Characteristics of blood flow in microchannels and relevant impact on modelling blood behaviour in biochip separators

This paper reports a perspective investigation of computational modelling of blood fluid in microchannel devices as a preparation for future research on fluid-structure interaction (FSI) in biofluid mechanics. The investigation is carried out through two aspects, respectively on physical behaviours of blood flow in microchannels and appropriate methodology for modelling. The physics of blood flow is targeted to the challenges for describing blood flow in microchannels, including rheology of blood fluid, suspension features of red blood cells (RBCs), laminar hydrodynamic influence and effect of surface roughness. The analysis shows that due to the hyperelastic property of RBC and its comparable dimension with microchannels, blood fluid shows complex behaviours of two phase flow. The trajectory and migration of RBCs require accurate description of RBC deformation and interaction with plasma. Following on a discussion of modelling approaches, i.e. Eulerian method and Lagrangian method, the main stream modelling methods for multiphase flow are reviewed and their suitability to blood flow is analysed. It is concluded that the key issue for blood flow modelling is how to describe the suspended blood cells, modelled by Lagrangian method, and couple them with the based flow, modelled by Eulerian method. The multiphase flow methods are thereby classified based on the number of points required for describing a particle, as follows: (i) single-point particle methods, (ii) mutli-point particle methods, (iii) functional particle methods, and (iv) fluid particle methods. While single-point particle methods concentrate on particle dynamic movement, multipoint and functional particle methods can take into account particle mechanics and thus offer more detailed information for individual particles. Fluid particle methods provide good compromise between two phases, but require additional information for particle mechanics. For furthermore detailed description, we suggest to investigate the possibility using two domain coupling method, in which particles and base flow are modelled by two separated solvers. It is expected that this paper could clarify relevant issues in numerical modelling of blood flow in microchannels and induce some considerations for modelling blood flow using multiphase flow methods. © 2012 IEEE.

Assessment of dry weight by monitoring changes in blood volume during hemodialysis using Crit-Line.

BACKGROUND: Routine assessment of dry weight in chronic hemodialysis patients relies primarily on clinical evaluation of patient fluid status. We evaluated whether measurement of postdialytic vascular refill could assist in the assessment of dry weight. METHODS: Twenty-eight chronic, stable hemodialysis patients were studied during routine treatment sessions using constant dialysate temperature and dialysate sodium concentration, and relative changes in blood volume were monitored using Crit-Line III monitors throughout this study. The study was divided into three phases. Phase 1 studies evaluated the time-dependence of vascular compartment refill after completion of hemodialysis. Phase 2 studies evaluated the relationships in patient subgroups between intradialytic changes in blood volume and the presence of postdialytic vascular compartment refill during that last 10 minutes of hemodialysis after stopping ultrafiltration. Phase 3 studies evaluated the extent of dry weight changes following the application of a protocol for blood volume reduction, postdialytic vascular compartment refill, and correlation with clinical evidence of intradialytic hypovolemia and/or postdialytic fatigue. Phase 3 included anywhere from three to five treatments. RESULTS: Phase 1 studies demonstrated that despite interpatient variability in the magnitude of postdialytic vascular compartment refill, when significant refill was evident, it always continued for at least 30 minutes. However, the majority of refill took place within 10 minutes postdialysis. Phase 2 studies identified 3 groups of patients: those who exhibited intradialytic reductions in blood volume but not postdialytic vascular compartment refill (group 1), those who exhibited intradialytic reductions in blood volume and postdialytic vascular compartment refill (group 2), and those whose blood volume did not change substantially during hemodialysis treatment (group 3). In phase 3 studies, use of an ultrafiltration protocol for blood volume reduction and monitoring of postdialytic vascular compartment refill combined with clinical assessment of hypovolemia and postdialytic fatigue demonstrated that patients often had a clinical dry weight assessment which was too low or too high. In all 28 patients studied, dry weight was either increased or decreased following use of this protocol. CONCLUSION: Determination of the extent of both intradialytic decreases in blood volume and postdialytic vascular compartment refill, combined with clinical assessment of intradialytic hypovolemia and postdialytic fatigue, can help assess patient dry weight and optimize volume status while reducing dialysis associated morbidity. The number of hospital admissions due to fluid overload may be reduced.

Effect of high dietary starch levels on the growth performance, blood chemistry and body composition of gibel carp (Carassius auratus var. gibelio)

An 8-week growth trial was carried out in a semi-recirculation system to investigate the effect of high dietary starch levels on the growth performance, blood chemistry, starch utilization and body composition of gibel carp (Carassius auratus var. gibelio). Five isonitrogenous and isocarloric experimental diets were formulated to contain different starch levels (24%, 28%, 32%, 36% and 40% respectively). Triplicate groups of fish (24 fish per tank with an average body weight, of 8.5 g) were assigned to each diet. The results showed that dietary carbohydrate levels significantly affected the growth performance, hepatopancreatic lipid content, pyruvate kinase (PK) activity and whole-body lipid content. Growth performance, body crude lipid and plasma glucose concentrations showed a decreasing trend with an increase in dietary starch from 24% to 40%. Pyruvate kinase activities and hepatopancreatic lipid content showed an increasing trend with the dietary starch increasing from 24% to 32%, and then a decreasing trend with the dietary starch increasing from 32% to 40%. No significant difference in the hepatopancreatic hexokinase (HK) activity, plasma triglyceride contents, body crude protein, ash and calcium (Ca) and phosphorus (P) contents was observed between different treatments. In conclusion, higher dietary starch levels (32-40%) significantly (P < 0.05) decreased the growth of gibel carp in the present study.

Plasma biochemical responses of the planktivorous filter-feeding silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) to prolonged toxic cyanobacterial blooms in natural waters

The planktivorous filter-feeding silver carp (Hypophthalmichthys molitrix) and bighead carp (Aristichthys nobilis) are the attractive candidates for bio-control of plankton communities to eliminate odorous populations of cyanobacteria. However, few studies focused on the health of such fishes in natural water body with vigorous toxic blooms. Blood parameters are useful and sensitive for diagnosis of diseases and monitoring of the physiological status of fish exposed to toxicants. To evaluate the impact of toxic cyanobacterial blooms on the planktivorous fish, 12 serum chemistry variables were investigated in silver carp and bighead carp for 9 months, in a large net cage in Meiliang Bay, a hypereutrophic region of Lake Taihu. The results confirmed adverse effects of cyanobacterial blooms on two phytoplanktivorous fish, which mainly characterized with potential toxicogenomic effects and metabolism disorders in liver, and kidney dysfunction. In addition, cholestasis was intensively implied by distinct elevation of all four related biomarkers (ALP, GGT, DBIL, TBIL) in bighead carp. The combination of LDH, AST activities and DBIL, URIC contents for silver carp, and the combination of ALT. ALP activities and TBIL, DBIL. URIC concentrations for bighead carps were found to most strongly indicate toxic effects from cyanobacterial blooms in such fishes by a multivariate discriminant analysis. (C) 2009 Elsevier B.V. All rights reserved.

Molecular identification and expression analysis of tumor necrosis factor receptor-associated factor 2 in grass carp Ctenopharyngodon idella

Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a crucial component of almost the entire tumor necrosis factor receptor superfamily signaling pathway. In the present study, a TRAF2 gene has been cloned from grass carp (Ctenopharyngodon idella) by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. The full-length cDNA is 3162 bp, including a 60 bp 5' untranslated region (UTR), a 1611 bp open reading frame, and a 1491 bp 3' UTR. The polyadenylation signal (AATAAA) and the mRNA instability motifs (ATTTTA, ATTTA) were followed by a poly(A) tail in the 3' UTR. No signal peptide or transmembrane region has been found in the putative amino acids of grass carp TRAF2 (gcTRAF2). Phylogenetic tree analysis clearly showed that gcTRAF2 is nearest to the TRAF2 gene of goldfish. The identity of gcTRAF2 with its homologs in other vertebrates ranges from 56% to 97%. It is characterized by one RING-type signature at the N-terminus, one zinc finger in the middle part, and one conserved TRAF domain consisting of a C-proximal (TRAF-C) subdomain and a N-proximal (TRAF-N) subdomain. The identity of TRAF-C among all TRAF2 homologs in vertebrates varies from 78% to 97%, whereas the identity of TRAF-N ranges from 56% to 100%. The recombinant gcTRAF2 has been expressed in Escherichia coli using pET-32a expression vector. The rabbit anti-gcTRAF2 polyclonal antibody was obtained. The expression of gcTRAF2 in different organs was examined by real-time quantitative polymerase chain reaction and Western blot analysis. It was widely distributed in heart, head kidney, thymus, brain, gill, liver, spleen, and trunk kidney. This is the first report of a TRAF2 homolog molecule in fish.

Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo

The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc.

Prenatal exposures to persistent organic pollutants as measured in cord blood and meconium from three localities of Zhejiang, China

Prenatal exposures to persistent organic pollutants were assessed using the levels of PCBs and organochlorine pesticides (OCPs) measured in cord blood and meconium samples from Luqiao and two other localities of the Zhejiang province in China. Luqiao is a town with the largest site for disassembly of PCB-containing obsolete transformers and electrical waste in China. The other two localities Pingqiao (100 km NW of Luqiao) and Lin'an (500 km NW of Luqiao) are towns without known electronic or electrical waste sites. A total of 23 PCB congeners (including 12 dioxin-like) and 6 OCPs were measured using the traditional GC-mu ECD technique. Micro-EROD bioassay was additionally used to measure TCDD-based TEQ levels of the 12 dioxin-like PCBs. Significant correlations were found between the TEQs measured by the two methods, supporting the application of micro-EROD as a practical toot for complementing the chemical analysis. The data showed that beta-HCH, p,p'-DDE, and 6 PCB congeners (101, 138 153, 180, 183, and 187) were the predominant pollutants, with PCB 138 being the best indicator (predictor) for total PCB levels. Cord blood and meconium from Luqiao have higher levels of PCBs than those from the other two localities, suggesting that a disassembly site for electronic and electric waste would provide an environment for greater exposure to these chemicals. The cord blood or meconium levels of beta-HCH, though likewise considerably high, were comparable in the three localities. Similar findings were observed for p,p'-DDE. Pollution by these OCPs might have come from past use of agricultural pesticides in the three localities. (c) 2007 Published by Elsevier B.V.

The first non-mammalian CXCR3 in a teleost fish: Gene and expression in blood cells and central nervous system in the grass carp (Ctenopharyngodon idella)

A novel fish chemokine receptor gene, chemokine (C-X-C motif) receptor 3 (CXCR3)-like was isolated from the grass carp Ctenopharyngodon idella , with its full-length genomic sequence. The cDNA of grass carp CXCR3-like (gcCXCR3-like) consists of 1261 bp with a 49bp 5'-UTR and a 189 bp 3'-UTR. An open reading frame of 1023 bp encodes a 341-amino acid peptide, with seven transmembrane helices. The deduced amino acid sequence showed the same sequence identities (37.8%) with its counterparts in goat and human. The gcCXCR3-like gene consists of two exons, with one intervening intron, spaced over approximately 2 kb of genomic sequence. Phylogenetic analyses clearly demonstrated that the gcCXCR3-like resembles the CXCR3s of other vertebrates. Real-time PCR analysis showed that gcCXCR3-like was expressed in all tested organs except heart and the expression level of gcCXCR3-like was highest in brain. Flow cytometric analyses showed the positive rate of labelled leukocytes from the healthy grass carp was 17.3%, and the labelled leukocytes were divided into three types by cell sorting. Immunohistochemical localization revealed that gcCXCR3-like expressed in whole brain regions including cerebel, diencephalon, medulla oblongata, optic lobe, and rhinencephalon, and that the labelled leukocytes are actually populations of monocyte and/or phagocyte, lymphocyte and the granulocyte. It is considered that fish CXCR expression and their function may need to be investigated in both nervous and immune systems. (c) 2006 Elsevier Ltd. All rights reserved.

Redescription of Trypanosoma ophiocephali Chen 1964 (Kinetoplastida : Trypanosomatina : Trypanosomatidae) and first record from the blood of dark sleeper (Odontobutis obscura Temminck and Schlegel) in China

During the parasite fauna investigation within 2004 and 2005, the freshwater fish trypanosomes were isolated from the blood of dark sleeper (Odontobutis obscura Temminck and Schlegel) and snakehead fish (Ophiocephalus argus Cantor) from Niushan Lake, Hubei Province, China. Blood trypomastigotes were used for light microscopy investigations. The detailed descriptions of three morphological groups of the genus Trypanosoma: Trypanosoma sp. I and Trypanosoma sp. II found in blood of O. obscura, and Trypanosoma sp. III found in blood of O. argus were provided. Morphological features and host species show Trypanosoma sp. III belong to Trypanosoma ophiocephali Chen 1964, an incompletely described species. Infection with trypanosomes of O. obscura was recorded for the first time. According to the size and appearance, the trypanosomes in O. obscura were also tentatively identified as T. ophiocephali Chen 1964.

Evidence of host blood feeding by the monogenean, Ancyrocephalus mogurndae (Monogenea : Ancyrocephalidae) from the gills of the mandarin fish, Siniperca chuatsi

By examining iron contents, it is demonstrated that the monogenean Ancyrocephalus mogurndae (Yamaguti, 1940) feeds on the blood of its host, the mandarin fish Siniperca chuatsi (Basilewsky). The iron content and then the quantity of blood necessary to produce this amount of iron are found different in young and fully-matured worms. Young worms contain higher levels of iron and estimated amount of blood. It is suggested that A. mogurndae may start to feed on host blood as attached on gills, and the amount of blood ingested by young worms may vary from 0.01 to 1.00 mu l before reproduction. The difference between young and fully-matured worms may be accounted for by the elimination of haematin and change of food composition in matured worms and may also be affected by reproduction. Experimental infections of the monogenean may provide supportive information for explaining the difference, and further studies should also examine the effect of immune components in host blood ol mucus on the intestines of the parasite.

The Influence of Age and Sex on the Cell Counts of Peripheral Blood Leukocyte Subpopulations in Chinese Rhesus Macaques

therapeutic drugs, vaccines and mechanisms of human diseases. Little is known about the normal levels of leukocyte subpopulations of Chinese rhesus macaques. To obtain these data, 100 blood samples from Chinese rhesus macaques were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, monocytes, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs), were quantitatively analyzed by flow cytometry through BD trucount tubes. The influence of age and sex on the cell counts of leukocyte subpopulations was analyzed. The counts of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and B cells decreased with age, but those of monocytes, mDCs and pDCs had no significant correlation with age. Significant differences existed in the cell counts of most leukocyte subpopulations between the male and female groups except pDCs. Furthermore the values of the females were higher than those of the males. The study provided basic information about the leukocyte subpopulations of Chinese rhesus macaques, and it may be valuable for immunobiological study of Chinese rhesus macaques. Cellular & Molecular Immunology. 2009;6(6):433-440.

Experimental verification of therapeutic doses for the superficially-placed tumor radiotherapy with heavy ions at HIRFL

Up to now, clinical trials of heavy-ion radiotherapy for superficially placed tumors have been carried out for six times and over 60 selected patients have been treated with 80—100 MeV/u carbon ions supplied by the Heavy Ion Research Facility in Lanzhou (HIRFL) at the Institute of Modern Physics, Chinese Academy of Sciences since November, 2006. A passive irradiation system and a dose optimization method for radiotherapy with carbon-ion beams have been developed. Experimental verification of longitudinally ...