Effect of an infusion device on the integrity of whole blood and packed red blood cells

The effects of the Gemini PC-2 linear peristaltic infusion device on the integrity of packed red blood cells (RBC) and whole blood products are reported. Thirty-eight units of blood products were infused at rates of 999, 100, 50, and 5 mL/hr under simulated clinical conditions. To evaluate the effect of hematocrit on cell survival, fresh and stored packed RBCs preserved with adenine-saline 3 (AS-3) and fresh and stored packed RBCs and fresh and stored whole blood preserved with citrate-phosphate-dextrose-adenine 1 (CPDA-1) were used. No two units tested came from the same donor. Plasma potassium and plasma free hemoglobin concentrations were determined before and after simulated infusion for 80 experimental runs. Preinfusion plasma potassium and free hemoglobin concentrations varied significantly among the blood products. Stored products were associated with higher plasma potassium and free hemoglobin levels than fresh units, both before and after infusion. Concentrations also differed significantly between AS-3-preserved and CPDA-1-preserved fresh and stored packed RBCs. Infusion did not change plasma potassium values appreciably under any conditions. Plasma free hemoglobin increased in the fresh products only. Donor-specific differences were significant for potassium but not for free hemoglobin. There was no significant effect of infusion rate on either biochemical marker. In all the experimental runs, less than 0.01% of cells were lysed. The Gemini PC-2 linear peristaltic infusion device delivered a variety of blood products at a wide range of infusion rates without inducing a substantial degree of hemolysis.     

The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites

The pharmacokinetics of ibuprofen and its two major metabolites, the hydroxy and carboxy derivatives, were studied in seven functionally anephric subjects undergoing hemodialysis therapy. Subjects received ibuprofen 800 mg tid for 14 days. Hemodialysis was performed three times weekly during this period. Arterial and venous blood samples were collected before dialysis and along with dialysate, and during the final dosing interval and dialysis session. No accumulation of ibuprofen plasma concentrations and an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly (mean plasma levels, carboxy 249 micrograms/mL and hydroxy 57 mu/mL); however, both were detected in dialysate. Mean extraction efficiencies were 0.16 (hydroxy) and 0.15 (carboxy). Dialysis clearance calculated by arterial-venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.     

Managing anemia in the critically ill patient

Anemia of critical illness is a multifactorial condition caused by phlebotomy, ongoing blood loss, and inadequate production of red blood cells. It occurs early in the course of critical illness. Although red blood cell transfusion is the treatment of choice for immediate management of anemia in the intensive care unit, controversy surrounds the most appropriate hemoglobin concentration or hematocrit "trigger." Therapeutic options, including blood-conservation tools, minimization of phlebotomy, erythropoietic agents, and investigational oxygen-carrying agents, may be alternatives to red blood cell transfusions in critically ill patients with anemia. Patient selection for erythropoietic agents will depend on further work dealing with outcomes and the total cost of care in managing the anemia of critical illness.     

The influence of ibuprofen,diclofenac and sulindac on the blood pressure lowering effect of hydrochlorothiazide

Summary In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg b.i.d. Only a slight, statistically non-significant change was found, with the exception of a significant increase in systolic blood pressure after 4 weeks treatment with ibuprofen. There was considerable variation in the blood pressure response during treatment with all three NSAIDs, with slight rises in blood pressure in 13 out of 24 periods. Body weight increased significantly on treatment both with ibuprofen and diclofenac, whereas the increase on sulindac was less and was transient. No significant change was found in various biochemical parameters, including plasma electrolytes, plasma renin activity (PRA), aldosterone, albumin and creatinine, in haematocrit or in the 24-h urinary excretion of sodium and potassium. The sole exception was a decrease in PRA during ibuprofen treatment. From these observations it is concluded that ibuprofen and diclofenac differ from sulindac in their interaction with the diuretic action of hydrochlorothiazide. It appears that all three NSAIDs can safely be combined with hydrochlorothiazide in hypertensive patients, but blood pressure should be monitored carefully when an NSAID are added.     

血浆抵抗素水平与2型糖尿病的关系研究

目的探讨血浆抵抗素与2型糖尿病的关系。方法选择2型糖尿病患者48例和年龄、体重指数相匹配的正常对照组30例,于清晨空腹测量身高、体重,并采集静脉血,采用酶联免疫分析法检测空腹血浆抵抗素水平。结果两组年龄相匹配,体重指数比较差异无统计学意义(P>0.05),平均血浆抵抗素水平糖尿病组(42±10)μg/L,正常对照组(21±5)μg/L,2型糖尿病组的血浆抵抗素水平明显高于正常对照组(P<0.05)。结论2型糖尿病患者血浆抵抗素水平升高,抵抗素可能对2型糖尿病的发生、发展起重要作用。     

Erythropoietin production rate in phlebotomy-induced acute anemia

OBJECTIVE: To estimate the rate of erythropoietin (EPO) production under physiological, conditions and to examine the regulatory mechanism of EPO production in response to acute phlebotomy-induced anemia. METHODS: Six sheep each underwent two phlebotomies in which the hemoglobin (Hb) was reduced to 3-4 g/dl over 4-5 h. The EPO plasma level, reticulocytes, Hb and EPO clearance were followed by frequent blood sampling. The EPO production rate was determined by a semi-parametric method based on a disposition decomposition analysis that accounts for the nonlinear disposition kinetics of EPO and corrects for time-dependent changes in the clearance. RESULTS: The controlled drop in hemoglobin resulted in an abrupt increase in the plasma EPO concentration (peak level 812+/-40 mU/ml, mean+/-CV%) that was followed by a rapid drop 2-4 days after the phlebotomy at a time when the sheep were still anemic (Hb=4.3+/-16 g/dl). The EPO production rate at baseline was 43+/-52 U/day/kg and the amounts of EPO produced over an 8 day period resulting from the first and second phlebotomy were 2927+/-40 U/kg and 3012+/-31 U/kg, respectively. CONCLUSIONS: The rapid reduction in the EPO plasma level observed 2-4 days following the phlebotomy cannot be explained solely by the increase in EPO clearance but also by a reduction in EPO production.     

参姜锁阳益气片对高寒地区运动性疲劳人群血液流变学的影响

 目的：探讨参姜锁阳益气片对高寒地区运动性疲劳人群的抗疲劳作用与血液流变学、血细胞分析指标改变的关系。方法：在黑河地区冬季-30 ℃的低温下,随机挑选120名健康运动员,分为试验组与对照组,每组60例。运动前各组抽取早餐前静脉血10 mL进行血液流变学与血细胞分析指标的检查,将试验组与对照组人员暴露在高寒环境中进行大强度长时间训练以建立运动性疲劳模型,运动结束后即刻抽取静脉血10 mL进行相同血液指标的检测,同时开始服药,试验组服用参姜锁阳益气片,对照组服用酵母片,持续服药14 d,在停药当天重复建立运动性疲劳模型并进行相同血液指标的检测。结果：与对照组相比,全血粘度、血浆粘度、红细胞聚集指数、红细胞变形指数、红细胞刚性指数、红细胞和血红蛋白均有显著下降（P<0.05）,血细胞压积未见明显改变。结论：参姜锁阳益气片能提高人体耐寒、抗缺氧能力,具有抗运动性疲劳的作用。     

Divalproex sodium increases plasma GABA levels in healthy volunteers

The purpose of this study was to ascertain the effects of divalproex sodium (DVP), an anticonvulsant and mood stabilizer, on plasma gamma-aminobutyric acid (GABA) levels in healthy humans. Twenty healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. Each subject received DVP 1000 mg per day for 1 week. Blood samples for assay of plasma levels of GABA were taken from each subject before and after the administration of DVP. GABA concentrations were analysed using high pressure liquid chromatography with fluorescence detection after derivatization with o-phthaldialdehyde. It was found that DVP administration for 1 week resulted in a small, but significant, increase in plasma levels of GABA. Our results suggest that DVP enhances GABA activity in humans. Further treatment studies of DVP on GABA function in patients with psychiatric disorders are needed to explore the significance of the enhancing effect of DVP on GABA activity.     

不同采血方法在血常规相关检验中的应用价值对比分析

目的探讨不同采血方法在血常规相关检验中的应用价值。方法笔者所在医院进行体检的健康人员90例,随机分为静脉组和末梢组各45例。分别采集静脉血和末梢血进行血常规检查,比较两组人员血常规检查中的白细胞计数、红细胞计数、红细胞比容、血红蛋白、平均红细胞血红蛋白浓度以及血小板等检查项目。结果静脉组45例患者的血常规检查结果为,WBC:(5.24±3.16)×109/L;RBC:(3.34±0.98)×1012/L;HCT:(42.35±20.46)%;HGB:(115.75±15.76)g/L;MCHC:(319.78±28.79)g/L;PLT:(228.75±84.78)×109/L。末梢组45例患者的血常规检查结果为,WBC:(5.86±3.18)×109/L;RBC:(3.86±0.87)×1012/L;HCT:(31.46±21.48)%;HGB:(101.56±16.48)g/L;MCHC:(322.43±28.94)g/L;PLT:(213.48±81.46)×109/L。两组患者的MCHC检查结果相比较,差异无统计学意义(P>0.05),而WBC、RBC、HCT、HGB、PLT的检查结果相比较,差异均有统计学意义(P<0.05)。结论不同的采血方法对血常规的检验结果具有很大的影响,应用静脉血代替末梢血可以有效的提高检验结果的准确性、提高仪器设备的使用寿命,值得在临床上推广使用。     

Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag,Tlow, Tmed,and a novel parameter,TCmaxRef

Objective: This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference).

Methods: In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400?mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6?h. Time between dosing and the start of absorption (T_lag); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (C_max) of the reference (standard ibuprofen acid) (T_CmaxRef); and time to achieve therapeutic plasma concentration were measured.

Results: Ibuprofen was absorbed more rapidly from the salt formulations than the reference; T_lag was 3.3–6.4?min for salt formulations compared with 10.9?min for the reference, and 100% of subjects had a T_lag ≤ 5?min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. T_CmaxRef was 3.22–5.74-times shorter for salt formulations than for the reference (all p?p?Conclusions: This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. T_lag and T_CmaxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia.     

Hematocrit,blood volume,and surface area of dried blood spots – a quantitative model

The use of the dried blood spot (DBS) sampling technique has extended the scope of clinical research, particularly in children. The effects of different hematocrit levels (25–55%) and different blood volumes (7.5–30 μL) on the surface area of the blood spots were investigated using ImageJ® software. Variation in hematocrit levels between patients and inaccuracies in blood volumes applied to Guthrie cards can have a marked effect on analyte concentrations measured in DBS samples. The current study presents a validated model that links blood volume and hematocrit to the surface area of the blood spot. The final model showed that both factors affect the blood spot surface area, however, the positive effect of blood volume is higher than the negative effect of hematocrit. The measurement of surface area could be added as an additional quality control step in clinical studies that have adopted fixed volume DBS sampling for the quantification of the analytes. This approach can be used in estimating the hematocrit if this is not known for a patient or estimating the volume in spots that are visually different in size from the norm, i.e. technical error.     

A comparison of venous versus capillary measurements of drug concentration

Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility that differences in assay results might occur if samples were collected by capillary stick vs. venous phlebotomy was examined by simultaneous sampling in 18 patients. Although correlation was very high (0.999) and percentage differences fairly low (range of 0 to 15.4%), a statistical difference was noted in the sampling methods. The precision was 6.5 +/- 6.58% and there was a slight negative bias (-3.76%), with capillary samples less than venous samples. Although there were statistical differences for the drugs studied in the concentration ranges evaluated, capillary samples should provide fairly small errors when compared to venous samples.     

Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.

1 After repeated single daily doses, the aldosterone antagonists prorenoate potassium and spironolactone were compared with regard to renal antimineralocorticoid activity, plasma potassium concentration and steady state plasma levels of their active metabolites, prorenone and canrenone respectively, in a balanced crossover study of twelve healthy subjects. 2 Following challenge with the mineralocorticoid, fludrocortisone, best estimates of the potency of prorenoate potassium relative to spironolactone were 3.6 (95% confidence limits 1.6-10.4) for urinary sodium excretion and 3.4 (95% confidence limits 2.0-6.5) for urinary log10 10Na/K. Estimates with respect to urinary potassium excretion and plasma potassium concentration were imprecise, confirming the limitations of the fludrocortisone model in the evaluation of aldosterone antagonists at steady state. 3 Both compounds exhibited directly proportional relationships between daily dose and steady state plasma levels of active metabolites. The approximate mean terminal elimination half-life of prorenone at steady state was 32.6 h (range 18-80 h).     

Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in Wistar rats

This study was conducted to characterize better the response of rats to blood loss and hemolysis and to incorporate automated methods into the routine evaluations of those responses. Serial phlebotomies of 1.5-2.0 ml of blood per day for 5 days, or intraperitoneal injection of 50 mg kg(-1) phenylhydrazine (PHZ) for 3 days, were used to cause anemia associated with blood loss or hemolysis, respectively. Maximum decreases in red blood counts were observed on Day 3 in PHZ-treated animals (68%) and Day 4 in blood-loss animals (35%). In the routine complete blood count (CBC), hemoglobin, hematocrit/hemoglobin ratio and erythrocyte indices could be used to discriminate between the two treatments. Free plasma hemoglobin in PHZ-treated animals resulted in marked elevations of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with a 2:1 hematocrit/hemoglobin ratio rather than the anticipated 3:1 ratio. Although both groups of animals had elevated white blood cell counts, PHZ-treated animals also had monocytosis and basophilia. Reticulocyte counts were more sensitive than erythropoietin (EPO) concentrations in predicting erythroid changes. Maximum mean reticulocyte values were ca. 24% in serially phlebotomized animals and >99% in PHZ-treated rats. Plasma EPO levels were 4-10-fold higher than EPO levels in urine, kidney or liver. Flow cytometric differentials of rat bone marrow using 2, 7-dichlorofluorescin successfully predicted erythroid hyperplasia in both experimental groups. Erythrocyte indices returned to normal within 14 days and the remaining CBC parameters were normal within 28 days for both treatment groups. Reticulocyte counts remained slightly elevated on Day 28, but were normal when assessed at Day 56 in blood-loss and PHZ-treated animals.     

Effect of ibuprofen on lithium plasma and red blood cell concentrations

The effect of ibuprofen on steady-state lithium plasma and red blood cell concentrations was studied in 11 normal volunteers. During the seven-day control phase, sustained-release lithium carbonate 450 mg was administered every 12 hours. Lithium plasma and red blood cell concentrations were determined on days 5, 6, and 7. During the treatment phase (days 7-15), ibuprofen 400 mg was administered four times a day concurrently with lithium. Lithium plasma and red blood cell concentrations were obtained on days 14, 15, and 16. Multiple blood samples were obtained over a 12-hour period on days 6 and 15. Urine samples were collected from six subjects. The mean minimum lithium concentration increased 15% when ibuprofen was added. Mean maximum lithium concentration, area under the curve, red blood cell concentrations, and the lithium red blood cell to plasma ratio were significantly higher during the treatment phase. Mean lithium total body and renal clearance values were significantly lower during the treatment with ibuprofen. The administration of ibuprofen can increase steady-state plasma lithium concentrations and decrease lithium clearance.     

Absence of an interaction between ibuprofen and zaleplon.

The potential interaction between zaleplon and ibuprofen was studied. Healthy adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen 600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg concomitantly in an open-label, randomized, three-period crossover study. There was a seven-day washout period between treatments. Venous blood samples were collected for pharmacokinetic analysis at various intervals up to 14 hours after drug administration. A total of 17 subjects (11 men and 6 women) completed the study. There were no significant differences between zaleplon monotherapy and combination therapy in mean +/- SD, of zaleplon clearance (CL) (2.80 +/- 0.72 versus 2.72 +/- 0.89 L/hr/kg, respectively), maximum plasma concentration (Cmax) (37.1 +/- 17.9 versus 39.8 +/- 20.0 ng/mL), or area under the concentration-versus-time curve (AUC) (56.7 +/- 22.8 versus 59.2 +/- 22.0 ng.hr/mL). There were no significant differences between ibuprofen monotherapy and combination therapy in ibuprofen CL (71.6 +/- 17.0 versus 71.7 +/- 14.9 L/hr/kg), Cmax (40.8 +/- 10.2 versus 40.4 +/- 10.0 micrograms/mL), or AUC (127.6 +/- 29.6 versus 126.4 +/- 29.7 micrograms.hr/mL). Three subjects had one or more adverse effects with zaleplon alone, one subject had one or more with ibuprofen alone, and one subject had one or more with combination therapy. The adverse effects were mild and resolved without intervention. There was no evidence of a significant interaction between zaleplon and ibuprofen.     

Use of a bioassay in healthy men to evaluate diuretic-spironolactone combinations.

The plasma potassium responses to 1 week's treatment with metolazone 0.625 mg, 1.25 mg and 2.5 mg in combination with spironolactone 50 mg, and metolazone 2.5 alone were examined in a double-blind, crossover study in twelve healthy subjects. Spironolactone attenuated the hypokalaemia induced by metolazone--addition of spironolactone 50 mg to metolazone 2.5 mg raised plasma potassium by 0.18 mmol/l (P less than 0.025). In the presence of spironolactone, a linear log metolazone dose-plasma potassium response relationship (P less than 0.01) was demonstrated. Spironolactone was unable to compensate fully for metolazone's hypokalaemic effect although in combination with metolazone 0.625 mg and 1.25 mg, plasma potassium concentration was maintained close to pretreatment levels. The human bioassay employed provided conveniently quantitative information which allows the rational development of a fixed dose diuretic-spironolactone combination tablet.     

Overall Similarities and a Possible Factor Affecting Plasma Metabolome Profiles Between Venous and Capillary Blood Samples From 20 Healthy Human Males

Amino acids and lipids are biomarkers used to assess the presence and severity of disease, as well as the toxicological response to drugs. Although upper-extremity venipuncture is a well-used standard technique, fingertip capillary sampling is a more convenient procedure. Delineating the global differences in amino acid and lipid levels in capillary and venous blood samples is paramount for expanding the application of capillary blood tests in biomarker assays. We recruited 20 healthy male subjects and collected plasma obtained from both fingertip capillary and antecubital venous blood. The samples were analyzed to determine the overall profiles of amino acids and lipids and to test for differences in their levels between both vessel types. The results demonstrated that the differences between capillary and venous blood had a lower impact than interindividual variations; however, trends of separation between them were observed for amino acids. The levels of 5 out of 28 amino acids scored fold changes over 30%, while 9 out of 498 lipids had a fold change over 30%. The time required for fingertip blood collection could be a factor for the differences in 3 metabolites. These findings provide useful information for the application of fingertip capillary blood sampling in biomarker assays.     

Toxicological effects of arsenate exposure on hematological,biochemical and liver transaminases activity in an Indian major carp, Catla catla

The impact of acute and sublethal toxicity of arsenate on hematological, biochemical and enzymological parameters of an Indian major carp Catla catla were estimated. The median lethal concentration of sodium arsenate to the fish Catla catla for 96 h was found to be 43.78 mg/L. During acute treatment (43.78 mg/L), hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), white blood cell count (WBC), plasma glucose, plasma protein, liver aspartate and alanine aminotransferase (AST and ALT) levels decreased, whereas corpuscular indices like mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) increased in arsenate treated fish. In sublethal treatment (4.378 mg/L), Hb, Ht, RBC, plasma protein levels decreased while MCHC and plasma glucose levels increased throughout the exposure period. A biphasic trend was noticed in WBC, MCV, MCH, liver AST and ALT levels. The alterations of these parameters can be effectively used as a rapid method to assess health of fish exposed to arsenate in the aquatic environment.     

肝硬化患者门静脉血内皮素增高的意义

采用放免法测定了１２例肝硬化患者门脉血及外周静脉血内皮素含量，同时测定了１３例正常人外周静脉血内皮素含量。其结果肝硬化患者外周血内皮素含量高于正常人（分别为５２．３１ｎｇ／Ｌ±６．４９ｎｇ／Ｌ；３５．８９ｎｇ／Ｌ±１３．２３ｎｇ／Ｌ），而肝硬化患者门静脉血内皮素含量明显高于外周血（前者为６８．５５ｎｇ／Ｌ±６．００ｎｇ／Ｌ）。结果表明，内皮素在肝硬化门静脉高压的形成中有一定的作用