胰岛素泵联合马来酸罗格列酮强化治疗2型糖尿病的临床研究

目的采用胰岛素泵联合马来酸罗格列酮强化治疗2型糖尿病（T2DM）以评价其临床疗效。方法将246例T2DM患者随机分为胰岛素泵（CSⅡ）联合马来酸罗格列酮治疗组（CSⅡ＋罗格列酮）组80例、单纯CSⅡ治疗组84例和多次皮下注射胰岛素治疗（MDⅠ）组82例，均连续2周。比较三组治疗前后血糖、HbA1c、血糖达标时间、胰岛素用量、Fins、C肽（C—P）水平及HOMA-IR、胰岛素敏感指数（IAI）。结果CSⅡ＋罗格列酮和单纯CSⅡ均能显著降低患者血糖和HbA。c（P〈0．01）；与MDI比达标时间短（P〈0．01），节省胰岛素用量（P〈0．01）。CSⅡ＋罗格列酮组胰岛素用量更少（P〈0．05）；与单纯CSⅡ和MDI比HOMA-IR明显降低、IAI明显增加（P〈0．05），且无心、肝、肾功能损害发生。结论胰岛素泵联合马来酸罗格列酮强化治疗T2DM更能有效地控制血糖、节省胰岛素用量、减轻胰岛素抵抗。     

马来酸罗格列酮联合格列美脲、二甲双胍治疗2型糖尿病的疗效观察

目的观察马来酸罗格列酮(RSG)对2型糖尿病(T2DM)患者的疗效和安全性。方法128例T2DM患者随机分为RSG组(66例)及对照(Con)组(62例),观察治疗前后空腹及餐后2小时血糖(FPG,2hPG)、糖化血红蛋白(HbA1c)及胰岛素(Ins)的变化。结果连续服RSG3个月后,其FPG、2hPG、HbA1c及FIns与试验前比较差异均有统计学意义(P<0·05);与Con组比较差异也有统计学意义(P<0·05);对肝肾功能等无影响。结论RSG能显著降低血糖并改善胰岛素的敏感性,本研究尚未发现其明显不良影响。     

罗格列酮和二甲双胍治疗新发2型糖尿病的疗效比较

为观察胰岛素增敏剂治疗初发2型糖尿病（T2DM）的临床疗效，新诊断T2DM患者120例被随机分为三组，分别给予马来酸罗格列酮、二甲双胍和二者联合治疗。结果马来酸罗格列酮和联合治疗明显降低新发T2DM的FPG、HbA1c、HOMA-IR，明显升高脂联素，使体重较治疗前增加。     

胰岛素增敏剂罗格列酮抗高血压作用探讨

目的　观察胰岛素增敏剂马来酸罗格列酮在超重和 (或 )肥胖的轻、中度高血压患者的降血压作用及其影响因素 ,探讨胰岛素增敏剂用于原发性高血压治疗或辅助治疗的可能性。方法　超重及肥胖 (体重指数≥ 2 5kg/m2 )的非糖尿病轻、中度原发性高血压 [14 0mmHg <收缩压 <190mmHg ,(1mmHg =0 133kPa) ]患者 89例。测定口服葡萄糖耐量试验各时点血糖及胰岛素浓度 ,排除糖尿病。原服用降血压药物者停用药物 2周后进入试验 ,原生活方式不变。仅服用胰岛素增敏剂马来酸罗格列酮 8mg/d ,疗程 4周。分析血压下降情况及影响因素。 结果　 (1)治疗 4周后收缩压平均降低了 17mmHg ,舒张压平均降低了 11mmHg。 (2 )治疗后比治疗前空腹、糖负荷后 1h及 2h血胰岛素水平分别下降 2 7%、35 %、4 1% (P <0 0 0 0 1)。胰岛素敏感性改善了 30 % (P <0 0 0 0 1)。(3)在基线血压水平较高、胰岛素抵抗程度较严重及无高血压家族史的患者中罗格列酮的降压幅度更大。结论　马来酸罗格列酮对超重或肥胖非糖尿病人群显示了良好的抗高血压效能 ,提示此类胰岛素增敏剂可能在某些人群原发高血压治疗或辅助治疗中有一定价值。     

胰岛素联合罗格列酮对初诊2型糖尿病患者胰岛β细胞功能的保护作用

目的探讨胰岛素与罗格列酮合用对初诊2型糖尿病(T2DM)患者胰岛β细胞功能和血糖控制的影响。方法新诊断的空腹血糖大于12 mmol/L的T2DM患者47例,随机分为胰岛素组(n=22)、胰岛素 罗格列酮组(n=25)治疗12 w,分别在治疗前后检测空腹血糖、胰岛素、糖化血红蛋白(HbA1 c)、高敏C反应蛋白(hs-CRP)和胰岛素敏感性指数(ISI)及Homa B胰岛素分泌指数,并随访胰岛素与罗格列酮合用对初诊T2DM患者长期血糖控制的影响。结果12 w后,胰岛素 罗格列酮组较胰岛素组hs-CRP及胰岛素日用量明显下降(P<0.05),ISI和Homa B治疗后较对照组明显升高(P<0.05)。随访12个月时,胰岛素 罗格列酮组有13例患者仅采用饮食控制,血糖就可达到理想水平,而对照组仅有5例。结论胰岛素联用罗格列酮可以明显恢复初诊T2DM患者的胰岛功能,改善胰岛素抵抗。     

马来酸罗格列酮对2型糖尿病患者的长期疗效与安全性的观察

目的观察罗格列酮对2型糖尿病（T2DM）患者的长期疗效及安全性。方法采用自身治疗前后对照的方法，42例合用磺脲类、双胍类和α糖苷酶抑制剂药物治疗3个月以上血糖控制不良的T2DM患者加服马来酸罗格列酮，随访36个月，观察治疗前后血糖、HbA1c、FIns、HOMAIR、ISI、血清高敏C反应蛋白（hsC-RP）、Hb、谷丙转氨酶（GPT）、谷草转氨酶（GOT）、谷氨酰转移酶（γ-GT）等的变化。结果马来酸罗格列酮治疗组FPG、2hPG、HbA1c、FIns、hsCRP均较治疗前明显下降（P〈0．01），且与时间成正比，约治疗9个月后疗效趋于稳定，GPT、GOT、γ-GT较治疗前明显下降（P〈0．05）；所见的不良反应为下肢水肿，发生率为4．8％，经对症处理后消失。结论马来酸罗格列酮能有效降低长期口服降糖药物控制不佳的T2DM患者的血糖水平，对因脂肪肝而致的肝脏酶谱的增高有治疗作用，有良好的安全性。     

罗格列酮联合胰岛素强化治疗2型糖尿病分析

42例胰岛素强化治疗血糖控制不良的T2DM患者随机分为：治疗组24例,胰岛素强化治疗加罗格列酮4mg,qd;对照组18例,单用胰岛素强化治疗。结果：治疗后治疗组FPG及HbA1c较对照组明显下降（P〈0.05）,胰岛素用量明显减少,有显著性差异（P〈0.01）。甘油三脂下降,有统计学意义（P〈0.05）。结论：罗格列酮能有效改善T2DM患者的血糖,减少胰岛素用量,降低甘油三脂。     

罗格列酮联合胰岛素强化治疗2型糖尿病分析

42例胰岛素强化治疗血糖控制不良的T2DM患者随机分为：治疗组24例,胰岛素强化治疗加罗格列酮4mg,qd;对照组18例,单用胰岛素强化治疗。结果：治疗后治疗组FPG及HbA1c较对照组明显下降（P〈0.05）,胰岛素用量明显减少,有显著性差异（P〈0.01）。甘油三脂下降,有统计学意义（P〈0.05）。结论：罗格列酮能有效改善T2DM患者的血糖,减少胰岛素用量,降低甘油三脂。     

罗格列酮对2型糖尿病患者血管内皮功能和高敏C反应蛋白的影响

目的 探讨罗格列酮(RGZ)对2型糖尿病(T2DM)患者血管内皮功能和高敏C反应蛋白(hsC-RP)的影响.方法 选择40例T2DM患者(DM组)给予口服RGZ 12周.观察治疗前后FPG、FIns、HbA1c、hsC-RP、血管性假血友病因子(vWF)和血栓调节蛋白(TM)水平.另设30名健康正常人为对照(NC)组.结果 DM组给药前与NC组比较,血浆vWF、TM和hsC-RP均明显升高;经RGZ治疗12周后,患者FPG、FIns、HbA1c和胰岛素敏感指数均明显改善,且血浆vWF、TM和hsC-RP均明显下降.结论 RGZ在降低血糖和提高胰岛素敏感性同时,能改善患者血管内皮功能,降低炎症反应.     

盐酸吡格列酮治疗2型糖尿病患者的临床研究

目的研究胰岛素增敏剂盐酸吡格列酮对2型糖尿病(T2DM)患者的胰岛素抵抗、血压、血脂的影响.方法对102例体质指数(BMI)≥25 kg/m2且使用磺脲类+双胍类药物后糖化血红蛋白(HbA1c)>7.0%的T2DM患者,在重新制定合理的饮食和运动的基础上,随机分为两组:治疗组使用盐酸吡格列酮15 mg/d连用12周,对照组使用原药物,观察两组患者治疗前后空腹血糖(FBG)、餐后两小时血糖(2hPG)、空腹胰岛素(FIns)、餐后2小时胰岛素(2hIns)HbA1c、甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血压(BP)、胰岛素抵抗指数(HOMA-IR)等指标的变化.结果治疗12周后,治疗组FBG、HbA1c、Ins、BP、TG、LDL-C及HOMA-IR较较对照组均下降.结论盐酸吡格列酮能减轻胰岛素抵抗,降低血糖,改善脂代谢.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

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.     

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.     

Variabilité des concentrations plasmatiques de l’angiotensinogène et risque d’hypertension artérielle chez le rat transgénique

Aim

Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5 mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors.

Methods

Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n = 3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction).

Results

At baseline, transgenic rats had +18 mmHg higher bood pressure and –8% lower body weight compared to non-transgenic rats (P < 0.05) without significant changes for the vehicle groups throughout the study (P > 0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P < 0.05) in transgenic and +25%, +5.3% and +6.7% (P > 0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P > 0.05).

Conclusion

Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.