Neonatal hyperthyrotropinemia in gestational diabetes mellitus and perinatal complications

The aim of this study is to explore the relationship between high cord blood thyroid-stimulating hormone (TSH) level and in-utero stress to the fetus in gestational diabetes mellitus (GDM). Cord blood TSH results were analyzed in 1,578 euthyroid infants from singleton pregnancies with GDM: 103 with elevated TSH (>16 mIU/l) and 1,475 with normal TSH. Maternal characteristics, pregnancy outcome and perinatal complications were compared between the two groups. Multiple logistic regression was used to study the association between high cord blood TSH level and various perinatal complications which reflect in-utero stress in GDM after adjusting for the confounding effects of parity, instrumental delivery, cesarean section and baby gender. High cord blood TSH level was found to be associated with the 1-min Apgar score <7 (OR 3.31, 95% CI 1.78-6.16), birth trauma (OR 3.44, 95% CI 1.11-10.69), neonatal jaundice requiring treatment (OR 2.08, 95% CI 1.30-3.32), neonatal sepsis (OR 2.34, 95% CI 1.24-4.42), respiratory complications (OR 3.45, 95% CI 1.37-8.70), neurological complications (OR 8.01, 95% CI 1.91-33.60) and overall perinatal morbidity (OR 2.41, 95% CI 1.58-3.67). Cord blood TSH level seems to be a better and independent indicator of the in-utero stress to the fetus in GDM when compared to the commonly used sugar profile result and HbA1c level.     

Effect of human hepatocyte growth factor on promoting wound healing and preventing scar formation by adenovirus-mediated gene transfer

Objective To evaluate the effects of hepatocyte growth factor (HGF) on the prevention of scar formation and the promotion of wound healing by gene transfer. Methods A total of 12 female New Zealand rabbits were used in this study. Rabbits were anesthetized with an intravenous injection of sodium pentobarbital, and identical wounds were made over the ventral surface of each ear. Five circular wounds, 7 mm in diameter, were created in each ear by excision through the skin to the underlying cartilage using sterile technique. After the surgical procedures, 10 of the rabbits were randomly allocated to five groups, with 2 rabbits in each group: Ad-HGF group 1, Ad-HGF group 2, Ad-HGF group 3, Ad-GFP (a reporter gene) group and the solvent group. Immediately after surgery, 6×10(7) pfu Ad-HGF, 6×10(8) pfu Ad-HGF, 6×10(9) pfu of Ad-HGF, 6×10(9) pfu of Ad-GFP, or same volume of solvent (PBS, pH 7.2) was applied once to each wound in groups 1 to 5, respectively. One additional rabbit was used to evaluate the transfer efficiency of the adenovirus vector by transferring Ad-GFP (6×10(9) pfu) into its wounds. Ice slides of wounds from this animal were observed under fluorescence microscopy. Another additional rabbit was used to evaluate the expression of HGF and TGFβ1 after transferring Ad-HGF (6×10(9) pfu) into each of its wound. Immunohistochemistry was used for detection. Results The effect of HGF on reducing excessive dermal scarring was observed by adenovirus-mediated gene transfer. Transfection of the human HGF cDNA into skin wounds through an adenoviral vector suppressed the over-expression of TGFβ1, which plays an essential role in the progression of dermal fibrogenesis. Application of HGF to the wounds significantly enhanced wound healing and inhibited over scarring.Conclusion HGF gene therapy could be a new approach for preventing excessive dermal scarring in wound healing.     

Does maternal glucose intolerance affect the length of gestation in singleton pregnancies?

OBJECTIVE: This study determined whether maternal glucose tolerance has a progressive effect on the length of gestation in singleton pregnancies and whether there is an increasing tendency towards spontaneous preterm birth with increasing glucose intolerance. METHODS: A total of 2,168 consecutive Chinese women with singleton pregnancies who underwent the 75-g oral glucose tolerance test (OGTT) over a 24-month period were categorized by their OGTT 2-hour value (mmol/L) into the following six groups: 5.9 or less, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-10.9, and 11.0 or greater mmol/L. Women with a 2-hour glucose value of 8.0 or more mmol/L were considered to have gestational diabetes mellitus (GDM) and received diet treatment. Women who eventually required insulin were excluded from the final analysis. The mean gestational age, birth weight, incidence of preterm birth, large for gestational age (LGA, birth weight > 90th percentile), and macrosomic (birth weight > or = 4.0 kg) infants were compared among the six groups. RESULTS: The incidence of preterm birth correlated significantly with increasing glucose intolerance. On further analysis, incidence of spontaneous birth before 37 weeks in the lowest to the highest 2-hour value groups was as follows: 5.5%, 2.6%, 3.7%, 4.9%, 8.5%, and 10.3% (P =.015) and that before 32 weeks went from 0.4%, 0.3%, 0.8%, 0.4%, 2.2%, to 3.4% (P =.018), respectively. There was no significant difference in the incidence of LGA or macrosomic infants. Regression analysis confirmed that the OGTT 2-hour glucose value was an independent determinant of gestational length. CONCLUSION: Gestational glucose intolerance affects gestation length and incidence of preterm birth, which should be considered a confounding factor in the analysis of the neonatal outcome of GDM pregnancies.     

Methionine synthase polymorphism is a risk factor for Alzheimer disease

Alzheimer disease (AD) patients show increased plasma levels of homocysteine, whose conversion to methionine is catalyzed by methionine synthase (MS). Although altered MS activity may result from the MS A2756G polymorphism, the latter's possible associ-ation with AD remains unexplored. To assess whether the MS A2756G polymorphism holds any influence on AD risk, we have analyzed 172 AD patients and 166 controls. We have also investigated whether the MS-A or MS-G allele interacts with the APOE4 allele. Our results indicate that association with the MS-AA genotype is an APOE4 allele-independent risk factor for AD. These findings provide novel evidence implicating genetic enzymatic alterations of homocysteine metabolic pathways in the pathogenesis of AD.     

The role of the protocol biopsies in renal allograft recipients

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-beta and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL +/- 0.5 in group A vs 1.54 mg/dL in group B; P <.05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-beta and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.     

TRAIL基因修饰联合阿霉素对大肠癌细胞株RKO作用的研究

目的:探讨肿瘤坏死因子(tumor necrsis factor,TNF)相关的凋亡诱导配体(TNF-related apoptosis-inducing ligand,TRAIL)基因联合阿霉索后,应用于人大肠癌细胞株RKO基因治疗的实验研究.方法:将重组腺病毒载体(Ad)介导的TRAIL基因作用于大肠癌细胞株RKO,并联合低剂量的阿霉素协同作用.通过MTF比色法与流式细胞仪研究分析其对RKO细胞的作用效果,并以RT-PCR检测联合应用阿霉素前后TRAIL基因的表达水平.结果:病毒载体对RKO细胞的生长有轻微的抑制作用,作用4 d抑制率为11.9%,但不增加RKO细胞的凋亡率.TRAIL对RKO细胞的生长抑制率及凋亡诱导率分别为50.1%和19.8%.联合阿霉素后,TRAIL对RKO细胞株的生长抑制率及凋亡率均有显著的增强作用,分别达60.3%及49.0%.RT-PCR结果提示联合应用阿霉素后,TRAIL基因的表达并未增强.结论:TRAIL能有效抑制RKO的生长,联合阿霉素后,其对RKO的生长抑制作用及凋亡诱导作用均明显增强.阿霉素不是通过增加TRAIL基因的表达来实现上述作用的.     

Analysis of Pathogenic Factors of Helicobacter Pylori in a High Prevalence Area of Gastric Cancer in Xinin,Qinghai Province

OBJECTIVE To analyze positive rates of the specific proteins CagA, VacA, UreA and UreB of Helicobacter pylori (Hp) in people in Xinin city Qinghai Province, a district with a high prevalence of gastric carcinoma, and to examine the relationship among the incidence, gross diagnosis and pathologic diagnosis. METHODS The gastric tissue biopsy specimens taken under endoscopy were examined by CLO,WS and Western Blot to judge the condition of the Hp infection. The positive rates of Hp CagA,VacA,UreA and UreB that had infected patients were evaluated. RESULTS The positive rate of UreA was markedly lower in chronic superficial gastritis (CSG) than in duodenal ulcer (DU) and compound ulcer, and also lower than in chronic atrophic gastritis(CAG), gastric ulcer(GU) and gastric cancinoma. However the positive rate of UreB was notably lower in duodenal ulcer and gastric ulcer than in chronic superficial gastritis and atrophic gastritis. The rates of UreB found in intestinal epithelial metaplasia, atrophic gastritis and gastric carcinoma were notably lower than in other diseases, however, it was markedly increased in chronic superficial gastritis, No differences were found among CagA and VacA of specimens with different endoscopic diagnosis or pathologic diagnosis. CONCLUSIONS The UreA in Hp may be relevant to the pathogenic mechanism of severe gastric diseases. However, UreB may have some protective effect on severe gastric diseases.     

改造的人乳头瘤病毒16型E6/E7融合蛋白疫苗抗肺癌作用的实验研究

目的 研究经改造的HPV16 E6／E7蛋白质疫苗(HPV16 mE6Δ／mE7)对表达HPV16 E6和E7的小鼠肺癌细胞的体内生长抑制作用，为肺癌免疫治疗提供新线索。方法 预防性实验：对C57BL／6小鼠先进行免疫，然后接种表达HPV16E6和E7癌蛋白的TC-1肿瘤细胞；第33天，对未出瘤小鼠进行第二次大剂量肿瘤细胞攻击。治疗性实验：C57BL／6小鼠先接种TC-1细胞，然后进行两次免疫治疗，再对末出瘤小鼠进行第二次大剂量TC-1细胞攻击实验。计算各组肿瘤发生率、肿瘤体积。采用MTT方法检测淋巴细胞增殖反应。结果预防性实验：在100天的观察时间内，免疫组小鼠可以有效抵抗第一、二次肿瘤细胞攻击，所有小鼠均未见肿瘤发生；而PBS组及单纯佐剂组小鼠在第一次肿瘤细胞接种后6～12天内均有肿瘤形成，30天内因肿瘤负荷出现衰竭。在治疗性实验中，免疫组、PBS组、单纯佐剂组小鼠成瘤率分别为20％、90％、60％；第二次攻击实验中，免疫组仍有87．5％的小鼠无肿瘤生长，而其他两组动物在4～6天内均有肿瘤形成。MTT实验表明经mE6Δ／mE7免疫的小鼠脾淋巴细胞增殖反应明显强于对照组。结论 经改造的HPV16型mE6Δ／mE7蛋白质疫苗对于实验动物肺癌有较好的抑制作用，为HPV16相关肺癌的免疫治疗提供了实验数据。