Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis

BACKGROUND & AIMS: Impaired mucosal barrier, cytokine imbalance, and dysregulated CD4(+) T cells play important roles in the pathogenesis of experimental colitis and human inflammatory bowel disease. Immunostimulatory DNA sequences (ISS-DNA) and their synthetic oligonucleotide analogs (ISS-ODNs) are derived from bacterial DNA, are potent activators of innate immunity at systemic and mucosal sites, and can rescue cells from death inflicted by different agents. We hypothesized that these combined effects of ISS-DNA could inhibit the damage to the colonic mucosa in chemically induced colitis and thereby limit subsequent intestinal inflammation. METHODS: The protective and the anti-inflammatory effect of ISS-ODN administration were assessed in dextran sodium sulfate-induced colitis and in 2 models of hapten-induced colitis in Balb/c mice. Similarly, these effects of ISS-ODN were assessed in spontaneous colitis occurring in IL-10 knockout mice. RESULTS: In all models of experimental and spontaneous colitis examined, ISS-ODN administration ameliorated clinical, biochemical, and histologic scores of colonic inflammation. ISS-ODN administration inhibited the induction of colonic proinflammatory cytokines and chemokines and suppressed the induction of colonic matrix metalloproteinases in both dextran sodium sulfate- and hapten-induced colitis. CONCLUSIONS: As the colon is continuously exposed to bacterial DNA, these findings suggest a physiologic, anti-inflammatory role for immunostimulatory DNA in the GI tract. Immunostimulatory DNA deserves further evaluation for the treatment of human inflammatory bowel disease.     

Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding

Objective

GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression.

Materials/Methods

Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4 h after spontaneous refeeding; ii) 2–4 h after T3 injection, without refeeding; and iii) 0.5–2 h after intravenous infusion of insulin, insulin + glucose and insulin + amino acids, without refeeding.

Results

Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~ 20%, P < 0.05 vs. fasting), but T3 injection induced a ~ 2-fold increase in Slc2a4 mRNA, 2–4 h later (P < 0.001). Moreover, T3 increased glycemia and insulinemia to the 2 h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding.

Conclusions

Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.     

Effect of maternal antibody on immunogenicity of hepatitis A vaccine in infants

OBJECTIVE: To determine the effect of maternal antibody on hepatitis A vaccine immunogenicity in infants.Study design Infants of mothers negative for antibody to hepatitis A virus (anti-HAV; group 1) were administered hepatitis A vaccine at 2, 4, and 6 months of age, and infants of anti-HAV-positive mothers were randomized to receive either hepatitis A vaccine (group 2) or hepatitis B vaccine (group 3) on the same schedule. Group 3 infants subsequently received hepatitis A vaccine at 8 and 10 months of age. RESULTS: At 15 months of age, 100% of infants in group 1, 93% in group 2, and 92% in group 3 had protective levels of antibody. However, there were significant differences in the geometric mean concentration (GMC) of anti-HAV between groups. Group 1 GMC was 231 mIU/mL, compared with 85 mIU/mL for group 2 and 84 mIU/mL for group 3 (P<.001, group 1 vs group 3). CONCLUSIONS: Passively acquired maternal anti-HAV resulted in a significantly lower final antibody response when infants were administered hepatitis A vaccine at 2, 4, and 6 months of age or at 8 and 10 months of age.     

阻断乙型肝炎e抗原阳性母亲宫内传播的研究

目的 探讨不同剂量乙肝免疫球蛋白对乙肝表面抗原和乙肝e抗原双阳性孕妇乙型肝炎病毒宫内传播的影响.方法 乙肝表面抗原和乙肝e抗原双阳性孕妇为病例组,乙肝表面抗原阳性但乙肝e抗原阴性的孕妇为对照组,对病例组和对照组均采用3种不同的干预方式:乙肝免疫球蛋白 400U、乙肝免疫球蛋白200U、no-乙肝免疫球蛋白进行干预,观察各组新生儿乙肝表面抗原、乙肝表面抗体、乙肝e抗原、乙肝e抗体、乙肝核心抗体检测情况.采用定性酶联免疫法检测.结果 观察病例乙肝免疫球蛋白400U组新生儿21例,乙肝表面抗原和乙肝e抗原检测均为阴性,未发现宫内感染者,追踪并复查仍未发现乙肝病毒抗原阳性者;观察病例乙肝免疫球蛋白 200U组新生儿22例,乙肝表面抗原均为阴性,1例乙肝e抗原阳性,宫内感染率为4.5%;病例no-乙肝免疫球蛋白组观察新生儿20例,检测乙肝表面抗原均为阴性,5例乙肝e抗原阳性,宫内感染率为25.0%;乙肝免疫球蛋白200U组宫内感染率低于no-乙肝免疫球蛋白组,但无显著性差异(χ2=3.58,P=0.058).结论 孕晚期注射乙肝免疫球蛋白400 U和200 U对阻断乙型肝炎e抗原阳性母亲宫内传播均有效果,乙肝免疫球蛋白400 U干预方案效果更好.     

Effect of intraperitoneal and intragastric loading with water and isosmotic solutions of saline and glucose on water intake of dehydrated rats

Female rats, dehydrated with food available for 24 hr, lost 6 to 8% of body weight. When allowed access to water, 40 to 60% of the weight deficit was replaced within the first hr. Either intraperitoneal (IP) or intragastric (IG) water loads (3% of body weight) administered just prior to return of water inhibited water intake of dehydrated rats nearly completely during the first hr of access to water. In contrast, similar loads of isotonic saline were much less effective. Even when 0.5 and 1.0 hr elapsed between IP loading (3% of body weight) with isotonic saline and access to water, water intake was not significantly different from that of untreated, dehydrated controls. In contrast, a similar IP load of water at these times completely inhibited water intake. Because of the contrasting effects of similar loads of water and isotonic saline on water intake of dehydrated rats, additional studies were carried out with an isosmotic solution of glucose (5%). IG administration (3% of body weight) of glucose inhibited water intake of dehydrated rats. IP administration (3% of body weight) attenuated the drinking response but did not reduce it to the level observed in dehydrated rats given an IP water load. When isosmotic glucose was administered at 0.5, 1.0, and 2.0 hr prior to allowing access to water, water intake was reduced significantly below that of dehydrated controls and to the same extent regardless of time of administration of the glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ziehl-Neelsen-维多利亚蓝-碘绿复合染色法显示抗酸杆菌

目的 :探讨显示皮肤活检组织中抗酸麻风杆菌、弹力纤维和细胞等组织成分的复合染色法。方法 :运用Ziehl Neelsen(Z N)苯酚复红染色液、维多利亚蓝 (Victoriablue ,VB)染色液、碘绿 (iodinegreen ,IG)和马汀氏黄 (Mar tiusyellow ,MY)染色液对皮肤活检组织进行复合染色。结果 :组织内结核样结节中麻风杆菌显示为红色 ,细胞核呈淡绿色 ,细胞浆无色 ,结节周围的弹性纤维呈蓝色 ,基质呈淡黄色。结论 :Z N原法染色单一 ,对比效果差 ,应用碘绿、马汀氏黄和维多利亚蓝复合的改造染色液 ,能更好显示组织中的麻风杆菌 ,以及包绕于结核样结节周围的弹力纤维等成分 ,该方法是一种对比清晰 ,可靠的复合染色法     

A vomiting phobia overcome by one session of flooding with hypnosis

A patient with a long-standing vomiting phobia was treated by flooding under a hypnotic trance. A follow-up 1 yr after treatment showed that she had remained free of her phobia.