肠道菌群与1型糖尿病的关系

1型糖尿病发病机制与遗传因素、环境因素及自身免疫因素均有关,是在遗传因素基础上,由环境因素启动,以T淋巴细胞介导的胰岛β细胞进行性损伤为主要特征的自身免疫性疾病.肠道菌群作为环境因素与1型糖尿病发生有直接关系,可通过改变肠壁通透性和宿主免疫系统影响发病.肠道菌群、宿主免疫及1型糖尿病三者之间存在相互联系,研究肠道菌群可为1型糖尿病的预防和治疗提供线索.     

1型糖尿病的免疫防治

1型糖尿病(T1DM)是遗传与环境因素共同作用所致的自身免疫性疾病.为预防和延缓T1DM高危人群自身免疫性胰岛炎的发生,阻止新发T1DM残存胰岛β细胞进一步遭受免疫破坏,T1DM的免疫防治有了较大进展.根据干预实施时机的不同,分为一级、二级和三级预防.主要通过饮食干预、自身抗原疫苗接种及单克隆抗体治疗等措施诱导自身免疫耐受,改善免疫调节,减少胰岛β细胞凋亡.许多临床研究对T1DM的免疫干预进行了探索,并进行了谷氨酸脱羧酶(GAD)疫苗、抗CD3单克隆抗体、DiaPep277等药物的临床研究,为T1DM的防治提供了新启示.     

自体外周造血干细胞移植——治疗1型糖尿病的新曙光

1型糖尿病以自身免疫性胰岛炎和胰岛β细胞损伤为病理特征.尽管胰岛素强化治疗能使1型糖尿病患者实现良好的血糖控制,但该方案难以完全阻止糖尿病并发症的发生.最大限度的保存1型糖尿病患者自身的胰岛功能,是预防或延缓糖尿病并发症的关键.近年研究显示:自体外周造血干细胞移植(AHSCT)可诱导1型糖尿病患者实现免疫耐受,并改善其胰岛功能.本文将重点介绍采用该方案治疗中国人群初发1型糖尿病患者(多以酮症酸中毒起病)的临床研究结果( NCT01341899,ClinicalTrials.gov),并简要阐述AHSCT治疗1型糖尿病的可能机制和应用前景.     

新诊断1型糖尿病患者的干预研究指南

1型糖尿病，是一种自身免疫性疾病，最终破坏胰岛中产生胰岛素的β细胞。对于自发1型糖尿病NOD大鼠模型的研究，证实此种疾病是可以预防的。1型糖尿病的患者及其亲属、研究者、政府以及企业都在共同努力，试图考察各种干预／预防治疗措施对人类的作用。这些治疗可能要承担一定的风险，包括加速β细胞功能的损失、恶性变和感染。从科学和伦理的角度讲，要求研究者通过干预研究得到最多的信息，最小的危险。为了达到这个目的应该将试验设计标准化。     

1型糖尿病的药物治疗动物实验获得成功

2型糖尿病属于代谢性疾病,而1型糖尿病则属于自身免疫性疾病。什么是自身免疫性疾病?就是人体的免疫系统出现异常,攻击自身的正常组织导致的疾病。在1型糖尿病中,患者的免疫系统攻击分     

1型糖尿病预测及预防研究新进展

1 型糖尿病(T1DM) 是一种慢性自身免疫性疾病,暂无有效的治愈方法。在临床诊断前数个月甚至数年可在 患者外周血中检测到胰岛自身抗体,使得T1DM 的预测和预防成为可能。文章就近几年在T1DM 的预测及预防方 面的最新进展进行概述。     

关注1型糖尿病并发症

<正>1型糖尿病是由致病性T细胞介导的免疫反应特异性攻击胰岛β细胞而导致胰岛β细胞破坏,胰岛功能进行性衰竭为特征的自身免疫性疾病。相较于2型糖尿病,1型患者由于胰岛功能差,更易合并糖尿病酮症酸中毒、严重低血糖事件等急性并发症。1型糖尿病常出现的慢性并发症主要为微血管并发症,如糖尿病视网膜病变、肾病、神经病变。此外,1型患者还常合并出现其他自身免疫性疾病,尤其是自身免疫性甲状腺疾病。下文结合2014年ADA1型糖尿病终生管理立场声明,具体分析     

脐血多能干细胞的免疫教育与1型糖尿病的治疗

目前,糖尿病的发病率和增长速度令人震惊,正严重威胁着人类的健康[1].特别是1型糖尿病,因患者机体免疫功能紊乱,T淋巴细胞特异性杀伤胰岛β细胞,而导致胰岛素缺乏和糖尿病的发生.全球数以百万计的1型糖尿病患者必须每天注射胰岛素治疗,以维持生命.但胰岛素的治疗只能对症＂治标＂,长期大剂量应用具有潜在副作用.因此,在临床实践中,如何有效地控制T细胞介导的自身免疫反应和再生胰岛β细胞,是治疗1型糖尿病亟待解决的两个关键问题.大量研究证明：1型糖尿病的自身免疫反应具有多克隆特性,且有多重的免疫细胞调节紊乱[2-3].一直以来,为攻克1型糖尿病,世界各国已对众多治疗方案进行了探索和临床尝试,多数以失败告终.     

1型糖尿病和自身免疫性甲状腺疾病的遗传易患性研究进展

1型糖尿病主要分为2型：IA型,与自身免疫相关;IB型,目前病因尚不清楚。本文将主要讨论IA型1型糖尿病。1型糖尿病是器官特异性自身免疫疾病,患者易合并其他自身免疫性疾病,其中最多见的是自身免疫性甲状腺疾病。     

2型糖尿病并局限性硬皮病一例

免疫因素损害是糖尿病发生、发展的重要因素之一.既往认为1型糖尿病的发生和免疫密切相关,但是2型糖尿病也同样存在免疫功能紊乱[1],不少免疫复合物的沉积参与肾脏等脏器的损害[2];临床上,国外曾报道多例青少年的1型糖尿病患者合并一种自身免疫性疾病——局限性硬皮病[3-5].但是成年人中2型糖尿病伴发局限性硬皮病在国内外报道甚少,现报道1例,以便于增加糖尿病合并皮肤硬化的鉴别诊断,加强2型糖尿病并发其他自身免疫性疾病的认识.     

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.     

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.     

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.     

Morphological and immunocytochemical heterogeneity of cultured pinealocytes from one-week-and two-month-old rats: Planimetric and densitometric investigations

Abstract: In vitro preparations of rat pinealocytes are widely used for biochemical analyses of signal transduction processes. This paper deals with morphological and immunocytochemical features of such preparations. Special attention was paid to the problems of whether pinealocytes represent a heterogeneous cell population and how such heterogeneity may develop during ontogeny. The investigations were performed with cells which were obtained from the pineal organ of one-week-and two-month-old rats, attached to synthetic peptide-coated coverslips or tissue culture chamber slides, and maintained under in vitro conditions overnight. The attached cells were then fixed with paraformaldehyde. These preparations yielded monolayers of spherical cells of different sizes; most cells were isolated, but some of them were aggregated and formed small clusters. On the average, the cells from the one-week-old animals were smaller than the cells from the two-month-old animals. Immunocytochemical demonstration of S-antigen, a pinealocyte-specific marker, showed that the majority of the cells from two-month-old animals were intensely or moderately labelled. Pinealocytes from one-week-old animals were less S-antigen immunoreactive. Only very few cells (less than 1% displayed glial fibrillary acidic protein (GFAP)-immunoreactivity. Planimetric investigations of the cell size and semiquantitative densitometric investigations of the intensity of the S-antigen immunoreaction revealed that (i) pinealocytes kept in vitro form a heterogeneous cell population, and that (ii) this heterogeneity increases during postnatal development from one-week-old to two-month-old animals. Two groups of pinealocytes can be distinguished based on their developmental fate: pinealocytes of one group grow dramatically, but show only a moderate increase in S-antigen immunoreactivity, and pinealocytes of the other group retain their size, but display a distinct increment in S-antigen immunoreacti vitv.     

Effects of pinealectomy and melatonin administration on certain indices of ovarian hyperplasia and/or hypertrophy in rats with both ovaries intact or after unilateral ovariectomy

Abstract: In earlier studies from other laboratories it was shown that melatonin decreased ovarian weight in rats and inhibited compensatory hypertrophy of the remaining ovary after unilateral ovariectomy. This study was designed to examine the influence of melatonin on certain indices of ovarian hyperplasia and/or hypertrophy in adult female rats with both ovaries preserved and with either an intact pineal gland or with the pineal gland removed (pinealectomy, PX) or, finally, in sham-PX animals. Similar studies were conducted on rats after unilateral ovariectomy, referring the examined parameters to the remaining intact ovary. The studies included mitotic activity of granulosa layer cells and corpus luteum cells, ovarian weight, ovarian cross-sectional area, cross-sectional area of the granulosa layer of all the Graafian follicles and the cross-sectional areas of the corpora lutea, visible on the ovarian cross-section. On the basis of results, we conclude that: 1) the effect of PX on the processes of ovarian hyperplasia and hypertrophy may vary; analogously, exogenous melatonin administration may influence ovarian hyperplasia and hypertrophy in different ways; 2) PX and exogenous melatonin may, under certain conditions, exert similar biological effects, even synergistic effects; 3) melatonin inhibits ovarian growth processes, while the effects of PX are variable; 4) the results indicate that in experiments performed on rats, with the use of two control groups, i.e., intact and sham-PX, melatonin effects on these two groups may differ.