Within-subject variation of elastase/α1-protease inhibitor complexes and lactoferrin in plasma

Antonsen S. Within-subject variation of elastase/a!-protease inhibitor complexes and lactoferrin in plasma. Scand J Clin Lab Invest 1993; 53: 611-616.

Several studies have shown increased plasma concentrations of neutrophil elas-tase in complex with a)-protease inhibitor and/or lactoferrin in inflammatory conditions, and serial measurements have been advocated in order to follow disease activity. However, data on the magnitude of the within-subject variation are necessary for evaluation of the significance of changes in results obtained on analysis of serial samples. Within-subject variation of elastase/oj)-protease inhibitor complexes and lactoferrin over a short time was studied in six young men who had blood samples drawn every 4h over 2 days. Within-subject variation over a longer time was investigated in 12 healthy adults, 6 females and 6 males, who had blood samples drawn in the morning once a week for 10 weeks. From five of the females and five of the males, blood samples were also drawn every morning on 5 consecutive days during 1 week. Within-subject variations over hours, days, and weeks were estimated as 0.050, 0.124, and 0.148 for elastase/ai-protease inhibitor complexes and as 0.101, 0.119, and 0.143 for lactoferrin. A tendency towards variation of LAC with menstrual cycle in fertile females was noticed. From within-subject variation, between-subject variation and analytical variation, indices of individuality were calculated as 1.1 and 1.8 for elastase/a]-protease inhibitor complexes and lactoferrin, respectively. This means that within-subject variation for lactoferrin is quite small compared to between-subject variation, and the usefulness of reference limits is very limited, when interpreting results from individual patients. For elastase/o)-protease inhibitor complexes, the use of reference limits might be more appropriate, although still not optimal.     

聚乙二醇干扰素α联合利巴韦林治疗难治性慢性丙型肝炎过程中血常规变化与疗效的相关性

目的观察难治性慢性丙型肝炎标准治疗过程中血常规的变化与抗病毒疗效的关系。方法收集2011年9月-2012年12月于首都医科大学附属北京佑安医院就诊的难治性慢性丙型肝炎初治患者63例,给予聚乙二醇干扰素α-2a(180μg/周)联合利巴韦林治疗48周,分别在基线、治疗4、12、24、48周和随访24周时进行HCV RNA及血常规的检测,分析血常规与疗效的相关性。根据是否获得持续病毒学应答(SVR),分为SVR组和n SVR组。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验;采用简单线性相关分析法进行相关性分析。结果 63例患者有3例失访,余下60例均完成抗病毒治疗和24周随访,其中46例获得SVR,SVR率为76.7%;SVR组患者治疗4、12、24周时的淋巴细胞计数(LYPH)、白细胞计数(WBC)及中性粒细胞计数(NUET)均低于n SVR组,并且在12周时差异均有统计学意义(t值分别为3.398、2.766、2.037,P值均0.05),在24周时两组WBC及NUET差异亦均有统计学意义(t值分别为2.559、2.151,P值均0.05);此外SVR组患者在治疗4周时上述3项指标较基线的下降幅度均大于n SVR组,其中LYPH下降幅度在两组间差异有统计学意义(t=2.26,P=0.03)。LYPH、WBC、NUET在治疗4、12周时与HCV RNA的下降幅度呈正相关(r值分别为0.36、0.45、0.37、0.47、0.61、0.33,P值均0.05)。结论血常规中LYPH、WBC及NEUT的变化及下降幅度在一定程度上可作为难治性慢性丙型肝炎抗病毒疗效的预测指标。     

CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity

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Guideline for the Out‐of‐Hospital Management of Human Exposures to Minimally Toxic Substances

Guideline Summary

All substances are capable of producing toxicity, so nothing is completely non‐toxic. Minimally toxic substances are those which produce little toxicity, minor self‐limited toxicity, or clinically insignificant effects at most doses. Examples include silica gel, A&D ointment, chalk, lipstick, and non‐camphor lip balms, watercolors, hand dishwashing detergents, non‐salicylate antacids (excluding magnesium or sodium bicarbonate containing products), calamine lotion, clay, crayons, diaper rash creams and ointments, fabric softeners/sheets, glow products, glue (white, arts, and crafts type), household plant food, oral contraceptives, pen ink, pencils, starch/sizing, throat lozenges without local anesthetics, topical antibiotics, topical antifungals, topical steroids, topical steroids with antibiotics, and water‐based paints. Minimally toxic exposures have the following characteristics: (1) The information specialist has confidence in the accuracy of the history obtained and the ability to communicate effectively with the caller. (2) The information specialist has confidence in the identity of the product(s) or substance(s) and a reasonable estimation of the maximum amount involved in the exposure. (3) The risks of adverse reactions or expected effects are acceptable to both the information specialist and the caller based on available medical literature and clinical experience. (4) The exposure does not require a healthcare referral since the potential effects are benign and self‐limited. However, decisions regarding patient disposition should take into account the patient's intent, symptoms, and social environment. In addition, individual patient circumstances (e.g., pregnancy, pre‐existing medical conditions, therapeutic interventions) need to be considered. Minimally toxic exposures may vary in route (dermal, inhalation, ingestion, ocular), chronicity (acute, chronic), and substance composition (single or multi‐ingredient, single or multiple product). Future categorization of substances as “minimally toxic” should be based on a process involving review of current knowledge, a thorough analysis of poisoning experience, and prospective validation.     

Phagocytosis of heat‐killed Staphylococcus aureus by eosinophils: comparison with neutrophils

Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16‐coated immunomagnetic beads and centrifugation through a Ficoll‐Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti‐FcγRIIa mAb (CD32 mAb), anti‐FcγRIIIb mAb (CD16 mAb), anti‐CR3 (CD11b mAb), or anti‐CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat‐killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2′,7′‐dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat‐inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35).     

Comparative Studies of Superoxide Production by Microbial Wall Product-Primed Neutrophils in Ulcerative Colitis

A diminished tolerance to the normal gut bacterial flora has been suggested to be pathogenic in ulcerative colitis (UC) and the aim of this study was to evaluate the priming effect of selected bacterial wall products on UC neutrophil granulocytes. Neutrophils from 10 UC patients and 10 healthy controls were primed with bacterial lipoprotein (BLP) or lipopolysaccharide (LPS) and subsequently activated. Extracellular superoxide production was measured by the cytochrome c reduction assay. Priming neutrophils with BLP or LPS dose dependently increased the superoxide production in both UC and controls (P < 0.01), and BLP was more potent than LPS (P < 0.05). No differences were found between UC and controls. UC neutrophils do not seem to have an intrinsic abnormality with reduced tolerance to bacterial substances. However, bacterial wall products such as BLP modify neutrophil tissue-destruction mechanisms and might be pivotal for perpetuation of chronic colonic inflammation.     

Liver inflammatory cells, apoptosis, regeneration and stellate cell activation in non-alcohol steatohepatitis

Background, The pathogenesis of non-alcoholic steatohepatitis remains unclear from several points of view. Minimal diagnostic criteria are still not defined. Aim. To gather information useful for diagnosis and to improve the understanding of pathogenic mechanisms.

Patients. A series of 14 patients with non-alcoholic steatohepatitis, identified among liver outpatients, were paired for age, sex and alanine amino transferase values with 14 patients with hepatitis C virus infection without steatosis.

Methods. Clinical, biochemical and immunohistological examination, including characterisation of inflammatory cell population, evaluation of type 111 collagen and tenascin deposition, activation of stellate cells, hepatocellular apoptosis and proliferation.

Results. Patients with non-alcoholic steatohepatitis were more frequently obese, had higher triglyceride concentrations and lower gamma-globulins. T lymphocytes outnumbered polymorphonuclear cells, both in hepatitis C and in steatohepatitis, with a larger number of CD8 lymphocytes in patients with viral hepatitis but a comparable number of granulocytes. This resulted in a higher granulocytes to T cells ratio in steatohepatitis, possibly making these cells more easily detectable in spite of similar absolute numbers. Portal fibrosis and piecemeal necrosis were prevalent in hepatitis C virus infection, pericentral fibrosis was similar. Hepatocellular, apoptosis and proliferation as well as stellate cell activation were less relevant in steatohepatitis than in hepatitis C virus infection in spite of similar alanine amino transferase levels.

Conclusions. These data provide a possible explanation for the relatively low tendency to progression of non-alcoholic steatohepatitis in most patients despite increased alanine amino transferase and suggest that non-death-related release of alanine amino transferase might occur in non-alcoholic steatohepatitis. This makes liver biopsy an essential part of the clinical setting supporting diagnosis, evaluation of severity and possibly definition of the evolutionary trend.