表达。结果与胰岛素抵抗组比较,吡格列酮组大鼠的体质量、空腹血糖、游离脂肪酸差异不明显,但胰岛素、胰岛素抵抗指数、葡萄糖耐量和胰岛素耐量明显改善（P〈0.01）,脂联素表达明显增高（P〈0.05）。结论脂肪内分泌功能紊乱在高脂诱导胰岛素抵抗的发生中起着重要的作用,预防性应用吡格列酮可明显延缓大鼠胰岛素抵抗的发生,改善脂肪内分泌功能。     

吡格列酮对高血压伴胰岛素抵抗的影响

近年研究证明,高血压多伴有胰岛素抵抗(IR)和高胰岛素血症,IR为心血管疾病的独立危险因素,因此对IR的干预成为高血压治疗的焦点之一。本研究旨在探讨胰岛素增敏剂吡格列酮对高血压伴IR的影响。     

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.