Rodent nutritional model of steatohepatitis: Effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency

Background and Aims: Intestinal endotoxin (lipopolysaccharide) is thought to contribute to liver injury in both alcoholic and nonalcoholic steatohepatitis (NASH). Tumor necrosis factor alpha (TNFα) is an important mediator of this process and is considered central to the inflammatory response in NASH. This study aimed to investigate the effects of lipopolysaccharide on liver injury in the methionine choline deficient (MCD) nutritional model of NASH, and to determine if TNFα is required for the development of steatohepatitis in this model. Method: Male C57/BL6 mice received a MCD diet for 4 weeks, whilst a control group received an identical diet supplemented with 0.2% choline bitartrate and 0.3% methionine. At 4 weeks, mice received either an intraperitoneal injection of lipopolysaccharide (0.5 µg/g body mass) or sterile saline, and were killed 24 h thereafter. In a separate study, TNFα knockout and wild type C57BL/6 mice received either MCD or control diets for 4 weeks. Serum transaminase levels, liver histology (steatosis, inflammation and apoptosis), hepatic triglyceride concentration and hepatic lipid peroxidation products (conjugated dienes, lipid hydroperoxides and thiobarbituric reactive substances, free and total) were evaluated. Results: Intraperitoneal administration of lipopolysaccharide augmented serum alanine aminotransferase (ALT) levels (P < 0.02), hepatic inflammation (P < 0.025), apoptosis (P < 0.01) and free thiobarbituric acid reactive substances (P < 0.025) in MCD mice. TNFα knockout mice fed the MCD diet developed steatohepatitis with histological and biochemical changes similar to those seen in wild type counterparts. Conclusions: Lipopolysaccharide augments liver injury in MCD mice, and TNFα is not required for the development of steatohepatitis in MCD mice.     

Detection of residual leukemia by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization after allogeneic bone marrow transplantation for AKR leukemia: a murine model for minimal residual disease

Disease relapse after allogeneic bone marrow transplantation (BMT) is a major cause of treatment failure and is thought to evolve from clinically occult residual disease in the recipient. However, the demonstration of minimal residual disease (MRD) in individual patients is of uncertain prognostic significance because the detection of residual disease has not consistently correlated with subsequent relapse. Moreover, the optimal therapeutic approach in patients with MRD after allogeneic BMT is unknown. The study of these issues has been hindered by the lack of clinically relevant animal models. In this report, we characterize a novel murine model for the study of MRD after allogeneic BMT. This model was designed to simulate high-risk BMT in humans in which patients receive transplants in relapse and disease recurrence in the major cause of treatment failure. The H-2-compatible, mixed lymphocyte culture nonreactive murine strains, AKR (H-2k) and CBA (H-2k), were chosen to parallel marrow transplants from HLA-matched siblings, which represent the majority of allo-transplants in humans. Male AKR leukemia cells were used in female donor/host chimeras permitting the Y chromosome to serve as a leukemia-specific marker for MRD. Detection of residual male leukemia cells in the peripheral blood of the primary host was facilitated by use of the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (SSOPH). Use of PCR/SSOPH was highly predictive of clinical outcome (relapse or cure) in animals receiving transplants (P < .00002) and detected disease recurrence earlier than comparative flow cytometric analysis studies. This murine model will be useful in evaluating the efficacy of therapeutic strategies aimed at reducing disease relapse posttransplant and can be adapted to other transplant murine tumor systems for the study of MRD.     

Blocking of Protein Pancreatic Secretion by Maximal Secretion Infusion in the Dog

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 C.U./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus.
The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections throughout the three hours.
The same protocol was followed in anesthetized dogs subjected to a mid line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlate well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose.
The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.     

2007年青海省碘缺乏病高危地区育龄妇女尿碘调查

Objective To investigate the iodine nourishment in women of child-beating age in high risk region of iodine deficiency disorders (IDD) in Qinghai Province. Methods According to The Notice to Launch a Reinforced Survey on IDD in High Risk Region issued by The Ministry of Public Health, 17 counties in 6 districts were selected as investigated area in Qinghai Province in 2007, using two stage cluster sampling and combining The National IDD Preliminary Surveillance Scheme, 30 women aged from 18 to 40 years were selected in each village, 1 or 2 villages in each town, 3 to 5 towns in each county, who were divided into newly wedding, pregnant, lactation and other women of child-bearing age. Iodine concentration in urine was detected by the method of As3+-Ce4+catalytic spectrophotometry. Results One thousand six hundreds and four urine iodine samples were analyzed. The median was 93.3 μg/L,52.1%(836/1604),31.8%(510/1604) and 12.4%(199/1604) was lower than 100,50 and 20 μg/L, respectively. It was 70.5%(527/747) and 43.0%(128/298) of women in Yushu and Haixi that had urinary iodine lower than 100 μg/L, respectively, while it was 50% of women in the 6 districts, to be specific, 88.3%(91/103) in Nangqian, 83.8% (62/74) in Zaduo and 70.7%(118/167) in Zhiduo Counties respectively. The median of urinary iodine in women who were not lactating and not pregnant was only 88.6 μg/L, of whom 53.9% (763/1415) lower than 100 μg/L. Conclusions The women of reproductive age in high risk region of IDD are deficient of iodine in Qinghai Province.     

Fibronectin: blood turnover in normal animals and during intravascular coagulation

Plasma fibronectin (FN) binds fibrin in vitro by both noncovalent and covalent bonds and is decreased in DIC. In rabbits, conventionally purified 125I-FN had a complex blood clearance with a late t1/2 of 71 hr. A large portion was apparently altered, as evinced by rapid clearance and an intravascular/total body ratio (C1) of 0.28-0.51. 3H- labeled FN, made in vivo by injection of 3H amino acids, had a t1/2 of 73 hr. Crosstransfusion of 131I-FN and 3H-FN into a second set of animals gave similar t1/2s and C1s of 0.74-0.82, indicating the altered 125I-FN was biologically screened in the first animals. Other animals were given 125I-fibrinogen and "screened" 131I-FN. Intravenous thrombin (50-60 U/kg/1 hr) caused a 25%-50% decrease in both 125I-fibrinogen and 131I-FN. Ancrod injection reduced fibrinogen by greater than 90% but had no effect on 131I-FN. 131I-FN levels did not change when thrombin was given after ancrod. No cross-linked FN-fibrinogen alpha-chain was found in the plasma, nor was the thrombin-induced fall in FN affected by spermidine blockade. These experiments demonstrate that FN and fibrin bind in vivo during defibrination and are rapidly cleared from the blood. The abnormal fibrin resulting from ancrod either does not bind FN in vivo or does so reversibly.     

自然周期与激素替代周期的冻融胚胎移植方案对单胎妊娠新生儿结局的影响研究

背景　冻融胚胎移植（FET）在辅助生殖技术（ART）中的应用越来越广泛,而自然周期或激素替代周期是其重要环节,二者的安全性逐渐被重视。目的　探究自然周期与激素替代周期的FET方案对单胎妊娠新生儿结局的影响。方法　回顾性收集2013年1月—2017年6月在新疆医科大学第一附属医院生殖医学中心行体外受精FET的419例单胎活产患者的临床资料。按内膜准备方案不同分为2组,A组（n=175）为自然周期FET患者,B组（n=244）为未能按时返院行排卵监测,给予激素替代周期FET患者。收集所有患者的基本资料,包括男女双方年龄、不孕年限、体质指数（BMI）、基础卵泡刺激素（FSH）、基础促黄体生成素（LH）、抗缪勒试管激素（AMH）、超促排周期的促性腺激素（Gn）总量及注射Gn的天数、人绒毛膜促性腺激素（HCG）注射日雌激素水平、获卵数、第二次减数分裂中期卵母细胞（MⅡ）数、正常受精卵（2PN）数、FET日子宫内膜厚度、移植胚胎数。随访其两组正常体质量儿发生率、早产儿发生率、低体质量儿发生率、早产低体质量儿发生率、足月低体质量儿发生率、巨大儿发生率、新生儿性别比、出生体质量、分娩孕周。结果　419例患者中,A组患者自然周期为175个周期,B组患者激素替代周期为244个周期。A组患者年龄、配偶年龄、不孕年限、BMI、基础FSH、基础LH、AMH、超促排周期的Gn总量、超促排周期的注射Gn的天数、HCG注射日雌激素水平、获卵数、MⅡ数、2PN数、FET日子宫内膜厚度、移植胚胎数比较,差异无统计学意义（P>0.05）。B组正常体质量儿发生率低于A组（P0.05）。结论　相较于激素替代周期的FET患者,自然周期的FET患者正常体质量儿发生率更高,妊娠结局更好。     

卵巢功能低下者添加DHEA获卵数随机对照研究

目的：评价接受体外受精-胚胎移植（IVF-ET）治疗卵巢储备功能低下患者,经脱氢表雄酮（DHEA）治疗后的效果。方法采用随机对照研究,对符合卵巢功能低下（DOR）拟行体外受精-胚胎移植（IVF-ET）助孕治疗的患者,随机分为两组（通过计算机产生随机数字表法）。试验组（n ＝53）为 IVF-ET前接受 DHEA治疗者,25 mg,每日3次;对照组（n ＝51）为不进行 DHEA治疗者。对两组基础内分泌激素、HCG日雌激素值、促排天数、Gn总量、获卵数、2PN数、可移植胚胎数、优胚数等进行比较。结果试验组与对照组患者年龄、不孕年限、基础内分泌激素 FSH水平差异无统计学意义（P ＞0．05）,试验组患者Gn用量少及获卵数、2PN数增加,差异有统计学意义（P ＜0．05）;试验组促排天数少、可移植胚胎数及优胚数多,但差异无统计学意义（P ＞0．05）;两组间 HCG日雌激素水平无明显变化。结论 DOR的不孕妇女,经DHEA治疗后,Gn用量减少,获卵数增加,降低 IVF-ET周期取消率,增加妊娠率。添加DHEA对接受 IVF-ET的DOR患者是有益的。