肠道菌群在糖尿病发生发展中的作用机制研究进展

糖尿病已经成为严重威胁人类健康的疾病之一。目前已有研究证明肠道菌群在糖尿病的发生、发展中发挥着重要作用。肠道菌群在人体中处于动态平衡,但容易受到饮食、环境、细菌的相互作用以及抗菌药物等多种因素的影响。肠道菌群的变化可以导致肥胖、胰岛素抵抗、肠道渗透压改变以及代谢性内毒素血症等,从而促进糖尿病(1型及2型)的发生、发展,而益生菌在预防糖尿病的发生和改善糖尿病预后中的作用不可小视。本文从糖代谢、脂代谢、免疫及并发症等方面分析肠道菌群影响糖尿病发生发展的机制。     

硫辛酸在糖尿病微血管病变治疗中的作用

糖尿病是危害人群健康的一种慢性疾病。糖尿病微血管病变是糖尿病的特异性病变,其并发症主要包括肾脏病变,视网膜病变及神经病变。而其发生受多种因素影响,其发生机制研究已形成多种学说,主要有非酶糖基化、多元醇通路、氧化应激及己糖胺通路学说等。近年来硫辛酸对糖尿病微血管并发症的治疗作用是国内外研究的热点,硫辛酸是高效抗氧化剂,清除自由基和活性氧,再生体内谷胱甘肽等其他抗氧化剂,减弱氧化应激,从而硫辛酸可减弱多种糖尿病微血管并发症的诱发因素,并干预多元醇通路与己糖胺通路,对糖尿病微血管并发症中的相应靶器官有保护作用,本文就硫辛酸在糖尿病微血管病变中的应用做一简要综述。     

糖尿病皮肤感染与微生物菌群关系的研究进展

糖尿病是以血糖升高为特征的内分泌疾病,由于高血糖状态,使吞噬细胞的趋化作用、吞噬作用以及杀菌功能受损,抗感染能力减弱。正常情况下,人体皮肤微生物菌群对维持人体健康发挥着重大屏障作用,并在皮肤表面保持着动态的平衡,而这种平衡因糖尿病被打破导致皮肤菌群发生紊乱时,人体就会患上各种皮肤感染性疾病,包括真菌、细菌、病毒等。探究如何调整糖尿病患者皮肤微生态平衡、预防及控制其感染,减少感染并发症具有重要意义。     

瘦素与高血压相关性研究进展

瘦素是一种由肥胖基因编码,主要由脂肪细胞合成分泌的肽类激素。研究表明,瘦素与高血压的发生发展相关,其机制可能是:瘦素对血管有舒张或收缩双向调节作用,该作用呈剂量、时间依赖性。在慢性高瘦素血症状态下,由于血管内皮功能障碍使瘦素诱导的一氧化氮合成减少,交感神经活性增加,交感神经的收缩血管效应占优势,导致血压升高。瘦素可以通过中枢或外周机制激活交感神经系统,前者包括激活POMC-MC3/4R通路和肾素-血管紧张素系统,后者可能与瘦素促进外周交感神经轴索生长有关。此外,在慢性高瘦素血症状态下,瘦素的局部促尿钠排泄作用被破坏,表现为对水钠的重吸收增加而导致水钠潴留,从而参与高血压的发生发展。瘦素与瘦素受体基因多态性与非肥胖相关高血压的发生有一定相关性。     

新生儿肠道双歧杆菌数量影响因素与其婴儿期腹泻关系

目的探讨新生儿肠道双歧杆菌数量的相关影响因素,并明确它们与婴儿期腹泻的关系。方法以120例新生儿为研究对象,生后5-7 d均做大便双歧杆菌定量培养,并做相关因素的准确登记,同时严密观察随访至1岁,准确记录其发生腹泻情况。结果母亲分娩方式、临产期及产后是否使用抗生素、母亲妊娠期饮食习惯以及新生儿黄疸期长短与新生儿肠道双歧杆菌数量有相关性。新生儿黄疸期长、母亲临产期及产后使用抗生素均是婴儿腹泻的危险因素;阴道分娩、母亲喜发酵制品及喜素食均是婴儿腹泻的保护因素。结论为避免导致新生儿肠道双歧杆菌数量不足的影响因素,提倡阴道分娩、临产期及产后不用抗生素、妊娠期多食发酵制品和素食,并尽量设法缩短新生儿黄疸时间,以减少婴儿腹泻的发生。     

母婴间菌群传递的研究进展

肠道菌群的结构对婴儿肠道系统发育及免疫系统构建具有重要的影响,研究表明最初的婴儿肠道菌群在母亲子宫内就已经存在并受分娩方式和喂养方式的影响。本研究从母亲怀孕、分娩、喂养三个阶段综述母婴间的菌群传递,为母婴间菌群传递机制及婴儿肠道菌群对其免疫系统构建的影响提供一定的理论依据。     

瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体mRNA表达的影响

目的研究瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体(Ob-R)mRNA表达的影响。方法采用六孔板培养皿培养鼠平滑肌细胞,5个孔作为一个浓度组,通过半定量的RT-PCR方法,分别观察了不同浓度的大鼠瘦素、胰岛素及IL-6对平滑肌细胞瘦素受体mRNA表达水平的影响。结果通过半定量RT-PCR,我们检测了短型瘦素受体(Ob-Ra)和长型瘦素受体(Ob-Rb)的mRNA表达水平,瘦素受体(Ob-R)mRNA表达水平随着瘦素及IL-6浓度增加而上升,随着胰岛素的浓度增加而下降。结论瘦素及IL-6可在体外上调平滑肌细胞瘦素受体的表达,胰岛素可下调平滑肌细胞瘦素受体的表达。这三个因子参与了瘦素受体的表达调控,对我们了解瘦素抵抗的发生机制有重要意义。     

糖尿病肾病致凝血异常的研究

糖尿病(DM)已成为世界性的常见病,其发病率高,并且随着生活水平的改善,其发病率必然还会进一步加剧。血管病变是DM的重要并发症之一,糖尿病肾病(DN)是糖尿病常见且严重的微血管并发症,与血栓形成密切相关。糖尿病肾病的进展伴随着体内凝血活性和抗凝活性的失调,同时激活自身免疫系统,发生炎症反应。炎症应答过程中释放的炎症因子损伤肾小球内皮细胞,导致抗凝活性减弱。DN患者体内血细胞激活,微粒形成增多会加强凝血活性。此外,纤溶酶抑制剂(PAI-1)与纤溶酶激活剂(t PA)的失衡会引起纤溶系统紊乱。这三个方面引起DN患者体内的高凝状态加重,并因此加速肾功能恶化,导致肾小球率过滤降低,系膜基质增多,最终引起肾小球硬化及终末期肾脏疾病。本文就糖尿病肾病致凝血异常的发生机制做一综述。     

脂代谢的测定对老年2型糖尿病患者临床意义

目的探讨老年2型糖尿病与血脂、载脂蛋白、脂蛋白(a)之间的关系及其临床测定的意义。方法对97例老年2型糖尿病患者及65例老年对照组进行了血清总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)及脂蛋白(a)[Lp(a)]的测定。结果老年2型糖尿病患者血清TC、TG、LDL-C、ApoB及Lp(a)水平均显著高于老年对照组。而血清HDL-C和ApoAI水平老年2型糖尿病组显著低于老年对照组。结论老年2型糖尿病患者由于体内胰岛素相对不足及胰岛素抵抗,使血脂、载脂蛋白、脂蛋白浓度和组成成分发生变化及功能发生异常,从而促进动脉粥样硬化,并伴随着血管并发症的发生。因此,在对老年糖尿病并发症的预防和控制上,应在控制血糖的基础上减少脂肪的摄入,以降低高脂血症的发生,从而降低血管并发症的发生。     

运动干预对肥胖机体体内瘦素等脂肪细胞因子作用的影响

肥胖是近年主要的流行病之一,是危害健康的全球公共卫生问题。肥胖是一种慢性低度全身性炎症,伴随着一些炎性细胞的浸润和改变,并存在脂肪细胞因子分泌紊乱。瘦素是由白色脂肪细胞分泌的一种蛋白类激素,也是促炎细胞因子,在调控体内能量与代谢等方面发挥重要作用。运动干预会使肥胖机体体内促炎因子(瘦素、TNF-α、IL-6)水平含量降低,抗炎因子(脂联素)水平含量升高。运动能够延缓肥胖机体体内炎症反应的发生。本文以体内瘦素的生理功能及作用机制为中心,系统综述了运动对肥胖性慢性炎症的调节,主要包括脂肪细胞因子瘦素、脂联素、IL-6、TNF-α,以此探讨运动干预减重降脂和减轻慢性炎症反应的机制,为防治慢性代谢性疾病提供新视角。     

Neonatal immune challenge does not affect body weight regulation in rats

The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter long-term body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 microg/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 microg/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.     

Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers.

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.     

Abnormalities in vascular arachidonic acid metabolism in the infant of the diabetic mother.

The infant of the diabetic mother has an increased incidence of thromboses in utero and in the neonatal period. In the adult with diabetes a decrease in prostacyclin formation has been suggested as a cause for the atherothrombotic tendency. We therefore evaluated arachidonic acid metabolism in infants of diabetic mothers. Endogenous radioimmunoassayable 6-keto prostaglandin F1 alpha (PGF1 alpha) was normal in umbilical vessels obtained from the infants of diabetic mothers whose glucose homoeostasis was maintained when compared with control values. Nevertheless, a significant inhibition of vascular production of 6-keto PGF1 alpha was observed in infants born to mothers with raised HbA1C concentrations. A decrease in the concentration of plasma 6-keto PGF1 alpha was also seen in the infants of diabetic mothers when compared with control neonates. The correlation observed between plasma 6-keto PGF1 alpha concentrations and endogenous vascular prostacyclin formation in the infants of diabetic mothers indicates that the in vitro deficiency of prostacyclin formation reflects a concomitant in vivo abnormality.     

Zinc effects on hyperglycemia and hypoleptinemia in streptozotocin-induced diabetic mice.

Zinc has an antihyperglycemic effect. Zinc can also influence the production of leptin, a satiety factor that reduces appetite and blood sugar level. In this study, we investigated the effect of zinc supplementation on food intake and circulating leptin and glucose concentrations in streptozotocin-induced diabetic mice. Male diabetic mice received zinc supplementation (20 ppm) from drinking water for two weeks. The results showed that zinc treatment did not affect body weight gain, body fat content or food intake in these diabetic mice. However, zinc supplementation markedly ameliorated the hyperglycemia of diabetic mice. After zinc treatment, serum leptin concentrations tended to increase in the diabetic mice. This study suggests that zinc is a mediator of leptin production.     

Neonatal vaccination against respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and is the most frequent cause of lower respiratory tract infections in children.Efficacious vaccination...     

Prenatal stress,immunity and neonatal health in farm animal species

The high pre-weaning mortality in farm animal species and poor welfare conditions of reproductive females question modern industrial farming acceptability. A growing body of literature has been produced recently, investigating the impact of maternal stress during gestation on maternal and offspring physiology and behavior in farm animals. Until now, the possible impact of prenatal stress on neonatal health, growth and survival could not be consistently demonstrated, probably because experimental studies use small numbers of animals and thus do not allow accurate estimations. However, the data from literature synthesized in the present review show that in ungulates, maternal stress can sometimes alter important maternal parameters of neonatal survival such as colostrum production (ruminants) and maternal care to the newborn (pigs). Furthermore, maternal stress during gestation can affect maternal immune system and impair her health, which can have an impact on the transfer of pathogens from the mother to her fetus or neonate. Finally, prenatal stress can decrease the ability of the neonate to absorb colostral immunoglobulins, and alter its inflammatory response and lymphocyte functions during the first few weeks of life. Cortisol and reproductive hormones in the case of colostrogenesis are pointed out as possible hormonal mediators. Field data and epidemiological studies are needed to quantify the role of maternal welfare problems in neonatal health and survival.     

Immunohistochemical Demonstration of Leptin in Pancreatic Islets of Non-Obese Diabetic and CD-1 mice: Co-localization in Glucagon Cells and its Attenuation at the Onset of Diabetes

Leptin is a 16 kD polypeptide hormone produced predominantly by white adipose tissue and exerts profound effects on food intake and energy balance. More recent studies have shown extra sites of leptin production in human and rodent tissues and have ascribed additional roles for the hormone, e.g., in immune and reproductive functions. A role for the hormone has also been implicated in insulin-dependent diabetes mellitus in the non-obese diabetic (NOD) mouse. However, whether leptin originates from islet cells of the mouse is not known. Here dual-label immunohistochemistry was employed to examine leptin expression in islet cells, and its distribution and cellular sources in pancreatic sections of female NOD/Ak and CD-1 mice of various ages. For comparison, leptin immunolabelling was examined in adult pancreatic sections from male NOD/Ak CD-1, Balb/c and FVB/N mice and female severe combined immunodeficient CB. 17 mice. Pancreatic tissues from adult female guinea pig, sheep and cattle and neonatal pigs were also studied. Our results show that in the day 1 NOD and CD-1 mice, leptin immunolabelling was observed in selective glucagon cells within the developing islets while at days 15 and 22, it became more intense and co-incident. This pattern of staining was maintained at days 40, 90, 150 and 250. In the female NOD mouse, leptin was absent in intra-islet immune cells. Its expression was variable in islets from male NOD and CD-1 mice. In spontaneously diabetic female NOD mice and following acceleration of diabetes with cyclophosphamide, despite the persistence of strong immunolabelling for glucagon in the re-distributed alpha cells, leptin expression was either absent, diminished or present in only a proportion of alpha cells. The reduction in leptin labelling was often associated with diabetic islets which had insulitis in association with only a small number of residual beta cells. Leptin expression was absent in guinea pig, ovine, bovine and neonatal porcine islet cells, despite the expression of intensely labelled glucagon cells. The present results demonstrate leptin co-localization in glucagon cells of the mouse islet. Its expression diminishes in the presence of inadequate insulin. Leptin produced within the mouse islet may have bi-directional influences on leptin and insulin regulation and may play local functions in islet development and metabolism.     

Leptin：a multifunctional hormone

Leptin is the protein product encoded by the obese(ob) gene.It is a circulating hormone produced primarily by the adipose tissue.ob/ob mice with mutations of the gene encoding leptin become morbidly obese,infertile,hyperphagic,hypothermic,and diabetic.Since the cloning of leptin in 1994,our knowledge in body weight regulation and the role played by leptin has increased substantially.We now know that leptin signals through its receptor,OB-R,which is a member of the cytokine receptor superfamily.Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure.Leptin also plays important roles in angiogenesis,immune function,fertility,and bone formation.Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin‘s activities in vivo may have potential therapeutic benefits.     

The BBZDR/Wor rat model for investigating the complications of type 2 diabetes mellitus

Congenic and inbred strains of rats offer researchers invaluable insight into the etiopathogenesis of diabetes and associated complications. The inbred Bio-Breeding Zucker diabetic rat (BBZDR)/Wor rat strain is a relatively new and emerging model of type 2 diabetes. This strain was created by classical breeding methods used to introgress the defective leptin receptor gene (Lepr(fa)) from insulin-resistant Zucker fatty rats into the inbred BBDR/Wor strain background. The diabetic male BBZDR/Wor rat is homozygous for the fatty mutation and shares the genetic background of the original BB strain. Although lean littermates are phenotypically normal, obese juvenile BBZDR/Wor rats are hyperlipidemic and hyperleptinemic, become insulin resistant, and ultimately develop hyperglycemia. Furthermore, the BBZDR/Wor rat is immune competent and does not develop autoimmunity. Similar to patients with clinical diabetes, the BBZDR/Wor rat develops complications associated with hyperglycemia. The BBZDR/Wor rat is a model system that fully encompasses the ability to study the complications that affect human type 2 diabetic patients. In this review, recent work that has evaluated type 2 diabetic complications in BBZDR/Wor rats is discussed, including the authors' preliminary unpublished studies on cardiovascular disease.     

Neonatal tooth with Riga-Fide disease affecting breastfeeding: a case report

Background

Neonatal teeth erupt during the neonatal period and natal teeth are the presence of teeth since birth. While rare, natal teeth and neonatal teeth can have a significant impact on breastfeeding. Neonatal teeth are less common, and although its exact etiology is still unknown, it can cause difficulties in breastfeeding to the mother and may eventually lead to discontinuation of breastfeeding. Other associated possible complications include tooth aspiration and sublingual ulceration. This paper was aimed to discuss the clinical features, complications, and management of neonatal tooth, in addition to its impact on breastfeeding and role in sublingual ulcer formation.

Case presentation

We present a baby girl who had a neonatal tooth with sublingual ulceration (Riga-Fede disease), which resulted in a difficulty to breastfeed for the baby and nipple pain to the mother. Following the extraction of the baby’s tooth, she immediately continued breastfeeding, and her tongue ulcer healed well.

Conclusion

Extraction of the neonatal tooth promoted rapid healing of oral ulcers and the reestablishment of breastfeeding.