Proton pump inhibitors and gastritis

Proton pump inhibitors (PPIs) are novel compounds that strongly inhibit the H(+)/K(+)-ATPase in the gastric parietal cells to cause profound suppression of acid secretion. Acid-generating ATPase, also known as vacuolar-type ATPase, is located in the lysozomes of leukocytes and osteoclasts and its activity is also reportedly influenced by treatment with PPIs. This concept is supported by the results of studies using autoradiography in which (3)H-Lansoprazole uptake sites were clearly detected in the cytoplasmic granules of neutrophils infiltrating the gastric mucosa. In vitro studies indicate that PPIs increase the intra-vacuolar pH in the lysosomes of purified neutrophils and attenuate the adherence of neutrophils to the vascular endothelium. In clinical practice, the acidic environment in the stomach plays a critical role in the development of gastritis induced by Helicobacter pylori (H. pylori). This is worthy of note, because persistent gastritis often results in atrophic and metaplastic changes in the gastric mucosa, which are believed to be preneoplastic abnormalities. In patients with H. pylori-infection, PPI therapy causes corpus-predominant gastritis, which is frequently found in the background mucosa in patients with gastric cancer. The efficacy and safety of long-term PPI-treatment have not been conclusive, thus we need to pay more attention to the additional pharmacological actions of PPIs.     

Association study of HLA-B alleles with idiopathic male infertility in Han population of China

Purpose  

To investigate the distributions of HLA-B alleles and estimate their associations with idiopathic male infertility in Chinese Han population.     

Areca nut extracts-activated secretion of leukotriene B4, and phosphorylation of p38 mitogen-activated protein kinase and elevated intracellular calcium concentrations in human polymorphonuclear leukocytes

BACKGROUND AND OBJECTIVE: Polymorphonuclear leukocytes are the major source of leukotriene B4, which is synthesized via the 5-lipoxygenase pathway. Activation of the 5-lipoxygenase pathway is regulated by intracellular calcium and the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The impact of areca nut extracts on the biosynthesis of leukotriene B4 by human polymorphonuclear leukocytes was evaluated, and some of the possible mechanisms underlying the responses were examined. MATERIAL AND METHODS: Polymorphonuclear leukocytes were treated with various concentrations of areca nut extracts. The concentrations of leukotriene B4 released into the supernatants were evaluated using enzyme immunoassay. The phosphorylation of p38 MAPK was monitored using immunoblotting, and the cytosolic calcium kinetics were assessed fluorometrically using Fura-2. RESULTS: Exposure of polymorphonuclear leukocytes to areca nut extracts led to a dose-dependent increase in the production of leukotriene B4, with levels peaking at 30 min and decreasing thereafter. Areca nut extracts enhanced the phosphorylation of p38 MAPK, an enzyme known to activate 5-lipoxygenase. Incubation with areca nut extracts also resulted in a rapid elevation of intracellular calcium concentrations in polymorphonuclear leukocytes. The induction of leukotriene B4 by areca nut extracts was suppressed with the p38 MAPK inhibitor, SB203580, or with the intracellular calcium chelator, BAPTA-AM. CONCLUSION: The interaction of areca nut extracts with polymorphonuclear leukocytes activated the arachidonic acid metabolic cascade. Incubation of polymorphonuclear leukocytes with areca nut extracts resulted in the activation of intracellular events, such as phosphorylation of p38 MAPK and Ca2+ mobilization, involved in the release of pro-inflammatory lipid mediators. The results of this study emphasize the potential importance of polymorphonuclear leukocytes as a source of leukotriene B4, which may modulate the inflammatory response in areca chewers.     

Chemiluminescent determination of leukocyte alkaline phosphatase: an advantageous alternative to the cytochemical assay

The determination of leukocyte alkaline phosphatase (LAP) is used as an aid to diagnose many diseases in the laboratory. For example, it can be used to distinguish chronic myeloid leukemia (CML) from other myeloproliferative disorders (particularly myelofibrosis and polycythemia) and leukemoid reactions (LR). Traditionally, this test is performed with the use of subjective cytochemical assays that assign a score to the level of LAP. Here we present a nonsubjective, quantitative, sensitive, and inexpensive chemiluminescent technique that determines LAP based on the commercial reagent Immulite (AMPPD). To validate this methodology, intact leukocytes obtained from 32 healthy subjects, nine CML patients, and nine LR patients were submitted to the optimized protocol. By measuring the light emission elicited by four concentrations of neutrophils, we were able to estimate the activity of LAP per cell (the slope of the curve obtained by linear regression). A high linear correlation was found between the chemiluminescent result (slope) and the cytochemical score. The slope for healthy individuals ranged between 0.61 and 8.49 (10(-5) mV.s/cell), with a median of 2.04 (10(-5) mV.s/cell). These results were statistically different from those of CML patients (range=0.07-1.75, median=0.79) and LR patients (range= 3.84-47.24, median=9.58; P<0.05).     

Microvascular cell death in spontaneously hypertensive rats during experimental inflammation

OBJECTIVE: Chronic hypertension is associated with an increased risk for tissue injury that may be mediated in part by endothelium and inflammatory cells. To clarify a possible underlying mechanisms, we examined leukocyte migration in the microcirculation and concomitant parenchymal cell death. METHODS: The mesentery of spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar Kyoto (WKY) rats, was examined with digital fluorescence microscopy after topical stimulation with an inflammatory mediator (f-met-leu-phe, 10(-8)M). The migratory pathways of individual leukocytes were traced, and at the same time cell death was detected by use of a life-death indicator (propidium iodide) over a period of 3 hours. RESULTS: Both WKY and SHR had a progressively increasing number of leukocytes migrating across the endothelium in postcapillary venules into the tissue parenchyma. But parenchymal cell death was detected in a random pattern in the mesentery tissue, without correlation to the migratory positions of the leukocytes. Although mature SHR rats (about 17 weeks) exhibited the same level of cell death as age-matched WKY rats, older WKY rats (about 30 weeks) had significantly lower levels of cell death, whereas the SHR rats maintained the same number of parenchymal cell death as mature animals. CONCLUSIONS: These results suggest that in the presence of an inflammatory mediator, the SHR may exhibit a stronger response to an inflammatory mediator than normotensive WKY rats in a fashion that is age, but not blood pressure, dependent. Parenchymal cell death does not correlate with migration of activated leukocytes at the microvascular level.     

鼻息肉与人类白细胞Ⅱ类抗原DR和DQ的相关性研究

[目的]了解鼻息肉患者与人类白细胞Ⅱ类抗原(HLA-Ⅱ)的相关性。[方法]实验组为临床上已确诊的鼻息肉患者30例,对照组为81例正常健康人。采用HLA基因分型技术PCR-SSP法(PCR-sequence specific primers)检测HLA-Ⅱ类抗原。[结果]实验检测了111例的HLA-DR和HLA-DQ共18个等位基因点,实验组和对照组之间HLA-DR16和HLA-DQ8,9的等位基因抗原频率差异有显著性意义,其中HLA-DR16的抗原频率实验组为10.00%,对照组为1.24%,相对危险度RR=8.90,P=0.03;而HLA-DQ 8的抗原频率实验组为20.00%,对照组为4.94%,相对危险度RR=4.81,P=0.01;HLA-DQ9的抗原频率实验组40.00%,对照组12.35%,相对危险度RR=4.73,P=0.001。[结论]HLA-DR16和HLA-DQ8,9与鼻息肉的发病有关,为鼻息肉的易感基因(阳性基因)。     

Differential effects of cadmium administration on peripheral blood granulocytes in rats

Infiltration of circulatory inflammatory cells is a common histopathological finding in target organs following cadmium administration, but there is paucity of data concerning their activity. In this study, the effects of sublethal (1 mg/kg) cadmium on peripheral blood polymorphonuclear (PMN) cells were examined 48 h following administration in rats, when tissue (liver and lung) infiltration of these cells was observed. Cadmium administration resulted in systemic inflammatory cytokine and acute phase response with an increase in circulatory neutrophil numbers and cells that express CD11b molecules. Rise in basic aspects of oxidative activity including intracellular myeloperoxidase (MPO), reactive oxygen (nitroblue tetrazolium/NBT cytochemical assay) and nitrogen (Griess assay) species production was observed in PMNs from cadmium-administered rats. A decrease in levels of mRNA for IL-1β, TNF-α and IL-6 was noted, but production of these cytokines was affected differentially. Described effects of cadmium on PMNs add further to the understanding of inflammatory potential of this environmental contaminant.     

急性脑梗死早期血白细胞计数动态变化及其临床意义

目的　探讨脑梗死急性期外周血白细胞计数与脑梗死发生发展及预后的相关性。方法　对 2 812例脑梗死患者进行回顾性统计 ,以白细胞计数 10× 10 9 L分组 ,大于此数患者归入异常组 ,小于则属于正常组 ,分别就两组在1～ 3d、4～ 6d、7～ 10d分三个阶段进行白细胞计数 ,并与死亡率 ,意识同时统计 ,并作死亡与生存患者的白细胞分析。结果　白细胞升高组的病死率明显高于正常组 ,白细胞计数逐步升高时病死率也随着递增 ,死亡组患者的白细胞计数显著高于生存组患者 ,白细胞计数递增与意识状态的障碍变化严重程度存在着相关性 ,同级意识状态在不同时段的白细胞变化无差异显著性。结论　脑梗死早期出现的白细胞计数升高的机制是脑损伤达到一定的严重程度后产生的应激反应 ,是脑梗死患者病情严重与预后差的一个重要原因 ,白细胞计数与后果存在明显的相关性 ,白细胞数的增加可作为判断脑血管病预后的简便易行指标     

A patient with a <Emphasis Type="Italic">Mycobacterium avium</Emphasis> complex infection complicated by systemic lupus erythematosus

A 41-year-old woman was admitted to our hospital because of fever and polyarthralgia. A diagnosis of systemic lupus erythematosus (SLE) was made based on the findings of polyarthritis, leukocytopenia, lymphocytopenia, proteinuria, and positive reactions for antinuclear antibody (ANA) and anti-double strand (ds)DNA antibody. She had also been suffering from a pulmonary Mycobacterium avium complex (MAC) infection with such symptoms as cough and sputum for the past 3 years. Antimicrobial drugs for MAC infection were administered first, and later she was given cyclophosphamide pulse therapy, consisting of methylprednisolone (8mg/day) and mizoribine (100mg/day). Owing to these therapeutic regimens, SLE was successfully treated without an exacerbation of the MAC infection. The risk factors for MAC infection and SLE are also discussed.