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Blood Stream (blood + stream)
Terms modified by Blood Stream Selected AbstractsInsulin resistance in type 2 diabetes: role of fatty acids,DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002Peter Arner Abstract Insulin resistance is one of the key factors responsible for hyperglycaemia in type 2 diabetes and can result in a number of metabolic abnormalities associated with cardiovascular disease (insulin resistance syndrome), even in the absence of overt diabetes. The mechanisms involved in the development of insulin resistance are multifactorial and are only partly understood, but increased availability of free fatty acids (FFAs) is of particular importance for the liver and skeletal muscle. The role of FFAs in type 2 diabetes is most evident in obese patients who have several abnormalities in FFA metabolism. Because of a mass effect, the release of FFAs from the total adipose tissue depot to the blood stream is increased and the high concentration of circulating FFAs impairs muscle uptake of glucose by competitive inhibition. In upper-body obesity, which predisposes individuals to type 2 diabetes, the rate of lipolysis is accelerated in visceral adipose tissue. This results in a selective increase in FFA mobilisation to the portal vein, which connects visceral fat to the liver. A high ,portal' FFA concentration has undesirable effects on the liver, resulting in dyslipidaemia, hyperinsulinaemia, hyperglycaemia and hepatic insulin resistance. Recently, a new class of antidiabetic agents, the thiazolidinediones (TZDs) or ,glitazones' has been developed. A prominent effect of these agents is the lowering of circulating FFA levels and it is believed, but not yet proven, that this interaction with FFAs constitutes a major mechanism behind the glucose-lowering effect of the TZDs. Copyright © 2002 John Wiley & Sons, Ltd. [source] The Hek outer membrane protein of Escherichia coli is an auto-aggregating adhesin and invasinFEMS MICROBIOLOGY LETTERS, Issue 2 2007Robert P. Fagan Abstract Escherichia coli is the principal gram-negative causative agent of sepsis and meningitis in neonates. The pathogenesis of meningitis due to E. coli K1 involves mucosal colonization, transcytosis of epithelial cells, survival in the blood stream and eventually invasion of the meninges. The latter two aspects have been well characterized at a molecular level in the last decade. Less is known about the early stages of pathogenesis, i.e. adhesion to and invasion of gastrointestinal cells. Here, the characterization of the Hek protein is reported, which is expressed by neonatal meningitic E. coli (NMEC) and is localized to the outer membrane. It is demonstrated that this protein can cause agglutination of red blood cells and can mediate autoaggregation. Escherichia coli expressing this protein can adhere to and invade epithelial cells. So far, this is the first outer membrane protein in NMEC to be directly implicated in epithelial cell invasion. [source] Kinetic studies during peripheral blood stem cell collection show CD34+ cell recruitment intra-apheresisJOURNAL OF CLINICAL APHERESIS, Issue 3 2001Lene Meldgaard Knudsen Abstract A sufficient number of CD34+ cells in the peripheral blood stem cell product is important to achieve a rapid and sustained engraftment. The purpose of the present work was to study CD34+ cell kinetics during leukapheresis. Blood samples before and after leukapheresis were analysed for CD34+ cells in 205 procedures. The number of CD34+ cells after plus the number of CD34+ cells harvested was 1.5-fold greater than the number available at the beginning of the procedure, indicating recruitment of CD34+ cells during leukapheresis. In a subgroup of 66 procedures, granulocytes and platelets were measured. In contrast to CD34+ cells, these cell fractions were not recruited to the blood stream during leukapheresis. An additional nine patients were studied with serial blood measurements during leukapheresis, showing an initial decline that was followed by an increase in CD34+ cells during leukapheresis. In conclusion, CD34+ cells are recruited to the blood during the leukapheresis procedure in contrast to granulocytes and platelets. J. Clin. Apheresis. 16:114,119, 2001. © 2001 Wiley-Liss, Inc. [source] Quantitative temporal and spatial distribution of adenovirus type 2 correlates with disease manifestations and organ failure during disseminated infectionJOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Dirk Forstmeyer Abstract Disseminated adenovirus (HAdV) infections are serious complications in allogenic stem cell transplant (SCT) recipients. Quantitative HAdV DNA detection in blood samples demonstrated the association of high virus loads with disease and improved early diagnosis. However, the pathogenesis of disseminated HAdV disease, for example sources of HAdV DNA shedding in the blood stream and association of HAdV replication sites with disease manifestations, remained obscure. In this report, 24 bioptic and autoptic organ and tissue samples of an adult SCT recipient suffering from disseminated infection were quantitatively analyzed for HAdV DNA. Results indicate subsequent virus replication in the colon, bone marrow and liver as origin of HAdV DNAemia, which increased from 1.4,×,104 copies/ml to a peak of 2,×,109 copies/ml over a period of 84 days in spite of antiviral therapy. Symptoms as diarrhoea, bone marrow failure and hepatic failure were clearly linked to high HAdV DNA concentrations in affected organs. For example, the HAdV DNA level was 2.2,× 103 copies/cell in a colon biopsy when the patient suffered from diarrhoea whereas only 1.1,× 101 copies/cell were detected when symptoms had improved. Focal HAdV infection of the liver as demonstrated by laser microdissection was followed by fulminant virus replication with 1.3,×,105 copies of HAdV DNA/cell causing terminal hepatic failure. In conclusion, pathogenesis of disseminated HAdV disease was associated with virus replication in affected organs and not immune mediated as suggested recently by a fatal case of gene therapy with a non-replication competent HAdV-C5 vector. J. Med. Virol. 80:294,297, 2008. © 2007 Wiley-Liss, Inc. [source] Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregatesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2009Rui Yang Abstract Chitosan-modified paclitaxel-loaded poly lactic- co -glycolic acid (PLGA) nanoparticles with a mean diameter of 200,300 nm in distilled water were prepared by a solvent evaporation method. The mean diameter increased dramatically in contact with the mouse (CDF1) plasma, as a function of chitosan concentration in the modification solution (e.g., 2670.5 nm for 0.7% chitosan-modified nanoparticles, NP3), but reverted to almost its original size (i.e., 350.7 nm for NP3) following 5 min of gentle agitation. The zeta potential of PLGA nanoparticles was changed to positive by the chitosan modification. The in vitro uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell line (A549) were significantly increased by the modification. Most importantly, a lung-specific increase in the distribution index of paclitaxel (i.e., AUClung/AUCplasma) was observed for chitosan-modified nanoparticles (e.g., 99.9 for NP3 vs. 5.4 for TaxolÔ) when nanoparticles were administered to lung-metastasized mice via the tail vein at a paclitaxel dose of 10 mg/kg. Transient formation of aggregates in the blood stream followed by enhanced trapping in the lung capillaries, and electrical interaction-mediated enhanced uptake across the endothelial cells of the lung tumor capillary appear to be responsible for the lung-tumor-specific distribution of the chitosan modified nanoparticles. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:970,984, 2009 [source] Quantification of the expression level of integrin receptor ,v,3 in cell lines and MR imaging with antibody-coated iron oxide particlesMAGNETIC RESONANCE IN MEDICINE, Issue 4 2006Sabrina Benedetto Abstract Targeted imaging requires site-specific accumulation of a contrast agent (CA), and the properties of that agent must be selected according to the abundance of the target to obtain a signal above the detection limit of the instrument. However, numerical estimates of receptors per cell are rarely found in the literature. Integrin receptors would be particularly promising targets because of their accessibility from the blood stream and expression on activated neovascular endothelial cells. We systematically estimated the number of integrin receptors of cell lines and primary cells by flow cytometry analysis. Since integrin receptors are heterodimeric molecules, and ,v forms complexes with various , subunits, the numbers of ,v and ,3 subunits are therefore dissimilar. The observed values are 3 · 103,1.4 · 104/cell for ,v, and 5.3 · 102,1.1 · 104/cell for ,3. Despite the low number of exposed receptors, we show that up to single-cell MR visualization can be achieved with the use of iron oxide beads complexed with antibodies as CAs. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Xenon-129 MR imaging and spectroscopy of rat brain using arterial delivery of hyperpolarized xenon in a lipid emulsionMAGNETIC RESONANCE IN MEDICINE, Issue 2 2001Guillaume Duhamel Abstract Hyperpolarized 129Xe dissolved in a lipid emulsion constitutes an NMR tracer that can be injected into the blood stream, enabling blood-flow measurement and perfusion imaging. A small volume (0.15 ml) of this tracer was injected in 1.5 s in rat carotid and 129Xe MR spectra and images were acquired at 2.35 T to evaluate the potential of this approach for cerebral studies. Xenon spectra consistently showed two resonances, at 194.5 ppm and 199.0 ppm relative to the gas peak. The signal-to-noise ratio (SNR) obtained for the two peaks was sufficient (ranging from 12 to 90) to follow their time courses. 2D transverse-projection xenon images were obtained with an in-plane resolution of 900 ,m per pixel (SNR range 8,15). Histological analysis revealed no brain damage except in two rats that had received three injections. Magn Reson Med 46:208,212, 2001. © 2001 Wiley-Liss, Inc. [source] Responsiveness of rabbits to superovulation treatment by a single injection of follicle-stimulating hormone with aluminum hydroxide gelMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2007Shu Hashimoto Abstract Aluminum hydroxide gel (Al-gel), which is used as an adjuvant, can absorb macromolecules. We investigated the applicability of Al-gel to the sustained release of follicle-stimulating hormone (FSH) as a simplified method of superovulation (SOV) in rabbits. The responsiveness of rabbits to SOV by a single injection of FSH dissolved in Al-gel suspension (3.2 mg Al/ml) and in 10% (w/v) polyvinylpyrrolidone (PVP), and by multiple injections of FSH in saline was examined. The numbers of total and fertilized eggs recovered from rabbits treated with FSH in Al-gel (40.5 and 26.3, respectively) were similar to multiple injections (47.4 and 28.6, respectively) and were significantly greater (P,<,0.05) than single injection of FSH with PVP (17.3 and 11.5, respectively). We also compared the plasma FSH levels of rabbits which were induced SOV by multiple or a single injection of Al-gel. Al-gel provided sustained release of FSH to the blood stream at a high enough dose for SOV. Moreover, the developmental competence of the pups of DNA-injected embryos from rabbits treated with a single injection of FSH mixed with Al-gel (18%) was similar to that of DNA-injected embryos, recovered from rabbits treated with FSH dissolved in saline (21%). Two transgenic pups were obtained from embryos recovered from rabbits by a single injection of FSH with Al-gel. These results indicate that a single injection of FSH with Al-gel is an effective method for SOV of rabbit and that this technique is applicable to research requiring large numbers of rabbit embryos such as the production of transgenic rabbits. Mol. Reprod. Dev. 74: 1208,1212, 2007. © 2007 Wiley-Liss, Inc. [source] Risk factors for nosocomial intensive care infection: a long-term prospective analysisACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2001P. Appelgren Background: To identify risk factors for nosocomial infection in intensive care and to provide a basis for allocation of resources. Methods: Long-term prospective incidence study of risk factors for nosocomial infection in the surgical-medical intensive care unit of a university hospital. Results: A total of 2671 patients were admitted during four years, and 562 of 574 patients staying >48 h were observed during 4921 patient days (median length of stay 5 days, range 2,114). Of these, 196 (34%) patients had 364 nosocomial infections after median 8,10 days, an infection rate of 14/100 admissions. Infection prolonged length of stay 8,9 days and doubled the risk of death. The infections were 17% blood stream, 26% pneumonias, 34% wound, 10% urinary tract and 13% other infections. The incidence of bloodstream infection declined significantly during the study years, from 12% to 5%. In multiple regression analysis, the important variables for infection were central venous catheter, mechanical ventilation, pleural drainage and trauma with open fractures. High age, immunosuppression and infection on admission did not influence the risk of acquiring infection. Trauma patients constituted 24% of the study population. Trauma with open fractures increased the risk of infection more than twice (P=0.003), mainly due to wound infections. Conclusion: Trauma cases, with open fractures, were the patients most at risk of infection, despite low disease severity scores. Resources to prevent nosocomial infection should be allocated to these patients. [source] Accelerator mass spectrometry offers new opportunities for microdosing of peptide and protein pharmaceuticalsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2010Mehran Salehpour Accelerator Mass Spectrometry (AMS) is an ultra-sensitive analytical method which has been instrumental in developing microdosing as a strategic tool in early drug development. Considerable data is available for AMS microdosing using typical pharmaceutical drugs with a molecular weight of a few hundred Daltons. The so-called biopharmaceuticals such as proteins offer interesting possibilities as drug candidates; however, experimental data for protein microdosing and AMS is scarce. The analysis of proteins in conjunction with early drug development and microdosing is overviewed and three case studies are presented on the topic. In the first case study AMS experimental data is presented, for the measured concentration of orally administered recombinant insulin in the blood stream of laboratory rabbits. Case study 2 concerns minimum sample size requirements. AMS samples normally require about 1,mg of carbon (10,µL of blood) which makes AMS analysis unsuitable in some applications due to the limited availability of samples such as human biopsies or DNA from specific cells. Experimental results are presented where the sample size requirements have been reduced by about two orders of magnitude. The third case study concerns low concentration studies. It is generally accepted that protein pharmaceuticals may be potentially more hazardous than smaller molecules because of immunological reactions. Therefore, future first-in-man microdosing studies might require even lower exposure concentrations than is feasible today, in order to increase the safety margin. This issue is discussed based on the current available analytical capabilities. Copyright © 2010 John Wiley & Sons, Ltd. [source] Vasculogenesis of the embryonic heart: Origin of blood island-like structuresTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 3 2006Anna Ratajska Abstract The earliest vascular structures (blood island-like) in the embryonic heart are clusters of angioblasts and nucleated red blood cells (NRBCs), which differentiate into endothelial cells and erythrocytes, respectively. Our purpose was to define the area and chronology of NRBC appearance in the mouse embryonic heart at the stages before a patency between coronary vessels and peripheral circulation is established (10.5,13.5 dpc). Before and at the onset of vascularization, NBCs were not present within the proepicardium; however, Ter/119+ differentiating erythroblasts and single scattered CD45+ were found in the heart beginning from 10.5 dpc. The Ter/119+ cells were in close apposition to angioblasts (PECAM1+) and were recognized as components of blood island-like structures or vascular vesicles in transmission electron microscope and were located mostly in the subepicardium. Some of the NRBCs were not accompanied by angioblasts and located close to the endocardial endothelium or at the border of the endocardial endothelium or in the subepicardium. These erythroblasts were beginning to assemble with angioblasts. CD34+ NBCs as well as progenitor cells of erythroid lineage were not detected in the heart at these stages of development. The state of differentiation of NRBCs of blood islands was similar/the same as the morphology of circulating blood cells at the respective stages of embryo development. The presence of mature NRBCs in the subendocardial area and lack of progenitor cells of erythroid lineage within the heart indicate that erythroid commitment occurs outside the heart. We suggest that NRBCs enter the heart from the blood stream at 10.5,12 dpc independently from angioblasts. © 2006 Wiley-Liss, Inc. [source] Structural and Histochemical Studies on the Teleostean Bulbus ArteriosusANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2009I. L. Leknes Summary The structure and histochemical properties of the bulbus arteriosus in two species from an evolutionary old teleost family, Characidae, and in three modern teleosts, family Cichlidae, are described. The bulbar wall was composed of an outer layer, a middle layer and a strongly folded inner layer covered by a thick, granule-rich endothelial cell layer towards the lumen. One of the cichlid species (Thorichthys meeki) was injected intraperitoneally with horse ferritin; the endothelial cell layer of the heart atrium and ventricle displayed high ability to endocytose ferritin particles from the blood stream, but the corresponding layer in the bulbus arteriosus displayed no such uptake. This finding suggests that the bulbar endothelial cell layer plays no scavenger or immunological blood cleansing roles in this species. The bulbar endothelial cell granules were strongly coloured by periodic acid,Schiff (PAS) in the present cichlids, but weakly coloured by PAS in the present characids. These cell layers were uncoloured by alkaline carmine in ethanol in both cichlids and characids. The negative carmine test combined with a positive PAS test for the bulbar endothelial cell layer in the present cichlids indicates that these cells contain only small amounts of polysaccharides. The weak PAS-colouring for the bulbar endothelial cell layer in characids indicates a very low content of sugars in these cells. These findings together with the fact that this cell layer in the present cichlids and characids was nearly uncoloured when treated with orcein, Heidenhain's Azan or Schmorl's solutions for elastic materials suggest that the bulbar endothelial granules do not play any role in the blood cleansing or in the rebuilding or maintenance of the ground substance or elastic material in the bulbar wall. Probably, the granules in the bulbar endothelial cell layer in the present species contain mainly proteins, connected to some PAS-positive polysaccharides to enhance their solubility. [source] SYMPOSIUM: Clearance of A, from the Brain in Alzheimer's Disease: A,-Degrading Enzymes in Alzheimer's DiseaseBRAIN PATHOLOGY, Issue 2 2008James Scott Miners Abstract In Alzheimer's disease (AD) A, accumulates because of imbalance between the production of A, and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of A, is partly, if not in some cases solely, because of defects in its removal,mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading A,. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced A,-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading A,in vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOE,4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to A, plaque load. Up-regulation of some A,-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other A,-clearance pathways, reductions in the activity of particular A,-degrading enzymes may become critical, leading to the development of AD and CAA. [source] EARLY ACTIVATION OF INTERNAL MEDIAL SMOOTH MUSCLE CELLS IN THE RABBIT AORTA AFTER MECHANICAL INJURY: RELATIONSHIP WITH INTIMAL THICKENING AND PHARMACOLOGICAL APPLICATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006Huguette Louis SUMMARY 1Smooth muscle cells (SMC) participate in both inflammatory and dedifferentiation processes during atherosclerosis, as well as during mechanical injury following angioplasty. In the latter, we studied medial SMC differentiation and inflammation processes implicated early after de-endothelialization in relation to mechanical stresses. We hypothesized that activation of a subpopulation of SMC within the media plays a crucial role in the early phase of neointimal formation. 2For this purpose, we used a rabbit model of balloon injury to study activation and differentiation of medial SMC in the early time after denudation and just before neointima thickening. Inflammation was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1, integrin a4b1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2 antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used as markers of differentiation. 3On day 2 after de-endothelialization, VCAM-1, a4b1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of the internal part of the media, in the vicinity of the blood stream. At the same time, the majority of SMC throughout the media expressed non-muscle myosin heavy chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared, SMC of the media were no longer activated, whereas some intimal SMC expressed the activation markers. Thus, after de-endothelialization, early dedifferentiation occurs in most of the medial SMC, whereas activation concerned only a subpopulation of SMC located in the internal media. Using the T-type voltage-operated calcium channel blocker mibefradil (0.1,1 mmol/L) in SMC culture, we showed that this agent exhibited an antiproliferative effect in a dose-dependant manner only on undifferentiated cells. 4In conclusion, the results suggest that the activated SMC represent cells that are potentially able to migrate and participate in the intimal thickening process. Thus, the medial SMC inflammatory process, without any contribution of inflammatory cells, may represent a major mechanism underlying the development of intimal thickening following mechanical stress. In humans, inhibition of T-type calcium channels may be a tool to prevent the early proliferation step leading to neointimal formation. [source] Lipophilicity affects the pharmacokinetics and toxicity of local anaesthetic agents administered by caudal blockCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Alejandro A Nava-Ocampo Summary 1.,Drugs administered into the epidural space by caudal block are cleared by means of a process potentially affected by the lipophilic character of the compounds. 2.,In the present study, we examined the relationship between the octanol,water partition coefficient (log Poct) and the time to reach the maximum plasma drug concentration (tmax) of lignocaine, bupivacaine and ropivacaine administered by caudal block in paediatric patients. We also examined the relationship between log Poct and the toxicity of these local anaesthetic agents in experimental models. The tmax and toxicity data were obtained from the literature. 3.,Ropivacaine, with a log Poct of 2.9, exhibited a tmax of 61.6 min. The tmax of lignocaine, with a log Poct of 2.4, and bupivacaine, with a log Poct of with 3.4, were approximately 50% shorter than ropivacaine. At log Poct of approximately 3.0, the toxicity of these local anaesthetic agents was substantially increased. The relationship between log Poct and the convulsive effect in dogs was similar to the relationship between log Poct and the lethal dose in sheep. 4.,With local anaesthetic agents, it appears that the relationship between log Poct and drug transfer from the epidural space to the blood stream is parabolic, being the slowest rate of transference at log Poct 3.0. Toxicity, due to plasma availability of these local anaesthetic agents, seems to be increased at log Poct equal or higher than 3.0 secondary to the highest transfer from plasma into the central nervous system. [source] | ||||||||||||||||