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[This corrects the article DOI: 10.3389/fphys.2023.1308632.].

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BACKGROUND: Cirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce. PURPOSE: We mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics. METHODS: Five cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3-matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions. RESULTS: Streamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio QRPV/QLPV demonstrates an increase in tandem with the volume ratio VR/VL, exhibiting a linear correlation with the Pearson correlation coefficient being 0.93. CONCLUSION: The differences in the blood distributions are consistent with the clinicians' knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches.

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Purpose: To investigate the predictive value of hemoglobin (Hb) to red blood cell distribution width (RDW) (Hb/RDW) ratio in combination with serum sodium for major adverse cardiovascular events (MACE) in elderly acute heart failure patients with preserved ejection fraction at 30 days after discharge. Methods: 130 elderly acute heart failure patients with preserved ejection fraction were enrolled and followed up at 30 days after discharge. They were classified into the MACE group (n=11) and none-MACE group (n=119). On the day of admission, clinical baseline characteristics were measured and results from laboratory tests were gathered. The correlation and predictive value of Hb/RDW and serum sodium with the occurrence of MACE at 30 days after discharge in acute heart failure patients with preserved ejection fraction in the elderly were analyzed. Results: Spearman correlation analysis showed that the occurrence of MACE was negatively correlated with Hb/RDW, serum sodium (r=-0.209, r=0.291, p<0.05) and Hb/RDW (OR=0.484, 95% CI:0.254, 0.922), serum sodium (OR=0.779, 95% CI:0.646,0.939) were independent risk factors (p<0.05) analyzed by multifactorial logistic. Receiver operating characteristic curves (ROC) analysis showed that the area under the curve (AUC) for the prediction of MACE by Hb/RDW was 0.73, with an optimal threshold of 9.28, sensitivity 81.80%, specificity 70.60%, positive predictive value (PPV) 20.50%, negative predictive value (NPV) 97.70%; the AUC of serum sodium for predicting the occurrence of MACE was 0.76, with an optimal threshold of 140.35 mmol/L, sensitivity 90.90%, specificity 57.10%, PPV 16.40%, NPV 98.60%; and the AUC of Hb/RDW combined serum sodium to predict the occurrence of MACE was 0.83, with sensitivity 90.90%, specificity 78.20%, PPV 27.80% and NPV 98.90%. Conclusion: Hb/RDW and serum sodium had negative correlation with MACE and were independent risk factors of 30-day MACE; Hb/RDW combined with serum sodium can predict 30-day MACE occurrence in elderly acute heart failure patients with preserved ejection fraction.

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This review focuses on the role of human red blood cells (RBCs) as drug carriers. First, a general introduction about RBC physiology is provided, followed by the presentation of several cases in which RBCs act as natural carriers of drugs. This is due to the presence of several binding sites within the same RBCs and is regulated by the diffusion of selected compounds through the RBC membrane and by the presence of influx and efflux transporters. The balance between the influx/efflux and the affinity for these binding sites will finally affect drug partitioning. Thereafter, a brief mention of the pharmacokinetic profile of drugs with such a partitioning is given. Finally, some examples in which these natural features of human RBCs can be further exploited to engineer RBCs by the encapsulation of drugs, metabolites, or target proteins are reported. For instance, metabolic pathways can be powered by increasing key metabolites (i.e., 2,3-bisphosphoglycerate) that affect oxygen release potentially useful in transfusion medicine. On the other hand, the RBC pre-loading of recombinant immunophilins permits increasing the binding and transport of immunosuppressive drugs. In conclusion, RBCs are natural carriers for different kinds of metabolites and several drugs. However, they can be opportunely further modified to optimize and improve their ability to perform as drug vehicles.

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OBJECTIVE: This work describes a simplified, 96-well plate method for determining the blood-to-plasma concentration ratio (BP ratio) for small molecules. METHODS: The need for calibration curves was eliminated using a matrix-matching approach in which blood samples were mixed with blank plasma and plasma samples were mixed with blank blood. As a result, both blood- and plasma-origin samples shared an equivalent matrix ahead of bioanalysis. In the in vitro assay, identical sample matrices were achieved by using the same source of blank plasma and blood. RESULTS: In humans, a good correlation (R2 = 0.84) was observed between the data obtained in this matrix-matching method and literature values for 11 commercial compounds possessing a wide range of logD values across multiple chemical classes. In addition, this method showed good agreement with in vitro BP ratios for 10 proprietary compounds determined radiometrically (R2 = 0.72) in human and preclinical species. Finally, the in vitro matrix matching method compared favorably to BP ratios determined ex vivo for 13 proprietary and literature compounds (R2 = 0.87) in rat. CONCLUSION: This method, suitable for in vitro and ex vivo BP ratio determinations, is operationally efficient, robust, and a useful improvement upon previously published methods.

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Objective:Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs,including many substrates of P-glycoprotein(P-gp).Levetiracetam,a kind of antiepileptic drugs,is a substrate of P-gp.Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. Methods:Wistar rats were divided into a low-altitude control group,a high-altitude group,a solvent group,and a P-gp induction group.After 24 h of exposure at altitude of 4 010 m,rats in the high-altitude group were given levetiracetam orally or intravenously.The plasma was respectively collected at 0.083,0.25,0.5,0.83,1.25,2,4,6,8,10,12,and 24 h after oral administration of the drug,while both plasma and brain were respectively collected at 5,45,60,120 and 240 min after intravenous injection.After 3 days administration of dexamethasone,plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam.Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The expression of P-gp in blood-brain barrier was detected by Western blotting. Results:Compared with the low-altitude control group,the area under the curve(AUC)and mean residence time(MRT)of levetiracetam were respectively decreased by 14.69%(P<0.01)and 15.42%(P<0.01),while the clearance(CL)was increased by 16.67%(P<0.01)in the high-altitude group.The ratio of brain/blood plasma drug concentration was decreased by 22.82%(P<0.05),12.42%(P<0.05),17.40%(P<0.01),and 13.22%(P<0.01)at 5,45,120,and 240 min after injection,respectively.The expression of P-gp on the blood-brain barrier was increased by 86.3%(P<0.05).Compared with the solvent control group,the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3%(P<0.05),the ratio of brain/blood plasma drug concentration was decreased by 19.3%(P<0.05). Conclusion:After acute plateau hypoxia exposure,the pharmacokinetic of levetiracetam in rats are altered,and the cerebral-blood distribution of the drug in rats is decreased,which may be related to the up-regulation of P-gp expression on the blood-brain barrier.

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OBJECTIVES: Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs, including many substrates of P-glycoprotein (P-gp). Levetiracetam, a kind of antiepileptic drugs, is a substrate of P-gp. Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear. This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. METHODS: Wistar rats were divided into a low-altitude control group, a high-altitude group, a solvent group, and a P-gp induction group. After 24 h of exposure at altitude of 4 010 m, rats in the high-altitude group were given levetiracetam orally or intravenously. The plasma was respectively collected at 0.083, 0.25, 0.5, 0.83, 1.25, 2, 4, 6, 8, 10, 12, and 24 h after oral administration of the drug, while both plasma and brain were respectively collected at 5, 45, 60,120 and 240 min after intravenous injection. After 3 days administration of dexamethasone, plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam. Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The expression of P-gp in blood-brain barrier was detected by Western blotting. RESULTS: Compared with the low-altitude control group, the area under the curve (AUC) and mean residence time (MRT) of levetiracetam were respectively decreased by 14.69% (P<0.01) and 15.42% (P<0.01), while the clearance (CL) was increased by 16.67% (P<0.01) in the high-altitude group. The ratio of brain/blood plasma drug concentration was decreased by 22.82% (P<0.05), 12.42% (P<0.05), 17.40% (P<0.01), and 13.22% (P<0.01) at 5, 45, 120, and 240 min after injection, respectively. The expression of P-gp on the blood-brain barrier was increased by 86.3% (P<0.05). Compared with the solvent control group, the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3% (P<0.05), the ratio of brain/blood plasma drug concentration was decreased by 19.3% (P<0.05). CONCLUSIONS: After acute plateau hypoxia exposure, the pharmacokinetic of levetiracetam in rats are altered, and the cerebral-blood distribution of the drug in rats is decreased, which may be related to the up-regulation of P-gp expression on the blood-brain barrier.

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Bisphenol S (BPS) has been widely used as a substitute for bisphenol A in industrial manufacturing. However, the safety of BPS is controversial, and the mechanism by which BPS exerts cardiovascular toxicity remains unclear. In this study, zebrafish embryos, including wild-type zebrafish and transgenic (flk1:eGFP), (gata1:DsRed) and (cmlc2:eGFP) zebrafish at 2 h postfertilization (hpf), were exposed to BPS at concentrations of 1, 10 and 100 µg/L for 24, 48 and 72 h, respectively. The data showed that BPS accelerated the expansion of the common cardinal vein and inhibited lumen formation between 24 hpf and 72 hpf. Moreover, low-dose BPS disturbed cardiac muscle contraction by breaking the calcium balance in cardiac muscle cells according to the RNA-seq results. As a consequence, increased heart rate and irregular blood circulation were observed in the BPS treatment groups. This result suggested that BPS at environmental relevant concentrations caused cardiovascular toxicity during the development of zebrafish embryos, possibly being an important inducer of cardiovascular injury later in life. These findings provide insight into the rational and safe application of BPS.

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Purpose: To overcome the side effects of repetitive administration of diazepam (Dzp) besidesgaining benefits from sustaining release of the drug, which contributes to patient compliance,we concentrated on designing and preparing Dzp solid lipid nanoparticles (SLNs). Methods: Using cholesterol (CHOL), stearic acid (SA), and glycerol monostearate (GMS), SLNswere prepared by high shear homogenization technique coupled with sonication. Polysorbate80 (Tween 80) was used as a nonionic surfactant. After modification of prepared SLNs, particlesize, zeta potential, drug-loading efficiency, morphology, and scanning calorimetry, as well asrelease studies were conducted. To increase the stability of desired particles, freeze-drying bycryoprotectant was carried out. In the final stage, In vivo studies were performed by oral (PO)and intraperitoneal (IP) administrations to Wistar male rats. Results: Results indicated that optimized prepared particles were on average 150 nm diameterin spherical shape with 79.06 % loading efficiency and release of more than 85% of the loadeddrug in 24 hours. In vivo investigations also illustrated differences in blood distribution of Dzpafter loading this drug into SLNs. Conclusion: Based on the findings, it seems that drug delivery using SLNs could be anopportunity for solving complications of Dzp therapy in the future.

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BACKGROUND: Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by the hyperinflammatory background. Our objective was to analyze RDW performance to predict outcome in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). METHODS: Retrospective observational study including 173 patients with COVID-19-associated ARDS. Data was analyzed at hospital admission, inclusion in the TOCICOV Study (day 0), days 1, 3, 7 and 15 post-inclusion. RESULTS: Overall, 57% patients received tocilizumab. Overall mortality was 20.8%. RDW was higher in non-survivors compared to survivors at admission (13.53% vs. 14.35, P=0.0016), day 0 (13.60% vs. 14.42, P=0.026), day 3 (13.43% vs. 14.36, P<0.001) and day 7 (13.41% vs. 14.31, P=0.046), presenting better discrimination ability for mortality than other prognostic markers [area under the curve-receiver operating characteristic (AUC-ROC) =0.668 for admission RDW, 0.680 for day 0 RDW, 0.695 for day 3 RDW and 0.666 for day 7 RDW]. RDW values did not vary significantly according to tocilizumab treatment. When adjusted by hemoglobin and tocilizumab treatment, only RDW at admission, day 0, day 3 and C reactive protein (CRP) at day 0 and day 1 were associated with mortality (P<0.05). Only in non-tocilizumab treated patients, IL-6 levels at day 0 were correlated with day 3 RDW (r=0.733, P=0.004) and with day 3 CRP (r=0.727, P=0.022). Both parameters showed significant statistical correlation (r=0.255 for day 1 RDW and CRP in the overall cohort and r=0.358 for day 3 RDW and CRP in patients not treated with tocilizumab, P<0.015). CONCLUSIONS: RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.

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BACKGROUND: Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown. METHODS: Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time-frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. RESULTS: SHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs. CONCLUSIONS: Pancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators.

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We sought to investigate the possible association between Red Blood Cell Distribution Width (RDW), vascular calcification, oxidative stress and renal function and all-cause/cardiovascular (CV) mortality, CV events and progression of kidney disease in a cohort of patients with Diabetic Kidney Disease (DKD). Carotid intima media thickness (cIMT) and oxidized low-density cholesterol were measured in 104 Type 2 Diabetes Mellitus (T2DM) patients with established DKD, distributed in all five stages of kidney disease and 38 diabetics with normal renal function. All patients were followed for 7 years with end-points all-cause and CV mortality, CV events and progression to End-Stage Renal Disease (ESRD). RDW was positively correlated with diabetes duration (r = 0.19, p = 0.023) and albuminuria (r = 0.29, p = 0.002). Multivariate regression analysis revealed that RDW was a strong, independent predictor of cIMT value (ß = 0.031, p = 0.012). Kaplan-Meier curves and Cox proportional hazard models revealed that after adjustment for several cofounders, RDW was a significant and independent predictor for all-cause mortality, CV mortality, CV event and progression to ESRD (HR 1.75, p = 0.001, HR 2.03, p = 0.001, HR = 1.66, p < 0.0001 and HR 2.14, p = 0.001 respectively). RDW predicts mortality, CV events and deterioration of renal function in DKD, probably reflecting atherosclerosis.

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Blood distribution and plasma protein binding are the important properties that can influence pharmacokinetics and ultimately the anticancer efficacy of photosensitizers in clinical photodynamic therapy. As a novel and promising phthalocyanine photosensitizer under clinical phase Ⅱ investigation in China, the superiority of PHOCYANINE is speculated on its attribution to its binding with plasma proteins. To verify this hypothesis, explore the targeting mechanism and further apply foundation for its clinical trial evaluation, we further study its in vitro and in vivo human blood distribution, in vitro plasma protein and lipoprotein binding in detail. PHOTOCYANINE was found to be mainly distributed in plasma with low KBP and KEP values. Moreover, its high binding rates to plasma proteins among various species (mouse, rat, dog, monkey, and human) were then determined. Among these plasma proteins, human serum albumin and α1-acid-glycoprotein were found to bind PHOTOCYANINE highly, and low-density lipoproteins have the highest percentage of PHOTOCYANINE over other lipoproteins. This study is expected to provide some guidance for PDT clinical evaluations and for further molecular design and development of photosensitizers.

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This study presents the statistical results of patients who had been recently discharged from hospital within one month after their treatment in the emergency department (ED). Using routine (14,881) MCV and RDW measurements and statistical tools, we could predict acute mortality in these patients (N = 1158), adjusted for age. It is likely that an increase in the MCV and RDW parameters may correlate in some of our older patients with a poor prognosis with an increased level of circulating IGF-I, which affects red blood cell parameters. The research presents the prognostic statistics of the analyzed clinical factors as well as speculates on the potential correlation of these parameters with the regenerative potential of stem-cell compartment. Analysis shows that both MCV and RDW are statistically significant (Area Under Curve [AUC], lower CI 95% >50%) predictors of acute mortality in ED patients. The classification of patients based on their MCV threshold (= 92.2 units) indicates a proper clinical prognosis in nearly 6 of 10 subjects (AUC >58%), whereas taking into account RDW (=13.8%) indicates a proper clinical prognosis in no more than 7 of 10 individuals. The report concludes that by employing strongly fitting (95%) quadratic modeling of the ORs against the biomarkers studied, one can notice a similar relationship between MCV and RDW as diagnostic tools to predict regenerative potential and clinical outcomes in older patients. Although RDW alone had a 10% higher diagnostic value in terms of predicting early death in the emergency department in patients that were admitted to the ED and subsequently hospitalized, also taking the MCV measurement improved accuracy in predicting clinical outcomes by 2.5% compared to RDW alone.

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OBJECTIVE: Transfusion safety is based on the availability of safe and compatible blood products at the right time and to the right patient, and requires close monitoring in order to detect possible incidents. The decree of June 20th 2018, which establishes the national blood transfusion's guiding plan, states that the organization that prevails throughout the national territory is built around an inseparable link between the implementation of erythrocyte immunohematology and the labile blood products delivery by authorised structures. METHOD: The article describes the two types of the link's organization, structural or functional, used to develop the comparative risk-benefit analysis. RESULTS: The structural link, which has fewer interfaces, reduces risk situations that lead to delays in release by default of a compatible product. The cases in which a functional link may have a greater benefit than the risks generated are those related to a geographical distance between the delivery site and the patient's place of care. In these cases, a functional link is possible provided that certain organizational points are mastered. CONCLUSION: The comparative analysis shows that the structural link is to be favoured since that the coherence of the patient's care and his care path is ensured. In certain situations, mainly geographical, the functional link can have a benefit that offsets the risks generated by the new interfaces; provided that the system is secured by a real tripartite collaboration between health care institution, biology laboratory and delivery site.

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Artemisinin and its derivatives have been widely used for treatment of malaria and the therapeutic targets are considered within the red blood cells. In the recent studies on the erythrocytes' uptake of artemisinin-derivatives in vitro, applying the radioisotope-labeled technology, it was trying to predict the in vivo disposition properties, but different distribution results were revealed from a preliminary study in one human. The pharmacokinetic differences among blood cells and plasma still remain unclear. To explore the therapeutic related pharmacokinetics and compare the in vitro-in vivo blood distribution in rats, an improving blood sample preparation and LC-MS/MS detection method was developed and successfully validated. The lower limit of quantification was smaller than the previous studies. In the in vitro blood distribution studies, the content ratios from blood cells to plasma were compared in the concentrations from 20 ng/mL to 1000 ng/mL. Such ratios were determined to be 1.1-1.6 for artemisinin, 0.9-1.2 for artemether, and around 0.7 for dihydroartemisinin. In the oral administration pharmacokinetic studies in rats, the concentration ratios from blood cells to plasma were from high (2.6-3.6) to medium (1.3-2.5), and low (0.5-1.5) for artemisinin, artemether, and dihydroartemisinin respectively in all measuring time points, displaying the similar affinity order toward blood cells in artemisinin > artemether > dihydroartemisinin as the in vitro measurements. The dosages of 10 mg/kg for intravenous administrations of artemisinin and 200 mg/kg for oral administrations of artemisinin or artemether were used for the pharmacokinetic study in rats. The geometric mean exposures (AUC(0-t)) of artemisinin, artemether and dihydroartemisinin in blood cells were determined to be 2.6 folds, 1.7 folds, or 1.2 folds greater than those in plasma, respectively. Referring to the in vitro distribution, the AUC(0-t) ratios from the blood cells measurements to the plasma measurements of these three antimalarial drugs were also in a similar trend as the in vitro distribution measurements. Furthermore, the half-life (t1/2) of artemether in blood cells was even longer than that in plasma, while the clearance of artemisinin, artemether, or dihydroartemisinin in blood cells was slower than that in plasma. Particularly, it was found that the concentrations of artemisinin and artemether were presented in blood cells over longer time period than in plasma above their antimalarial IC50, which might result from both the affinity toward blood cells and the drugs clearance differences between blood cells and plasma. These results were indicated that the exposures and pharmacokinetic properties in the whole blood or the blood cells should be taken into account for the drug candidates with higher distribution affinity toward blood cells especially for the antimalarial drugs.

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BACKGROUND: The information about the dynamics of blood collection, components preparation and distribution in Iran was measured and compared during 2008-2012. STUDY DESIGNS AND METHODS: The survey instruments were based on collecting data from all 220 blood collections and blood processing centers over the country, registering them in the validated data base and reporting them to headquarter of Iranian Blood Transfusion Organization. RESULTS: Total blood collection increased during this period, and in 2012 represented a 12.6 percent increase compared to that in 2008. On average, red blood cells, fresh frozen plasma and platelet concentrate were prepared from 95.5 ± 2.4, 81 ± 3.8 and 47 ± 8.8 percent of all whole blood collection. From 2008 to 2011, the distribution of whole blood and fresh frozen plasma revealed different patterns. For whole blood, declines were noted, while for fresh frozen plasma increases were reported. In addition the distribution of red blood cells and platelet concentrate did not change considerably. Also between 2008 and 2012, the mean percentage of outdated and discarded units was 3.6 ± 1 and 5.2 ± 4.6. CONCLUSION: This study as a first national survey provides comprehensive information about the blood supply, components preparation and distribution, and helps to define strategy for the future.

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OBJECTIVE: Red blood cell distribution width (RDW) is a numerical measure, reported as part of a standard complete blood count, usually employed for differential diagnosis of anemic state. Some lines of evidence demonstrate that RDW associates with type 2 diabetes incidence and its complications. To further explore the role of RDW as predictor of abnormal glucose metabolism, we have analyzed the relationship between RDW and 2-hours plasma glucose concentration during an oral glucose tolerance test (OGTT). METHODS: Forty-five outpatients were enrolled for the present study. Participants underwent 75 g OGTT and measurements of hematological parameters. Cardiovascular disease risk factors (blood pressure, blood lipids, cigarette smoking, obesity) were evaluated by routine methods. RESULTS: In simple regression analysis 2-hours post-load glucose was directly associated with age (r = 0.36, p = 0.01), fasting glucose levels (r = 0.40, p = 0.002) and RDW (r = 0.31, p = 0.037). In multiple regression analysis fasting glucose, RDW, triglycerides and age significantly and independently predicted 2-hours plasma glucose (p <  0.01 for all coefficients). CONCLUSION: The present findings demonstrate that RDW associates with plasma glucose concentration after a 75-g oral glucose tolerance test. Our results highlight the role of RDW as predictor of glucose metabolism disturbance.

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BACKGROUND: The present study aimed to explore the association between RDW and CAS in patients with ischemic stroke, expecting to find a new and significant diagnosis index for clinical practice. METHODS: This cross-sectional study involves 432 consecutive patients with primary ischemic stroke (within 72 h). All subjects were confirmed by magnetic resonance imaging, and underwent physical examination, laboratory tests and carotid ultrasonography check. Finally, 392 patients were included according to the exclusion criteria. The odds ratios of independent variables were calculated using stepwise multiple logistic regression. RESULTS: Carotid intimal-medial thickness (IMT) and RDW are both significantly different between CAS group and control group. Univariate analyses show that high-sensitive C-reactive protein (Hs-CRP) and RDW (r=0.436) are both in significantly positive association with IMT. Stepwise multiple logistic regression shows that RDW is an independent protective factor of CAS in patients with ischemic stroke. Compared with the lowest quartile, the second to fourth quartiles are 1.13 (95% CI: 1.13-3.05), 2.02 (95% CI: 1.66-4.67), and 3.10 (95% CI: 2.46-7.65), respectively. CONCLUSION: The present study suggested that RDW level were higher than non-CAS in patients with primary ischemic stroke. Our results facilitated a bridge to connect RDW with ischemic stroke and further confirmed the role of RDW in the progression of the ischemic stroke.

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OBJECTIVES: Pharmacokinetic disposition of bortezomib in the blood has not been fully characterized in humans. This study aimed to evaluate the blood distribution of bortezomib and its kinetics in multiple myeloma patients. DESIGN AND METHOD: Eighteen multiple myeloma patients receiving bortezomib-dexamethasone combination therapy were enrolled. Blood specimens were drawn just before bortezomib administration on days 1 and 8 in the second and third cycles and after discontinuation. The relationships between bortezomib concentration and blood components were evaluated. RESULTS: Bortezomib concentration in the blood on day 1 was higher than that on day 8 in the second cycle. No difference was observed in bortezomib blood concentrations between day 8 in the second and third cycles. The bortezomib concentration in the blood and blood cells was 3- and 7-fold higher than that in plasma. Bortezomib concentration in the blood was correlated with the red blood cell count. The half-life of bortezomib in the blood was 23days. CONCLUSION: Bortezomib was taken up into red blood cells to only a limited extent and eliminated in parallel to the red blood cells' lifespan. The turnover of red blood cells can affect the pharmacokinetic disposition of bortezomib in multiple myeloma patients.

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