血浆置换联合持续性血液滤过透析对慢性重型乙型病毒性肝炎临床症状及生化指标的影响——附87例报告

目的:探讨血浆置换联合持续性血液滤过透析治疗对慢性重型乙型病毒性肝炎(慢重肝)临床症状及生化指标的影响.方法:记录87例慢重肝患者(A组)在应用血浆置换及持续性血液滤过透析联合内科综合治疗前后临床症状和生化指标的改善情况,并与94例行血浆置换联合内科综合治疗的慢重肝患者(B组)进行对比.结果:治疗后,A组临床症状改善100%(87/87),低钾血症复常率为80%(33/41)、低钠血症复常率为93%(27/29),肝性脑病清醒率55%(12/22);B组则相应为48%(45/94)、7%(3/42)、7%(2/30)和20%(5/25),2组上述各项指标比较差异均有统计学意义(均为P＜0.05).A组近期有效率、近期生存率分别为80%、48%,B组为47%、31%,2组比较差异均有统计学意义(均为P＜0.05).不良反应以血浆过敏反应为主,均未发生低血压、肺水肿等严重不良反应.结论:血浆置换及持续性血液滤过透析联合内科综合治疗可有效纠正慢重肝患者的电解质紊乱,保持内环境平衡,且能提高其近期生存率和肝性脑病清醒率,为慢重肝的治疗提供了新的选择.     

Elevated plasma S100B levels in high altitude hypobaric hypoxia do not correlate with acute mountain sickness

Abstract

Objectives:

Ascent to high altitude may result in a hypobaric hypoxic brain injury. The development of acute mountain sickness (AMS) is considered a multifactorial process with hypoxia-induced blood–brain barrier (BBB) dysfunction and resultant vasogenic oedema cited as one potential mechanism. Peripheral S100B is considered a biomarker of BBB dysfunction. This study aims to investigate the S100B release profile secondary to hypoxic brain injury and comment on BBB disturbance and AMS.

Methods:

A prospective field study of 12 subjects who ascended Mt Fuji (3700 m) was undertaken.

Results:

The mean baseline plasma S100B level was 0·11 μg/l (95% CI 0·09–0·12), which increased to 0·22 μg/l (95% CI 0·17–0·27) at the average of three high altitude levels (2590, 3700, and 2590 m on descent) (P < 0·001). The mean level for the seven subjects who experienced AMS rose from 0·10 to 0·19 μg/l compared to 0·12 to 0·25 μg/l for the five subjects who did not develop AMS (P = 0·33).

Conclusion:

Ascending to 3700 m resulted in elevated plasma S100B levels but this was not associated with AMS.     

Preanalytical,analytical, and biological variation of blood plasma submicron particle levels measured with nanoparticle tracking analysis and tunable resistive pulse sensing

Background: Nanoparticle tracking analysis (NTA) and tunable resistive pulse sensing (TRPS) enable measurement of extracellular vesicles (EVs) in blood plasma but also measure other particles present in plasma. Complete isolation of EVs from similarly sized particles with full EV recovery is currently not possible due to limitations in existing isolation techniques.

Aim: This study aimed to evaluate preanalytical, analytical, and biological variation of particle measurements with NTA and TRPS on blood plasma.

Methods: Blood from 20 healthy subjects was sampled in the fasting and postprandial state. Platelet free plasma (PFP) was analyzed immediately and after a freeze-thaw cycle. Additionally, the effect of prandial state and a freeze-thaw cycle on EV-enriched particle fractions obtained via size-exclusion chromatography (SEC) was examined.

Results: We observed analytical linearity in the range of 1.0–10.0?×?10⁸ particles/mL for NTA and 1.0?×?10⁸–1.8?×?10⁹ particles/mL for TRPS. The analytical variation was generally below 10%. A considerable intra- and inter-individual variation was demonstrated with estimated reference intervals of 1.4?×?10¹¹–1.2?×?10¹² particles/mL for NTA and 1.8?×?10⁸–1.6?×?10⁹ particles/mL for TRPS. Food intake and to a lesser extent a freeze-thaw cycle affected particle populations in PFP and, similarly, in EV-enriched fractions.

Conclusion: In this study NTA and TRPS enabled acceptably precise concentration and size measurement of submicron particles in PFP. An appreciable intra- and inter-individual biological variation was observed. In studies on particle populations in PFP or EV-enriched fractions, we recommend analysis of fresh, fasting samples.     

Plasma β-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer's disease

Aging dogs naturally demonstrate cognitive impairment and neuropathology that model early Alzheimer's disease (AD). In particular, there is evidence that canine cognitive dysfunction syndrome (CDS) in aged dogs is accompanied by cortical deposition of Aβ peptides and neurodegeneration. Plasma Aβ levels have been examined in humans as putative biomarkers for AD, but to date, no similar studies have been conducted for canine dementia. The aim of the present study was to assess plasma Aβ1-42 and Aβ1-40 levels in a blind study using pet dogs that were either successfully aging or exhibiting CDS. The severity of cognitive impairment was assessed using an owner-based questionnaire. On average, young dogs presented significantly higher plasma levels of Aβ1-42 and Aβ1-40 than aged, cognitively unimpaired dogs. Notably, among aged dogs, the levels of Aβ1-42 and the Aβ42/40 ratio were significantly higher in those showing mild cognitive impairment than in either cognitively unimpaired or severely affected dogs. These results suggest that increased plasma Aβ1-42 levels and Aβ42/40 ratio could be a biomarker for canine cognitive dysfunction, which is considered an excellent natural model of early AD.     

Calcitonin gene-related peptide potentiates substance P-induced plasma extravasation in the rat trachea

Antidromic stimulation of vagal sensory nerves is known to produce plasma extravasation in the rat trachea. This neurogenic inflammation is thought to be mediated by substance P or other tachykinins released from sensory nerve endings. We sought to determine whether calcitonin gene-related peptide (CGRP), which is also released from sensory nerve endings, can potentiate substance P-induced plasma extravasation in the rat trachea. To accomplish this, we measured the amounts of Evans blue dye extravasated into the trachea after intravenous injections of substance P alone and combined with CGRP. We found that when substance P and CGRP were injected together, the amount of plasma extravasation produced in the trachea was substantially greater than the amount produced when substance P was injected alone. This potentiation was critically dependent on the dosage of CGRP and was not observed when relatively high dosages were used. We also found that CGRP had a potent hypotensive effect and speculate that reduced blood pressure may account for the lack of potentiation observed at the higher CGRP dosages. Based on these findings, we conclude that CGRP can potentiate substance P-induced plasma extravasation in the rat trachea and may therefore play a role in modulating neurogenic inflammation of the airways. Offprint requests to: J.J. Brokaw     

Validated RP-HPLC method for quantification of felodipine in rabbit plasma: Application in a bioequivalence study

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Method for Simultaneous Determination of Free Concentration,Total Concentration,and Plasma Binding Capacity in Clinical Samples

Most quantitative research methods are based on measuring either the total or the free concentration of an analyte in a sample. However, this is often insufficient for the study of complex biological systems. The main objective of this research was to develop new methods for providing more information from samples: the free concentration (C_f), the total concentration (C_t), and the plasma binding capacity (PBC). Samples were processed using microextraction and ultrafiltration. For each of these techniques, two quantification procedures were used: addition of isotopically labeled standard and repeated analysis of the same sample. The new methods were validated by analyzing clinical samples and samples with known concentrations. Methods based on addition of labeled compound were found to be the fastest, and most reproducible. For analysis of clinical samples, methods based on microextraction were more sensitive and more accurate than those based on ultrafiltration. For analysis of pooled plasma samples, the overall accuracy of all approaches to determine PBC, testosterone C_f, and testosterone C_t was between 94 and 109%, 87–113%, and 94–122% respectively. The new approach goes beyond a simple concentration measurement, giving more information from clinical samples, with great potential for personalizing drug dosage and therapy to the needs of individual patients.     

Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus associated with antiphospholipid antibodies: usefulness of monitoring coagulation–fibrinolysis markers

Abstract

We report on a 24-year-old woman with systemic lupus erythematosus and lupus anticoagulant who developed chronic thrombotic microangiopathic hemolytic anemia. The patient responded well to a combination of plasma exchange and anticoagulant therapy. Changes in the molecular markers for coagulation and fibrinolysis corresponded with the disease activity. We suggest that thrombotic microangiopathic hemolytic anemia should be suspected when anemia and thrombocytopenia of unknown etiologies occur in systemic lupus erythematosus. In such cases, the evaluation of molecular markers for coagulation and fibrinolysis might be helpful both for diagnosis and for assessing the response to therapy.