Development and Significance of Cysteamine and Propionitrile Models of Duodenal Ulcer

Cysteamine is widely used in rodents to induce duodenal ulcer. Herein, the pathogenesis of duodenal ulceration in its earliest stages was reviewed using findings from cysteamine-and propionitrile-induced duodenal ulcer in rodent models, especially taking into account changes in the secretion of gastric acid, duodenal and pancreatic bicarbonate as well asgastroduodenal motility. The effect of cysteamine-HCl in inducing ulcers in rats is circadian rhythm-dependent. The effect is greatest from just before the end of diurnal rest to just after the start of nocturnal activity. The chronobiologic effect may be in part due to the circadian rhythm-dependent increased gastric acid production from cysteamine. Titratable acidity was found to be twice as great in the gastric juice of rodents when cysteamine was given by injection at 2000 (just after the start of nocturnal activity) in comparison to when given at 0800 or 1200 (at the beginning or middle span of daily rest). Further studies have shown that adrenalectomy of rats 7 days before cysteamine administration obliterated the observed circadian susceptibility to ulcer formation. Duodenal ulceration, at least in the cysteamine model, appears to be under chronobiologic neuroendocrine control or influence, seemingly mediated by the adrenal glands.     

P2Y receptors play a critical role in epithelial cell communication and migration

Cellular injury induces a complex series of events that involves Ca2+ signaling, cell communication, and migration. One of the first responses following mechanical injury is the propagation of a Ca2+ wave (Klepeis et al. [2001] J Cell Sci 114(Pt 23):4185-4195). The wave is generated by the extracellular release of ATP, which also induces phosphorylation of ERK (Yang et al. [2004] J Cell Biochem 91(5):938-950). ATP and other nucleotides, which bind to and activate specific purinergic receptors were used to mimic injury. Our goal was to determine which of the P2Y purinergic receptors are expressed and stimulated in corneal epithelial cells and which signaling pathways are activated leading to changes in cell migration, an event critical for wound closure. In this study, we demonstrated that the P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11 receptors were present in corneal epithelial cells. A potency profile was determined by Ca2+ imaging for nucleotide agonists as follows: ATP > or = UTP > ADP > or = UDP. In contrast, negligible responses were seen for beta,gamma-meATP, a general P2X receptor agonist and adenosine, a P1 receptor agonist. Homologous desensitization of the Ca2+ response was observed for the four nucleotides. However, P2Y receptor internalization and degradation was not detected following stimulation with ATP, which is in contrast to EGFR internalization observed in response to EGF. ATP induced cell migration was comparable to that of EGF and was maximal at 1 microM. Cells exposed to ATP, UTP, ADP, and UDP demonstrated a rapid twofold increase in phosphorylation of paxillin at Y31 and Y118, however, there was no activation elicited by beta,gamma-meATP or adenosine. Additional studies demonstrated that wound closure was inhibited by reactive blue 2. These results indicate that P2Y receptors play a critical role in the injury repair process.     

基于低相干光干涉的眼睛光学生物参数测量研究

目的 眼睛的光学生物参数中的眼轴长度(AL)和角膜曲率半径(CR)可以作为预防和监测眼球近视的两个重要参数。为了提高测量眼轴长度的速度与精度和同步实现角膜曲率高精度动态测量,本文提出一种基于低相干光干涉技术眼睛光学生物参数测量的系统。方法 该系统使用旋转光学延迟线快速改变参考光的光程,利用曲率半径为8 mm的标准件标定人眼角膜顶点到靶环之间的距离,利用角膜的干涉信号对相机和数据采集卡进行触发实现同步采集,从而实现眼轴长度的快速测量和精准定位靶环到角膜顶点之间的距离,同时保证成像系统的放大倍率恒定和数据的实时采集。结果 实验结果表明,这种低相干光干涉测量系统,可以实时测量眼轴长度和角膜曲率半径,眼轴长度误差低于40μm,人眼角膜曲率半径方差为2.082 36×10^-2μm。结论 该系统能够快速、精准地测量AL和CR,可在近视的预防和监测中发挥重要作用。     

Evidence for coupled transport of bicarbonate and sodium in cultured bovine corneal endothelial cells

Summary Usin gintracellular microelectrode technique, the response of the voltageV across the plasma membrane of cultured bovine corneal endothelial cells to changes in sodium and bicarbonate concentrations was investigated. (1) The electrical response to changes in [HCO ₃ ^– ] _o (depolarization upon lowering and hyperpolarization upon raising [HCO ₃ ^– ] _o ) was dependent on sodium. Lithium could fairly well be substituted for sodium, whereas potassium or choline were much less effective. (2) Removal of external sodium caused a depolarization, while a readdition led to a hyperpolarization, which increased with time of preincubation in the sodium-depleted medium. (3) The response to changes in [Na⁺] _o was dependent on bicarbonate. In a nominally bicarbonate-free medium, its amplitude was decreased or even reversed in sign. (4) Application of SITS or DIDS (10^–3 m) had a similar effect on the response to sodium as bicarbonate-depleted medium. (5) At [Na⁺] _o =151mm and [HCO ₃ ^– ] _o =46mm, the transients ofV depended, with 39.0±9.0 (sd) mV/decade, on bicarbonate and, with 15.3±5.8 (sd) mV/decade, on sodium. (6) After the preincubation of cells with lithium, replacement of Li by choline led to similar effects as the replacement of sodium by choline, though the response ofV was smaller with Li. This response could be reduced or reversed by the removal of bicarbonate or by the application of SITS. (7) Amiloride (10^–3 m) caused a reversible hyperpolarization of the steady-state potential by 8.5±2.6 mV (sd). It did not affect the immediate response to changes in [Na⁺] _o or [HCO ₃ ^– ] _o , but reduced the speed of regaining the steady-state potential after a change in [HCO ₃ ^– ] _o . (8) Ouabain (10^–4 m) caused a fast depolarization of –6.8±1.1 (sd) mV, which was followed by a continuing slower depolarization. The effect was almost identical at 10^–5 m. (9) It is suggested, that corneal endothelial cells possess a cotransport for sodium and bicarbonate, which transports net negative charage with these ions. It is inhibitable by stilbenes, but not directly affected by amiloride or ouabain. Lithium is a good substitute for sodium with respect to bicarbonate transport and is transported itself. In addition, the effect of amiloride provides indirect evidence for the existence of a Na⁺/H⁺-antiport. A model for the transepithelial transport of bicarbonate across the corneal endothelium is proposed.     

胃大部切除术后消化性溃疡患者残胃癌危险因素分析及其干预措施

目的:探究消化性溃疡患者胃大部切除术后发生残胃癌的危险因素,并提出相应干预措施。方法:选取我院收治的行胃大部切除术治疗后的消化性溃疡患者180例作为研究对象,将其随机分为两组,每组90例。对照组给予常规干预,观察组给予综合干预,观察两组的干预效果,同时将发生残胃癌患者与未发生残胃癌患者各项资料进行对比,分析影响残胃癌发生的危险因素。结果:观察组中没有患者发生残胃癌,对照组中有10例患者发生残胃癌,发生率为11.11%,显著高于观察组(P0.05);两组患者在首次手术年龄、性别、HP感染上进行对比差异无统计学意义(P0.05);两组患者在首次手术吻合方式、首次手术溃疡位置上对比具有统计学意义(P0.05),残胃癌组组采用毕Ⅰ式2例,毕Ⅱ式7例,Roux-Y式1例;未发生残胃癌组采用毕Ⅰ式82例,毕Ⅱ式74例,Roux-Y式14例,残胃癌组首次手术溃疡位置以十二指肠球部为主,未发生残胃癌组以十二指肠球部、胃体部为主;Logistics回归分析结果证实首次手术吻合方式、首次手术溃疡位置属于残胃癌发生的主要危险因素。结论:术后残胃癌发生危险因素包括首次手术吻合方式、首次手术溃疡位置,同时相关并发症的发生同样会增加术后残胃癌发生风险,应加强引流管干预、并发症干预,并将此作为基础制定综合干预方案。     

埃索美拉唑为基础的四联疗法对消化性溃疡患者幽门螺杆菌根除率、炎性因子及生活质量的影响

目的:探讨埃索美拉唑为基础的四联疗法对消化性溃疡(PU)患者幽门螺杆菌(Hp)根除率、炎性因子及生活质量的影响。方法:选取2016年3月～2018年11月间我院接收的117例PU患者,根据数表法将患者随机分为对照组(n=58)和研究组(n=59),对照组给予以奥美拉唑为基础的四联疗法治疗,研究组给予以埃索美拉唑为基础的四联疗法治疗,比较两组患者临床疗效、Hp根除率、炎性因子、生活质量及不良反应。结果:研究组治疗后总有效率为74.58%(44/59),高于对照组患者的53.45%(31/58)(P0.05)。两组患者治疗后白介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)较治疗前降低,且研究组低于对照组(P0.05)。研究组的HP根除率高于对照组(P0.05)。两组患者治疗后临床症状、心理情感、社交及任务完成评分均较治疗前升高,且研究组高于对照组(P0.05)。两组不良反应发生率比较无统计学差异(P0.05)。结论:埃索美拉唑为基础的四联疗法治疗PU,可有效改善炎性因子水平、Hp根除率和生活质量,疗效确切,安全性好,临床应用价值较高。     

埃索美拉唑对糜烂性胃溃疡患者血清ERK1/2及EGFR水平的影响

目的:探讨埃索美拉唑对糜烂性胃溃疡患者血清ERK1/2及EGFR水平的影响及临床疗效。方法:收集我院糜烂性胃溃疡患者106例,随机分为实验组和对照组。对照组予以奥美拉唑治疗,实验组予以埃索美拉唑治疗。检测并比较两组患者治疗前后血清ERK1/2及EGFR水平变化,观察患者溃疡面积、愈合情况以及临床症状的改善情况等。结果:与治疗前比较,治疗后两组患者血清ERK1/2及EGFR水平上升,差异有统计学意义(P0.05);与对照组比较,实验组治疗后ERK1/2及EGFR水平较高,差异有统计学意义(P0.05)。与治疗前比较,治疗后两组患者溃疡面积均减小,差异有统计学意义(P0.05);与对照组比较,实验组治疗后溃疡愈合情况更显著,差异有统计学意义(P0.05)。与治疗前比较,治疗后两组患者临床症状均获得缓解,差异有统计学意义(P0.05);与对照组比较,实验组治疗后症状改善更明显,差异有统计学意义(P0.05)。结论:埃索美拉唑可调节糜烂性胃溃疡患者血清ERK1/2及EGFR水平,改善溃疡情况,缓解临床症状,提高临床疗效,值得临床推广应用。     

Up- and down-regulation of membrane receptors as possible mechanisms related to the antiulcer actions of milk in rat gastric mucosa

The effects of a cow's milk diet on receptor activity and histamine metabolism in gastric glands and mucosa isolated from adult rats were examined. The milk diet was associated with (1) a decreased mobilization of H₂ receptors by histamine and (2) an increased mobilization of PGE₂ (prostaglandin E₂) receptors in mucous cells (cytoprotective effect) and parietal cells (antiacid effect). These changes are not observed for the receptors reducing pentagastrin- and histamine-induced gastric acid secretion (pancreatic/enteroglucagons, somatostatin) and stimulating mucus, bicarbonate and pepsin secretions in the rat (secretin). Cimetidine produced a parallel displacement of the histamine dose-response curve, suggesting competitive inhibition between this classical H₂ receptor antagonist and histamine in the two experimental groups. Prostaglandins and other components in milk such as EGF (epidermal growth factor) and somatostatin might therefore protect gastric mucosa by a differential control of PGE₂ and histamine H₂ receptor activity eitherdirectly (PGE₂ in milk) orindirectly (inhibition of endogeneous histamine synthesis/release and stimulation of PGE-I synthesis/release).     

Genetic associations of common deletion polymorphisms in families with Avellino corneal dystrophy

Although the locations of many common deletion variants in the human genome are unknown, such deletions may be causative in rare disorders. Deletions can be mapped through the identification of Mendelian inconsistencies in pedigrees. Data for a total of 341,577 SNPs from an ACD family cohort (n = 551) and 341,039 SNPs from a Korean-Vietnamese family cohort (n = 554) were collected for a genome-wide association study using Illumina 370K-Duo Beadchips^®. In the present study, a Mendelian inconsistency analysis of genotype data identified 1029 deletion variants in Korean and Korean-Vietnam family cohorts of 404 trios comprising 1105 individuals. Small-deletion copy number variations adjacent to 10 deletion variants were then validated by the real-time quantitative polymerase chain reaction. The expected copy numbers of each deletion variant were directly matched to its genotype cluster image. Deletion variants were also in strong linkage disequilibrium with nearby SNPs. To determine the overall contribution of the 1029 deletion variants, we analyzed case-control trio associations with the risk for Avellino corneal dystrophy. One SNP marker (rs885945) neighboring the gene encoding major histocompatibility complex class I F (HLA-F) was significantly associated with the risk of Avellino corneal dystrophy (P = 0.0003). rs885945 showed high LD with SNPs within the HLA-F gene. Therefore, HLA-F may be a potential candidate gene for Avellino corneal dystrophy.     

Cell-surface associated proteins of corneal fibroblasts: dissection with monoclonal antibodies

It is now generally accepted that the cell surface is involved in the interaction of the cells with the extracellular matrix. To identify and characterize cell-surface-associated components of corneal fibroblasts, several monoclonal antibodies were developed. Hybridomas were developed by fusing mouse myeloma cells SP2/OAg14 with spleen cells from mice immunized with membrane fractions of corneal fibroblasts grown in culture. Twenty-five hybridomas secreting monoclonal antibodies to cell-surface components were selected by an enzyme-linked immunosorbent assay using corneal fibroblasts grown in microtiter plates as the substrate. Immunohistochemical staining demonstrated that the antigenic determinants recognized by these antibodies were not present on corneal epithelial cells, but were present on skin fibroblasts. The antigenic determinants recognized by two of these antibodies, designated 10D2 and 716, were matrix components of the corneal stroma. Immunochemical characterization of the antigens was carried out by indirect precipitation of the radioactively labeled cellular proteins with the monoclonal antibodies and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the precipitates. Four antibodies were able to precipitate antigens from cell extract in detectable amounts. Antibodies designated 5E2, 9G2, and 10D2 recognized antigens consisting of polypeptides of approximate molecular weights 105K and 110K, while antibody 716 recognized an antigen of 100K molecular weight. However, based on the tissue distribution and cell-surface distribution, these antibodies reacted with different antigenic determinants. The antigen recognized by 716 was also secreted by cells in culture but consisted of 220K and 200K polypeptide chains. It was tentatively identified as cellular fibronectin, based on the reaction of this antigen with polyclonal antibodies to plasma fibronectin.