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Sample records for pk system blood

  1. One hundred cases of laparoscopic subtotal hysterectomy using the PK and Lap Loop systems.

    Science.gov (United States)

    Erian, John; El-Toukhy, Tarek; Chandakas, Stefanos; Theodoridis, Theo; Hill, Nicholas

    2005-01-01

    To evaluate the safety and short-term outcomes of laparoscopic subtotal hysterectomy using the PK and Lap Loop systems. Prospective observational study (Canadian Task Force classification II-2). Princess Royal University and Chelsfield Park Hospitals, Kent, UK. One hundred women who underwent laparoscopic subtotal hysterectomy for menorrhagia from February 2003 through July 2004. The procedure was performed using the Plasma Kinetic (PK) system to seal the vascular pedicles and the Lap Loop system to separate the uterus at the level of the internal os. The uterus was removed from the abdominal cavity mainly by morcellation or posterior colpotomy. Of 100 patients, 59 were operated on as outpatients. Mean patient age was 44.6 years, median parity was 2, mean body mass index was 26.8, and mean duration of symptoms was 4 years. Clinically, the uterus was enlarged in 70 patients, and preoperative ultrasound scanning suggested the presence of uterine myomas in 42 patients. In addition to hysterectomy, 47 patients had concomitant pelvic surgery. The mean total operating time was 45.5 minutes, and mean estimated blood loss was 114 mL. The overall major complication rate was 2%; two patients required blood transfusion after surgery. There were no bowel or urinary tract injuries, unintended laparotomy, return to operating room, or anesthetic complications. At follow-up, all patients were satisfied with surgery. Laparoscopic subtotal hysterectomy using the PK and Lap Loop systems for treatment of therapy-resistant menorrhagia is safe, can be performed as an outpatient procedure, and is associated with reduced operating time and high patient satisfaction.

  2. Adequate & Equitable U.S. PK-12 Infrastructure: Priority Actions for Systemic Reform. A Report from the Planning for PK-12 School Infrastructure National Initiative

    Science.gov (United States)

    Filardo, Mary; Vincent, Jeffrey M.

    2017-01-01

    To formulate a "systems-based" plan to address the PK-12 infrastructure crisis, in 2016, the 21st Century School Fund (21CSF) and the University of California-Berkeley's Center for Cities + Schools (CC+S), in partnership with the National Council on School Facilities and the Center for Green Schools at the U.S. Green Building Council,…

  3. Seizing the Opportunity: Building PK3 Systems in New Jersey's School Districts. Policy Brief

    Science.gov (United States)

    Rice, Cynthia

    2008-01-01

    This policy brief discusses how the implementation of high quality preschool required by the expansion initiative can set the stage for a more expansive view of the first stage of children's education: the development of a preschool-through third-grade (PK3) system. By adopting a broader view of early childhood education as a period extending from…

  4. Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats.

    Science.gov (United States)

    Matsui, Ryutaro; Hattori, Ryutaro; Usami, Youhei; Koyama, Masumi; Hirayama, Yuki; Matsuba, Emi; Hashimoto, Yukiya

    2018-02-01

    We have recently found an H + /quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H + /lipophilic cation antiport system is expressed in porcine LLC-PK 1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK 1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK 1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK 1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK 1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H + /lipophilic cation antiport system is expressed in the apical membrane of LLC-PK 1 cells. Moreover, the H + /lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  5. Bessong, PK

    African Journals Online (AJOL)

    Bessong, PK. Vol 11, No 2 (2012) - Articles The Accounting Implication of Cultural Dimensions on Financial Reporting: A Study of Selected Manufacturing Companies in Nigeria Abstract PDF · Vol 11, No 2 (2012) - Articles Human Resource Valuation and the Performance of Selected Banks in Nigeria Abstract PDF.

  6. Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

    OpenAIRE

    Westerhout, J.

    2014-01-01

    In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in human cerebrospinal fluid (CSF) are used as a surrogate for human brainECF concentrations. Due to qualitative and quantitative differences in processes that govern the pharmacokinetics (PK) of drugs in...

  7. In vivo evaluation in mice and metabolism in blood of human volunteers of [123I]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation

    International Nuclear Information System (INIS)

    Dumont, F.; Vos, F. de; Slegers, G.; Versijpt, J.; Jansen, H.M.L.; Dierckx, R.A.; Korf, J.

    1999-01-01

    We report the in vivo evaluation (biodistribution, displacement and metabolization in blood, brain and heart) in mice and the metabolism in blood of human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide ([ 123 I]iodo-PK11195), a potential radioligand for visualization of inflammation in humans by single-photon emission tomography. In three series of 18 white mice (NMRI, 20-25 g), the concentration of radioactivity was measured during 48 h. Blood samples were taken, organs and intestines were excised, excretion was collected and all tissues were weighed and counted for radioactivity. The tissue uptake of radioactivity was measured as % of the injected activity/g of tissue. The excretion was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [ 123 I]iodo-PK11195 in the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK11195, there was a decrease in accumulation in the latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was performed using high-performance liquid chromatography (HPLC). First, the extraction yield of [ 123 I]iodo-PK11195 from blood and tissue was assessed, and found to be >90%. From blank blood samples and organs spiked with [ 123 I]iodo-PK11195 it was concluded that no metabolization took place during the extraction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [ 123 I]iodo-PK11195 was the only significant (ca. 95%) radioactive compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [ 123 I]iodo-PK11195 rapidly decomposes into two polar metabolites, which at

  8. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography

    International Nuclear Information System (INIS)

    Altar, C.A.; Baudry, M.

    1990-01-01

    Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration

  9. PK-yritysten kybervalmius

    OpenAIRE

    Matilainen, Juhani

    2018-01-01

    Pienet ja keskisuuret yritykset joutuvat yhä enenemissä määrin kyberhyökkäyksen kohteeksi. PK-yrityksen päätöksenteko keskittyy yrityksen toimitusjohtajalle ja häntä avustaville avainhenkilöille, joiden tietämys ei aina riitä kattamaan yrityksen kyberturvallisuutta. Johtuen pienestä henkilöstömäärästä ja suurista suhteellisista koulutuskustannuksista, PK-yritykset suhtautuvat epäröiden henkilöstön kouluttamiseen kyberturvallisuuden alalla. Kyberturvallisuuden näkökulmasta PK-yritystä uhkaavat...

  10. Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA).

    Science.gov (United States)

    Kraus, V B; Conaghan, P G; Aazami, H A; Mehra, P; Kivitz, A J; Lufkin, J; Hauben, J; Johnson, J R; Bodick, N

    2018-01-01

    Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg, N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week 20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK (non-compartmental analysis models), and adverse events (AEs) were assessed. SF TA concentrations following FX006 were quantifiable through Week 12 (pg/mL: 231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only two of eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly declined to IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand [3H]PK 14105

    International Nuclear Information System (INIS)

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.

    1989-01-01

    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with [ 3 H]PK 14105. In thymus sections, [ 3 H]PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands

  12. Genetic Diversity, Natural Selection and Haplotype Grouping of Plasmodium knowlesi Gamma Protein Region II (PkγRII): Comparison with the Duffy Binding Protein (PkDBPαRII).

    Science.gov (United States)

    Fong, Mun Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee Ling

    2016-01-01

    Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPαRII) and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkγRII) is not involved in the invasion of P. knowlesi into humans. PkγRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPαRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPαRII was observed to be undergoing purifying (negative) selection. The present study aimed to determine whether similar phenomena occur in PkγRII. Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00) programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00). Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3). A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd) and nucleotide diversity (π) with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative) selection, geographical clustering of haplotypes

  13. Genetic Diversity, Natural Selection and Haplotype Grouping of Plasmodium knowlesi Gamma Protein Region II (PkγRII: Comparison with the Duffy Binding Protein (PkDBPαRII.

    Directory of Open Access Journals (Sweden)

    Mun Yik Fong

    Full Text Available Plasmodium knowlesi is a simian malaria parasite that has been reported to cause malaria in humans in Southeast Asia. This parasite invades the erythrocytes of humans and of its natural host, the macaque Macaca fascicularis, via interaction between the Duffy binding protein region II (PkDBPαRII and the Duffy antigen receptor on the host erythrocytes. In contrast, the P. knowlesi gamma protein region II (PkγRII is not involved in the invasion of P. knowlesi into humans. PkγRII, however, mediates the invasion of P. knowlesi into the erythrocytes of M. mulata, a non-natural host of P. knowlesi via a hitherto unknown receptor. The haplotypes of PkDBPαRII in P. knowlesi isolates from Peninsular Malaysia and North Borneo have been shown to be genetically distinct and geographically clustered. Also, the PkDBPαRII was observed to be undergoing purifying (negative selection. The present study aimed to determine whether similar phenomena occur in PkγRII.Blood samples from 78 knowlesi malaria patients were used. Forty-eight of the samples were from Peninsular Malaysia, and 30 were from Malaysia Borneo. The genomic DNA of the samples was extracted and used as template for the PCR amplification of the PkγRII. The PCR product was cloned and sequenced. The sequences obtained were analysed for genetic diversity and natural selection using MEGA6 and DnaSP (version 5.10.00 programmes. Genetic differentiation between the PkγRII of Peninsular Malaysia and North Borneo isolates was estimated using the Wright's FST fixation index in DnaSP (version 5.10.00. Haplotype analysis was carried out using the Median-Joining approach in NETWORK (version 4.6.1.3.A total of 78 PkγRII sequences was obtained. Comparative analysis showed that the PkγRII have similar range of haplotype (Hd and nucleotide diversity (π with that of PkDBPαRII. Other similarities between PkγRII and PkDBPαRII include undergoing purifying (negative selection, geographical clustering of

  14. The old and the new in prekallikrein deficiency: historical context and a family from Argentina with PK deficiency due to a new mutation (Arg541Gln) in exon 14 associated with a common polymorphysm (Asn124Ser) in exon 5.

    Science.gov (United States)

    Girolami, Antonio; Vidal, Josè; Sabagh, Marcela; Salagh, Marcela; Gervan, Nora; Parody, Maria; Peroni, Edoardo; Sambado, Luisa; Guglielmone, Hugo

    2014-07-01

    Prekallikrein (PK) is one of the clotting factors involved in the contact phase of blood. PK has an important historical role as its deficiency state represents the second instance of a clotting defect without bleeding manifestations, the first one being factor XII deficiency. PK deficiency is a rare clotting disorder. Moreover, only 11 patients have been investigated so far by molecular biology techniques. In this article, we briefly review some of the history around PK and also present some recent data on a newly identified family from Argentina suffering from PK deficiency. Two patients are homozygous whereas other family members are heterozygous. PK activity and antigen are 1% of normal in the homozygotes and around 60 to 70% of normal in the heterozygotes. As expected, all patients are asymptomatic of bleeding or thrombosis presentations. However, the two homozygotes showed essential hypertension. The PK deficiency in this family is due to a new mutation (Arg541Gln) in exon 14. The defect segregates together with a known polymorphism, Asn124Ser, in exon 5. The significance of the presence of hypertension in the two homozygotes is discussed in view of the extra coagulation effects of PK on vasodilation, vessel permeability, and the control of blood pressure. Structure function analysis indicates that the substitution of Arg with Gln probably impedes the transmembrane diffusion of the molecule, which therefore cannot be secreted in the homozygotes. The presence of hypertension in patients with PK deficiency has been previously reported in some but not all patients. Future research activities will probably concentrate on the effect of PK and other contact phase factors on the vascular system. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Prediction of brain target site concentrations on the basis of CSF PK : impact of mechanisms of blood-to-brain transport and within brain distribution

    NARCIS (Netherlands)

    Westerhout, J.

    2014-01-01

    In the development of drugs for the treatment of central nervous system (CNS) disorders, the prediction of human CNS drug action is a big challenge. Direct measurement of brain extracellular fluid (brainECF) concentrations is highly restricted in human. Therefore, unbound drug concentrations in

  16. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  17. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  18. PK/DB: database for pharmacokinetic properties and predictive in silico ADME models.

    Science.gov (United States)

    Moda, Tiago L; Torres, Leonardo G; Carrara, Alexandre E; Andricopulo, Adriano D

    2008-10-01

    The study of pharmacokinetic properties (PK) is of great importance in drug discovery and development. In the present work, PK/DB (a new freely available database for PK) was designed with the aim of creating robust databases for pharmacokinetic studies and in silico absorption, distribution, metabolism and excretion (ADME) prediction. Comprehensive, web-based and easy to access, PK/DB manages 1203 compounds which represent 2973 pharmacokinetic measurements, including five models for in silico ADME prediction (human intestinal absorption, human oral bioavailability, plasma protein binding, blood-brain barrier and water solubility). http://www.pkdb.ifsc.usp.br

  19. A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim.

    Science.gov (United States)

    Niederalt, Christoph; Kuepfer, Lars; Solodenko, Juri; Eissing, Thomas; Siegmund, Hans-Ulrich; Block, Michael; Willmann, Stefan; Lippert, Jörg

    2018-04-01

    Proteins are an increasingly important class of drugs used as therapeutic as well as diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving the distribution and clearance of large molecules like therapeutic proteins. The model was built as an extension of the PK-Sim model for small molecules incorporating (i) the two-pore formalism for drug extravasation from blood plasma to interstitial space, (ii) lymph flow, (iii) endosomal clearance and (iv) protection from endosomal clearance by neonatal Fc receptor (FcRn) mediated recycling as especially relevant for antibodies. For model development and evaluation, PK data was used for compounds with a wide range of solute radii. The model supports the integration of knowledge gained during all development phases of therapeutic proteins, enables translation from pre-clinical species to human and allows predictions of tissue concentration profiles which are of relevance for the analysis of on-target pharmacodynamic effects as well as off-target toxicity. The current implementation of the model replaces the generic protein PBPK model available in PK-Sim since version 4.2 and becomes part of the Open Systems Pharmacology Suite.

  20. Utility of a Novel Three-Dimensional and Dynamic (3DD Cell Culture System for PK/PD Studies: Evaluation of a Triple Combination Therapy at Overcoming Anti-HER2 Treatment Resistance in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Anusha Ande

    2018-05-01

    Full Text Available Background: Emergence of Human epidermal growth factor receptor 2 (HER2 therapy resistance in HER2-positive (HER2+ breast cancer (BC poses a major clinical challenge. Mechanisms of resistance include the over-activation of the PI3K/mTOR and Src pathways. This work aims to investigate a novel combination therapy that employs paclitaxel (PAC, a mitotic inhibitor, with everolimus (EVE, an mTOR inhibitor, and dasatinib (DAS, an Src kinase inhibitor, as a modality to overcome resistance.Methods: Static (two dimensional, 2D and three-dimensional dynamic (3DD cell culture studies were conducted using JIMT-1 cells, a HER2+ BC cell line refractory to HER2 therapies. Cell viability and caspase-3 expression were examined after JIMT-1 cell exposure to agents as monotherapy or in combination using a 2D setting. A pharmacokinetic/pharmacodynamic (PK/PD combination study with PAC+DAS+EVE was conducted over 3 weeks in a 3DD setting. PAC was administered into the system via a 3 h infusion followed by the addition of a continuous infusion of EVE+DAS 24 h post-PAC dosing. Cell counts and caspase-3 expression were quantified every 2 days. A semi-mechanistic PK/PD model was developed using the 2D data and scaled up to capture the 3DD data. The final model integrated active caspase-3 as a biomarker to bridge between drug exposures and cancer cell dynamics. Model fittings were performed using Monolix software.Results: The triple combination significantly induced caspase-3 activity in the 2D cell culture setting. In the 3DD cell culture setting, sequential dosing of PAC then EVE+DAS showed a 5-fold increase in caspase-3 activity and 8.5-fold decrease in the total cell number compared to the control. The semi-mechanistic PK/PD models fit the data well, capturing the time-course profiles of drug concentrations, caspase-3 expression, and cell counts in the 2D and 3DD settings.Conclusion: A novel, sequential triple combination therapeutic regimen was successfully evaluated

  1. Pharmacological considerations for predicting PK/PD at the site of action for therapeutic proteins.

    Science.gov (United States)

    Wang, Weirong; Zhou, Honghui

    For therapeutic proteins whose sites of action are distal to the systemic circulation, both drug and target concentrations at the tissue sites are not necessarily proportional to those in systemic circulation, highlighting the importance of understanding pharmacokinetic/pharmacodynamic (PK/PD) relationship at the sites of action. This review summarizes the pharmacological considerations for predicting local PK/PD and the importance of measuring PK and PD at site of action. Three case examples are presented to show how mechanistic and physiologically based PK/PD (PBPK/PD) models which incorporated the PK and PD at the tissue site can be used to facilitate understanding the exposure-response relationship for therapeutic proteins. Copyright © 2016. Published by Elsevier Ltd.

  2. E-KAUPPAPORTAALIN MAHDOLLISUUDET PK-YRITYKSELLE

    OpenAIRE

    Järvenpää, Juho

    2011-01-01

    Opinnäytetyön aiheena oli tutkia e-kauppaportaalin mahdollisuuksia ja hyötyjä pk-yritykselle. Opinnäytetyön tarkoituksena oli tarjota pk-yrityksille tietoa, miksi e-kauppaportaalin käyttöönotto olisi varteen otettava vaihtoehto, kun yritys harkitsee verkkokaupan perustamista. Opinnäyte jakaantuu teorioiden ja tutkimusten esittelyyn ja niiden soveltamiseen pk-yrityksen hyväksi. Opinnäytetyössä käytettiin hyväksi Tieken tutkimuksia ja muita e-kauppaan liittyviä tutkimuksia ja teorioita. Opi...

  3. Physiologically-based PK/PD modelling of therapeutic macromolecules.

    Science.gov (United States)

    Thygesen, Peter; Macheras, Panos; Van Peer, Achiel

    2009-12-01

    Therapeutic proteins are a diverse class of drugs consisting of naturally occurring or modified proteins, and due to their size and physico-chemical properties, they can pose challenges for the pharmacokinetic and pharmacodynamic studies. Physiologically-based pharmacokinetics (PBPK) modelling has been effective for early in silico prediction of pharmacokinetic properties of new drugs. The aim of the present workshop was to discuss the feasibility of PBPK modelling of macromolecules. The classical PBPK approach was discussed with a presentation of the successful example of PBPK modelling of cyclosporine A. PBPK model was performed with transport of the cyclosporine across cell membranes, affinity to plasma proteins and active membrane transporters included to describe drug transport between physiological compartments. For macromolecules, complex PBPK modelling or permeability-limited and/or target-mediated distribution was discussed. It was generally agreed that PBPK modelling was feasible and desirable. The role of the lymphatic system should be considered when absorption after extravascular administration is modelled. Target-mediated drug disposition was regarded as an important feature for generation of PK models. Complex PK-models may not be necessary when a limited number of organs are affected. More mechanistic PK/PD models will be relevant when adverse events/toxicity are included in the PK/PD modelling.

  4. MIDAS/PK code development using point kinetics model

    International Nuclear Information System (INIS)

    Song, Y. M.; Park, S. H.

    1999-01-01

    In this study, a MIDAS/PK code has been developed for analyzing the ATWS (Anticipated Transients Without Scram) which can be one of severe accident initiating events. The MIDAS is an integrated computer code based on the MELCOR code to develop a severe accident risk reduction strategy by Korea Atomic Energy Research Institute. In the mean time, the Chexal-Layman correlation in the current MELCOR, which was developed under a BWR condition, is appeared to be inappropriate for a PWR. So as to provide ATWS analysis capability to the MIDAS code, a point kinetics module, PKINETIC, has first been developed as a stand-alone code whose reference model was selected from the current accident analysis codes. In the next step, the MIDAS/PK code has been developed via coupling PKINETIC with the MIDAS code by inter-connecting several thermal hydraulic parameters between the two codes. Since the major concern in the ATWS analysis is the primary peak pressure during the early few minutes into the accident, the peak pressure from the PKINETIC module and the MIDAS/PK are compared with the RETRAN calculations showing a good agreement between them. The MIDAS/PK code is considered to be valuable for analyzing the plant response during ATWS deterministically, especially for the early domestic Westinghouse plants which rely on the operator procedure instead of an AMSAC (ATWS Mitigating System Actuation Circuitry) against ATWS. This capability of ATWS analysis is also important from the view point of accident management and mitigation

  5. Novel Mechanism of Plasma Prekallikrein (PK) Activation by Vascular Smooth Muscle Cells: Evidence of the presence of PK Activator

    OpenAIRE

    Keum, Joo-Seob; Jaffa, Miran A; Luttrell, Louis M; Jaffa, Ayad A.

    2014-01-01

    The contribution of plasma prekallikrein (PK) to vascular remodeling is becoming increasingly recognized. Plasma PK is activated when the zymogen PK is digested to an active enzyme by activated factor XII (FXII). Here, we present our findings that vascular smooth muscle cells (VSMC) activate plasma PK in the absence of FXII. Extracted plasma membrane and cytosolic fractions of VSMCs activate PK, but the rate of PK activation was greater by the membrane fraction. FXII neutralizing antibody did...

  6. A Blood Bank Information Management System

    Science.gov (United States)

    Farmer, James J.

    1982-01-01

    A computerized Blood Bank Management system is described. Features include product oriented data input, inventory control reports, product utilization reports, rapid retrieval of individual patient reports. Relative benefits of the system are discussed.

  7. Designing an automated blood fractionation system.

    Science.gov (United States)

    McQuillan, Adrian C; Sales, Sean D

    2008-04-01

    UK Biobank will be collecting blood samples from a cohort of 500 000 volunteers and it is expected that the rate of collection will peak at approximately 3000 blood collection tubes per day. These samples need to be prepared for long-term storage. It is not considered practical to manually process this quantity of samples so an automated blood fractionation system is required. Principles of industrial automation were applied to the blood fractionation process leading to the requirement of developing a vision system to identify the blood fractions within the blood collection tube so that the fractions can be accurately aspirated and dispensed into micro-tubes. A prototype was manufactured and tested on a range of human blood samples collected in different tube types. A specially designed vision system was capable of accurately measuring the position of the plasma meniscus, plasma/buffy coat interface and the red cells/buffy coat interface within a vacutainer. A rack of 24 vacutainers could be processed in blood fractionation system offers a solution to the problem of processing human blood samples collected in vacutainers in a consistent manner and provides a means of ensuring data and sample integrity.

  8. Blood as integral system of an organism

    Directory of Open Access Journals (Sweden)

    Майя Розметовна Верголяс

    2016-02-01

    Full Text Available Relevance of use of hematological blood parameters for monitoring as markers of various physiological and pathological processes is substantiated. It is shown that the blood is an important system of the body, has all the reactive characteristics of tissues, its sensitivity to pathological stimuli is very high. The reaction of the organism to the irritation of toxic or infectious nature manifests itself in the change of quantitative composition of peripheral blood cells

  9. Algebra task sheets : grades pk-2

    CERN Document Server

    Reed, Nat

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the algebraic concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  10. Geometry task sheets : grades pk-2

    CERN Document Server

    Rosenberg, Mary

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the geometry concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  11. Beyond DNA repair: DNA-PK function in cancer

    OpenAIRE

    Goodwin, Jonathan F.; Knudsen, Karen E.

    2014-01-01

    The DNA-dependent protein kinase (DNA-PK) is a pivotal component of the DNA repair machinery that governs the response to DNA damage, serving to maintain genome integrity. However, the DNA-PK kinase component was initially isolated with transcriptional complexes, and recent findings have illuminated the impact of DNA-PK-mediated transcriptional regulation on tumor progression and therapeutic response. DNA-PK expression has also been correlated with poor outcome in selected tumor types, furthe...

  12. One System for Blood Program Information Management

    Science.gov (United States)

    Gero, Michael G.; Klickstein, Judith S.; Hurst, Timm M.

    1980-01-01

    A system which integrates the diverse functions of a Blood Program within one structure is being assembled at the American National Red Cross Blood Services, Northeast Region. When finished, it will provide technical support for collection scheduling, donor recruitment, recordkeeping, laboratory processing, inventory management, HLA typing and matching, distribution, and administration within the Program. By linking these applications, a reporting structure useful to top management will be provided.

  13. Instagram-opas pk-yrityksille

    OpenAIRE

    Seppälä, Marjaana

    2016-01-01

    Tämän opinnäytetyön aihe on Instagram-opas pienille ja keskisuurille yrityksille. Tarkoituksena on luoda pk-yrityksille sopiva Instagram-opas, jonka sisältöä voidaan hyödyntää Instagram-palvelun käyttöönotossa ja markkinointia suunniteltaessa. Opas toteutetaan Business-to-Consumer (B2C)– kentällä toimivan yrityksen näkökulmasta. Oppaan tarkoituksena on laskea pk-yrityksen kynnystä lähteä mukaan Instagram-palveluun ja lisätä tietämystä palvelun käytöstä. Tässä opinnäytetyössä tarkastella...

  14. Adaptation of the migrant worker’s body to the occupational risk factors from the position of functional system of P.K. Anokhin

    Directory of Open Access Journals (Sweden)

    М. Khodzhiev

    2016-12-01

    Full Text Available The adverse factors of labor process of migrants were studied as the factors of risk of formation of unsatisfactory adaptation and damage to health. The results of the study of adaptation of migrants to the labor process from the standpoint of the theory of functional systems were presented. The first subsystem of physical activities and neuro-emotional tension of labor determines the formation of certain stages of the adaptation process in terms of heart rate variability (the second sub-system. The result of migrant workers’ sympathetic chain of regulation’s activity level shows that the adaptive stress syndrome on the physiological indicators is expressed in a change of heart rate variability: different levels of stress index of SI associated with high physical (muscle, neuro-emotional stresses; marked increase in the power of spectrum of very low-frequency component (VLF, while the increase in heart rate. The features of the functional state of the body and the degree of adaptation in terms of activity of regulatory systems – PARS (optimal 1.19 ± 0.28; allowable stress 40.5 ± 0.62; overvoltage 6.21 ± 0.82 points were determined. On the basis of the production studies of migrant workers, the approaches to quantitative evaluation to the degree of adaptation of workers to the labor process associated with the combined effects of physical, neural and emotional labor intensity on the human body were science-based and developed. The degree of stress adaptation process corresponds to the stage of self-control (optimum stress activation (allowable stress, the mobilization of the 1st, 2nd, 3-th degree (degrees of over-stress of 1,2,3 degrees. Unfavorable stage of mobilization of 2–3 degrees of migrant workers was determined (an increase in the stress index S1, PARS indicator, the relative power of VLF range, a reduction in the SDNN. Events of medical and social support represent the third sub-system in the general system theory.

  15. Modeling and simulation of blood collection systems.

    Science.gov (United States)

    Alfonso, Edgar; Xie, Xiaolan; Augusto, Vincent; Garraud, Olivier

    2012-03-01

    This paper addresses the modeling and simulation of blood collection systems in France for both fixed site and mobile blood collection with walk in whole blood donors and scheduled plasma and platelet donors. Petri net models are first proposed to precisely describe different blood collection processes, donor behaviors, their material/human resource requirements and relevant regulations. Petri net models are then enriched with quantitative modeling of donor arrivals, donor behaviors, activity times and resource capacity. Relevant performance indicators are defined. The resulting simulation models can be straightforwardly implemented with any simulation language. Numerical experiments are performed to show how the simulation models can be used to select, for different walk in donor arrival patterns, appropriate human resource planning and donor appointment strategies.

  16. Semi-physiological pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil for thrombocytopenia in rats.

    Science.gov (United States)

    Kobuchi, Shinji; Ito, Yukako; Hayakawa, Taro; Nishimura, Asako; Shibata, Nobuhito; Takada, Kanji; Sakaeda, Toshiyuki

    2015-01-01

    1. The aim of this study was to develop a simple pharmacokinetic-pharmacodynamic (PK-PD) model that could characterize the complete time-course of alterations in platelet counts to predict the onset and degree of thrombocytopenia, which severely limits the use of the anticancer agent 5-fluorouracil (5-FU), in rats. 2. Platelet counts were measured in rats following the intravenous administration of various doses of 5-FU for 4 days to obtain data for an analysis of the PK-PD model. Our PK-PD model consisted of a two-compartment PK model, with three compartments for the PD model and 10 structural PK-PD model parameters. 3. After the 5-FU treatment, platelet counts transiently decreased to a nadir level, showed a rebound to above the baseline level before recovering to baseline levels. Nadir platelet counts and rebounds varied with the AUC0-∞ level. The final PK-PD model effectively characterized platelet count data and final PD parameters were estimated with high certainty. 4. This PK-PD model and simulation may represent a valuable tool for quantifying and predicting the complete time-course of alterations in blood cell counts, and could contribute to the development of therapeutic strategies with 5-FU and assessments of various novel anticancer agents that are difficult to examine in humans.

  17. Blood Sample Transportation by Pneumatic Transportation Systems

    DEFF Research Database (Denmark)

    Nybo, Mads; Lund, Merete E; Titlestad, Kjell

    2018-01-01

    BACKGROUND: Pneumatic transportation systems (PTSs) are increasingly used for transportation of blood samples to the core laboratory. Many studies have investigated the impact of these systems on different types of analyses, but to elucidate whether PTSs in general are safe for transportation...... analysis, and the hemolysis index). CONCLUSIONS: Owing to their high degree of heterogeneity, the retrieved studies were unable to supply evidence for the safety of using PTSs for blood sample transportation. In consequence, laboratories need to measure and document the actual acceleration forces...

  18. Search for a narrow baryonic state decaying to pK0S and anti pK0S in deep inelastic scattering at HERA

    International Nuclear Information System (INIS)

    Abramowicz, H.; Abt, I.; Adamczyk, L.

    2016-06-01

    A search for a narrow baryonic state in the pK 0 S and anti pK 0 S system has been performed in ep collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb -1 taken in 2003-2007. The search was performed with deep inelastic scattering events at an ep centre-of-mass energy of 318 GeV for exchanged photon virtuality, Q 2 , between 20 and 100 GeV 2 . Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb -1 taken in 1996-2000, no resonance peak was found in the p(anti p)K 0 S invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set.

  19. Liikelahjat mikro- ja pk-yrityksissä

    OpenAIRE

    Danhammer, Joni

    2014-01-01

    Liikelahjat ovat osa yrityksen menekinedistämistä ja kuuluvat tiiviisti yrityksen markkinointiviestintään. Kuitenkin yleinen talouden kiristynyt tilanne ja vuoden 2014 alussa voimaan astunut verouudistus liikelahjojen verovähennyksissä ovat asioita, jotka vaikuttavat liikelahjojen menekkiin ja niiden antamistapojen muuttumiseen mikro- ja pk-yrityksissä. Näin ollen yrityksillä tulisi tässä tilanteessa olla selkeä käsitys siitä, millaisia liikelahjoja yritys haluaa nykyisin henkilökunnalleen ja...

  20. Small molecules, inhibitors of DNA-PK, targeting DNA repair and beyond

    Directory of Open Access Journals (Sweden)

    David eDavidson

    2013-01-01

    Full Text Available Many current chemotherapies function by damaging genomic DNA in rapidly dividing cells ultimately leading to cell death. This therapeutic approach differentially targets cancer cells that generally display rapid cell division compared to normal tissue cells. However, although these treatments are initially effective in arresting tumor growth and reducing tumor burden, resistance and disease progression eventually occur. A major mechanism underlying this resistance is increased levels of cellular DNA repair. Most cells have complex mechanisms in place to repair DNA damage that occurs due to environmental exposures or normal metabolic processes. These systems, initially overwhelmed when faced with chemotherapy induced DNA damage, become more efficient under constant selective pressure and as a result chemotherapies become less effective. Thus, inhibiting DNA repair pathways using target specific small molecule inhibitors may overcome cellular resistance to DNA damaging chemotherapies. Non-homologous end joining (NHEJ a major mechanism for the repair of double strand breaks (DSB in DNA is regulated in part by the serine/threonine kinase, DNA dependent protein kinase (DNA-PK. The DNA-PK holoenzyme acts as a scaffold protein tethering broken DNA ends and recruiting other repair molecules. It also has enzymatic activity that may be involved in DNA damage signaling. Because of its’ central role in repair of DSBs, DNA-PK has been the focus of a number of small molecule studies. In these studies specific DNA-PK inhibitors have shown efficacy in synergizing chemotherapies in vitro. However, compounds currently known to specifically inhibit DNA-PK are limited by poor pharmacokinetics: these compounds have poor solubility and have high metabolic lability in vivo leading to short serum half-lives. Future improvement in DNA-PK inhibition will likely be achieved by designing new molecules based on the recently reported crystallographic structure of DNA-PK

  1. Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.

    Science.gov (United States)

    Gomez, David S; Sanches-Giraud, Cristina; Silva, Carlindo V; Oliveira, Amanda M Ribas Rosa; da Silva, Joao Manoel; Gemperli, Rolf; Santos, Silvia R C J

    2015-03-01

    Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

  2. Changes in the responsiveness of hypothalamic PK2 and PKR1 gene expression to fasting in developing male rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Kawami, Takako; Yamasaki, Mikio; Murakami, Masahiro; Kato, Takeshi; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2014-11-01

    Prokineticin (PK2) and its receptors (PKRs) are expressed in several regions of the central nervous system, including the hypothalamus. It has been reported that PK2 inhibits food intake via PKR1 and that the hypothalamic PK2 mRNA levels of adult rodents were reduced by food deprivation. However, some hypothalamic factors do not exhibit sensitivity to undernutrition in the early neonatal period, but subsequently become sensitive to it during the neonatal to pre-pubertal period. In this study, we investigated the changes in the sensitivity of hypothalamic PK2 and PKR1 mRNA expression to fasting during the developmental period in male rats. Under the fed conditions, the rats' hypothalamic PK2 and/or PKR1 mRNA levels were higher on postnatal day (PND) 10 than on PND20 or PND30. In addition, the hypothalamic PK2 and/or PKR1 mRNA levels of the male rats were higher than those of the females at all examined ages (PND10, 20, and 30). Hypothalamic PK2 mRNA expression was decreased by 24h fasting at PND10 and 30, but not at PND20. In addition, hypothalamic PKR1 mRNA expression was decreased by 24h fasting at PND10, but not at PND20 or 30. These results indicate that both PK2 and PKR1 are sensitive to nutritional status in male rats and that this sensitivity has already been established by the early neonatal period. It can be speculated that the PK2 system might compensate for the immaturity of other appetite regulatory factors in the early neonatal period. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Quantification of (R)-[11C]PK11195 binding in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Kropholler, M.A.; Boellaard, R.; Kloet, R.W.; Lammertsma, A.A.; Elzinga, E.H.; Voskuyl, A.E.; Laken, C.J. van der; Dijkmans, B.A.C.; Maruyama, K.

    2009-01-01

    Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[ 11 C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)-[ 11 C]PK11195 binding in the knee joints of RA patients. Data from six patients with RA were analysed. Dynamic PET scans were acquired in 3-D mode following (R)-[ 11 C]PK11195 injection. During scanning arterial radioactivity concentrations were measured to determine the plasma (R)-[ 11 C]PK11195 concentrations. Data were analysed using irreversible and reversible one-tissue and two-tissue compartment models and input functions with various types of metabolite correction. Model preferences according to the Akaike information criterion (AIC) and correlations between measures were evaluated. Correlations between distribution volume (V d ) and standardized uptake values (SUV) were evaluated. AIC indicated optimal performance for a one-tissue reversible compartment model including blood volume. High correlations were observed between V d obtained using different input functions (R 2 =0.80-1.00) and between V d obtained with one- and two-tissue reversible compartment models (R 2 =0.75-0.94). A high correlation was observed between optimal V d and SUV after injection (R 2 =0.73). (R)-[ 11 C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V d , SUV is a practical alternative for clinical use. (orig.)

  4. Population PK modelling and simulation based on fluoxetine and norfluoxetine concentrations in milk: a milk concentration-based prediction model.

    Science.gov (United States)

    Tanoshima, Reo; Bournissen, Facundo Garcia; Tanigawara, Yusuke; Kristensen, Judith H; Taddio, Anna; Ilett, Kenneth F; Begg, Evan J; Wallach, Izhar; Ito, Shinya

    2014-10-01

    Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration-time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk. Using a previously published data set of drug concentrations in milk from 25 women treated with FX, a pop PK model predictive of milk concentration-time profiles of FX and NFX was developed. Simulation was performed with the model to generate FX and NFX concentration-time profiles in milk of 1000 mothers. This milk concentration-based pop PK model was compared with the previously validated plasma/milk concentration-based pop PK model of FX. Milk FX and NFX concentration-time profiles were described reasonably well by a one compartment model with a FX-to-NFX conversion coefficient. Median values of the simulated relative infant dose on a weight basis (sRID: weight-adjusted daily doses of FX and NFX through breastmilk to the infant, expressed as a fraction of therapeutic FX daily dose per body weight) were 0.028 for FX and 0.029 for NFX. The FX sRID estimates were consistent with those of the plasma/milk-based pop PK model. A predictive pop PK model based on only milk concentrations can be developed for simultaneous estimation of milk concentration-time profiles of a parent (FX) and an active metabolite (NFX). © 2014 The British Pharmacological Society.

  5. Particle swarm optimization algorithm for optimizing assignment of blood in blood banking system.

    Science.gov (United States)

    Olusanya, Micheal O; Arasomwan, Martins A; Adewumi, Aderemi O

    2015-01-01

    This paper reports the performance of particle swarm optimization (PSO) for the assignment of blood to meet patients' blood transfusion requests for blood transfusion. While the drive for blood donation lingers, there is need for effective and efficient management of available blood in blood banking systems. Moreover, inherent danger of transfusing wrong blood types to patients, unnecessary importation of blood units from external sources, and wastage of blood products due to nonusage necessitate the development of mathematical models and techniques for effective handling of blood distribution among available blood types in order to minimize wastages and importation from external sources. This gives rise to the blood assignment problem (BAP) introduced recently in literature. We propose a queue and multiple knapsack models with PSO-based solution to address this challenge. Simulation is based on sets of randomly generated data that mimic real-world population distribution of blood types. Results obtained show the efficiency of the proposed algorithm for BAP with no blood units wasted and very low importation, where necessary, from outside the blood bank. The result therefore can serve as a benchmark and basis for decision support tools for real-life deployment.

  6. Particle Swarm Optimization Algorithm for Optimizing Assignment of Blood in Blood Banking System

    Science.gov (United States)

    Olusanya, Micheal O.; Arasomwan, Martins A.; Adewumi, Aderemi O.

    2015-01-01

    This paper reports the performance of particle swarm optimization (PSO) for the assignment of blood to meet patients' blood transfusion requests for blood transfusion. While the drive for blood donation lingers, there is need for effective and efficient management of available blood in blood banking systems. Moreover, inherent danger of transfusing wrong blood types to patients, unnecessary importation of blood units from external sources, and wastage of blood products due to nonusage necessitate the development of mathematical models and techniques for effective handling of blood distribution among available blood types in order to minimize wastages and importation from external sources. This gives rise to the blood assignment problem (BAP) introduced recently in literature. We propose a queue and multiple knapsack models with PSO-based solution to address this challenge. Simulation is based on sets of randomly generated data that mimic real-world population distribution of blood types. Results obtained show the efficiency of the proposed algorithm for BAP with no blood units wasted and very low importation, where necessary, from outside the blood bank. The result therefore can serve as a benchmark and basis for decision support tools for real-life deployment. PMID:25815046

  7. Observation of $S=+1$ Narrow Resonances in the System $pK^0_s$ from $p+\\rm {C_3H_8}$ Collision at 10 GeV/$c$

    CERN Document Server

    Aslanyan, P Zh; Rikhvitskaya, G G

    2004-01-01

    Experimental data from a 2 m propane bubble chamber have been analyzed to search for an exotic baryon state, the $\\Theta^+$ baryon, in the $pK^0_s$ decay mode for the reaction $p+{\\rm C_3H_8}$ at 10 GeV/$c$. The $pK^0_s$ invariant mass spectrum shows resonant structures with $M_{p K_s^0}=1540\\pm 8$, $1613\\pm10$, $1821\\pm11$ MeV/$c^2$ and $\\Gamma_{p K_s^0}= 9.2\\pm1.8$, $16.1\\pm4.1$, $28.0\\pm9.4$ MeV/$c^2$. The statistical significance of these peaks has been estimated as $5.5$, $4.8$ and $5.0$ s.d., respectively. There are also small peaks in mass regions of 1487 (3.0 s.d.), 1690 (3.6 s.d.) and 1980 (3.0 s.d.) MeV/$c^2$.

  8. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

    NARCIS (Netherlands)

    Sweeney, R.E.; Langenberg, J.P.; Maxwell, D.M.

    2006-01-01

    A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50),

  9. Development of blood extraction system for health monitoring system

    Science.gov (United States)

    Tsuchiya, Kazuyoshi; Nakanishi, Naoyuki; Nakamachi, Eiji

    2004-03-01

    The purpose of this research is to develop the compact human blood sampling device applied for a health monitoring system(HMS), which is called "Mobile Hospital". The HMS consists of (1) a micro electrical pumping system for blood extraction, (2) a bio-sensor to detect and evaluate an amount of Glucose, Cholesterol and Urea in extracted blood, by using enzyme such as Glucoseoxidase (GOD), Cholesteroloxidase and Urease. The mechanical design elements of the device are bio-compatible microneedle, indentation unit using a shape memory alloy(SMA) actuator and pumping unit using a piezoelectric microactuator. The design concept is the biomimetic micromachine of female mosquito"s blood sampling mechanism. The performances of the main mechanical elements such as indentation force of the microneedle, actual stroke of the indentation unit using a SMA actuator and liquid sampling ability of the pumping unit using PZT piezoelectric microactuator were measured. The 3 mm stroke of the indentation load generated by SMA actuator was 0.8mN. The amount of imitation blood extracted by using bimorph PZT actuators was about 0.5 microliters for 10 sec. A 60-micrometer outer diameter and 25-micrometer inner diameter Titanium microneedle, which size is same as female mosquito"s labium, was produced by sputter deposition.

  10. 21 CFR 862.1120 - Blood gases (PCO2, PO2) and blood pH test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood gases (PCO2, PO2) and blood pH test system... Test Systems § 862.1120 Blood gases (PCO2, PO2) and blood pH test system. (a) Identification. A blood gases (PCO2, PO2) and blood pH test system is a device intended to measure certain gases in blood, serum...

  11. Tools for predicting the PK/PD of therapeutic proteins.

    Science.gov (United States)

    Diao, Lei; Meibohm, Bernd

    2015-07-01

    Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships. In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development. A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.

  12. [Development of a continuous blood pressure monitoring and recording system].

    Science.gov (United States)

    Zhang, Yang; Li, Yong; Gao, Shumei; Song, Yilin

    2012-09-01

    A small experimental system is constructed with working principle of continuous blood pressure monitoring based on the volume compensation method. The preliminary experimental results show that the system can collect blood pressure signals at the radial artery effectively. The digital PID algorithm can track the variation of blood pressure. And the accuracy of continuous blood pressure detecting achieve the level of same kind of product.

  13. Can a decentralized blood system ensure self-sufficiency and blood safety? The Lebanese experience.

    Science.gov (United States)

    Haddad, Antoine; Bou Assi, Tarek; Garraud, Olivier

    2017-08-01

    Lebanon has adopted a liberal economic system that also applies to healthcare procurement. There is no national Lebanese blood transfusion service and the blood supply is divided between a large number of licensed (45 per cent) and unlicensed (55 per cent) blood banks, many of them issuing a very limited number of blood components. All blood banks are hospital based and operate the entire transfusion chain, from collection to the release of blood units. Blood donation is voluntary and non-remunerated in 20-25 per cent of donations; it relies principally on replacement donations. Recently, Lebanon has faced political instability and war, and now welcomes an enormous number of refugees from neighboring countries at war. This has had an important impact on heath care and on the transfusion supply. We discuss the impact of the blood donation organization on the transfusion safety and ethics, to set the foundation for a more developed and safer transfusion programs.

  14. Open Circuit Potential Changes upon Protonation/Deprotonation of ω-Functionalized Alkanethiols on Au: Determination of Surface pK {sub 1/2} in Aqueous and Non-Aqueous System

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seung Ryul; Park, Kyung Soon; Jang, Jae Won; Hwang, Seong Pil [Korea Univ., Sejong (Korea, Republic of)

    2016-09-15

    The controlled assembly of functional nanomaterials has been drawing significant interest for making devices by integration of nanomaterials. The building blocks of functional nanomaterials might be confined spatially on the chemically patterned surface through both covalent and non-covalent bonds. Potentiometric measurement is affordable technique for various researchers because it requires only voltmeter and reference electrode. Moreover, it can be applied to various polar solvent such as methanol and ethanol. The open circuit potential (OCP) is measured indicating the potential difference between reference electrode and working electrode. The potential of working electrode might be affected by redox chemical reaction and charge state/separation. Our results provide the simple and affordable method to investigate pK {sub 1/2} of thin film both in aqueous phase and in non-aqueous phase, which has significant role in colloidal chemistry, nanochemistry, surface chemistry, electrochemistry, and others.

  15. Intelligent micro blood typing system using a fuzzy algorithm

    International Nuclear Information System (INIS)

    Kang, Taeyun; Cho, Dong-Woo; Lee, Seung-Jae; Kim, Yonggoo; Lee, Gyoo-Whung

    2010-01-01

    ABO typing is the first analysis performed on blood when it is tested for transfusion purposes. The automated machines used in hospitals for this purpose are typically very large and the process is complicated. In this paper, we present a new micro blood typing system that is an improved version of our previous system (Kang et al 2004 Trans. ASME, J. Manuf. Sci. Eng. 126 766, Lee et al 2005 Sensors Mater. 17 113). This system, fabricated using microstereolithography, has a passive valve for controlling the flow of blood and antibodies. The intelligent micro blood typing system has two parts: a single-line micro blood typing device and a fuzzy expert system for grading the strength of agglutination. The passive valve in the single-line micro blood typing device makes the blood stop at the entrance of a micro mixer and lets it flow again after the blood encounters antibodies. Blood and antibodies are mixed in the micro mixer and agglutination occurs in the chamber. The fuzzy expert system then determines the degree of agglutination from images of the agglutinated blood. Blood typing experiments using this device were successful, and the fuzzy expert system produces a grading decision comparable to that produced by an expert conducting a manual analysis

  16. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    Science.gov (United States)

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  17. PK-ISIS: a new superconducting ECR ion source at Pantechnik

    International Nuclear Information System (INIS)

    Villari, A.C.; Bieth, C.; Bougy, W.; Brionne, N.; Donzel, X.; Gaubert, G.; Leroy, R.; Sineau, A.; Tasset, O.; Vallerand, C.; Thuillier, T.

    2012-01-01

    The new ECR ion source PK-ISIS was recently commissioned at Pantechnik. Three superconducting coils generate the axial magnetic field configuration while the radial magnetic field is done with multi-layer permanent magnets. Special care was devoted in the design of the hexapolar structure, allowing a maximum magnetic field of 1.32 T at the wall of the 82 mm diameter plasma chamber. The three superconducting coils using Low Temperature Superconducting wires are cooled by a single double stage cryo-cooler (4.2 K). Cryogen-free technology is used, providing reliability, easy maintenance at low cost. The maximum installed RF power (18.0 GHz) is of 2 kW. Metallic beams can be produced with an oven (T max = 1400 C) installed with an angle of 5 degrees with respect to the source axis or a sputtering system, mounted in the axis of the source. The beam extraction system is constituted of three electrodes in accel-decel configuration. The new source of Pantechnik is conceived for reaching optimum performances at 18 GHz RF frequencies. PK-ISIS delivers 5 to 10 times more beam intensity than the original PK-DELIS and/or shifting the charge state distribution to higher values. PK-ISIS is built with Low Temperature Superconducting wire technology (LTS), but keeps the He-free concept, extremely important for a reliable and easy operation. The radial field circuit is permanent magnet made. Finally, PK-ISIS is also conceived for using in a High-Voltage platform with minor power consumption. The paper is followed by the slides of the presentation. (A.C.)

  18. Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Christensen, H

    1991-01-01

    Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage uni.......0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism.......Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit...

  19. Autographa californica multiple nucleopolyhedrovirus PK-1 is essential for nucleocapsid assembly

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Changyong, E-mail: cyliang@yzu.edu.cn [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Li, Min; Dai, Xuejuan; Zhao, Shuling; Hou, Yanling; Zhang, Yongli; Lan, Dandan [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Wang, Yun; Chen, Xinwen [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

    2013-09-01

    PK-1 (Ac10) is a baculovirus-encoded serine/threonine kinase and its function is unclear. Our results showed that a pk-1 knockout AcMNPV failed to produce infectious progeny, while the pk-1 repair virus could rescue this defect. qPCR analysis demonstrated that pk-1 deletion did not affect viral DNA replication. Analysis of the repaired recombinants with truncated pk-1 mutants demonstrated that the catalytic domain of protein kinases of PK-1 was essential to viral infectivity. Moreover, those PK-1 mutants that could rescue the infectious BV production defect exhibited kinase activity in vitro. Therefore, it is suggested that the kinase activity of PK-1 is essential in regulating viral propagation. Electron microscopy revealed that pk-1 deletion affected the formation of normal nucleocapsids. Masses of electron-lucent tubular structures were present in cell transfected with pk-1 knockout bacmid. Therefore, PK-1 appears to phosphorylate some viral or cellular proteins that are essential for DNA packaging to regulate nucleocapsid assembly. - Highlights: • A pk-1 knockout AcMNPV failed to produce infectious progeny. • The pk-1 deletion did not affect viral DNA replication. • The catalytic domain of protein kinases (PKc) of PK-1 was essential to viral infectivity. • The kinase activity of PK-1 is essential in regulating viral propagation. • PK-1 appears to phosphorylate some viral proteins that are essential for DNA packaging to regulate nucleocapsid assembly.

  20. Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

    Science.gov (United States)

    Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling

    2015-02-21

    Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from

  1. An Automatic Lab-on-Disc System for Blood Typing.

    Science.gov (United States)

    Chang, Yaw-Jen; Fan, Yi-Hua; Chen, Shia-Chung; Lee, Kuan-Hua; Lou, Liao-Yong

    2018-04-01

    A blood-typing assay is a critical test to ensure the serological compatibility of a donor and an intended recipient prior to a blood transfusion. This article presents a lab-on-disc blood-typing system to conduct a total of eight assays for a patient, including forward-typing tests, reverse-typing tests, and irregular-antibody tests. These assays are carried out in a microfluidic disc simultaneously. A blood-typing apparatus was designed to automatically manipulate the disc. The blood type can be determined by integrating the results of red blood cell (RBC) agglutination in the microchannels. The experimental results of our current 40 blood samples show that the results agree with those examined in the hospital. The accuracy reaches 97.5%.

  2. A system for oxygen-15 labeled blood for medical applications

    International Nuclear Information System (INIS)

    Subramanyam, R.; Bucelewicz, W.M.; Hoop, B. Jr.; Jones, S.C.

    1977-01-01

    Oxygen-15 labeled compounds in blood have been used successfully for cerebral circulation and cerebral oxygen metabolism measurements. The present paper describes a system for the rapid sequential production of 15 O-HgB, C 15 O-Hgb and H 2 15 O in blood under sterile and pyrogen-free conditions. A tonometer has been adopted for labeling blood without hemolysis and foam production. (author)

  3. Development of blood extraction system designed by female mosquito's blood sampling mechanism for bio-MEMS

    Science.gov (United States)

    Tsuchiya, Kazuyoshi; Nakanishi, Naoyuki; Nakamachi, Eiji

    2005-02-01

    A compact and wearable wristwatch type Bio-MEMS such as a health monitoring system (HMS) to detect blood sugar level for diabetic patient, was newly developed. The HMS consists of (1) a indentation unit with a microneedle to generate the skin penetration force using a shape memory alloy(SMA) actuator, (2) a pumping unit using a bimorph PZT piezoelectric actuator to extract the blood and (3) a gold (Au) electrode as a biosensor immobilized GOx and attached to the gate electrode of MOSFET to detect the amount of Glucose in extracted blood. GOx was immobilized on a self assembled spacer combined with an Au electrode by the cross-link method using BSA as an additional bonding material. The device can extract blood in a few microliter through a painless microneedle with the negative pressure by deflection of the bimorph PZT piezoelectric actuator produced in the blood chamber, by the similar way the female mosquito extracts human blood with muscle motion to flex or relax. The performances of the liquid sampling ability of the pumping unit through a microneedle (3.8mm length, 100μm internal diameter) using the bimorph PZT piezoelectric microactuator were measured. The blood extraction micro device could extract human blood at the speed of 2μl/min, and it is enough volume to measure a glucose level, compared to the amount of commercial based glucose level monitor. The electrode embedded in the blood extraction device chamber could detect electrons generated by the hydrolysis of hydrogen peroxide produced by the reaction between GOx and glucose in a few microliter extracted blood, using the constant electric current measurement system of the MOSFET type hybrid biosensor. The output voltage for the glucose diluted in the chamber was increased lineally with increase of the glucose concentration.

  4. An automated blood sampling system used in positron emission tomography

    International Nuclear Information System (INIS)

    Eriksson, L.; Bohm, C.; Kesselberg, M.

    1988-01-01

    Fast dynamic function studies with positron emission tomography (PET), has the potential to give accurate information of physiological functions of the brain. This capability can be realised if the positron camera system accurately quantitates the tracer uptake in the brain with sufficiently high efficiency and in sufficiently short time intervals. However, in addition, the tracer concentration in blood, as a function of time, must be accurately determined. This paper describes and evaluates an automated blood sampling system. Two different detector units are compared. The use of the automated blood sampling system is demonstrated in studies of cerebral blood flow, in studies of the blood-brain barrier transfer of amino acids and of the cerebral oxygen consumption. 5 refs.; 7 figs

  5. Bedside arterial blood gas monitoring system using fluorescent optical sensors

    Science.gov (United States)

    Bartnik, Daniel J.; Rymut, Russell A.

    1995-05-01

    We describe a bedside arterial blood gas (ABG) monitoring system which uses fluorescent optical sensors in the measurement of blood pH, PCO2 and PO2. The Point-of-Care Arterial Blood Gas Monitoring System consists of the SensiCathTM optical sensor unit manufactured by Optical Sensors Incorporated and the TramTM Critical Care Monitoring System with ABG Module manufactured by Marquette Electronics Incorporated. Current blood gas measurement techniques require a blood sample to be removed from the patient and transported to an electrochemical analyzer for analysis. The ABG system does not require removal of blood from the patient or transport of the sample. The sensor is added to the patient's existing arterial line. ABG measurements are made by drawing a small blood sample from the arterial line in sufficient quantity to ensure an undiluted sample at the sensor. Measurements of pH, PCO2 and PO2 are made within 60 seconds. The blood is then returned to the patient, the line flushed and results appear on the bedside monitor. The ABG system offers several advantages over traditional electrochemical analyzers. Since the arterial line remains closed during the blood sampling procedure the patient's risk of infection is reduced and the caregiver's exposure to blood is eliminated. The single-use, disposable sensor can be measure 100 blood samples over 72 hours after a single two-point calibration. Quality Assurance checks are also available and provide the caregiver the ability to assess system performance even after the sensor is patient attached. The ABG module integrates with an existing bedside monitoring system. This allows ABG results to appear on the same display as ECG, respiration, blood pressure, cardiac output, SpO2, and other clinical information. The small module takes up little space in the crowded intensive care unit. Performance studies compare the ABG system with an electrochemical blood gas analyzer. Study results demonstrated accurate and precise blood

  6. Clinical comparison of two commercial blood culture systems

    NARCIS (Netherlands)

    Spanjaard, L.; Kuijper, E. J.; Dankert, J.

    2000-01-01

    A prospective, volume-controlled comparison of the BacT/Alert FAN (Organon Teknika, USA) and Vital (bioMérieux, France) blood culture systems was performed in a university hospital during a period of 11 months. Twenty to 40 ml of blood drawn from an adult patient was distributed equally between a

  7. Portable blood extraction device integrated with biomedical monitoring system

    Science.gov (United States)

    Khumpuang, S.; Horade, M.; Fujioka, K.; Sugiyama, S.

    2006-01-01

    Painless and portable blood extraction device has been immersed in the world of miniaturization on bio-medical research particularly in manufacturing point-of-care systems. The fabrication of a blood extraction device integrated with an electrolyte-monitoring system is reported in this paper. The device has advantages in precise controlled dosage of blood extracted including the slightly damaged blood vessels and nervous system. The in-house blood diagnostic will become simple for the patients. Main components of the portable system are; the blood extraction device and electrolyte-monitoring system. The monitoring system consists of ISFET (Ion Selective Field Effect Transistor) for measuring the concentration level of minerals in blood. In this work, we measured the level of 3 ions; Na+, K+ and Cl-. The mentioned ions are frequently required the measurement since their concentration levels in the blood can indicate whether the kidney, pancreas, liver or heart is being malfunction. The fabrication of the whole system and experimentation on each ISM (Ion Sensitive Membrane) will be provided. Taking the advantages of LIGA technology, the 100 hollow microneedles fabricated by Synchrotron Radiation deep X-ray lithography through PCT (Plane-pattern to Cross-section Transfer) technique have been consisted in 5x5 mm2 area. The microneedle is 300 μm in base-diameter, 500 μm-pitch, 800 μm-height and 50 μm hole-diameter. The total size of the blood extraction device is 2x2x2 cm 3. The package is made from a plastic socket including slots for inserting microneedle array and ISFET connecting to an electrical circuit for the monitoring. Through the dimensional design for simply handling and selection of disposable material, the patients can self-evaluate the critical level of the body minerals in anywhere and anytime.

  8. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

    Directory of Open Access Journals (Sweden)

    Tsuda Yuko

    2010-12-01

    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  9. Data analysis & probability task sheets : grades pk-2

    CERN Document Server

    Cook, Tanya

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the data analysis & probability concepts addressed by the NCTM standards and encourages your students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  10. Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

    Science.gov (United States)

    Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

    2013-01-01

    Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

  11. Identification and red blood cell automated counting from blood smear images using computer-aided system.

    Science.gov (United States)

    Acharya, Vasundhara; Kumar, Preetham

    2018-03-01

    Red blood cell count plays a vital role in identifying the overall health of the patient. Hospitals use the hemocytometer to count the blood cells. Conventional method of placing the smear under microscope and counting the cells manually lead to erroneous results, and medical laboratory technicians are put under stress. A computer-aided system will help to attain precise results in less amount of time. This research work proposes an image-processing technique for counting the number of red blood cells. It aims to examine and process the blood smear image, in order to support the counting of red blood cells and identify the number of normal and abnormal cells in the image automatically. K-medoids algorithm which is robust to external noise is used to extract the WBCs from the image. Granulometric analysis is used to separate the red blood cells from the white blood cells. The red blood cells obtained are counted using the labeling algorithm and circular Hough transform. The radius range for the circle-drawing algorithm is estimated by computing the distance of the pixels from the boundary which automates the entire algorithm. A comparison is done between the counts obtained using the labeling algorithm and circular Hough transform. Results of the work showed that circular Hough transform was more accurate in counting the red blood cells than the labeling algorithm as it was successful in identifying even the overlapping cells. The work also intends to compare the results of cell count done using the proposed methodology and manual approach. The work is designed to address all the drawbacks of the previous research work. The research work can be extended to extract various texture and shape features of abnormal cells identified so that diseases like anemia of inflammation and chronic disease can be detected at the earliest.

  12. Performance of Gram staining on blood cultures flagged negative by an automated blood culture system.

    Science.gov (United States)

    Peretz, A; Isakovich, N; Pastukh, N; Koifman, A; Glyatman, T; Brodsky, D

    2015-08-01

    Blood is one of the most important specimens sent to a microbiology laboratory for culture. Most blood cultures are incubated for 5-7 days, except in cases where there is a suspicion of infection caused by microorganisms that proliferate slowly, or infections expressed by a small number of bacteria in the bloodstream. Therefore, at the end of incubation, misidentification of positive cultures and false-negative results are a real possibility. The aim of this work was to perform a confirmation by Gram staining of the lack of any microorganisms in blood cultures that were identified as negative by the BACTEC™ FX system at the end of incubation. All bottles defined as negative by the BACTEC FX system were Gram-stained using an automatic device and inoculated on solid growth media. In our work, 15 cultures that were defined as negative by the BACTEC FX system at the end of the incubation were found to contain microorganisms when Gram-stained. The main characteristic of most bacteria and fungi growing in the culture bottles that were defined as negative was slow growth. This finding raises a problematic issue concerning the need to perform Gram staining of all blood cultures, which could overload the routine laboratory work, especially laboratories serving large medical centers and receiving a large number of blood cultures.

  13. Pharmacokinetic modeling of therapies for systemic lupus erythematosus

    OpenAIRE

    Yang, Xiaoyan; Sherwin, Catherine MT; Yu, Tian; Yellepeddi, Venkata K; Brunner, Hermine I; Vinks, Alexander A

    2015-01-01

    With the increasing use of different types of therapies in treating autoimmune diseases such as systemic lupus erythematosus (SLE), there is a need to utilize pharmacokinetic (PK) strategies to optimize the clinical outcome of these treatments. Various PK analysis approaches, including population PK modeling and physiologically based PK modeling, have been used to evaluate drug PK characteristics and population variability or to predict drug PK profiles in a mechanistic manner. This review ou...

  14. Ultrasound systems for blood velocity estimation

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt

    1998-01-01

    Medical ultrasound scanners can be used both for displayinggray-scale images of the anatomy and for visualizing theblood flow dynamically in the body.The systems can interrogate the flow at a single position in the bodyand there find the velocity distribution over time. They can also show adynamic...

  15. Do autologous blood transfusion systems reduce allogeneic blood transfusion in total knee arthroplasty?

    Science.gov (United States)

    Pawaskar, Aditya; Salunke, Abhijeet Ashok; Kekatpure, Aashay; Chen, Yongsheng; Nambi, G I; Tan, Junhao; Sonawane, Dhiraj; Pathak, Subodhkumar

    2017-09-01

    To study whether autologus blood transfusion systems reduce the requirement of allogneic blood transfusion in patients undergoing total knee arthroplasty. A comprehensive search of the published literature with PubMed, Scopus and Science direct database was performed. The following search terms were used: (total knee replacement) OR (total knee arthroplasty) OR (TKA) AND (blood transfusion) OR (autologous transfusion) OR (autologous transfusion system). Using search syntax, a total of 748 search results were obtained (79 from PubMed, 586 from Science direct and 83 from Scopus). Twenty-one randomized control trials were included for this meta-analysis. The allogenic transfusion rate in autologus blood transfusion (study) group was significantly lower than the control group (28.4 and 53.5 %, respectively) (p value 0.0001, Relative risk: 0.5). The median units of allogenic blood transfused in study control group and control group were 0.1 (0.1-3.0) and 1.3 (0.3-2.6), respectively. The median hospital stay in study group was 9 (6.7-15.6) days and control group was 8.7 (6.6-16.7) days. The median cost incurred for blood transfusion per patient in study and control groups was 175 (85.7-260) and 254.7 (235-300) euros, respectively. This meta-analysis demonstrates that the use of auto-transfusion systems is a cost-effective method to reduce the need for and quantity of allogenic transfusion in elective total knee arthroplasty. Level I.

  16. Translational PK/PD of anti-infective therapeutics.

    Science.gov (United States)

    Rathi, Chetan; Lee, Richard E; Meibohm, Bernd

    Translational PK/PD modeling has emerged as a critical technique for quantitative analysis of the relationship between dose, exposure and response of antibiotics. By combining model components for pharmacokinetics, bacterial growth kinetics and concentration-dependent drug effects, these models are able to quantitatively capture and simulate the complex interplay between antibiotic, bacterium and host organism. Fine-tuning of these basic model structures allows to further account for complicating factors such as resistance development, combination therapy, or host responses. With this tool set at hand, mechanism-based PK/PD modeling and simulation allows to develop optimal dosing regimens for novel and established antibiotics for maximum efficacy and minimal resistance development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Sandia reactor kinetics codes: SAK and PK1D

    International Nuclear Information System (INIS)

    Pickard, P.S.; Odom, J.P.

    1978-01-01

    The Sandia Kinetics code (SAK) is a one-dimensional coupled thermal-neutronics transient analysis code for use in simulation of reactor transients. The time-dependent cross section routines allow arbitrary time-dependent changes in material properties. The one-dimensional heat transfer routines are for cylindrical geometry and allow arbitrary mesh structure, temperature-dependent thermal properties, radiation treatment, and coolant flow and heat-transfer properties at the surface of a fuel element. The Point Kinetics 1 Dimensional Heat Transfer Code (PK1D) solves the point kinetics equations and has essentially the same heat-transfer treatment as SAK. PK1D can address extended reactor transients with minimal computer execution time

  18. The accuracy of self monitoring blood glucose meter systems in ...

    African Journals Online (AJOL)

    Many patients were referred to Kololo polyclinic laboratory to have their blood glucose checked because the values obtained on the patients' glucose meter systems did not tally with familiar clinical signs and symptoms. This prompted an experimental set up to check glucose meter systems using a larger number of patients.

  19. Five strands of math tasks big book : grades pk-2

    CERN Document Server

    Reed, Nat; Forest, Chris

    2009-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Included are challenging problem-solving tasks which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  20. Five strands of math drills big book : grades PK-2

    CERN Document Server

    Reed, Nat; Forest, Chris

    2011-01-01

    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Included are warm-up and timed drill activities which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  1. PK Tradesman Tmi Developing marketing in a multicultural environment

    OpenAIRE

    Juutilainen, Tomi; Kangasperko, Pyry

    2010-01-01

    Purpose of the thesis was to find ways to improve PK Tradesman Tmi's customer and partner relations and marketing processes as well as research the viability of its product offering. This was accomplished by researching the concepts of guerrilla marketing and customer relationship management, and comparing different aspects of the Finnish and Chinese culture. The thesis consists in part of exploring the theory of aforementioned concepts, and in part of a ques-tionnaire which was implement...

  2. Role of neurotensin and opioid receptors in the cardiorespiratory effects of [Ile⁹]PK20, a novel antinociceptive chimeric peptide.

    Science.gov (United States)

    Kaczyńska, Katarzyna; Szereda-Przestaszewska, Małgorzata; Kleczkowska, Patrycja; Lipkowski, Andrzej W

    2014-10-15

    Ile(9)PK20 is a novel hybrid of opioid-neurotensin peptides synthesized from the C-terminal hexapeptide of neurotensin and endomorphin-2 pharmacophore. This chimeric compound shows potent central and peripheral antinociceptive activity in experimental animals, however nothing is known about its influence on the respiratory and cardiovascular parameters. The present study was designed to determine the cardiorespiratory effects exerted by an intravenous injection (i.v.) of [Ile(9)]PK20. Share of the vagal afferentation and the contribution of NTS1 neurotensin and opioid receptors were tested. Intravenous injection of the hybrid at a dose of 100 μg/kg in the intact, anaesthetized rats provoked an increase in tidal volume preceded by a prompt short-lived decrease. Immediately after the end of injection brief acceleration of the respiratory rhythm appeared, and was ensued by the slowing down of breathing. Changes in respiration were concomitant with a bi-phasic response of the blood pressure: an immediate increase was followed by a sustained hypotension. Midcervical vagotomy eliminated the increase in tidal volume and respiratory rate responses. Antagonist of opioid receptors - naloxone hydrochloride eliminated only [Ile(9)]PK20-evoked decline in tidal volume response. Blockade of NTS1 receptors with an intravenous dose of SR 142,948, lessened the remaining cardiorespiratory effects. This study depicts that [Ile(9)]PK20 acting through neurotensin NTS1 receptors augments the tidal component of the breathing pattern and activates respiratory timing response through the vagal pathway. Blood pressure effects occur outside vagal afferentation and might result from activation of the central and peripheral vascular NTS1 receptors. In summary the respiratory effects of the hybrid appeared not to be profound, but they were accompanied with unfavourable prolonged hypotension. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. EARLY ULTRAVIOLET OBSERVATIONS OF A TYPE IIn SUPERNOVA (2007pk)

    International Nuclear Information System (INIS)

    Pritchard, T. A.; Roming, P. W. A.; Brown, P. J.; Kuin, N. P. M.; Oates, S. R.; Bayless, Amanda J.; Holland, S. T.; Immler, S.; Milne, P.

    2012-01-01

    We present some of the earliest UV observations of a Type IIn supernova (SN)—SN 2007pk, where UV and optical observations using Swift's Ultra-Violet/Optical Telescope began 3 days after discovery or ∼5 days after shock breakout. The SN observations commence at approximately maximum light in the UV and u-band filters, suggesting that the UV light curve peaks begin very rapidly after the initial explosion, and subsequently exhibit a linear decay of 0.20, 0.21, 0.16 mag day –1 in the UVOT uvw2, uvm2, uvw1 (λ c = 1928, 2246, 2600 Å) filters. Meanwhile the b- and v-band light curves begin approximately seven days before v-band peak and exhibit a shallow rise followed by a subsequent decay. A series of optical/near-IR spectra taken with the Hobby-Eberly Telescope at days 3-26 after discovery show spectra similar to that of the peculiar Type IIn 1998S. The emission from 2007pk falls below detection ∼20 days after discovery in the UV and 50 days in the optical, showing no sign of the long duration emission seen in other Type IIn SNe. We examine the physical and spectral characteristics of 2007pk and compare its UV light curve and decay rate with other Type II SNe.

  4. Point-of-care, portable microfluidic blood analyzer system

    Science.gov (United States)

    Maleki, Teimour; Fricke, Todd; Quesenberry, J. T.; Todd, Paul W.; Leary, James F.

    2012-03-01

    Recent advances in MEMS technology have provided an opportunity to develop microfluidic devices with enormous potential for portable, point-of-care, low-cost medical diagnostic tools. Hand-held flow cytometers will soon be used in disease diagnosis and monitoring. Despite much interest in miniaturizing commercially available cytometers, they remain costly, bulky, and require expert operation. In this article, we report progress on the development of a battery-powered handheld blood analyzer that will quickly and automatically process a drop of whole human blood by real-time, on-chip magnetic separation of white blood cells (WBCs), fluorescence analysis of labeled WBC subsets, and counting a reproducible fraction of the red blood cells (RBCs) by light scattering. The whole blood (WB) analyzer is composed of a micro-mixer, a special branching/separation system, an optical detection system, and electronic readout circuitry. A droplet of un-processed blood is mixed with the reagents, i.e. magnetic beads and fluorescent stain in the micro-mixer. Valve-less sorting is achieved by magnetic deflection of magnetic microparticle-labeled WBC. LED excitation in combination with an avalanche photodiode (APD) detection system is used for counting fluorescent WBC subsets using several colors of immune-Qdots, while counting a reproducible fraction of red blood cells (RBC) is performed using a laser light scatting measurement with a photodiode. Optimized branching/channel width is achieved using Comsol Multi-Physics™ simulation. To accommodate full portability, all required power supplies (40v, +/-10V, and +3V) are provided via step-up voltage converters from one battery. A simple onboard lock-in amplifier is used to increase the sensitivity/resolution of the pulse counting circuitry.

  5. SBR-Blood: systems biology repository for hematopoietic cells.

    Science.gov (United States)

    Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

    2016-01-04

    Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2pk)

    Science.gov (United States)

    Downs, Meghan E.; Lee, Stuart M. C.; Ploutz-Snyder, Lori; Feiveson, Alan

    2016-01-01

    Maximal oxygen (VO2pk) is the maximum amount of oxygen that the body can use during intense exercise and is used for benchmarking endurance exercise capacity. The most accurate method to determineVO2pk requires continuous measurements of ventilation and gas exchange during an exercise test to maximal effort, which necessitates expensive equipment, a trained staff, and time to set-up the equipment. For astronauts, accurate VO2pk measures are important to assess mission critical task performance capabilities and to prescribe exercise intensities to optimize performance. Currently, astronauts perform submaximal exercise tests during flight to predict VO2pk; however, while submaximal VO2pk prediction equations provide reliable estimates of mean VO2pk for populations, they can be unacceptably inaccurate for a given individual. The error in current predictions and logistical limitations of measuring VO2pk, particularly during spaceflight, highlights the need for improved estimation methods.

  7. How Should Blood Glucose Meter System Analytical Performance Be Assessed?

    Science.gov (United States)

    Simmons, David A

    2015-08-31

    Blood glucose meter system analytical performance is assessed by comparing pairs of meter system and reference instrument blood glucose measurements measured over time and across a broad array of glucose values. Consequently, no single, complete, and ideal parameter can fully describe the difference between meter system and reference results. Instead, a number of assessment tools, both graphical (eg, regression plots, modified Bland-Altman plots, and error grid analysis) and tabular (eg, International Organization for Standardization guidelines, mean absolute difference, and mean absolute relative difference) have been developed to evaluate meter system performance. The strengths and weaknesses of these methods of presenting meter system performance data, including a new method known as Radar Plots, are described here. © 2015 Diabetes Technology Society.

  8. Variability in blood and blood component utilization as assessed by an anesthesia information management system.

    Science.gov (United States)

    Frank, Steven M; Savage, Will J; Rothschild, Jim A; Rivers, Richard J; Ness, Paul M; Paul, Sharon L; Ulatowski, John A

    2012-07-01

    Data can be collected for various purposes with anesthesia information management systems. The authors describe methods for using data acquired from an anesthesia information management system to assess intraoperative utilization of blood and blood components. Over an 18-month period, data were collected on 48,086 surgical patients at a tertiary care academic medical center. All data were acquired with an automated anesthesia recordkeeping system. Detailed reports were generated for blood and blood component utilization according to surgical service and surgical procedure, and for individual surgeons and anesthesiologists. Transfusion hemoglobin trigger and target concentrations were compared among surgical services and procedures, and between individual medical providers. For all patients given erythrocytes, the mean transfusion hemoglobin trigger was 8.4 ± 1.5, and the target was 10.2 ± 1.5 g/dl. Variation was significant among surgical services (trigger range: 7.5 ± 1.2-9.5 ± 1.1, P = 0.0001; target range: 9.1 ± 1.2-11.3 ± 1.4 g/dl, P = 0.002), surgeons (trigger range: 7.2 ± 0.7-9.8 ± 1.0, P = 0.001; target range: 8.8 ± 0.9-11.8 ± 1.3 g/dl, P = 0.001), and anesthesiologists (trigger range: 7.2 ± 0.8-9.6 ± 1.2, P = 0.001; target range: 9.0 ± 0.9-11.7 ± 1.3 g/dl, P = 0.0004). The use of erythrocyte salvage, fresh frozen plasma, and platelets varied threefold to fourfold among individual surgeons compared with their peers performing the same surgical procedure. The use of data acquired from an anesthesia information management system allowed a detailed analysis of blood component utilization, which revealed significant variation among surgical services and surgical procedures, and among individual anesthesiologists and surgeons compared with their peers. Incorporating these methods of data acquisition and analysis into a blood management program could reduce unnecessary transfusions, an outcome that may increase patient safety and reduce costs.

  9. Some central nervous system and blood pressure lowering effects of ...

    African Journals Online (AJOL)

    The methanol extract of the leaves of Spondias mombin (SP) was evaluated for some central nervous system and blood pressure lowering effect in albino wistar rats and mice. The extract was administered to pre-weighed mice (20-35 g), divided into five groups of five mice each at the doses of 50, 100 and 200 mg/kg for the ...

  10. 21 CFR 864.9145 - Processing system for frozen blood.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Processing system for frozen blood. 864.9145 Section 864.9145 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture...

  11. Antioxidant status, immune system, blood metabolites and carcass ...

    African Journals Online (AJOL)

    This experiment was conducted to evaluate the effects of dietary turmeric rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of organs in pre and post heat stressed broilers. Two hundred and sixty-four (264) day-old male Arian broiler chicks were randomly ...

  12. New approach to 'top-and-bottom' whole blood separation using the multiunit TACSI WB system: quality of blood components.

    Science.gov (United States)

    Lotens, A; Najdovski, T; Cellier, N; Ernotte, B; Lambermont, M; Rapaille, A

    2014-10-01

    TACSI whole blood system is designed to combine primary and secondary processing of six whole blood bags into plasma units, buffy coat and red blood cell concentrates. The aim of this study was to investigate the specifications and in vitro storage parameters of blood components compared with standard centrifugation and separation processing. Whole blood bags, collected in CRC kits, were treated on a TACSI whole blood system. They were compared with whole blood bags collected in Composelect kits. In addition to routine quality control analyses, conservation studies were performed on red blood cell concentrates for 42 days and on plasma for 6 months. Platelets pools with five buffy coats were also created, and cellular contamination was evaluated. Red blood cell concentrates produced from TACSI whole blood met European quality requirements. For white blood cell count, one individual result exceeded 1 × 10(6) cells/unit. All plasma units fell within specifications for residual cellular contamination and storage parameters. The performances of the TACSI whole blood system allow for the preparation of low volume buffy coats with a recovery of 90% of whole blood platelets. Haemoglobin losses in TACSI BC are smaller, but this did not result in higher haemoglobin content of red cells. These BC are suitable for the production of platelet concentrates. From these in vitro data, red blood cell concentrates produced using TACSI whole blood are suitable for clinical use with a quality at least equivalent to the control group. © 2014 International Society of Blood Transfusion.

  13. Towards a Hyperconnected Transportation Management System: Application to Blood Logistics

    OpenAIRE

    Schoen , Quentin; Lauras , Matthieu; Truptil , Sébastien; Fontanili , Franck; Anquetil , Anne-Ghislaine

    2016-01-01

    Part 1: Hyperconnectivity and Interoperation - Hyperconnected Systems; International audience; Internet of Things, connected devices, and other wireless sensors networks offer a number of new opportunities to manage transportation flows. This is particularly interesting for critical Supply Chains like Blood Supply Chains. In this research work, we investigate how such new technologies can enhance transportation system by better managing hazards and changes. By developing an event-driven decis...

  14. A Business Plan for PK Handbags Manufacturing Company

    OpenAIRE

    Somchatvong, Laddaporn

    2009-01-01

    PK Co. Limited is a small family-business-owned company located in Thailand. Since established in 1998, the company’s business is manufacturing women’s fashion handbags for wholesale apparel trading company in Thailand. The company also produces and merchandises premium gifts for Kasikorn Bank, one of the largest banks in Thailand. Over the past ten years, the company has generated more than 200 million Baht in revenue or £ 3.6 million . The founders, Likit and Duangporn Somchatvong, have ...

  15. Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

    Science.gov (United States)

    Fernández-Varón, Emilio; Cárceles-García, Carlos; Serrano-Rodríguez, Juan Manuel; Cárceles-Rodríguez, Carlos M

    2016-10-13

    Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica

  16. [Evaluation of the quality control system in blood transfusion service].

    Science.gov (United States)

    Jovanović, R

    2000-01-01

    Implementation of quality system improvement at the Blood Transfusion Institute Novi Sad, included adjustments in practice to the request of ISO 9001 standard. Quality improvement must be a permanent activity of the Institute. The audit is a management tool for monitoring the quality assurance system and is either a quality audit or a medical audit. A well planned, comprehensive quality audit covers each activity of the Blood Transfusion Institute. The procedures may be internal or external. Quality manager is responsible for annual internal quality audits. The purpose of internal audits is to check the efficiency of the quality system in terms of realization of quality policy, fulfullment of designed targets and implementation of quality system documents. An internal quality audit is performed in accordance with the procedure and audit findings are reported to the management in a form of internal quality report as a part of quality system review. The findings must be communicated to all persons responsible for the controlled area. Quality manager can initiate an internal quality audit whenever it is realized that problems about the quality system have occurred. Audits are conducted by the quality manager or an audit team. The accurate list of internal auditors is kept in the Institute archive. Medical audit carried out by a transfusion committee, evaluates the quality of blood transfusion for determining the degree of compliance with established local or national guidelines, in order to promote optimal transfusion practice. Audits are not only used for determining further quality management activities, but also make basis for creating and maintenance of excellent relations with product and service users. Considering all this, Blood Transfusion Institute exceeds the requirements of ISO 9000 standards series.

  17. Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First Time in Children and PK Study Design.

    Science.gov (United States)

    Vozmediano, Valvanera; Sologuren, Ander; Lukas, John C; Leal, Nerea; Rodriguez, Mónica

    2017-12-01

    Bilastine is an H 1 antagonist whose pharmacokinetics (PK) and pharmacodynamics (PD) have been resolved in adults with a therapeutic oral dose of 20 mg/day. Bilastine has favorable characteristics for use in pediatrics but the PK/PD and the optimal dose in children had yet to be clinically explored. The purpose is to: (1) Develop an ontogenic predictive model of bilastine PK linked to the PD in adults by integrating current knowledge; (2) Use the model to design a PK study in children; (3) Confirm the selected dose and the study design through the evaluation of model predictability in the first recruited children; (4) Consider for inclusion the group of younger children (design an adaptive PK trial in children that was then confirmed using data from the first recruits by comparing observations with model predictions. PK/PD simulations supported the selection of 10 mg/day in 2 to design hence trial continuation. The model successfully predicted bilastine PK in pediatrics and optimally assisted the selection of the dose and sampling scheme for the trial in children. The selected dose was considered suitable for younger children and the forthcoming safety study in children aged 2 to <12 years.

  18. Blood

    Science.gov (United States)

    ... a reduced production of red blood cells, including: Iron deficiency anemia. Iron deficiency anemia is the most common type of anemia and ... inflammatory bowel disease are especially likely to have iron deficiency anemia. Anemia due to chronic disease. People with chronic ...

  19. 21 CFR 864.9175 - Automated blood grouping and antibody test system.

    Science.gov (United States)

    2010-04-01

    ...) Identification. An automated blood grouping and antibody test system is a device used to group erythrocytes (red blood cells) and to detect antibodies to blood group antigens. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated blood grouping and antibody test system...

  20. Miniaturized Blood Pressure Telemetry System with RFID Interface

    Directory of Open Access Journals (Sweden)

    Michele Caldara

    2016-08-01

    Full Text Available This work deals with the development and characterization of a potentially implantable blood pressure telemetry system, based on an active Radio-Frequency IDentification (RFID tag, International Organization for Standardization (ISO 15693 compliant. This approach aims to continuously measure the average, systolic and diastolic blood pressure of the small/medium animals. The measured pressure wave undergoes embedded processing and results are stored onboard in a non-volatile memory, providing the data under interrogation by an external RFID reader. In order to extend battery lifetime, RFID energy harvesting has been investigated. The paper presents the experimental characterization in a laboratory and preliminary in-vivo tests. The device is a prototype mainly intended, in a future engineered version, for monitoring freely moving test animals for pharmaceutical research and drug safety assessment purposes, but it could have multiple uses in environmental and industrial applications.

  1. Latest Results on Complex Plasmas with the PK-3 Plus Laboratory on Board the International Space Station

    Science.gov (United States)

    Schwabe, M.; Du, C.-R.; Huber, P.; Lipaev, A. M.; Molotkov, V. I.; Naumkin, V. N.; Zhdanov, S. K.; Zhukhovitskii, D. I.; Fortov, V. E.; Thomas, H. M.

    2018-03-01

    Complex plasmas are low temperature plasmas that contain microparticles in addition to ions, electrons, and neutral particles. The microparticles acquire high charges, interact with each other and can be considered as model particles for effects in classical condensed matter systems, such as crystallization and fluid dynamics. In contrast to atoms in ordinary systems, their movement can be traced on the most basic level, that of individual particles. In order to avoid disturbances caused by gravity, experiments on complex plasmas are often performed under microgravity conditions. The PK-3 Plus Laboratory was operated on board the International Space Station from 2006 - 2013. Its heart consisted of a capacitively coupled radio-frequency plasma chamber. Microparticles were inserted into the low-temperature plasma, forming large, homogeneous complex plasma clouds. Here, we review the results obtained with recent analyzes of PK-3 Plus data: We study the formation of crystallization fronts, as well as the microparticle motion in, and structure of crystalline complex plasmas. We investigate fluid effects such as wave transmission across an interface, and the development of the energy spectra during the onset of turbulent microparticle movement. We explore how abnormal particles move through, and how macroscopic spheres interact with the microparticle cloud. These examples demonstrate the versatility of the PK-3 Plus Laboratory.

  2. Noninvasive biosensor and wireless interrogating system for glucose in blood

    Science.gov (United States)

    Varadan, Vijay K.; Whitchurch, Ashwin K.; Sarukesi, K.

    2003-07-01

    Hypoglycemia-abnormal decrease in blood sugar-is a major obstacle in the management of diabetes and prevention of long-term complications, and it may impose serious effects on the brain, including impairment of memory and other cognitive functions. This paper presents the development of a non-invasive sensor with miniaturized telemetry device in a wrist-watch for monitoring glucose concentration in blood. The sensor concept is based on optical chirality of glucose level in the interstitial fluid. The wrist watch consists of a laser power source of the wavelength compatible with the glucose. A nanofilm with specific chirality is placed at the bottom of the watch. The light then passes through the film and illuminates a small area on the skin. It has been documented that there is certain concentration of sugar level is taken by the intertitial fluid from the blood stream and deposit a portion of it at the dead skin. The wrist-watch when in contact with the outer skin of the human will thus monitor the glucose concentration. A wireless monitoring system in the watch then downloads the data from the watch to a Palm or a laptop computer.

  3. A physiologically-based pharmacokinetic(PB-PK) model for ethylene dibromide : relevance of extrahepatic metabolism

    NARCIS (Netherlands)

    Hissink, A M; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, D.J.; Commandeur, J N; Vermeulen, N P; van Bladeren, P.J.

    A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new

  4. A physiologically-based pharmacokinetic (PB-PK) model for ethylene dibromide : relevance of extrahepatic metabolism

    NARCIS (Netherlands)

    Hissink, A.M.; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, J.D.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, P.J. van

    2000-01-01

    A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new

  5. Native American Women Perceptions in Pk-12 Administrative Positions in North Dakota Public Schools

    Science.gov (United States)

    DeCoteau, Lanelia Irene

    2012-01-01

    Historically Native American women have experienced barriers in their rise to Pk-12 educational leadership positions. There is limited research available on Native American women in educational leadership. Therefore, the purpose for this survey study was to discover what inspired current Pk-12 Native American women educational leaders to choose…

  6. Impact of Shed/Soluble targets on the PK/PD of approved therapeutic monoclonal antibodies.

    Science.gov (United States)

    Samineni, Divya; Girish, Sandhya; Li, Chunze

    2016-12-01

    Suboptimal treatment for monoclonal antibodies (mAbs) directed against endogenous circulating soluble targets and the shed extracellular domains (ECD) of the membrane-bound targets is an important clinical concern due to the potential impact of mAbs on the in vivo efficacy and safety. Consequently, there are considerable challenges in the determination of an optimal dose and/or dosing regimen. Areas covered: This review outlines the impact of shed antigen targets from membrane-bound proteins and soluble targets on the PK and/or PD of therapeutic mAbs that have been approved in the last decade. We discuss various bioanalytical techniques that have facilitated the interpretation of the PK/PD properties of therapeutic mAbs and also considered the factors that may impact such measurements. Quantitative approaches include target-mediated PK models and bi- or tri-molecular interaction PK/PD models that describe the relationships between the antibody PK and the ensuing effects on PD biomarkers, to facilitate the mAb PK/PD characterization. Expert commentary: The proper interpretation of PK/PD relationships through the integrated PK/PD modeling and bioanalytical strategy facilitates a mechanistic understanding of the disease processes and dosing regimen optimization, thereby offering insights into developing effective therapeutic regimens. This review provides an overview of the impact of soluble targets or shed ECD on mAb PK/PD properties. We provide examples of quantitative approaches that facilitate the characterization of mAb PK/PD characteristics and their corresponding bioanalytical strategies.

  7. Uptake of inflammatory cell marker [{sup 11}C]PK11195 into mouse atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Laitinen, Iina; Marjamaeki, Paeivi; Naagren, Kjell; Roivainen, Anne; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Laine, V.J.O. [Turku University Hospital, Department of Pathology, Turku (Finland); Wilson, Ian [GE Healthcare Biosciences, Medical Diagnostics, London (United Kingdom); Leppaenen, Pia; Ylae-Herttuala, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland)

    2009-01-15

    The ligand [{sup 11}C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [{sup 11}C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [{sup 11}C]PK11195 in imaging inflammation in the atherosclerotic plaques. The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [{sup 3}H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [{sup 11}C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. The [{sup 3}H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [{sup 11}C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of {sup 11}C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Our results indicate that the uptake of [{sup 11}C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [{sup 11}C]PK11195 in clinical imaging of atherosclerotic plaques. (orig.)

  8. Model based population PK-PD analysis of furosemide for BP lowering effect: A comparative study in primary and secondary hypertension.

    Science.gov (United States)

    Shukla, Mahendra; Ibrahim, Moustafa M A; Jain, Moon; Jaiswal, Swati; Sharma, Abhisheak; Hanif, Kashif; Lal, Jawahar

    2017-11-15

    Though numerous reports have demonstrated multiple mechanisms by which furosemide can exert its anti-hypertensive response. However, lack of studies describing PK-PD relationship for furosemide featuring its anti-hypertensive property has limited its usage as a blood pressure (BP) lowering agent. Serum concentrations and mean arterial BP were monitored following 40 and 80mgkg -1 multiple oral dose of furosemide in spontaneously hypertensive rats (SHR) and DOCA-salt induced hypertensive (DOCA-salt) rats. A simultaneous population PK-PD relationship using E max model with effect compartment was developed to compare the anti-hypertensive efficacy of furosemide in these rat models. A two-compartment PK model with Weibull-type absorption and first-order elimination best described the serum concentration-time profile of furosemide. In the present study, post dose serum concentrations of furosemide were found to be lower than the EC 50 . The EC 50 predicted in DOCA-salt rats was found to be lower (4.5-fold), whereas the tolerance development was higher than that in SHR model. The PK-PD parameter estimates, particularly lower values of EC 50 , K e and Q in DOCA-salt rats as compared to SHR, pinpointed the higher BP lowering efficacy of furosemide in volume overload induced hypertensive conditions. Insignificantly altered serum creatinine and electrolyte levels indicated a favorable side effect profile of furosemide. In conclusion, the final PK-PD model described the data well and provides detailed insights into the use of furosemide as an anti-hypertensive agent. Copyright © 2017. Published by Elsevier B.V.

  9. An Analysis of and Recommendations for the Peruvian Blood Collection and Transfusion System.

    Science.gov (United States)

    George, Paul E; Vidal, Julio; Garcia, Patricia J

    2016-05-01

    Peru experienced a crisis in its blood collection and supply system in the mid-2000s, as contaminated blood led to several transfusion-transmitted infections (TTI), occurring in the backdrop of extremely low voluntary donation rates and a national blood supply shortage. Thus, the Peruvian Ministry of Health (MINSA) implemented a national investigation on the safety and quality of the Peruvian blood collection/transfusion network. Every Peruvian blood bank was evaluated by MINSA from 2007-2008. These evaluations consisted of an update of the national registry of blood banks and visits to each blood bank from MINSA oversight teams. Information was collected on the condition of the blood bank personnel, equipment, supplies, and practices. Further, previously-collected blood at each blood bank was randomly selected and screened for TTI-causing pathogens. Uncovered in this investigation was a fragmented, under-equipped, and poorly-staffed blood collection and transfusion network, consisting of 241 independent blood banks and resulting in suboptimal allocation of resources. Further, blood with evidence of TTI-causing pathogens (including Hepatitis B, Hepatitis C, and syphilis) and set for transfusion was discovered at three separate blood banks as part of the random screening process. Using the successful reorganizations of national blood supply systems in other Latin American countries as examples, Peru would be well-served to form large, high-volume, regional blood collection and transfusion centers, responsible for blood collection and screening for the entire country. The small, separate blood banks would then be transformed into a network of blood transfusion centers, not responsible for blood collection. This reorganization would allow Peru to better utilize its resources, standardize the blood collection and transfusion process, and increase voluntary donation, resulting in a safer, more abundant national blood product.

  10. A novel system for providing compatible blood to patients during surgery: "self-service" electronic blood banking by nursing staff.

    Science.gov (United States)

    Cheng, G; Chiu, D S; Chung, A S; Wong, H F; Chan, M W; Lui, Y K; Choy, F M; Chan, J C; Chan, A H; Lam, S T; Fan, T C

    1996-04-01

    A good blood bank must be able to provide compatible blood units promptly to operating room patients with minimal wastage. A "self-service" by nursing staff blood banking system that is safe, efficient, and well-accepted has been developed. Specific blood units are no longer assigned to surgical patients who have a negative pretransfusion antibody screen, irrespective of the type of surgery. A computer-generated list of the serial numbers of all group-identical blood units currently in the blood bank inventory is provided for each patient. The units themselves are not labeled with a patient's name. The group O list will be provided for group O patients, the group A list for group A patients, and so forth. Should the patient require transfusion during surgery, the operating room nurses go to the refrigerator, remove any group-identical unit, and check the serial number of the unit against the serial numbers on the patient's list. If the serial number is on that list, the blood bank will accept responsibility for compatibility. The system was implemented in 1995. Since implementation, a total of 2154 patients have undergone operations at this hospital. Thirty-two patients received more than 10 units of red cells each. There were no transfusion errors. The crossmatch-to-transfusion ratio was reduced from 1.67 to 1.12. Turnaround time for supplying additional or urgent units to patients in operating room was shortened from 33 to 2.5 minutes. There was no incidence of a blood unit's serial number not being on the list. Work by nurses and technical staff was reduced by nearly 50 percent. The "self-service" (by nursing staff) blood banking system described is safe and efficient. It saves staff time and can be easily set up.

  11. Mycobacterium tuberculosis bacteremia detected by the Isolator lysis-centrifugation blood culture system.

    OpenAIRE

    Kiehn, T E; Gold, J W; Brannon, P; Timberger, R J; Armstrong, D

    1985-01-01

    Mycobacterium tuberculosis was detected by the Isolator lysis-centrifugation blood culture system from the blood of a patient with tuberculosis of the breast. The organism also grew on conventional laboratory media inoculated with pleural fluid from the patient.

  12. Synthesis and characterization of [{sup 11}C]PK11195 as a PET radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Fernanda A. F.; Silveira, Marina B.; Oliveira, Amanda P.; Nascimento, Leonardo T.C.; Silva, Juliana B.; Mamede, Marcelo, E-mail: nanda10a@gmail.com, E-mail: mamede.mm@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizontge, MG (Brazil). Unidade de Pesquisa e Produção de Radiofármacos

    2017-07-01

    The radiopharmaceutical [{sup 11}C]PK11195 has been used for Positron Emission Tomography (PET) imaging of neuroinflammatory diseases. PK11195 is a tracer that binds to the benzodiazepine peripheral receptor (PBR) currently known as membrane translocator protein (TSPO). [{sup 11}C]PK11195 is differentially accumulated in tissues which have high TSPO expression, typically microglia activation in brain tissue, which has normally low TSPO expression. The aim of this work was to synthesize and characterize [{sup 11}C]PK11195 at the Radiopharmaceutical Production Unit of CDTN to make it available for future studies and applications in major brain inflammatory diseases. The [{sup 11}C]PK11195 syntheses were performed using Tracerlab™ FXC PRO (GE) by [{sup 11}C]methylation of the precursor (R)-[N-desmethyl] PK11195. Optimizations of the reaction conditions for the synthesis of [{sup 11}C]PK11195 were: Anhydrous dimethylsulfoxide (DMSO) volume, mass of precursor, and potassium hydroxide (KOH), labelling reaction temperature and time. After comparison of the results obtained for each condition evaluated, the standard best reaction parameters were defined as: 1mg of the precursor dissolved in 300 μL of DMSO (anhydrous); 10-15mg of KOH; and labeling reaction temperature of 40°C during 2 minutes. The total synthesis time was 40 minutes and the mean non-decay-corrected radiochemical yield was 10.93 ± 3.44%. All quality control criteria were met according to previous specifications. (author)

  13. Synthesis and characterization of [11C]PK11195 as a PET radiopharmaceutical

    International Nuclear Information System (INIS)

    Almeida, Fernanda A. F.; Silveira, Marina B.; Oliveira, Amanda P.; Nascimento, Leonardo T.C.; Silva, Juliana B.; Mamede, Marcelo

    2017-01-01

    The radiopharmaceutical [ 11 C]PK11195 has been used for Positron Emission Tomography (PET) imaging of neuroinflammatory diseases. PK11195 is a tracer that binds to the benzodiazepine peripheral receptor (PBR) currently known as membrane translocator protein (TSPO). [ 11 C]PK11195 is differentially accumulated in tissues which have high TSPO expression, typically microglia activation in brain tissue, which has normally low TSPO expression. The aim of this work was to synthesize and characterize [ 11 C]PK11195 at the Radiopharmaceutical Production Unit of CDTN to make it available for future studies and applications in major brain inflammatory diseases. The [ 11 C]PK11195 syntheses were performed using Tracerlab™ FXC PRO (GE) by [ 11 C]methylation of the precursor (R)-[N-desmethyl] PK11195. Optimizations of the reaction conditions for the synthesis of [ 11 C]PK11195 were: Anhydrous dimethylsulfoxide (DMSO) volume, mass of precursor, and potassium hydroxide (KOH), labelling reaction temperature and time. After comparison of the results obtained for each condition evaluated, the standard best reaction parameters were defined as: 1mg of the precursor dissolved in 300 μL of DMSO (anhydrous); 10-15mg of KOH; and labeling reaction temperature of 40°C during 2 minutes. The total synthesis time was 40 minutes and the mean non-decay-corrected radiochemical yield was 10.93 ± 3.44%. All quality control criteria were met according to previous specifications. (author)

  14. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

    Directory of Open Access Journals (Sweden)

    Cynthia L. Hendrickson

    2010-01-01

    Full Text Available In mammalian cells, DNA double-strand breaks (DSBs are primarily repaired by nonhomologous end joining (NHEJ. The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, the presence of DNA-PKcs appears to inhibit DNA-PK-independent NHEJ, and in vitro analysis of DNA-PK-independent NHEJ in the presence of the DNA-PKcs protein remains problematic. We have developed an in vitro assay that is preferentially active for DNA-PK-independent DSB repair based solely on its reaction conditions, facilitating coincident differential biochemical analysis of the two pathways. The results indicate the biochemically distinct nature of the end-joining mechanisms represented by the DNA-PK-dependent and -independent NHEJ assays as well as functional differences between the two pathways.

  15. Portable real time analysis system for regional cerebral blood flow

    International Nuclear Information System (INIS)

    Tiernan, T.; Entine, G.; Stump, D.A.; Prough, D.S.

    1988-01-01

    A very portable, regional cerebral blood flow (rCBF) analysis instrument system suitable for use in the operating theater during surgery is under development. Cadmium telluride (CdTe) solid state radiation detectors, an 8086 based data acquisition and communications module and a DEC Microvax computer are used so that the instrument is very compact, yet has the computational power to provide real time data analysis in the clinical environment. The instrument is currently being used at Bowman Gray School of Medicine to study rCBF during cardiopulmonary bypass surgery (CPB). Preliminary studies indicate that monitoring rCBF during this surgical procedure may provide insights into the mechanism that causes a significant fraction of these patients to suffer post operative neuropsychological deficit

  16. Digital Blood Flow In Systemic Lupus Erythematosus By Photoplethysmography

    Directory of Open Access Journals (Sweden)

    Ghosh Sanjay

    2002-01-01

    Full Text Available Digital vascular status in 10 patients of systemic lupus erythematous (SLE suffering for 1 to 5 years and 5 control (normal subjects was assessed by a highly sensitive, non-invasive technique called photoplethysmography (PPG. Six patients (Group A showed clinical sign. PPG recordings were done by applying the PPG probe serially to the distal phalanges of all the digits of four limbs with Velcro-strap at an ambient temperature of 27 to 31C and humidity 60 to 65% Diminished capillary flow. On average, 12 digits (60% in Group A and 8 digits (40% in group B patients showed reduced blood circulation. Degree of vascular impairment had no bearing upon the duration of the disease. The PPG has objectively shown digital vascular impairment in all SLE patients having no correlation with the extent of clinical manifestations and the duration of the disease.

  17. Cellular response to DNA damage. Link between p53 and DNA-PK

    International Nuclear Information System (INIS)

    Salles-Passador, I.; Fotedar, R.; Fotedar, A.

    1999-01-01

    Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to ionizing radiation and display an inability to repair double-strand DNA breaks. DNA-PK is a member of a protein kinase family that includes ATR and ATM which have strong homology in their carboxy-terminal kinase domain with Pl-3 kinase. ATM has been proposed to act upstream of p53 in cellular response to ionizing radiation. DNA-PK may similarly interact with p53 in cellular growth control and in mediation of the response to ionizing radiation. (author)

  18. Discovering objects in a blood recipient information system.

    Science.gov (United States)

    Qiu, D; Junghans, G; Marquardt, K; Kroll, H; Mueller-Eckhardt, C; Dudeck, J

    1995-01-01

    Application of object-oriented (OO) methodologies has been generally considered as a solution to the problem of improving the software development process and managing the so-called software crisis. Among them, object-oriented analysis (OOA) is the most essential and is a vital prerequisite for the successful use of other OO methodologies. Though there are already a good deal of OOA methods published, the most important aspect common to all these methods: discovering objects classes truly relevant to the given problem domain, has remained a subject to be intensively researched. In this paper, using the successful development of a blood recipient information system as an example, we present our approach which is based on the conceptual framework of responsibility-driven OOA. In the discussion, we also suggest that it may be inadequate to simply attribute the software crisis to the waterfall model of the software development life-cycle. We are convinced that the real causes for the failure of some software and information systems should be sought in the methodologies used in some crucial phases of the software development process. Furthermore, a software system can also fail if object classes essential to the problem domain are not discovered, implemented and visualized, so that the real-world situation cannot be faithfully traced by it.

  19. Code development of the national hemovigilance system and expansion strategies for hospital blood banks

    Directory of Open Access Journals (Sweden)

    Kim Jeongeun

    2012-01-01

    Full Text Available Objectives : The aims of this study were to develop reportable event codes that are applicable to the national hemovigilance systems for hospital blood banks, and to present expansion strategies for the blood banks. Materials and Methods : The data were obtained from a literature review and expert consultation, followed by adding to and revising the established hemovigilance code system and guidelines to develop reportable event codes for hospital blood banks. The Medical Error Reporting System-Transfusion Medicine developed in the US and other codes of reportable events were added to the Korean version of the Biologic Products Deviation Report (BPDR developed by the Korean Red Cross Blood Safety Administration, then using these codes, mapping work was conducted. We deduced outcomes suitable for practice, referred to the results of the advisory councils, and conducted a survey with experts and blood banks practitioners. Results : We developed reportable event codes that were applicable to hospital blood banks and could cover blood safety - from blood product safety to blood transfusion safety - and also presented expansion strategies for hospital blood banks. Conclusion : It was necessary to add 10 major categories to the blood transfusion safety stage and 97 reportable event codes to the blood safety stage. Contextualized solutions were presented on 9 categories of expansion strategies of hemovigilance system for the hospital blood banks.

  20. Model-based decision making in early clinical development: minimizing the impact of a blood pressure adverse event.

    Science.gov (United States)

    Stroh, Mark; Addy, Carol; Wu, Yunhui; Stoch, S Aubrey; Pourkavoos, Nazaneen; Groff, Michelle; Xu, Yang; Wagner, John; Gottesdiener, Keith; Shadle, Craig; Wang, Hong; Manser, Kimberly; Winchell, Gregory A; Stone, Julie A

    2009-03-01

    We describe how modeling and simulation guided program decisions following a randomized placebo-controlled single-rising oral dose first-in-man trial of compound A where an undesired transient blood pressure (BP) elevation occurred in fasted healthy young adult males. We proposed a lumped-parameter pharmacokinetic-pharmacodynamic (PK/PD) model that captured important aspects of the BP homeostasis mechanism. Four conceptual units characterized the feedback PD model: a sinusoidal BP set point, an effect compartment, a linear effect model, and a system response. To explore approaches for minimizing the BP increase, we coupled the PD model to a modified PK model to guide oral controlled-release (CR) development. The proposed PK/PD model captured the central tendency of the observed data. The simulated BP response obtained with theoretical release rate profiles suggested some amelioration of the peak BP response with CR. This triggered subsequent CR formulation development; we used actual dissolution data from these candidate CR formulations in the PK/PD model to confirm a potential benefit in the peak BP response. Though this paradigm has yet to be tested in the clinic, our model-based approach provided a common rational framework to more fully utilize the limited available information for advancing the program.

  1. In vitro evaluation of the anti-leishmanial activity and toxicity of PK11195

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Sampaio Guedes

    2018-02-01

    Full Text Available BACKGROUND Leishmaniasis, one of the most neglected diseases, is a serious public health problem in many countries, including Brazil. Currently available treatments require long-term use and have serious side effects, necessitating the development of new therapeutic interventions. Because translocator protein (TSPO levels are reduced in Leishmania amazonensis-infected cells and because this protein participates in apoptosis and immunomodulation, TSPO represents a potential target for Leishmania chemotherapy. The present study evaluated PK11195, a ligand of this protein, as an anti-leishmanial agent. OBJECTIVE To evaluate the leishmanicidal activity of PK11195 against L. amazonensis in infected CBA mouse macrophages in vitro. METHODS The viability of axenic L. amazonensis, Leishmania major, and Leishmania braziliensis promastigotes was assessed after 48 h treatment with PK11195 (0.2-400 µM. Additionally, intracellular parasite viability was evaluated to determine IC50 values and the number of viable parasites in infected macrophages treated with PK11195 (50-100 µM. Infected macrophages were then treated with PK11195 (25-100 µM to determine the percentage of L. amazonensis-infected cells and the number of parasites per infected cell. Electron microscopy was used to investigate morphological changes caused by PK11195. The production of free oxygen radicals, nitric oxide, and pro-inflammatory cytokines was also evaluated in infected macrophages treated with PK11195 and primed or not primed with IFN-γ. FINDINGS Median IC50 values for PK11195 were 14.2 µM for L. amazonensis, 8.2 µM for L. major, and 3.5 µM for L. braziliensis. The selective index value for L. amazonensis was 13.7, indicating the safety of PK11195 for future testing in mammals. Time- and dose-dependent reductions in the percentage of infected macrophages, the number of parasites per infected macrophage, and the number of viable intracellular parasites were observed. Electron

  2. Characterization of CoPK02, a Ca2+/calmodulin-dependent protein kinase in mushroom Coprinopsis cinerea.

    Science.gov (United States)

    Yamashita, Masashi; Sueyoshi, Noriyuki; Yamada, Hiroki; Katayama, Syouichi; Senga, Yukako; Takenaka, Yasuhiro; Ishida, Atsuhiko; Kameshita, Isamu; Shigeri, Yasushi

    2018-04-20

    We surveyed genome sequences from the basidiomycetous mushroom Coprinopsis cinerea and isolated a cDNA homologous to CMKA, a calmodulin-dependent protein kinase (CaMK) in Aspergillus nidulans. We designated this sequence, encoding 580 amino acids with a molecular weight of 63,987, as CoPK02. CoPK02 possessed twelve subdomains specific to protein kinases and exhibited 43, 35, 40% identity with rat CaMKI, CaMKII, CaMKIV, respectively, and 40% identity with CoPK12, one of the CaMK orthologs in C. cinerea. CoPK02 showed significant autophosphorylation activity and phosphorylated exogenous proteins in the presence of Ca 2+ /CaM. By the CaM-overlay assay we confirmed that the C-terminal sequence (Trp346-Arg358) was the calmodulin-binding site, and that the binding of Ca 2+ /CaM to CoPK02 was reduced by the autophosphorylation of CoPK02. Since CoPK02 evolved in a different clade from CoPK12, and showed different gene expression compared to that of CoPK32, which is homologous to mitogen-activated protein kinase-activated protein kinase, CoPK02 and CoPK12 might cooperatively regulate Ca 2+ -signaling in C. cinerea.

  3. Modelling of the Blood Coagulation Cascade in an In Vitro Flow System

    DEFF Research Database (Denmark)

    Andersen, Nina Marianne; Sørensen, Mads Peter; Efendiev, Messoud A.

    2010-01-01

    We derive a mathematical model of a part of the blood coagulation cascade set up in a perfusion experiment. Our purpose is to simulate the influence of blood flow and diffusion on the blood coagulation pathway. The resulting model consists of a system of partial differential equations taking...... and flow equations, which guarantee non negative concentrations at all times. The criteria is applied to the model of the blood coagulation cascade....

  4. Influence of ionizing radiation and 12-crown-4 on coagulation system components of rat blood

    International Nuclear Information System (INIS)

    Kratenko, R.Yi.

    2006-01-01

    The influence of 12-crown-4 and ionizing radiation on some components of blood coagulation system: Ca 2+ contents and prostaglandin concentrations in the blood serum, and erythrocyte contents in the blood plasma are studied. The influence of 12-crown-4 and ionizing radiation increases the coagulational properties of erythrocytes. The synergism of ionizing irradiation and 12-crown-4 influence blood coagulation process points out at the occurrence of radiomimetic properties of the latter

  5. [Development of an automatic pneumatic tourniquet system that determines pressures in synchrony with systolic blood pressure].

    Science.gov (United States)

    Liu, Hongyun; Li, Kaiyuan; Zhang, Zhengbo; Guo, Junyan; Wang, Weidong

    2012-11-01

    The correlation coefficients between arterial occlusion pressure and systolic blood pressure, diastolic blood pressure, limb circumference, body mass etc were obtained through healthy volunteer experiments, in which tourniquet were applied on upper/lower extremities. The prediction equations were derived from the data of experiments by multiple regression analysis. Based on the microprocessor C8051F340, a new pneumatic tourniquet system that can determine tourniquet pressure in synchrony with systolic blood pressure was developed and verified the function and stability of designed system. Results showed that the pneumatic tourniquet which automatically adjusts occlusion pressure in accordance with systolic blood pressure could stop the flow of blood to get a bloodless field.

  6. Relationship between systemic hemodynamics and ambulatory blood pressure level are sex dependent.

    Science.gov (United States)

    Alfie, J; Waisman, G D; Galarza, C R; Magi, M I; Vasvari, F; Mayorga, L M; Cámera, M I

    1995-12-01

    Sex-related differences in systemic hemodynamics were analyzed by means of cardiac index and systemic vascular resistance according to the level of daytime ambulatory blood pressure. In addition, we assessed the relations between ambulatory blood pressure measurements and systemic hemodynamics in male and female patients. We prospectively included 52 women and 53 men referred to our unit for evaluation of arterial hypertension. Women and men were grouped according to the level of daytime mean arterial pressure: or = 110 mm Hg. Patients underwent noninvasive evaluation of resting hemodynamics (impedance cardiography) and 24-hour ambulatory blood pressure monitoring. Compared with women men with lower daytime blood pressure had a 12% higher systemic vascular resistance index (P = NS) and a 14% lower cardiac index (P < .02), whereas men with higher daytime blood pressure had a 25% higher vascular resistance (P < .003) and a 21% lower cardiac index (P < .0004). Furthermore, in men systemic vascular resistance correlated positively with both daytime and nighttime systolic and diastolic blood pressures, whereas cardiac index correlated negatively only with daytime diastolic blood pressure. In contrast, women did not exhibit any significant correlation between hemodynamic parameters and ambulatory blood pressure measurements. In conclusion, sex-related differences in systemic hemodynamics were more pronounced in the group with higher daytime hypertension. The relations between systemic hemodynamics and ambulatory blood pressure level depended on the sex of the patient. In men a progressive circulatory impairment underlies the increasing level of ambulatory blood pressure, but this was not observed in women.

  7. Mafic inclusions in Yosemite granites and Lassen Pk lavas: records of complex crust-mantle interactions

    Energy Technology Data Exchange (ETDEWEB)

    Reid, J.B. Jr.; Flinn, J.E.

    1985-01-01

    This study compares three small-scale magmatic systems dominated by mafic/felsic interaction that appear to be analogs to the evolution of their larger host systems: mafic inclusions from modern Lassen Pk lavas along with inclusions and related synplutonic dike materials from granitoids in the Tuolumne Intrusive Series. Each system represents quickly chilled mafic melt previously contaminated by digestion of rewarmed, super-solidus felsic hosts. Contaminants occur in part as megacrysts of reworked oligoclase with lesser hb and biot. Within each group MgO-variation diagrams for Fe, Ca, Ti, Si are strikingly linear (r>.96); alkalis are decidedly less regular, and many hybrid rocks show a curious, pronounced Na enrichment. Field data, petrography, and best fit modeling suggests this may result from flow concentration of oligoclase xenocrysts within contaminated synplutonic dikes, and is preserved in the inclusions when dike cores chill as pillows in their felsic host. Dissolution of mafic inclusions erases these anomalies and creates a more regular series of two-component mafic-felsic mixtures in the large host system. The inclusions and dikes thus appear to record a variety of late-stage mafic-felsic interactive processes that earlier and on a larger scale created much of the compositional variety of their intermediate host rocks.

  8. Increasing the reach of the PK-3R continuous Miner; Desarrollo y Ensayo de un Sistema para aumentar el alcance de la Pina de Rozado en un Minador PK-3R

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    The objective of this project is the development and implementation of a system designed to increase the reach of the cutting head of a PK-3R continuous miner working in our coal operations. Justification for the project stems from our method of coal extraction, whereby once the sub-level gallery has been advanced to it`s limit, extraction of the coal is undertaken by retreat mining, using a room and pillar method. In this method the roof is blasted to allow greater coal recovery. Due to it`s short length, the original position of the cutting arm of the PK-3R miner did not permit the total recovery of the blasted coal piled up on the gallery floor. Therefore an increase in the reach of the arm is very beneficial, facilitating the recovery of coal that previously could not be recovered. The system also permits excavation for support methods to be undertaken more rapidly, and a better adaptation of the miner to the irregularities of the wall, thus permitting it to move up or down more quickly, reducing the movements required. The system has not caused significant breakdowns, and the availability of the miner is good. In addition, the substitution of the turret in the case of a breakdown is an easy task, as during the design stage, the ease of mounting and dismounting the turret was considered as a fundamental parameter. (Author)

  9. Performance evaluation of continuous blood sampling system for PET study. Comparison of three detector-systems

    CERN Document Server

    Matsumoto, K; Sakamoto, S; Senda, M; Yamamoto, S; Tarutani, K; Minato, K

    2002-01-01

    To measure cerebral blood flow with sup 1 sup 5 O PET, it is necessary to measure the time course of arterial blood radioactivity. We examined the performance of three different types of continuous blood sampling system. Three kinds of continuous blood sampling system were used: a plastic scintillator-based beta detector (conventional beta detector (BETA)), a bismuth germinate (BGO)-based coincidence gamma detector (Pico-count flow-through detector (COINC)) and a Phoswich detector (PD) composed by a combination of plastic scintillator and BGO scintillator. Performance of these systems was evaluated for absolute sensitivity, count rate characteristic, sensitivity to background gamnra photons, and reproducibility for nylon tube geometry. The absolute sensitivity of the PD was 0.21 cps/Bq for sup 6 sup 8 Ga positrons at the center of the detector. This was approximately three times higher than BETA, two times higher than COINC. The value measured with BETA was stable, even when background radioactivity was incre...

  10. An implantable centrifugal blood pump with a recirculating purge system (Cool-Seal system).

    Science.gov (United States)

    Yamazaki, K; Litwak, P; Tagusari, O; Mori, T; Kono, K; Kameneva, M; Watach, M; Gordon, L; Miyagishima, M; Tomioka, J; Umezu, M; Outa, E; Antaki, J F; Kormos, R L; Koyanagi, H; Griffith, B P

    1998-06-01

    A compact centrifugal blood pump has been developed as an implantable left ventricular assist system. The impeller diameter is 40 mm, and pump dimensions are 55 x 64 mm. This first prototype, fabricated from titanium alloy, resulted in a pump weight of 400 g including a brushless DC motor. The weight of a second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon (DLC) to improve blood compatibility. Flow rates of over 7 L/min against 100 mm Hg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system (Cool-Seal) is used for the shaft seal. In this seal system, the seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. Purge fluid is continuously purified and sterilized by an ultrafiltration unit which is incorporated in the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular (LV) apex descending aorta bypass was performed utilizing an expanded polytetrafluoroethylene (ePTFE) vascular graft with the pump placed in the left thoracic cavity. In 2 in vivo experiments, the pump flow rate was maintained at 5-9 L/min, and pump power consumption remained stable at 9-10 W. All plasma free Hb levels were measured at less than 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (<0.5 ml/day). In both calves, the pumps demonstrated trouble free continuous function over 6 month (200 days and 222 days).

  11. The circulatory system: blood procurement, AIDS, and the social body in China.

    Science.gov (United States)

    Erwin, Kathleen

    2006-06-01

    The market for blood thrived in China for more than a decade, preying on rural villagers desperate for cash. Profit motives and unhygienic collection created an AIDS epidemic, where now up to 80 percent of adults in some villages are HIV infected. Today, illegal blood banks continue to operate in some areas. Moreover, better screening and blood testing do little to address the underlying cultural reluctance to give blood. This article examines what is at stake for blood donors in the circulation of blood through both the physical and the social bodies in China today. I argue that public health and social policy solutions require consideration of the symbolic meanings of blood and the body, kin relations, and gift exchange. China's HIV-contaminated blood procurement crisis demands a critical reexamination of the hidden processes embedded in a "circulatory system" that has inseparably bound the "gift of life" and a "commodity of death".

  12. Differential Rheology Among ABO Blood Group System In Nigerians

    African Journals Online (AJOL)

    Research Article. Differential Rheology ... alterations in membrane and cytoskeletal properties that could affect the rheology of blood. This study was ... depending on the concentration of plasma proteins especially ... Laboratory Analysis:.

  13. Using an integrated automated system to optimize retention and increase frequency of blood donations.

    Science.gov (United States)

    Whitney, J Garrett; Hall, Robert F

    2010-07-01

    This study examines the impact of an integrated, automated phone system to reinforce retention and increase frequency of donations among blood donors. Cultivated by incorporating data results over the past 7 years, the system uses computerized phone messaging to contact blood donors with individualized, multilevel notifications. Donors are contacted at planned intervals to acknowledge and recognize their donations, informed where their blood was sent, asked to participate in a survey, and reminded when they are eligible to donate again. The report statistically evaluates the impact of the various components of the system on donor retention and blood donations and quantifies the fiscal advantages to blood centers. By using information and support systems provided by the automated services and then incorporating the phlebotomists and recruiters to reinforce donor retention, both retention and donations will increase. © 2010 American Association of Blood Banks.

  14. Systems biology of stored blood cells: can it help to extend the expiration date?

    Science.gov (United States)

    Paglia, Giuseppe; Palsson, Bernhard Ø; Sigurjonsson, Olafur E

    2012-12-05

    With increasingly stringent regulations regarding deferral and elimination of blood donors it will become increasingly important to extend the expiration date of blood components beyond the current allowed storage periods. One reason for the storage time limit for blood components is that platelets and red blood cells develop a condition called storage lesions during their storage in plastic blood containers. Systems biology provides comprehensive bio-chemical descriptions of organisms through quantitative measurements and data integration in mathematical models. The biological knowledge for a target organism can be translated in a mathematical format and used to compute physiological properties. The use of systems biology represents a concrete solution in the study of blood cell storage lesions, and it may open up new avenues towards developing better storage methods and better storage media, thereby extending the storage period of blood components. This article is part of a Special Issue entitled: Integrated omics. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Determination of degree of RBC agglutination for blood typing using a small quantity of blood sample in a microfluidic system.

    Science.gov (United States)

    Chang, Yaw-Jen; Ho, Ching-Yuan; Zhou, Xin-Miao; Yen, Hsiu-Rong

    2018-04-15

    Blood typing assay is a critical test to ensure the serological compatibility of a donor and an intended recipient prior to a blood transfusion. This paper presents a microfluidic blood typing system using a small quantity of blood sample to determine the degree of agglutination of red blood cell (RBC). Two measuring methods were proposed: impedimetric measurement and electroanalytical measurement. The charge transfer resistance in the impedimetric measurement and the power parameter in the electroanalytical measurement were used for the analysis of agglutination level. From the experimental results, both measuring methods provide quantitative results, and the parameters are linearly and monotonically related to the degree of RBC agglutination. However, the electroanalytical measurement is more reliable than the impedimetric technique because the impedimetric measurement may suffer from many influencing factors, such as chip conditions. Five levels from non-agglutination (level 0) to strong agglutination (level 4+) can be discriminated in this study, conforming to the clinical requirement to prevent any risks in transfusion. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Cytotoxic effects of 125I-labeled PBZr ligand PK 11195 in prostatic tumor cells: therapeutic implications

    International Nuclear Information System (INIS)

    Alenfall, J.; Kant, R.; Batra, S.

    1998-01-01

    The effect of [ 125 I]PK 11195 was examined in human prostatic tumor cells (DU 145) in culture and compared with Na[ 125 I] and non-radioactive PK 11195. [ 125 I]PK 11195 was clearly cytocidal. The data for dose-related cell survival with [ 125 I]PK 11195 showed a linear relationship. Na[ 125 I] or non-labeled PK 11195 at similar concentrations did not lead to any cell killing. The uptake of [ 125 I]PK 11195 and [ 3 H]PK 11195 in cells was very similar. Fragmentation of DNA measured by agarose gel electrophoresis showed that exposure of DU 145 cells to [ 125 I]PK 11195 for 1, 4 or 24 h caused no fragmentation. These results indicate that nuclear DNA is not the prime binding site for [ 125 I]PK 11195, which is consistent with the presence of specific peripheral benzodiazepine receptors (PBZr) in the mitochondria. The cell killing effect of [ 125 I]PK 11195 suggests the use of PBZr ligand for radiotherapy

  17. Evaluation of 12 blood glucose monitoring systems for self-testing: system accuracy and measurement reproducibility.

    Science.gov (United States)

    Freckmann, Guido; Baumstark, Annette; Schmid, Christina; Pleus, Stefan; Link, Manuela; Haug, Cornelia

    2014-02-01

    Systems for self-monitoring of blood glucose (SMBG) have to provide accurate and reproducible blood glucose (BG) values in order to ensure adequate therapeutic decisions by people with diabetes. Twelve SMBG systems were compared in a standardized manner under controlled laboratory conditions: nine systems were available on the German market and were purchased from a local pharmacy, and three systems were obtained from the manufacturer (two systems were available on the U.S. market, and one system was not yet introduced to the German market). System accuracy was evaluated following DIN EN ISO (International Organization for Standardization) 15197:2003. In addition, measurement reproducibility was assessed following a modified TNO (Netherlands Organization for Applied Scientific Research) procedure. Comparison measurements were performed with either the glucose oxidase method (YSI 2300 STAT Plus™ glucose analyzer; YSI Life Sciences, Yellow Springs, OH) or the hexokinase method (cobas(®) c111; Roche Diagnostics GmbH, Mannheim, Germany) according to the manufacturer's measurement procedure. The 12 evaluated systems showed between 71.5% and 100% of the measurement results within the required system accuracy limits. Ten systems fulfilled with the evaluated test strip lot minimum accuracy requirements specified by DIN EN ISO 15197:2003. In addition, accuracy limits of the recently published revision ISO 15197:2013 were applied and showed between 54.5% and 100% of the systems' measurement results within the required accuracy limits. Regarding measurement reproducibility, each of the 12 tested systems met the applied performance criteria. In summary, 83% of the systems fulfilled with the evaluated test strip lot minimum system accuracy requirements of DIN EN ISO 15197:2003. Each of the tested systems showed acceptable measurement reproducibility. In order to ensure sufficient measurement quality of each distributed test strip lot, regular evaluations are required.

  18. Changes in the blood system after extracorporeal radiation

    International Nuclear Information System (INIS)

    Bobkov, Yu.I.; Yalikov, V.Ya.; Belopol'skij, A.A.; Alekseeva, L.M.; Apollonova, L.A.; Babayan, S.S.; Burkov, I.M.; Vasina, T.A.

    1985-01-01

    The effect of singles extracorporal blood irradiation (ECBI) on cellular and biochemical blood composition, activity of non specific immunity factors has been studied using no breed dogs. A shunt of plastic tube has been superimposed between the femoral artery and vein of the anesthetized animals and during 3h blood irradiation has been carried out for creating dose load from 6.0 to 12.0 Gy. It has been found that hematologic factors upon ECBI are changed unambiguously. Hemoglobin content and hematocrit are increased after irradiation. ESR factor somewhat increases during 7 days then it decreases, attainig 44% of the initial one by the end of the experiment. During 7 days upon ECBI a strongly pronounced leukocytosis is developed. Erythrocytes content for certain is increased on the 3-rd, 5-th and 7-th weeks of the experiment, respectively by 15, 17 and 31%. The change in the quantity of erythrocytes is accompanied by reconstruction in them of energy processes revealed on changing G-6-EDG and transketolaze activity. Simultaneously nucleic acids quantity in blood is increased in animals. In the course of 7-30 days upon irradiation the change of activity of a series of factors of natural immunity such as activity of lysozymb, β lysines content activity of β lytic properties is observed. When administering penicillin the increase of antibiotic activity in irradiated blood is pointed out. The data obtained in the authors opinion show the prospects in using the ECBI method for stimulation in organism of non specific protective mechanisms

  19. Validation of capillary blood analysis and capillary testing mode on the epoc Point of Care system

    Directory of Open Access Journals (Sweden)

    Jing Cao

    2017-12-01

    Full Text Available Background: Laboratory test in transport is a critical component of patient care, and capillary blood is a preferred sample type particularly in children. This study evaluated the performance of capillary blood testing on the epoc Point of Care Blood Analysis System (Alere Inc. Methods: Ten fresh venous blood samples was tested on the epoc system under the capillary mode. Correlation with GEM 4000 (Instrumentation Laboratory was examined for Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pO2, pCO2, and pH, and correlation with serum tested on Vitros 5600 (Ortho Clinical Diagnostics was examined for creatinine. Eight paired capillary and venous blood was tested on epoc and ABL800 (Radiometer for the correlation of Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Capillary blood from 23 apparently healthy volunteers was tested on the epoc system to assess the concordance to reference ranges used locally. Results: Deming regression correlation coefficients for all the comparisons were above 0.65 except for ionized Ca2+. Accordance of greater than 85% to the local reference ranges were found in all assays with the exception of pO2 and Cl-. Conclusion: Data from this study indicates that capillary blood tests on the epoc system provide comparable results to reference method for these assays, Na+, K+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Further validation in critically ill patients is needed to implement the epoc system in patient transport. Impact of the study: This study demonstrated that capillary blood tests on the epoc Point of Care Blood Analysis System give comparable results to other chemistry analyzers for major blood gas and critical tests. The results are informative to institutions where pre-hospital and inter-hospital laboratory testing on capillary blood is a critical component of patient point of care testing. Keywords: Epoc, Capillary, Transport, Blood gas, Point of care

  20. In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage

    International Nuclear Information System (INIS)

    Sharma, Mukesh Kumar; Imamichi, Shoji; Fukuchi, Mikoto; Samarth, Ravindra Mahadeo; Tomita, Masanori; Matsumoto, Yoshihisa

    2016-01-01

    XRCC4 is a protein associated with DNA Ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non-homologous end joining. In response to treatment with ionizing radiation or DNA damaging agents, XRCC4 undergoes DNA-PK-dependent phosphorylation. Furthermore, Ser260 and Ser320 (or Ser318 in alternatively spliced form) of XRCC4 were identified as the major phosphorylation sites by purified DNA-PK in vitro through mass spectrometry. However, it has not been clear whether these sites are phosphorylated in vivo in response to DNA damage. In the present study, we generated an antibody that reacts with XRCC4 phosphorylated at Ser320 and examined in cellulo phosphorylation status of XRCC4 Ser320. The phosphorylation of XRCC4 Ser320 was induced by γ-ray irradiation and treatment with Zeocin. The phosphorylation of XRCC4 Ser320 was detected even after 1 Gy irradiation and increased in a manner dependent on radiation dose. The phosphorylation was observed immediately after irradiation and remained mostly unchanged for up to 4 h. The phosphorylation was inhibited by DNA-PK inhibitor NU7441 and was undetectable in DNA-PKcs-deficient cells, indicating that the phosphorylation was mainly mediated by DNA-PK. These results suggested potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells

  1. [Advenella kashmirensis subsp. methylica PK1, a facultative methylotroph from carex rhizosphere].

    Science.gov (United States)

    Poroshina, M N; Doronina, N V; Kaparullina, E N; Trotsenko, Iu A

    2015-01-01

    A strain (PK1) of facultative methylobacteria growing on methanol as a carbon and energy source was isolated from carex rhizosphere (Pamukkale National Park, Turkey). The cells were nonmotile gram-negative rods propagating by binary fission. The organism was a strict anaerobe, oxidase- and catalase-positive. Optimal growth occurred at 29°C, pH 8.0-8.5, and 0.5% NaCl; no growth occurred at 2% NaCl. The organism used the ribulose bisphosphate pathway of C1 assimilation. Predominant fatty acids were 11-octodecenoic (18:1ω7) and cis-hexadecenoic (16:1ω7c). Phosphatidylethanolamine and diphosphatidylglycerol were the dominant phospholipids. Q8 was the main ubiquinone. DNA G+C content was 55.4 mol % (mp). Sequencing of the 16S rRNA gene revealed that strain PK1 belonged to the genus Advenella with 98.8 and 99.2% similarity to the type strains A. incenata CCUG 45225T and A. kashmirensis WT001T, respectively. DNA-DNA homology of strain PK1 and A. kashmirensis WT001T was 70%. While MALDI analysis confirmed their close clusterization, RAPD analysis revealed the differences between strain PKI and other Advenella strains. Based on its geno- and phenotypic properties, the isolate PK1 was classified as A. kashmirensis subsp. methylica PK1 (VKM-B 2850 = DSM 27514), the first known methylotroph of the genus Advenella.

  2. Porcine circovirus-2 capsid protein induces cell death in PK15 cells

    Energy Technology Data Exchange (ETDEWEB)

    Walia, Rupali; Dardari, Rkia, E-mail: rdardari@ucalgary.ca; Chaiyakul, Mark; Czub, Markus

    2014-11-15

    Studies have shown that Porcine circovirus (PCV)-2 induces apoptosis in PK15 cells. Here we report that cell death is induced in PCV2b-infected PK15 cells that express Capsid (Cap) protein and this effect is enhanced in interferon gamma (IFN-γ)-treated cells. We further show that transient PCV2a and 2b-Cap protein expression induces cell death in PK15 cells at rate similar to PCV2 infection, regardless of Cap protein localization. These data suggest that Cap protein may have the capacity to trigger different signaling pathways involved in cell death. Although further investigation is needed to gain deeper insights into the nature of the pathways involved in Cap-induced cell death, this study provides evidence that PCV2-induced cell death in kidney epithelial PK15 cells can be mapped to the Cap protein and establishes the need for future research regarding the role of Cap-induced cell death in PCV2 pathogenesis. - Highlights: • IFN-γ enhances PCV2 replication that leads to cell death in PK15 cells. • IFN-γ enhances nuclear localization of the PCV2 Capsid protein. • Transient PCV2a and 2b-Capsid protein expression induces cell death. • Cell death is not dictated by specific Capsid protein sub-localization.

  3. Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

    Science.gov (United States)

    Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M

    2017-04-30

    Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t 1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t 1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

  4. Structure of Pseudoknot PK26 Shows 3D Domain Swapping in an RNA

    Science.gov (United States)

    Lietzke, Susan E; Barnes, Cindy L.

    1998-01-01

    3D domain swapping provides a facile pathway for the evolution of oligomeric proteins and allosteric mechanisms and a means for using monomer-oligomer equilibria to regulate biological activity. The term "3D domain swapping" describes the exchange of identical domains between two protein monomers to create an oligomer. 3D domain swapping has, so far, only been recognized in proteins. In this study, the structure of the pseudoknot PK26 is reported and it is a clear example of 3D domain swapping in RNA. PK26 was chosen for study because RNA pseudoknots are required structures in several biological processes and they arise frequently in in vitro selection experiments directed against protein targets. PK26 specifically inhibits HIV-1 reverse transcriptase with nanomolar affinity. We have now determined the 3.1 A resolution crystal structure of PK26 and find that it forms a 3D domain swapped dimer. PK26 shows extensive base pairing between and within strands. Formation of the dimer requires the linker region between the pseudoknot folds to adopt a unique conformation that allows a base within a helical stem to skip one base in the stacking register. Rearrangement of the linker would permit a monomeric pseudoknot to form. This structure shows how RNA can use 3D domain swapping to build large scale oligomers like the putative hexamer in the packaging RNA of bacteriophage Phi29.

  5. Effect of volume expansion on systemic hemodynamics and central and arterial blood volume in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Bendtsen, F; Henriksen, Jens Henrik Sahl

    1995-01-01

    , and arterial pressure were determined before and during a volume expansion induced by infusion of a hyperosmotic galactose solution. RESULTS: During volume expansion, the central and arterial blood volume increased significantly in patients with class A and controls, whereas no significant change was found...... in patients with either class B or class C. Conversely, the noncentral blood volume increased in patients with class B and C. In both patients and controls, the cardiac output increased and the systemic vascular resistance decreased, whereas the mean arterial blood pressure did not change significantly......BACKGROUND & AIMS: Systemic vasodilatation in cirrhosis may lead to hemodynamic alterations with reduced effective blood volume and decreased arterial blood pressure. This study investigates the response of acute volume expansion on hemodynamics and regional blood volumes in patients with cirrhosis...

  6. Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

    Science.gov (United States)

    Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

    2017-11-01

    The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently

  7. Validation of capillary blood analysis and capillary testing mode on the epoc Point of Care system.

    Science.gov (United States)

    Cao, Jing; Edwards, Rachel; Chairez, Janette; Devaraj, Sridevi

    2017-12-01

    Laboratory test in transport is a critical component of patient care, and capillary blood is a preferred sample type particularly in children. This study evaluated the performance of capillary blood testing on the epoc Point of Care Blood Analysis System (Alere Inc). Ten fresh venous blood samples was tested on the epoc system under the capillary mode. Correlation with GEM 4000 (Instrumentation Laboratory) was examined for Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pO2, pCO2, and pH, and correlation with serum tested on Vitros 5600 (Ortho Clinical Diagnostics) was examined for creatinine. Eight paired capillary and venous blood was tested on epoc and ABL800 (Radiometer) for the correlation of Na+, K+, Cl-, Ca2+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Capillary blood from 23 apparently healthy volunteers was tested on the epoc system to assess the concordance to reference ranges used locally. Deming regression correlation coefficients for all the comparisons were above 0.65 except for ionized Ca2+. Accordance of greater than 85% to the local reference ranges were found in all assays with the exception of pO2 and Cl-. Data from this study indicates that capillary blood tests on the epoc system provide comparable results to reference method for these assays, Na+, K+, glucose, lactate, hematocrit, hemoglobin, pCO2, and pH. Further validation in critically ill patients is needed to implement the epoc system in patient transport. This study demonstrated that capillary blood tests on the epoc Point of Care Blood Analysis System give comparable results to other chemistry analyzers for major blood gas and critical tests. The results are informative to institutions where pre-hospital and inter-hospital laboratory testing on capillary blood is a critical component of patient point of care testing.

  8. Air bubbles and hemolysis of blood samples during transport by pneumatic tube systems.

    Science.gov (United States)

    Mullins, Garrett R; Bruns, David E

    2017-10-01

    Transport of blood samples through pneumatic tube systems (PTSs) generates air bubbles in transported blood samples and, with increasing duration of transport, the appearance of hemolysis. We investigated the role of air-bubble formation in PTS-induced hemolysis. Air was introduced into blood samples for 0, 1, 3 or 5min to form air bubbles. Hemolysis in the blood was assessed by (H)-index, lactate dehydrogenase (LD) and potassium in plasma. In an effort to prevent PTS-induced hemolysis, blood sample tubes were completely filled, to prevent air bubble formation, and compared with partially filled samples after PTS transport. We also compared hemolysis in anticoagulated vs clotted blood subjected to PTS transport. As with transport through PTSs, the duration of air bubble formation in blood by a gentle stream of air predicted the extent of hemolysis as measured by H-index (pair space in a blood sample prevented bubble formation and fully protected the blood from PTS-induced hemolysis (ptransport and was partially protected from hemolysis vs anticoagulated blood as indicated by lower LD (ptransport. Prevention of air bubble formation in blood samples during PTS transport protects samples from hemolysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. What's Blood?

    Science.gov (United States)

    ... Body Make Blood? It's not made in a kitchen, but blood has ingredients, just like a recipe. ... these ingredients together and you have blood — an essential part of the circulatory system. Thanks to your ...

  10. SYSTEMIC COMPLICATIONS AND THEIR RISK FACTORS AMONG TEHRANIAN BLOOD DONOR, 2005

    OpenAIRE

    F. Majlessi; S. Ghafari; A. Rahimi-Foroushani M. Maghsoodlou

    2008-01-01

    The systemic complications of blood donation are the first reasons why patients fail to return for further blood donation. This study was designed to determine the frequency of these complications and their associated risk factors among blood donors in Tehran. Also, we aimed to provide suitable methods to decrease the frequency of these adverse events, thereby eliminating the most important causes of withdrawal, while maintaining the health of the donors. This analytical descriptive cross-sec...

  11. Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites -current status

    International Nuclear Information System (INIS)

    Pike, V.W.; Osman, S.; Shah, F.; Turton, D.R.; Waters, S.L.; Crouzel, C.; Nutt, D.J.

    1993-01-01

    The status of the radiochemical development and biological evaluation of radioligands for PET studies of central benzodiazepine (BZ) receptors and the so-called peripheral benzodiazepine binding sites, here discriminated and referred to as PK binding sites, is reviewed against current pharmacological knowledge, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies, [N-methyl- 11 C]flumazenil for central BZ receptors, and [N-methyl- 11 C]PK 11195 for PK binding sites. Quality assurance and plasma metabolite analysis are also reviewed for these radioligands and practical recommendations are given on methodology for their performance. (Author)

  12. Pulmonary and systemic blood flow contributions to upper airways in canine lung

    International Nuclear Information System (INIS)

    Barman, S.A.; Ardell, J.L.; Parker, J.C.; Perry, M.L.; Taylor, A.E.

    1988-01-01

    The blood flow contributions and drainage patterns of the pulmonary and systemic circulations in the upper airways (trachea and main bronchi) were assessed in anesthetized dogs by injecting 15-μm radiolabeled microspheres into the right and left heart, respectively. After the animals were killed, the tracheal cartilage, tracheal muscle-mucosa, and main bronchi were excised. The tracheal cartilage and tracheal muscle-mucosa were divided into lower, middle, and upper segments for blood flow determinations. The pulmonary contribution to tracheal blood flow was very small, being higher in the lower segments. The systemic contribution to these same tracheal regions was significantly higher, and higher in the upper segments. The pulmonary and systemic circulations each contributed ∼50% to the main bronchi blood flow. The pulmonary blood flow contribution alone to the trachea and main bronchi was also determined in subsequent experiments that utilized the isolated lung, and these blood flows were not significantly different from the pulmonary contribution measured in the intact lungs. The present results indicate that the systemic (bronchial) circulation is the primary source of tracheal blood flow and that both the pulmonary and systemic circulations may contribute ∼50% of the blood flow to the main bronchi in dog lungs

  13. Prevalence of antibodies to a new histo-blood system: the FORS system.

    Science.gov (United States)

    Jesus, Carlos; Hesse, Camilla; Rocha, Clara; Osório, Nádia; Valado, Ana; Caseiro, Armando; Gabriel, António; Svensson, Lola; Moslemi, Ali-Reza; Siba, Wafa Abu; Srour, Mahmoud A; Pereira, Cristina; Tomaz, Jorge; Teixeira, Paulo; Mendes, Fernando

    2018-02-01

    In 1987, three unrelated English families were reported with a putative blood subgroup called A pae . Swedish researchers later found evidence leading to abolishment of the A pae subgroup and establishment instead of the FORS blood group system (System 31 - ISBT, 2012). It is important to know the prevalence of antibodies in order to make the best decisions in transfusion medicine. Cells expressing the Forssman saccharide, such as sheep erythrocytes, are needed to detect the anti-Forssman antibody. The aim of this study was to define the prevalence of human anti-Forssman antibody. Plasma samples from 800 individuals were studied. Sheep erythrocytes or Forssman "kodecytes" were mixed with the plasma samples using the tube technique. Plasma from an A pae individual was used as a negative control and monoclonal anti-Forssman antibody (M1/22.25.8HL cell line supernatant) was used as the positive control. Of the 800 individuals tested, one was negative for the presence of anti-Forssman antibody. We compared the anti-Forssman antibody reaction pattern between genders and found that males have weaker reactions than females, both at room temperature (p=0.026) and at 37 °C (p=0.043). We also investigated the reaction pattern of anti-Forssman antibody in relation to ABO and Rh blood group types without finding any significant differences. Sheep erythrocytes are suitable for searching for human anti-Forssman antibody. The quantity of anti-Forssman antibodies in plasma is higher in females than in males. In the population (n=800) studied here, we found one individual lacking the anti-Forssman antibody. These results contribute to the data already published, confirming that FORS is a rare blood group.

  14. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents.

    Science.gov (United States)

    Asín-Prieto, Eduardo; Rodríguez-Gascón, Alicia; Isla, Arantxazu

    2015-05-01

    The alarming increase of resistance against multiple currently available antibiotics is leading to a rapid lose of treatment options against infectious diseases. Since the antibiotic resistance is partially due to a misuse or abuse of the antibiotics, this situation can be reverted when improving their use. One strategy is the optimization of the antimicrobial dosing regimens. In fact, inappropriate drug choice and suboptimal dosing are two major factors that should be considered because they lead to the emergence of drug resistance and consequently, poorer clinical outcomes. Pharmacokinetic/pharmacodynamic (PK/PD) analysis in combination with Monte Carlo simulation allows to optimize dosing regimens of the antibiotic agents in order to conserve their therapeutic value. Therefore, the aim of this review is to explain the basis of the PK/PD analysis and associated techniques, and provide a brief revision of the applications of PK/PD analysis from a therapeutic point-of-view. The establishment and reevaluation of clinical breakpoints is the sticking point in antibiotic therapy as the clinical use of the antibiotics depends on them. Two methodologies are described to establish the PK/PD breakpoints, which are a big part of the clinical breakpoint setting machine. Furthermore, the main subpopulations of patients with altered characteristics that can condition the PK/PD behavior (such as critically ill, elderly, pediatric or obese patients) and therefore, the outcome of the antibiotic therapy, are reviewed. Finally, some recommendations are provided from a PK/PD point of view to enhance the efficacy of prophylaxis protocols used in surgery. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  15. Sosiaalisen median kehittäminen pk-yrityksissä Töpseli-verkoston avulla

    OpenAIRE

    Palander, Laura

    2010-01-01

    Tämän opinnäytetyön tarkoituksena oli selvittää, minkälaisena mahdollisuutena pk-yrittäjät kokevat sosiaalisen median ja miten he ymmärtävät sen. Läntisellä Uudellamaalla toimivia yrityksiä on osallistunut Laurea-ammattikorkeakoulun Lohjan toimipisteen Töpseli-verkostoon. Verkoston tarkoituksena on vahvistaa länsi Uudellamaalla toimivien pk-yritysten kilpailukykyä, parantamalla yrittäjien ymmärrystä sosiaalisen median tarjoamista mahdollisuuksista. Työtä varten selvitettiin myös ammattikorkea...

  16. Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring.

    Science.gov (United States)

    Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue

    2017-12-01

    Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery-powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface. The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. We conducted in vivo human clinical trials. The noninvasive measurement results for intravascular blood glucose showed a high correlation (>0.9) with clinically measured blood glucose levels. The system opens up new prospects for clinical-grade noninvasive continuous glucose monitoring.

  17. The applying of multisensory system to assessment of blood samples by composition of equilibrium gaseous phase

    Directory of Open Access Journals (Sweden)

    T. A. Kuchmenko

    2013-01-01

    Full Text Available In the article discussed the possibility of blood sample’s assessment with the following diagnostic characteristics: "endometriosis", "fibroids", "uterine body cancer" by the signals of multisensor system. It has been found that blood samples can be reliably ranking into groups according to their diagnostic characteristics using the geometry, square of "visual prints" and the sorption effectiveness parameters max ij А.

  18. Prenatal typing of Rh and Kell blood group system antigens: The edge of a watershed

    NARCIS (Netherlands)

    van der Schoot, C. Ellen; Tax, G. H. Martine; Rijnders, Robbert J. P.; de Haas, Masja; Christiaens, Godelieve C. M. L.

    2003-01-01

    Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal material obtained by invasive means (chorionic villus sampling or amniocentesis) are available

  19. Directly measuring spinal cord blood flow and spinal cord perfusion pressure via the collateral network: correlations with changes in systemic blood pressure.

    Science.gov (United States)

    Kise, Yuya; Kuniyoshi, Yukio; Inafuku, Hitoshi; Nagano, Takaaki; Hirayasu, Tsuneo; Yamashiro, Satoshi

    2015-01-01

    During thoracoabdominal surgery in which segmental arteries are sacrificed over a large area, blood supply routes from collateral networks have received attention as a means of avoiding spinal cord injury. The aim of this study was to investigate spinal cord blood supply through a collateral network by directly measuring spinal cord blood flow and spinal cord perfusion pressure experimentally. In beagle dogs (n = 8), the thoracoabdominal aorta and segmental arteries L1-L7 were exposed, and a temporary bypass was created for distal perfusion. Next, a laser blood flow meter was placed on the spinal dura mater in the L5 region to measure the spinal cord blood flow. The following were measured simultaneously when the direct blood supply from segmental arteries L2-L7 to the spinal cord was stopped: mean systemic blood pressure, spinal cord perfusion pressure (blood pressure within the aortic clamp site), and spinal cord blood flow supplied via the collateral network. These variables were then investigated for evidence of correlations. Positive correlations were observed between mean systemic blood pressure and spinal cord blood flow during interruption of segmental artery flow both with (r = 0.844, P flow with and without distal perfusion (r = 0.803, P network from outside the interrupted segmental arteries, and high systemic blood pressure (∼1.33-fold higher) was needed to obtain the preclamping spinal cord blood flow, whereas 1.68-fold higher systemic blood pressure was needed when distal perfusion was halted. Spinal cord blood flow is positively correlated with mean systemic blood pressure and spinal cord perfusion pressure under spinal cord ischemia caused by clamping a wide range of segmental arteries. In open and endovascular thoracic and thoracoabdominal surgery, elevating mean systemic blood pressure is a simple and effective means of increasing spinal cord blood flow, and measuring spinal cord perfusion pressure seems to be useful for monitoring

  20. Enrichment of reticulocytes from whole blood using aqueous multiphase systems of polymers.

    Science.gov (United States)

    Kumar, Ashok A; Lim, Caeul; Moreno, Yovany; Mace, Charles R; Syed, Abeer; Van Tyne, Daria; Wirth, Dyann F; Duraisingh, Manoj T; Whitesides, George M

    2015-01-01

    This paper demonstrates the enrichment of reticulocytes by centrifuging whole blood through aqueous multiphase systems (AMPSs)-immiscible phases of solutions of polymers that form step-gradients in density. The interfaces of an AMPS concentrate cells; this concentration facilitates the extraction of blood enriched for reticulocytes. AMPS enrich reticulocytes from blood from both healthy and hemochromatosis donors. Varying the osmolality and density of the phases of AMPS provides different levels of enrichment and yield of reticulocytes. A maximum enrichment of reticulocytemia of 64 ± 3% was obtained from donors with hemochromatosis. When used on peripheral blood from normal donors, AMPS can provide a higher yield of enriched reticulocytes and a higher proportion of reticulocytes expressing CD71 than differential centrifugation followed by centrifugation over Percoll. Blood enriched for reticulocytes by AMPS could be useful for research on malaria. Several species of malaria parasites show a preference to invade young erythrocytes and reticulocytes; this preference complicates in vitro cultivation of these species in human blood. Plasmodium knowlesi malaria parasites invade normal human blood enriched for reticulocytes by AMPSs at a rate 2.2 times greater (P blood. Parasite invasion in normal blood enriched by AMPS was 1.8 times greater (P blood enriched to a similar reticulocytemia by differential centrifugation followed by centrifugation over Percoll. The enrichment of reticulocytes that are invaded by malaria parasites demonstrates that AMPSs can provide a label-free method to enrich cells for biological research. © 2014 Wiley Periodicals, Inc.

  1. Transport of S-cysteine conjugates in LL-PK1 cells and its role in toxicity

    International Nuclear Information System (INIS)

    Schaeffer, V.; Stevens, J.

    1986-01-01

    In order to study its role in S-cysteine conjugate toxicity, the transport of the nephrotoxic cysteine conjugate, S-1,2-dichlorovinyl-L-cysteine (L-DCVC), was investigated in the kidney cell line, LLC-PK1. When incubated with [ 35 S]-DCVC, accumulation of radioactivity within the cells was linear for at least 5 min with 92% of the 35 S present as unmetabolized L-DCVC. Kinetic analysis indicated two saturable uptake systems; Km = 6.8 μM and 1.6 mM; V/sub max/ = .048 and 1.4 nmol/min/mg protein. Both systems were Na + -independent and were inhibited by amino acid transport system L substrates but not substrates of systems A, ASC or organic anion transport. L-DCVC uptake at 5 μM and 500 μM was significantly greater in subconfluent cells than in confluent cultures by 5 and 2.8 fold, respectively. The presence of the non-toxic conjugates S-methyl-(SMC), S-ethyl-(SEC), S-benzyl-L- cysteine (SBC) and the D isomer of DCVC blocked the toxicity and inhibited the transport of L-DCVC in LLC-PK1 cells in the rank order of SBC > SEC congruent to D-DCVC > SMC. The metabolism of L-DCVC, previously shown to be required for cytotoxicity, was only slightly inhibited by these conjugates and did not correlate with their relative protection against toxicity. This study suggests that L-DCVC is transported into these cells by the system L transporter and that protection against toxicity by non-toxic S-cysteine conjugates is due to the inhibition of transport

  2. A portable system for processing donated whole blood into high quality components without centrifugation.

    Science.gov (United States)

    Gifford, Sean C; Strachan, Briony C; Xia, Hui; Vörös, Eszter; Torabian, Kian; Tomasino, Taylor A; Griffin, Gary D; Lichtiger, Benjamin; Aung, Fleur M; Shevkoplyas, Sergey S

    2018-01-01

    The use of centrifugation-based approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of 'whole blood' into distinct red blood cell (RBC), platelet, and plasma products. However, the logistical complications and potential cellular damage associated with centrifugation/apheresis manufacturing of blood products are well documented. The objective of this study was to evaluate a proof-of-concept system for whole blood processing, which does not employ electromechanical parts, is easily portable, and can be operated immediately after donation with minimal human labor. In a split-unit study (n = 6), full (~500mL) units of freshly-donated whole blood were divided, with one half processed by conventional centrifugation techniques and the other with the new blood separation system. Each of these processes took 2-3 hours to complete and were performed in parallel. Blood products generated by the two approaches were compared using an extensive panel of cellular and plasma quality metrics. Comparison of nearly all RBC parameters showed no significant differences between the two approaches, although the portable system generated RBC units with a slight but statistically significant improvement in 2,3-diphosphoglyceric acid concentration (p applications in remote or resource-limited settings, or for patients requiring highly functional platelet product.

  3. SYSTEMIC COMPLICATIONS AND THEIR RISK FACTORS AMONG TEHRANIAN BLOOD DONOR, 2005

    Directory of Open Access Journals (Sweden)

    F. Majlessi

    2008-06-01

    Full Text Available The systemic complications of blood donation are the first reasons why patients fail to return for further blood donation. This study was designed to determine the frequency of these complications and their associated risk factors among blood donors in Tehran. Also, we aimed to provide suitable methods to decrease the frequency of these adverse events, thereby eliminating the most important causes of withdrawal, while maintaining the health of the donors. This analytical descriptive cross-sectional study was performed on 554 blood donors who had donated blood from February 2005 through September 2005 in four fixed blood donation bases and four mobile blood collection buses. Each base was considered as a stratum, and a stratified random sampling proportional to size was done to select the donors. Results showed donor reaction rate to be 13.4%, the most common of which were blackout of vision (7%, dizziness (6.3%, fatigue (6.1% and nausea (1.8%. There was no significant relationship between the incidence of these complications and type of base blood donation or fasting at the time of blood donation. Logistic Regression analysis showed that sex, condition of blood donor, exercise or walking, duration of donation, and practice to recommendation had significant effects on the odds ratio of systemic complication. Regarding the frequency values derived for the different systemic complications it can be concluded that attention to risk factors of these complications and their control can help encourage donors to become repeated donors as well as to prevent their withdrawal for further blood donation.

  4. Blood Pressure Mobile Monitoring for Pregnant Woman Based Android System

    Science.gov (United States)

    Supriyanti, Retno; Erfayanto, Uji; Ramadani, Yogi; Murdyantoro, Eko; Widodo, Haris B.

    2016-01-01

    Currently, at least 18,000 women die every year in Indonesia due to pregnancy or childbirth. It means that every half hour a woman dies due to pregnancy or childbirth. As a result, every year 36,000 children became orphans. The high maternal mortality rate was put Indonesia on top in ASEAN. The main causes of maternal mortality are high-risk pregnancy. Mothers who have diseases like high blood pressure, pre-eclampsia, diabetes, hyperthyroidism, and already over 40 years old and infectious diseases such as rubella, hepatitis and HIV can be factors that lead to high-risk pregnancy. This paper will discuss the development of a blood pressure monitoring device that is suitable for pregnant women. It is based on convenience for pregnant women to get the equipment that is flexible with her presence. Results indicate that the equipment is in use daily support for pregnant women therefore, one of the causes of maternal mortality can be detected earlier.

  5. Influence of partial pressure of oxygen in blood samples on measurement performance in glucose-oxidase-based systems for self-monitoring of blood glucose.

    Science.gov (United States)

    Baumstark, Annette; Schmid, Christina; Pleus, Stefan; Haug, Cornelia; Freckmann, Guido

    2013-11-01

    Partial pressure of oxygen (pO2) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO2 values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not. Aliquots of 20 venous samples were adjusted to the following pO2 values: oxygen sensitive. © 2013 Diabetes Technology Society.

  6. Mechanism-based PK/PD modeling of selective serotonin reuptake inhibitors

    NARCIS (Netherlands)

    Geldof, Marian

    2007-01-01

    The main objective of the investigations was to explore the PK/PD correlations of fluvoxamine, as a prototype for the Selective Serotonin Reuptake Inhibitors (SSRIs). In the various investigations, a spectrum of different biomarkers was used, each reflecting a specific process on the causal path

  7. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

  8. The influence of ebselen on the toxicity of cisplatin in LLC-PK1 cells

    NARCIS (Netherlands)

    Baldew, G S; Boymans, A P; Mol, J G; Vermeulen, N P

    1992-01-01

    LLC-PK1 cells have been used as an in vitro model to study the nephrotoxicity of the antitumor drug cisplatin. A concentration-dependent cytotoxicity of cisplatin, measured as lactate dehydrogenase leakage and amount of protein remaining attached to the culture plate, was observed. At a cisplatin

  9. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Directory of Open Access Journals (Sweden)

    Ijaz Ahmad

    2016-01-01

    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  10. Neuroinflammation in bipolar disorder : A [C-11]-(R)-PK11195 positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C.M.; Riemersma -van der Lek, Rixt; de Groot, Jan Cees; Ruhe, Eric; Klein, Hans C; Zandstra, Tjitske E; Burger, Huibert; Schoevers, Robert A.; de Vries, Erik F.J.; Drexhage, Hemmo A; Nolen, Willem A.; Doorduin, Janine

    Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential

  11. Skin-like biosensor system via electrochemical channels for noninvasive blood glucose monitoring

    OpenAIRE

    Chen, Yihao; Lu, Siyuan; Zhang, Shasha; Li, Yan; Qu, Zhe; Chen, Ying; Lu, Bingwei; Wang, Xinyan; Feng, Xue

    2017-01-01

    Currently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement accuracy, weak blood glucose correlation, and inability to detect hyperglycemia/hypoglycemia during sleep. We present a strategy to design and fabricate a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery–powered electrochemical twin channels (ETCs). The ...

  12. Asymptotic tracking and disturbance rejection of the blood glucose regulation system.

    Science.gov (United States)

    Ashley, Brandon; Liu, Weijiu

    2017-07-01

    Type 1 diabetes patients need external insulin to maintain blood glucose within a narrow range from 65 to 108 mg/dl (3.6 to 6.0 mmol/l). A mathematical model for the blood glucose regulation is required for integrating a glucose monitoring system into insulin pump technology to form a closed-loop insulin delivery system on the feedback of the blood glucose, the so-called "artificial pancreas". The objective of this paper is to treat the exogenous glucose from food as a glucose disturbance and then develop a closed-loop feedback and feedforward control system for the blood glucose regulation system subject to the exogenous glucose disturbance. For this, a mathematical model for the glucose disturbance is proposed on the basis of experimental data, and then incorporated into an existing blood glucose regulation model. Because all the eigenvalues of the disturbance model have zero real parts, the center manifold theory is used to establish blood glucose regulator equations. We then use their solutions to synthesize a required feedback and feedforward controller to reject the disturbance and asymptotically track a constant glucose reference of 90  mg/dl. Since the regulator equations are nonlinear partial differential equations and usually impossible to solve analytically, a linear approximation solution is obtained. Our numerical simulations show that, under the linear approximate feedback and feedforward controller, the blood glucose asymptotically tracks its desired level of 90 mg/dl approximately. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Performance of arthroscopic irrigation systems assessed with automatic blood detection

    NARCIS (Netherlands)

    Tuijthof, G. J. M.; de Vaal, M. M.; Sierevelt, I. N.; Blankevoort, L.; van der List, M. P. J.

    2011-01-01

    During arthroscopies, bleeding episodes occur as a result of tissue damage. Irrigation systems assist in minimizing these disturbances. The performance of three arthroscopic irrigation systems in clearing bleeding episodes was evaluated objectively. One surgeon performed 99 shoulder arthroscopies

  14. Computed aided system for separation and classification of the abnormal erythrocytes in human blood

    Science.gov (United States)

    Wąsowicz, Michał; Grochowski, Michał; Kulka, Marek; Mikołajczyk, Agnieszka; Ficek, Mateusz; Karpieńko, Katarzyna; Cićkiewicz, Maciej

    2017-12-01

    The human peripheral blood consists of cells (red cells, white cells, and platelets) suspended in plasma. In the following research the team assessed an influence of nanodiamond particles on blood elements over various periods of time. The material used in the study consisted of samples taken from ten healthy humans of various age, different blood types and both sexes. The markings were leaded by adding to the blood unmodified diamonds and oxidation modified. The blood was put under an impact of two diamond concentrations: 20μl and 100μl. The amount of abnormal cells increased with time. The percentage of echinocytes as a result of interaction with nanodiamonds in various time intervals for individual specimens was scarce. The impact of the two diamond types had no clinical importance on red blood cells. It is supposed that as a result of longlasting exposure a dehydratation of red cells takes place, because of the function of the cells. The analysis of an influence of nanodiamond particles on blood elements was supported by computer system designed for automatic counting and classification of the Red Blood Cells (RBC). The system utilizes advanced image processing methods for RBCs separation and counting and Eigenfaces method coupled with the neural networks for RBCs classification into normal and abnormal cells purposes.

  15. Evaluation of the antimicrobial removal device when used with the BACTEC blood culture system

    International Nuclear Information System (INIS)

    Strand, C.L.

    1982-01-01

    A study to determine the value of the Antimicrobial Removal Device (ARD) used in conjunction with radiometric detection of bacteremia using three media was conducted. During a 12-month period, 622 duplicate ARD/BACTEC blood-culture sets were collected. There were 88 positive cultures that yielded 68 pathogenic isolates and 28 probable contaminant isolates. When all patients were considered, 31 pathogenic isolates were detected by both systems, 25 pathogenic isolates were detected faster or only by the BACTEC system, and 12 pathogenic isolates were detected faster or only when the ARD was employed. This difference is statistically significant (P less than 0.05). Thus, the standard BACTEC blood-culture system using three different media was superior to the same BACTEC system using ARD-processed blood specimens. When only patients receiving antimicrobial therapy were considered, there were more pathogenic isolates detected from unprocessed blood than from blood processed in the ARD; however, this difference was not statistically significant. In conclusion, there appears to be no advantage to using the ARD system in conjunction with the three-bottle BACTEC blood-culture system

  16. Continuous blood pressure recordings simultaneously with functional brain imaging: studies of the glymphatic system

    Science.gov (United States)

    Zienkiewicz, Aleksandra; Huotari, Niko; Raitamaa, Lauri; Raatikainen, Ville; Ferdinando, Hany; Vihriälä, Erkki; Korhonen, Vesa; Myllylä, Teemu; Kiviniemi, Vesa

    2017-03-01

    The lymph system is responsible for cleaning the tissues of metabolic waste products, soluble proteins and other harmful fluids etc. Lymph flow in the body is driven by body movements and muscle contractions. Moreover, it is indirectly dependent on the cardiovascular system, where the heart beat and blood pressure maintain force of pressure in lymphatic channels. Over the last few years, studies revealed that the brain contains the so-called glymphatic system, which is the counterpart of the systemic lymphatic system in the brain. Similarly, the flow in the glymphatic system is assumed to be mostly driven by physiological pulsations such as cardiovascular pulses. Thus, continuous measurement of blood pressure and heart function simultaneously with functional brain imaging is of great interest, particularly in studies of the glymphatic system. We present our MRI compatible optics based sensing system for continuous blood pressure measurement and show our current results on the effects of blood pressure variations on cerebral brain dynamics, with a focus on the glymphatic system. Blood pressure was measured simultaneously with near-infrared spectroscopy (NIRS) combined with an ultrafast functional brain imaging (fMRI) sequence magnetic resonance encephalography (MREG, 3D brain 10 Hz sampling rate).

  17. Perioperative blood ordering optimization process using information from an anesthesia information management system.

    Science.gov (United States)

    Rinehart, Joseph B; Lee, Tiffany C; Kaneshiro, Kayleigh; Tran, Minh-Ha; Sun, Coral; Kain, Zeev N

    2016-04-01

    As part of ongoing perioperative surgical home implantation process, we applied a previously published algorithm for creation of a maximum surgical blood order schedule (MSBOS) to our operating rooms. We hypothesized that using the MSBOS we could show a reduction in unnecessary preoperative blood testing and associated costs. Data regarding all surgical cases done at UC Irvine Health's operating rooms from January 1, 2011, to January 1, 2014 were extracted from the anesthesia information management systems (AIMS). After the data were organized into surgical specialties and operative sites, blood order recommendations were generated based on five specific case characteristics of the group. Next, we assessed current ordering practices in comparison to actual blood utilization to identify potential areas of wastage and performed a cost analysis comparing the annual hospital costs from preoperative blood orders if the blood order schedule were to be followed to historical practices. Of the 19,138 patients who were categorized by the MSBOS as needing no blood sample, 2694 (14.0%) had a type and screen (T/S) ordered and 1116 (5.8%) had a type and crossmatch ordered. Of the 6073 procedures where MSBOS recommended only a T/S, 2355 (38.8%) had blood crossmatched. The cost analysis demonstrated an annual reduction in actual hospital costs of $57,335 with the MSBOS compared to historical blood ordering practices. We showed that the algorithm for development of a multispecialty blood order schedule is transferable and yielded reductions in preoperative blood product screening at our institution. © 2016 AABB.

  18. [The blood-brain barrier and drug delivery in the central nervous system].

    Science.gov (United States)

    Loch-Neckel, Gecioni; Koepp, Janice

    2010-08-01

    To provide an updated view of the difficulties due to barriers and strategies used to allow the release of drugs in the central nervous system. The difficulty for the treatment of many diseases of the central nervous system, through the use of intra-venous drugs, is due to the presence of barriers that prevent the release of the same: the blood-brain barrier, blood-cerebro-spinal fluid barrier and the blood-arachnoid barrier. The blood-brain barrier is the main barrier for the transport of drugs in the brain that also acts as a immunologic and metabolic barrier. The endothelial cells of the blood-brain barrier are connected to a junction complex through the interaction of transmembrane proteins that protrude from de inside to the outside, forming a connection between the endothelial cells. The transport of substances to the brain depends on the mechanisms of transport present in the barrier and the diffusion of these compounds also depends on the physicochemical characteristics of the molecule. Some diseases alter the permeability of the blood-brain barrier and thus the passage of drugs. Strategies such as the use of methods for drug delivery in the brain have been investigated. Further details regarding the mechanisms of transport across the blood-brain barrier and the changes in neuropathology would provide important information about the etiology of diseases and lead to better therapeutic strategies.

  19. Effects of Topical Phenylephrine HCl 2.5% used before Cataract Surgery on Systemic Blood Pressure

    Directory of Open Access Journals (Sweden)

    Emre Ayıntap

    2011-06-01

    Full Text Available Purpose: To evaluate the effect of topical phenylephrine HCl 2.5% (Mydfrin, used as a fast and effective mydriatic before cataract surgery, on systemic blood pressure. Material and Method: Topical phenylephrine HCl 2.5% was administered 3 times with 5-minute intervals before cataract surgery to 44 eyes of 44 patients. The systemic blood pressure was measured preoperatively and at 15 and 30 minutes. Results: The mean systolic blood pressure before the topical administration of phenylephrine HCl 2.5% was 119.7mmHg, while 15 and 30 minutes later, it was 125.3 mmHg and 121.2 mmHg, respectively. The mean diastolic blood pressure before the topical administration of phenylephrine HCl 2.5% was 75.9 mmHg; 15 and 30 minutes later, it was 76.9 mmHg and 75.3 mmHg, respectively. The increase in systolic blood pressure at 15 and 30 minutes was statistically significant (p=0.003 and p=0.042. The change in diastolic blood pressure was not statistically significant. Discussion: Phenylephrine HCl 2.5%, which is used preoperatively as a fast and effective mydriatic for cataract surgery, can increase the systolic blood pressure. This effect is most significant at 15 minutes and lasts at least 30 minutes. This agent should be used with care in hypertensive patients. (Turk J Ophthalmol 2011; 41: 164-6

  20. Comparison of the lysis-centrifugation and agitated biphasic blood culture systems for detection of fungemia.

    Science.gov (United States)

    Murray, P R

    1991-01-01

    Although the detection of fungemia has been improved by the use of vented or biphasic blood culture bottles, the best recovery and earliest detection have been reported in the Isolator lysis-centrifugation system. It was recently demonstrated that improved detection of both bacteria and fungi was accomplished by mechanically agitating blood culture bottles for the first 24 h of incubation. In this study the detection of fungemia by use of the Isolator system was compared with that of an agitated biphasic system. A total of 182 fungi were isolated from blood specimens inoculated into both culture systems. No difference in the overall recovery of fungi or individual species of yeasts was observed between the two systems. However, all seven isolates of Histoplasma capsulatum were recovered in the Isolator system only. The time required to detect fungemia with each of the two systems was also compared. No statistically significant difference was observed. From the data collected during this 18-month study, it can be concluded that the overall recovery and time of detection of yeasts are equivalent in the lysis-centrifugation system and the agitated biphasic blood culture system. The lysis-centrifugation system is still superior for the detection of filamentous fungi such as H. capsulatum. PMID:1993772

  1. Monooxignase ensymic system of a liver of rats exposed to intravascular laser irradiation of blood

    International Nuclear Information System (INIS)

    Ibadova, G.A.

    1997-01-01

    Experimental study of the dynamic monooxidation of liver enzymic system was carried out on rats with experimental salmonellosis and the influence of the blood intravascular laser irradiation of blood on these enzymes was revealed. It was determined that by experimental salmonellosis oppression of the MOES activity of hepatocytes occurred. The blood intravascular irradiation by He-Ne laser promotes MOES oppression in rats suffered from salmonellosis. IVLIB as well as UV-laser show pronounced effect on the enzymes detoxication protection, mobilize their resistance to endogenic intoxication under the conditions of experimental salmonellosis. (author)

  2. Blood compounds irradiation process: assessment of absorbed dose using Fricke and Thermoluminescent dosimetric systems

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Gabriela de Amorim; Squair, Peterson Lima; Pinto, Fausto Carvalho; Belo, Luiz Claudio Meira; Grossi, Pablo Andrade [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: gas@cdtn.br, e-mail: pls@cdtn.br, e-mail: fcp@cdtn.br, e-mail: lcmb@cdtn.br, e-mail: pabloag@cdtn.br

    2009-07-01

    The assessment of gamma absorbed doses in irradiation facilities allows the quality assurance and control of the irradiation process. The liability of dose measurements is assign to the metrological procedures adopted including the uncertainty evaluation. Fricke and TLD 800 dosimetric systems were used to measure absorbed dose in the blood compounds using the methodology presented in this paper. The measured absorbed doses were used for evaluating the effectiveness of the irradiation procedure and the gamma dose absorption inside the irradiation room of a gamma irradiation facility. The radiation eliminates the functional and proliferative capacities of donor T-lymphocytes, preventing Transfusion associated graft-versus-host disease (TA-GVHD), a possible complication of blood transfusions. The results show the applicability of such dosimetric systems in quality assurance programs, assessment of absorbed doses in blood compounds and dose uniformity assign to the blood compounds irradiation process by dose measurements in a range between 25 Gy and 100 Gy. (author)

  3. Blood compounds irradiation process: assessment of absorbed dose using Fricke and Thermoluminescent dosimetric systems

    International Nuclear Information System (INIS)

    Soares, Gabriela de Amorim; Squair, Peterson Lima; Pinto, Fausto Carvalho; Belo, Luiz Claudio Meira; Grossi, Pablo Andrade

    2009-01-01

    The assessment of gamma absorbed doses in irradiation facilities allows the quality assurance and control of the irradiation process. The liability of dose measurements is assign to the metrological procedures adopted including the uncertainty evaluation. Fricke and TLD 800 dosimetric systems were used to measure absorbed dose in the blood compounds using the methodology presented in this paper. The measured absorbed doses were used for evaluating the effectiveness of the irradiation procedure and the gamma dose absorption inside the irradiation room of a gamma irradiation facility. The radiation eliminates the functional and proliferative capacities of donor T-lymphocytes, preventing Transfusion associated graft-versus-host disease (TA-GVHD), a possible complication of blood transfusions. The results show the applicability of such dosimetric systems in quality assurance programs, assessment of absorbed doses in blood compounds and dose uniformity assign to the blood compounds irradiation process by dose measurements in a range between 25 Gy and 100 Gy. (author)

  4. Tumor Growth Model with PK Input for Neuroblastoma Drug Development

    Science.gov (United States)

    2015-09-01

    Your credit card order has been processed on  Tuesday  2 December 2014 at 3:05 PM. Status: Complete 12/3/2014 Oasis, The Online Abstract Submission System...pharmacokinetic models. Toxicol Ind Health, 1997. 13(4): p. 407-84. PMID: 9249929 4. Davies, B. and T. Morris , Physiological parameters in laboratory animals and humans. Pharm Res, 1993. 10(7): p. 1093-5. PMID: 8378254

  5. Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment

    Directory of Open Access Journals (Sweden)

    R.A. Orujov

    2017-12-01

    Full Text Available Benzene is a widely spread chemical health risk factor. Our research goal was to examine the nervous system state and the blood system state under benzene intoxication during an experiment. An acute experiment was performed on 45 white mice with 5-fold poisoning with benzene; a chronic one was performed on 72 rabbits being under inhalation exposure to benzene during 4 months, its concentrations increasing and fluctuating. We determined the following blood parameters: number of reticulocytes, eosinophils, basocytes, and erythrocytes; erythrocytes sedimentation rate; blood clotting period; blood clot retraction; plasma re-calcification period; plasma tolerance to heparin; prothrombin time; prothrombin index; fibrinogen concentration; blood fibrinolytic activity; acetylcholine and choline esterase contents. We also determined adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine contents in urine. Acute experiments results revealed that one-time exposure to benzene exerted a narcotic effect on the central nervous system which had an excitation phase and inhibition phase. Under a repeat exposure to benzene animals' drug intoxication was shorter. And here neutrophils / leucocytes gradient first increased to 139.5 % from its standards value and then when down under consequent intoxications. We detected relevant changes in morphological picture of animals' peripheral blood and their central and vegetative nervous system under chronic exposure to intermittent and increasing benzene concentrations. So, our research revealed that effects exerted by benzene in small concentrations led to apparent shifts in white blood and catecholamines (adrenalin, noradrenalin, dopamine, and dihydroxyphenylalanine. We also detected certain signs that cate-cholamines endogenous reserves (dihydroxyphenylalanine were depleted and, and also signs of eosinophils-basocytes disso-ciation; such prognostic signs were considered to be unfavorable as it was exactly at that

  6. Plasma fractionation, a useful means to improve national transfusion system and blood safety: Iran experience.

    Science.gov (United States)

    Cheraghali, A M; Abolghasemi, H

    2009-03-01

    In 1974, the government of Iran established Iranian Blood Transfusion Organization (IBTO) as national and centralized transfusion system. Since then donations of blood may not be remunerated and therapy with blood and its components are free of charges for all Iranian patients. Donations are meticulously screened through interviewing donors and lab testing the donations using serological methods. Currently, Iranian donors donate 1735 00 units of blood annually (donation index: 25/1000 population). Implementation of a highly efficient donor selection programme, including donors interview, establishment of confidential unit exclusion programme and laboratory screening of donated bloods by IBTO have led to seroprevalence rates of 0.41%, 0.12% and 0.004% for HBV, HCV and HIV in donated bloods respectively. Since 2004, IBTO has initiated a programme to enter into a contract fractionation agreement for the surplus of recovered plasma produced in its blood collecting centres. Although IBTO has used this project as a mean to improve national transfusion system through upgrading its quality assurance systems, IBTO fractionation project has played a major role in improving availability of plasma-derived medicines in Iran. During 2006-2007, this project furnished the Iran market with 44% and 14% of its needs to the intravenous immunoglobulin and albumin, respectively. Iranian experience showed that contract fractionation of plasma in countries with organized centralized transfusion system, which lack national plasma fractionation facility, in addition to substantial saving on national health resource and enhancing availability of plasma-derived medicines, could serve as a useful means to improve national blood safety profile.

  7. Involvement of DNA-PK and ATM in radiation- and heat-induced DNA damage recognition and apoptotic cell death

    International Nuclear Information System (INIS)

    Tomita, Masanori

    2010-01-01

    Exposure to ionizing radiation and hyperthermia results in important biological consequences, e.g. cell death, chromosomal aberrations, mutations, and DNA strand breaks. There is good evidence that the nucleus, specifically cellular DNA, is the principal target for radiation-induced cell lethality. DNA double-strand breaks (DSBs) are considered to be the most serious type of DNA damage induced by ionizing radiation. On the other hand, verifiable mechanisms which can lead to heat-induced cell death are damage to the plasma membrane and/or inactivation of heat-labile proteins caused by protein denaturation and subsequent aggregation. Recently, several reports have suggested that DSBs can be induced after hyperthermia because heat-induced phosphorylated histone H2AX (γ-H2AX) foci formation can be observed in several mammalian cell lines. In mammalian cells, DSBs are repaired primarily through two distinct and complementary mechanisms: non-homologous end joining (NHEJ), and homologous recombination (HR) or homology-directed repair (HDR). DNA-dependent protein kinase (DNA-PK) and ataxia-telangiectasia mutated (ATM) are key players in the initiation of DSB repair and phosphorylate and/or activate many substrates, including themselves. These phosphorylated substrates have important roles in the functioning of cell cycle checkpoints and in cell death, as well as in DSB repair. Apoptotic cell death is a crucial cell suicide mechanism during development and in the defense of homeostasis. If DSBs are unrepaired or misrepaired, apoptosis is a very important system which can protect an organism against carcinogenesis. This paper reviews recently obtained results and current topics concerning the role of DNA-PK and ATM in heat- or radiation-induced apoptotic cell death. (author)

  8. [A capillary blood flow velocity detection system based on linear array charge-coupled devices].

    Science.gov (United States)

    Zhou, Houming; Wang, Ruofeng; Dang, Qi; Yang, Li; Wang, Xiang

    2017-12-01

    In order to detect the flow characteristics of blood samples in the capillary, this paper introduces a blood flow velocity measurement system based on field-programmable gate array (FPGA), linear charge-coupled devices (CCD) and personal computer (PC) software structure. Based on the analysis of the TCD1703C and AD9826 device data sheets, Verilog HDL hardware description language was used to design and simulate the driver. Image signal acquisition and the extraction of the real-time edge information of the blood sample were carried out synchronously in the FPGA. Then a series of discrete displacement were performed in a differential operation to scan each of the blood samples displacement, so that the sample flow rate could be obtained. Finally, the feasibility of the blood flow velocity detection system was verified by simulation and debugging. After drawing the flow velocity curve and analyzing the velocity characteristics, the significance of measuring blood flow velocity is analyzed. The results show that the measurement of the system is less time-consuming and less complex than other flow rate monitoring schemes.

  9. Optimizing preoperative blood ordering with data acquired from an anesthesia information management system.

    Science.gov (United States)

    Frank, Steven M; Rothschild, James A; Masear, Courtney G; Rivers, Richard J; Merritt, William T; Savage, Will J; Ness, Paul M

    2013-06-01

    The maximum surgical blood order schedule (MSBOS) is used to determine preoperative blood orders for specific surgical procedures. Because the list was developed in the late 1970s, many new surgical procedures have been introduced and others improved upon, making the original MSBOS obsolete. The authors describe methods to create an updated, institution-specific MSBOS to guide preoperative blood ordering. Blood utilization data for 53,526 patients undergoing 1,632 different surgical procedures were gathered from an anesthesia information management system. A novel algorithm based on previously defined criteria was used to create an MSBOS for each surgical specialty. The economic implications were calculated based on the number of blood orders placed, but not indicated, according to the MSBOS. Among 27,825 surgical cases that did not require preoperative blood orders as determined by the MSBOS, 9,099 (32.7%) had a type and screen, and 2,643 (9.5%) had a crossmatch ordered. Of 4,644 cases determined to require only a type and screen, 1,509 (32.5%) had a type and crossmatch ordered. By using the MSBOS to eliminate unnecessary blood orders, the authors calculated a potential reduction in hospital charges and actual costs of $211,448 and $43,135 per year, respectively, or $8.89 and $1.81 per surgical patient, respectively. An institution-specific MSBOS can be created, using blood utilization data extracted from an anesthesia information management system along with our proposed algorithm. Using these methods to optimize the process of preoperative blood ordering can potentially improve operating room efficiency, increase patient safety, and decrease costs.

  10. Effectiveness of a Novel Specimen Collection System in Reducing Blood Culture Contamination Rates.

    Science.gov (United States)

    Bell, Mary; Bogar, Catherine; Plante, Jessica; Rasmussen, Kristen; Winters, Sharon

    2018-04-20

    False-positive blood-culture results due to skin contamination of samples remain a persistent problem for health care providers. Our health system recognized that our rates of contamination across the 4 emergency department campuses were above the national average. A unique specimen collection system was implemented throughout the 4 emergency departments and became the mandatory way to collect adult blood cultures. The microbiology laboratory reported contamination rates weekly to manage potential problems; 7 months of data are presented here. There was an 82.8% reduction in false positives with the unique specimen collection system compared with the standard method (chi-squared test with Yates correction, 2-tailed, P = 0.0001). Based on the historical 3.52% rate of blood-culture contamination for our health facilities, 2.92 false positives were prevented for every 100 blood cultures drawn, resulting from adoption of the unique specimen collection system as the standard of care. This unique collection system can reduce the risk of blood culture contamination significantly and is designed to augment, rather than replace, the standard phlebotomy protocol already in use in most health care settings. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Comparative Analysis of Clinical Samples Showing Weak Serum Reaction on AutoVue System Causing ABO Blood Typing Discrepancies

    OpenAIRE

    Jo, Su Yeon; Lee, Ju Mi; Kim, Hye Lim; Sin, Kyeong Hwa; Lee, Hyeon Ji; Chang, Chulhun Ludgerus; Kim, Hyung-Hoi

    2016-01-01

    Background ABO blood typing in pre-transfusion testing is a major component of the high workload in blood banks that therefore requires automation. We often experienced discrepant results from an automated system, especially weak serum reactions. We evaluated the discrepant results by the reference manual method to confirm ABO blood typing. Methods In total, 13,113 blood samples were tested with the AutoVue system; all samples were run in parallel with the reference manual method according to...

  12. An experimental system for the study of ultrasound exposure of isolated blood vessels

    NARCIS (Netherlands)

    Tokarczyk, Anna; Rivens, Ian; van Bavel, E.; Symonds-Tayler, Richard; ter Haar, Gail

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and

  13. Automated DBS microsampling, microscale automation and microflow LC-MS for therapeutic protein PK.

    Science.gov (United States)

    Zhang, Qian; Tomazela, Daniela; Vasicek, Lisa A; Spellman, Daniel S; Beaumont, Maribel; Shyong, BaoJen; Kenny, Jacqueline; Fauty, Scott; Fillgrove, Kerry; Harrelson, Jane; Bateman, Kevin P

    2016-04-01

    Reduce animal usage for discovery-stage PK studies for biologics programs using microsampling-based approaches and microscale LC-MS. We report the development of an automated DBS-based serial microsampling approach for studying the PK of therapeutic proteins in mice. Automated sample preparation and microflow LC-MS were used to enable assay miniaturization and improve overall assay throughput. Serial sampling of mice was possible over the full 21-day study period with the first six time points over 24 h being collected using automated DBS sample collection. Overall, this approach demonstrated comparable data to a previous study using single mice per time point liquid samples while reducing animal and compound requirements by 14-fold. Reduction in animals and drug material is enabled by the use of automated serial DBS microsampling for mice studies in discovery-stage studies of protein therapeutics.

  14. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers

    International Nuclear Information System (INIS)

    Chauveau, Fabien; Camp, Nadja van; Tavitian, Bertrand; Boutin, Herve; Dolle, Frederic

    2008-01-01

    Neurodegenerative, inflammatory and neoplastic brain disorders involve neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful for diagnostic, drug development and therapy control of these frequent diseases. In vivo imaging can document the expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO) that is linked to microglial activation and considered a hallmark of neuroinflammation. The prototype positron emission tomography tracer for PBR, [ 11 C]PK11195, has shown limitations that until now have slowed the clinical applications of PBR imaging. In recent years, dozens of new PET and SPECT radioligands for the PBR have been radiolabelled, and several have been evaluated in imaging protocols. Here we review the new PBR ligands proposed as challengers of [ 11 C]PK11195, critically analyze preclinical imaging studies and discuss their potential as neuroinflammation imaging agents. (orig.)

  15. The Chikungunya epidemic in Italy and its repercussion on the blood system.

    Science.gov (United States)

    Liumbruno, Giancarlo Maria; Calteri, Deanna; Petropulacos, Kyriakoula; Mattivi, Andrea; Po, Claudio; Macini, Pierluigi; Tomasini, Ivana; Zucchelli, Paolo; Silvestri, Anna Rita; Sambri, Vittorio; Pupella, Simonetta; Catalano, Liviana; Piccinini, Vanessa; Calizzani, Gabriele; Grazzini, Giuliano

    2008-10-01

    The Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and recently caused a massive epidemic on La Réunion Island, in the Indian Ocean. Between July and September 2007 it caused the first autochthonous epidemic outbreak in Europe, in the Region of Emilia-Romagna in the north-east of Italy. After the first reports of an unusually high number of patients with a febrile illness of unknown origin in two contiguous villages, an outbreak investigation was carried out to identify the primary source of infection, the modes of transmission and the dynamics of the epidemic. An active surveillance system was also implemented. Laboratory diagnosis was performed through serology and polymerase chain reaction (PCR) analysis. Blood donation was discontinued in the areas involved from September to October 2007 and specific precautionary blood safety and self-sufficiency measures were adopted by the regional health and blood authorities and the National Blood Centre. An estimate method to early assess the risk of viraemic blood donations by asymptomatic donors was developed, as a tool for "pragmatic" risk assessment and management, aiming at providing a reliable order of magnitude of the mean risk of CHIKV transmission through blood transfusion. Two hundred and seventeen cases of CHIKV infection were identified between 4th July and 28th September. The disease was fairly mild in most of the cases. The precautionary measures adopted in the blood system caused a considerable reduction of the collection of blood components and of the delivery of plasma to the pharmaceutical industry for contract manufacturing. The estimated risk of CHIKV transmission through blood transfusion peaked in the third week of August. ACHIKV epidemic poses considerable problems for public health authorities, who not only need good routine programmes of vector control and epidemiological surveillance but also local and national emergency plans to sustain the blood supply, so as to promptly deal

  16. Critical role of bioanalytical strategies in investigation of clinical PK observations, a Phase I case study

    Science.gov (United States)

    Peng, Kun; Xu, Keyang; Liu, Luna; Hendricks, Robert; Delarosa, Reginald; Erickson, Rich; Budha, Nageshwar; Leabman, Maya; Song, An; Kaur, Surinder; Fischer, Saloumeh K

    2014-01-01

    RG7652 is a human immunoglobulin 1 (IgG1) monoclonal antibody (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and is designed for the treatment of hypercholesterolemia. A target-binding enzyme-linked immunosorbent assay (ELISA) was developed to measure RG7652 levels in human serum in a Phase I study. Although target-binding assay formats are generally used to quantify free therapeutic, the actual therapeutic species being measured are affected by assay conditions, such as sample dilution and incubation time, and levels of soluble target in the samples. Therefore, in the presence of high concentrations of circulating target, the choice of reagents and assay conditions can have a significant effect on the observed pharmacokinetic (PK) profiles. Phase I RG7652 PK analysis using the ELISA data resulted in a nonlinear dose normalized exposure. An investigation was conducted to characterize the ELISA to determine whether the assay format and reagents may have contributed to the PK observation. In addition, to confirm the ELISA results, a second orthogonal method, liquid chromatography tandem mass spectrometry (LC-MS/MS) using a signature peptide as surrogate, was developed and implemented. A subset of PK samples, randomly selected from half of the subjects in the 6 single ascending dose (SAD) cohorts in the Phase I clinical study, was analyzed with the LC-MS/MS assay, and the data were found to be comparable to the ELISA data. This paper illustrates the importance of reagent characterization, as well as the benefits of using an orthogonal approach to eliminate bioanalytical contributions when encountering unexpected observations. PMID:25484037

  17. Effects of cyclosporin A on a kidney epithelial cell line (LLC-PK1).

    Science.gov (United States)

    Becker, G M; Gandolfi, A J; Nagle, R B

    1987-05-01

    Cyclosporin A (CSA), a potent immunosuppressant with the adverse side effect of nephrotoxicity, inhibited cell growth of pig kidney tubule cells (LLC-PK1) in culture. CSA (10(-5) M) also induced intense cytoplasmic vacuolation and the formation of dense granules. At the same concentration an analogue of CSA, cyclosporin G, had much less effect. This cell line may prove useful for revealing the mechanism of CSA-nephrotoxicity and testing the nephrotoxic potential of new analogues of cyclosporine.

  18. Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Han-Chung Wu

    2010-01-01

    Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

  19. Hepatobiliary system functional analysis by blood flow and clearance delay model

    International Nuclear Information System (INIS)

    Aboltins, A.; Reinholds, E.

    2002-01-01

    A mathematical model for describing liver uptake-excretion is developed and approved. Model is based on different timing delays in hepatobiliary and blood flow system elements. Series of scintigraphic images with 99m Tc-mebrofenins or 99m Tc-HIDA taken with standard nuclear medicine gamma camera are used as the real data for calculations. The time-activity curves are obtained from many regions of human body - heart, liver, gallbladder, spleen, aorta, vein, etc. Both first pass and dynamic acquisition data are used. Results are calculated using real system parameters and compared to real scintigraphy data. Mathematical simulations are made to show difference of hepatobiliary system function at three main points: normal function, good blood flow with bad hepatic function and bad blood flow with good hepatic function. (authors)

  20. Comparison of exercise blood pressure measured by technician and an automated system.

    Science.gov (United States)

    Garcia-Gregory, J A; Jackson, A S; Studeville, J; Squires, W G; Owen, C A

    1984-05-01

    We evaluated the automated system Blood Pressure Measuring System (BPMS) developed by NASA on 277 adult males who elected to have a treadmill test as part of their annual physical. The BPMS uses acoustic transduction with a computer-assisted ECG gating to detect nonsynchronous noise. The BPMS readings were compared to pressures simultaneously measured by trained technicians. For all stages of work, BPMS readings were higher for systolic and lower for diastolic than technician readings. At peak stages of work, BPMS systolic pressures were about 20 mmHg higher than technician readings. Within each 3-min workstage, BPMS readings were found to be more inconsistent than technician readings. The standard errors of measurement for BPMS were from two to three times higher than technician values. These data showed automated blood pressure readings were significantly different than technician values and subject to more random fluctuations. These findings demonstrate the need to view exercise blood pressure measured by automated systems with caution.

  1. HARP preferentially co-purifies with RPA bound to DNA-PK and blocks RPA phosphorylation.

    Science.gov (United States)

    Quan, Jinhua; Yusufzai, Timur

    2014-05-01

    The HepA-related protein (HARP/SMARCAL1) is an ATP-dependent annealing helicase that is capable of rewinding DNA structures that are stably unwound due to binding of the single-stranded DNA (ssDNA)-binding protein Replication Protein A (RPA). HARP has been implicated in maintaining genome integrity through its role in DNA replication and repair, two processes that generate RPA-coated ssDNA. In addition, mutations in HARP cause a rare disease known as Schimke immuno-osseous dysplasia. In this study, we purified HARP containing complexes with the goal of identifying the predominant factors that stably associate with HARP. We found that HARP preferentially interacts with RPA molecules that are bound to the DNA-dependent protein kinase (DNA-PK). We also found that RPA is phosphorylated by DNA-PK in vitro, while the RPA-HARP complexes are not. Our results suggest that, in addition to its annealing helicase activity, which eliminates the natural binding substrate for RPA, HARP blocks the phosphorylation of RPA by DNA-PK.

  2. The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics.

    Science.gov (United States)

    Fishburn, C Simone

    2008-10-01

    Conjugation of macromolecules to polyethylene glycol (PEG) has emerged recently as an effective strategy to alter the pharmacokinetic (PK) profiles of a variety of drugs, and thereby to improve their therapeutic potential. PEG conjugation increases retention of drugs in the circulation by protecting against enzymatic digestion, slowing filtration by the kidneys and reducing the generation of neutralizing antibodies. Often, PEGylation leads to a loss in binding affinity due to steric interference with the drug-target binding interaction. This loss in potency is offset by the longer circulating half-life of the drugs, and the resulting change in PK-PD profile has led in some cases to enabling of drugs that otherwise could not be developed, and in others to improvements in existing drugs. Thus, whereas most approaches to drug development seek to increase the activity of drugs directly, the creation of PEGylated drugs seeks to balance the pharmacodynamic (PD) and pharmacokinetic properties to produce novel therapies that will meet with both increased efficacy and greater compliance in the clinical setting. This review examines some of the PEGylated drugs developed in recent years, and highlights some of the different strategies taken to employ PEG to maximize the overall PK-PD profiles of these compounds. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  3. Nano Copper Induces Apoptosis in PK-15 Cells via a Mitochondria-Mediated Pathway.

    Science.gov (United States)

    Zhang, Hui; Chang, Zhenyu; Mehmood, Khalid; Abbas, Rao Zahid; Nabi, Fazul; Rehman, Mujeeb Ur; Wu, Xiaoxing; Tian, Xinxin; Yuan, Xiaodan; Li, Zhaoyang; Zhou, Donghai

    2018-01-01

    Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40-100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly (P nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.

  4. Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans.

    Science.gov (United States)

    Ichinose, Masashi; Ichinose-Kuwahara, Tomoko; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-11-15

    Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. Copyright © 2015 the American Physiological Society.

  5. Economic and workflow analysis of a blood bank automated system.

    Science.gov (United States)

    Shin, Kyung-Hwa; Kim, Hyung Hoi; Chang, Chulhun L; Lee, Eun Yup

    2013-07-01

    This study compared the estimated costs and times required for ABO/Rh(D) typing and unexpected antibody screening using an automated system and manual methods. The total cost included direct and labor costs. Labor costs were calculated on the basis of the average operator salaries and unit values (minutes), which was the hands-on time required to test one sample. To estimate unit values, workflows were recorded on video, and the time required for each process was analyzed separately. The unit values of ABO/Rh(D) typing using the manual method were 5.65 and 8.1 min during regular and unsocial working hours, respectively. The unit value was less than 3.5 min when several samples were tested simultaneously. The unit value for unexpected antibody screening was 2.6 min. The unit values using the automated method for ABO/Rh(D) typing, unexpected antibody screening, and both simultaneously were all 1.5 min. The total cost of ABO/Rh(D) typing of only one sample using the automated analyzer was lower than that of testing only one sample using the manual technique but higher than that of testing several samples simultaneously. The total cost of unexpected antibody screening using an automated analyzer was less than that using the manual method. ABO/Rh(D) typing using an automated analyzer incurs a lower unit value and cost than that using the manual technique when only one sample is tested at a time. Unexpected antibody screening using an automated analyzer always incurs a lower unit value and cost than that using the manual technique.

  6. Histopathological Study of Central Nervous System Lesions: Emphasizing Association of Neoplasms with ABO Blood Groups.

    Science.gov (United States)

    Kumarguru, B N; Pallavi, P; Sunila; Manjunath, G V; Vasan, T S; Rajalakshmi, B R

    2017-04-01

    The Central Nervous System (CNS) lesions show considerable geographic and racial variations with respect to the incidence and the pattern of distribution of lesions. The ABO blood status is a readily accessible factor in genetic constitution of the patients. It has been shown to be associated with many diseases. But the influence of blood group status on the pathogenesis of brain tumours is still unclear. To study various histopathological patterns of CNS lesions and to evaluate the association of CNS tumours with the distribution of ABO blood groups in documented cases. In the present study, 147 cases were analyzed. It was an analytical type of study, done at JSS Medical College, Mysore, over a period of 2 years and 8 months from January 2009 to August 2011. Histopathology slides were routinely stained by Haematoxylin and Eosin (H&E) stain. Special stains were performed in selected cases. Blood group of the patients and the control group were documented. Blood group distribution pattern was assessed in relation to histopathological diagnosis of various CNS tumours. Histopathological diagnosis of 147 cases included neoplastic lesions (84.35%) and non-neoplastic lesions (15.64%). Neoplastic lesions (84.35%) constituted the majority, which included neuroepithelial tumours (29.25%) as predominant pattern. Non-neoplastic lesions constituted only 15.64%, which included inflammatory lesion (8.16%) as the predominant pattern. ABO blood group data was available in 92 cases (84.4%) of neoplastic lesions, which included 71 cases (48.29%) of primary CNS neoplasms categorized according to WHO grades. The control group constituted 21,067 healthy voluntary donors. Blood group O was the most frequent blood group in neoplastic lesions (40.21%) and primary CNS neoplasms categorized according to WHO grades (45.07%). The association between the CNS neoplasms and ABO blood groups was not statistically significant (p = 0.055). But a definite change in the pattern of distribution of ABO

  7. Tumor blood flow and systemic shunting in patients receiving intraarterial chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Wheeler, R.H.; Ziessman, H.A.; Medvec, B.R.; Juni, J.E.; Thrall, J.H.; Keyes, J.W.; Pitt, S.R.; Baker, S.R.

    1986-01-01

    Radionuclide techniques have been used to estimate the systemic shunt and to quantitate blood flow to the tumor and a reference normal tissue in nine patients undergoing intraarterial chemotherapy for head and neck cancer. The systemic shunt was calculated as the percentage of pulmonary trapping of intraarterially injected /sup 99m/Tc-labeled macroaggregated albumin. The mean systemic shunt in the 12 separate arteries studied was 23 +/- 13% (SE) (range 8-43%). Quantitative blood flow was determined from the slope of the washout curve of intraarterially injected 133 Xe. The mean tumor blood flow was 13.6 +/- 6.7 ml/100 g/min, while the mean blood flow to the scalp was 4.2 +/- 2.1 ml/100 g/min providing a mean tumor/normal tissue ratio of 3.9 +/- 2.7. An estimate of blood flow distribution was obtained by calculating the ratio of counts/pixel in the tumor mass versus the remainder of the head as determined by single photon emission computed tomography following an intraarterial injection of /sup 99m/Tc-labeled macroaggregated albumin. The mean ratio of tumor to normal tissue perfusion by this technique was 5.6 +/- 3.7. These techniques have allowed noninvasive determination of the blood flow parameters associated with intraarterial chemotherapy. At least part of the therapeutic advantage of regional chemotherapy in patients with head and neck cancer is due to a tumor/normal tissue blood flow ratio that favors drug delivery to the tumor contained within the infused volume

  8. Electronic remote blood issue: a combination of remote blood issue with a system for end-to-end electronic control of transfusion to provide a "total solution" for a safe and timely hospital blood transfusion service.

    Science.gov (United States)

    Staves, Julie; Davies, Amanda; Kay, Jonathan; Pearson, Oliver; Johnson, Tony; Murphy, Michael F

    2008-03-01

    The rapid provision of red cell (RBC) units to patients needing blood urgently is an issue of major importance in transfusion medicine. The development of electronic issue (sometimes termed "electronic crossmatch") has facilitated rapid provision of RBC units by avoidance of the serologic crossmatch in eligible patients. A further development is the issue of blood under electronic control at blood refrigerator remote from the blood bank. This study evaluated a system for electronic remote blood issue (ERBI) developed as an enhancement of a system for end-to-end electronic control of hospital transfusion. Practice was evaluated before and after its introduction in cardiac surgery. Before the implementation of ERBI, the median time to deliver urgently required RBC units to the patient was 24 minutes. After its implementation, RBC units were obtained from the nearby blood refrigerator in a median time of 59 seconds (range, 30 sec to 2 min). The study also found that unused requests were reduced significantly from 42 to 20 percent, the number of RBC units issued reduced by 52 percent, the number of issued units that were transfused increased from 40 to 62 percent, and there was a significant reduction in the workload of both blood bank and clinical staff. This study evaluated a combination of remote blood issue with an end-to-end electronically controlled hospital transfusion process, ERBI. ERBI reduced the time to make blood available for surgical patients and improved the efficiency of hospital transfusion.

  9. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

    NARCIS (Netherlands)

    Tangden, T.; Martin, V.; Felton, T.W.; Nielsen, E.I.; Marchand, S.; Bruggemann, R.J.M.; Bulitta, J.B.; Bassetti, M.; Theuretzbacher, U.; Tsuji, B.T.; Wareham, D.W.; Friberg, L.E.; Waele, J.J. De; Tam, V.H.; Roberts, J.A.

    2017-01-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed.

  10. Expression of manganese superoxide dismutase in rat blood, heart and brain during induced systemic hypoxia

    Directory of Open Access Journals (Sweden)

    Septelia I. Wanandi

    2011-02-01

    Full Text Available Background: Hypoxia results in an increased generation of ROS. Until now, little is known about the role of MnSOD - a major endogenous antioxidant enzyme - on the cell adaptation response against hypoxia. The aim of this study was to  determine the MnSOD mRNA expression and levels of specific activity in blood, heart and brain of rats during induced systemic hypoxia.Methods: Twenty-five male Sprague Dawley rats were subjected to systemic hypoxia in an hypoxic chamber (at 8-10% O2 for 0, 1, 7, 14 and 21 days, respectively. The mRNA relative expression of MnSOD was analyzed using Real Time RT-PCR. MnSOD specific activity was determined using xanthine oxidase inhibition assay.Results: The MnSOD mRNA relative expression in rat blood and heart was decreased during early induced systemic hypoxia (day 1 and increased as hypoxia continued, whereas the mRNA expression in brain was increased since day 1 and reached its maximum level at day 7. The result of MnSOD specific activity during early systemic hypoxia was similar to the mRNA expression. Under very late hypoxic condition (day 21, MnSOD specific activity in blood, heart and brain was significantly decreased. We demonstrate a positive correlation between MnSOD mRNA expression and specific activity in these 3 tissues during day 0-14 of induced systemic hypoxia. Furthermore, mRNA expression and specific activity levels in heart strongly correlate with those in blood.Conclusion: The MnSOD expression at early and late phases of induced systemic hypoxia is distinctly regulated. The MnSOD expression in brain differs from that in blood and heart revealing that brain tissue can  possibly survive better from induced systemic hypoxia than heart and blood. The determination of MnSOD expression in blood can be used to describe its expression in heart under systemic hypoxic condition. (Med J Indones 2011; 20:27-33Keywords: MnSOD, mRNA expression, ROS, specific activity, systemic hypoxia

  11. Non-association between anti-Toxoplasma gondii antibodies and ABO blood group system

    Directory of Open Access Journals (Sweden)

    ACF Rodrigues

    2011-01-01

    Full Text Available Toxoplasma gondii infects humans through the gastrointestinal tract (GIT, which elicits humoral immune response with specific antibodies. The expression of the ABO blood group glycoconjugates also occurs in this same system and may influence the human susceptibility of infection by T. gondii. The aim of the present study was to investigate the association between ABO blood group phenotypes and the presence of anti-T. gondii antibodies. Data - including age, results of serology tests for T. gondii infection and ABO blood group phenotypes - were assembled from the medical records of 1,006 pregnant women attended in the Base Hospital of the Medical School of São José do Rio Preto, Brazil, between 2001 and 2004. The chi-square test was used to compare the results with the level of significance set at 5%. Of the studied cases, 64.1% (645/1006 and 35.9% (391/1006 presented respectively positive and negative serology tests for anti-T. gondii antibodies. The mean age of those who tested positive was higher than those with negative serology tests (p = 0.0004. The frequencies of ABO blood group phenotypes were similar in those with and without anti-T. gondii antibodies (p = 0.35. In conclusion, the ABO blood group system is not associated with the presence or absence of anti-T. gondii antibodies.

  12. Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Houben Roland

    2005-12-01

    Full Text Available Abstract Background Activation of Ras or Raf contributes to tumorigenesis of melanoma. However, constitutive Raf activation is also a characteristic of the majority of benign melanocytic nevi and high intensity signaling of either Ras or Raf was found to induce growth inhibition and senescence rather than transformation. Since the chromosome 3p kinase (3pK is a target of the Ras/Raf/Mek/Erk signaling pathway which antagonizes the function of the oncogene and anti-differentiation factor Bmi-1, 3pK may function as a tumor suppressor in tumors with constitutive Ras/Raf activation. Consequently, we tested whether inactivating 3pK mutations are present in melanoma. Methods 30 metastatic melanoma samples, which were positive for activating mutations of either BRaf or NRas, were analyzed for possible mutations in the 3pk gene. The 10 coding exons and their flanking intron sequences were amplified by PCR and direct sequencing of the PCR products was performed. Results This analysis revealed that besides the presence of some single nucleotide polymorphisms in the 3pk gene, we could not detect any possible loss of function mutation in any of these 30 metastatic melanoma samples selected for the presence of activating mutations within the Ras/Raf/Mek/Erk signaling pathway. Conclusion Hence, in melanoma with constitutively active Ras/Raf inactivating mutations within the 3pk gene do not contribute to the oncogenic phenotype of this highly malignant tumor.

  13. Accuracy and precision evaluation of seven self-monitoring blood glucose systems.

    Science.gov (United States)

    Kuo, Chih-Yi; Hsu, Cheng-Teng; Ho, Cheng-Shiao; Su, Ting-En; Wu, Ming-Hsun; Wang, Chau-Jong

    2011-05-01

    Self-monitoring blood glucose (SMBG) systems play a critical role in management of diabetes. SMBG systems should at least meet the minimal requirement of the World Health Organization's ISO 15197:2003. For tight glycemic control, a tighter accuracy requirement is needed. Seven SMBG systems were evaluated for accuracy and precision: Bionime Rightest(™) GM550 (Bionime Corp., Dali City, Taiwan), Accu-Chek(®) Performa (Roche Diagnostics, Indianapolis, IN), OneTouch(®) Ultra(®)2 (LifeScan Inc., Milpitas, CA), MediSense(®) Optium(™) Xceed (Abbott Diabetes Care Inc., Alameda, CA), Medisafe (TERUMO Corp., Tokyo, Japan), Fora(®) TD4227 (Taidac Technology Corp., Wugu Township, Taiwan), and Ascensia Contour(®) (Bayer HealthCare LLC, Mishawaka, IN). The 107 participants (44 men and 63 women) were between 23 and 91 years old. The analytical results of seven SMBG systems were compared with those of plasma analyzed with the hexokinase method (Olympus AU640, Olympus America Inc., Center Valley, PA). The imprecision of the seven blood glucose meters ranged from 1.1% to 4.7%. Three of the seven blood glucose meters (42.9%) fulfilled the minimum accuracy criteria of ISO 15197:2003. The mean absolute relative error value for each blood glucose meter was calculated and ranged from 6.5% to 12.0%. More than 40% of evaluated SMBG systems meet the minimal accuracy criteria requirement of ISO 15197:2003. However, considering tighter criteria for accuracy of ±15%, only the Bionime Rightest GM550 meets this requirement. Because SMBG systems play a critical role in management of diabetes, manufacturers have to strive to improve accuracy and precision and to ensure the good quality of blood glucose meters and test strips.

  14. 78 FR 18353 - Guidance for Industry: Blood Establishment Computer System Validation in the User's Facility...

    Science.gov (United States)

    2013-03-26

    ... SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. Submit electronic comments on... document entitled ``Guidance for Industry: Blood Establishment Computer System Validation in the User's... document to http://www.regulations.gov or written comments to the Division of Dockets Management (see...

  15. Central Gi(2) proteins, sympathetic nervous system and blood pressure regulation

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef

    2016-01-01

    Roč. 216, č. 3 (2016), s. 258-259 ISSN 1748-1708 Institutional support: RVO:67985823 Keywords : inhibitory G proteins * sympathetic nervous system * central blood pressure control Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.867, year: 2016

  16. Large-scale clinical comparison of the lysis-centrifugation and radiometric systems for blood culture

    International Nuclear Information System (INIS)

    Brannon, P.; Kiehn, T.E.

    1985-01-01

    The Isolator 10 lysis-centrifugation blood culture system (E. I. du Pont de Nemours and Co., Inc., Wilmington, Del.) was compared with the BACTEC radiometric method (Johnston Laboratories, Inc., Towson, Md.) with 6B and 7D broth media for the recovery of bacteria and yeasts. From 11,000 blood cultures, 1,174 clinically significant organisms were isolated. The Isolator system recovered significantly more total organisms, members of the family Enterobacteriaceae, Staphylococcus spp., and yeasts. The BACTEC system recovered significantly more Pseudomonas spp., Streptococcus spp., and anaerobes. Of the Isolator colony counts, 87% measured less than 11 CFU/ml of blood. Organisms, on an average, were detected the same day from each of the two culture systems. Only 13 of the 975 BACTEC isolates (0.01%) were recovered by subculture of growth-index-negative bottles, and 12 of the 13 were detected in another broth blood culture taken within 24 h. Contaminants were recovered from 4.8% of the Isolator 10 and 2.3% of the BACTEC cultures

  17. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients.

    Science.gov (United States)

    Kanadani, Fabio N; Figueiredo, Carlos R; Miranda, Rafaela Morais; Cunha, Patricia Lt; M Kanadani, Tereza Cristina; Dorairaj, Syril

    2015-01-01

    Glaucomatous neuropathy can be a consequence of insufficient blood supply, increase in intraocular pressure (IOP), or other risk factors that diminish the ocular blood flow. To determine the ocular perfusion pressure (OPP) in normal and systemic hypertensive patients. One hundred and twenty-one patients were enrolled in this prospective and comparative study and underwent a complete ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, stereoscopic fundus examination, and pulsatile ocular blood flow (POBF) measurements. The OPP was calculated as being the medium systemic arterial pressure (MAP) less the IOP. Only right eye values were considered for calculations using Student's t-test. The mean age of the patients was 57.5 years (36-78), and 68.5% were women. There was a statistically significant difference in the OPP of the normal and systemic hypertensive patients (p cite this article: Kanadani FN, Figueiredo CR, Miranda RM, Cunha PLT, Kanadani TCM, Dorairaj S. Ocular Perfusion Pressure and Pulsatile Ocular Blood Flow in Normal and Systemic Hypertensive Patients. J Curr Glaucoma Pract 2015;9(1):16-19.

  18. 21 CFR 864.9900 - Cord blood processing system and storage container.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cord blood processing system and storage container. 864.9900 Section 864.9900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That...

  19. 21 CFR 864.9125 - Vacuum-assisted blood collection system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vacuum-assisted blood collection system. 864.9125 Section 864.9125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture...

  20. Proteolytic system of blood-feeding ticks: An update on protein structures

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Zuzana; Hobizalová, Radka; Žebrakovská, Iva; Brynda, Jiří; Řezáčová, Pavlína; Horn, Martin; Mareš, Michael

    2015-01-01

    Roč. 22, č. 1 (2015), s. 43-44 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : blood-feeding ticks * protein structure * proteolytic system Subject RIV: CE - Biochemistry

  1. HB&L System: rapid determination of antibiotic sensitivity of bacteria isolated from blood cultures.

    Directory of Open Access Journals (Sweden)

    Simone Barocci

    2010-03-01

    Full Text Available Introduction. Blood culture is an important method to detect microbial pathogens on blood, very useful for diagnosing bacterial infections. Unfortunately, classical diagnostic protocols cannot directly identify bacteria responsible for sepsis and accordingly their antimicrobial profiles. This problem causes a delay of almost two days in the availability of a specific antimicrobial profile. Objective. Among the main causes of death, sepsis have a relevant importance. For this reason it is important both to identify pathogens and to perform an antimicrobial susceptibility test in the shortest time as possible. For this purpose, the main aim of this study is the evaluation of the performances of an antimicrobial susceptibility determination directly performed on positive blood cultures. Materials and methods. This study has been performed on 70 positive blood cultures, during the period from January to July 2009. A number of 35 blood cultures were positive for Gram negative bacteria, and 35 were positive for Gram positive bacteria. From these positive blood cultures, after a short sample preparation, it has been possible to directly determine antimicrobial susceptibility profiles by using the HB&L (formerly URO-QUICK instrument. Results. The HB&L system results showed a very good correlation with both the classical disk diffusion method and VITEK 2 automatic system.The performances between the methods carried out in this study were equivalent. Conclusions. From data reported, thanks to the rapidity and simplicity of the method used, we can assert that the direct susceptibility test available with the HB&L system, is useful for a rapid and early choice of the antibiotic treatment.

  2. Suppression of spleen pathological function by roentgenoendovascular occlussion in some blood systemic diseases

    International Nuclear Information System (INIS)

    Rabkin, I.Kh.; Matevosov, A.L.; Gotman, L.N.

    1987-01-01

    It is shown that REO of splenic artery in thrombocytopenic purpura, hypoplastic and autoimmune hemolytic anemia manifests the same clinical effect as splenectomy. This treatment procedure may substitute splenectomy in a definite group of patients with above-mentioned blood systemic diseases or precede it as a preparation and prognosis stage. Stage-by-stage total embolization of splenic artery is a necessary technical method permitting to attain the necessary medical effect without risk of developing acute spleen infarction. At present REO is used in some blood diseases in patients with high risk of operation, particularly with active hemorrhagic syndrome of adrenal insufficiency, concomitant inflammatory processes

  3. Performance of two updated blood glucose monitoring systems: an evaluation following ISO 15197:2013.

    Science.gov (United States)

    Pleus, Stefan; Baumstark, Annette; Rittmeyer, Delia; Jendrike, Nina; Haug, Cornelia; Freckmann, Guido

    2016-05-01

    Objective For patients with diabetes, regular self-monitoring of blood glucose (SMBG) is essential to ensure adequate glycemic control. Therefore, accurate and reliable blood glucose measurements with SMBG systems are necessary. The international standard ISO 15197 describes requirements for SMBG systems, such as limits within which 95% of glucose results have to fall to reach acceptable system accuracy. The 2013 version of this standard sets higher demands, especially regarding system accuracy, than the currently still valid edition. ISO 15197 can be applied by manufacturers to receive a CE mark for their system. Research design and methods This study was an accuracy evaluation following ISO 15197:2013 section 6.3 of two recently updated SMBG systems (Contour * and Contour TS; Bayer Consumer Care AG, Basel, Switzerland) with an improved algorithm to investigate whether the systems fulfill the requirements of the new standard. For this purpose, capillary blood samples of approximately 100 participants were measured with three test strip lots of both systems and deviations from glucose values obtained with a hexokinase-based comparison method (Cobas Integra † 400 plus; Roche Instrument Center, Rotkreuz, Switzerland) were determined. Percentages of values within the acceptance criteria of ISO 15197:2013 were calculated. This study was registered at clinicaltrials.gov (NCT02358408). Main outcome Both updated systems fulfilled the system accuracy requirements of ISO 15197:2013 as 98.5% to 100% of the results were within the stipulated limits. Furthermore, all results were within the clinically non-critical zones A and B of the consensus error grid for type 1 diabetes. Conclusions The technical improvement of the systems ensured compliance with ISO 15197 in the hands of healthcare professionals even in its more stringent 2013 version. Alternative presentation of system accuracy results in radar plots provides additional information with certain advantages. In addition

  4. Characterization of 3D PET systems for accurate quantification of myocardial blood flow

    OpenAIRE

    Renaud, Jennifer M.; Yip, Kathy; Guimond, Jean; Trottier, Mikaël; Pibarot, Philippe; Turcotte, Éric; Maguire, Conor; Lalonde, Lucille; Gulenchyn, Karen; Farncombe, Troy; Wisenberg, Gerald; Moody, Jonathan; Lee, Benjamin; Port, Steven C.; Turkington, Timothy G

    2016-01-01

    Three-dimensional (3D) mode imaging is the current standard for positron emission tomography-computed tomography (PET-CT) systems. Dynamic imaging for quantification of myocardial blood flow (MBF) with short-lived tracers, such as Rb-82- chloride (Rb-82), requires accuracy to be maintained over a wide range of isotope activities and scanner count-rates. We propose new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative...

  5. Can sibutramine alter systemic blood pressure in obese patients? Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Hernani Pinto de Lemos Júnior

    Full Text Available CONTEXT: Systemic arterial hypertension is part of the metabolic syndrome resulting from obesity. OBJECTIVE: To evaluate the effect of sibutramine on overweight and obese patients' blood pressure through a systematic review. METHODS: All the studies included needed to be randomized controlled trials. The methodological quality of the selected trials was assessed using the criteria described in the Cochrane Handbook. The participants were overweight and obese patients; the intervention was sibutramine compared with placebo. The primary outcome measurement was systolic and diastolic blood pressure and the secondary measurement was blood pressure. Studies were identified by searching the following sources: Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs, Medline, Cochrane reviews, manual searches, personal communication and contact with the pharmaceutical industry. There were no language, date or other restrictions. Data collection and extraction was performed by two reviewers, who independently obtained the full articles of all eligible papers. RESULTS: Three meta-analyses were produced: 1 systolic blood pressure outcome (eight studies did not show statistical significance between sibutramine and placebo: weighted mean difference (WMD 1.57, confidence interval (CI -0.03 to 3.18; 2 diastolic blood pressure outcome (ten studies did not show statistical significance between sibutramine and placebo: WMD 1.13, CI -0.49 to 2.76; 3 blood pressure outcome (two studies also did not show statistical significance between the groups: relative risk (RR 0.69, CI 0.07 to 7.01. CONCLUSIONS: The meta-analyses presented in this systematic review show that sibutramine does not have a statistically significant effect on blood pressure, compared with placebo.

  6. The Impact of an Electronic Ordering System on Blood Bank Specimen Rejection Rates.

    Science.gov (United States)

    Forest, Stefanie K; Shirazi, Maryam; Wu-Gall, Charlotte; Stotler, Brie A

    2017-01-01

    To evaluate the impact that an electronic ordering system has on the rate of rejection of blood type and screen testing samples and the impact on the number of ABO blood-type discrepancies over a 4-year period. An electronic ordering system was implemented in May 2011. Rejection rates along with reasons for rejection were tracked between January 2010 and December 2013. A total of 40,104 blood samples were received during this period, of which 706 (1.8%) were rejected for the following reasons: 382 (54.0%) unsigned samples, 235 (33.0%) mislabeled samples, 57 (8.0%) unsigned requisitions, 18 (2.5%) incorrect tubes, and 14 (1.9%) ABO discrepancies. Of the samples, 2.5% were rejected in the year prior to implementing the electronic ordering system compared with 1.2% in the year following implementation ( P  blood sample rejection. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  7. Influence of Partial Pressure of Oxygen in Blood Samples on Measurement Performance in Glucose-Oxidase-Based Systems for Self-Monitoring of Blood Glucose

    Science.gov (United States)

    Baumstark, Annette; Schmid, Christina; Pleus, Stefan; Haug, Cornelia; Freckmann, Guido

    2013-01-01

    Background Partial pressure of oxygen (pO2) in blood samples can affect blood glucose (BG) measurements, particularly in systems that employ the glucose oxidase (GOx) enzyme reaction on test strips. In this study, we assessed the impact of different pO2 values on the performance of five GOx systems and one glucose dehydrogenase (GDH) system. Two of the GOx systems are labeled by the manufacturers to be sensitive to increased blood oxygen content, while the other three GOx systems are not. Methods Aliquots of 20 venous samples were adjusted to the following pO2 values: pO2 ~70 mmHg, which is considered to be similar to pO2 in capillary blood samples, and the mean BG result at pO2 pO2 pO2 ≥150 mmHg. For both pO2 levels, relative differences of all tested GOx systems were significant (p pO2 values pO2 variations lead to clinically relevant BG measurement deviations in GOx systems, even in GOx systems that are not labeled as being oxygen sensitive. PMID:24351177

  8. Systemic arterial hypertension, blood pressure levels and associated factors in schoolchildren

    Directory of Open Access Journals (Sweden)

    Priscila Heleno

    Full Text Available Summary Introduction: Hypertension is a major public health problem in contemporary times and it has high prevalence throughout the world. Objective: To investigate the situation of Systemic Arterial Hypertension in schoolchildren aged 6 to 10 years in Divinópolis/MG-Brazil and associated factors. Method: This is a cross-sectional, epidemiological, descriptive and analytical study, whose population was children aged 6 to 10 years enrolled in public schools in Divinópolis-MG-Brazil. Data collection was conducted from October 2014 to May 2015. Multivariate linear regressions were used to test associations between blood pressure, socioeconomic, anthropometric, dietary and physical activity. Results: The prevalence of hypertension was 15.2% in a sample of 284 children and mean values of systolic blood pressure of 101.7 (±13.2 mmHg and diastolic blood pressure of 66.0 (±11.2 mmHg. The body fat percentage showed significant differences between the genders, with 24.2 and 26.2%, respectively for boys and girls. Significant associations were made between blood pressure levels, body weight, body mass index, waist circumference, body fat percentage, consumption of yogurt, beef /chicken, beans, pizza, sandwich and some behaviors variables. Conclusion: The presented data show important aspects of school profile in the age range 6-10 years, especially related to the behavior of blood pressure.

  9. Inhibition of chemiluminescence by carvedilol in the cell-free system, whole human blood and blood cells

    Czech Academy of Sciences Publication Activity Database

    Nosál, R.; Jančinová, V.; Číž, Milan; Drábiková, K.; Lojek, Antonín; Fábryová, V.

    2005-01-01

    Roč. 65, č. 1 (2005), s. 55-64 ISSN 0036-5513 Institutional research plan: CEZ:AV0Z50040507 Keywords : blood platelets * carvedilol * chemiluminescence Subject RIV: BO - Biophysics Impact factor: 0.946, year: 2005

  10. Fast Blood Vector Velocity Imaging using ultrasound: In-vivo examples of complex blood flow in the vascular system

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Lindskov; Udesen, Jesper; Gran, Fredrik

    2008-01-01

    Conventional ultrasound methods for acquiring color flow images of the blood motion are restricted by a relatively low frame rate and angle dependent velocity estimates. The Plane Wave Excitation (PWE) method has been proposed to solve these limitations. The frame rate can be increased, and the 2-D...... vector velocity of the blood motion can be estimated. The transmitted pulse is not focused, and a full speckle image of the blood can be acquired for each emission. A 13 bit Barker code is transmitted simultaneously from each transducer element. The 2-D vector velocity of the blood is found using 2-D...... speckle tracking between segments in consecutive speckle images. The flow patterns of six bifurcations and two veins were investigated in-vivo. It was shown: 1) that a stable vortex in the carotid bulb was present opposed to other examined bifurcations, 2) that retrograde flow was present...

  11. Mutant prevention concentration and PK-PD relationships of enrofloxacin for Pasteurella multocida in buffalo calves.

    Science.gov (United States)

    Balaje, R M; Sidhu, P K; Kaur, G; Rampal, S

    2013-12-01

    This study validated the use of mutant prevention concentration (MPC) and pharmacokinetic and pharmacodynamic (PK-PD) modeling approach for optimization of dose regimen of enrofloxacin to contain the emergence of Pasteurella multocida resistance. The PK and PD characteristics of enrofloxacin were investigated in buffalo calves after intramuscular administration at a dose rate of 12 mg/kg. The concentration of enrofloxacin and ciprofloxacin in serum were determined by high-performance liquid chromatography. The serum peak concentration (Cmax), terminal half-life (t1/2K10), volume of distribution (Vd(area)/F) and mean residence time (MRT) of enrofloxacin were 1.89 ± 0.35 μg/ml, 5.14 ± 0.66 h, 5.59 ± 0.99 l/kg/h and 8.52 ± 1.29 h, respectively. The percent metabolite conversion ratio of ciprofloxacin to enrofloxacin was 79. The binding of enrofloxacin to plasma proteins was 11%. The MIC, MBC and MPC for enrofloxacin against P. multocida were 0.05, 0.06 μg/ml and 1.50 μg/ml.In vitro and ex-vivo bactericidal activity of enrofloxacin was concentration dependent. Modeling of ex-vivo growth inhibition data to the sigmoid Emax equation provided AUC24h/MIC values to produce bacteriostatic (19 h), bactericidal (43 h) and bacterial eradication (64 h). PK-PD data in conjunction with MPC and MIC90 data predicted dosage schedules for enrofloxacin that may achieve optimum efficacy in respect of bacteriological and clinical cure and minimize the risk of emergence of resistance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Blood Conservation.

    Science.gov (United States)

    Martin, Jeremiah T; Ferraris, Victor A

    2015-01-01

    Patient blood management requires multi-modality and multidisciplinary collaboration to identify patients who are at increased risk of requiring blood transfusion and therefore decrease exposure to blood products. Transfusion is associated with poor postoperative outcomes, and guidelines exist to minimize transfusion requirements. This review highlights recent studies and efforts to apply patient blood management across disease processes and health care systems. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. On cerebrae blood circulation from data of radiocirculography in some diseases of central nervous system in children

    International Nuclear Information System (INIS)

    Dolgov, A.G.; Stroganova, L.I.; Chirkin, N.I.

    1980-01-01

    Results of radioisotope investigation of cerebral blood circulation in 202 children with different pathology of central nervous system are presented. Velocity of cerebral blood flow and time of semiaccumulation and semimoving a preparate were investigated by means of sup(113m)In. It is established that radiocirculography shows clearly the changes in the system of cerebral blood supply and in such diseases as vegetovascular distonia and hypertension syndrome, the radiocirculography data pass ahead the clinical picture

  14. A PK-PD model of ketamine-induced high-frequency oscillations

    Science.gov (United States)

    Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.

    2015-10-01

    Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent

  15. [11C]-(R)-PK11195 positron emission tomography in patients with complex regional pain syndrome

    Science.gov (United States)

    Jeon, So Yeon; Seo, Seongho; Lee, Jae Sung; Choi, Soo-Hee; Lee, Do-Hyeong; Jung, Ye-Ha; Song, Man-Kyu; Lee, Kyung-Jun; Kim, Yong Chul; Kwon, Hyun Woo; Im, Hyung-Jun; Lee, Dong Soo; Cheon, Gi Jeong; Kang, Do-Hyung

    2017-01-01

    Abstract Complex regional pain syndrome (CRPS) is characterized by severe and chronic pain, but the pathophysiology of this disease are not clearly understood. The primary aim of our case–control study was to explore neuroinflammation in patients with CRPS using positron emission tomography (PET), with an 18-kDa translocator protein specific radioligand [11C]-(R)-PK11195. [11C]-(R)-PK11195 PET scans were acquired for 11 patients with CRPS (30–55 years) and 12 control subjects (30–52 years). Parametric image of distribution volume ratio (DVR) for each participant was generated by applying a relative equilibrium-based graphical analysis. The DVR of [11C]-(R)-PK11195 in the caudate nucleus (t(21) = −3.209, P = 0.004), putamen (t(21) = −2.492, P = 0.022), nucleus accumbens (t(21) = −2.218, P = 0.040), and thalamus (t(21) = −2.395, P = 0.026) were significantly higher in CRPS patients than in healthy controls. Those of globus pallidus (t(21) = −2.045, P = 0.054) tended to be higher in CRPS patients than in healthy controls. In patients with CRPS, there was a positive correlation between the DVR of [11C]-(R)-PK11195 in the caudate nucleus and the pain score, the visual analog scale (r = 0.661, P = 0.026, R2 = 0.408) and affective subscales of McGill Pain Questionnaire (r = 0.604, P = 0.049, R2 = 0.364). We demonstrated that neuroinflammation of CRPS patients in basal ganglia. Our results suggest that microglial pathology can be an important pathophysiology of CRPS. Association between the level of caudate nucleus and pain severity indicated that neuroinflammation in this region might play a key role. These results may be essential for developing effective medical treatments. PMID:28072713

  16. Role of DNA-PK in cellular responses to DNA double-strand breaks

    International Nuclear Information System (INIS)

    Chen, D.J.

    2003-01-01

    DNA double-strand breaks (DSBs) are probably the most dangerous of the many different types of DNA damage that occur within the cell. DSBs are generated by exogenous agents such as ionizing radiation (IR) or by endogenously generated reactive oxygen species and occur as intermediates during meiotic and V(D)J recombination. The repair of DSBs is of paramount importance to the cell as misrepair of DSBs can lead to cell death or promote tumorigenesis. In eukaryotes there exists two distinct mechanisms for DNA DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). In mammalian cells, however, it is clear that nonhomologous repair of DSBs is highly active and plays a major role in conferring radiation resistance to the cell. The NHEJ machinery minimally consists of the DNA-dependent Protein Kinase (DNA-PK) and a complex of XRCC4 and DNA Ligase IV. The DNA-PK complex is composed of a 470 kDa catalytic subunit (DNA-PKcs), and the heterodimeric Ku70 and Ku80 DNA end-binding complex. DNA-PKcs is a PI-3 kinase with homology to ATM and ATR in its C-terminal kinase domain. The DNA-PK complex protects and tethers the ends, and directs assembly and, perhaps, the activation of other NHEJ proteins. We have previously demonstrated that the kinase activity of DNA-PK is essential for DNA DSB repair and V(D)J recombination. It is, therefore, of immense interest to determine the in vivo targets of DNA-PKcs and the mechanisms by which phosphorylation of these targets modulates NHEJ. Recent studies have resulted in the identification of a number of protein targets that are phosphorylated by and/or interact with DNA-PKcs. Our laboratory has recently identified autophosphorylation site(s) on DNA-PKcs. We find that phosphorylation at these sites in vivo is an early and essential response to DSBs and demonstrate, for the first time, the localization of DNA-PKcs to the sites of DNA damage in vivo. Furthermore, mutation of these phosphorylation sites in mammalian

  17. Liver-inherent immune system: its role in blood-stage malaria.

    Science.gov (United States)

    Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A

    2014-01-01

    The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main "antipodal" functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with "self" and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of "protective" autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system.

  18. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Science.gov (United States)

    Fricke, Lisa; Petroff, David; Desch, Steffen; Lurz, Philipp; Reinhardt, Sebastian; Sonnabend, Melanie; Classen, Joseph; Baum, Petra

    2017-01-01

    Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1) and normal or enhanced in nine patients (group 2). The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145 mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p = 0.045). Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  19. Molecular – genetic variance of RH blood group system within human population of Bosnia and Herzegovina

    Directory of Open Access Journals (Sweden)

    Lejla Lasić

    2013-02-01

    Full Text Available There are two major theories for inheritance of Rh blood group system: Fisher - Race theory and Wiener theory. Aim of this study was identifying frequency of RHDCE alleles in Bosnian - Herzegovinian population and introduction of this method in screening for Rh phenotype in B&H since this type of analysis was not used for blood typing in B&H before. Rh blood group was typed by Polymerase Chain Reaction, using the protocols and primers previously established by other authors, then carrying out electrophoresis in 2-3% agarose gel. Percentage of Rh positive individuals in our sample is 84.48%, while the percentage of Rh negative individuals is 15.52%. Inter-rater agreement statistic showed perfect agreement (K=1 between the results of Rh blood system detection based on serological and molecular-genetics methods. In conclusion, molecular - genetic methods are suitable for prenatal genotyping and specific cases while standard serological method is suitable for high-throughput of samples.

  20. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Directory of Open Access Journals (Sweden)

    Lisa Fricke

    2017-04-01

    Full Text Available Objectives: Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. Methods: A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Results: Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1 and normal or enhanced in nine patients (group 2. The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1–21 mmHg, p = 0.035 and from 166 to 145 mmHg (8–34 mmHg, p = 0.005, respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3–22 mmHg greater in group 2 than in group 1 (p = 0.045. Conclusion: Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  1. Impact of partial pressure of oxygen in blood samples on the performance of systems for self-monitoring of blood glucose.

    Science.gov (United States)

    Schmid, Christina; Baumstark, Annette; Pleus, Stefan; Haug, Cornelia; Tesar, Martina; Freckmann, Guido

    2014-03-01

    The partial pressure of oxygen (pO2) in blood samples can affect glucose measurements with oxygen-sensitive systems. In this study, we assessed the influence of different pO2 levels on blood glucose (BG) measurements with five glucose oxidase (GOD) systems and one glucose dehydrogenase (GDH) system. All selected GOD systems were indicated by the manufacturers to be sensitive to increased oxygen content of the blood sample. Venous blood samples of 16 subjects (eight women, eight men; mean age, 52 years; three with type 1 diabetes, four with type 2 diabetes, and nine without diabetes) were collected. Aliquots of each sample were adjusted to the following pO2 values: ≤45 mm Hg, approximately 70 mm Hg, and ≥150 mm Hg. For each system, five consecutive measurements on each sample were performed using the same test strip lot. Relative differences between the mean BG value at a pO2 level of approximately 70 mm Hg, which was considered to be similar to pO2 values in capillary blood samples, and the mean BG value at pO2 levels ≤45 mm Hg and ≥150 mm Hg were calculated. The GOD systems showed mean relative differences between 11.8% and 44.5% at pO2 values ≤45 mm Hg and between -14.6% and -21.2% at pO2 values ≥150 mm Hg. For the GDH system, the mean relative differences were -0.3% and -0.2% at pO2 values ≤45 mm Hg and ≥150 mm Hg, respectively. The magnitude of the pO2 impact on BG measurements seems to vary among the tested oxygen-sensitive GOD systems. The pO2 range in which oxygen-sensitive systems operate well should be provided in the product information.

  2. Performance of a new test strip for freestyle blood glucose monitoring systems.

    Science.gov (United States)

    Lock, John Paul; Brazg, Ronald; Bernstein, Robert M; Taylor, Elizabeth; Patel, Mona; Ward, Jeanne; Alva, Shridhara; Chen, Ting; Welsh, Zoë; Amor, Walter; Bhogal, Claire; Ng, Ronald

    2011-01-01

    a new strip, designed to enhance the ease of use and minimize interference of non-glucose sugars, has been developed to replace the current FreeStyle (Abbott Diabetes Care, Alameda, CA) blood glucose test strip. We evaluated the performance of this new strip. laboratory evaluation included precision, linearity, dynamic range, effects of operating temperature, humidity, altitude, hematocrit, interferents, and blood reapplication. System accuracy, lay user performance, and ease of use for finger capillary blood testing and accuracy for venous blood testing were evaluated at clinics. Lay users also compared the speed and ease of use between the new strip and the current FreeStyle strip. for glucose concentrations blood glucose results obtained by lay users fell within ± 5, 10, and 15 mg/dL, respectively, of the reference. For glucose concentrations ≥75 mg/dL, 68%, 95%, 99%, and 99% of the lay user results fell within  ±  5%, 10%, 15%, and 20%, respectively, of the reference. Comparable accuracy was obtained in the venous blood study. Lay users found the new test strip easy to use and faster and easier to use than the current FreeStyle strip. The new strip maintained accuracy under various challenging conditions, including high concentrations of various interferents, sample reapplication up to 60 s, and extremes in hematocrit, altitude, and operating temperature and humidity. our results demonstrated excellent accuracy of the new FreeStyle test strip and validated the improvements in minimizing interference and enhancing ease of use.

  3. A SYSTEM AND A DEVICE FOR ISOLATING CIRCULATING TUMOR CELLS FROM THE PERIPHERAL BLOOD IN VIVO

    Directory of Open Access Journals (Sweden)

    Michal Mego

    2015-08-01

    Full Text Available Circulating tumor cells (CTC play a crucial role in disseminating tumors and in the metastatic cascade. CTCs are found only in small numbers, and the limited amount of isolated CTCs makes it impossible to characterize them closely. This paper presents a proposal for a new system for isolating CTCs from the peripheral blood in vivo. The system enables CTCs to be isolated from the whole blood volume for further research and applications. The proposed system consists of magnetic nanoparticles covered by monoclonal antibodies against a common epithelial antigen, large supermagnets, which are used to control the position of the nanoparticles within the human body, and a special wire made of a magnetic core wrapped in a non-magnetic shell. The system could be used not only for isolating CTCs, but also for in vivo isolation of other rare cells from the peripheral blood, including hematopoietic and/or mesenchymal stem cells, with applications in regenerative medicine and/or in stem cell transplantation.

  4. Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery.

    Science.gov (United States)

    Pardridge, William M; Boado, Ruben J

    2009-10-01

    Glial-derived neurotrophic factor (GDNF) is a potential therapy for stroke, Parkinson's disease, or drug addiction. However, GDNF does not cross the blood-brain barrier (BBB). GDNF is re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR), which acts as a molecular Trojan horse to deliver the GDNF across the BBB. The pharmacokinetics (PK), toxicology, and safety pharmacology of the HIRMAb-GDNF fusion protein were investigated in Rhesus monkeys. The fusion protein was administered as an intravenous injection at doses up to 50 mg/kg over a 60 h period to 56 Rhesus monkeys. The plasma concentration of the HIRMAb-GDNF fusion protein was measured with a 2-site sandwich ELISA. No adverse events were observed in a 2-week terminal toxicology study, and no neuropathologic changes were observed. The PK analysis showed a linear relationship between plasma AUC and dose, a large systemic volume of distribution, as well as high clearance rates of 8-10 mL/kg/min. A no-observable-adverse-effect level is established in the Rhesus monkey for the acute administration of the HIRMAb-GDNF fusion protein. The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule.

  5. Methodological Guidelines for Reducing the Complexity of Data Warehouse Development for Transactional Blood Bank Systems.

    Science.gov (United States)

    Takecian, Pedro L; Oikawa, Marcio K; Braghetto, Kelly R; Rocha, Paulo; Lucena, Fred; Kavounis, Katherine; Schlumpf, Karen S; Acker, Susan; Carneiro-Proietti, Anna B F; Sabino, Ester C; Custer, Brian; Busch, Michael P; Ferreira, João E

    2013-06-01

    Over time, data warehouse (DW) systems have become more difficult to develop because of the growing heterogeneity of data sources. Despite advances in research and technology, DW projects are still too slow for pragmatic results to be generated. Here, we address the following question: how can the complexity of DW development for integration of heterogeneous transactional information systems be reduced? To answer this, we proposed methodological guidelines based on cycles of conceptual modeling and data analysis, to drive construction of a modular DW system. These guidelines were applied to the blood donation domain, successfully reducing the complexity of DW development.

  6. Determination of lead in whole blood: Comparison of the LeadCare blood lead testing system with zeeman longitudinal electrothermal atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Pineau, A.; Viallefont, A.; Fauconneau, B.; Rafael, M.; Guillard, O.

    2002-01-01

    This study compares the efficiency of blood lead level analysis by graphite furnace atomic absorption spectrometry (GFAAS) and the portable LeadCare Blood lead testing system (LCS). Recoveries of two added lead concentrations of 22 and 42 μg/dL ranged from 102.4 to 105.5% for LCS and from 96.3 to 97.2% for GFAAS. Measurement of a certified sample (Certified Danish Whole Blood) at a blood lead concentration of 26.2 μg/dL gave within- and between-run coefficients of variation which were both approximately 8% by LCS and 2% by GFAAS. Comparison of the tested method (LCS) versus GFAAS from analysis of 76 samples of blood lead collected from workers in different industrial sectors showed imperfect overall correlation (r = 0.95). The LCS is quite suitable for screening purposes, but requires the use of non-frozen blood collected less than 24 h before. Conservative threshold values should be applied when using the LCS for initial screening in the field. (orig.)

  7. Intraoperative evaluation of renal blood flow during laparoscopic partial nephrectomy with a novel Doppler system.

    Science.gov (United States)

    Mues, Adam C; Okhunov, Zhamshid; Badani, Ketan; Gupta, Mantu; Landman, Jaime

    2010-12-01

    Hemostasis remains a major challenge associated with laparoscopic renal surgery. We evaluated a cost-effective novel Doppler probe (DP) for assessment of vascular control during laparoscopic partial nephrectomy (LPN). We prospectively collected data during LPN procedures. We documented tumor location and size as well as subjective quality of the hilar dissection. The DP was compared with our standard intraoperative ultrasound system (SUS) for the ability to detect blood flow during hilar dissection and to determine parenchymal ischemia around the tumor after clamping of the renal vessels. Twenty patients underwent LPN by a single surgeon. The mean tumor size was 3.0 cm (range: 1.2-6.3 cm). The times to assess the kidney using the SUS and DP were 68.6 seconds (range: 20-155) and 44.5 seconds (range: 15-180), respectively. Evaluation prior to renal hilar clamping demonstrated the presence of blood flow in all 20 patients (100%) using the SUS and in 17 of 20 (85%) using the DP. Similarly, cessation of blood flow with clamping was documented in 100% of cases with SUS and 85% with DP. Persistent flow was detected by both SUS and DP in two patients requiring further dissection and reclamping. Then, both systems detected the absence of flow before tumor resection. With blood flow interruption confirmation, no patient had significant bleeding at the time of renal parenchymal transection. Intraoperative Doppler ultrasound technologies minimize the risk of significant bleeding during LPN. The DP is a small, simple, effective probe that can be used to assess blood flow interruption to the kidney during laparoscopic renal surgery.

  8. Evaluation of the BD BACTEC FX blood volume monitoring system as a continuous quality improvement measure.

    Science.gov (United States)

    Coorevits, L; Van den Abeele, A-M

    2015-07-01

    The yield of blood cultures is proportional to the volume of blood cultured. We evaluated an automatic blood volume monitoring system, recently developed by Becton Dickinson within its BACTEC EpiCenter module, that calculates mean volumes of negative aerobic bottles and generates boxplots and histograms. First, we evaluated the filling degree of 339 aerobic glass blood cultures by calculating the weight-based volume for each bottle. A substantial amount of the bottles (48.3%) were inadequately filled. Evaluation of the accuracy of the monitoring system showed a mean bias of -1.4 mL (-15.4%). Additional evaluation, using the amended software on 287 aerobic blood culture bottles, resulted in an acceptable mean deviation of -0.3 mL (-3.3%). The new software version was also tested on 200 of the recently introduced plastic bottles, which will replace the glass bottles in the near future, showing a mean deviation of +2.8 mL (+26.7%). In conclusion, the mean calculated volumes can be used for the training of a single phlebotomist. However, filling problems appear to be masked when using them for phlebotomist groups or on wards. Here, visual interpretation of boxplots and histograms can serve as a useful tool to observe the spread of the filling degrees and to develop a continuous improvement program. Re-adjustment of the software has proven to be necessary for use with plastic bottles. Due to our findings, BD has developed further adjustments to the software for validated use with plastic bottles, which will be released soon.

  9. Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

    Science.gov (United States)

    Wilkinson, A L; Pedersen, S H; Urassa, M; Michael, D; Andreasen, A; Todd, J; Kinung'hi, S M; Changalucha, J; McDermid, J M

    2017-01-01

    HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  10. Pathways for Small Molecule Delivery to the Central Nervous System Across the Blood-Brain Barrier

    OpenAIRE

    Mikitsh, John L; Chacko, Ann-Marie

    2014-01-01

    The treatment of central nervous system (CNS) disease has long been difficult due to the ineffectiveness of drug delivery across the blood-brain barrier (BBB). This review summarizes important concepts of the BBB in normal versus pathophysiology and how this physical, enzymatic, and efflux barrier provides necessary protection to the CNS during drug delivery, and consequently treatment challenging. Small molecules account for the vast majority of available CNS drugs primarily due to their abi...

  11. Artificial heart system thermal converter and blood pump component research and development

    International Nuclear Information System (INIS)

    Pouchot, W.D.; Bifano, N.J.; Hanson, J.P.

    1975-01-01

    A bench model version of a nuclear-powered artificial heart system to be used as a replacement for the natural heart was constructed and tested as a part of a broader U. S. ERDA program. The objective of the broader program has been to develop a prototype of a fully implantable nuclear-powered total artificial heart system powered by the thermal energy of plutonium-238 and having minimum weight and volume and a minimum life of ten years. As a forward step in this broader program, component research and development has been carried out directed towards a fully implantable and advanced version of the bench model (IVBM). Some of the results of the component research and development effort on a Stirling engine, blood pump drive mechanisms, and coupling mechanisms are presented. The Stirling-mechanical system under development is shown. There are three major subassemblies: the thermal converter, the coupling mechanism, and the blood pump drive mechanism. The thermal converter uses a Stirling cycle to convert the heat of the plutonium-238 fueled heat source to a rotary shaft power output. The coupling mechanism changes the orientation of the output shaft by 90 degrees and transmits the pumping power by wire-wound core flexible shafting to the pumping mechanism. The coupling mechanism also provides routing of the coolant lines which carry the cycle waste heat from the thermal converter to the blood pump. The change in orientation of the thermal converter output shaft is for convenience in implanting in a calf. This orientation of thermal converter to blood pump seemed to give the best overall system fit in a calf based on fit trials with wooden models in a calf cadaver

  12. Optimization of sugar and blood feeding regimen in Anopheles gambiae mass production system

    International Nuclear Information System (INIS)

    Sedofia, B. K

    2013-07-01

    The sterile insect technique (SIT) is being developed for the control of malaria transmitting mosquitoes. Critical to the success of applying the SIT is the establishment of standardized mass production systems for the target species. As part of efforts to develop standardised mass production systems for malaria vectors, this project sought to optimize adult blood and sugar feeding in a mass production system. Different sugar types (glucose, sucrose and honey) were evaluated at 6% and 10% concentrations in water to determine the best sugar diet and concentration for feeding adult An. gambiae. Different blood feeding methods, restrained Guinea pig, anaesthetised Guinea pig and human arm feeding were evaluated. Adult survival, female insemination and egg production were used as criteria to determine optimum sugar and blood feeding. The effect of anaesthetics on blood feeding response and egg production of female An. gambiae was determined by comparing feeding response and egg production of females fed with anaesthetised Guinea pigs as against physically restrained Guinea pigs (Control). The specific effect of different anaesthetic agents on blood feeding response and egg production of female mosquitoes were was also determined by comparing the feeding response and egg production of females fed with either Ketamine/Xylazine anaesthetised Guinea pigs or Ketamine/Diazepam anaesthetised Guinea pigs. Effects due to sugar types and concentrations on percentage survival of male and female mosquitoes were observed to be significant at (p 0.05). However, human ann feeding (HAP) method and Ketamine/Xylazine (KX) anaesthetics fed for 25 minutes recorded higher percentage feeding (76.0% and 68.0% respectively) and egg production of 19.0% and 20.8% respectively. Anaesthetised Guinea pig feeding (AGF) of adults for 15 minutes followed closely with 60.0% and 15.1% blood feeding and egg production respectively whilst restrained Guinea pig feeding (RGF) method and Ketamine

  13. Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

    Science.gov (United States)

    Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

    2015-06-01

    In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

  14. Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair.

    Science.gov (United States)

    Sharma, Aruna; Menon, Preeti; Muresanu, Dafin F; Ozkizilcik, Asya; Tian, Z Ryan; Lafuente, José V; Sharma, Hari S

    2016-01-01

    The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.

  15. Design of a Continuous Blood Pressure Measurement System Based on Pulse Wave and ECG Signals.

    Science.gov (United States)

    Li, Jian-Qiang; Li, Rui; Chen, Zhuang-Zhuang; Deng, Gen-Qiang; Wang, Huihui; Mavromoustakis, Constandinos X; Song, Houbing; Ming, Zhong

    2018-01-01

    With increasingly fierce competition for jobs, the pressures on people have risen in recent years, leading to lifestyle and diet disorders that result in significantly higher risks of cardiovascular disease. Hypertension is one of the common chronic cardiovascular diseases; however, mainstream blood pressure measurement devices are relatively heavy. When multiple measurements are required, the user experience and the measurement results may be unsatisfactory. In this paper, we describe the design of a signal collection module that collects pulse waves and electrocardiograph (ECG) signals. The collected signals are input into a signal processing module to filter the noise and amplify the useful physiological signals. Then, we use a wavelet transform to eliminate baseline drift noise and detect the feature points of the pulse waves and ECG signals. We propose the concept of detecting the wave shape associated with an instance, an approach that minimizes the impact of atypical pulse waves on blood pressure measurements. Finally, we propose an improved method for measuring blood pressure based on pulse wave velocity that improves the accuracy of blood pressure measurements by 58%. Moreover, the results meet the american medical instrument promotion association standards, which demonstrate the feasibility of our measurement system.

  16. The Effect of Pneumatic Tube Systems on the Hemolysis of Biochemistry Blood Samples.

    Science.gov (United States)

    Cakirca, Gokhan; Erdal, Huseyin

    2017-05-01

    Pneumatic tube systems (PTSs) are widely used in many hospitals because they lead to reduced turnaround times and cost efficiency. However, PTSs may affect the quality of the blood samples transported to the laboratory. The aim of this study was to investigate the effect of the PTS used in our hospital on the hemolysis of the biochemical blood samples transported to the laboratory. A total of 148 samples were manually transported to the laboratory by hospital staff, 148 samples were transported with the PTS, and 113 were transported with the PTS without use of sponge-rubber inserts (PTSws). Hemolysis rates and the levels of biochemical analytes for the different transportation methods were compared. No significant difference was found between the samples transported manually and with the PTS with regard to hemolysis rate and the levels of biochemical analytes. However, the samples transported with the PTSws showed a significant difference compared with the samples transported manually and with the PTS with regard to hemolysis rate and potassium and lactate dehydrogenase levels. The percentages of the samples that exceeded the permissible threshold for the hemolysis among the samples transported manually, with the PTS, and with the PTSws were 10%, 8%, and 47%, respectively. A PTS can be used safely for transporting biochemistry blood samples to the laboratory. However, a sponge-rubber insert that holds sample tubes must be used with the PTS to prevent the hemolysis of blood samples. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  17. Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

    International Nuclear Information System (INIS)

    Fonseca, Fernando LA; Sant Ana, Aleksandra VL; Bendit, Israel; Arias, Vitor; Costa, Luciano J; Pinhal, Aparecida A; Giglio, Auro del

    2005-01-01

    Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

  18. Changes in blood lead levels associated with use of chloramines in water treatment systems.

    Science.gov (United States)

    Miranda, Marie Lynn; Kim, Dohyeong; Hull, Andrew P; Paul, Christopher J; Galeano, M Alicia Overstreet

    2007-02-01

    More municipal water treatment plants are using chloramines as a disinfectant in order to reduce carcinogenic by-products. In some instances, this has coincided with an increase in lead levels in drinking water in those systems. Lead in drinking water can be a significant health risk. We sought to test the potential effect of switching to chloramines for disinfection in water treatment systems on childhood blood lead levels using data from Wayne County, located in the central Coastal Plain of North Carolina. We constructed a unified geographic information system (GIS) that links blood lead screening data with age of housing, drinking water source, and census data for 7,270 records. The data were analyzed using both exploratory methods and more formal multivariate techniques. The analysis indicates that the change to chloramine disinfection may lead to an increase in blood lead levels, the impact of which is progressively mitigated in newer housing. Introducing chloramines to reduce carcinogenic by-products may increase exposure to lead in drinking water. Our research provides guidance on adjustments in the local childhood lead poisoning prevention program that should accompany changes in water treatment. As similar research is conducted in other areas, and the underlying environmental chemistry is clarified, water treatment strategies can be optimized across the multiple objectives that municipalities face in providing high quality drinking water to local residents.

  19. [Invasive arterial blood pressure measurement using an aneroid pressure system in cattle].

    Science.gov (United States)

    Mosing, M; Franz, S; Iff, I; Schwendenwein, I

    2009-06-01

    The aim of this study was to compare the results of invasive arterial blood pressure measurement using an electronic pressure transducer (EPT) or an aneroid pressure system (APS) in cattle. A catheter was placed in the auricular artery of 11 adult cattle and connected to a pressure transducer via pressure line. The aneroid system was connected to the same catheter using a three-way stop-cock in the pressure line. On five occasions three consecutive measurements were performed with the APS. The mean blood pressure values of the EPT were recorded before each individual measurement. Values from each device were compared using Passing and Bablok regression of agreement and a Bland and Altman difference plot. One hundred and forty-seven paired measurements were analysed. The average bias between the two methods (EPT vs. APS) was -1.6 mmHg (95 % confidence interval [CI]: -3.0 to -0.2 mmHg). The coefficient of correlation was 1.0084. The aneroid system showed an almost perfect agreement with the EPT. This study shows that it can be used in a clinical setting as well as under field conditions to measure arterial blood pressure in cattle.

  20. System design of blood supply chain management based on Supplier Customer Relationship Management (SCRM approach

    Directory of Open Access Journals (Sweden)

    Allamsyah Zuhdi

    2018-01-01

    Full Text Available Blood supply chain management is very complex system. By considering blood’s demand that characterized as stochastic, therefore information and communication among stakeholders are considered as important cycle in supply chain. This research is objected to design interactive communication model based on information technology with android as platform to create effective customer-supplier relationship to support Customer Relationship Management or better known as CRM. The methods that suggested in designing its information system are Quality Function Deployment (QFD approach, Kano Model and Morphological Chart. From mentioned methods, attributes of design and specification priorities of purposed android system technology design are established. Attributes of design will be adjusted with customers’ requirements derived from customer voice that will further be integrated with technical responds in QFD. Technical responds will provide priorities on each design’s attribute of android information system and will be forwarded to the specifications determination by using morphological chart. Later, work flow of design system will be generated by using Data Flow Diagram (DFD. The result of the research will demonstrate the design of information system technology based on android that already adjusted with the requirement of donors as means of communication between suppliers and customers in blood supply chain.

  1. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    OpenAIRE

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented o...

  2. Multicenter Clinical Evaluation of BacT/Alert Virtuo Blood Culture System.

    Science.gov (United States)

    Jacobs, Michael R; Mazzulli, Tony; Hazen, Kevin C; Good, Caryn E; Abdelhamed, Ayman M; Lo, Pauline; Shum, Bianche; Roman, Katharine P; Robinson, Danielle C

    2017-08-01

    BacT/Alert Virtuo is an advanced, automated blood culture system incorporating improved automation and an enhanced detection algorithm to shorten time to detection. A multicenter study of the investigational Virtuo system (bioMérieux, Inc., Durham, NC) compared to BacT/Alert 3D (BTA3D) for detection of bacteremia/fungemia in four bottle types, SA and FA Plus (aerobic) and SN and FN Plus (anaerobic), was performed in a clinical setting with patient samples in a matched system design clinical trial. Blood was added to paired aerobic or anaerobic bottles, with the volume in each bottle in each pair required to be ≤10 ml and with the volumes required to be within 30% of each other. Of 5,709 bottle sets (52.5% aerobic pairs and 47.5% anaerobic pairs), 430 (7.5%) were positive for bacterial or fungal growth, with 342 (6.0%) clinically significant and 83 (1.5%) contaminated. A total of 3,539 sets (62.0%) were volume compliant, with 203 sets (5.7%) clinically significant. The positivity rates for volume-compliant bottle pairs determined by the two systems were comparable, with 68.7% of clinically significant isolates detected by both instruments, 15.7% by Virtuo only, and 15.7% by BTA3D only. Virtuo detected microbial growth nearly 2 h sooner overall than BTA3D (mean, 15.9 h versus 17.7 h). Shorter time to detection by Virtuo was related to organism group, with the time to detection being significantly shorter for enteric Gram-negative bacilli and enterococci (means, 3.6 h and 2.3 h shorter, respectively). This large clinical study demonstrated that the Virtuo blood culture system produced results comparable to those seen with the long-established BTA3D system, with significantly shorter time to detection. Copyright © 2017 Jacobs et al.

  3. [PK/PD breakpoints and clinical/bacteriological effects of cefcapene pivoxil fine granules for children at free drug concentrations in pediatric patients with respiratory infection].

    Science.gov (United States)

    Toyonaga, Yoshikiyo; Iwai, Naoichi; Motohiro, Takashi; Sunakawa, Keisuke; Fujii, Ryochi

    2008-06-01

    A post-marketing clinical study was previously conducted in pediatric patients with respiratory infection to evaluate the pharmacokinetics, efficacy and safety of cefcapene pivoxil (CFPN-PI) fine granules for children. Based on the results from this study, we evaluated PK/PD breakpoints and clinical/bacteriological effects of CFPN-PI at free drug concentrations in pediatric patients with respiratory infection to determine an effective and safe dosage regimen of CFPN-PI. The following results were obtained from 61 pediatric patients evaluated in our research. 1) The response rate of pediatric respiratory infection to CFPN-PI was 100% for laryngopharyngitis, 84.6% for acute bronchitis, 100% for tonsillitis, 100% for pneumonia and 95.8% for all. 2) The bacteriological response (eradication rate of Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis, Streptococcus pneumoniae, etc.) of pediatric respiratory infection to CFPN-PI was 87.5% for laryngopharyngitis, 66.7% for acute bronchitis, 75.0% for tonsillitis, 63.6% for pneumonia and 73.8% for all. 3) The blood concentration simulation demonstrated that the PK/PD breakpoint exceeding the time above MIC (TAM) of 40% after administration of CFPN-PI 3 mg/kg three times daily was 0.27 microg/mL. 4) The pediatric patients with respiratory infection were stratified by the TAM (%) of CFPN-PI into 40% to 100% (TAM > or = 40% group) and 0% to 40% (TAM or = 40% group, and 88.9% and 62.5% in the TAM or = 40% group than in the TAM < 40% group, although the between-group difference was not statistically significant.

  4. PK of immunoconjugate anticancer agent CMD-193 in rats: ligand-binding assay approach to determine in vivo immunoconjugate stability.

    Science.gov (United States)

    Hussain, Azher; Gorovits, Boris; Leal, Mauricio; Fluhler, Eric

    2014-01-01

    Antibody-drug conjugates (ADCs) are a new generation of anticancer therapeutics. The objective of this manuscript is to propose a methodology that can be used to assess the stability of the ADCs by using the PK data obtained by ligand-binding assays that measure various components of ADCs. The ligand-binding assays format of different components of ADCs provided unique valuable PK information. The mathematical manipulation of the bioanalytical data provided an insight into the in vivo integrity, indicating that the loading of the calicheamicin on the G193 antibody declines in an apparent slow first-order process. This report demonstrates the value of analyzing various components of the ADC and their PK profiles to better understand the disposition and in vivo stability of ADCs.

  5. Designing and Constructing Blood Flow Monitoring System to Predict Pressure Ulcers on Heel

    Directory of Open Access Journals (Sweden)

    Akbari H.

    2014-06-01

    Full Text Available Background: A pressure ulcer is a complication related to the need for the care and treatment of primarily disabled and elderly people. With the decrease of the blood flow caused by the pressure loaded, ulcers are formed and the tissue will be wasted with the passage of time. Objective: The aim of this study was to construct blood flow monitoring system on the heel tissue which was under external pressure in order to evaluate the tissue treatment in the ulcer. Methods: To measure the blood flow changes, three infrared optical transmitters were used at the distances of 5, 10, and 15 mm to the receiver. Blood flow changes in heels were assessed in pressures 0, 30, and 60 mmHg. The time features were extracted for analysis from the recorded signal by MATLAB software. Changes of the time features under different pressures were evaluated at the three distances by ANOVA in SPSS software. The level of significance was considered at 0.05. Results: In this study, 15 subjects, including both male and female, with the mean age of 54±7 participated. The results showed that the signal amplitude, power and absolute signal decreased significantly when pressure on the tissue increased in different layers (p<0.05. Heart rate only decreased significantly in pressures more than 30 mmHg (p=0.02. In pressures more than 30 mmHg, in addition to a decrease in the time features, the pattern of blood flow signal changed and it wasn’t the same as noload signal. Conclusion: By detecting the time features, we can reach an early diagnosis to prognosticate the degeneration of the tissue under pressure and it can be recommended as a method to predict bedsores in the heel.

  6. Dynamics of digestive proteolytic system during blood feeding of the hard tick Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Sojka Daniel

    2010-12-01

    Full Text Available Abstract Background Ticks are vectors of a wide variety of pathogens causing severe diseases in humans and domestic animals. Intestinal digestion of the host blood is an essential process of tick physiology and also a limiting factor for pathogen transmission since the tick gut represents the primary site for pathogen infection and proliferation. Using the model tick Ixodes ricinus, the European Lyme disease vector, we have previously demonstrated by genetic and biochemical analyses that host blood is degraded in the tick gut by a network of acidic peptidases of the aspartic and cysteine classes. Results This study reveals the digestive machinery of the I. ricinus during the course of blood-feeding on the host. The dynamic profiling of concentrations, activities and mRNA expressions of the major digestive enzymes demonstrates that the de novo synthesis of peptidases triggers the dramatic increase of the hemoglobinolytic activity along the feeding period. Overall hemoglobinolysis, as well as the activity of digestive peptidases are negligible at the early stage of feeding, but increase dramatically towards the end of the slow feeding period, reaching maxima in fully fed ticks. This finding contradicts the established opinion that blood digestion is reduced at the end of engorgement. Furthermore, we show that the digestive proteolysis is localized intracellularly throughout the whole duration of feeding. Conclusions Results suggest that the egressing proteolytic system in the early stage of feeding and digestion is a potential target for efficient impairment, most likely by blocking its components via antibodies present in the host blood. Therefore, digestive enzymes are promising candidates for development of novel 'anti-tick' vaccines capable of tick control and even transmission of tick-borne pathogens.

  7. Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

    Science.gov (United States)

    Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

    2017-02-01

    To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to

  8. DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells

    International Nuclear Information System (INIS)

    Urushihara, Yusuke; Kobayashi, Junya; Matsumoto, Yoshihisa; Komatsu, Kenshi; Oda, Shoji; Mitani, Hiroshi

    2012-01-01

    Highlights: ► We investigated the effect of DNA-PK inhibition on DSB repair using fish cells. ► A radiation sensitive mutant RIC1 strain showed a low level of DNA-PK activity. ► DNA-PK dysfunction leads defects in HR repair and DNA-PKcs autophosphorylation. ► DNA-PK dysfunction leads a slight increase in the number of 53BP1 foci after DSBs. ► DNA-PK dysfunction leads an alternative NHEJ that depends on 53BP1. -- Abstract: Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK, a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ deficiency. However, in this study, we demonstrate that a wild-type cell line treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes). Previously, we reported that the radiation-sensitive mutant RIC1 strain has a defect in the Histone H2AX phosphorylation after γ-irradiation. Here, we showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant reduction in the number of γH2AX foci after γ-irradiation in wild-type cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells showed significantly lower levels of DNA-PK kinase activity compared with wild-type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild-type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency. These results indicated that aberrant DNA-PK causes the reduction in the number of γH2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated DNA-PKcs (Thr2609) and 53BP1 focus assay after γ-irradiation. RIC1 cells showed significant reduction in the number of phosphorylated DNA-PKcs foci and no deference in the number of 53BP1 foci compared with wild-type cells. These results suggest that low level of DNA-PK activity causes aberrant DNA-PKcs autophosphorylation

  9. Duffy blood group system and the malaria adaptation process in humans

    Directory of Open Access Journals (Sweden)

    Gledson Barbosa de Carvalho

    2011-02-01

    Full Text Available Malaria is an acute infectious disease caused by the protozoa of the genus Plasmodium. The antigens of the Duffy Blood Group System, in addition to incompatibilities in transfusions and hemolytic disease of the newborn, are of great interest in medicine due to their association with the invasion of red blood cells by the parasite Plasmodium vivax. For invasions to occur an interaction between the parasites and antigens of the Duffy Blood Group System is necessary. In Caucasians six antigens are produced by the Duffy locus (Fya, Fyb, F3, F4, F5 and F6. It has been observed that Fy(a-b- individuals are resistant to Plasmodium knowlesi and P. vivax infection, because the invasion requires at least one of these antigens. The P. vivax Duffy Binding Protein (PvDBP is functionally important in the invasion process of these parasites in Duffy / DARC positive humans. The proteins or fractions may be considered, therefore, an important and potential inoculum to be used in immunization against malaria.

  10. A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; YANG Lin; WANG Ke-qiang; XU Shi-xiong; DAI Pei-dong

    2009-01-01

    Objective:To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods:A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic response (MR), tubuloglomerular feedback (TGF) and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results:The results predict the dynamics of renal autoregulation on its blood pressure and flow,and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion:The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.

  11. Dual-modality arterial pulse monitoring system for continuous blood pressure measurement.

    Science.gov (United States)

    Wen-Xuan Dai; Yuan-Ting Zhang; Jing Liu; Xiao-Rong Ding; Ni Zhao

    2016-08-01

    Accurate and ambulatory measurement of blood pressure (BP) is essential for efficient diagnosis, management and prevention of cardiovascular diseases (CVDs). However, traditional cuff-based BP measurement methods provide only intermittent BP readings and can cause discomfort with the occlusive cuff. Although pulse transit time (PTT) method is promising for cuffless and continuous BP measurement, its pervasive use is restricted by its limited accuracy and requirement of placing sensors on multiple body sites. To tackle these issues, we propose a novel dual-modality arterial pulse monitoring system for continuous blood pressure measurement, which simultaneously records the pressure and photoplethysmography (PPG) signals of radial artery. The obtained signals can be used to generate a pressure-volume curve, from which the elasticity index (EI) and viscosity index (VI) can be extracted. Experiments were carried out among 7 healthy subjects with their PPG, ECG, arterial pressure wave and reference BP collected to examine the effectiveness of the proposed indexes. The results of this study demonstrate that a linear regression model combining EI and VI has significantly higher BP tracking correlation coefficient as compared to the PTT method. This suggests that the proposed system and method can potentially be used for convenient and continuous blood pressure estimation with higher accuracy.

  12. Increased occupational coal dust toxicity in blood of central heating system workers.

    Science.gov (United States)

    Tuluce, Yasin; Ozkol, Halil; Koyuncu, Ismail; Ine, Hatice

    2011-02-01

    Coal dust causes lung diseases in occupational exposure. Reactive oxygen species have been implicated in the pathogenesis of its toxicity. In this study, serum enzymes, lipid profile and other biochemical values with oxidant/antioxidant status in whole blood and serum of central heating system workers (CHSW; the persons responsible for heating the apartment with coal) were determined to reflect the cell injury. Blood samples were obtained from CHSW (n = 25) and healthy individuals (n = 25). All values were measured in whole blood and serum. ANOVA was used for the estimation of statistical data. In the group of CHSW, creatinine, ferritin, alanin aminotransferase, aspartate aminotransferase, creatine phosphokinase, gamma glutamyl transferase, lactate dehydrogenase and glutathione reductase activities as well as triglyceride, very low density lipoprotein, protein carbonyl and malondialdehide were significantly higher, while transferrin, high density lipoprotein and catalase (CAT) activities were lower than the group of healthy individuals. This result is consistent with hypothesis that respirable coal dust generates lipid and protein oxidation and induces leakage of serum enzymes by cell damage. It also leads to imbalance in antioxidant defense system, lipid profile and other biochemical parameters.

  13. SUPER-RAMP PK2 cases by START-3. Preliminary Report

    International Nuclear Information System (INIS)

    Novikov, Vladimir; Kuznetsov, Vladimir; Chulkin, Dmitriy

    2013-01-01

    The Studsvik SUPER-RAMP Project, an internationally sponsored research project, investigated the failure propensity of typical LWR fuel in the form of test rods when subjected to power ramps, after base irradiation to high burn-up. The following information summarizing the project is abstracted from the Final Report of the SUPER-RAMP project (STSR-32). The Project power ramped 28 individual PWR rods and 16 BWR rods. The PWR rods were all tested using high ramp rates. Due to different objectives for the BWR subprogramme, one set of the BWR rods was tested using a high ramp rate, and another set were tested with a very slow ramp rate. All rods underwent a thorough examination programme, comprising characterisation prior to base irradiation, examination between base and ramp irradiation and examination after ramp irradiation. This consisted of 6 groups of rods with variations in design and material parameters. The rods were base irradiated in a power reactor environment KK Obrigheim or BR-3 at time averaged heat ratings mainly in the range 14-26 kW/m to peak burn-ups in the range 33-45 MWd/kgU and were subsequently ramp tested in the research reactor R2 at Studsvik, Sweden. The result can be summarized as follows: In this document some calculations are made on the PK2 group fuel rods. The rods were standard rods manufactured by Kraftwerk Union AG/Combustion Engineering (KWU/CE). All these rods sustained ramping to power levels in the range 41 to 49 kW/m and power changes 16-24 kW/m without failure, in spite of large deformations, fuel restructuring and fission gas release particularly for the PK2 rods. Though the results of this paper seem to be based on the incomplete dataset (ambiguity in power raise rates, undefined fuel pellet and cladding surface roughness), we think that START-3 Zircalloy-4 model requires further improvements. In order to do them, we kindly ask IAEA to provide us with more detailed irradiation histories (more than 3 axial zones, power increase

  14. Nanoparticles and the blood coagulation system. Part I: benefits of nanotechnology.

    Science.gov (United States)

    Ilinskaya, Anna N; Dobrovolskaia, Marina A

    2013-05-01

    Nanotechnology is proven to provide certain benefits in drug delivery by improving solubility, increasing uptake to target sites and changing pharmacokinetics profiles of traditional drugs. Since properties of many materials change tremendously at the nanoscale levels, nanotechnology is also being explored in various industrial applications. As such, nanoparticles are rapidly entering various areas of industry, biology and medicine. The benefits of using nanotechnology for industrial and biomedical applications are often tempered by concerns about the safety of these new materials. One such area of concern includes their effect on the immune system. While nanoparticle interactions with various constituents of the immune system have been reviewed before, little attention was given to nanoparticle effects on the blood coagulation system. Nanoparticle interface with the blood coagulation system may lead to either benefits to the host or adverse reactions. This article reviews recent advances in our understanding of nanoparticle interactions with plasma coagulation factors, platelets, endothelial cells and leukocytes. Part I is focused on desirable interactions between nanoparticles and the coagulation system, and discusses benefits of using nanotechnology to intervene in coagulation disorders. Undesirable interactions posing safety concerns are covered in part II, which will be published in the June issue of Nanomedicine.

  15. Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

    Science.gov (United States)

    Renaud, Jennifer M; Yip, Kathy; Guimond, Jean; Trottier, Mikaël; Pibarot, Philippe; Turcotte, Eric; Maguire, Conor; Lalonde, Lucille; Gulenchyn, Karen; Farncombe, Troy; Wisenberg, Gerald; Moody, Jonathan; Lee, Benjamin; Port, Steven C; Turkington, Timothy G; Beanlands, Rob S; deKemp, Robert A

    2017-01-01

    Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82 Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. 82 Rb or 13 N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  16. Optimizing an online SPE-HPLC method for analysis of (R)-[11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)- 3-isoquinolinecarboxamide [(R)-[11C]PK11195] and its metabolites in humans

    International Nuclear Information System (INIS)

    Greuter, Henri N.J.M.; van Ophemert, Patricia L.B.; Luurtsema, Gert; van Berckel, Bart N.M.; Franssen, Eric J.F.; Windhorst, Bert D.; Lammertsma, Adriaan A.

    2005-01-01

    (R)-[ 11 C]PK11195 is used as a positron emission tomography tracer for activated microglia in several neurological disorders. Quantification of specific binding requires a metabolite-corrected plasma input function. In this study, a high-performance liquid chromatography (HPLC) procedure with online solid phase extraction was modified for analyzing (R)-[ 11 C]PK11195 plasma samples, yielding total sample recoveries of more than 98%. When applied to human studies, the use of two HPLC systems enabled analysis of up to seven plasma samples under regular conditions. Online radioactivity detection was compared with offline sample measurements of HPLC profiles. Offline measurements provided the most reliable results especially for late plasma samples. In 10 patients, an average decrease of parent compound from 94.6% at 2.5 min to 45.2% at 1 h after administration was observed

  17. Infiltration Pattern of Blood Monocytes into the Central Nervous System during Experimental Herpes Simplex Virus Encephalitis.

    Directory of Open Access Journals (Sweden)

    Rafik Menasria

    Full Text Available The kinetics and distribution of infiltrating blood monocytes into the central nervous system and their involvement in the cerebral immune response together with resident macrophages, namely microglia, were evaluated in experimental herpes simplex virus 1 (HSV-1 encephalitis (HSE. To distinguish microglia from blood monocyte-derived macrophages, chimeras were generated by conditioning C57BL/6 recipient mice with chemotherapy regimen followed by transplantation of bone morrow-derived cells that expressed the green fluorescent protein. Mice were infected intranasally with a sub-lethal dose of HSV-1 (1.2 x 10(6 plaque forming units. Brains were harvested prior to and on days 4, 6, 8 and 10 post-infection for flow cytometry and immunohistochemistry analysis. The amounts of neutrophils (P < 0.05 and "Ly6C hi" inflammatory monocytes (P < 0.001 significantly increased in the CNS compared to non-infected controls on day 6 post-infection, which corresponded to more severe clinical signs of HSE. Levels decreased on day 8 for both leukocytes subpopulations (P < 0.05 for inflammatory monocytes compared to non-infected controls to reach baseline levels on day 10 following infection. The percentage of "Ly6C low" patrolling monocytes significantly increased (P < 0.01 at a later time point (day 8, which correlated with the resolution phase of HSE. Histological analysis demonstrated that blood leukocytes colonized mostly the olfactory bulb and the brainstem, which corresponded to regions where HSV-1 particles were detected. Furthermore, infiltrating cells from the monocytic lineage could differentiate into activated local tissue macrophages that express the microglia marker, ionized calcium-binding adaptor molecule 1. The lack of albumin detection in the brain parenchyma of infected mice showed that the infiltration of blood leukocytes was not necessarily related to a breakdown of the blood-brain barrier but could be the result of a functional recruitment. Thus

  18. Pk-yrityksen kansainvälistyminen : Taide esineitä liikelahjoina Japaniin ja Etelä-Koreaan

    OpenAIRE

    Takala, Sanna; Ristikankare, Roosa

    2009-01-01

    Tämän opinnäytetyön taustalla oli Laurea-ammattikorkeakoulun ESR-rahoitteinen projekti “Teollisen palveluliiketoiminnan koulutustarpeen selvittäminen Lohjan ja Tammisaaren seutukunnissa ja näiden alueiden pk-yritysten osaamisperustan kehittäminen”. Opinnäytetyö sijoittui hankkeen toimenpidekokonaisuuteen ”Teemakoulutus ja kehityshankkeet yritysryppäälle”, pk-yrityksen kansainvälistymiseen liittyvänä tutkimus- ja kehittämishankkeena. Tutkimus- ja kehittämishankkeen tarkoituksena oli tuotta...

  19. IPv6:n käyttöönotto PK-yrityksessä

    OpenAIRE

    Salonen, Arttu Petteri

    2011-01-01

    Tämän opinnäytetyön tarkoituksena on selvittää, kuinka IPv6-yhteydet otetaan käyt-töön PK-yrityksessä. Työssä selvitetään minkälaiset vaatimukset IPv6 asettaa lait-teistolle ja minkälaisia käytännön asioita yrityksen täytyy huomioida IPv6:n käyt-töönotossa. Lisäksi työssä on laboratoriosimulaation avulla havainnollistettu eri käyt-töjärjestelmien tukea IPv6:lle ja käyttöönottoon liittyviä reititin- ja osoitekonfiguraati-oita. Käyttöönoton lisäksi opinnäytetyössä esitellään IPv6-protokoll...

  20. Semiparametric mixed-effects analysis of PK/PD models using differential equations.

    Science.gov (United States)

    Wang, Yi; Eskridge, Kent M; Zhang, Shunpu

    2008-08-01

    Motivated by the use of semiparametric nonlinear mixed-effects modeling on longitudinal data, we develop a new semiparametric modeling approach to address potential structural model misspecification for population pharmacokinetic/pharmacodynamic (PK/PD) analysis. Specifically, we use a set of ordinary differential equations (ODEs) with form dx/dt = A(t)x + B(t) where B(t) is a nonparametric function that is estimated using penalized splines. The inclusion of a nonparametric function in the ODEs makes identification of structural model misspecification feasible by quantifying the model uncertainty and provides flexibility for accommodating possible structural model deficiencies. The resulting model will be implemented in a nonlinear mixed-effects modeling setup for population analysis. We illustrate the method with an application to cefamandole data and evaluate its performance through simulations.

  1. The state of glutathion system of blood, brain and liver of white rats after chronic gamma-irradiation

    International Nuclear Information System (INIS)

    Petushok, N.Eh.; Lashak, L.K.; Trebukhina, R.V.

    1999-01-01

    The effects of 3-fold gamma-irradiation in total dose 0,75 Gy on the glutathion system in different periods after exposure (1 hour, 1 day, 1 and 4 weeks) in blood, brain and liver of white rats were studied. It was concluded that liver and brain have higher ability to maintain the stability of antioxidant system than blood has. After shot disturbances caused by irradiation in brain and liver the state of glutathion system of detoxication has normalized, while concentration of malonic dialdehyde was raised in all terms. The most pronounced changes of antioxidant system were registered in blood at early terms (1 hour) after irradiation that was manifested in increasing of reduced glutathion content, raising of glutathion reductase and catalase activity. In remote period the activity of this system in blood was exhausted

  2. White blood cells identification system based on convolutional deep neural learning networks.

    Science.gov (United States)

    Shahin, A I; Guo, Yanhui; Amin, K M; Sharawi, Amr A

    2017-11-16

    White blood cells (WBCs) differential counting yields valued information about human health and disease. The current developed automated cell morphology equipments perform differential count which is based on blood smear image analysis. Previous identification systems for WBCs consist of successive dependent stages; pre-processing, segmentation, feature extraction, feature selection, and classification. There is a real need to employ deep learning methodologies so that the performance of previous WBCs identification systems can be increased. Classifying small limited datasets through deep learning systems is a major challenge and should be investigated. In this paper, we propose a novel identification system for WBCs based on deep convolutional neural networks. Two methodologies based on transfer learning are followed: transfer learning based on deep activation features and fine-tuning of existed deep networks. Deep acrivation featues are extracted from several pre-trained networks and employed in a traditional identification system. Moreover, a novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and built from scratch. Finally, a limited balanced WBCs dataset classification is performed through the WBCsNet as a pre-trained network. During our experiments, three different public WBCs datasets (2551 images) have been used which contain 5 healthy WBCs types. The overall system accuracy achieved by the proposed WBCsNet is (96.1%) which is more than different transfer learning approaches or even the previous traditional identification system. We also present features visualization for the WBCsNet activation which reflects higher response than the pre-trained activated one. a novel WBCs identification system based on deep learning theory is proposed and a high performance WBCsNet can be employed as a pre-trained network. Copyright © 2017. Published by Elsevier B.V.

  3. Pharmacokinetics, bioavailability and PK/PD relationship of cefquinome for Escherichia coli in Beagle dogs.

    Science.gov (United States)

    Zhou, Y F; Zhao, D H; Yu, Y; Yang, X; Shi, W; Peng, Y B; Liu, Y H

    2015-12-01

    The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2β (h), Vss (L/kg), ClB (L/kg/h) and AUC (μg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel , t1/2Ka , tmax (h), Cmax (μg/mL) and AUC (μg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 μg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study. © 2015 John Wiley & Sons Ltd.

  4. Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    2010-07-01

    Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

  5. Gentamicin-induced apoptosis in LLC-PK1 cells: Involvement of lysosomes and mitochondria

    International Nuclear Information System (INIS)

    Servais, Helene; Van Der Smissen, Patrick; Thirion, Gaetan; Van der Essen, Gauthier; Van Bambeke, Francoise; Tulkens, Paul M.; Mingeot-Leclercq, Marie-Paule

    2005-01-01

    Gentamicin accumulates in lysosomes and induces apoptosis in kidney proximal tubules and renal cell lines. Using LLC-PK1 cells, we have examined the concentration- and time-dependency of the effects exerted by gentamicin (1-3 mM; 0-3 days) on (i) lysosomal stability; (ii) activation of mitochondrial pathway; (iii) occurrence of apoptosis (concentrations larger than 3 mM caused extensive necrosis as assessed by the measurement of lactate dehydrogenase release). Within 2 h, gentamicin induced a partial relocalization [from lysosomes to cytosol] of the weak organic base acridine orange. We thereafter observed (a) a loss of mitochondrial membrane potential (as from 10 h, based on spectrophotometric and confocal microscopy using JC1 probe) and (b) the release of cytochrome c from granules to cytosol, and the activation of caspase-9 (as from 12 h; evidenced by Western blot analysis). Increase in caspase-3 activity (assayed with Ac-DEVD-AFC in the presence of z-VAD-fmk]) and appearance of fragmented nuclei (DAPI staining) was then detected as from 16 to 24 h together with nuclear fragmentation. Gentamicin produces a fast (within 4 h) release of calcein from negatively-charged liposomes at pH 5.4, which was slowed down by raising the pH to 7.4, or when phosphatidylinositol was replaced by cardiolipin (to mimic the inner mitochondrial membrane). The present data provide temporal evidence that gentamicin causes apoptosis in LLC-PK1 with successive alteration of the permeability of lysosomes, triggering of the mitochondrial pathway, and activation of caspase-3

  6. The Diabetes Assistant: A Smartphone-Based System for Real-Time Control of Blood Glucose

    Directory of Open Access Journals (Sweden)

    Patrick Keith-Hynes

    2014-11-01

    Full Text Available Type 1 Diabetes Mellitus (T1DM is an autoimmune disease in which the insulin-producing beta cells of the pancreas are destroyed and insulin must be injected daily to enable the body to metabolize glucose. Standard therapy for T1DM involves self-monitoring of blood glucose (SMBG several times daily with a blood glucose meter and injecting insulin via a syringe, pen or insulin pump. An “Artificial Pancreas” (AP is a closed-loop control system that uses a continuous glucose monitor (CGM, an insulin pump and an internal algorithm to automatically manage insulin infusion to keep the subject’s blood glucose within a desired range. Although no fully closed-loop AP systems are currently commercially available there are intense academic and commercial efforts to produce safe and effective AP systems. In this paper we present the Diabetes Assistant (DiAs, an ultraportable AP research platform designed to enable home studies of Closed Loop Control (CLC of blood glucose in subjects with Type 1 Diabetes Mellitus. DiAs consists of an Android (Google Inc., Mountain View, CA, USA smartphone equipped with communication, control and user interface software wirelessly connected to a continuous glucose monitor and insulin pump. The software consists of a network of mobile applications with well-defined Application Programming Interfaces (APIs running atop an enhanced version of Android with non-essential elements removed. CLC and safety applications receive real-time data from the CGM and pump, estimate the patient’s metabolic state and risk of hypo- and hyperglycemia, adjust the insulin infusion rate, raise alarms as needed and transmit de-identified data to a secure remote server. Some applications may be replaced by researchers wishing to conduct outpatient ambulatory studies of novel Closed Loop Control, Safety or User Interface modules. Over the past three years the DiAs platform has been used in a series of AP clinical trials sponsored by the National

  7. Valores, Creencias Y Objectivos: Base del programa de la Escuela Experimental P.K. Yonge. (Values, Beliefs and Objectives: The Basis of Experimental Schools P.K. Yonge's Program.)

    Science.gov (United States)

    Florida Univ., Gainesville. Coll. of Education.

    The values, beliefs, and objectives that form the core of the program at the Experimental School P.K. Yonge in the University of Florida are presented in this paper which is written in Spanish. This experimental school serves approximately 900 students from grades one through twelve. The function of the school is to conduct research to solve…

  8. Engineering blood meal-activated systemic immunity in the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Kokoza, V; Ahmed, A; Cho, W L; Jasinskiene, N; James, A A; Raikhel, A

    2000-08-01

    Progress in molecular genetics makes possible the development of alternative disease control strategies that target the competence of mosquitoes to transmit pathogens. We tested the regulatory region of the vitellogenin (Vg) gene of Aedes aegypti for its ability to express potential antipathogen factors in transgenic mosquitoes. Hermes-mediated transformation was used to integrate a 2.1-kb Vg-promoter fragment driving the expression of the Defensin A (DefA) coding region, one of the major insect immune factors. PCR amplification of genomic DNA and Southern blot analyses, carried out through the ninth generation, showed that the Vg-DefA transgene insertion was stable. The Vg-DefA transgene was strongly activated in the fat body by a blood meal. The mRNA levels reached a maximum at 24-h postblood meal, corresponding to the peak expression time of the endogenous Vg gene. High levels of transgenic defensin were accumulated in the hemolymph of bloodfed female mosquitoes, persisting for 20-22 days after a single blood feeding. Purified transgenic defensin showed antibacterial activity comparable to that of defensin isolated from bacterially challenged control mosquitoes. Thus, we have been able to engineer the genetically stable transgenic mosquito with an element of systemic immunity, which is activated through the blood meal-triggered cascade rather than by infection. This work represents a significant step toward the development of molecular genetic approaches to the control of vector competence in pathogen transmission.

  9. New method for rapid Susceptibility Testing on blood culture with HB&L system: preliminary data

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2010-12-01

    Full Text Available Blood culture, although represents the gold standard in detecting the ethiological agent of sepsis, is rather rarely required in relation to the real diagnostic importance. The result of this test depends in fact on many factors (sample volume, time of collection, accuracy, antibiotic therapy, contamination, number of drawings, drawing site, interpretation difficulties, etc. that are often considered by many clinicians so limited as to doubt about their actual value. The disadvantages are therefore represented by the lack of standardization but also by the low sensitivity and above all by the technical times too long for the clinical needs. Blood culture begins with the drawing of samples from the “septic” patient followed incubation of the bottles in automatic thermostated systems. In case of positive result (36 hours, the culture is Gram stained and streaked on solid media in order to obtain isolated colonies for the identification and the susceptibility testing (48 hours from positive result. The long time required for pathogen identification and susceptibility testing involves empirical broad spectrum antibiotic therapy that can promote the increase of bacterial resistance but also patient management costs. A clinically useful report should be available on short notice in order to guide the clinician to choose the most appropriate antibiotic. The microbiologist has therefore the hard work of reviewing the organization and the management of the procedures.We have therefore started to consider the possibility of treating the blood as an biological liquid in order to quickly determine the susceptibility of bacteria to antibiotics.

  10. Blood metabolites and some fertility parameters in dairy cows under intensive management system

    International Nuclear Information System (INIS)

    Osman, Awad Ali

    1998-08-01

    Dairy farms (1, 2, 3 and 4) of the intensive management system were selected. They are located 50 kilometers south of Khartoum state in a semi-arid zone. The effect of management on some fertility parameters, blood metabolites and minerals were investigated. Changes in blood metabolites with stage of lactation were also monitored. Other parameters studied were body weight, body condition score at calving. The results revealed that days to first P 4 rise after calving and number of services per conception (NSPC) were lower in the farm s contained the cross-bred (Fresian X Zebu) compared to the farm contained the pure Fresian breed. The pure Fresian cows showed heavier weights and less body score at calving compared to the cross breed. Blood metabolites reflected the nutritional status of the dairy cows under study, plasma total protein, albumin, globulin, urea and Glucose did not show significant changes either either either between farms or in response to lactation stages. However, high levels of Globulins might indicate inflammation due to some diseases such as mastitis, metritis and lameness. Plasma level of Calcium and Phosphorous did not change significantly either between farms or due to stages of lactation.(Author)

  11. Blood metabolites and some fertility parameters in dairy cows under intensive management system

    Energy Technology Data Exchange (ETDEWEB)

    Osman, Awad Ali [Faculty of Animal Production, University of Khartoum, Khartoum (Sudan)

    1998-08-01

    Dairy farms (1, 2, 3 and 4) of the intensive management system were selected. They are located 50 kilometers south of Khartoum state in a semi-arid zone. The effect of management on some fertility parameters, blood metabolites and minerals were investigated. Changes in blood metabolites with stage of lactation were also monitored. Other parameters studied were body weight, body condition score at calving. The results revealed that days to first P{sup 4} rise after calving and number of services per conception (NSPC) were lower in the farm s contained the cross-bred (Fresian X Zebu) compared to the farm contained the pure Fresian breed. The pure Fresian cows showed heavier weights and less body score at calving compared to the cross breed. Blood metabolites reflected the nutritional status of the dairy cows under study, plasma total protein, albumin, globulin, urea and Glucose did not show significant changes either either either between farms or in response to lactation stages. However, high levels of Globulins might indicate inflammation due to some diseases such as mastitis, metritis and lameness. Plasma level of Calcium and Phosphorous did not change significantly either between farms or due to stages of lactation.(Author) 129 refs. , 12 tabs.

  12. Phage FR38 Treatment on Sprague Dawley Rat Inferred from Blood Parameters and Organ Systems

    Directory of Open Access Journals (Sweden)

    DEWI SARTIKA

    2012-09-01

    Full Text Available The ability of phage FR38 to lysis indigenous Salmonella P38 from feces of diarrheal patient has been studied. However, effects of phage FR38 on organ system were not revealed as yet. This study was conducted to observe the effect of phage FR38 on blood chemistry, kidney functions, and liver functions. Twelve Sprague-Dawley rats were used as a model for this study that were divided into two groups; (i control and (ii treated group with phage FR38. For treated phage group, each rat was administered by 5 ml/kg bw of 1.59•107 pfu/ml of phage intragastric. The blood parameters were analysed on day 16. The results revealed that body and organs weight, erythrocyte, hematocrit, hemoglobin, leukocyte, total protein, creatinine, SGOT, and SGPT of phage treatment rats were not significantly different with the control rats on day 16 (P > 0.05. Therefore, this study showed was no effect of phage FR38 on body weight, blood chemistry, kidney and liver functions of the rat (P > 0.05.

  13. Phage FR38 Treatment on Sprague Dawley Rat Inferred from Blood Parameters and Organ Systems

    Directory of Open Access Journals (Sweden)

    DEWI SARTIKA

    2012-09-01

    Full Text Available The ability of phage FR38 to lysis indigenous Salmonella P38 from feces of diarrheal patient has been studied. However, effects of phage FR38 on organ system were not revealed as yet. This study was conducted to observe the effect of phage FR38 on blood chemistry, kidney functions, and liver functions. Twelve Sprague-Dawley rats were used as a model for this study that were divided into two groups; (i control and (ii treated group with phage FR38. For treated phage group, each rat was administered by 5 ml/kg bw of 1.59-107 pfu/ml of phage intragastric. The blood parameters were analysed on day 16. The results revealed that body and organs weight, erythrocyte, hematocrit, hemoglobin, leukocyte, total protein, creatinine, SGOT, and SGPT of phage treatment rats were not significantly different with the control rats on day 16 (P > 0.05. Therefore, this study showed was no effect of phage FR38 on body weight, blood chemistry, kidney and liver functions of the rat (P > 0.05.

  14. Providing Hemostatic and Blood Conservation Options for Jehovah's Witness Patients in a Large Medical System.

    Science.gov (United States)

    Bai, Yu; Castillo, Brian S; Tchakarov, Amanda; Escobar, Miguel A; Cotton, Bryan A; Holcomb, John B; Brown, Robert E

    2016-12-01

    People of the Jehovah's Witness faith believe that they shall "abstain from blood." Because of this belief, we encounter the challenges from Jehovah's Witness patients who actively seek medical care for themselves and their children, but refuse the transfusion of blood products, which may result in increased morbidity and mortality in this patient population. With the development/availability of new hemostatic/coagulation products and the advances in medical technology, we, in collaboration with our clinical colleagues and our local Jehovah's Witness leadership, have developed a clinical guideline comprising medical protocol and surgical strategy for patients refusing blood products. Included in the medical protocol is an informative handout on related details to help treating physicians and patients make informed decisions about transfusion alternatives. Together, we have entered the medical protocol into the entire Memorial Hermann Hospital's electronic system. We report the detailed development and implementation process in order to share our experience and encourage others to develop their own management plan for this patient population. © 2016 by the Association of Clinical Scientists, Inc.

  15. Does Pneumatic Tube System Transport Contribute to Hemolysis in ED Blood Samples?

    Directory of Open Access Journals (Sweden)

    Fredric M. Hustey

    2016-09-01

    Full Text Available Introduction: Our goal was to determine if the hemolysis among blood samples obtained in an emergency department and then sent to the laboratory in a pneumatic tube system was different from those in samples that were hand-carried. Methods: The hemolysis index is measured on all samples submitted for potassium analysis. We queried our hospital laboratory database system (SunQuest® for potassium results for specimens obtained between January 2014 and July 2014. From facility maintenance records, we identified periods of system downtime, during which specimens were hand-carried to the laboratory. Results: During the study period, 15,851 blood specimens were transported via our pneumatic tube system and 92 samples were hand delivered. The proportions of hemolyzed specimens in the two groups were not significantly different (13.6% vs. 13.1% [p=0.90]. Results were consistent when the criterion was limited to gross (3.3% vs 3.3% [p=0.99] or mild (10.3% vs 9.8% [p=0.88] hemolysis. The hemolysis rate showed minimal variation during the study period (12.6%–14.6%. Conclusion: We found no statistical difference in the percentages of hemolyzed specimens transported by a pneumatic tube system or hand delivered to the laboratory. Certain features of pneumatic tube systems might contribute to hemolysis (e.g., speed, distance, packing material. Since each system is unique in design, we encourage medical facilities to consider whether their method of transport might contribute to hemolysis in samples obtained in the emergency department.

  16. Does Pneumatic Tube System Transport Contribute to Hemolysis in ED Blood Samples?

    Science.gov (United States)

    Phelan, Michael P; Reineks, Edmunds Z; Hustey, Fredric M; Berriochoa, Jacob P; Podolsky, Seth R; Meldon, Stephen; Schold, Jesse D; Chamberlin, Janelle; Procop, Gary W

    2016-09-01

    Our goal was to determine if the hemolysis among blood samples obtained in an emergency department and then sent to the laboratory in a pneumatic tube system was different from those in samples that were hand-carried. The hemolysis index is measured on all samples submitted for potassium analysis. We queried our hospital laboratory database system (SunQuest(®)) for potassium results for specimens obtained between January 2014 and July 2014. From facility maintenance records, we identified periods of system downtime, during which specimens were hand-carried to the laboratory. During the study period, 15,851 blood specimens were transported via our pneumatic tube system and 92 samples were hand delivered. The proportions of hemolyzed specimens in the two groups were not significantly different (13.6% vs. 13.1% [p=0.90]). Results were consistent when the criterion was limited to gross (3.3% vs 3.3% [p=0.99]) or mild (10.3% vs 9.8% [p=0.88]) hemolysis. The hemolysis rate showed minimal variation during the study period (12.6%-14.6%). We found no statistical difference in the percentages of hemolyzed specimens transported by a pneumatic tube system or hand delivered to the laboratory. Certain features of pneumatic tube systems might contribute to hemolysis (e.g., speed, distance, packing material). Since each system is unique in design, we encourage medical facilities to consider whether their method of transport might contribute to hemolysis in samples obtained in the emergency department.

  17. Odors generated from the Maillard reaction affect autonomic nervous activity and decrease blood pressure through the olfactory system.

    Science.gov (United States)

    Zhou, Lanxi; Ohata, Motoko; Owashi, Chisato; Nagai, Katsuya; Yokoyama, Issei; Arihara, Keizo

    2018-02-01

    Systolic blood pressure (SBP) of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. This study identified active odorants that affect blood pressure and demonstrated the mechanism of action. Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM) decreased SBP significantly. The earliest decrease in blood pressure was observed 5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to DMHF. It is indicated that DMHF affects blood pressure through the olfactory system, and the mechanism for the effect of DMHF on blood pressure involves the autonomic nervous system. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Hospital blood bank information systems accurately reflect patient transfusion: results of a validation study.

    Science.gov (United States)

    McQuilten, Zoe K; Schembri, Nikita; Polizzotto, Mark N; Akers, Christine; Wills, Melissa; Cole-Sinclair, Merrole F; Whitehead, Susan; Wood, Erica M; Phillips, Louise E

    2011-05-01

    Hospital transfusion laboratories collect information regarding blood transfusion and some registries gather clinical outcomes data without transfusion information, providing an opportunity to integrate these two sources to explore effects of transfusion on clinical outcomes. However, the use of laboratory information system (LIS) data for this purpose has not been validated previously. Validation of LIS data against individual patient records was undertaken at two major centers. Data regarding all transfusion episodes were analyzed over seven 24-hour periods. Data regarding 596 units were captured including 399 red blood cell (RBC), 95 platelet (PLT), 72 plasma, and 30 cryoprecipitate units. They were issued to: inpatient 221 (37.1%), intensive care 109 (18.3%), outpatient 95 (15.9%), operating theater 45 (7.6%), emergency department 27 (4.5%), and unrecorded 99 (16.6%). All products recorded by LIS as issued were documented as transfused to intended patients. Median time from issue to transfusion initiation could be calculated for 535 (89.8%) components: RBCs 16 minutes (95% confidence interval [CI], 15-18 min; interquartile range [IQR], 7-30 min), PLTs 20 minutes (95% CI, 15-22 min; IQR, 10-37 min), fresh-frozen plasma 33 minutes (95% CI, 14-83 min; IQR, 11-134 min), and cryoprecipitate 3 minutes (95% CI, -10 to 42 min; IQR, -15 to 116 min). Across a range of blood component types and destinations comparison of LIS data with clinical records demonstrated concordance. The difference between LIS timing data and patient clinical records reflects expected time to transport, check, and prepare transfusion but does not affect the validity of linkage for most research purposes. Linkage of clinical registries with LIS data can therefore provide robust information regarding individual patient transfusion. This enables analysis of joint data sets to determine the impact of transfusion on clinical outcomes. © 2010 American Association of Blood Banks.

  19. Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

    Science.gov (United States)

    Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

    2015-11-01

    Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

  20. The polymorphism of the Knops blood group system among five Chinese ethnic groups.

    Science.gov (United States)

    Li, Qin; Han, Sha-Sha; Guo, Zhong-Hui; Yang, Ying; Zhou, Jie; Zhu, Zi-Yan

    2010-12-01

    This work aims to explain the complexity of the Knops blood group system in the Chinese population. The Knops blood group system consists of antigens encoded by CR1 gene exon 29. A total of 281 individuals from the Han, Uigur, Tu, Lisu and Dong ethnic groups were studied. The coding region of the CR1 gene of 11 Han donors was analysed using reverse transcription-polymerase chain reaction (PCR) and sequencing. CR1 gene exon 29 in the 39 samples was analysed through genomic DNA sequencing. According to the sequencing result, a PCR-sequence-specific primers system was designed to screen the A4646G and A4870G alleles in the Chinese population. Twelve single nucleotide polymorphisms (SNPs) were observed in the coding region of the CR1 gene in the Han population. Two SNPs (A4646G and A4870G) were detected in the CR1 gene exon 29. The 4646G allele was found only in the Uigur and Tu ethnic groups, in which the allele frequencies were 0·11 and 0·06, respectively. The frequencies of the 4870A allele in the Han, Uigur, Tu, Lisu and Dong ethnic groups were 0·82, 0·83, 0·82, 0·57 and 0·57, respectively. The CR1 gene in the Chinese people is more conservative than that in the Caucasian or African people. Different Chinese ethnic groups may have their own different CR1 gene characteristics. The existence of 4646G in the Uigur and Tu ethnic groups suggests that both may carry certain Caucasian characteristics in the CR1 gene. The frequency of 4870G in the Lisu and Dong ethnic groups implies possible incidence of evolutionary pressure similar to what the Africans had experienced. © 2010 The Authors. Transfusion Medicine © 2010 British Blood Transfusion Society.

  1. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed.

    Science.gov (United States)

    van der Schoot, C Ellen; Tax, G H Martine; Rijnders, Robbert J P; de Haas, Masja; Christiaens, Godelieve C M L

    2003-01-01

    Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal material obtained by invasive means (chorionic villus sampling or amniocentesis) are available for all clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and e) and K1 genotyping assays are discussed in this review. Importantly, one must remember that results of genotyping assays will not always be concordant with serological typing. Thus, the RhD genotyping assays have to be modified in response to increased understanding of the molecular biology of this blood group system. RhD typing assays should produce negative results when tested on the black RhD-negative RHD alleles, RHDpsi and r's. PCR-based assays can be used to determine paternal zygosity. For RhD zygosity testing, the real-time quantitative PCR approach and the direct detection of the hybrid Rhesus box, which is the result of the deletion of the RHD gene are available. Recently, methods for noninvasive prenatal genotyping have been investigated. The use of fetal cells circulating in the maternal circulation has been explored; however, the scarcity of circulating fetal cells has limited the use of this approach. More promising are the results obtained with RhD typing assays with cell-free fetal DNA, which is present in the maternal circulation in a concentration of 25 genomic equivalents per milliliter of maternal blood in early pregnancy increasing to 100 copies per milliliter in the third trimester, which is cleared from the circulation within a few hours of delivery. The positive predictive value of this approach is virtually 100%, but false-negative results are (infrequently) encountered. Therefore, this assay can at present only be used for screening of RhD-negative women to make the use of antenatal prophylaxis more targeted and hence more cost-effective. For the clinical

  2. Cannula Tip With Integrated Volume Sensor for Rotary Blood Pump Control: Early-Stage Development.

    Science.gov (United States)

    Cysyk, Joshua; Newswanger, Ray; Popjes, Eric; Pae, Walter; Jhun, Choon-Sik; Izer, Jenelle; Weiss, William; Rosenberg, Gerson

    2018-05-10

    The lack of direct measurement of left ventricular unloading is a significant impediment to the development of an automatic speed control system for continuous-flow left ventricular assist devices (cf-LVADs). We have developed an inlet cannula tip for cf-LVADs with integrated electrodes for volume sensing based on conductance. Four platinum-iridium ring electrodes were installed into grooves on a cannula body constructed from polyetheretherketone (PEEK). A sinusoidal current excitation waveform (250 μA pk-pk, 50 kHz) was applied across one pair of electrodes, and the conductance-dependent voltage was sensed across the second pair of electrodes. The conductance catheter was tested in an acute ovine model (n = 3) in conjunction with the HeartMate II rotary blood pump to provide circulatory support and unload the ventricle. Echocardiography was used to measure ventricular size during pump support for verification for the conductance measurements. The conductance measurements correlated linearly with the echocardiography dimension measurements more than the full range of pump support from minimum support to suction. This cannula tip will enable the development of automatic control systems to optimize pump support based on a real-time measurement of ventricular size.

  3. Assessment of a continuous blood gas monitoring system in animals during circulatory stress

    Directory of Open Access Journals (Sweden)

    Renzulli Attilio

    2011-01-01

    Full Text Available Abstract Background The study was aimed to determine the measurement accuracy of The CDI™ blood parameter monitoring system 500 (Terumo Cardiovascular Systems Corporation, Ann Arbor MI in the real-time continuous measurement of arterial blood gases under different cardiocirculatory stress conditions Methods Inotropic stimulation (Dobutamine 2.5 and 5 μg/kg/min, vasoconstriction (Arginine-vasopressin 4, 8 and 16 IU/h, hemorrhage (-10%, -20%, -35%, and -50% of the theoretical volemia, and volume resuscitation were induced in ten swine (57.4 ± 10.7 Kg.Intermittent blood gas assessments were carried out using a routine gas analyzer at any experimental phase and compared with values obtained at the same time settings during continuous monitoring with CDI™ 500 system. The Bland-Altman analysis was employed. Results Bias and precision for pO2 were - 0.06 kPa and 0.22 kPa, respectively (r2 = 0.96; pCO2 - 0.02 kPa and 0.15 kPa, respectively; pH -0.001 and 0.01 units, respectively ( r2 = 0.96. The analysis showed very good agreement for SO2 (bias 0.04,precision 0.33, r2 = 0.95, Base excess (bias 0.04,precision 0.28, r2 = 0.98, HCO3 (bias 0.05,precision 0.62, r2 = 0.92,hemoglobin (bias 0.02,precision 0.23, r2 = 0.96 and K+ (bias 0.02, precision 0.27, r2 = 0.93. The sensor was reliable throughout the experiment during hemodynamic variations. Conclusions Continuous blood gas analysis with the CDI™ 500 system was reliable and it might represent a new useful tool to accurately and timely monitor gas exchange in critically ill patients. Nonetheless, our findings need to be confirmed by larger studies to prove its reliability in the clinical setting.

  4. [Xeroproteinography of the blood serum system in patients with diabetes mellitus].

    Science.gov (United States)

    Savina, L V; Chirvinskiĭ, N P; Tuev, A V; Bulavskaia, N V

    1987-01-01

    A study of the structure of a dry gel of proteins of the blood serum system (BSS) in diabetes mellitus patients brings to light, to a certain degree, the problem of possible conformation conversions in its proteins. A study was made of networks of xeroproteinograms (XPG) in patients with average and severe forms of insulin dependent type of diabetes mellitus. A study of the XPG structure has a diagnostic and prognostic value for obtaining data on the conformation stability of BSS globular proteins in diabetes mellitus.

  5. Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging - A Simulation Study

    NARCIS (Netherlands)

    Maksuti, Elira; Westerhof, Nico; Westerhof, Berend E.; Broomé, Michael; Stergiopulos, Nikos

    2016-01-01

    During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular

  6. Noninvasive continuous blood pressure monitoring by the ClearSight system during robot-assisted laparoscopic radical prostatectomy.

    Science.gov (United States)

    Sakai, Yoko; Yasuo M, Tsutsumi; Oyama, Takuro; Murakami, Chiaki; Kakuta, Nami; Tanaka, Katsuya

    2018-01-01

    Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.

  7. IMPLEMENTASI PEMERINTAHAN YANG BERSIH DALAM KERANGKA RENCANA AKSI DAERAH PEMBERANTASAN KORUPSI (RAD-PK (Studi Di Kabupaten Pemalang

    Directory of Open Access Journals (Sweden)

    Muhammad Fauzan

    2012-03-01

    Full Text Available This research related to the implementation of good governance, free from corruption, collusion and nepotism. The approach used in this research is a descriptive qualitative approach. The Location of research conducted in the District of Pemalang. Based on the research results can presented that the District of Pemalang is committed and fully supports the government policy in eradicating corruption. District of Pemalang support to efforts to more information accelerate the eradication of corruption stated in the the Regional Action Plan to Accelerate the Eradication of Corruption (RAD-PK in 2011 -2016 which refers to the Medium Term Development Plan (RPJM District of Pemalang from 2011 to 2016 and the National Action Plan for Eradication of Corruption (RAN-PK and the President of Republic of Indonesia Instruction No. 5 Year 2004 on Accelerating the eradication of corruption. RAD-PK 2011-2016 District of Pemalang is a document that contains an action program that aims to accelerate the eradication of corruption. RAD-PK as a program of action containing concrete measures that have been agreed by the stakeholders in the area, so it has been a commitment of local governments prevention efforts corruption through the development of programs and activities aimed at improving public services and the application of the principles of good governance.

  8. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.

    Science.gov (United States)

    Tängdén, T; Ramos Martín, V; Felton, T W; Nielsen, E I; Marchand, S; Brüggemann, R J; Bulitta, J B; Bassetti, M; Theuretzbacher, U; Tsuji, B T; Wareham, D W; Friberg, L E; De Waele, J J; Tam, V H; Roberts, Jason A

    2017-07-01

    Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes. In this article, we describe the potential of in vitro and in vivo infection models, clinical pharmacokinetic data and pharmacokinetic/pharmacodynamic models to guide the design of more effective antimicrobial dosing regimens. Individualised dosing, based on population PK models and patient factors (e.g. renal function and weight) known to influence antimicrobial PK, increases the probability of achieving therapeutic drug exposures while at the same time avoiding toxic concentrations. When therapeutic drug monitoring (TDM) is applied, early dose adaptation to the needs of the individual patient is possible. TDM is likely to be of particular importance for infected critically ill patients, where profound PK changes are present and prompt appropriate antibiotic therapy is crucial. In the light of the continued high mortality rates in critically ill patients with severe infections, a paradigm shift to refined dosing strategies for antimicrobials is warranted to enhance the probability of achieving drug concentrations that increase the likelihood of clinical success.

  9. Comparison of the proteomes of three yeast wild type strains: CEN.PK2, FY1679 and W303

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.; Mose Larsen, P.; Blomberg, A.

    2001-01-01

    Yeast deletion strains created during gene function analysis projects very often show drastic phenotypic differences depending on the genetic background used. These results indicate the existence of important molecular differences between the CEN.PK2, FY1679 and W303 wild type strains...

  10. Effect of α1-adrenergic stimulation on phosphoinositide metabolism and protein kinase C (PK-C) in rat cardiomyocytes

    International Nuclear Information System (INIS)

    Kaku, T.; Lakatta, E.; Filburn, C.R.

    1986-01-01

    Alpha 1 -adrenergic stimulation is known to enhance membrane phospholipid metabolism resulting in increases in inositol phosphates (IP's) and diacylglycerol (DAG). Cardiomyocytes prelabeled with 3 H-myo-inositol were treated with norepinephrine (NE) for 1-15 min, acid extracted, and IP's separated by ion exchange chromatography. Addition of NE (10 -5 M) in the presence of propranolol (10 -5 M) and LiCl (9 mM) enhanced the accumulation of IP's, linearly with time up to 15 min, and reached 7.3, and 1.5-fold at 15 min for IP 1 , IP 2 , and IP 3 , respectively. KCl at 30 mM had no effect on accumulation of IP's, but augmented the effect of NE. PK-C activity was measured in both cytosol (S) and particulate (P) fractions of treated cells. NE alone had a negligible effect on membrane PK-C, while 30 mM KCl caused a small increase. However, pretreatment with KCl followed by NE produced a significant increase above that seen with KCl alone. Dioctanoylglycerol also stimulated membrane association of PK-C in these cells. These data suggest that α 1 -adrenergic stimulation of membrane association of myocardial PK-C is mediated by DAG but may be dependent on membrane potential and/or the extent of Ca 2+ loading

  11. DNA-PK. The major target for wortmannin-mediated radiosensitization by the inhibition of DSB repair via NHEJ pathway

    International Nuclear Information System (INIS)

    Hashimoto, Mitsumasa; Rao, S.; Tokuno, Osamu; Utsumi, Hiroshi; Takeda, Shunichi

    2003-01-01

    The effect of wortmannin posttreatment was studied in cells derived from different species (hamster, mouse, chicken, and human) with normal and defective DNA-dependent protein kinase (DNA-PK) activity, cells with and without the ataxia telangiectasia mutated (ATM) gene, and cells lacking other regulatory proteins involved in the DNA double-strand break (DSB) repair pathways. Clonogenic assays were used to obtain all results. Wortmannin radiosensitization was observed in Chinese hamster cells (V79-B310H, CHO-K1), mouse mammary carcinoma cells (SR-1), transformed human fibroblast (N2KYSV), chicken B lymphocyte wild-type cells (DT40), and chicken Rad54 knockout cells (Rad54 -/- ). However, mouse mammary carcinoma cells (SX9) with defects in the DNA-PK and chicken DNA-PK catalytic subunit (DNA-PKcs) knockout cells (DNA-PKcs -/-/- ) failed to exhibit wortmannin radiosensitization. On the other hand, severe combined immunodeficiency (SCID) mouse cells (SC3VA2) exposed to wortmannin exhibited significant increases in radiosensitivity, possibly because of some residual function of DNA-PKcs. Moreover, the transformed human cells derived from AT patients (AT2KYSV) and chicken ATM knockout cells (ATM -/- ) showed pronounced wortmannin radiosensitization. These studies demonstrate confirm that the mechanism underlying wortmannin radiosensitization is the inhibition of DNA-PK, but not of ATM, thereby resulting in the inhibition of DSB repair via nonhomologous endjoining (NHEJ). (author)

  12. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods

    NARCIS (Netherlands)

    Schuitemaker, Alie; van Berckel, Bart N. M.; Kropholler, Marc A.; Veltman, Dick J.; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A.; Boellaard, Ronald

    2007-01-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to

  13. Identification of RFLP and NBS/PK profiling markers for disease resistance loci in genetic maps of oats

    NARCIS (Netherlands)

    Sanz, M.J.; Loarce, Y.; Fominaya, A.; Vossen, J.H.; Ferrer, E.

    2013-01-01

    Two of the domains most widely shared among R genes are the nucleotide binding site (NBS) and protein kinase (PK) domains. The present study describes and maps a number of new oat resistance gene analogues (RGAs) with two purposes in mind: (1) to identify genetic regions that contain R genes and (2)

  14. The pkI gene encoding pyruvate kinase I links to the luxZ gene which enhances bioluminescence of the lux operon from Photobacterium leiognathi.

    Science.gov (United States)

    Lin, J W; Lu, H C; Chen, H Y; Weng, S F

    1997-10-09

    Partial 3'-end nucleotide sequence of the pkI gene (GenBank accession No. AF019143) from Photobacterium leiognathi ATCC 25521 has been determined, and the encoded pyruvate kinase I is deduced. Pyruvate kinase I is the key enzyme of glycolysis, which converts phosphoenol pyruvate to pyruvate. Alignment and comparison of pyruvate kinase Is from P. leiognathi, E. coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that the pkI gene is linked to the luxZ gene that enhances bioluminescence of the lux operon from P. leiognathi. The gene order of the pkI and luxZ genes is-pk1-ter-->-R&R"-luxZ-ter"-->, whereas ter is transcriptional terminator for the pkI and related genes, and R&R" is the regulatory region and ter" is transcriptional terminator for the luxZ gene. It clearly elicits that the pkI gene and luxZ gene are divided to two operons. Functional analysis confirms that the potential hairpin loop omega T is the transcriptional terminator for the pkI and related genes. It infers that the pkI and related genes are simply linked to the luxZ gene in P. leiognathi genome.

  15. Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail: s.pimlott@clinmed.gla.ac.uk; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)

    2008-07-15

    Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

  16. Rapid and efficient radiosynthesis of [123I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Pimlott, Sally L.; Stevenson, Louise; Wyper, David J.; Sutherland, Andrew

    2008-01-01

    Introduction: [ 123 I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [ 123 I]I-PK11195 in order to develop a rapid and efficient method that obtains [ 123 I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [ 123 I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [ 123 I]I-PK11195. Conclusions: [ 123 I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [ 123 I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved

  17. Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology.

    Science.gov (United States)

    Tournier, Nicolas; Declèves, Xavier; Saubaméa, Bruno; Scherrmann, Jean-Michel; Cisternino, Salvatore

    2011-01-01

    Some of the ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp; ABCB1, MDR1), BCRP (ABCG2) and MRPs (ABCCs) that are present at the blood-brain barrier (BBB) influence the brain pharmacokinetics (PK) of their substrates by restricting their uptake or enhancing their clearance from the brain into the blood, which has consequences for their CNS pharmacodynamics (PD). Opioid drugs have been invaluable tools for understanding the PK-PD relationships of these ABC-transporters. The effects of morphine, methadone and loperamide on the CNS are modulated by P-gp. This review examines the ways in which other opioid drugs and some of their active metabolites interact with ABC transporters and suggests new mechanisms that may be involved in the variability of the response of the CNS to these drugs like carrier-mediated system belonging to the solute carrier (SLC) superfamily. Exposure to opioids may also alter the expression of ABC transporters. P-gp can be overproduced during morphine treatment, suggesting that the drug has a direct or, more likely, an indirect action. Variations in cerebral neurotransmitters during exposure to opioids and the release of cytokines during pain could be new endogenous stimuli affecting transporter synthesis. This review concludes with an analysis of the pharmacotherapeutic and clinical impacts of the interactions between ABC transporters and opioids.

  18. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System.

    Directory of Open Access Journals (Sweden)

    Urs M Nater

    Full Text Available Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separate studies.In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies.Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest.Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals.

  19. Comparison of the clinical and microbiological characteristics of Campylobacter and Helicobacter bacteremia: the importance of time to blood culture positivity using the BACTEC blood culture systems.

    Science.gov (United States)

    Yamamoto, Kei; Hayakawa, Kayoko; Nagashima, Maki; Shimada, Kayo; Kutsuna, Satoshi; Takeshita, Nozomi; Kato, Yasuyuki; Kanagawa, Shuzo; Yamada, Koji; Mezaki, Kazuhisa; Kirikae, Teruo; Ohmagari, Norio

    2017-11-28

    Campylobacter spp. and Helicobacter spp. are rare but important causes of bacteremia in humans. Distinguishing these bacteria is complicated because of their similar phenotypic profiles. We conducted clinical and microbiological investigations of Campylobacter spp. or Helicobacter spp. bacteremia. Patients diagnosed with bacteremia from 2008 to 2014 were included. The clinical and microbiological characteristics of Campylobacter spp. and Helicobacter spp. bacteremia were compared. The BACTEC system was used in blood cultures. A receiver operating characteristic curve was plotted based on the time to blood culture positivity. Sixteen cases of Helicobacter spp. bacteremia (patient age: 61 ± 18 years) and 14 cases of Campylobacter spp. bacteremia (patient age: 49 ± 21 years) were identified. Median time to blood culture positivity was longer for the Helicobacter spp. cases than the Campylobacter spp. cases (91.4 h vs 55.3 h, p culture positivity > 75 h predicted Helicobacter spp. bacteremia with a sensitivity of 0.88 and a specificity of 0.93 (area under the receiver operating characteristic curve of 0.90). In conclusion, a time to blood culture positivity was useful in distinguishing Helicobacter spp. bacteremia from Campylobacter spp. bacteremia.

  20. Biomeasures and mechanistic modeling highlight PK/PD risks for a monoclonal antibody targeting Fn14 in kidney disease.

    Science.gov (United States)

    Chen, Xiaoying; Farrokhi, Vahid; Singh, Pratap; Ocana, Mireia Fernandez; Patel, Jenil; Lin, Lih-Ling; Neubert, Hendrik; Brodfuehrer, Joanne

    2018-01-01

    Discovery of the upregulation of fibroblast growth factor-inducible-14 (Fn14) receptor following tissue injury has prompted investigation into biotherapeutic targeting of the Fn14 receptor for the treatment of conditions such as chronic kidney diseases. In the development of monoclonal antibody (mAb) therapeutics, there is an increasing trend to use biomeasures combined with mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modeling to enable decision making in early discovery. With the aim of guiding preclinical efforts on designing an antibody with optimized properties, we developed a mechanistic site-of-action (SoA) PK/PD model for human application. This model incorporates experimental biomeasures, including concentration of soluble Fn14 (sFn14) in human plasma and membrane Fn14 (mFn14) in human kidney tissue, and turnover rate of human sFn14. Pulse-chase studies using stable isotope-labeled amino acids and mass spectrometry indicated the sFn14 half-life to be approximately 5 hours in healthy volunteers. The biomeasures (concentration, turnover) of sFn14 in plasma reveals a significant hurdle in designing an antibody against Fn14 with desired characteristics. The projected dose (>1 mg/kg/wk for 90% target coverage) derived from the human PK/PD model revealed potential high and frequent dosing requirements under certain conditions. The PK/PD model suggested a unique bell-shaped relationship between target coverage and antibody affinity for anti-Fn14 mAb, which could be applied to direct the antibody engineering towards an optimized affinity. This investigation highlighted potential applications, including assessment of PK/PD risks during early target validation, human dose prediction and drug candidate optimization.

  1. Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576.

    Science.gov (United States)

    Bursi, Roberta; Erdemli, Gul; Campbell, Robert; Hutmacher, Matthew M; Kerbusch, Thomas; Spanswick, David; Jeggo, Ross; Nations, Kari R; Dogterom, Peter; Schipper, Jacques; Shahid, Mohammed

    2011-12-01

    The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor potentiator Org 26576 represents an interesting pharmacological tool to evaluate the utility of glutamatergic enhancement towards the treatment of psychiatric disorders. In this study, a rat-human translational pharmacokinetic-pharmacodynamic (PK-PD) model of AMPA receptor modulation was used to predict human target engagement and inform dose selection in efficacy clinical trials. Modelling and simulation was applied to rat plasma and cerebrospinal fluid (CSF) pharmacokinetic and pharmacodynamic measurements to identify a target concentration (EC(80)) for AMPA receptor modulation. Human plasma pharmacokinetics was determined from 33 healthy volunteers and eight major depressive disorder patients. From four out of these eight patients, CSF PK was also determined. Simulations of human CSF levels were performed for several doses of Org 26576. Org 26576 (0.1-10 mg/kg, i.v.) potentiated rat hippocampal AMPA receptor responses in an exposure-dependant manner. The rat plasma and CSF PK data were fitted by one-compartment model each. The rat CSF PK-PD model yielded an EC(80) value of 593 ng/ml (90% confidence interval 406.8, 1,264.1). The human plasma and CSF PK data were simultaneously well described by a two-compartment model. Simulations showed that in humans at 100 mg QD, CSF levels of Org 26576 would exceed the EC(80) target concentration for about 2 h and that 400 mg BID would engage AMPA receptors for 24 h. The modelling approach provided useful insight on the likely human dose-molecular target engagement relationship for Org 26576. Based on the current analysis, 100 and 400 mg BID would be suitable to provide 'phasic' and 'continuous' AMPA receptor engagement, respectively.

  2. Population PK and IgE pharmacodynamic analysis of a fully human monoclonal antibody against IL4 receptor.

    Science.gov (United States)

    Kakkar, Tarundeep; Sung, Cynthia; Gibiansky, Leonid; Vu, Thuy; Narayanan, Adimoolam; Lin, Shao-Lee; Vincent, Michael; Banfield, Christopher; Colbert, Alex; Hoofring, Sarah; Starcevic, Marta; Ma, Peiming

    2011-10-01

    For AMG 317, a fully human monoclonal antibody to interleukin receptor IL-4Rα, we developed a population pharmacokinetic (PK) model by fitting data from four early phase clinical trials of intravenous and subcutaneous (SC) routes simultaneously, investigated important PK covariates, and explored the relationship between exposure and IgE response. Data for 294 subjects and 2183 AMG 317 plasma concentrations from three Phase 1 and 1 Phase 2 studies were analyzed by nonlinear mixed effects modeling using first-order conditional estimation with interaction. The relationship of IgE response with post hoc estimates of exposure generated from the final PK model was explored based on data from asthmatic patients. The best structural model was a two-compartment quasi-steady-state target-mediated drug disposition model with linear and non-linear clearances. For a typical 80-kg, 40-year subject, linear clearance was 35.0 mL/hr, central and peripheral volumes of distribution were 1.78 and 5.03 L, respectively, and SC bioavailability was 24.3%. Body weight was an important covariate on linear clearance and central volume; age influenced absorption rate. A significant treatment effect was observable between the cumulative AUC and IgE response measured. The population PK model adequately described AMG 317 PK from IV and SC routes over a 60-fold range of doses with two dosing strengths across multiple studies covering healthy volunteers and patients with mild to severe asthma. IgE response across a range of doses and over the sampling time points was found to be related to cumulative AMG 317 exposure.

  3. Global fluctuations of cerebral blood flow indicate a global brain network independent of systemic factors.

    Science.gov (United States)

    Zhao, Li; Alsop, David C; Detre, John A; Dai, Weiying

    2017-01-01

    Global synchronization across specialized brain networks is a common feature of network models and in-vivo electrical measurements. Although the imaging of specialized brain networks with blood oxygenation sensitive resting state functional magnetic resonance imaging (rsfMRI) has enabled detailed study of regional networks, the study of globally correlated fluctuations with rsfMRI is confounded by spurious contributions to the global signal from systemic physiologic factors and other noise sources. Here we use an alternative rsfMRI method, arterial spin labeled perfusion MRI, to characterize global correlations and their relationship to correlations and anti-correlations between regional networks. Global fluctuations that cannot be explained by systemic factors dominate the fluctuations in cerebral blood flow. Power spectra of these fluctuations are band limited to below 0.05 Hz, similar to prior measurements of regional network fluctuations in the brain. Removal of these global fluctuations prior to measurement of regional networks reduces all regional network fluctuation amplitudes to below the global fluctuation amplitude and changes the strength and sign of inter network correlations. Our findings support large amplitude, globally synchronized activity across networks that require a reassessment of regional network amplitude and correlation measures.

  4. Multielement surface plasmon resonance immunosensor for monitoring of blood circulation system

    Science.gov (United States)

    Kostyukevych, Sergey A.; Kostyukevych, Kateryna V.; Khristosenko, Roman V.; Lysiuk, Viktor O.; Koptyukh, Anastasiya A.; Moscalenko, Nadiya L.

    2017-12-01

    The problems related to the development of a multielement immunosensor device with the prism type of excitation of a surface plasmon resonance in the Kretschmann configuration and with the scanning of the incidence angle of monochromatic light aimed at the reliable determination of the levels of three molecular markers of the system of hemostasis (fibrinogen, soluble fibrin, and D-dimer) are considered. We have analyzed the influence of a technology for the production of a gold coating, modification of its surface, and noise effects on the enhancement of sensitivity and stability of the operation of devices. A means of oriented immobilization of monoclonal antibodies on the surface of gold using a multilayer film of copper aminopentacyanoferrate is developed. For the model proteins of studied markers, the calibrating curves (maximum sensitivity of 0.5 μg/ml) are obtained, and the level of fibrinogen in blood plasma of donors is determined. A four-channel modification of the device with an application of a reference channel for comparing the elimination of the noise of temperature fluctuations has been constructed. This device allows one to execute the express-diagnostics of prethrombotic states and the monitoring of the therapy of diseases of the blood circulation system.

  5. Multispectral photoacoustic characterization of ICG and porcine blood using an LED-based photoacoustic imaging system

    Science.gov (United States)

    Shigeta, Yusuke; Sato, Naoto; Kuniyil Ajith Singh, Mithun; Agano, Toshitaka

    2018-02-01

    Photoacoustic imaging is a hybrid biomedical imaging modality that has emerged over the last decade. In photoacoustic imaging, pulsed-light absorbed by the target emits ultrasound that can be detected using a conventional ultrasound array. This ultrasound data can be used to reconstruct the location and spatial details of the intrinsic/extrinsic light absorbers in the tissue. Recently we reported on the development of a multi-wavelength high frame-rate LED-based photoacoustic/ultrasound imaging system (AcousticX). In this work, we photoacoustically characterize the absorption spectrum of ICG and porcine blood using LED arrays with multiple wavelengths (405, 420, 470, 520, 620, 660, 690, 750, 810, 850, 925, 980 nm). Measurements were performed in a simple reflection mode configuration in which LED arrays where fixed on both sides of the linear array ultrasound probe. Phantom used consisted of micro-test tubes filled with ICG and porcine blood, which were placed in a tank filled with water. The photoacoustic spectrum obtained from our measurements matches well with the reference absorption spectrum. These results demonstrate the potential capability of our system in performing clinical/pre-clinical multispectral photoacoustic imaging.

  6. Multimodal flow visualization and optimization of pneumatic blood pump for sorbent hemodialysis system.

    Science.gov (United States)

    Shu, Fangjun; Parks, Robert; Maholtz, John; Ash, Steven; Antaki, James F

    2009-04-01

    Renal Solutions Allient Sorbent Hemodialysis System utilizes a two-chambered pneumatic pump (Pulsar Blood Pump, Renal Solutions, Inc., Warrendale, PA, USA) to avoid limitations associated with peristaltic pumping systems. Single-needle access is enabled by counter-pulsing the two pump chambers, thereby obviating compliance chambers or blood reservoirs. Each chamber propels 20 cc per pulse of 3 s (dual access) or 6 s (single access) duration, corresponding to a peak Reynolds number of approximately 8000 (based on inlet velocity and chamber diameter). A multimodal series of flow visualization studies (tracer particle, dye washout, and dye erosion) was conducted on a sequence of pump designs with varying port locations and diaphragms to improve the geometry with respect to risk of thrombogenesis. Experiments were conducted in a simplified flow loop using occluders to simulate flow resistance induced by tubing and dialyzer. Tracer visualization revealed flow patterns and qualitatively indicated turbulence intensity. Dye washout identified dwell volume and areas of flow stagnation for each design. Dye erosion results indicated the effectiveness and homogeneity of surface washing. Compared to a centered inlet which resulted in a fluid jet that produced two counter-rotating vortices, a tangential inlet introduced a single vortex, and kept the flow laminar. It also provided better surface washing on the pump inner surface. However, a tangential outlet did not present as much benefit as expected. On the contrary, it created a sharp defection to the flow when transiting from filling to ejection.

  7. Proposed Application of Fast Fourier Transform in Near Infra Red Based Non Invasive Blood Glucose Monitoring System

    Science.gov (United States)

    Jenie, R. P.; Iskandar, J.; Kurniawan, A.; Rustami, E.; Syafutra, H.; Nurdin, N. M.; Handoyo, T.; Prabowo, J.; Febryarto, R.; Rahayu, M. S. K.; Damayanthi, E.; Rimbawan; Sukandar, D.; Suryana, Y.; Irzaman; Alatas, H.

    2017-03-01

    Worldwide emergence of glycaemic status related health disorders, such as diabetes and metabolic syndrome, is growing in alarming rate. The objective was to propose new methods for non invasive blood glucose level measurement system, based on implementation of Fast Fourier Transform methods. This was an initial-lab-scale-research. Data on non invasive blood glucose measurement are referred from Scopus, Medline, and Google Scholar, from 2011 until 2016, and was used as design references, combined with in house verification. System was developed in modular fashion, based on aforementioned compiled references. Several preliminary tests to understand relationship between LED and photo-diode responses have been done. Several references were used as non invasive blood glucose measurement tools design basis. Solution is developed in modular fashion. we have proven different sensor responses to water and glucose. Human test for non invasive blood glucose level measurement system is needed.

  8. Protection of Rhesus Monkeys by a DNA Prime/Poxvirus Boost Malaria Vaccine Depends on Optimal DNA Priming and Inclusion of Blood Stage Antigens

    Science.gov (United States)

    Weiss, Walter R.; Kumar, Anita; Jiang, George; Williams, Jackie; Bostick, Anthony; Conteh, Solomon; Fryauff, David; Aguiar, Joao; Singh, Manmohan; O'Hagan, Derek T.; Ulmer, Jeffery B.; Richie, Thomas L.

    2007-01-01

    Background We have previously described a four antigen malaria vaccine consisting of DNA plasmids boosted by recombinant poxviruses which protects a high percentage of rhesus monkeys against Plasmodium knowlesi (Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine. Methodology In three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given iv 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-γ, and by ELISA. Conclusions 1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher

  9. Search for a narrow baryonic state decaying to ${pK^0_S}$ and ${\\overline{p}K^0_S}$ in deep inelastic scattering at HERA

    CERN Document Server

    Abramowicz, H.; Adamczyk, L.; Adamus, M.; Antonelli, S.; Aushev, V.; Behnke, O.; Behrens, U.; Bertolin, A.; Bhadra, S.; Bloch, I.; Boos, E.G.; Brock, I.; Brook, N.H.; Brugnera, R.; Bruni, A.; Bussey, P.J.; Caldwell, A.; Capua, M.; Catterall, C.D.; Chwastowski, J.; Ciborowski, J.; Ciesielski, R.; Cooper-Sarkar, A.M.; Corradi, M.; Dementiev, R.K.; Devenish, RCE; Dusini, S.; Foster, B.; Gach, G; Gallo, E.; Garfagnini, A.; Geiser, A.; Gizhko, A.; Gladilin, L.K.; Golubkov, Yu.A.; Grzelak, G.; Guzik, M.; Gwenlan, C.; Hain, W.; Hlushchenko, O.; Hochman, D.; Hori, R.; Ibrahim, Z.A.; Iga, Y.; Ishitsuka, M.; Januschek, F.; Jomhari, N.Z.; Kadenko, I.; Kananov, S.; Karshon, U.; Kaur, P.; Kisielewska, D.; Klanner, R.; Klein, U.; Korzhavina, I.A.; Kotański, A.; Kötz, U.; Kovalchuk, N.; Kowalski, H.; Krupa, B.; Kuprash, O.; Kuze, M; Levchenko, B.B.; Levy, A.; Limentani, S.; Lisovyi, M.; Lobodzinska, E.; Löhr, B.; Lohrmann, E.; Longhin, A.; Lontkovskyi, D.; Lukina, O.Yu.; Makarenko, I.; Malka, J.; Mastroberardino, A.; Mohamad Idris, F.; Mohammad Nasir, N; Myronenko, V.; Nagano, K.; Nobe, T.; Nowak, R.J.; Onishchuk, Yu.; Paul, E.; Perlański, W.; Pokrovskiy, N.S.; Polini, A.; Przybycien, M.; Roloff, P.; Ruspa, M.; Saxon, D.H.; Schioppa, M.; Schneekloth, U.; Schörner-Sadenius, T.; Shcheglova, L.M.; Shevchenko, R.; Shkola, O.; Shyrma, Yu.; Singh, I.; Skillicorn, I.O.; Słomiński, W.; Solano, A.; Stanco, L.; Stefaniuk, N.; Stern, A.; Stopa, P.; Sztuk-Dambietz, J.; Tassi, E.; Tokushuku, K.; Tomaszewska, J.; Tsurugai, T.; Turcato, M.; Turkot, O.; Tymieniecka, T.; Verbytskyi, A.; Wan Abdullah, W.A.T.; Wichmann, K.; Wing, M.; Yamada, S.; Yamazaki, Y.; Zakharchuk, N.; Żarnecki, A.F.; Zawiejski, L.; Zenaiev, O.; Zhautykov, B.O.; Zotkin, D.S.; Mastroberardino, A

    2016-08-10

    A search for a narrow baryonic state in the $pK^0_S$ and $\\overline{p}K^0_S$ system has been performed in $ep$ collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb$^{-1}$ taken in 2003-2007. The search was performed with deep inelastic scattering events at an $ep$ centre-of-mass energy of 318 GeV for exchanged photon virtuality, $Q^2$, between 20 and 100 $\\rm{} GeV^{2}$. Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb$^{-1}$ taken in 1996-2000, no resonance peak was found in the $p(\\overline{p})K^0_S$ invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set.

  10. Direct blood culturing on solid medium outperforms an automated continuously monitored broth-based blood culture system in terms of time to identification and susceptibility testing

    Directory of Open Access Journals (Sweden)

    E.A. Idelevich

    2016-03-01

    Full Text Available Pathogen identification and antimicrobial susceptibility testing (AST should be available as soon as possible for patients with bloodstream infections. We investigated whether a lysis-centrifugation (LC blood culture (BC method, combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS identification and Vitek 2 AST, provides a time advantage in comparison with the currently used automated broth-based BC system. Seven bacterial reference strains were added each to 10 mL human blood in final concentrations of 100, 10 and 1 CFU/mL. Inoculated blood was added to the Isolator 10 tube and centrifuged at 3000 g for 30 min, then 1.5 mL sediment was distributed onto five 150-mm agar plates. Growth was observed hourly and microcolonies were subjected to MALDI-TOF MS and Vitek 2 as soon as possible. For comparison, seeded blood was introduced into an aerobic BC bottle and incubated in the BACTEC 9240 automated BC system. For all species/concentration combinations except one, successful identification and Vitek 2 inoculation were achieved even before growth detection by BACTEC. The fastest identification and inoculation for AST were achieved with Escherichia coli in concentrations of 100 CFU/mL and 10 CFU/mL (after 7 h each, while BACTEC flagged respective samples positive after 9.5 h and 10 h. Use of the LC-BC method allows skipping of incubation in automated BC systems and, used in combination with rapid diagnostics from microcolonies, provides a considerable advantage in time to result. This suggests that the usefulness of direct BC on solid medium should be re-evaluated in the era of rapid microbiology.

  11. Portable regional cerebral blood flow system based on IBM PC/AT and microprocessor electronics

    International Nuclear Information System (INIS)

    Mun, S.K.; Mun, I.K.; Petite, J.; Cohan, S.L.; Fahey, F.H.

    1986-01-01

    A portable 16-channel reginal cerebral blood flow (rCBF) measuring system has been developed using an IBM PC/AT and new microelectronics to improve processing speed and portability. The detector electronics were developed by Scan Detectronics A/S of Denmark. The counter module contains 18 16-bit counters, each programmable in four different modes. The rate meter has three independent microprocessor controllers for rate meter functions, window controller, and channel controller. The detector electronics and detection parameters can be fully controlled by the host PC/AT. The menu-driven system (Better Basic) assists the operator at each step. The collected data from 16 channels can be processed automatically or postprocessed using more flexible and sophisticated techniques within 20 minutes. The headgear holding 16 sodium iodide detectors is fabricated by modifying a motorcycle helmet

  12. Effect of Metoclopramide on Portal Blood Flow in Patients with Liver Cirrhosis: Evaluation by the Pulsed Doppler System

    International Nuclear Information System (INIS)

    Baik, Soon Koo; Lee, Yong Gyu; Hong, Sa Joon; Lee, Seong Wu; Lee, Dong Ki; Kwong, Sang Ok

    1994-01-01

    Metoclopramide is known to lower the intravariceal flow by raising the lower esophageal sphincter pressure and consequently decreases the portal blood flow. So we designed this study to assess the effect of metoclopramide on portal blood flow in cirrhotic patients using pulsed Doppler system. By using pulsed Doppler ultrasound, portal blood velocity, diameter of the portal vein, portal blood flow, blood pressure and pulse rate were measured at 15, 30 and 60 minutes after administration of 20mg metoclopramide in 16cirrhotic patients and compared with the basal values. In order 10 cirrhotic patients, normal saline was administrated, and the above mentioned parameters were measured. Wothin 15 minutes after intravenous administration of 20mg metoclopramide, portal blood velocity and portal blood flow decreased significantly, from 12.45+2.64 to 11.80+2.55cm/sec and from 1006.3+407.1 to 974.4+414.7ml/min, respectively(P<0.05). In placebo group,there was no significant change in measured parameters after administration of normal saline. These results support the hypothesis that metoclopramide significantly decreases the portal blood flow transiently in cirrhotic patients with portal hypertension

  13. Detection of cytomegalovirus in blood donors by PCR using the digene SHARP signal system assay: effects of sample preparation and detection methodology.

    OpenAIRE

    Krajden, M; Shankaran, P; Bourke, C; Lau, W

    1996-01-01

    Cytomegalovirus (CMV) is an important cause of transfusion-associated morbidity and mortality; however, only 0.4 to 12% of the blood products obtained from seropositive blood donors transmit infection. The effects of three commercially available whole-blood sample preparation kits on the detection of CMV PCR products by a semiquantitative adaptation of the Digene SHARP Signal System Assay (DSSSA) in samples from volunteer blood donors was assessed. Of 101 samples from seropositive blood donor...

  14. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

    2016-10-01

    Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Symptoms of Blood Disorders

    Science.gov (United States)

    ... or immune system proteins can cause increased blood viscosity (thickening of the blood). Increased platelets or blood ... by anemia Pica (eating of ice, dirt, or clay) suggests iron deficiency anemia Drugs Mentioned In This ...

  16. Accuracy evaluation of contour next compared with five blood glucose monitoring systems across a wide range of blood glucose concentrations occurring in a clinical research setting.

    Science.gov (United States)

    Klaff, Leslie J; Brazg, Ronald; Hughes, Kristen; Tideman, Ann M; Schachner, Holly C; Stenger, Patricia; Pardo, Scott; Dunne, Nancy; Parkes, Joan Lee

    2015-01-01

    This study evaluated the accuracy of Contour(®) Next (CN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ) compared with five blood glucose monitoring systems (BGMSs) across a wide range of clinically occurring blood glucose levels. Subjects (n=146) were ≥ 18 years and had type 1 or type 2 diabetes. Subjects' glucose levels were safely lowered or raised to provide a wide range of glucose values. Capillary blood samples were tested on six BGMSs and a YSI glucose analyzer (YSI Life Sciences, Inc., Yellow Springs, OH) as the reference. Extreme glucose values were achieved by glucose modification of the blood sample. System accuracy was assessed by mean absolute difference (MAD) and mean absolute relative difference (MARD) across several glucose ranges, with glucose range (Abbott Diabetes Care, Inc., Alameda, CA), 2.77 mg/dL; OneTouch(®) Ultra(®) 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; OneTouch(®) Verio(®) Pro (LifeScan, Inc.), 4.53 mg/dL; and Truetrack(®) (Nipro Diagnostics, Inc., Fort Lauderdale, FL), 11.08 mg/dL. The lowest MAD in the low glucose range, from CN, was statistically significantly lower than those of the other BGMSs with the exception of the FSL. CN also had a statistically significantly lower MARD than all other BGMSs in the low glucose range. In the overall glucose range (21-496 mg/dL), CN yielded the lowest MAD and MARD values, which were statistically significantly lower in comparison with the other BGMSs. When compared with other BGMSs, CN demonstrated the lowest mean deviation from the reference value (by MAD and MARD) across multiple glucose ranges.

  17. Comparison of four methods for rapid identification of Staphylococcus aureus directly from BACTEC 9240 blood culture system

    Directory of Open Access Journals (Sweden)

    N S Ozen

    2011-01-01

    Full Text Available Purpose: Differentiation of Staphylococcus aureus (S. aureus from coagulase-negative staphylococci is very important in blood stream infections. Identification of S. aureus and coagulase-negative staphylococci (CoNS from blood cultures takes generally 18-24 h after positive signaling on continuously monitored automated blood culture system. In this study, we evaluated the performance of tube coagulase test (TCT, slide agglutination test (Dry Spot Staphytect Plus, conventional polymerase chain reaction (PCR and LightCycler Staphylococcus MGrade kit directly from blood culture bottles to achieve rapid identification of S. aureus by using the BACTEC 9240 blood culture system. Materials and Methods: A total of 129 BACTEC 9240 bottles growing gram-positive cocci suggesting Staphylococci were tested directly from blood culture broths (BCBs with TCT, Dry Spot Staphytect Plus, conventional PCR and LightCycler Staphylococcus MGrade kit for rapid identification of S. aureus. Results: The sensitivities of the tests were 99, 68, 99 and 100%, respectively. Conclusion: Our results suggested that 2 h TCT was found to be simple and inexpensive method for the rapid identification of S. aureus directly from positive blood cultures.

  18. Comparison of four methods for rapid identification of Staphylococcus aureus directly from BACTEC 9240 blood culture system.

    Science.gov (United States)

    Ozen, N S; Ogunc, D; Mutlu, D; Ongut, G; Baysan, B O; Gunseren, F

    2011-01-01

    Differentiation of Staphylococcus aureus (S. aureus) from coagulase-negative staphylococci is very important in blood stream infections. Identification of S. aureus and coagulase-negative staphylococci (CoNS) from blood cultures takes generally 18-24 h after positive signaling on continuously monitored automated blood culture system. In this study, we evaluated the performance of tube coagulase test (TCT), slide agglutination test (Dry Spot Staphytect Plus), conventional polymerase chain reaction (PCR) and LightCycler Staphylococcus MGrade kit directly from blood culture bottles to achieve rapid identification of S. aureus by using the BACTEC 9240 blood culture system. A total of 129 BACTEC 9240 bottles growing gram-positive cocci suggesting Staphylococci were tested directly from blood culture broths (BCBs) with TCT, Dry Spot Staphytect Plus, conventional PCR and LightCycler Staphylococcus MGrade kit for rapid identification of S. aureus. The sensitivities of the tests were 99, 68, 99 and 100%, respectively. Our results suggested that 2 h TCT was found to be simple and inexpensive method for the rapid identification of S. aureus directly from positive blood cultures.

  19. Next generation of non-mammalian blood-brain barrier models to study parasitic infections of the central nervous system

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Edwards-Smallbone, James; Flynn, Robin; Khan, Naveed Ahmed

    2012-01-01

    Transmigration of neuropathogens across the blood-brain barrier is a key step in the development of central nervous system infections, making it a prime target for drug development. The ability of neuropathogens to traverse the blood-brain barrier continues to inspire researchers to understand the specific strategies and molecular mechanisms that allow them to enter the brain. The availability of models of the blood-brain barrier that closely mimic the situation in vivo offers unprecedented opportunities for the development of novel therapeutics. PMID:21921682

  20. Smart point-of-care systems for molecular diagnostics based on nanotechnology: whole blood glucose analysis

    Science.gov (United States)

    Devadhasan, Jasmine P.; Kim, Sanghyo

    2015-07-01

    Complementary metal oxide semiconductor (CMOS) image sensors are received great attention for their high efficiency in biological applications. The present work describes a CMOS image sensor-based whole blood glucose monitoring system through a point-of-care (POC) approach. A simple poly-ethylene terephthalate (PET) film chip was developed to carry out the enzyme kinetic reaction at various concentrations of blood glucose. In this technique, assay reagent was adsorbed onto amine functionalized silica (AFSiO2) nanoparticles in order to achieve glucose oxidation on the PET film chip. The AFSiO2 nanoparticles can immobilize the assay reagent with an electrostatic attraction and eased to develop the opaque platform which was technically suitable chip to analyze by the camera module. The oxidized glucose then produces a green color according to the glucose concentration and is analyzed by the camera module as a photon detection technique. The photon number decreases with increasing glucose concentration. The simple sensing approach, utilizing enzyme immobilized AFSiO2 nanoparticle chip and assay detection method was developed for quantitative glucose measurement.

  1. Bio-Inspiered Blood-Contacting Materials Elaborated For The Heart Assist System

    Directory of Open Access Journals (Sweden)

    Major R.

    2015-09-01

    Full Text Available The paper presents the main achievements of the author on the development of blood contacting materials. The main objective of the work is to elaborate materials dedicated for the heart support systems. Appropriately designed biomaterial surfaces enable fully controlled cellular differentiation, proliferation, and even restoration of the tissue structure on solids. The paper presents two approaches to modify the surface, which can control the life processes of tissue. The first solution considers the topography in the form of cell niches. The main objective of the study is a modified surface of thin films deposited on the polymer substrate constituting the microenvironment for the cells caused by residual stress and optimized stiffness of the surface using the plasma methods. The research hypothesis was the plasma surface modification method generating a controlled contribution of residual stress in the coating affect the surface topography in the form of nano- wrinkles similar to the niches in the tissue environment. Topography and stiffness of the surface coating allows the targeted cellular differentiation. The properly formed surface topography effectively inhibits blood clotting processes. The second solution considers implementation of self-organizing feature of extracellular matrix like coatings and selective cell mobilization. The multiscale analysis and phenomenologic description were performed to experimental research. For this purpose, the deposition method was based on electrostatic interactions in polyelectrolytes. This type of cell-polymer structure imitate the native structures.

  2. Black blood MRI in suspected large artery primary angiitis of the central nervous system.

    Science.gov (United States)

    Pfefferkorn, Thomas; Linn, Jennifer; Habs, Maximilian; Opherk, Christina; Cyran, Clemens; Ottomeyer, Caroline; Straube, Andreas; Dichgans, Martin; Nikolaou, Konstantin; Saam, Tobias

    2013-07-01

    Single case reports suggest that black blood MRI (T1-weighted fat and blood suppressed sequences with and without contrast injection; BB-MRI) may visualize intracranial vessel wall contrast enhancement (CE) in primary angiitis of the central nervous system (PACNS). In this single-center observational pilot study we prospectively investigated the value of BB-MRI in the diagnosis of large artery PACNS. Patients with suspected large artery PACNS received a standardized diagnostic program including BB-MRI. Vessel wall CE was graded (grade 0-2) by two experienced readers blinded to clinical data and correlated to the final diagnosis. Four of 12 included patients received a final diagnosis of PACNS. All of them showed moderate (grade 1) to strong (grade 2) vessel wall CE at the sites of stenosis. A moderate (grade 1) vessel wall CE grade was also observed in 6 of the remaining 8 patients in whom alternative diagnoses were made: arteriosclerotic disease (n = 4), intracranial dissection (n = 1), and Moyamoya disease (n = 1). Our pilot study demonstrates that vessel wall CE is a frequent finding in PACNS and its mimics. Larger trials will be necessary to evaluate the utility of BB-MRI in the diagnostic workup of PACNS. Copyright © 2012 by the American Society of Neuroimaging.

  3. Interaction between blood-brain barrier and glymphatic system in solute clearance.

    Science.gov (United States)

    Verheggen, I C M; Van Boxtel, M P J; Verhey, F R J; Jansen, J F A; Backes, W H

    2018-03-30

    Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Blood glucose monitoring during aerobic and anaerobic physical exercise using a new artificial pancreas system.

    Science.gov (United States)

    Quirós, Carmen; Bertachi, Arthur; Giménez, Marga; Biagi, Lyvia; Viaplana, Judith; Viñals, Clara; Vehí, Josep; Conget, Ignacio; Bondia, Jorge

    To assess an artificial pancreas system during aerobic (AeE) and anaerobic exercise (AnE). A pilot clinical trial on five subjects with type 1 diabetes (4 males) aged 37±10.9 years, diabetes diagnosed 21.2±12.2 years before, insulin pump users, and with a mean HbA 1c level of 7.8±0.5%. Every subject did three AeE and three AnE sessions. Blood glucose levels were monitored by the artificial pancreas system during exercise and up to four hours later. Before the start of exercise, 23g of carbohydrates were administered orally. The mean glucose level was 124.0±25.1mg/dL in the AeE studies and 152.1±34.1mg/dL in the AnE studies. Percent times in the different glucose ranges of 70-180, >180 and 18.6% and 75.9±27.6%; 7.7±18.4% and 23.2±28.0%; and 2.5±6.3% and 1.0±3.6% during the AeE and AnE sessions, respectively. Only six rescues with carbohydrates (15g) were required during the studies (4 in AeE and 2 in AnE). Total insulin dose during the five hours of the study was 3.1±1.0IU in the AeE studies and 3.5±1.3IU in the AnE studies. Blood glucose response to AeE and AnE exercise is different. The evaluated artificial pancreas system appeared to achieve effective and safe blood glucose control during exercise and up to four hours later. However, new control strategies that minimize patient intervention should be designed. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

    Science.gov (United States)

    Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

    2012-02-01

    Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

  6. Magnetic navigation system for the precise helical and translational motions of a microrobot in human blood vessels

    Science.gov (United States)

    Jeon, S. M.; Jang, G. H.; Choi, H. C.; Park, S. H.; Park, J. O.

    2012-04-01

    Different magnetic navigation systems (MNSs) have been investigated for the wireless manipulation of microrobots in human blood vessels. Here we propose a MNS and methodology for generation of both the precise helical and translational motions of a microrobot to improve its maneuverability in complex human blood vessel. We then present experiments demonstrating the helical and translational motions of a spiral-type microrobot to verify the proposed MNS.

  7. Order of draw practices in venous blood sampling at clinical biochemistry departments in the Danish health care system

    DEFF Research Database (Denmark)

    Jacobsen, Katja Kemp; Brandt, Ida; Christensen, Anne Vindahl

    2018-01-01

    the procedures in venous blood sampling among clinical biochemistry departments to assess the uniformity of order of blood draw and adherence to international guidelines in the Danish health care system. METHODS: We collected venous order of draw procedures from 49 clinical biochemistry departments at 22 public...... 15189:2012 accreditation (p = .57). CONCLUSIONS: Venous order of draw procedures is diverse at Danish clinical biochemistry departments and show moderate adherence to international guidelines....

  8. Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients.

    Science.gov (United States)

    Nassar, Ala F; Wisnewski, Adam V; King, Ivan

    2017-05-01

    1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis. 3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V 1 ) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V 2 were 73.2 L/h and 29.9 L, and inter-patient variability in V 2 was 63.1%, respectively. 4. The estimate of V ss (75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.

  9. Perpendicular diffusion of a dilute beam of charged particles in the PK-4 dusty plasma

    Science.gov (United States)

    Liu, Bin; Goree, John

    2015-09-01

    We study the random walk of a dilute beam of projectile dust particles that drift through a target dusty plasma. This random walk is a diffusion that occurs mainly due to Coulomb collisions with target particles that have a different size. In the direction parallel to the drift, projectiles exhibit mobility-limited motion with a constant average velocity. We use a 3D molecular dynamics (MD) simulation of the dust particle motion to determine the diffusion and mobility coefficients for the dilute beam. The dust particles are assumed to interact with a shielded Coulomb repulsion. They also experience gas drag. The beam particles are driven by a prescribed net force that is not applied to the target particles; in the experiments this net force is due to an imbalance of the electric and ion drag forces. This simulation is motivated by microgravity experiments, with the expectation that the scattering of projectiles studied here will be observed in upcoming PK-4 experiments on the International Space Station. Supported by NASA and DOE.

  10. Calcidiol and vitamin D binding protein uptake by LLC-PK1 cells

    International Nuclear Information System (INIS)

    Keenan, M.J.; Holmes, R.P.

    1986-01-01

    The process by which target cells take up vitamin D and its metabolites is not known. The authors studied the uptake of both 3 H-calcidiol and 125 I-Vitamin D Binding Protein (DBP) by LLC-PK 1 cells. Uptake was directly related to their extracellular concentrations. In the presence of 55 serum in the growth media cells previously incubated with 10 nM calcitriol for 4 hr had a greater uptake of calcidiol than those cells not incubated with calcitriol. This effect of calcitriol on calcidiol uptake was absent when cells were grown in hormone-supplemented, serum-free media, despite these cells having a cytosolic calcitriol receptor. Equal uptake of calcidiol occurred when DBP was absent and when DBP was present in a one to one molar ratio to calcidiol. With a 1:1 ratio of DBP to calcidiol and a measured K/sub D/ of 2 x 10 -8 M, the uptake of calcidiol could not be accounted for by uptake of the free ligand alone. A large excess of DBP (100:1) in relation to calcidiol suppressed uptake of calcidiol by approx. 90%. The authors have not been able to identify a saturable, specific uptake of either calcidiol or DBP despite DBP appearing to facilitate calcidiol uptake

  11. Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies

    Science.gov (United States)

    2015-01-01

    Whole-cell screening of 20,000 drug-like small molecules led to the identification of nitrofuranyl methylpiperazines as potent anti-TB agents. In the present study, validation followed by medicinal chemistry has been used to explore the structure–activity relationship. Ten compounds demonstrated potent MIC in the range of 0.17–0.0072 μM against H37Rv Mycobacterium tuberculosis (MTB) and were further investigated against nonreplicating and resistant (RifR and MDR) strains of MTB. These compounds were also tested for cytotoxicity. Among the 10 tested compounds, five showed submicromolar to nanomolar potency against nonreplicating and resistant (RifR and MDR) strains of MTB along with a good safety index. Based on their overall in vitro profiles, the solubility and pharmacokinetic properties of five potent compounds were studied, and two analogues, 14f and 16g, were found to have comparatively better solubility than others tested and acceptable pharmacokinetic properties. This study presents the rediscovery of a nitrofuranyl class of compounds with improved aqueous solubility and acceptable oral PK properties, opening a new direction for further development. PMID:26487909

  12. Validation and Application of a Dried Blood Spot Ceftriaxone Assay

    Science.gov (United States)

    Page-Sharp, Madhu; Nunn, Troy; Salman, Sam; Moore, Brioni R.; Batty, Kevin T.; Davis, Timothy M. E.

    2015-01-01

    Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic/pharmacodynamic (PK/PD) studies in situations where venous blood sampling is logistically and/or ethically problematic. In this study, we aimed to develop, validate, and apply a DBS ceftriaxone assay. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) DBS ceftriaxone assay was assessed for matrix effects, process efficiency, recovery, variability, and limits of quantification (LOQ) and detection (LOD). The effects of hematocrit, protein binding, red cell partitioning, and chad positioning were evaluated, and thermal stability was assessed. Plasma, DBS, and cell pellet ceftriaxone concentrations in 10 healthy adults were compared, and plasma concentration-time profiles of DBS and plasma ceftriaxone were incorporated into population PK models. The LOQ and LOD for ceftriaxone in DBS were 0.14 mg/liter and 0.05 mg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations (r > 0.95, P 95% initial concentrations in DBS for 14 h, 35 h, 30 days, 21 weeks, and >11 months, respectively. The present DBS ceftriaxone assay is robust and can be used as a surrogate for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including in studies of young children and of those in remote or resource-poor settings. PMID:26438505

  13. Application of mobile blood purification system in the treatment of acute renal failure dog model in the field environment

    Directory of Open Access Journals (Sweden)

    Zhi-min ZHANG

    2014-01-01

    Full Text Available Objective To evaluate the stability, safety and efficacy of mobile blood purification system in the treatment of acute renal failure dog model in the field environment. Methods The acute renal failure model was established in 4 dogs by bilateral nephrectomy, which was thereafter treated with the mobile blood purification system. The evaluation of functional index of the mobile blood purification system was performed after a short-time (2 hours and conventional (4 hours dialysis treatment. Results The mobile blood purification system ran stably in the field environment at a blood flow of 150-180ml/min, a dialysate velocity of 2000ml/h, a replacement fluid velocity of 2000ml/h, and ultrafiltration rate of 100-200ml/h. All the functions of alarming system worked well, including static upper limit alarm of ultrafiltration pressure (>100 mmHg, upper limit alarm of ambulatory arterial pressure (>400mmHg, upper limit alarm of ambulatory venous pressure (>400mmHg, bubble alarm of vascular access, bubble alarm during the infusion of solutions, pressure alarm at the substitution pump segment and blood leaking alarm. The vital signs of the 4 dogs with acute renal failure kept stable during the treatment. After the treatment, a remarkable decrease was seen in the levels of serum urea nitrogen, creatinine and serum potassium (P0.05. Conclusions The mobile blood purification system runs normally even in a field environment. It is a flexible and portable device with a great performance in safety and stability in the treatment of acute renal failure. DOI: 10.11855/j.issn.0577-7402.2013.12.15

  14. Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model.

    Directory of Open Access Journals (Sweden)

    Shamim H Rahman

    2015-05-01

    Full Text Available In vitro disease modeling based on induced pluripotent stem cells (iPSCs provides a powerful system to study cellular pathophysiology, especially in combination with targeted genome editing and protocols to differentiate iPSCs into affected cell types. In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID, a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK activity. Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. Furthermore, in vitro T-cell differentiation from iPSCs was employed to model the stage-specific T-cell maturation block induced by the disease causing mutation. Genetic correction of the RS-SCID iPSCs restored T-lymphocyte maturation, polyclonal V(DJ recombination of the T-cell receptor followed by successful beta-selection. In conclusion, we provide proof that iPSC-based in vitro T-cell differentiation is a valuable paradigm for SCID disease modeling, which can be utilized to investigate disorders of T-cell development and to validate gene therapy strategies for T-cell deficiencies. Moreover, this study emphasizes the significance of designer nucleases as a tool for generating isogenic disease models and their future role in producing autologous, genetically corrected transplants for various clinical applications.

  15. Semi quantification study of [{sup 11}C]-(R)-PK11195 PET brain images in multiple sclerosis; Estudo da semiquantificacao de imagens PET cerebrais de [{sup 11}C]-(R)-PK11195 na esclerose multipla

    Energy Technology Data Exchange (ETDEWEB)

    Narciso, Lucas D.L.; Schuck, Phelipi N.; Dartora, Caroline M.; Matushita, Cristina S.; Becker, Jefferson; Silva, Ana M. Marques da, E-mail: lucas.narciso@acad.pucrs.br [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil)

    2016-07-01

    PET brain images with [{sup 11}C]-(R)-PK11195 are being widely used to visualize microglial activation in vivo in neuro degenerative diseases, such as multiple sclerosis (MS). The aim of this study is to investigate the uptake behavior in justacortical and periventricular regions of [{sup 11}C]-(R)-PK11195 PET brain images reformatted in different time intervals by applying three methods, seeking method and time interval that significantly differentiate MS patients from healthy controls. Semi-quantitative SUV and uptake relative to a reference region methods were applied to PET images from different time intervals acquired from 10 patients with MS and 5 healthy controls. The results show significant SUV values difference (p = 0.01, 40 to 60 min) in justacortical and periventricular regions between groups and using the normalization method in which the uptake is relative to the mean concentration activity in the white matter (p <0.01, 10 to 60 min). (author)

  16. Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

    Science.gov (United States)

    Ruaro, B; Sulli, A; Pizzorni, C; Paolino, S; Smith, V; Cutolo, M

    2016-05-01

    To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (pnailfold capillaroscopy scores of microangiopathy. Copyright © 2016. Published by Elsevier Inc.

  17. The expression of one ankyrin pk2 allele of the WO prophage is correlated with the Wolbachia feminizing effect in isopods

    Directory of Open Access Journals (Sweden)

    Pichon Samuel

    2012-04-01

    Full Text Available Abstract Background The maternally inherited α-Proteobacteria Wolbachia pipientis is an obligate endosymbiont of nematodes and arthropods, in which they induce a variety of reproductive alterations, including Cytoplasmic Incompatibility (CI and feminization. The genome of the feminizing wVulC Wolbachia strain harboured by the isopod Armadillidium vulgare has been sequenced and is now at the final assembly step. It contains an unusually high number of ankyrin motif-containing genes, two of which are homologous to the phage-related pk1 and pk2 genes thought to contribute to the CI phenotype in Culex pipiens. These genes encode putative bacterial effectors mediating Wolbachia-host protein-protein interactions via their ankyrin motifs. Results To test whether these Wolbachia homologs are potentially involved in altering terrestrial isopod reproduction, we determined the distribution and expression of both pk1 and pk2 genes in the 3 Wolbachia strains that induce CI and in 5 inducing feminization of their isopod hosts. Aside from the genes being highly conserved, we found a substantial copy number variation among strains, and that is linked to prophage diversity. Transcriptional analyses revealed expression of one pk2 allele (pk2b2 only in the feminizing Wolbachia strains of isopods. Conclusions These results reveal the need to investigate the functions of Wolbachia ankyrin gene products, in particular those of Pk2, and their host targets with respect to host sex manipulation.

  18. Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol.

    Science.gov (United States)

    Klonoff, David C; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A; Arreaza-Rubin, Guillermo; Burk, Robert D; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W

    2016-05-01

    Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled "Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program" is attached as supplementary material. This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. © 2015 Diabetes Technology Society.

  19. Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol

    Science.gov (United States)

    Klonoff, David C.; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A.; Arreaza-Rubin, Guillermo; Burk, Robert D.; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B.; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W.

    2015-01-01

    Background: Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. Methods: The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. Results: A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled “Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program” is attached as supplementary material. Conclusion: This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. PMID:26481642

  20. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov

    2005-01-01

    Full Text Available Objective. To assess coagulation parameters and activity indices in pts with systemic lupus erythematosus (SLE. Material and methods . 86 pts with SLE (83 female and 3 male were examined. 12 of them had antiphospholipid syndrome. Mean age was 35,9±1,5 years (from 18 to 58 years, mean disease duration was 9,8+1,4 years. Control group consisted of 60 healthy volunteers with mean age 37,1+4,1 years. SLE activity assessment was performed with SLAM, SLEDAI and ECLAM indices. Results. SLE pts showed 5-fold (p<0,01 increase of spontaneous platelets aggregation and more than 3-fold increase of factor von Willebrand antigen (FWA concentration. Platelet activation in pts was accompanied by decrease of platelet aggregation with collagen (on 27%, p<0,01. Characteristic sign of coagulation hemostasis activation was significant increase of soluble fibrin-monomer complexes (SFMC concentration on 81 % (p<0,01 so as increase D-dimers level in 53,3% of pts. Fibrinogen concentration was increased on 29%, spontaneous fibrinolysis parameters were decreased on 20%, antithrombin (AT 111 - on 21% in comparison with control. Direct correlation between activity indiccs and SFMC(ECLAM, r=0,5, fibrinogen concentration (SLAM, r=0,34, D- dimers level (ECLAM, r=0,5, spontaneous platelet aggregation (ECLAM, r=0,5 so as inverse correlation with AT III activity (SLEDAI, r-0,73 was revealed. Conclusion. Changes of hemostasis parameters in SLE may serve as predictors of thrombotic disorders development and indication to drug correction of blood coagulation disorders. Direct correlation between blood coagulation system activity and indices of SLE activity.

  1. Blood Test: Testosterone

    Science.gov (United States)

    ... Test: Estradiol Precocious Puberty Understanding Puberty Endocrine System Male Reproductive System Getting a Blood Test (Video) All About Puberty Blood Test (Video) Male Reproductive System View more About Us Contact Us Partners Editorial ...

  2. Lactate versus pH levels in fetal scalp blood during labor--using the Lactate Scout System

    DEFF Research Database (Denmark)

    Lundin, Ingeborg Christina Rørbye; Perslev, Anette; Nickelsen, Carsten Nahne Amtoft

    2016-01-01

    OBJECTIVE: To assess if lactate measured with the Scout Lactate System is a reliable alternative to pH in intrapartum monitoring of the fetus. METHODS: A prospective study analyzing (1) the correlation between scalp lactate measured by the Scout Lactate System and the Automatic Blood Laboratory (...

  3. The development of a national surveillance system for monitoring blood use and inventory levels at sentinel hospitals in South Korea.

    Science.gov (United States)

    Lim, Y A; Kim, H H; Joung, U S; Kim, C Y; Shin, Y H; Lee, S W; Kim, H J

    2010-04-01

    We developed a web-based program for a national surveillance system to determine baseline data regarding the supply and demand of blood products at sentinel hospitals in South Korea. Sentinel hospitals were invited to participate in a 1-month pilot-test. The data for receipts and exports of blood from each hospital information system were converted into comma-separated value files according to a specific conversion rule. The daily data from the sites could be transferred to the web-based program server using a semi-automated submission procedure: pressing a key allowed the program to automatically compute the blood inventory level as well as other indices including the minimal inventory ratio (MIR), ideal inventory ratio (IIR), supply index (SI) and utilisation index (UI). The national surveillance system was referred to as the Korean Blood Inventory Monitoring System (KBIMS) and the web-based program for KBIMS was referred to as the Blood Inventory Monitoring System (BMS). A total of 30 256 red blood cell (RBC) units were submitted as receipt data, however, only 83% of the receipt data were submitted to the BMS server as export data (25 093 RBC units). Median values were 2.67 for MIR, 1.08 for IIR, 1.00 for SI, 0.88 for UI and 5.33 for the ideal inventory day. The BMS program was easy to use and is expected to provide a useful tool for monitoring hospital inventory levels. This information will provide baseline data regarding the supply and demand of blood products in South Korea.

  4. Gene distribution of ABO blood type system on the Dengue Hemorrhagic Fever (DHF) patients in the working area of Puskesmas Bonto Bangun, District of Rilau Ale, Bulukumba

    Science.gov (United States)

    Sjafaraenan; Alvionita, D. N.; Agus, R.; Sabran, A.

    2018-03-01

    This research is about gene distribution of ABO blood type system on the Dengue Hemorrhagic Fever (DHF) patients in the working area of Puskesmas Bonto Bangun, District of Rilau Ale, Bulukumba. This research aimed to determine the blood type which is most affected by DHF using ABO blood type system. In this research, there are 104 samples, 8 of them were attacked by DF and 96 were attacked by DHF. From the 96 patients of DHF, there were 38 patients with A-blood type, 17 patients with B-blood type, 36 patients with O-blood type and 5 patients of AB-blood type. The data were tested using genotype frequency test and the results showed that the percentage of A-homozygous blood type (IAIA) is 0:09%; A heterozygous blood type (IAIo) is 0:36%; B-homozygous blood type (IBIB) is 0.01%; B heterozygous blood type (IB Io) is 0.12%; AB blood type (IAIB) is 0.06% and O blood type (IoIo) is 12:36%. So the biggest frequency of genotype are IAIo (0.36%) and IoIo (0.36%). The results showed that O blood type gene is the most affected by DHF. Then continued by the regression test between blood type and DHF, it is obtained that the correlation value is 1 which indicated that there is a strong relationship.

  5. Blood irradiation

    International Nuclear Information System (INIS)

    Chandy, Mammen

    1998-01-01

    Viable lymphocytes are present in blood and cellular blood components used for transfusion. If the patient who receives a blood transfusion is immunocompetent these lymphocytes are destroyed immediately. However if the patient is immunodefficient or immunosuppressed the transfused lymphocytes survive, recognize the recipient as foreign and react producing a devastating and most often fatal syndrome of transfusion graft versus host disease [T-GVHD]. Even immunocompetent individuals can develop T-GVHD if the donor is a first degree relative since like the Trojan horse the transfused lymphocytes escape detection by the recipient's immune system, multiply and attack recipient tissues. T-GVHD can be prevented by irradiating the blood and different centers use doses ranging from 1.5 to 4.5 Gy. All transfusions where the donor is a first degree relative and transfusions to neonates, immunosuppressed patients and bone marrow transplant recipients need to be irradiated. Commercial irradiators specifically designed for irradiation of blood and cellular blood components are available: however they are expensive. India needs to have blood irradiation facilities available in all large tertiary institutions where immunosuppressed patients are treated. The Atomic Energy Commission of India needs to develop a blood irradiator which meets international standards for use in tertiary medical institutions in the country. (author)

  6. Comparison of two plethysmography systems in assessment of forearm blood flow.

    Science.gov (United States)

    Leslie, Stephen J; Attinà, Teresa; Hultsch, Ellen; Bolscher, Luc; Grossman, Matthias; Denvir, Martin A; Webb, David J

    2004-05-01

    Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 +/- 1.5%, n = 240, P 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.

  7. Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.

    Science.gov (United States)

    De Luca, Ciro; Virtuoso, Assunta; Maggio, Nicola; Papa, Michele

    2017-10-12

    Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix. The pleiotropy of these effects is produced through different receptors, expressed in various cell types, in a dose- and time-dependent pattern. We reviewed how these pathways may be involved in neurodegenerative diseases (amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases), multiple sclerosis, ischemic stroke and post-ischemic epilepsy, CNS cancer, addiction, and mental health. These data open up a new path for the potential therapeutic use of the agonist/antagonist of these proteins in the management of several central nervous system diseases.

  8. FUNCTIONAL STUDIES ON BLOOD MICROCIRCULATION SYSTEM WITH LASER DOPPLER FLOWMETRY IN CLINICAL MEDICINE: PROBLEMS AND PROSPECTS

    Directory of Open Access Journals (Sweden)

    D. G. Lapitan

    2016-01-01

    Full Text Available The paper presents a  review of the research update on the blood microcirculation system assessed with laser Doppler flowmetry (LDF. Specific procedures for measurement of the microcirculation index by LDF and individual variability of microcirculation parameters during their real time assessment in vivo are discussed. In physiological conditions, a relative deviation of the results of measurements by LDF is within the range±35% and above from the mean value of the microcirculation index. This imposes certain limitations on the interpretation of the diagnostic results in terms of the “normal or pathologic”. Specifics of performance of functional stress tests on the microcirculation system are reviewed. Diagnostic criteria based on functional stress testing of the microcirculation system, which can be implemented with methodologically strict normatives and regulations, for examples, those for the occlusion test, are more reliable from metrologic perspective and significant compared to the results obtained without stress testing. Problems of implementation of the functional tests into clinical practice are discussed. It was shown that they may have a potentially wide spectrum of clinical indications, from functional diagnostics and early detection of microcirculatory abnormalities in diabetes mellitus, arterial hypertension and other diseases associated with microcirculatory disorders, to the physical rationale of exposure parameters, as well as objectification of efficiency of medical procedures aimed to stimulation of the microcirculatory functions in a patient's tissues and organs.

  9. An experimental system for the study of ultrasound exposure of isolated blood vessels

    International Nuclear Information System (INIS)

    Tokarczyk, Anna; Rivens, Ian; Symonds-Tayler, Richard; Ter Haar, Gail; Van Bavel, E

    2013-01-01

    An experimental system designed for the study of the effects of diagnostic or therapeutic ultrasound exposure on isolated blood vessels in the presence or absence of intraluminal contrast agent is described. The system comprised several components. A microscope was used to monitor vessel size (and thus vessel functionality), and potential leakage of intraluminal 70 kDa FITC-dextran fluorescence marker. A vessel chamber allowed the mounting of an isolated vessel whilst maintaining its viability, with pressure regulation for the control of intraluminal pressure and induction of flow for the infusion of contrast microbubbles. A fibre-optic hydrophone sensor mounted on the vessel chamber using a micromanipulator allowed pre-exposure targeting of the vessel to within 150 µm, and monitoring of acoustic cavitation emissions during exposures. Acoustic cavitation was also detected using changes in the ultrasound drive voltage and by detection of audible emissions using a submerged microphone. The suitability of this system for studying effects in the isolated vessel model has been demonstrated using a pilot study of 6 sham exposed and 18 high intensity focused ultrasound exposed vessels, with or without intraluminal contrast agent (SonoVue) within the vessels. (paper)

  10. Comparative Analysis of Clinical Samples Showing Weak Serum Reaction on AutoVue System Causing ABO Blood Typing Discrepancies.

    Science.gov (United States)

    Jo, Su Yeon; Lee, Ju Mi; Kim, Hye Lim; Sin, Kyeong Hwa; Lee, Hyeon Ji; Chang, Chulhun Ludgerus; Kim, Hyung Hoi

    2017-03-01

    ABO blood typing in pre-transfusion testing is a major component of the high workload in blood banks that therefore requires automation. We often experienced discrepant results from an automated system, especially weak serum reactions. We evaluated the discrepant results by the reference manual method to confirm ABO blood typing. In total, 13,113 blood samples were tested with the AutoVue system; all samples were run in parallel with the reference manual method according to the laboratory protocol. The AutoVue system confirmed ABO blood typing of 12,816 samples (97.7%), and these results were concordant with those of the manual method. The remaining 297 samples (2.3%) showed discrepant results in the AutoVue system and were confirmed by the manual method. The discrepant results involved weak serum reactions (serum reactions, samples from patients who had received stem cell transplants, ABO subgroups, and specific system error messages. Among the 98 samples showing ≤1+ reaction grade in the AutoVue system, 70 samples (71.4%) showed a normal serum reaction (≥2+ reaction grade) with the manual method, and 28 samples (28.6%) showed weak serum reaction in both methods. ABO blood tying of 97.7% samples could be confirmed by the AutoVue system and a small proportion (2.3%) needed to be re-evaluated by the manual method. Samples with a 2+ reaction grade in serum typing do not need to be evaluated manually, while those with ≤1+ reaction grade do.

  11. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

    International Nuclear Information System (INIS)

    Moroz, L.A.; MacLean, L.D.; Langleben, D.

    1986-01-01

    Fibrinolytic activities of whole blood and plasma were determined by 125 I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism

  12. Surface binding and uptake of cadmium (Cd2+) by LLC-PK1 cells on permeable membrane supports

    International Nuclear Information System (INIS)

    Prozialeck, W.C.; Lamar, P.C.

    1993-01-01

    Recent studies have shown that Cd 2+ has relatively specific damaging effects on cell-cell junctions in the renal epithelial cell line, LLC-PK 1 . The objective of the present studies was to examine the surface binding and uptake of Cd 2+ by LLC-PK 1 cells in relation to the disruption of cell-cell junctions. LLC-PK 1 cells on Falcon Cell Culture Inserts were exposed to CdCl 2 containing trace amounts of 109 Cd 2+ from either the apical or the basolateral compartments, and the accumulation of 109 Cd 2+ was monitored for up to 8 h. The integrity of cell-cell junctions was assessed by monitoring the transepithelial electrical resistance. The results showed that the cells accumulated 3-4 times more Cd 2+ from the basolateral compartment than from the apical compartment. The accumulation of Cd 2+ from the basolateral compartment occurred in two phases: a rapid, exponential phase that occurred in 1-2 h and coincided with a decrease in transepithelial resistance, and a slower, linear phase that continued for 6-8 h. The Cd 2+ that accumulated during the rapid phase was easily removed by washing the cells in EGTA, indicating that most of it was bound to sites on the cell surface. By contrast, most of the Cd 2+ that accumulated during the slower phase could not be removed by EGTA, indicating that it had been taken up by the cells. Additional studies showed that the rapid phase of Cd 2+ accumulation was enhanced when Ca 2+ was present at low concentrations (0.1 mM), and was greatly reduced when Ca 2+ was present at high concentrations (10 mM). These results suggest that ld 2+ damages the junctions between LLC-PK 1 cells by interacting with Ca 2+ -sensitive sites on the basolateral cell surface. (orig.)

  13. Study on the PK profiles of magnoflorine and its potential interaction in Cortex phellodendri decoction by LC-MS/MS.

    Science.gov (United States)

    Tian, Xiaoting; Li, Zhixiong; Lin, Yunfei; Chen, Mingcang; Pan, Guoyu; Huang, Chenggang

    2014-01-01

    Magnoflorine, an aporphine alkaloid in Cortex phellodendri, is increasingly attracting research attention because of its antidiabetic effects. However, at present, little information on its pharmacokinetics (PK) in vivo is available. In this study, a sensitive, rapid, and selective method was developed to determine the magnoflorine content in rat plasma using liquid chromatography-tandem mass spectrometry. Following liquid-liquid extraction, the calibration curve showed good linearity within the concentration range of 2.93 to 1,500 ng ml(-1). The intra- and inter-day precisions were all below 7.8 %, and the accuracy ranged from 94.9 to 103.4 %. The method was successfully applied in investigating the PK of magnoflorine in rats. The compound had low bioavailability, a high absorption rate, and a high elimination rate. However, area under the curve, T 1/2, and MRT increased approximately twofold when the same dosage of the compound was administered in a C. phellodendri decoction (20.8 g kg(-1)). Moreover, T max was prolonged from 0.3 to 3.33 h. Furthermore, a comparison of coadministration of the mixture group, magnoflorine (40 mg kg(-1)) and berberine (696.4 mg kg(-1)), with the C. phellodendri decoction group, revealed that no statistical difference (P > 0.05) was found in the parameter AUC, and certain similar changes in the PK trend to the herbal medicine group were also observed. These results suggested that oral administration of the herbal medicine decreased the absorption and elimination rates of magnoflorine and increased its bioavailability. Berberine played a significant role in interacting with magnoflorine and in affecting the PK profiles of magnoflorine in the C. phellodendri decoction group.

  14. Dual Identification and Analysis of Differentially Expressed Transcripts of Porcine PK-15 Cells and Toxoplasma gondii during in vitro Infection

    Directory of Open Access Journals (Sweden)

    Chun-Xue eZhou

    2016-05-01

    Full Text Available Toxoplasma gondii is responsible for causing toxoplasmosis, one of the most prevalent zoonotic parasitoses worldwide. The mechanisms that mediate T. gondii infection of pigs (the most common source of human infection and renal tissues are still unknown. To identify the critical alterations that take place in the transcriptome of both porcine kidney (PK-15 cells and T. gondii following infection, infected cell samples were collected at 1, 3, 6, 9, 12, 18, and 24 h post infection and RNA-Seq data were acquired using Illumina Deep Sequencing. Differential Expression of Genes (DEGs analysis was performed to study the concomitant gene-specific temporal patterns of induction of mRNA expression of PK-15 cells and T. gondii. High sequence coverage enabled us to thoroughly characterize T. gondii transcriptome and identify the activated molecular pathways in host cells. More than 6G clean bases/ sample, including > 40 million clean reads were obtained. These were aligned to the reference genome of T. gondii and wild boar (Sus scrofa. DEGs involved in metabolic activities of T. gondii showed time-dependent down-regulation. However, DEGs involved in immune or disease related pathways of PK-15 cells peaked at 6 h PI, and were highly enriched as evidenced by KEGG analysis. Protein-protein interaction analysis revealed that TGME49_120110 (PCNA, TGME49_049180 (DHFR-TS, TGME49_055320 and TGME49_002300 (ITPase are the four hub genes with most interactions with T. gondii at the onset of infection. These results reveal altered profiles of gene expressed by PK-15 cells and T. gondii during infection and provide the groundwork for future virulence studies to uncover the mechanisms of T. gondii interaction with porcine renal tissue by functional analysis of these DEGs.

  15. Effects on field- and bottom-layer species in an experiment with repeated PK- and NPK-fertilization

    International Nuclear Information System (INIS)

    Nohrstedt, H.Oe.

    1994-01-01

    Long-term changes in forest ground vegetation because of repeated PK- and NPK-fertilization were examined in an old field experiment, located in a 85-year-old Pinus sylvestris stand in northern Sweden. Fertilizers were added at 5-(PK, NPK) or 10-(PK) year intervals, beginning 26 years prior to the study. The treatments were tested in two replicates on plots sized 40 x 40 m. The total doses added were N 720 kg/ha, P 222-380 kg/ha and K 318-620 kg/ha. N was given as ammonium nitrate, P as superphosphate and K as potassium chloride. The vegetation on control plots was of the Vaccinium vitis-idaea type. The field layer was dominated by V.vitis-idaea and V.myrtillus, and the bottom layer by Pleurozium schreberi. The effect of fertilization was quantified by examining the areal cover of individual species. This was done in 25 0.25 m 2 frames systematically placed in a grid over each treatment plot. The only pronounced effect in the field layer was on V.myrtillus. The cover was strongly reduced by fertilization with PK. The reduction was 70% for the 5-year interval and 34% for the 10-year interval. The cover more than doubled after NPK-fertilization. Among the cryptogams, a reduction in cover was indicated for Cladina arbuscula and C.rangiferina because of fertilization with NPK. NPK reduced the number of species that were found, totally depending on negative effects on several lichen species. For species absent in the examined frame areas but present somewhere else on the treatment plots, it was seen that Deschampsia flexuosa increased after NPK-fertilization, while Peltigera apthosa and Steroecaulon tomentosum decreased. Hylocomium splendens occurred on both control plots, but only on one fertilized plot. 30 refs, 1 fig, 5 tabs

  16. Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

    International Nuclear Information System (INIS)

    Zhang, Hongling; Huang, Yong; Du, Qian; Luo, Xiaomao; Zhang, Liang; Zhao, Xiaomin; Tong, Dewen

    2015-01-01

    Highlights: • PPV reduces PK-15 cells viability by inducing apoptosis. • PPV infection induces apoptosis through mitochondria-mediated pathway. • PPV infection activates p53 to regulate the mitochondria apoptotic signaling. - Abstract: Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection

  17. Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

    International Nuclear Information System (INIS)

    Arriba, G. de; Perez de Hornedo, J.; Ramirez Rubio, S.; Calvino Fernandez, M.; Benito Martinez, S.; Maiques Camarero, M.; Parra Cid, T.

    2009-01-01

    Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry and confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.

  18. Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hongling; Huang, Yong; Du, Qian; Luo, Xiaomao; Zhang, Liang; Zhao, Xiaomin; Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn

    2015-01-09

    Highlights: • PPV reduces PK-15 cells viability by inducing apoptosis. • PPV infection induces apoptosis through mitochondria-mediated pathway. • PPV infection activates p53 to regulate the mitochondria apoptotic signaling. - Abstract: Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection.

  19. Tainted blood

    DEFF Research Database (Denmark)

    Deleuran, Ida; Sheikh, Zainab Afshan; Hoeyer, Klaus

    2015-01-01

    The existing literature on donor screening in transfusion medicine tends to distinguish between social concerns about discrimination and medical concerns about safety. In this article, we argue that the bifurcation into social and medical concerns is problematic. We build our case on a qualitative...... study of the historical rise and current workings of safety practices in the Danish blood system. Here, we identify a strong focus on contamination in order to avoid 'tainted blood', at the expense of working with risks that could be avoided through enhanced blood monitoring practices. Of further...... significance to this focus are the social dynamics found at the heart of safety practices aimed at avoiding contamination. We argue that such dynamics need more attention, in order to achieve good health outcomes in transfusion medicine. Thus, we conclude that, to ensure continuously safe blood systems, we...

  20. DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair.

    Science.gov (United States)

    Serrano, M A; Li, Z; Dangeti, M; Musich, P R; Patrick, S; Roginskaya, M; Cartwright, B; Zou, Y

    2013-05-09

    Homologous recombination (HR) and nonhomologous end joining (NHEJ) are two distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-dependent protein kinase (DNA-PK), the core component of NHEJ, partnering with DNA-damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), regulates HR repair of DSBs. The regulation was accomplished through modulation of the p53 and replication protein A (RPA) interaction. We show that upon DNA damage, p53 and RPA were freed from a p53-RPA complex by simultaneous phosphorylations of RPA at the N-terminus of RPA32 subunit by DNA-PK and of p53 at Ser37 and Ser46 in a Chk1/Chk2-independent manner by ATR and ATM, respectively. Neither the phosphorylation of RPA nor of p53 alone could dissociate p53 and RPA. Furthermore, disruption of the release significantly compromised HR repair of DSBs. Our results reveal a mechanism for the crosstalk between HR repair and NHEJ through the co-regulation of p53-RPA interaction by DNA-PK, ATM and ATR.

  1. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity

    International Nuclear Information System (INIS)

    Dittmann, Klaus; Mayer, Claus; Rodemann, Hans-Peter

    2005-01-01

    Background and purpose: Inhibition of EGFR-function can induce radiosensitization in tumor cells. Purpose of our investigation was to identify the possible molecular mechanism of radiosensitization following treatment with anti-EGFR-antibody C225 (Cetuximab). Materials and methods: The effect of C225 on radiation response was determined in human cell lines of bronchial carcinoma (A549) and breast adenoma cells (MDA MB 231). The molecular effects of C225 on EGFR-function after irradiation were analyzed applying western blotting, immune-precipitation and kinase assays. Effects on DNA-repair were detected by quantification of γ-H2AX positive foci 24 h after irradiation. Results: The EGFR specific antibody C225 induced radiosensitization in A549 and also in MDA MB 231 cells. Radiosensitization in A549 was associated with blockage of radiation-induced EGFR transport into the nucleus, and immobilized the complex of EGFR with DNA-dependent protein kinase (DNA-PK) in the cytoplasm. As a consequence radiation-induced DNA-PK activation was abolished, a process that is essential for DNA-repair after radiation exposure. Likewise C225 treatment increased the residual amount of γ-H2AX-positive foci 24 h after irradiation in A549 and in MDA MB 231 cells. Conclusions: Our results suggest that irradiation induced DNA-PK activation-essential for DNA repair-may be hampered specifically by use of the anti-EGFR-antibody C225. This process is associated with radiosensitization

  2. Latanoprost systemic exposure in pediatric and adult patients with glaucoma

    DEFF Research Database (Denmark)

    Raber, Susan; Courtney, Rachel; Maeda-Chubachi, Tomoko

    2011-01-01

    To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose.......To evaluate short-term safety and steady-state systemic pharmacokinetics (PK) of latanoprost acid in pediatric subjects with glaucoma or ocular hypertension who received the adult latanoprost dose....

  3. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation....

  4. An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images

    Science.gov (United States)

    Chin Neoh, Siew; Srisukkham, Worawut; Zhang, Li; Todryk, Stephen; Greystoke, Brigit; Peng Lim, Chee; Alamgir Hossain, Mohammed; Aslam, Nauman

    2015-01-01

    This research proposes an intelligent decision support system for acute lymphoblastic leukaemia diagnosis from microscopic blood images. A novel clustering algorithm with stimulating discriminant measures (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of nucleus and cytoplasm of lymphocytes/lymphoblasts. Specifically, the proposed between-cluster evaluation is formulated based on the trade-off of several between-cluster measures of well-known feature extraction methods. The SDM measures are used in conjuction with Genetic Algorithm for clustering nucleus, cytoplasm, and background regions. Subsequently, a total of eighty features consisting of shape, texture, and colour information of the nucleus and cytoplasm sub-images are extracted. A number of classifiers (multi-layer perceptron, Support Vector Machine (SVM) and Dempster-Shafer ensemble) are employed for lymphocyte/lymphoblast classification. Evaluated with the ALL-IDB2 database, the proposed SDM-based clustering overcomes the shortcomings of Fuzzy C-means which focuses purely on within-cluster scatter variance. It also outperforms Linear Discriminant Analysis and Fuzzy Compactness and Separation for nucleus-cytoplasm separation. The overall system achieves superior recognition rates of 96.72% and 96.67% accuracies using bootstrapping and 10-fold cross validation with Dempster-Shafer and SVM, respectively. The results also compare favourably with those reported in the literature, indicating the usefulness of the proposed SDM-based clustering method. PMID:26450665

  5. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    Science.gov (United States)

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

  6. Confidence limits for regional cerebral blood flow values obtained with circular positron system, using krypton-77

    International Nuclear Information System (INIS)

    Meyer, E.; Yamamoto, Y.L.; Thompson, C.J.

    1978-01-01

    The 90% confidence limits have been determined for regional cerebral blood flow (rCBF) values obtained in each cm 2 of a cross section of the human head after inhalation of radioactive krypton-77, using the MNI circular positron emission tomography system (Positome). CBF values for small brain tissue elements are calculated by linear regression analysis on the semi-logarithmically transformed clearance curve. A computer program displays CBF values and their estimated error in numeric and gray scale forms. The following typical results have been obtained on a control subject: mean CBF in the entire cross section of the head: 54.6 + - 5 ml/min/100 g tissue, rCBF for small area of frontal gray matter: 75.8 + - 9 ml/min/100 g tissue. Confidence intervals for individual rCBF values varied between + - 13 and + - 55% except for areas pertaining to the ventricular system where particularly poor statistics have been obtained. Knowledge of confidence limits for rCBF values improves their diagnostic significance, particularly with respect to the assessment of reduced rCBF in stroke patients. A nomogram for convenient determination of 90% confidence limits for slope values obtained in linear regression analysis has been designed with the number of fitted points (n) and the correlation coefficient (r) as parameters. (author)

  7. Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results

    Directory of Open Access Journals (Sweden)

    C. Pizzorni

    2011-06-01

    Full Text Available Objectives: Systemic sclerosis (SSc is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Methods: 27 SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns (“Early”, “Active”, “Late”. LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36°C. Statistical evaluation was carried out by non-parametric procedures. Results: Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05. The heating of the probe to 36°C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05, however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05. The SSc patients with NVC “Late” pattern, showed lower values of peripheral blood flow than patients with NVC “Active” or “Early” patterns (p<0.05. Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud’s phenomenon (p <0.03. Conclusions: LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC.

  8. [Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results].

    Science.gov (United States)

    Secchi, M E; Sulli, A; Pizzorni, C; Cutolo, M

    2009-01-01

    Systemic sclerosis (SSc) is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC) is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF) can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Twenty-seven SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns ("Early", "Active", "Late"). LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36 degrees C. Statistical evaluation was carried out by non-parametric procedures. Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05). The heating of the probe to 36 degrees C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05), however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05). The SSc patients with NVC "Late" pattern, showed lower values of peripheral blood flow than patients with NVC "Active" or "Early" patterns (p<0.05). Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud's phenomenon (p <0.03). LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC.

  9. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of sympathetic nervous system.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Suh, Hong-Won

    2012-07-01

    The relationship between interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. We found in the present study that intrathecal (i.t.) injection of IL-1β increased pain behavior. In addition, i.t. IL-1β injection caused an elevation of the blood glucose level. The time-course study showed that maximal blood glucose level was observed 30 and 60 min after i.t. IL-1β administration. Furthermore, i.t. injection of IL-1β enhanced the blood glucose level when mice were orally fed with d-glucose. The i.t. administration of IL-1β antagonist (AF12198) inhibited the hyperglycemia and pain behaviors induced by IL-1β. We found in the present study that adrenal tyrosine hydroxylase (TH) mRNA level was also increased by i.t. IL-1β injection. Furthermore, intraperitoneal (i.p.) pretreatment with phentolamine (an α(1)-adrenergic blocker) or yohimbine (an α(2)-adrenergic blocker) significantly attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. However, the blood glucose level and pain behavior were not affected by butoxamine (a β(2)-adrenergic blocker), whereas metoprolol (a β(2)-adrenergic blocker) enhanced IL-1β-induced blood glucose level and pain behavior in mice fed with d-glucose. However, its effect was not statistically significant. Our results suggest that IL-1β administered i.t. increases the blood glucose level via an activation of α adrenergic nervous system. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. A method for red blood cell biotinylation in a closed system

    NARCIS (Netherlands)

    de Back, Djuna Z.; Vlaar, Richard; Beuger, Boukje; Daal, Brunette; Lagerberg, Johan; Vlaar, Alexander P. J.; de Korte, Dirk; van Kraaij, Marian; van Bruggen, Robin

    2018-01-01

    Several circumstances require the accurate measurement of red blood cell (RBC) survival and clearance, such as determination of posttransfusion recovery of stored RBCs to investigate the effect of new additive solutions. To this end, biotin as a marker of RBCs to track donor RBCs in the blood of the

  11. Cationic liposomal drug delivery system for specific targeting of human cd14+ monocytes in whole blood

    DEFF Research Database (Denmark)

    2013-01-01

    blood when compared to adherence to granulocytes, T-lymphocytes, B- lymphocytes and/or NK cells in freshly drawn blood, to a lipid-based pharmaceutical composition comprising said liposomes and their use in monocytic associated prophylaxis, treatment or amelioration of a condition such as cancer...

  12. Donor Tracker: An Innovative Real-Time Tracking System for Blood ...

    African Journals Online (AJOL)

    In this paper, we explore the possibility of using location-aware computing to track blood donors in Mauritius and locate the nearest donor in cases of emergencies and whenever fresh blood is ... Keywords: Context-awareness, location-awareness, mobile and ubiquitous computing, location sensing technique, real-time.

  13. Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

    Science.gov (United States)

    Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

    2015-01-14

    The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. Copyright © 2015 the authors 0270-6474/15/350518-09$15.00/0.

  14. Improvement of a sensor unit for wrist blood pressure monitoring system

    Science.gov (United States)

    Koo, Sangjun; Kwon, Jongwon; Park, Yongman; Ayuzenara, Odgerel; Kim, Hiesik

    2007-12-01

    A blood pressure sensor unit for ubiquitous healthcare monitoring was newly developed. The digital wrist band-type blood pressure devices for home are popular already in the market. It is useful for checking blood pressure level at home and control of hypertension. Especially, it is very essential home device to check the health condition of blood circulation disease. Nowadays many product types are available. But the measurement of blood pressure is not accurate enough compared with the mechanical type. It needs to be upgraded to assure the precise health data enough to use in the hospital. The structure, feature and output signal of capacitor type pressure sensors are analyzed. An improved design of capacitor sensor is suggested. It shows more precise health data after use on a wrist band type health unit. They can be applied for remote u-health medical service.

  15. Transcellular transport of radioiodinated 3-iodo-α-methyl-L-tyrosine across monolayers of kidney epithelial cell line LLC-PK1

    International Nuclear Information System (INIS)

    Shikano, Naoto; Nakajima, Syuichi; Kubota, Nobuo; Ishikawa, Nobuyoshi; Kawai, Keiichi; Kubodera, Akiko; Saji, Hideo

    2004-01-01

    3-[ 123 I]iodo-α-methyl-L-tyrosine ([ 123 I]IMT) is an imaging agent for amino acid transport. In order to obtain fundamental data related to tumor imaging with [ 123 I]IMT and renal physiological accumulation of [ 123 I]IMT, we investigated the transport characteristics of [ 125 I]IMT in porcine kidney epithelial cell line LLC-PK 1 using cell monolayers grown on microporous membrane filters. LLC-PK 1 monolayers were created on a collagen-coated microporous (3 μm) membrane (4.7 cm 2 ). To examine transcellular transport (secretion and reabsorption) and accumulation, the monolayers were incubated for up to 90 min at 37 deg C with 18.5 kBq [ 125 I]IMT in Dulbecco's phosphate-buffered saline (pH 7.4) as an uptake solution. After incubation, transcellular transport was assessed by quantifying the radioactivity of the solutions on each side of the monolayer. For the accumulation experiment, the cells were solubilized in NaOH solution, and the radioactivity was quantified. For the inhibition experiment, the inhibitor was added at a final concentration of 1 mM. For the pH dependence experiment, the pH of the apical-side uptake solution was varied from pH 5 to pH 8. Transport of [ 14 C]Tyr was examined for comparison. Bi-directional transcellular transport of [ 125 I]IMT was observed, corresponding to secretion and reabsorption in proximal tubule. Accumulation of [ 125 I]IMT from the basolateral side (1.62±0.15%) and the apical side (2.62±0.35%) was observed at 90 min. 2-Amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L), L -Tyr (mother compound of [ 125 I]IMT) and 2-aminoisobutyric acid (an inhibitor of system L and A) inhibited both directional transport (p 125 I]IMT from both sides (p 125 I]IMT transport is system L, rather than Na + -dependent transport, in both apical and basolateral membrane. [ 125 I]IMT was transported by the system that transported L-Tyr, but the observed pH dependence of transport suggests that different

  16. DNA-activated protein kinase (DNA-PK) and significance in its responses to radiation. The end is the beginning of the story

    International Nuclear Information System (INIS)

    Matsumoto, Yoshihisa

    1996-01-01

    This review described findings hitherto and future perspective on the DNA-PK. The enzyme was activated by double-strand DNA, required the end of the DNA and was the major component of p350 protein. Ku-antigen (an autoimmune antigen) was found a subunit. It phosphorylated p53, c-Myc, RPAp34, DNA ligase I, DNA topoisomerase I and II. Therefore DNA-PK can be a trigger factor which recognizes DNA break induced by radiation, and phosphorylates proteins participating in the DNA repair, cell cycle regulation and cell death. Recently p350 was found to be a responsible gene product to SCID syndrome of mice hypersensitive to ionizing radiation. The review included; On the DNA-PK: Discovery, relation to Ku antigen and molecular properties. On the DNA-PK and radiation sensitivity, and V(D)J recombination: Ku80 was the product of X-ray repair cross-complementing (XRCC). p350 was found the gene product whose lack causing SCID syndrome of radiosensitive mice. On the significance of phosphorylation of DNA-PK and the substrate: p53. RPA (replication protein A, alias RF-A or SSB). P1/MCM3, a possible substrate. On the other properties of DNA-PK: DNA-helicase activity. Suppression of transcription by RNA polymerase. DNA-PKp350 and ATM (ataxia-telangiectasia). Family molecules of p53 and ATM (MEI-41, Tel1p and Mec1p, and Rad3). (H.O). 70 refs

  17. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation.

    Science.gov (United States)

    Licata, Stephanie C; Lowen, Steven B; Trksak, George H; Maclean, Robert R; Lukas, Scott E

    2011-08-15

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABA(A) receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 min after acute oral administration of zolpidem (0, 5, 10, or 20mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem's modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABA(A) receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Fluorescent blood glucose monitor by hemin-functionalized graphene quantum dots based sensing system

    Energy Technology Data Exchange (ETDEWEB)

    He, Yuezhen; Wang, Xiaoxun; Sun, Jian; Jiao, Shoufeng; Chen, Hongqi; Gao, Feng; Wang, Lun, E-mail: wanglun@mail.ahnu.edu.cn

    2014-01-31

    Graphical abstract: -- Highlights: •Hemin is assembled onto the surfaces of graphene quantum dots (GQDs). •With the aid of hemin, H{sub 2}O{sub 2} could quench the FL signal of GQDs obviously. •Based on this effect, a fluorescent platform is proposed for the sensing of glucose. •The proposed method provides a new pathway to explore practical application of GQDs. -- Abstract: In the present work, a highly sensitive and specific fluorescent biosensor for blood glucose monitoring is developed based on hemin-functionalized graphene quantum dots (GQDs) and glucose oxidase (GOx) system. The GQDs which are simply prepared by pyrolyzing citric acid exhibit strong fluorescence and good water-solubility. Due to the noncovalent assembly between hemin and GQDs, the addition of hemin can make hydrogen peroxide (H{sub 2}O{sub 2}) to destroy the passivated surface of GQDs, leading to significant fluorescence quenching of GQDs. Based on this effect, a novel fluorescent platform is proposed for the sensing of glucose. Under the optimized conditions, the linear range of glucose is from 9 to 300 μM, and the limit of detection is 0.1 μM. As unique properties of GQDs, the proposed biosensor is green, simple, cost-efficient, and it is successfully applied to the determination of glucose in human serum. In addition, the proposed method provides a new pathway to further design the biosensors based on the assembly of GQDs with hemin for detection of biomolecules.

  19. Gpr124 is essential for blood-brain barrier integrity in central nervous system disease.

    Science.gov (United States)

    Chang, Junlei; Mancuso, Michael R; Maier, Carolina; Liang, Xibin; Yuki, Kanako; Yang, Lu; Kwong, Jeffrey W; Wang, Jing; Rao, Varsha; Vallon, Mario; Kosinski, Cynthia; Zhang, J J Haijing; Mah, Amanda T; Xu, Lijun; Li, Le; Gholamin, Sharareh; Reyes, Teresa F; Li, Rui; Kuhnert, Frank; Han, Xiaoyuan; Yuan, Jenny; Chiou, Shin-Heng; Brettman, Ari D; Daly, Lauren; Corney, David C; Cheshier, Samuel H; Shortliffe, Linda D; Wu, Xiwei; Snyder, Michael; Chan, Pak; Giffard, Rona G; Chang, Howard Y; Andreasson, Katrin; Kuo, Calvin J

    2017-04-01

    Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling. Constitutive activation of Wnt-β-catenin signaling fully corrected the BBB disruption and hemorrhage defects of Gpr124-CKO mice, with rescue of the endothelial gene tight junction, pericyte coverage and extracellular-matrix deficits. We thus identify Gpr124 as an endothelial GPCR specifically required for endothelial Wnt signaling and BBB integrity under pathological conditions in adult mice. This finding implicates Gpr124 as a potential therapeutic target for human CNS disorders characterized by BBB disruption.

  20. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    Science.gov (United States)

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess the effects of zolpidem within the brain. Healthy participants (n=12) were scanned 60 minutes after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured in the visual cortex during presentation of a flashing checkerboard. Heart rate and oxygen saturation were monitored continuously throughout the session. Zolpidem (10 and 20 mg) reduced the robust visual system activation produced by presentation of this stimulus, but had no effects on physiological activity during the fMRI scan. Zolpidem’s modulation of the BOLD signal within the visual cortex is consistent with the abundant distribution of GABAA receptors localized in this region, as well as previous studies showing a relationship between increased GABA-mediated neuronal inhibition and a reduction in BOLD activation. PMID:21640782

  1. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events.

    Science.gov (United States)

    Kario, Kazuomi

    2016-07-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events.

  2. System Identification Algorithm Analysis of Acupuncture Effect on Mean Blood Flux of Contralateral Hegu Acupoint

    Directory of Open Access Journals (Sweden)

    Guangjun Wang

    2012-01-01

    Full Text Available Background. Acupoints (belonging to 12 meridians which have the same names are symmetrically distributed on the body. It has been proved that acupoints have certain biological specificities different from the normal parts of the body. However, there is little evidence that acupoints which have the same name and are located bilaterally and symmetrically have lateralized specificity. Thus, researching the lateralized specificity and the relationship between left-side and right-side acupuncture is of special importance. Methodology and Principal Findings. The mean blood flux (MBF in both Hegu acupoints was measured by Moor full-field laser perfusion imager. With the method of system identification algorithm, the output distribution in different groups was acquired, based on different acupoint stimulation and standard signal input. It is demonstrated that after stimulation of the right Hegu acupoint by needle, the output value of MBF in contralateral Hegu acupoint was strongly amplified, while after acupuncturing the left Hegu acupoint, the output value of MBF in either side Hegu acupoint was amplified moderately. Conclusions and Significance. This paper indicates that the Hegu acupoint has lateralized specificity. After stimulating the ipsilateral Hegu acupoint, symmetry breaking will be produced in contrast to contralateral Hegu acupoint stimulation.

  3. Thermal degradation kinetics of xanthophylls from blood orange in model and real food systems.

    Science.gov (United States)

    Hadjal, Thiziri; Dhuique-Mayer, Claudie; Madani, Khodir; Dornier, Manuel; Achir, Nawel

    2013-06-15

    Thermal degradation kinetics of the major blood orange xanthophylls (cis-violaxanthin, lutein, β-cryptoxanthin, zeaxanthin and cis-antheraxanthin) were investigated at 45, 60, 75, and 90°C in real juice and three model systems formulated to evaluate the impact of xanthophyll form (esterified or free) and pH (acid or neutral). Xanthophylls were monitored by HPLC-DAD and kinetic parameters were identified by non-linear regression. A second order model best fitted the degradation curves of xanthophylls. All degradation rates were the lowest in real juice. Esterified forms were more stable than were the free forms. In all acidic media, β-cryptoxanthin exhibited the lowest degradation rates followed by lutein and zeaxanthin. In comparison, the epoxy carotenoids cis-violaxanthin and cis-antheraxanthin degraded around 3-fold faster in their esterified form. In their free form, cis-antheraxanthin degraded 30-fold faster while cis-violaxanthin instantaneously disappeared because of the isomerisation of its 5,6-epoxy groups into 5,8-epoxy. By contrast, in neutral medium, free epoxy-xanthophylls were about 2-fold more stable than were the free hydroxy xanthophylls lutein, zeaxanthin and β-cryptoxanthin. Kinetic behaviours of xanthophylls were closely dependent on their chemical structures. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. [Evaluation of a new blood gas analysis system: RapidPoint 500(®)].

    Science.gov (United States)

    Nicolas, Thierry; Cabrolier, Nadège; Bardonnet, Karine; Davani, Siamak

    2013-01-01

    We present here evaluation of a new blood gas analysis system, RapidPoint 500(®) (Siemens Healthcare Diagnostics). The aim of this research was to compare the ergonomics and analytical performances of this analyser with those of the RapidLab 1265 for the following parameters: pH, partial oxygen pressure, partial carbon dioxide pressure, sodium, potassium, ionized calcium, lactate and the CO-oximetry parameters: hemoglobin, oxyhemoglobin, carboxyhemoglobin, methemoglobin, reduced hemoglobin, neonatal bilirubin; as well as with the Dimension Vista 500 results for chloride and glucose. The Valtec protocol, recommended by the French Society of Clinical Biology (SFBC), was used to analyze the study results. The experiment was carried out over a period of one month in the Department of medical biochemistry. One hundred sixty five samples from adult patients admitted to the ER or hospitalized in intensive care were tested. The RapidPoint 500(®) was highly satisfactory from an ergonomic point of view. Intra-and inter- assay coefficients of variation (CV) with the three control levels were below those recommended by the SFBC for all parameters, and the comparative study gave coefficients of determination higher than 0.91. Taken together, the RapidPoint 500(®) appears fully satisfactory in terms of ergonomics and analytical performance.

  5. The characterization of NMR signal for blood pressure monitoring system and its testing

    Directory of Open Access Journals (Sweden)

    Bambang Murdaka Eka Jati

    2016-02-01

    Full Text Available ABSTRACT A blood monitoring system based on NMR method has been designed on constructed. This set-up of equipment used magnetic permanent, radio frequency (RF, receiver coil (RC, function generator (FG, amplifier which included the filter, as well as the oscilloscope digital storage. The background of this research was based on the sensitivity of NMR signal. The signal must be separated from signals background. This method was done by adjusting the frequency on FG, which was connected to radio frequency (RF coil, on empty sample. Subsequently, NMR signal was received by RC, and that signal could be shown on oscilloscope at resonance condition. The true frequency on NMR signal was Larmor frequency, and the other was background. The two variables of this experiment were the position of RF coil and the location temperature (20 up to 30oC. In conclusion, the resonance frequency of NMR signal (as Larmor frequency was 4.7 MHz (at static magnetic field of 1,600 gauss and it could be separated from background signals (3.4 and 6.2 MHz, and that signal was almost constant to room temperature. The equipment was used for sample testing. It gave systole/diastole data of 110/70 mmHg (on sphygmomanometer that was similar to 17/9 mV (on NMR signal. ABSTRAK Telah dikembangkan alat pemantauan tekanan darah berdasar prinsip NMR.

  6. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system philadelphia chromosome positive leukemia

    NARCIS (Netherlands)

    K. Porkka (Kimmo); P. Koskenvesa (Perttu); T. Lundan (Tuija); J. Rimpiläinen (Johanna); S. Mustjoki (Satu); R. Smykla (Richard); R. Wild (Robert); R. Luo (Roger); M. Arnan (Montserrat); B. Brethon (Benoit); L. Eccersley (Lydia); H. Hjorth-Hansen (Henrik); M. Höglund (Martin); H. Klamova (Hana); H. Knutsen (Håvar); S. Parikh (Suhag); E. Raffoux (Emmanuel); F. Gruber (Franz); F. Brito-Babapulle (Finella); H. Dombret (Hervé); R.F. Duarte (Rafael); E. Elonen (Erkki); R. Paquette (Ron); C.M. Zwaan (Christian Michel); F.Y.F. Lee (Francis)

    2008-01-01

    textabstractAlthough imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph+) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasatinib (a

  7. Renal hyperfiltration and systemic blood pressure in patients with uncomplicated type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Gary K Yang

    Full Text Available Patients with type 1 diabetes mellitus (DM and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m(2 or normofiltration (n = 40, DM-N, and 56 healthy controls (HC. Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.BP, glomerular filtration rate (GFR - inulin, effective renal plasma flow (paraaminohippurate and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L. Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L.Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2, p<0.0001. Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004 and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001 were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01. GFR (p<0.0001 and SBP (p<0.0001 increased during hyperglycemia in DM-N but not in DM-H.DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

  8. Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

    Science.gov (United States)

    Morita, Shigemichi; Takahashi, Toshiya; Yoshida, Yasushi; Yokota, Naohisa

    2016-04-01

    Hydroxychloroquine (HCQ) is an effective treatment for patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) and has been used for these patients in more than 70 nations. However, in Japan, HCQ has not been approved for CLE or SLE. To establish an appropriate therapeutic regimen and to clarify the pharmacokinetics (PK) of HCQ in Japanese patients with CLE with or without SLE (CLE/SLE), a population pharmacokinetic (PopPK) analysis was performed. In a clinical study of Japanese patients with a diagnosis of CLE irrespective of the presence of SLE, blood and plasma drug concentration-time data receiving multiple oral doses of HCQ sulfate (200-400 mg daily) were analyzed using nonlinear mixed-effects model software. The blood and plasma concentrations of HCQ were analyzed using a high-performance liquid chromatography tandem mass spectrometry method. Model evaluation and validation were performed using goodness-of-fit (GOF) plots, visual predictive check, and a bootstrap. The PopPKs of HCQ in the blood and plasma of 90 Japanese patients with CLE/SLE were well described by a 1-compartment model with first-order absorption and absorption lag time. Body weight was a significant (P < 0.001) covariate of oral clearance of HCQ. The final model was assessed using GOF plots, a bootstrap, and visual predictive check, and this model was appropriate. Simulations based on the final model suggested that the recommended daily doses of HCQ sulfate (200-400 mg) based on the ideal body weight in Japanese patients with CLE/SLE were in the similar concentration ranges. The PopPK models derived from both blood and plasma HCQ concentrations of Japanese patients with CLE/SLE were developed and validated. Based on this study, the dosage regimens of HCQ sulfate for Japanese patients with CLE/SLE should be calculated using the individual ideal body weight.

  9. SMA Diagnosis: Detection of SMN1 Deletion with Real-Time mCOP-PCR System Using Fresh Blood DNA.

    Science.gov (United States)

    Niba, Emma Tabe Eko; Ar Rochmah, Mawaddah; Harahap, Nur Imma Fatimah; Awano, Hiroyuki; Morioka, Ichiro; Iijima, Kazumoto; Saito, Toshio; Saito, Kayoko; Takeuchi, Atsuko; Lai, Poh San; Bouike, Yoshihiro; Nishio, Hisahide; Shinohara, Masakazu

    2017-12-18

    Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders. The symptoms are caused by defects of lower motor neurons in the spinal cord. More than 95% of SMA patients are homozygous for survival motor neuron 1 (SMN1) deletion. We previously developed a screening system for SMN1 deletion based on a modified competitive oligonucleotide priming-PCR (mCOP-PCR) technique using dried blood spot (DBS) on filter paper. This system is convenient for mass screening in the large population and/or first-tier diagnostic method of the patients in the remote areas. However, this system was still time-consuming and effort-taking, because it required pre-amplification procedure to avoid non-specific amplification and gel-electrophoresis to detect the presence or absence of SMN1 deletion. When the fresh blood samples are used instead of DBS, or when the gel-electrophoresis is replaced by real-time PCR, we may have a simpler and more rapid diagnostic method for SMA. To establish a simpler and more rapid diagnostic method of SMN1 deletion using fresh blood DNA. DNA samples extracted from fresh blood and stored at 4 ℃ for 1 month. The samples were assayed using a real-time mCOP-PCR system without pre-amplification procedures. DNA samples had already been genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP), showing the presence or absence of SMN1 exon 7. The DNA samples were directly subjected to the mCOP-PCR step. The amplification of mCOP-PCR was monitored in a real-time PCR apparatus. The genotyping results of the real-time mCOP-PCR system using fresh blood DNA were completely matched with those of PCR-RFLP. In this real-time mCOP-PCR system using fresh blood-DNA, it took only four hours from extraction of DNA to detection of the presence or absence of SMN1 deletion, while it took more than 12 hours in PCR-RFLP. Our real-time mCOP-PCR system using fresh blood DNA was rapid and accurate, suggesting it may be useful for the first

  10. PK-PD Integration Modeling and Cutoff Value of Florfenicol against Streptococcus suis in Pigs

    Directory of Open Access Journals (Sweden)

    Zhixin Lei

    2018-01-01

    Full Text Available The aims of the present study were to establish optimal doses and provide an alternate COPD for florfenicol against Streptococcus suis based on pharmacokinetic-pharmacodynamic integration modeling. The recommended dose (30 mg/kg b.w. were administered in healthy pigs through intramuscular and intravenous routes for pharmacokinetic studies. The main pharmacokinetic parameters of Cmax, AUC0-24h, AUC, Ke, t1/2ke, MRT, Tmax, and Clb, were estimated as 4.44 μg/ml, 88.85 μg⋅h/ml, 158.56 μg⋅h/ml, 0.048 h-1, 14.46 h, 26.11 h, 4 h and 0.185 L/h⋅kg, respectively. The bioavailability of florfenicol was calculated to be 99.14% after I.M administration. A total of 124 Streptococcus suis from most cities of China were isolated to determine the minimum inhibitory concentration (MIC of florfenicol. The MIC50 and MIC90 were calculated as 1 and 2 μg/ml. A serotype 2 Streptococcus suis (WH-2, with MIC value similar to MIC90, was selected as a representative for an in vitro and ex vivo pharmacodynamics study. The MIC values of WH-2 in TSB and plasma were 2 μg/ml, and the MBC/MIC ratios were 2 in TSB and plasma. The MPC was detected to be 3.2 μg/ml. According to inhibitory sigmoid Emax model, plasma AUC0-24h/MIC values of florfenicol versus Streptococcus suis were 37.89, 44.02, and 46.42 h for the bactericidal, bacteriostatic, and elimination activity, respectively. Monte Carlo simulations the optimal doses for bactericidal, bacteriostatic, and elimination effects were calculated as 16.5, 19.17, and 20.14 mg/kg b.w. for 50% target attainment rates (TAR, and 21.55, 25.02, and 26.85 mg/kg b.w. for 90% TAR, respectively. The PK-PD cutoff value (COPD analyzed from MCS for florfenicol against Streptococcus suis was 1 μg/ml which could provide a sensitivity cutoff value. These results contributed an optimized alternative to clinical veterinary medicine and showed that the dose of 25.02 mg/kg florfenicol for 24 h could have a bactericidal action against

  11. Factors Related to Blood Hydroxychloroquine Concentration in Patients With Systemic Lupus Erythematosus.

    Science.gov (United States)

    Yeon Lee, Ji; Lee, Jennifer; Ki Kwok, Seung; Hyeon Ju, Ji; Su Park, Kyung; Park, Sung-Hwan

    2017-04-01

    To identify factors associated with blood concentrations of hydroxychloroquine (HCQ) and its major metabolite, N-desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE; lupus) receiving long-term oral HCQ treatment. SLE patients who had been taking HCQ for more than 3 months were recruited. Various clinical characteristics, laboratory values, and SLE Disease Activity Index (SLEDAI) scores were examined. The concentrations of HCQ and DHCQ ([HCQ] and [DHCQ]) were measured by liquid chromatography mass spectrometry, and the relationship between [HCQ], [DHCQ], and [HCQ]:[DHCQ] ratio to various factors was investigated. In total, 189 SLE patients receiving long-term HCQ treatment were included in the analysis. The median (interquartile range [IQR]) [HCQ] was 515 (IQR 353-720) ng/ml, the median [DHCQ] was 417 (IQR 266-591) ng/ml, and the median [HCQ]:[DHCQ] ratio was 1.3 (range 1.0-1.7). [HCQ] was closely associated with [DHCQ] (r = 0.81, P < 0.0001). The weight-adjusted oral HCQ dose was strongly associated with both [HCQ] (P < 0.001) and [DHCQ] (P < 0.001). Time since last dose was associated with [HCQ] (P < 0.001). No statistically significant association was found between renal function or smoking and [HCQ] or [DHCQ]. Use of additional immunosuppressants increased both [HCQ] and [DHCQ] after adjusting for possible confounders (P = 0.04 and P = 0.03, respectively). The lower SLEDAI score was significantly related to higher [HCQ], after adjusting for age, sex, weight-adjusted HCQ dose, time since last dose, number of other immunosuppressants, and smoking status (P = 0.007). Various factors affected blood levels of [HCQ], [DHCQ], or the [HCQ]:[DHCQ] ratio of SLE patients receiving long-term oral HCQ treatment. Notably, higher [HCQ] was associated with a lower SLEDAI score in our typical outpatient clinic population with lupus. © 2016, American College of Rheumatology.

  12. Iron telluride nanorods-based system for the detection of total mercury in blood

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Prathik; Lin, Zong-Hong [Department of Chemistry, National Taiwan University, 1, Section 4, Roosevelt Road, Taipei 106, Taiwan (China); Liang, Chi-Te [Department of Physics, National Taiwan University, 1, Section 4, Roosevelt Road, Taipei 106, Taiwan (China); Chang, Huan-Tsung, E-mail: changht@ntu.edu.tw [Department of Chemistry, National Taiwan University, 1, Section 4, Roosevelt Road, Taipei 106, Taiwan (China)

    2012-12-15

    Graphical abstract: Elucidation of the detection of mercury using iron telluride nanorods (FeTe NRs), and dose-response curve for varying concentrations of Hg{sup 2+}. Highlights: Black-Right-Pointing-Pointer Iron telluride nanorods (FeTe NRs) are prepared from tellurium nanowires (Te NWs). Black-Right-Pointing-Pointer Mercury telluride nanorods (HgTe NRs) form by cation exchange reaction of FeTe NRs. Black-Right-Pointing-Pointer Fe{sup 2+} ions released catalyze the oxidation of ABTS by H{sub 2}O{sub 2}. Black-Right-Pointing-Pointer Mercury is effectively determined in blood with an LOD of 1.31 nM at S/N ratio 3. - Abstract: We have developed a simple, colorimetric iron telluride (FeTe) nanorods (NRs) based system for the detection of mercury, mainly based on the cation exchange reaction between FeTe NRs and Hg{sup 2+}. FeTe NRs (length, 105 {+-} 21 nm) react with Hg{sup 2+} to form HgTe NRs (length, 112 {+-} 26 nm) and consequently release Fe{sup 2+} ions that catalyzes the oxidation between a peroxidase substrate 2,2 Prime -azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and H{sub 2}O{sub 2}. The concentration of Fe{sup 2+} and thereby Hg{sup 2+} can be determined by measuring the absorbance of the ABTS oxidized product at 418 nm. This approach allows the detection of Hg{sup 2+}, with a limit of detection of 1.31 nM at a signal-to-noise ratio 3 and a linear range 5-100 nM (R{sup 2} = 0.99). The low-cost, simple, sensitive, and reproducible assay has been validated for the detection of Hg{sup 2+} in a blood sample (SRM 955c), with the result being in good agreement with that provided by National Institute of Standards and Technology.

  13. Observation of the Decays Λ_{b}^{0}→χ_{c1}pK^{-} and Λ_{b}^{0}→χ_{c2}pK^{-}.

    Science.gov (United States)

    Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Baszczyk, M; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bitadze, A; Bizzeti, A; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; Bondar, N; Bonivento, W; Bordyuzhin, I; Borgheresi, A; Borghi, S; Borisyak, M; Borsato, M; Bossu, F; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britton, T; Brodzicka, J; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D H; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cavallero, G; Cenci, R; Chamont, D; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S F; Chobanova, V; Chrzaszcz, M; Chubykin, A; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombs, G; Coquereau, S; Corti, G; Corvo, M; Costa Sobral, C M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Da Cunha Marinho, F; Dall'Occo, E; Dalseno, J; Davis, A; De Aguiar Francisco, O; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Serio, M; De Simone, P; Dean, C T; Decamp, D; Deckenhoff, M; Del Buono, L; Dembinski, H-P; Demmer, M; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Nezza, P; Dijkstra, H; Dordei, F; Dorigo, M; Dosil Suárez, A; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Dungs, K; Durante, P; Dzhelyadin, R; Dziewiecki, M; Dziurda, A; Dzyuba, A; Déléage, N; Easo, S; Ebert, M; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Farley, N; Farry, S; Fay, R; Fazzini, D; Ferguson, D; Fernandez, G; Fernandez Prieto, A; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fini, R A; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Franco Lima, V; Frank, M; Frei, C; Fu, J; Funk, W; Furfaro, E; Färber, C; Gabriel, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; Garcia Martin, L M; García Pardiñas, J; Garra Tico, J; Garrido, L; Garsed, P J; Gascon, D; Gaspar, C; Gavardi, L; Gazzoni, G; Gerick, D; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianì, S; Gibson, V; Girard, O G; Giubega, L; Gizdov, K; Gligorov, V V; Golubkov, D; Golutvin, A; Gomes, A; Gorelov, I V; Gotti, C; Govorkova, E; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Greim, R; Griffith, P; Grillo, L; Gruber, L; Gruberg Cazon, B R; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Göbel, C; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hamilton, B; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hatch, M; He, J; Head, T; Heister, A; Hennessy, K; Henrard, P; Henry, L; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hombach, C; Hopchev, P H; Huard, Z-C; Hulsbergen, W; Humair, T; Hushchyn, M; Hutchcroft, D; Idzik, M; Ilten, P; Jacobsson, R; Jalocha, J; Jans, E; Jawahery, A; Jiang, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Karacson, M; Kariuki, J M; Karodia, S; Kecke, M; Kelsey, M; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Klimkovich, T; Koliiev, S; Kolpin, M; Komarov, I; Kopecna, R; Koppenburg, P; Kosmyntseva, A; Kotriakhova, S; Kozachuk, A; Kozeiha, M; Kravchuk, L; Kreps, M; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kurek, K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Leflat, A; Lefrançois, J; Lefèvre, R; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, T; Li, Y; Li, Z; Likhomanenko, T; Lindner, R; Lionetto, F; Liu, X; Loh, D; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Maev, O; Maguire, K; Malde, S; Malinin, A; Maltsev, T; Manca, G; Mancinelli, G; Manning, P; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marinangeli, M; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurice, E; Maurin, B; Mazurov, A; McCann, M; McNab, A; McNulty, R; Meadows, B; Meier, F; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Minard, M-N; Mitzel, D S; Mogini, A; Molina Rodriguez, J; Monroy, I A; Monteil, S; Morandin, M; Morello, M J; Morgunova, O; Moron, J; Morris, A B; Morris, A P; Mountain, R; Muheim, F; Mulder, M; Mussini, M; Müller, D; Müller, J; Müller, K; Müller, V; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, T D; Nguyen-Mau, C; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Nogay, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Oldeman, R; Onderwater, C J G; Ossowska, A; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pais, P R; Palano, A; Palutan, M; Papanestis, A; Pappagallo, M; Pappalardo, L L; Pappenheimer, C; Parker, W; Parkes, C; Passaleva, G; Pastore, A; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petrov, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Placinta, V; Playfer, S; Plo Casasus, M; Poikela, T; Polci, F; Poli Lener, M; Poluektov, A; Polyakov, I; Polycarpo, E; Pomery, G J; Ponce, S; Popov, A; Popov, D; Popovici, B; Poslavskii, S; Potterat, C; Price, E; Prisciandaro, J; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, C; Qian, W; Quagliani, R; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Ratnikov, F; Raven, G; Ravonel Salzgeber, M; Reboud, M; Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Gonzalo, D; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubert, K; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stevens, H; Stoica, S; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szczekowski, M; Szumlak, T; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Tourneur, S; Trabelsi, K; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M A; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zonneveld, J B; Zucchelli, S

    2017-08-11

    The first observation of the decays Λ_{b}^{0}→χ_{c1}pK^{-} and Λ_{b}^{0}→χ_{c2}pK^{-} is reported using a data sample corresponding to an integrated luminosity of 3.0  fb^{-1}, collected by the LHCb experiment in pp collisions at center-of-mass energies of 7 and 8 TeV. The following ratios of branching fractions are measured: B(Λ_{b}^{0}→χ_{c1}pK^{-})/B(Λ_{b}^{0}→J/ψpK^{-})=0.242±0.014±0.013±0.009,B(Λ_{b}^{0}→χ_{c2}pK^{-})/B(Λ_{b}^{0}→J/ψpK^{-})=0.248±0.020±0.014±0.009,B(Λ_{b}^{0}→χ_{c2}pK^{-})/B(Λ_{b}^{0}→χ_{c1}pK^{-})=1.02±0.10±0.02±0.05,where the first uncertainty is statistical, the second systematic, and the third due to the uncertainty on the branching fractions of the χ_{c1}→J/ψγ and χ_{c2}→J/ψγ decays. Using both decay modes, the mass of the Λ_{b}^{0} baryon is also measured to be m_{Λ_{b}^{0}}=5619.44±0.28±0.26  MeV/c^{2}, where the first and second uncertainties are statistical and systematic, respectively.

  14. Blood Transfusion (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Blood Transfusions KidsHealth / For Parents / Blood Transfusions What's in this ... and help put your child at ease. About Blood Transfusions Blood is like the body's transportation system. As ...

  15. Comparative evaluation of Oxoid Signal and BACTEC radiometric blood culture systems for the detection of bacteremia and fungemia

    International Nuclear Information System (INIS)

    Weinstein, M.P.; Mirrett, S.; Reller, L.B.

    1988-01-01

    The Oxoid Signal blood culture system is a newly described, innovative method for visually detecting growth of microorganisms. We did 5,999 paired comparisons of equal volumes (10 ml) of blood in the Oxoid Signal and BACTEC radiometric blood culture systems at two university hospitals that use identical methods of obtaining and processing specimens. Overall, more microorganisms were detected in the BACTEC system (P less than 0.001), in particular, streptococci (P less than 0.01), fungi (P less than 0.001), and nonfermentative gram-negative rods, especially Acinetobacter species (P less than 0.001). Trends favoring the BACTEC system for detection of Pseudomonas aeruginosa, Haemophilus species, and Neisseria species were noted. There were no differences in the yield of staphylococci, members of the family Enterobacteriaceae, and anaerobic bacteria. When both systems detected sepsis, the BACTEC did so earlier (P less than 0.001). This advantage was most notable at 24 h (70% of BACTEC positives detected versus 48% of Oxoid positives). The proportion of positives detected after 48 h, however, was similar (BACTEC, 84%; Oxoid, 78%). Revisions in the Oxoid Signal system itself or in the processing of Oxoid bottles appear to be necessary to improve its performance in detecting certain microorganism groups, especially fungi

  16. Laboratory rearing of Cimex hemipterus F. (Hemiptera: Cimicidae feeding on different types of human blood compositions by using modifid artifiial feeding system

    Directory of Open Access Journals (Sweden)

    Abd Hafis Abd Rahim

    2015-12-01

    Full Text Available Objective: To investigate the effects of three types of human blood compositions: whole blood, red blood cells and red blood cells mixed with plasma, and determine the suitable blood source that can be used to feed the bed bugs [Cimex hemipterus (C. hemipterus], in comparison to the direct feeding method. Methods: C. hemipterus were fed with the three types of blood compositions by using an artificial feeding system. Then the number of live and dead individuals as well as the number of adults produced was counted. Results: Red blood cells caused 72.7% death of C. hemipterus, followed by red blood cells mixed with plasma (52.0% and whole blood (48.7%. There were significant differences in the number of live individuals after seven weeks of feeding. However, there were no significant differences between the number of live individuals fed on whole blood, red blood cells and red blood cells mixed with plasma after seven weeks. Conclusions: The components in the blood sources may be the key to their different effects on the growth dynamics of C. hemipterus.

  17. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    2010-09-01

    Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

  18. Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system.

    Science.gov (United States)

    Jopling, Jeffery; Henry, Erick; Wiedmeier, Susan E; Christensen, Robert D

    2009-02-01

    "Reference ranges" are developed when it is impossible or inappropriate to establish "normal ranges" by drawing blood on healthy normal volunteers. Reference ranges for the hematocrit and the blood hemoglobin concentration of newborn infants have previously been reported from relatively small sample sizes by using measurement methods that now are considered outmoded. We sought to develop reference ranges for hematocrit and hemoglobin during the neonatal period (28 days) by using very large sample sizes and modern hematology analyzers, accounting for gestational and postnatal age and gender. Data were assembled from a multihospital health care system after exclusion of patients with a high likelihood of an abnormal value and those who were receiving blood transfusions. During the interval from 22 to 40 weeks' gestation, the hematocrit and blood hemoglobin concentration increased approximately linearly. For every week advance in gestational age, the hematocrit increased by 0.64% and the hemoglobin concentration increased by 0.21 g/dL. No difference was seen on the basis of gender. During the 4-hour interval after birth, hematocrit/hemoglobin values of late preterm and term neonates (35-42 weeks' gestation) increased by 3.6% +/- 0.5% (mean +/- SD), those of neonates of 29 to 34 weeks' gestation remained unchanged, and those of hematocrit/hemoglobin occurred. The figures presented herein describe reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period, accounting for gestational and postnatal age.

  19. Blood pressure

    Science.gov (United States)

    Normal blood pressure is important for proper blood flow to the body's organs and tissues. The force of the blood on the walls of the arteries is called blood pressure. Blood pressure is measured both as the heart ...

  20. Blood Types

    Science.gov (United States)

    ... blood, safe blood transfusions depend on careful blood typing and cross-matching. There are four major blood ... cause exceptions to the above patterns. ABO blood typing is not sufficient to prove or disprove paternity ...

  1. Radioprotective action of beta-carotin and vitamin A, C and E complexes at reproductive system and indices of antioxidant system in male rat blood and liver

    International Nuclear Information System (INIS)

    Vereshchako, G.G.; Konoplya, E.F.; Khodosovskaya, A.M.; Rutkovskaya, Zh.A.

    2008-01-01

    Effects of total irradiation in low dose at the state of rat mail reproductive system, lipid peroxidation processes and antioxidant system in rat blood and liver tissues as well as radioprotective capacity of beta-carotin with vitamin A, C and E complexes were investigated. It was established that injection of this substances to rat's organism one day before irradiation in 1.0 Gy dose led to normalization of spermatogenic cells number, increase of nucleic acids content in testes and significant improvement of antioxidant status of blood and liver tissue. (authors)

  2. Grey-Box Modelling of Pharmacokinetic /Pharmacodynamic Systems

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Jacobsen, Judith L.; Pedersen, Oluf

    2004-01-01

    Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling...

  3. [A Survey for Colton and Other 3 Rare Blood Group Systems in Chinese Nanjing Han Population].

    Science.gov (United States)

    Chen, Yan; Ma, Ling; Liu, Yan-Chun

    2015-10-01

    To investigate the distribution of Colton, Diego, Kell and Yt rare blood groups in Chinese Nanjing Han population, so as to improve the transfusion capability of patients with rare blood group and to further enrich the rare-blood-donor bank. A total of 2 015 blood samples from the blood donors were selected randomly to screen the presence of K⁺ and Kp(c+) (Kell), Yt(b+) (Yt), Co(b+) (Colton), Di(a+b+) and Di(a+b-) (Digeo) antigen allele by using PCR and multiplex PCR. Out of 2005 samples, 1 case with K⁺ gene, 8 cases with Yt(b+) gene and 100 cases with Di(a+b+) gene, 2 cases with Di(a+b-) were identified, while no Kp(c+) and Co(b+) were detected. The frequencies of K⁺, Yt(b+) and Di(a+), Di(b+) are 0.0003, 0.0013 and 0.0258, 0.9742, respectively. They are very rare blood groups in Chinese Nanjing Han population.

  4. BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells.

    Science.gov (United States)

    Poplawski, Tomasz; Blasiak, Janusz

    2010-06-01

    Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.

  5. Morphology and physiology of the olfactory system of blood-feeding insects.

    Science.gov (United States)

    Guidobaldi, F; May-Concha, I J; Guerenstein, P G

    2014-01-01

    Several blood-feeding (hematophagous) insects are vectors of a number of diseases including dengue, Chagas disease and leishmaniasis which persistently affect public health throughout Latin America. The vectors of those diseases include mosquitoes, triatomine bugs and sandflies. As vector control is an efficient way to prevent these illnesses it is important to understand the sensory biology of those harmful insects. We study the physiology of the olfactory system of those insects and apply that knowledge on the development of methods to manipulate their behavior. Here we review some of the latest information on insect olfaction with emphasis on hematophagous insects. The insect olfactory sensory neurons are housed inside hair-like organs called sensilla which are mainly distributed on the antenna and mouthparts. The identity of many of the odor compounds that those neurons detect are already known in hematophagous insects. They include several constituents of host (vertebrate) odor, sex, aggregation and alarm pheromones, and compounds related to egg-deposition behavior. Recent work has contributed significant knowledge on how odor information is processed in the insect first odor-processing center in the brain, the antennal lobe. The quality, quantity, and temporal features of the odor stimuli are encoded by the neural networks of the antennal lobe. Information regarding odor mixtures is also encoded. While natural mixtures evoke strong responses, synthetic mixtures that deviate from their natural counterparts in terms of key constituents or proportions of those constituents evoke weaker responses. The processing of olfactory information is largely unexplored in hematophagous insects. However, many aspects of their olfactory behavior are known. As in other insects, responses to relevant single odor compounds are weak while natural mixtures evoke strong responses. Future challenges include studying how information about odor mixtures is processed in their brain

  6. Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

    Science.gov (United States)

    Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

    2017-05-01

    Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

  7. Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

    Science.gov (United States)

    Oda, Kenji; Matsushima, Eisuke; Okubo, Yoshiro; Ohta, Katsuya; Murata, Yuji; Koike, Ryuji; Miyasaka, Nobuyuki; Kato, Motoichiro

    2005-07-01

    Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

  8. Effects of computerized decision support systems on blood glucose regulation in critically ill surgical patients.

    Science.gov (United States)

    Fogel, Sandy L; Baker, Christopher C

    2013-04-01

    The use of computerized decision support systems (CDSS) in glucose control for critically ill surgical patients has been reported in both diabetic and nondiabetic patients. Prospective studies evaluating its effect on glucose control are, however, lacking. The objective of this study was to evaluate patient-specific computerized IV insulin dosing on blood glucose levels (BGLs) by comparing patients treated pre-CDSS with those treated post-CDSS. A prospective study was performed in 4 surgical ICUs and 1 progressive care unit comparing patient data pre- and post-implementation of CDSS. The primary outcomes measures were the impact of the CDSS on glycemic control in this population and on reducing the incidence of severe hypoglycemia. Data on 1,682 patient admissions were evaluated, which corresponded to 73,290 BGLs post-CDSS compared with 44,972 BGLs pre-CDSS. The percentage of hyperglycemic events improved, with BGLs of >150 mg/dL decreasing by 50% compared with 6-month historical controls during the 18-month study period from July 2010 through December 2011. This was true for all 5 units individually (p < 0.0001, by one sample sign test). In addition, severe hypoglycemia (defined as BGL <40 mg/dL) decreased from 1% to 0.05% after implementing CDSS (p < 0.0001 by 2-sided binomial test). Patients whose BGLs were managed using CDSS were statistically significantly more likely to have a glucose reading under control (<150 mg/dL) than in the 6-month historical controls and to avoid serious hypoglycemia (p < 0.0001). Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Blood Tests

    Science.gov (United States)

    ... of your immune system, which fights infections and diseases. Abnormal white blood cell levels may be a sign ... fall outside the normal range for many reasons. Abnormal results might be a sign of a disorder or disease. Other factors—such as diet, menstrual ...

  10. Performance evaluation of photoacoustic oximetry imaging systems using a dynamic blood flow phantom with tunable oxygen saturation

    Science.gov (United States)

    Vogt, William C.; Zhou, Xuewen; Andriani, Rudy; Wear, Keith A.; Garra, Brian S.; Pfefer, Joshua

    2018-02-01

    Photoacoustic Imaging (PAI) is an emerging technology with strong potential for broad clinical applications from breast cancer detection to cerebral monitoring due to its ability to compute maps of blood oxygen saturation (SO2) distribution in deep tissues using multispectral imaging. However, no well-validated consensus test methods currently exist for evaluating oximetry-specific performance characteristics of PAI devices. We have developed a phantombased flow system capable of rapid SO2 adjustment to serve as a test bed for elucidation of factors impacting SO2 measurement and quantitative characterization of device performance. The flow system is comprised of a peristaltic pump, membrane oxygenator, oxygen and nitrogen gas, and in-line oxygen, pH, and temperature sensors that enable real-time estimation of SO2 reference values. Bovine blood was delivered through breast-relevant tissue phantoms containing vessel-mimicking fluid channels, which were imaged using a custom multispectral PAI system. Blood was periodically drawn for SO2 measurement in a clinical-grade CO-oximeter. We used this flow phantom system to evaluate the impact of device parameters (e.g.,wavelength-dependent fluence corrections) and tissue parameters (e.g. fluid channel depth, blood SO2, spectral coloring artifacts) on oximetry measurement accuracy. Results elucidated key challenges in PAI oximetry and device design trade-offs, which subsequently allowed for optimization of system performance. This approach provides a robust benchtop test platform that can support PAI oximetry device optimization, performance validation, and clinical translation, and may inform future development of consensus test methods for performance assessment of photoacoustic oximetry imaging systems.

  11. Quantitative blood flow measurements in the small animal cardiopulmonary system using digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Lin Mingde; Marshall, Craig T.; Qi, Yi; Johnston, Samuel M.; Badea, Cristian T.; Piantadosi, Claude A.; Johnson, G. Allan [Department of Radiology, Center for In Vivo Microscopy and Department of Biomedical Engineering, Duke University Medical Center, Box 3302, Durham, North Carolina 27710 (United States); Division of Pulmonary and Critical Care Medicine and Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Box 3823, Durham, North Carolina 27710 (United States); Department of Radiology, Center for In Vivo Microscopy, Duke University Medical Center, Box 3302, Durham, North Carolina 27710 (United States); Department of Radiology, Center for In Vivo Microscopy and Department of Biomedical Engineering, Duke University Medical Center, Box 3302, Durham, North Carolina 27710 (United States); Department of Radiology, Center for In Vivo Microscopy, Duke University Medical Center, Box 3302, Durham, North Carolina 27710 (United States); Division of Pulmonary and Critical Care Medicine and Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Box 3823, Durham, North Carolina 27710 (United States); Department of Radiology, Center for In Vivo Microscopy and Department of Biomedical Engineering, Duke University Medical Center, Box 3302, Durham, North Carolina 27710 (United States)

    2009-11-15

    Purpose: The use of preclinical rodent models of disease continues to grow because these models help elucidate pathogenic mechanisms and provide robust test beds for drug development. Among the major anatomic and physiologic indicators of disease progression and genetic or drug modification of responses are measurements of blood vessel caliber and flow. Moreover, cardiopulmonary blood flow is a critical indicator of gas exchange. Current methods of measuring cardiopulmonary blood flow suffer from some or all of the following limitations--they produce relative values, are limited to global measurements, do not provide vasculature visualization, are not able to measure acute changes, are invasive, or require euthanasia. Methods: In this study, high-spatial and high-temporal resolution x-ray digital subtraction angiography (DSA) was used to obtain vasculature visualization, quantitative blood flow in absolute metrics (ml/min instead of arbitrary units or velocity), and relative blood volume dynamics from discrete regions of interest on a pixel-by-pixel basis (100x100 {mu}m{sup 2}). Results: A series of calibrations linked the DSA flow measurements to standard physiological measurement using thermodilution and Fick's method for cardiac output (CO), which in eight anesthetized Fischer-344 rats was found to be 37.0{+-}5.1 ml/min. Phantom experiments were conducted to calibrate the radiographic density to vessel thickness, allowing a link of DSA cardiac output measurements to cardiopulmonary blood flow measurements in discrete regions of interest. The scaling factor linking relative DSA cardiac output measurements to the Fick's absolute measurements was found to be 18.90xCO{sub DSA}=CO{sub Fick}. Conclusions: This calibrated DSA approach allows repeated simultaneous visualization of vasculature and measurement of blood flow dynamics on a regional level in the living rat.

  12. Quantitative blood flow measurements in the small animal cardiopulmonary system using digital subtraction angiography

    International Nuclear Information System (INIS)

    Lin Mingde; Marshall, Craig T.; Qi, Yi; Johnston, Samuel M.; Badea, Cristian T.; Piantadosi, Claude A.; Johnson, G. Allan

    2009-01-01

    Purpose: The use of preclinical rodent models of disease continues to grow because these models help elucidate pathogenic mechanisms and provide robust test beds for drug development. Among the major anatomic and physiologic indicators of disease progression and genetic or drug modification of responses are measurements of blood vessel caliber and flow. Moreover, cardiopulmonary blood flow is a critical indicator of gas exchange. Current methods of measuring cardiopulmonary blood flow suffer from some or all of the following limitations--they produce relative values, are limited to global measurements, do not provide vasculature visualization, are not able to measure acute changes, are invasive, or require euthanasia. Methods: In this study, high-spatial and high-temporal resolution x-ray digital subtraction angiography (DSA) was used to obtain vasculature visualization, quantitative blood flow in absolute metrics (ml/min instead of arbitrary units or velocity), and relative blood volume dynamics from discrete regions of interest on a pixel-by-pixel basis (100x100 μm 2 ). Results: A series of calibrations linked the DSA flow measurements to standard physiological measurement using thermodilution and Fick's method for cardiac output (CO), which in eight anesthetized Fischer-344 rats was found to be 37.0±5.1 ml/min. Phantom experiments were conducted to calibrate the radiographic density to vessel thickness, allowing a link of DSA cardiac output measurements to cardiopulmonary blood flow measurements in discrete regions of interest. The scaling factor linking relative DSA cardiac output measurements to the Fick's absolute measurements was found to be 18.90xCO DSA =CO Fick . Conclusions: This calibrated DSA approach allows repeated simultaneous visualization of vasculature and measurement of blood flow dynamics on a regional level in the living rat.

  13. Regulation of blood glucose level by kainic acid in mice: involvement of glucocorticoid system and non-NMDA receptors.

    Science.gov (United States)

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Jung, Jun-Sub; Sharma, Naveen; Suh, Hong-Won

    2017-02-28

    Kainic acid (KA) is a well-known excitatory neurotoxic substance. In the present study, effects of KA-injected intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level were investigated in ICR mice. We found that KA administered intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) increased the blood glucose and corticosterone levels, suggesting that KA-induced hyperglycemia appeared to be due to increased blood corticosterone level. In support of this finding, adrenalectomy causes a reduction of KA-induced hyperglycemia and neuronal cell death in CA3 regions of the hippocampus. In addition, pretreatment with i.c.v. or i.t. injection of CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione; a non-NMDA receptor blocker) attenuated the i.p. and i.c.v. administered KA-induced hyperglycemia. KA administered i.c.v. caused an elevation of the blood corticosterone level whereas the plasma insulin level was reduced. Moreover, i.c.v. pretreatment with CNQX inhibited the decrease of plasma insulin level induced by KA i.c.v. injection, whereas the KA-induced plasma corticosterone level was further enhanced by CNQX pretreatment. Our results suggest that KA administered systemically or centrally produces hyperglycemia. A glucocorticoid system appears to be involved in KA-induced hyperglycemia. Furthermore, central non-N-methyl-D-aspartate receptors may be responsible for KA-induced hyperglycemia.

  14. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of glucocorticoid system.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Choi, Seong-Soo; Suh, Hong-Won

    2013-10-01

    The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D-glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D-glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

    Science.gov (United States)

    Lim, Khai Lone; Amir, Amirah; Lau, Yee Ling; Fong, Mun Yik

    2017-08-11

    The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated. The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes. Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P < 0.0001). However, no difference in binding activity level was seen in the binding assay using M. fascicularis erythrocytes. This study is the first report of phenotypic difference between PkDBPαII haplotypes. The biological implication of this finding is yet to be determined. Therefore, further studies need to be carried out to determine whether this differential binding level can be associated with severity of knowlesi malaria in human.

  16. Lesions inflammatory activity quantification in multiple sclerosis using [{sup 11}C]-(R)-PK11195 PET brain images; Quantificacao da atividade inflamatoria em lesoes na esclerose multipla usando imagens PET cerebrais com [{sup 11}C]-(R)-PK11195

    Energy Technology Data Exchange (ETDEWEB)

    Schuck, Phelipi N.; Narciso, Lucas D.L.; Dartora, Caroline M.; Silva, Ana M. Marques da, E-mail: phelipi.schuck@acad.pucrs.br [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil). Nucleo de Pesquisa em Imagens Medicas

    2016-07-01

    The criteria for multiple sclerosis (MS) diagnosis include the presence of lesions in brain regions called black holes (BH), characterized by low signal on magnetic resonance imaging T1-weighted. Studies suggest that lesions in MS, if there is an inflammatory process, can be detected in PET imaging with [{sup 11}C]- (R)-PK11195. The aim of this study is to investigate the uptake of [{sup 11}C]-(R)-PK11195 in BH in PET images, searching for inflammation activity in lesions and neighborhoods. Semiquantitative methods of SUV and uptake normalization were applied to PET images, in different time intervals, acquired from 8 MS patients and 5 healthy controls. Higher uptake was identified in BH and its edges, when compared with health controls white matter, when the SUV method is applied (p < 0,01, 40 to 60 min). When uptake normalization method is applied, smaller uptake in black holes and its your edges is observed, when compared with white matter apparently healthy (p < 0,01, 0 to 60 min). (author)

  17. A blood pressure monitor with robust noise reduction system under linear cuff inflation and deflation.

    Science.gov (United States)

    Usuda, Takashi; Kobayashi, Naoki; Takeda, Sunao; Kotake, Yoshifumi

    2010-01-01

    We have developed the non-invasive blood pressure monitor which can measure the blood pressure quickly and robustly. This monitor combines two measurement mode: the linear inflation and the linear deflation. On the inflation mode, we realized a faster measurement with rapid inflation rate. On the deflation mode, we realized a robust noise reduction. When there is neither noise nor arrhythmia, the inflation mode incorporated on this monitor provides precise, quick and comfortable measurement. Once the inflation mode fails to calculate appropriate blood pressure due to body movement or arrhythmia, then the monitor switches automatically to the deflation mode and measure blood pressure by using digital signal processing as wavelet analysis, filter bank, filter combined with FFT and Inverse FFT. The inflation mode succeeded 2440 measurements out of 3099 measurements (79%) in an operating room and a rehabilitation room. The new designed blood pressure monitor provides the fastest measurement for patient with normal circulation and robust measurement for patients with body movement or severe arrhythmia. Also this fast measurement method provides comfortableness for patients.

  18. [Application of multiplex PCR for the screening of genotyping system for the rare blood groups Fy(a-), s-,k-,Di(b-) and Js(b-)].

    Science.gov (United States)

    Jiao, Wei; Xie, Li; Li, Hailan; Lan, Jiao; Mo, Zhuning; Yang, Ziji; Liu, Fei; Xiao, Ruiping; He, Yunlei; Ye, Luyi; Zhu, Ziyan

    2014-04-01

    To screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population. Sequence-specific primers were designed based on single nucleotide polymorphism (SNP) sites of blood group antigens Fy(b) and s. A specific multiplex PCR system I was established. Multiplex PCR system II was applied to detect alleles antigens Di(b), k, Js(b)1910 and Js(b) 2019 at the same time. The two systems was were used to screen for rare blood group antigens in 4490 randomly selected healthy donors of Guangxi Zhuang ethnic origin. We successfully made the multiplex PCR system I. We detected the rare blood group antigens using the two PCR system. There are five Fy(a-), three s(-), two Di(b-) in 4490 Guangxi zhuang random samples. The multiplex PCR system I has achieved good accuracy and stability. With multiplex PCR systems I and II, 4490 samples were screened. Five Fy(a-), three s(-) and two Di(b-) samples were discovered. Multiplex PCR is an effective methods, which can be used for high throughput screening of rare blood groups. The rare blood types of Guangxi Zhuang ethnic origin obtained through the screening can provide valuable information for compatible blood transfusion. Through screening we obtained precious rare blood type materials which can be used to improve the capability of compatible infusion and reduce the transfusion reactions.

  19. Haematophagous arthropod saliva and host defense system: a tale of tear and blood

    Directory of Open Access Journals (Sweden)

    Andrade Bruno B.

    2005-01-01

    Full Text Available The saliva from blood-feeding arthropod vectors is enriched with molecules that display diverse functions that mediate a successful blood meal. They function not only as weapons against host's haemostatic, inflammatory and immune responses but also as important tools to pathogen establishment. Parasites, virus and bacteria taking advantage of vectors' armament have adapted to facilitate their entry in the host. Today, many salivary molecules have been identified and characterized as new targets to the development of future vaccines. Here we focus on current information on vector's saliva and the molecules responsible to modify host's hemostasis and immune response, also regarding their role in disease transmission.

  20. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  1. DNA ligase III is involved in a DNA-PK independent pathway of NHEJ in human cells

    International Nuclear Information System (INIS)

    Wang, H.; Perrault, A.R.; Qin, W.; Wang, H.; Iliakis, G.

    2003-01-01

    Full text: Double strand breaks (DSB) induced by ionizing radiation (IR) and other cytotoxic agents in the genome of higher eukaryotes are thought to be repaired either by homologous recombination repair (HRR), or non-homologous endjoining (NHEJ). We previously reported the operation of two components of NHEJ in vivo: a DNA-PK dependent component that operates with fast kinetics (D-NHEJ), and a DNA-PK independent component that acts as a backup (basic or B-NHEJ) and operates with kinetics an order of magnitude slower. To gain further insight into the mechanisms of B-NHEJ, we investigated DNA endjoining in extracts 180BR, a human cell line deficient in DNA ligase IV, using an in vitro plasmid-based DNA endjoining assay. An anti DNA ligase III antibody inhibited almost completely DNA endjoining activity in these extracts. On the other hand, an anti DNA ligase I antibody had no measurable effect in DNA endjoining activity. Immunodepletion of DNA ligase III from 180BR cell extracts abolished the DNA endjoining activity, which could be restored by addition of purified human DNA ligase IIIb. Full-length DNA ligase III bound to double stranded DNA and stimulated DNA endjoining in both intermolecular and intramolecular ligation. Furthermore, fractionation of HeLa cell extracts demonstrated the presence of an activity stimulating the function of DNA ligase III. Based on these observations we propose that DNA ligase III is the ligase operating in B-NHEJ

  2. Lesions inflammatory activity quantification in multiple sclerosis using ["1"1C]-(R)-PK11195 PET brain images

    International Nuclear Information System (INIS)

    Schuck, Phelipi N.; Narciso, Lucas D.L.; Dartora, Caroline M.; Silva, Ana M. Marques da

    2016-01-01

    The criteria for multiple sclerosis (MS) diagnosis include the presence of lesions in brain regions called black holes (BH), characterized by low signal on magnetic resonance imaging T1-weighted. Studies suggest that lesions in MS, if there is an inflammatory process, can be detected in PET imaging with ["1"1C]- (R)-PK11195. The aim of this study is to investigate the uptake of ["1"1C]-(R)-PK11195 in BH in PET images, searching for inflammation activity in lesions and neighborhoods. Semiquantitative methods of SUV and uptake normalization were applied to PET images, in different time intervals, acquired from 8 MS patients and 5 healthy controls. Higher uptake was identified in BH and its edges, when compared with health controls white matter, when the SUV method is applied (p < 0,01, 40 to 60 min). When uptake normalization method is applied, smaller uptake in black holes and its your edges is observed, when compared with white matter apparently healthy (p < 0,01, 0 to 60 min). (author)

  3. Evaluation of OneTouch Verio, a new blood glucose self-monitoring system for patients with diabetes

    DEFF Research Database (Denmark)

    Littman, Karin; Petersen, Eva R.B.; Pussinen, Christel

    2013-01-01

    (ADA) quality goals. Blood samples were collected and measured on the OneTouch Verio® by laboratory personnel and patients with diabetes (n = 91, randomized into groups receiving personal training or mail instructions for the OneTouch Verio® system). Results were compared to a validated routine method......, imprecision and bias were calculated. User-friendliness was evaluated with a questionnaire. Results. Quality specifications for blood glucose concentration monitoring systems according to ISO 15197 were fulfilled. The mean coefficients of variation (CV%) of repeatability was 3.4% when tested by laboratory...... personnel and within the goal of imprecision suggested by ADA. Mean CV% of repeatability for patient self-monitoring was 5.0% and 5.1% in the training- and the mail group, respectively. Total error was 6.4-10.0%. The OneTouch Verio® showed no hematocrit interference or variation between strip lots...

  4. Resolving the composite trait of hypertension into its pharmacogenetic determinants by acute pharmacological modulation of blood pressure regulatory systems

    Czech Academy of Sciences Publication Activity Database

    Ueno, T.; Tremblay, J.; Kuneš, Jaroslav; Zicha, Josef; Dobešová, Zdenka; Pausova, Z.; Deng, A. Y.; Sun, Y. L.; Jacob, H. J.; Hamet, P.

    2003-01-01

    Roč. 81, č. 1 (2003), s. 51-60 ISSN 0946-2716 R&D Projects: GA AV ČR IAA7011711 Grant - others:CIHR(CA) MOP-11463; CIHR(CA) MT-12574; CIHR(CA) MOP-36378; AHA(US) AD-12-FMCQ 0140149N Institutional research plan: CEZ:AV0Z5011922 Keywords : genetic analysis * blood pressure * vasoactive system balance Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.101, year: 2003

  5. Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf.

    Science.gov (United States)

    Toutain, P-L; Potter, T; Pelligand, L; Lacroix, M; Illambas, J; Lees, P

    2017-01-01

    The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller-Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC (0-24 h) /MIC) to achieve a bactericidal effect was estimated from in vitro time-kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single-dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts. © 2016 John Wiley & Sons Ltd.

  6. DNA-dependent protein kinase (DAN-PK), a key enzyme in the re-ligation of DNA double-strand breaks

    International Nuclear Information System (INIS)

    Hennequin, C.; Averbeck, D.

    1999-01-01

    Repair pathways of DNA are now defined and some important findings have been discovered in the last few years. DNA non-homologous end-joining (NEH) is a crucial process in the repair of radiation-induced double-strand breaks (DSBs). NHEj implies at least three steps: the DNA free-ends must get closer, preparation of the free-ends by exonucleases and then a transient hybridization in a region of DNA with weak homology. DNA-dependent protein kinase (DNA-PK) is the key enzyme in this process. DNA-PK is a nuclear serine/threonine kinase that comprises three components: a catalytic subunit (DNA-PK cs ) and two regulatory subunits, DNA-binding proteins, Ku80 and Ku70. The severe combined immuno-deficient (scid) mice are deficient in DNA-PK cs : this protein is involved both in DNA repair and in the V(D)J recombination of immunoglobulin and T-cell receptor genes. It is a protein-kinase of the P13-kinase family and which can phosphorylate Ku proteins, p53 and probably some other proteins still unknown. DNA-PK is an important actor of DSBs repair (induced by ionising radiations or by drugs like etoposide), but obviously it is not the only mechanism existing in the cell for this function. Some others, like homologous recombination, seem also to have a great importance for cell survival. (authors)

  7. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    Science.gov (United States)

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2014-05-01

    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; pholes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Inborn defects in the antioxidant systems of human red blood cells

    NARCIS (Netherlands)

    van Zwieten, Rob; Verhoeven, Arthur J.; Roos, Dirk

    2014-01-01

    Red blood cells (RBCs) contain large amounts of iron and operate in highly oxygenated tissues. As a result, these cells encounter a continuous oxidative stress. Protective mechanisms against oxidation include prevention of formation of reactive oxygen species (ROS), scavenging of various forms of

  9. Systems pharmacology and blood-brain barrier functionality in Parkinson's disease

    NARCIS (Netherlands)

    Ravenstijn, Paulien Gerarda Maria

    2009-01-01

    Parkinson’s disease is a progressive neurodegenerative disease, which is composed of many components, each caused by interplay of a number of genetic and nongenetic causes. As the blood-brain barrier (BBB) is a key player in the relationship between plasma and brain pharmacokinetics, the influences

  10. Improved detection of Candida albicans by PCR in blood of neutropenic mice with systemic candidiasis

    NARCIS (Netherlands)

    A.J.M. Munting-van Deventer; W.H.F. Goessens (Wil); A.F. van Belkum (Alex); H.J. van Vliet; E.W.M. van Etten (Els); H.A. Verbrugh (Henri)

    1995-01-01

    textabstractA PCR using primers aimed at the multicopy gene coding for the small subunit rRNA and resulting in the synthesis of a 180-bp fragment was evaluated for its use in diagnosing invasive candidiasis in comparison with blood culture. With the use of a C.

  11. Effect of nano-scale curvature on the intrinsic blood coagulation system

    Science.gov (United States)

    Kushida, Takashi; Saha, Krishnendu; Subramani, Chandramouleeswaran; Nandwana, Vikas; Rotello, Vincent M.

    2014-01-01

    The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation ‘silent’ surface, while nanoparticles with lower surface curvature shows denaturation and concomitant coagulation. PMID:25341004

  12. Use of pharmacist blood pressure telemonitoring systems in diagnosis of nocturnal hypertension in a young healthy male

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2014-09-01

    Full Text Available Tomohiro Mizuno,1,* Chizuru Matsumoto,1,* Nobuko Nabetani,2 Yoshinari Yasuda,3 Tadashi Nagamatsu,1 Norimasa Umemura2 1Department of Analytical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan; 2Haruka Community Pharmacy, Nagoya, Japan; 3Department of Chronic Kidney Disease Initiatives, Nagoya University Graduate School of Medicine, Nagoya, Japan *These authors contributed equally to this work Abstract: Blood pressure (BP telemonitoring systems and pharmacist management programs were introduced into Haruka Community Pharmacy. A 22-year-old healthy male came to the community pharmacy, although he was not in a diseased state, he had been informed previously that he had a moderately high BP during a routine examination. He continued home BP telemonitoring for 28 days. A pharmacist intervention was conducted at 2 week intervals. His average nighttime systolic BP was higher than the daytime systolic BP. The pharmacist consulted a doctor based on the BP telemonitoring results, and ambulatory blood pressure monitoring (ABPM was initiated. The doctor detected nocturnal hypertension based on the results of ABPM monitoring. BP telemonitoring systems have been introduced into a small percentage of pharmacies in Japan, and this is the first case report for the usefulness of these systems in a community pharmacy. Keywords: community pharmacy, management, ambulatory blood pressure monitoring

  13. Contribution of the Arterial System and the Heart to Blood Pressure during Normal Aging - A Simulation Study.

    Science.gov (United States)

    Maksuti, Elira; Westerhof, Nico; Westerhof, Berend E; Broomé, Michael; Stergiopulos, Nikos

    2016-01-01

    During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contributes to the age-related blood pressure progression as well. In the present study we quantified the blood pressure changes in normal aging by using a Windkessel model for the arterial system and the time-varying elastance model for the heart, and compared the simulation results with data from the Framingham Heart Study. Parameters representing arterial changes (resistance and stiffness) during aging were based on literature values, whereas parameters representing cardiac changes were computed through physiological rules (compensated hypertrophy and preservation of end-diastolic volume). When taking into account arterial changes only, the systolic and diastolic pressure did not agree well with the population data. Between 20 and 80 years, systolic pressure increased from 100 to 122 mmHg, and diastolic pressure decreased from 76 to 55 mmHg. When taking cardiac adaptations into account as well, systolic and diastolic pressure increased from 100 to 151 mmHg and decreased from 76 to 69 mmHg, respectively. Our results show that not only the arterial system, but also the heart, contributes to the changes in blood pressure during aging. The changes in arterial properties initiate a systolic pressure increase, which in turn initiates a cardiac remodelling process that further augments systolic pressure and mitigates the decrease in diastolic pressure.

  14. Determinants of the renin-angiotensin-aldosterone system in cirrhosis with special emphasis on the central blood volume

    DEFF Research Database (Denmark)

    Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H

    2006-01-01

    OBJECTIVE: Several studies have shown activation of the renin-angiotensin-aldosterone system (RAAS) in cirrhosis. Although the activated RAAS may have several determinants, the system is often considered a surrogate marker of effective hypovolaemia. In this study we investigated the activity...... of the RAAS and its potential determinants with special focus on the central and arterial blood volume (CBV). MATERIAL AND METHODS: Eighty-nine patients (Child class A/B/C: 19/41/29) and 32 controls were included in the study. All were given a haemodynamic examination with measurement of determinants...

  15. Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation

    DEFF Research Database (Denmark)

    Vinther, Anne Mette L.; Skovgaard, Kerstin; Heegaard, Peter M. H.

    2015-01-01

    Background: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS......) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic...... were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty...

  16. Effect of agitation and terminal subcultures on yield and speed of detection of the Oxoid Signal blood culture system versus the BACTEC radiometric system

    International Nuclear Information System (INIS)

    Weinstein, M.P.; Mirrett, S.; Reimer, L.G.; Reller, L.B.

    1989-01-01

    In an initial evaluation, we found the Oxoid Signal blood culture system inferior to the BACTEC radiometric system for detection of some microorganisms causing septicemia. To determine whether modified processing of the Oxoid Signal blood culture system could improve its yield and speed of detecting positive cultures relative to the BACTEC radiometric system, we agitated all Oxoid bottles during the first 24 to 48 h of incubation and performed aerobic and anaerobic subcultures of all Oxoid bottles negative after 7 days of incubation. These modifications improved the overall performance of the Oxoid system, particularly with regard to the yield of streptococci, members of the family Enterobacteriaceae, and Haemophilus, Neisseria, and Acinetobacter spp. The speed of detecting positive cultures also was improved, especially within the first 24 h of incubation. However, the BACTEC system still detected more positive cultures (P less than 0.005), especially of obligate aerobes such as Pseudomonas aeruginosa (P less than 0.05) and yeasts (P less than 0.005). The BACTEC system also detected positive cultures earlier than the Oxoid system (e.g., at 24 h of incubation, 70.5% of BACTEC positive cultures detected versus 62.1% of Oxoid positive cultures detected). Further modifications of the Oxoid system which might include a revised medium, additional processing modifications, altered headspace atmosphere, or a complementary second broth medium should be considered, since the system is attractive in concept and is easy to use in the clinical laboratory

  17. Longitudinal associations of long-term exposure to ultrafine particles with blood pressure and systemic inflammation in Puerto Rican adults.

    Science.gov (United States)

    Corlin, Laura; Woodin, Mark; Hart, Jaime E; Simon, Matthew C; Gute, David M; Stowell, Joanna; Tucker, Katherine L; Durant, John L; Brugge, Doug

    2018-04-05

    Few longitudinal studies have examined the association between ultrafine particulate matter (UFP, particles blood pressure and high sensitivity C-reactive protein (hsCRP, a biomarker of systemic inflammation). Residential annual average UFP exposure (measured as particle number concentration, PNC) was assigned using a model accounting for spatial and temporal trends. We also adjusted PNC values for participants' inhalation rate to obtain the particle inhalation rate (PIR) as a secondary exposure measure. Multilevel linear models with a random intercept for each participant were used to examine the association of UFP with blood pressure and hsCRP. Overall, in adjusted models, an inter-quartile range increase in PNC was associated with increased hsCRP (β = 6.8; 95% CI = - 0.3, 14.0%) but not with increased systolic blood pressure (β = 0.96; 95% CI = - 0.33, 2.25 mmHg), pulse pressure (β = 0.70; 95% CI = - 0.27, 1.67 mmHg), or diastolic blood pressure (β = 0.55; 95% CI = - 0.20, 1.30 mmHg). There were generally stronger positive associations among women and never smokers. Among men, there were inverse associations of PNC with systolic blood pressure and pulse pressure. In contrast to the primary findings, an inter-quartile range increase in the PIR was positively associated with systolic blood pressure (β = 1.03; 95% CI = 0.00, 2.06 mmHg) and diastolic blood pressure (β = 1.01; 95% CI = 0.36, 1.66 mmHg), but not with pulse pressure or hsCRP. We observed that exposure to PNC was associated with increases in measures of CVD risk markers, especially among certain sub-populations. The exploratory PIR exposure metric should be further developed.

  18. Institutional blood glucose monitoring system for hospitalized patients: an integral component of the inpatient glucose control program.

    Science.gov (United States)

    Boaz, Mona; Landau, Zohar; Matas, Zipora; Wainstein, Julio

    2009-09-01

    The ability to measure patient blood glucose levels at bedside in hospitalized patients and to transmit those values to a central database enables and facilitates glucose control and follow-up and is an integral component in the care of the hospitalized diabetic patient. The goal of this study was to evaluate the performance of an institutional glucometer employed in the framework of the Program for the Treatment of the Hospitalized Diabetic Patient (PTHDP) at E. Wolfson Medical Center, Holon, Israel. As part of the program to facilitate glucose control in hospitalized diabetic patients, an institutional glucometer was employed that permits uploading of data from stands located in each inpatient department and downloading of that data to a central hospital-wide database. Blood glucose values from hospitalized diabetic patients were collected from August 2007 to October 2008. The inpatient glucose control program was introduced gradually beginning January 2008. During the follow-up period, more than 150,000 blood glucose measures were taken. Mean glucose was 195.7 +/- 99.12 mg/dl during the follow-up period. Blood glucose values declined from 206 +/- 105 prior to PTHDP (August 2007-December 2007) to 186 +/- 92 after its inception (January 2008-October 2008). The decline was associated significantly with time (r = 0.11, p < 0.0001). The prevalence of blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI) 0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP. Concomitantly, a significant increase in the proportion of blood glucose values between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs 61.6% after program initiation (p < 0.0001). The present study was designed to observe changes in institution-wide glucose values following implementation of the PTHDP. Information was extracted from the glucometer system itself. Because the aforementioned study was not a clinical trial, we cannot rule out

  19. Effect of nano-scale curvature on the intrinsic blood coagulation system

    Science.gov (United States)

    Kushida, Takashi; Saha, Krishnendu; Subramani, Chandramouleeswaran; Nandwana, Vikas; Rotello, Vincent M.

    2014-11-01

    The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation `silent' surface, while nanoparticles with lower surface curvature show denaturation and concomitant coagulation.The intrinsic coagulation activity of silica nanoparticles strongly depends on their surface curvature. Nanoparticles with higher surface curvature do not denature blood coagulation factor XII on its surface, providing a coagulation `silent' surface, while nanoparticles with lower surface curvature show denaturation and concomitant coagulation. Electronic supplementary information (ESI) available: Physical properties and scanning electron micrographs (SEM) of silica NPs, intrinsic coagulation activity after 3 h. See DOI: 10.1039/c4nr04128c

  20. Frequencies of Blood Group Systems MNS, Diego, and Duffy and Clinical Phases of Carrion’s Disease in Amazonas, Peru

    Directory of Open Access Journals (Sweden)

    Oscar Acosta

    2014-01-01

    Full Text Available Carrion’s disease (CD, is a human bartonellosis, that is, endemic in the Andes of Peru, Ecuador, and Colombia. Bartonella bacilliformis, a native hemotrophic bacteria, is the causative agent of CD, and the interaction with the host could have produced changes in the gene frequencies of erythrocyte antigens. The goal here is to investigate the relationship between allele frequencies of blood group systems MNS, Diego, and Duffy and the clinical phases of CD, within a genetic context. In this associative and analytical study, 76 individuals from Bagua Grande, the province of Utcubamba, and the department of Amazonas in Peru, were enrolled. Forty of them resided in Tomocho-Collicate-Vista Hermosa area (high prevalence of cases in chronic phase, verrucous, or eruptive phase, without previous acute phase. Thirty-six individuals were from the area of Miraflores (high prevalence of cases in acute phase only and were evaluated for blood group systems MNS, Diego, and Duffy. This study constitutes one of the first attempts at evaluating the genetic factors and clinical phases of CD. No significant statistical differences (P>0.05 between allele frequencies of blood groups MNS, Diego, and Duffy and the prevalence of chronic and acute phases were detected in the two areas of Amazonas, Peru.

  1. Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation

    OpenAIRE

    Licata, Stephanie C.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

    2011-01-01

    Zolpidem is a short-acting imidazopyridine hypnotic that binds at the benzodiazepine binding site on specific GABAA receptors to enhance fast inhibitory neurotransmission. The behavioral and receptor pharmacology of zolpidem has been studied extensively, but little is known about its neuronal substrates in vivo. In the present within-subject, double-blind, and placebo-controlled study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) at 3 Tesla was used to assess...

  2. Effect of Adding Different Vegetable Oils to Quail Diets On Some Blood Parameters and Immune System

    International Nuclear Information System (INIS)

    Abu Taleb, A.M.; Wakwak, M.; Sabek, E.M.; Elaroussi, M.A.; El-Gendy, H.M.; Hammad, M.R.

    2007-01-01

    A total number of 1400 one-day old Japanese quail birds were used in this study, the birds were divided into seven equal groups, six treated while the 7 t h served as the control. The diet of the six treated groups was supplemented with 8 % of either one of the following tested oils: soybean (SBO), sunflower (SFO), corn (CO), cottonseed (CSO), olive (OO) or palm (PO). At the end of the 4 t hand 8 t h weeks of age blood samples were collected for blood picture, proteins and cortisol determination. Antibody titer against sheep red blood cells (SRBCs) and NewCastle disease virus (NDV) were determined at 7 and 8 weeks of age respectively. The results showed significant increase in relative lymphoid organ weights, RBCs, WBCs, Hb and PCV, total protein, globulin and cortisol hormone in treated groups compared to the control. The immunological parameters showed a significant increase in (HA) and (HI) against (SRBCs) and (NDV), respectively, in all treated groups compared to the control group. The present results confirm the beneficial effects of dietary oil supplementation to quail birds and in particular olive oil.

  3. A phenylalanine ammonia-lyase ortholog (PkPAL1) from Picrorhiza kurrooa Royle ex. Benth: molecular cloning, promoter analysis and response to biotic and abiotic elicitors.

    Science.gov (United States)

    Bhat, Wajid Waheed; Razdan, Sumeer; Rana, Satiander; Dhar, Niha; Wani, Tariq Ahmad; Qazi, Parvaiz; Vishwakarma, Ram; Lattoo, Surrinder K

    2014-09-01

    Picrorhiza kurrooa Royle ex Benth. is a highly reputed medicinal herb utilised in the preparation of a number of herbal drug formulations, principally due to the presence of novel monoterpene iridoid glycosides kenned as picrosides. Phenylalanine ammonia-lyase catalyses an important rate-limiting step in phenylpropanoid pathway and supplies precursors like cinnamic acid, vanillic acid, ferulic acid, etc., to a variety of secondary metabolites including picrosides. The imperilled status of P. kurrooa coupled with lack of information regarding biogenesis of picrosides necessitates deciphering the biosynthetic pathway for picrosides. In the present study, a PAL gene, designated PkPAL1 was isolated from P. kurrooa. The cDNA is 2312 bp in length, consisting of an ORF of 2142 bp encoding for a 713 amino acid protein having a predicted molecular weight of 77.66 kDa and an isoelectric point of pH 6.82. qRT-PCR analysis of various tissues of P. kurrooa showed that PkPAL1 transcript levels were highest in the leaves, consistent with picroside accumulation pattern. Using Genome walking, a 718 bp promoter region was also isolated resulting in identification of distinct cis-regulatory elements including TGA-element, TGACG-motif, CGTCA-motif, etc. qRT-PCR indicated up-regulation of PkPAL1 by methyl jasmonate, salicylic acid, 2,4-dicholorophenoxy acetic acid and UV-B elicitations that corroborated positively with the identified cis-elements within the promoter region. Moreover, altitude was found to have a positive effect on the PkPAL1 transcript levels, driving the expression of PkPAL1 abundantly. Based on docking analysis, we identified eight residues as potentially essential for substrate binding in PkPAL1. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Tacrolimus Updated Guidelines through popPK Modeling: How to Benefit More from CYP3A Pre-emptive Genotyping Prior to Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Woillard

    2017-06-01

    Full Text Available Tacrolimus (Tac is a profoundly effective immunosuppressant that reduces the risk of rejection after solid organ transplantation. However, its use is hampered by its narrow therapeutic window along with its highly variable pharmacological (pharmacokinetic [PK] and pharmacodynamic [PD] profile. Part of this variability is explained by genetic polymorphisms affecting the metabolic pathway. The integration of CYP3A4 and CY3A5 genotype in tacrolimus population-based PK (PopPK modeling approaches has been proven to accurately predict the dose requirement to reach the therapeutic window. The objective of the present study was to develop an accurate PopPK model in a cohort of 59 kidney transplant patients to deliver this information to clinicians in a clear and actionable manner. We conducted a non-parametric non-linear effects PopPK modeling analysis in Pmetrics®. Patients were genotyped for the CYP3A4∗22 and CYP3A5∗3 alleles and were classified into 3 different categories [poor-metabolizers (PM, Intermediate-metabolizers (IM or extensive-metabolizers (EM]. A one-compartment model with double gamma absorption route described very accurately the tacrolimus PK. In covariate analysis, only CYP3A genotype was retained in the final model (Δ-2LL = -73. Our model estimated that tacrolimus concentrations were 33% IC95%[20–26%], 41% IC95%[36–45%] lower in CYP3A IM and EM when compared to PM, respectively. Virtually, we proved that defining different starting doses for PM, IM and EM would be beneficial by ensuring better probability of target concentrations attainment allowing us to define new dosage recommendations according to patient CYP3A genetic profile.

  5. Role of XRCC4 phosphorylation by DNA-PK in the regulation of NHEJ repair pathway of DNA double strand break

    International Nuclear Information System (INIS)

    Sharma, Mukesh Kumar; Imamichi, Shoji; Fukuchi, Mikoto; Kamdar, Radhika P.; Sicheng, Liu; Wanotayan, Rujira; Matsumoto, Yoshihisa

    2014-01-01

    Non-homologous end-joining (NHEJ) is the predominant pathway of DNA double strand breaks in higher eukaryotes and is active throughout the cell cycle. NHEJ repair includes many factors as Ku70/86, DNA-PKcs, XRCC4-Ligase IV complex and XLF (also known as Cernunnos). In these factors, DNA-PKcs acts as central regulator in NHEJ repair. It recruited at the DNA damages site after DNA damage and after association with Ku its kinase activity is activated. It phosphorylates many of important NHEJ proteins in vitro including XRCC4, Ku 70/86, Artemis, and even DNA-PKcs but till now, very less studies have been done to know the role and significance of phosphorylation in the NHEJ repair. Studies by other researchers identified various phosphorylation sites in XRCC4 by DNA-PK using mass spectrometry but these phosphorylation sites were shown to be dispensable for DSB repair. In the present investigation, we identified 3 serine and one new threonine phosphorylation sites in XRCC4 protein by DNA-PK. In vivo phosphorylation at these sites was verified by generating phosphorylation specific antibodies and the requirement for DNA-PK therein was verified by using DNA-PK inhibitor and DNA-PK proficient and deficient cell lines in response to radiation and zeocin treatment. We have also found that phosphorylation at these sites showed dose dependency in response to radiation treatment. The two serine and one threonine phosphorylation site is also biological important as their mutation into alanine significantly elevated radiosensitivity as measured by colony formation assay. Neutral comet assay showed delayed kinetics in DSB repair of these mutants. Furthermore, we have found a protein, with putative DSB repair function, which interacts with domain including the phosphorylation sites.These results indicate that these phosphorylation sites would mediate functional link between XRCC4 and DNA-PK. (author)

  6. Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK-15 cells

    Directory of Open Access Journals (Sweden)

    Lin Tong

    2011-09-01

    Full Text Available Abstract Background shRNA targeting the integrin αv subunit, which is the foot-and-mouth disease virus (FMDV receptor, plays a key role in virus attachment to susceptible cells. We constructed a RNAi lentiviral vector, iαv pLenti6/BLOCK -iT™, which expressed siRNA targeting the FMDV receptor, the porcine integrin αv subunit, on PK-15 cells. We also produced a lentiviral stock, established an iαv-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using real-time qRT-PCR, integrand αv expression by indirect immunofluorescence assay (IIF and cell enzyme linked immunosorbent assays (cell ELISA, and investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15 cells. Results Our results indicated successful establishment of the iαv U6 RNAi entry vector and the iαv pLenti6/BLOCK -iT expression vector. The functional titer of obtained virus was 1.0 × 106 TU/mL. To compare with the control and mock group, the iαv-PK-15 group αv mRNA expression rate in group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated suppression in the experimental group. Thus, iαv-PK-15 cells could reduce virus growth by more than three-fold and there was a > 99% reduction in virus titer when cells were challenged with 102 TCID50 of FMDV. Conclusions Iαv-PK-15 cells were demonstrated as a cell model for anti-FMDV potency testing, and this study suggests that shRNA could be a viable therapeutic approach for controlling the severity of FMD infection and spread.

  7. Changes in zinc status and zinc transporters expression in whole blood of patients with Systemic Inflammatory Response Syndrome (SIRS).

    Science.gov (United States)

    Florea, Daniela; Molina-López, Jorge; Hogstrand, Christer; Lengyel, Imre; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Planells, Elena

    2018-09-01

    Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of many nutrients and especially zinc, depleting their body reserves. This study was designed to assess the zinc status in critical care patients with systemic inflammatory response syndrome (SIRS), comparing them with a group of healthy people, and studying the association with expression of zinc transporters. This investigation was a prospective, multicentre, comparative, observational and analytic study. Twelve critically ill patients from different hospitals and 12 healthy subjects from Granada, Spain, all with informed consent were recruited. Data on daily nutritional assessment, ICU severity scores, inflammation, clinical and nutritional parameters, plasma and blood cell zinc concentrations, and levels of transcripts for zinc transporters in whole blood were taken at admission and at the seventh day of the ICU stay. Zinc levels on critical ill patient are diminish comparing with the healthy control (HS: 0.94 ± 0.19; CIPF: 0.67 ± 0.16 mg/dL). The 58% of critical ill patients showed zinc plasma deficiency at beginning of study while 50.0% of critical ill after 7 days of ICU stay. ZnT7, ZIP4 and ZIP9 were the zinc transporters with highest expression in whole blood. In general, all zinc transporters were significantly down-regulated (P < 0.05) in the critical ill population at admission in comparison with healthy subjects. Severity scores and inflammation were significantly associated (P < 0.05) with zinc plasma levels, and zinc transporters ZIP3, ZIP4, ZIP8, ZnT6, ZnT7. Expression of 11 out of 24 zinc transporters was analysed, and ZnT1, ZnT4, ZnT5 and ZIP4, which were downregulated by more than 3-fold in whole blood of patients. In summary, in our study an alteration of zinc status was related with the severity-of-illness scores and inflammation in critical ill patients since admission in ICU stay. SIRS

  8. Evaluation of OneTouch Verio(®), a new blood glucose self-monitoring system for patients with diabetes

    DEFF Research Database (Denmark)

    Littmann, Karin; Petersen, Eva; Pussinen, Christel

    2013-01-01

    tested by laboratory personnel and within the goal of imprecision suggested by ADA. Mean CV% of repeatability for patient self-monitoring was 5.0% and 5.1% in the training- and the mail group, respectively. Total error was 6.4-10.0%. The OneTouch Verio(®) showed no hematocrit interference or variation...... Association (ADA) quality goals. Blood samples were collected and measured on the OneTouch Verio(®) by laboratory personnel and patients with diabetes (n = 91, randomized into groups receiving personal training or mail instructions for the OneTouch Verio(®) system). Results were compared to a validated...... between strip lots. Conclusion. The OneTouch Verio(®) displayed sufficient analytical quality and satisfactory user-friendliness. It is suitable for point-of-care testing of blood glucose concentration when handled by patients and healthcare professionals....

  9. A Pediatric Case of Systemic Lupus Erythematosus Developed 10 Years after Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Masayuki Nagasawa

    2012-01-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT is a most powerful immunotherapy for hematological malignancies. However, the impact of immunological disturbances as a result of allo-HSCT is not understood well. We experienced an 11-year-old boy who presented with systemic lupus erythemathosus (SLE 10 years after unrelated cord blood transplantation of male origin for juvenile myelomonocytic leukemia (JMML with monosomy 7. Bone marrow examination showed complete remission without monosomy 7. Genetic analysis of peripheral blood revealed mixed chimera with recipient cells consisting of <5% of T cells, 50–60% of B cells, 60–75% of NK cells, 70–80% of macrophages, and 50–60% of granulocytes. Significance of persistent mixed chimera as a cause of SLE is discussed.

  10. CLINICAL-PATHOGENIC IMPORTANCE OF CORRELATION BETWEEN HISTOCHEMICAL INDICES OF BLOOD SYSTEM AND RHEUMATOID FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A B Zborovsky

    2001-01-01

    Full Text Available Summary Relation between rheumatoid factor (RF and levels of Myeloperoxidase (MPO, Na*-K +-A TPh- ase (ATPh-ase, 5'-Nucleotidase (5 ’-NT, Succinate dehydrogenase (SDG in cells of peripheral blood of rheumatoid arthritis (RA patients was investigated. 83 RA patients were observed. The activities of MPO, ATP-ase, 5’NT, SDG in blood cells were determined by hystochemical methods. In patients having increasing MPO activity in monocytes, normal level of SDG in lymphocytes and decreasing of 5'NT in monocytes and lymphocytes increasing of RF level was noted in 3 weeks after hystochemical changes (p<0.05. Determination of MPO in monocytes was the most informative test for forecasting of immunological changes in RA. The role of macrophage system in RA is discussed.

  11. Development of a system for measuring wall shear stress in blood vessels using magnetic resonance imaging and computational fluid dynamics

    International Nuclear Information System (INIS)

    Yoshida, Keita; Nagao, Taisuke; Okada, Kouji; Miyazaki, Shohei; Yang, Xiaomei; Yamazaki, Youichi; Murase, Kenya

    2008-01-01

    We developed a system for measuring the wall shear stress (WSS) in blood vessels using magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). The time-dependent velocity at the center of the blood vessel was measured by phase-contrast MRI and was approximated by finite Fourier series, which was used for generating the velocity profile at the inlet for the boundary condition to the CFD method. To validate the CFD method, we compared the WSS obtained by the CFD method with the theoretical value in a straight cylinder with various radii for both steady and pulsatile flows. We also investigated the dependence of the WSS on the inlet velocity profile incorporated into the CFD method. For steady flow, there was a good agreement between the WSS obtained by the CFD method and the theoretical value. For pulsatile flow, there was a relatively good agreement between them when the radius of the cylinder was 2.5 mm and the inlet velocity profile was given by the Womersley solution for fully developed pulsatile flow in a straight circular cylinder. When the radius of the cylinder was 5 mm and/or the inlet velocity profile was assumed to be parabolic, large differences were observed between them, suggesting that the assumption of fully developed flow does not hold true in these cases. In human studies, the vortex due to the secondary blood flow in the carotid arterial sinus was clearly observed. The WSS in the bifurcation was the highest, while that in the carotid arterial sinus was the smallest. In conclusion, the system presented here appears to be useful for measuring the WSS in blood vessels and for analyzing the cause and/or extent of atherosclerosis, and our results suggest that the inlet velocity profile should be carefully considered. (author)

  12. In vitro blood flow in a rectangular PDMS microchannel: experimental observations using a confocal micro-PIV system.

    Science.gov (United States)

    Lima, Rui; Wada, Shigeo; Tanaka, Shuji; Takeda, Motohiro; Ishikawa, Takuji; Tsubota, Ken-ichi; Imai, Yohsuke; Yamaguchi, Takami

    2008-04-01

    Progress in microfabricated technologies has attracted the attention of researchers in several areas, including microcirculation. Microfluidic devices are expected to provide powerful tools not only to better understand the biophysical behavior of blood flow in microvessels, but also for disease diagnosis. Such microfluidic devices for biomedical applications must be compatible with state-of-the-art flow measuring techniques, such as confocal microparticle image velocimetry (PIV). This confocal system has the ability to not only quantify flow patterns inside microchannels with high spatial and temporal resolution, but can also be used to obtain velocity measurements for several optically sectioned images along the depth of the microchannel. In this study, we investigated the ability to obtain velocity measurements using physiological saline (PS) and in vitro blood in a rectangular polydimethysiloxane (PDMS) microchannel (300 microm wide, 45 microm deep) using a confocal micro-PIV system. Applying this combination, measurements of trace particles seeded in the flow were performed for both fluids at a constant flow rate (Re = 0.02). Velocity profiles were acquired by successive measurements at different depth positions to obtain three-dimensional (3-D) information on the behavior of both fluid flows. Generally, the velocity profiles were found to be markedly blunt in the central region, mainly due to the low aspect ratio (h/w = 0.15) of the rectangular microchannel. Predictions using a theoretical model for the rectangular microchannel corresponded quite well with the experimental micro-PIV results for the PS fluid. However, for the in vitro blood with 20% hematocrit, small fluctuations were found in the velocity profiles. The present study clearly shows that confocal micro-PIV can be effectively integrated with a PDMS microchannel and used to obtain blood velocity profiles along the full depth of the microchannel because of its unique 3-D optical sectioning ability

  13. Saponin, an inhibitory agent of carbon dioxide production by white cells : its use in the microbiologic examination of blood components in an automated bacterial culture system

    NARCIS (Netherlands)

    van Doorne, Hans; van der Tuuk Adriani, W.P A; van der Ven, L.I; Bosch, E.H; de Natris, T; Smit Sibinga, C.Th.

    1998-01-01

    BACKGROUND: Blood components with a white cell count >100 x 10(9) per L may cause false-positive results when the BacT/Alert system is used for the microbiologic examination. The effects of different concentrations of saponin on bacterial growth and on carbon dioxide production by blood fractions

  14. [Measures to prevent patient identification errors in blood collection/physiological function testing utilizing a laboratory information system].

    Science.gov (United States)

    Shimazu, Chisato; Hoshino, Satoshi; Furukawa, Taiji

    2013-08-01

    We constructed an integrated personal identification workflow chart using both bar code reading and an all in-one laboratory information system. The information system not only handles test data but also the information needed for patient guidance in the laboratory department. The reception terminals at the entrance, displays for patient guidance and patient identification tools at blood-sampling booths are all controlled by the information system. The number of patient identification errors was greatly reduced by the system. However, identification errors have not been abolished in the ultrasound department. After re-evaluation of the patient identification process in this department, we recognized that the major reason for the errors came from excessive identification workflow. Ordinarily, an ultrasound test requires patient identification 3 times, because 3 different systems are required during the entire test process, i.e. ultrasound modality system, laboratory information system and a system for producing reports. We are trying to connect the 3 different systems to develop a one-time identification workflow, but it is not a simple task and has not been completed yet. Utilization of the laboratory information system is effective, but is not yet perfect for patient identification. The most fundamental procedure for patient identification is to ask a person's name even today. Everyday checks in the ordinary workflow and everyone's participation in safety-management activity are important for the prevention of patient identification errors.

  15. The real world of blood glucose point-of-care testing (POCT) system running in China teaching hospital.

    Science.gov (United States)

    Li, Feng-Fei; Xie, Yun; Shi, Bing-Yin; Niu, Min; Guo, Hui; Cao, Yan; Liu, Bing-Li; Yan, Reng-Na; Su, Xiao-Fei; Wu, Jin-Dan; Zhang, Dan-Feng; Chen, Li-Ming; Ma, Jian-Hua

    2018-06-01

     The blood glucose point-of-care testing (POCT) system is important in the decision-making process involving patients suspected of having hypoglycemia. To investigate the real world of the POCT system being used in teaching hospitals in China. The survey was conducted by Hisend Research Group from May 2015 to July 2015 in four teaching hospitals in China. The survey questions were referred to the ISO 15197:2013 standard requirements for the use of the POCT system in a hospital setting. A total of 170 subjects were included from 4 hospitals, which included nursing staff, nurse unit managers, employees from the department of medical instruments, and staff members employed by the clinical laboratories in the Tianjin Metabolism Hospital, Nanjing First Hospital, First Affiliated Hospital of Dalian Medical University, and the First hospital affiliated with the Xi'an Transportation University. The average score for the four hospitals surveyed in this study was 66.6, which varied from 46.1 to 79.7. The main factors influencing the scores were the multiple choices of blood-glucose meters, and the quality control assessment. Our data indicates that the real world use of the POCT system in hospital settings in China needs more closer adherence to a quality management framework.

  16. Blind Deconvolution for Distributed Parameter Systems with Unbounded Input and Output and Determining Blood Alcohol Concentration from Transdermal Biosensor Data.

    Science.gov (United States)

    Rosen, I G; Luczak, Susan E; Weiss, Jordan

    2014-03-15

    We develop a blind deconvolution scheme for input-output systems described by distributed parameter systems with boundary input and output. An abstract functional analytic theory based on results for the linear quadratic control of infinite dimensional systems with unbounded input and output operators is presented. The blind deconvolution problem is then reformulated as a series of constrained linear and nonlinear optimization problems involving infinite dimensional dynamical systems. A finite dimensional approximation and convergence theory is developed. The theory is applied to the problem of estimating blood or breath alcohol concentration (respectively,