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.

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

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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.

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

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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

Tools for predicting the PK/PD of therapeutic proteins.

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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.

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.

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

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

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...

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

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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.

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

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.

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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.

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),

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

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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.

Improving the Accuracy of Predicting Maximal Oxygen Consumption (VO2pk)

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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.

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

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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.

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

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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.

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

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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.

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

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

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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.

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...

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

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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.

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)

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

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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.

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

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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.)

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.

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

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)

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.

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)

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

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.

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.

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.

[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.

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.

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

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.

Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

Directory of Open Access Journals (Sweden)

Muzamil Mahdi Abdel Hamid

Full Text Available Plasmodium falciparum apical membrane antigen 1 (PfAMA1 is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1 was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i Yeast-expressed PkAMA1 can protect against blood stage challenge; ii Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii GIA IC(50 values correlated with estimated in vivo growth rates.

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.

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

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.

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

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

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

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…

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...

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

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.

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.

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.

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...

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.

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.

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.

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

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

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

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)

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...

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)

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.

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

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.

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

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

TK Modeler version 1.0, a Microsoft® Excel®-based modeling software for the prediction of diurnal blood/plasma concentration for toxicokinetic use.

Science.gov (United States)

McCoy, Alene T; Bartels, Michael J; Rick, David L; Saghir, Shakil A

2012-07-01

TK Modeler 1.0 is a Microsoft® Excel®-based pharmacokinetic (PK) modeling program created to aid in the design of toxicokinetic (TK) studies. TK Modeler 1.0 predicts the diurnal blood/plasma concentrations of a test material after single, multiple bolus or dietary dosing using known PK information. Fluctuations in blood/plasma concentrations based on test material kinetics are calculated using one- or two-compartment PK model equations and the principle of superposition. This information can be utilized for the determination of appropriate dosing regimens based on reaching a specific desired C(max), maintaining steady-state blood/plasma concentrations, or other exposure target. This program can also aid in the selection of sampling times for accurate calculation of AUC(24h) (diurnal area under the blood concentration time curve) using sparse-sampling methodologies (one, two or three samples). This paper describes the construction, use and validation of TK Modeler. TK Modeler accurately predicted blood/plasma concentrations of test materials and provided optimal sampling times for the calculation of AUC(24h) with improved accuracy using sparse-sampling methods. TK Modeler is therefore a validated, unique and simple modeling program that can aid in the design of toxicokinetic studies. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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.

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.

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

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)

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 ...

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.

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.

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.

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.

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.

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

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

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.

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.

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...

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.

Optimization of conditions to extract high quality DNA for PCR analysis from whole blood using SDS-proteinase K method

Directory of Open Access Journals (Sweden)

Wajhul Qamar

2017-11-01

Full Text Available In case of studies associated with human genetics, genomics, and pharmacogenetics the genomic DNA is extracted from the buccal cells, whole blood etc. Several methods are exploited by the researchers to extract DNA from the whole blood. One of these methods, which utilizes cell lysis and proteolytic properties of sodium dodecyl sulfate (SDS and proteinase K respectively, might also be called SDS-PK method. It does not include any hazardous chemicals such as phenol or chloroform and is inexpensive. However, several researchers report the same method with different formulas and conditions. During our experiments with whole blood DNA extraction we experienced problems such as protein contamination, DNA purity and yield when followed some SDS-PK protocols reported elsewhere. A260/A280 and A260/A230 ratios along with PCR amplification give a clear idea about the procedure that was followed to extract the DNA. In an effort to increase the DNA purity from human whole blood, we pointed out some steps of the protocol that play a crucial role in determining the extraction of high quality DNA.

Generation of static PET images with [{sup 11}C]-(R)-PK11195: Defining time interval; Geração de imagens PET Estáticas com [{sup 11}C]-(R)-PK11195: definição do intervalo temporal

Energy Technology Data Exchange (ETDEWEB)

Schuck, Phelipi Nunes; Dartora, Caroline Machado; Silva, Ana Maria Marques da, E-mail: phelipi.schuck@acad.pucrs.br [Pontificia Universidade catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil). Núcleo de Pesquisa em Imagens Médicas

2017-07-01

[{sup 11}C]-(R)-PK11195 radiotracer shows microglia affinity in PET images and can be used as neuro inflammatory disease indicator, such as in Multiple Sclerosis (MS). There is no consensus about appropriate time interval to generate static PET images with [{sup 11}C]-(R)-PK11195. The aim of this study is to define the most appropriate time interval to generate static brain PET images with [{sup 11}C]-(R)-PK11195 for quantification. For this study, images from 10 remittent-recurrent MS patients and 5 healthy controls were used. Static images were generated from list-mode dynamic acquisition in the following time intervals: 0-60min, 5-20min, 5-30min, 10-60min, 30-60min e 40-60min. The ratio between SUV mean of juxtacortical and periventricular regions and normal appearing white matter, denominated SUVR{sup WM}, was used for image quantification. Results shown high variation in time intervals that include radiotracer perfusion. SUVRWM higher stability was observed in two time intervals (30-60min and 40-60min), for both control and MS patients groups. In conclusion, the best acquisition time interval to generate static PET images for quantification is from 40 to 60 minutes after administration, meaning an image acquired 40 minutes after [{sup 11}C]-(R)-PK11195 injection, during 20 min. (author)

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.

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.

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

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.

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.

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.)

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.

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…

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)

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.

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

Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections

Science.gov (United States)

Knippenberg, Ben; Page-Sharp, Madhu; Clark, Ben; Dyer, John; Batty, Kevin T.; Davis, Timothy M. E.

2016-01-01

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections. PMID:27270283

[18F]DPA-714: Direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats

International Nuclear Information System (INIS)

Boutin, Herve; Prenant, Christian; Smigova, Alison; Cawthorne, Christopher; Brown, Gavin; Herholz, Karl; Maroy, Renaud; Galea, James; Greenhalgh, Andrew D.; Rothwell, Nancy J.; Julyan, Peter; Wilkinson, Shane M.; Banister, Samuel D.; Kassiou, Michael

2013-01-01

Neuro-inflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated micro-glia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [ 18 F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuro-inflammation. To further examine the potential of [ 18 F]DPA-714, it was compared directly to [ 11 C]PK11195 in experimental cerebral ischaemia in rats. Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [ 11 C]PK11195 and/or [ 18 F]DPA-714 under anaesthesia. Uptake of [ 11 C]PK11195 vs [ 18 F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.8460.67 vs 2.2860.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [ 11 C]PK11195 or with [ 18 F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [ 11 C]PK11195 and [ 18 F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.3561.21 vs 4.6662.50 for [ 11 C]PK11195 vs [ 18 F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [ 18 F]DPA-714. In a clinically relevant model of neuro-inflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [ 18 F]DPA-714 displayed a higher signal-to-noise ratio than [ 11 C]PK11195. Our results suggest that, with the longer half-life of [ 18 F

[18F]DPA-714: direct comparison with [11C]PK11195 in a model of cerebral ischemia in rats.

Directory of Open Access Journals (Sweden)

Hervé Boutin

Full Text Available PURPOSE: Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [(18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [(18F]DPA-714, it was compared directly to [(11C]PK11195 in experimental cerebral ischaemia in rats. METHODS: Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [(11C]PK11195 and/or [(18F]DPA-714 under anaesthesia. RESULTS: Uptake of [(11C]PK11195 vs [(18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively, but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [(11C]PK11195 or with [(18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [(11C]PK11195 and [(18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [(11C]PK11195 vs [(18F]DPA-714 respectively showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI fold by linear regression for [(18F]DPA-714. CONCLUSIONS: In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [(18F]DPA-714 displayed a higher signal-to-noise ratio than [(11C]PK11195. Our results suggest

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.

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.

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...

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)

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...

Optimal transfection methods and comparison of PK-15 and Dulac cells for rescue of chimeric porcine circovirus type 1-2.

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Li, Jizong; Yu, Tianqi; Zhou, Jinzhu; Tu, Wei; Gao, Song; Liu, Xiufan

2014-11-01

A chimeric porcine circovirus type 1-2 (PCV1-2) infectious DNA clone has low transfection efficiency and exhibits low levels of proliferation. Electroporation and lipofection parameters were optimized for PK-15 and Dulac cells with the purpose of increasing the efficiency for rescuing infectious PCV1-2. Titers of PCV1-2 in Dulac cells were 100-fold higher than those in PK-15 cells following transfection. The electroporation efficiency into Dulac cells was high when three 400 μs pulses at 250 V with 6 μg of plasmid DNA was used, lipofection efficiency was high when the ratio of DNA to transfection reagent was 1:3. The proportion of infected cells was 55.6% compared with 44.2%, for the electroporation and lipofection techniques respectively. Virus titers were higher in Dulac cells, from 10(4.44) to 10(5.32)TCID50/mL compared with 10(1.90)-10(3.38)TCID(50)/mL for PK-15 cells. Dulac cells were more permissive to PCV1-2 than PK-15 cells regardless of the transfection technique. Copyright © 2014 Elsevier B.V. All rights reserved.

DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair.

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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.

The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.

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Temesi, David; Swales, John; Keene, Warren; Dick, Samuel

2013-03-25

Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown. Both N-oxide metabolites reverted to parent compound under standard drying (2hr) and extraction conditions. Card type significantly affected the outcome, with 14% and 22% degradation occurring for clozapine-N-oxide and amitriptyline-N-oxide on a brand of untreated DBS cards, compared to 59 and 88% on a brand of treated DBS cards. Enrichment of the parent compound ex vivo leads to overestimation of circulating blood concentration and inaccurate determination of the PK profile. Copyright © 2012 Elsevier B.V. All rights reserved.

Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT in DNA repair, apoptosis and necrosis after cisplatin

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Calkins Anne S

2011-06-01

Full Text Available Abstract Background Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK binds to DNA double strand breaks (DSBs through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity. Results Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1, Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT. The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis. Conclusions DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and

Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf.

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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.

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

Population Pharmacokinetics of Hydroxychloroquine in Japanese Patients With Cutaneous or Systemic Lupus Erythematosus.

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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.

The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes.

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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.

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

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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.

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

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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

Tacrolimus Updated Guidelines through popPK Modeling: How to Benefit More from CYP3A Pre-emptive Genotyping Prior to Kidney Transplantation

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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.

Cimetidine-induced Leydig cell apoptosis and reduced EG-VEGF (PK-1) immunoexpression in rats: Evidence for the testicular vasculature atrophy.

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Beltrame, Flávia L; Cerri, Paulo S; Sasso-Cerri, Estela

2015-11-01

The antiulcer drug cimetidine has shown to cause changes in the testicular microvasculature of adult rats. Since Leydig cells (LCs) produce the pro-angiogenic factor, EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK-1), this study examined the effect that cimetidine might have on LCs in testes with damaged vasculature. Rats received intraperitoneal injections of 100mg/kg of cimetidine (cimetidine group) or saline vehicle (control group) for 50 days. Serum testosterone levels were measured by chemiluminescence immunoassay and testicular sections were subjected to TUNEL and immunohistochemical reactions for caspase-3, 17β-HSD6, CD163 (ED2 macrophage), PK-1 and androgen receptor (AR). LCs in the cimetidine group showed TUNEL and caspase-3 positive labeling and apoptotic ultrastructural features. Moreover, the presence of 17β-HSD6-positive inclusions inside macrophages and the reduced number of LCs, AR immunoreactivity and serum testosterone levels correlated with a decrease in either the number of PK-1-immunostained LCs or PK-1 immunoreactivity. Although it is not clear which cell type is the primary target of cimetidine in the testicular interstitial compartment, these findings support a direct link between cimetidine-induced testicular vascular atrophy and LCs damage. Copyright © 2015 Elsevier Inc. All rights reserved.

An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

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Airhart, Sophia E; Shireman, Laura M; Risler, Linda J; Anderson, Gail D; Nagana Gowda, G A; Raftery, Daniel; Tian, Rong; Shen, Danny D; O'Brien, Kevin D

2017-01-01

The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR and its effects on blood NAD+ levels in healthy volunteers.

Directory of Open Access Journals (Sweden)

Sophia E Airhart

Full Text Available The co-primary objectives of this study were to determine the human pharmacokinetics (PK of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+ levels.Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR, improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss were observed for both NR (p = 0.03 and NAD+ (p = 0.001; the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008.Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.

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

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

Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

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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.

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

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

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/$c^2$.

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

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

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

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

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.)

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)

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...

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.

Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells

Science.gov (United States)

Song, Jia-Le; Choi, Jung-Ho; Seo, Jae-Hoon; Kil, Jeung-Ha

2014-01-01

BACKGROUND/OBJECTIVES This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (•OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS The ability of FSeS to scavenge DPPH, •OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 µM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity. PMID:24741396

Differential effect of detergents on [3H]Ro 5-4864 and [3H]PK 11195 binding to peripheral-type benzodiazepine-binding sites

International Nuclear Information System (INIS)

Awad, M.; Gavish, M.

1988-01-01

The present study demonstrates a differential effect of various detergent treatments on [ 3 H]Ro 5-4864 and [ 3 H]PK 11195 binding to peripheral benzodiazepine binding sites (PBS). Triton X-100 caused a decrease of about 70% in [ 3 H]Ro 5-4864 binding to membranes from various peripheral tissues of rat, but had only a negligible effect on [ 3 H]PK 11195 binding. A similar effect of Triton X-100 was observed on guinea pig and rabbit kidney membranes. The decrease in [ 3 H]Ro 5-4864 binding after treatment with Triton X-100 was apparently due to a decrease in the density of PBS, since the affinity remained unaltered. The detergents 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS), Tween 20, deoxycholic acid, or digitonin (0.0125%) caused only a minor change in [ 3 H]Ro 5-4864 and [ 3 H]PK 11195 binding to rat kidney membranes; but when concentrations were substantially increased (0.1%), all detergents caused a decrease of at least 50% in [ 3 H]Ro 5-4864 binding, while [ 3 H]PK 11195 binding to rat kidney membranes remained unaffected by the first three detergents, with only a minor decrease (15%) after treatment with digitonin

Pharmacokinetic-pharmacodynamic (PK-PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs.

Science.gov (United States)

Papich, Mark G

2014-07-16

One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic-pharmacodynamic (PK-PD) principles to dosing regimens. If antimicrobials are used appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK-PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK-PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration. Copyright © 2014 Elsevier B.V. All rights reserved.

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...

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

International Nuclear Information System (INIS)

Cha, Seho; Lim, Chunghun; Lee, Jae Young; Song, Yoon-Jae; Park, Junsoo; Choe, Joonho; Seo, Taegun

2010-01-01

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

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.

Biomass Yield and N Uptake in Tall Fescue and Reed Canary Grass Depending on N and PK Fertilization on Two Marginal Sites in Denmark

DEFF Research Database (Denmark)

Ugilt Larsen, Søren; Jørgensen, Uffe; Lærke, Poul Erik

2016-01-01

areas with limited suitability for cereal production. Plots with TF and RCG were sown in April 2011, and fertilization trials were established in spring 2012 with three factors: (a) grass species, (b) PK fertilization (either no P and K or 24 and 250 kg ha−1 y−1 of P and K, respectively), and (c) N...... fertilization (0, 150, 300, or 450 kg ha−1 y−1 N). Three cuts were taken annually from 2012 to 2014. Both species responded strongly to N fertilization. In TF, 450 kg ha−1 y−1 N combined with PK fertilization gave DM yields of 19.3, 12.1, and 14.2 t ha−1 y−1 in the 3 years, respectively, and corresponding...... yields for RCG were 17.3, 14.4, and 14.3 t ha−1 y−1. Without PK fertilization yields were significantly lower: 15.2, 7.5, and 7.3 t ha−1 y−1 in TF and 16.3, 8.7, and 4.8 ha−1 y−1 in RCG. When fertilized with PK, N uptake in harvested biomass balanced with N fertilization at rates of 244, 187, and 172 kg...

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.

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

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.

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.

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

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.

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.

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.

[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.

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.

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.

Rapid Bioavailability and Disposition protocol: A novel higher throughput approach to assess pharmacokinetics and steady-state brain distribution with reduced animal usage.

Science.gov (United States)

Fu, Tingting; Gao, Ruina; Scott-Stevens, Paul; Chen, Yan; Zhang, Chalmers; Wang, Jianfei; Summerfield, Scott; Liu, Houfu; Sahi, Jasminder

2018-05-29

Besides routine pharmacokinetic (PK) parameters, unbound brain-to-blood concentration ratio (K p,uu ) is an index particularly crucial in drug discovery for central nervous system (CNS) indications. Despite advantages of K p,uu from steady state after constant intravenous (i.v.) infusion compared with one- or multiple time points after transient dosing, it is seldom obtained for compound optimization in early phase of CNS drug discovery due to requirement of prerequisite PK data to inform the study design. Here, we designed a novel rat in vivo PK protocol, dubbed as Rapid Bioavailability and Disposition (RBD), which combined oral (p.o.) dosing and i.v. infusion to obtain steady-state brain penetration, along with blood clearance, oral exposure and oral bioavailability for each discovery compound, within a 24 hour in-life experiment and only a few (e.g., 3) animals. Protocol validity was verified through simulations with a range of PK parameters in compartmental models as well as data comparison for nine compounds with distinct PK profiles. PK parameters (K p,brain , CL b and oral AUC) measured from the RBD protocol for all compounds, were within two-fold and/or statistically similar to those derived from conventional i.v./p.o. crossover PK studies. Our data clearly indicates that the RBD protocol offers reliable and reproducible data over a wide range of PK properties, with reduced turnaround time and animal usage. Copyright © 2017. Published by Elsevier B.V.

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.

Dual Identification and Analysis of Differentially Expressed Transcripts of Porcine PK-15 Cells and Toxoplasma gondii during in vitro Infection

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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.

Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

Science.gov (United States)

Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

2016-01-01

Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

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

TANGGUNGJAWAB REKTOR SEBAGAI KPA DALAM PENGELOLAAN KEUANGAN PERGURUAN TINGGI NEGERI YANG MENYELENGGARAKAN PENGELOLAAN KEUANGAN BADAN LAYANAN UMUM (PTN PK-BLU

Directory of Open Access Journals (Sweden)

Dewi Kania Sugiharti

2013-11-01

Full Text Available Perguruan Tinggi yang menerapkan konsep Badan Layanan Umum (PTN PKBLU dalam menjalankan fungsi sebagai organ yang bergerak dalam bidang pelayanan adalah dukungan sarana dan prasarana melalui barang atau jasa. Sebagai institusi yang berada dalam naungan pemerintah dan menerima anggaran negara maka PTN PK-BLU melaksanakan mekanisme untuk memperoleh barang atau jasa sesuai ketentuan hukum. Namun proses pengadaan dalam memperoleh barang atau jasa terkadang menimbulkan persoalan yang muncul sebagai konsekuensi berjalannya proses pengadaan barang atau jasa yang melibatkan organ-organ di dalamnya seperti PA/KPA, PPK, ULP, dan Panitia/Pejabat Penerima Pengadaan. Rektor sebagai KPA dalam PTN PK-BLU memiliki wewenang dalam melakukan kontrol terhadap organ-organ yang melaksanakan proses pengadaan barang/jasa pada lingkungannya. Kesalahan dalam proses pengadaan barang/jasa yang dilakukan oleh PPK dan ULP/Pejabat Pengadaan menyebabkan kerugian negara akibat kesalahan tersebut, baik akibat kelalaian atau tindakan melanggar hukum. Sebagai KPA dalam proses pengadaan barang/jasa Rektor dapat melakukan kontrol pada organ-organ tersebut sesuai dengan wewenang yang diberikan. Konsekuensi yang diterima jika pada akhirnya pejabat pelaksanaan pengadaan barang/jasa tidak mengindahkan teguran Rektor maka pejabat yang terkait proses pengadaan barang/jasa akan menerima sanksi. Universities that apply the concept of Public Service Agency (BLU - PK PTN in performing functions as an organ which isengaged in the service infrastructure support through goods or services . As an institution under the auspices of the government and the state budget receives PTN PK - BLU implement mechanisms to acquire goods or services in accordance with the law . However, the procurement process in obtaining goods or services sometimes poses problems that arise as a consequence of the passage of the procurement of goods or services involving the organs in it as PA / KPA , KDP , ULP , and

Volumetric adsorptive microsampling-liquid chromatography tandem mass spectrometry assay for the simultaneous quantification of four antibiotics in human blood: Method development, validation and comparison with dried blood spot.

Science.gov (United States)

Barco, Sebastiano; Castagnola, Elio; Moscatelli, Andrea; Rudge, James; Tripodi, Gino; Cangemi, Giuliana

2017-10-25

In this paper we show the development and validation of a volumetric absorptive microsampling (VAMS™)-LC-MS/MS method for the simultaneous quantification of four antibiotics: piperacillin-tazobactam, meropenem, linezolid and ceftazidime in 10μL human blood. The novel VAMS-LC-MS/MS method has been compared with a dried blood spot (DBS)-based method in terms of impact of hematocrit (HCT) on accuracy, reproducibility, recovery and matrix effect. Antibiotics were extracted from VAMS and DBS by protein precipitation with methanol after a re-hydration step at 37°C for 10min. LC-MS/MS was carried out on a Thermo Scientific™ TSQ Quantum™ Access MAX triple quadrupole coupled to an Accela ™UHPLC system. The VAMS-LC-MS/MS method is selective, precise and reproducible. In contrast to DBS, it allows an accurate quantification without any HCT influence. It has been applied to samples derived from pediatric patients under therapy. VAMS is a valid alternative sampling strategy for the quantification of antibiotics and is valuable in support of clinical PK/PD studies and consequently therapeutic drug monitoring (TDM) in pediatrics. Copyright © 2017 Elsevier B.V. All rights reserved.

[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.

Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter

Science.gov (United States)

Wang, Fu; Yang, Kai; Wang, Zhe; Ma, Ying; Gutkind, J. Silvio; Hida, Naoki; Niu, Gang; Tian, Jie

2016-02-01

Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real-time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies.Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery

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)

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...

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.

Assessing the relative potency of (S)- and (R)-warfarin with a new PK-PD model, in relation to VKORC1 genotypes.

Science.gov (United States)

Ferrari, Myriam; Pengo, Vittorio; Barolo, Massimiliano; Bezzo, Fabrizio; Padrini, Roberto

2017-06-01

The purpose of this study is to develop a new pharmacokinetic-pharmacodynamic (PK-PD) model to characterise the contribution of (S)- and (R)-warfarin to the anticoagulant effect on patients in treatment with rac-warfarin. Fifty-seven patients starting warfarin (W) therapy were studied, from the first dose and during chronic treatment at INR stabilization. Plasma concentrations of (S)- and (R)-W and INRs were measured 12, 36 and 60 h after the first dose and at steady state 12-14 h after dosing. Patients were also genotyped for the G>A VKORC1 polymorphism. The PK-PD model assumed a linear relationship between W enantiomer concentration and INR and included a scaling factor k to account for a different potency of (R)-W. Two parallel compartment chains with different transit times (MTT 1 and MTT 2 ) were used to model the delay in the W effect. PD parameters were estimated with the maximum likelihood approach. The model satisfactorily described the mean time-course of INR, both after the initial dose and during long-term treatment. (R)-W contributed to the rac-W anticoagulant effect with a potency of about 27% that of (S)-W. This effect was independent of VKORC1 genotype. As expected, the slope of the PK/PD linear correlation increased stepwise from GG to GA and from GA to AA VKORC1 genotype (0.71, 0.90 and 1.49, respectively). Our PK-PD linear model can quantify the partial pharmacodynamic activity of (R)-W in patients contemporaneously exposed to therapeutic (S)-W plasma levels. This concept may be useful in improving the performance of future algorithms aiming at identifying the most appropriate W maintenance dose.

Increased cerebral (R-[11C]PK11195 uptake and glutamate release in a rat model of traumatic brain injury: a longitudinal pilot study

Directory of Open Access Journals (Sweden)

Lammertsma Adriaan A

2011-06-01

Full Text Available Abstract Background The aim of the present study was to investigate microglia activation over time following traumatic brain injury (TBI and to relate these findings to glutamate release. Procedures Sequential dynamic (R-[11C]PK11195 PET scans were performed in rats 24 hours before (baseline, and one and ten days after TBI using controlled cortical impact, or a sham procedure. Extracellular fluid (ECF glutamate concentrations were measured using cerebral microdialysis. Brains were processed for histopathology and (immuno-histochemistry. Results Ten days after TBI, (R-[11C]PK11195 binding was significantly increased in TBI rats compared with both baseline values and sham controls (p -1 as compared with the sham procedure (6.4 ± 3.6 μmol·L-1. Significant differences were found between TBI and sham for ED-1, OX-6, GFAP, Perl's, and Fluoro-Jade B. Conclusions Increased cerebral uptake of (R-[11C]PK11195 ten days after TBI points to prolonged and ongoing activation of microglia. This activation followed a significant acute posttraumatic increase in ECF glutamate levels.

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...

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...

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.

DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

Energy Technology Data Exchange (ETDEWEB)

Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

2010-04-16

During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

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...

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

Measurement of $CP$ asymmetries in $\\Lambda_{b}^{0} \\to pK^{-}$ and $\\Lambda_{b}^{0} \\to p\\pi^-$ decays at LHCb

CERN Document Server

Ferrari, F

2016-01-01

The LHCb experiment has been designed to perform precision measurements in the flavour physics sector at the Large Hadron Collider (LHC). The measurement of the CP-violating observable defined as ΔACP = ACP (Λ0b → pK − ) − ACP (Λ0b → pπ − ), where ACP (Λ0b → pK − ) and ACP (Λ0b → pπ − ) are the direct CP asymmetries in Λ0b → pK − and Λ0b → pπ − decays, is presented for the first time using LHCb data. Using the full 2011 and 2012 data sets of pp collisions collected with the LHCb detector, corresponding to an integrated luminosity of about 3 fb −1, the value ΔACP = (0.8 ± 2.1 ± 0.2)% is obtained. The first uncertainty is statistical and the second corresponds to one of the dominant systematic effects. As the result is compatible with zero, no evidence of CP violation is found. This is the most precise measurement of CP violation in the decays of baryons containing the b quark to date. Once the analysis will be completed with an exhaustive study of systematic uncertainti...

Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay.

Science.gov (United States)

Godinho, Bruno M D C; Gilbert, James W; Haraszti, Reka A; Coles, Andrew H; Biscans, Annabelle; Roux, Loic; Nikan, Mehran; Echeverria, Dimas; Hassler, Matthew; Khvorova, Anastasia

2017-12-01

Therapeutic oligonucleotides, such as small interfering RNAs (siRNAs), hold great promise for the treatment of incurable genetically defined disorders by targeting cognate toxic gene products for degradation. To achieve meaningful tissue distribution and efficacy in vivo, siRNAs must be conjugated or formulated. Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligonucleotides in vivo. In this study, we describe a simple and reproducible methodology for the evaluation of in vivo blood/plasma PK profiles and tissue distribution of oligonucleotides. The method is based on serial blood microsampling from the saphenous vein, coupled to peptide nucleic acid hybridization assay for quantification of guide strands. Performed with minimal number of animals, this method allowed unequivocal detection and sensitive quantification without the need for amplification, or further modification of the oligonucleotides. Using this methodology, we compared plasma clearances and tissue distribution profiles of two different hydrophobically modified siRNAs (hsiRNAs). Notably, cholesterol-hsiRNA presented slow plasma clearances and mainly accumulated in the liver, whereas, phosphocholine-docosahexaenoic acid-hsiRNA was rapidly cleared from the plasma and preferably accumulated in the kidney. These data suggest that the PK/biodistribution profiles of modified hsiRNAs are determined by the chemical nature of the conjugate. Importantly, the method described in this study constitutes a simple platform to conduct pilot assessments of the basic clearance and tissue distribution profiles, which can be broadly applied for evaluation of new chemical variants of siRNAs and micro-RNAs.

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)

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.

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.

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.

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)

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.

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

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.

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.

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

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

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....

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.

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.

Enzymes and membrane proteins of ADSOL-preserved red blood cells

Directory of Open Access Journals (Sweden)

Maria Sueli Soares Leonart

2000-03-01

Full Text Available CONTEXT: The preservative solution ADSOL (adenine, dextrose, sorbitol, sodium chloride and mannitol maintains red cell viability for blood trans-fusion for 6 weeks. It would be useful to know about its preservation qualities over longer periods. OBJECTIVE: To determine some red cell biochemical parameters for peri-ods of up to 14 weeks in order to determine whether the red cell metabo-lism integrity would justify further studies aiming at increasing red cell preservation and viability. DESIGN: Biochemical evaluation designed to study red cell preservation. SETTING: São Paulo University erythrocyte metabolism referral center. SAMPLE: Six normal blood donors from the University Hospital of the Universidade Federal do Paraná, Curitiba, Brazil. MAIN MEASUREMENTS: Weekly assay of erythrocyte adenosine-5´-triphosphate (ATP, 2,3-diphosphoglycerate (2,3DPG, hexokinase (HX, phosphofructokinase (PFK, pyruvate kinase (PK, glucose-6-phosphate dehydrogenase (G-6-PD, 6-phosphogluconic dehydrogenase (6-PGD, glyceraldehyde-3-phosphate dehydrogenase (GAPD, glutathione reduc-tase (GR, glutathione peroxidase (GSHPx, plasma sodium and potas-sium, blood pH, and membrane proteins of red cells preserved in ADSOL were studied during storage for 14 weeks storage. RESULTS: During ADSOL preservation, erythrocyte ATP concentration decreased 60% after 5 weeks, and 90% after 10 weeks; the pH fell from 6.8 to 6.4 by the 14th week. 2,3-DPG concentration was stable during the first week, but fell 90% after 3 weeks and was exhausted after 5 weeks. By the end of the 5th week, an activity decrease of 16-30% for Hx, GAPD, GR, G-6-PD and 6-PGD, 35% for PFK and GSHPx, and 45% for PK were observed. Thereafter, a uniform 10% decay was observed for all enzymes up to the 14th week. The red blood cell membrane pro-teins did not show significant alterations in polyacrylamide gel electro-phoresis (SDS-PAGE during the 14 weeks. CONCLUSION: Although the blood viability was shown to be poor

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)

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.

Preclinical PK/PD model for combined administration of erlotinib and sunitinib in the treatment of A549 human NSCLC xenograft mice.

Science.gov (United States)

Li, Jing-Yun; Ren, Yu-Peng; Yuan, Yin; Ji, Shuang-Min; Zhou, Shu-Pei; Wang, Li-Jie; Mou, Zhen-Zhen; Li, Liang; Lu, Wei; Zhou, Tian-Yan

2016-07-01

Combined therapy of EGFR TKI and VEGFR TKI may produce a greater therapeutic benefit and overcome EGFR TKI-induced resistance. However, a previous study shows that a combination of EGFR TKI erlotinib (ER) with VEGFR TKI sunitinib (SU) did not improve the overall survival in patients with non-small-cell lung cancer (NSCLC). In this study we examined the anticancer effect of ER, SU and their combination in the treatment of A549 human NSCLC xenograft mice, and conducted PK/PD modeling and simulations to optimize the dose regimen. ER (20, 50 mg·kg(-1)·d(-1)) or SU (5, 10, 20 mg·kg(-1)·d(-1)) alone, or their combination were administered to BALB/c nude mice bearing A549 tumors for 22 days. The tumor size and body weight were recorded daily. The experimental data were used to develop PK/PD models describing the quantitative relationship between the plasma concentrations and tumor suppression in different dose regimens. The models were further evaluated and validated, and used to predict the efficacy of different combination regimens and to select the optimal regimen. The in vivo anticancer efficacy of the combination groups was much stronger than that of either drug administered alone. A PK/PD model was developed with a combination index (φ) of 4.4, revealing a strong synergistic effect between ER and SU. The model simulation predicted the tumor growth in different dosage regimens, and showed that the dose of SU played a decisive role in the combination treatment, and suggested that a lower dose of ER (≤5 mg·kg(-1)·d(-1)) and adjusting the dose of SU might yield a better dosage regimen for clinical research. The experimental data and modeling confirm synergistic anticancer effect of ER and SU in the treatment of A549 xenograft mice. The optimal dosage regimen determined by the PK/PD modeling and simulation can be used in future preclinical study and provide a reference for clinical application.

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.

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

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

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%.

Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine

Science.gov (United States)

Heo, Young‐A; Holford, Nick; Kim, Yukyung; Son, Mijeong

2016-01-01

Aims The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. Methods PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. Results A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. Conclusion PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. PMID:27504853

Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model.

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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.

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.

In Silico Absorption, Distribution, Metabolism, Excretion, and Pharmacokinetics (ADME-PK): Utility and Best Practices. An Industry Perspective from the International Consortium for Innovation through Quality in Pharmaceutical Development.

Science.gov (United States)

Lombardo, Franco; Desai, Prashant V; Arimoto, Rieko; Desino, Kelly E; Fischer, Holger; Keefer, Christopher E; Petersson, Carl; Winiwarter, Susanne; Broccatelli, Fabio

2017-11-22

In silico tools to investigate absorption, distribution, metabolism, excretion, and pharmacokinetics (ADME-PK) properties of new chemical entities are an integral part of the current industrial drug discovery paradigm. While many companies are active in the field, scientists engaged in this area do not necessarily share the same background and have limited resources when seeking guidance on how to initiate and maintain an in silico ADME-PK infrastructure in an industrial setting. This work summarizes the views of a group of industrial in silico and experimental ADME scientists, participating in the In Silico ADME Working Group, a subgroup of the International Consortium for Innovation through Quality in Pharmaceutical Development (IQ) Drug Metabolism Leadership Group. This overview on the benefits, caveats, and impact of in silico ADME-PK should serve as a resource for medicinal chemists, computational chemists, and DMPK scientists working in drug design to increase their knowledge in the area.

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

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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.

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

PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Vowinckel, E; Reutens, D; Becher, B

1997-01-01

Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...... examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites...... of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission...

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

Halogenated benzimidazole inhibitors of phosphorylation, ''in vitro'' and ''in vivo'', of the surface acidic proteins of the yeast ribosomal 60S subunit by endogenous protein kinases CK-II and PK60S

International Nuclear Information System (INIS)

Szyszka, Ryszard; Boguszewska, Aleksandra; Grankowski, Nikodem; Shugar, David

1996-01-01

Several halogeno benzimidazoles and 2-azabenzimidazoles, previously shown to be relatively selective inhibitors of protein kinases CK-I and/or CK-II from various sources, including CK-II from yeast [Szyszka et al. (1995) Biochem. Biophys. Res. Commun. 208, 418-424] inhibit also the yeast ribosomal protein kinase PK60S. The most effective inhibitor of CK-II and PK60S was tetrabromo-2-azabenzimidazole (TetraBr-2-azaBz), which was competitive with respect to ATP (and GTP in the case of CK-II) with K i values of 0.7 μM for CK-II, and 0.1 μM for PK60S. PK60S phosphorylates only three (YP1β, YB1β', YP2α) out of five polypeptides of pp13 kDa acidic proteins of 60S subunit phosphorylated by CK-II [Szyszka et al. (1995) Acta Biochim. Polon. 42, 357-362]. Accordingly, TetraBr-azaBz inhibits phosphorylation only of these polypeptides, catalysed by PK60S. Addition of TetraBr-2Bz to cultures of yeast cells, at concentrations which were without effect on cell growth, led to inhibition of intracellular phosphorylation of ribosomal acidic proteins, paralleling that observed ''in vitro''. TetraBr-2-azaBz is shown to be a useful tool for studies on the intracellular regulation of phosphorylation of the ribosomal 60S acidic proteins, which are involved in formation of active ribosomes. (author). 36 refs, 4 figs, 2 tabs

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.

Predictive performance of two PK-PD models of D2 receptor occupancy of the antipsychotics risperidone and paliperidone in rats

NARCIS (Netherlands)

Kozielska, Magdalena; Johnson, Martin; Pilla Reddy, Venkatesh; Vermeulen, An; de Greef, Rik; Li, Cheryl; Grimwood, Sarah; Liu, Jing; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

2010-01-01

Objectives: The level of dopamine D2 receptor occupancy is predictive of efficacy and safety in schizophrenia. Population PK-PD modelling has been used to link observed plasma and brain concentrations to receptor occupancy. The objective of this study was to compare the predictive performance of two

Effects of MicroRNA-34a on the Pharmacokinetics of Cytochrome P450 Probe Drugs in Mice.

Science.gov (United States)

Jilek, Joseph L; Tian, Ye; Yu, Ai-Ming

2017-05-01

MicroRNAs (miRNAs or miRs), including miR-34a, have been shown to regulate nuclear receptor, drug-metabolizing enzyme, and transporter gene expression in various cell model systems. However, to what degree miRNAs affect pharmacokinetics (PK) at the systemic level remains unknown. In addition, miR-34a replacement therapy represents a new cancer treatment strategy, although it is unknown whether miR-34a therapeutic agents could elicit any drug-drug interactions. To address this question, we refined a practical single-mouse PK approach and investigated the effects of a bioengineered miR-34a agent on the PK of several cytochrome P450 probe drugs (midazolam, dextromethorphan, phenacetin, diclofenac, and chlorzoxazone) administered as a cocktail. This approach involves manual serial blood microsampling from a single mouse and requires a sensitive liquid chromatography-tandem mass spectrometry assay, which was able to illustrate the sharp changes in midazolam PK by ketoconazole and pregnenolone 16 α -carbonitrile as well as phenacetin PK by α -naphthoflavone and 3-methylcholanthrene. Surprisingly, 3-methylcholanthrene also decreased systemic exposure to midazolam, whereas both pregnenolone 16 α -carbonitrile and 3-methylcholanthrene largely reduced the exposure to dextromethorphan, diclofenac, and chlorzoxazone. Finally, the biologic miR-34a agent had no significant effects on the PK of cocktail drugs but caused a marginal (45%-48%) increase in systemic exposure to midazolam, phenacetin, and dextromethorphan in mice. In vitro validation of these data suggested that miR-34a slightly attenuated intrinsic clearance of dextromethorphan. These findings from single-mouse PK and corresponding mouse liver microsome models suggest that miR-34a might have minor or no effects on the PK of coadministered cytochrome P450-metabolized drugs. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

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.

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.

Evaluation of a lateral flow-based technology card for blood typing using a simplified protocol in a model of extreme blood sampling conditions.

Science.gov (United States)

Clavier, Benoît; Pouget, Thomas; Sailliol, Anne

2018-02-01

Life-threatening situations requiring blood transfusion under extreme conditions or in remote and austere locations, such as the battlefield or in traffic accidents, would benefit from reliable blood typing practices that are easily understood by a nonscientist or nonlaboratory technician and provide quick results. A simplified protocol was developed for the lateral flow-based device MDmulticard ABO-D-Rh subgroups-K. Its performance was compared to a reference method (PK7300, Beckman Coulter) in native blood samples from donors. The method was tested on blood samples stressed in vitro as a model of hemorrhage cases (through hemodilution using physiologic serum) and dehydration (through hemoconcentration by removing an aliquot of plasma after centrifugation), respectively. A total of 146 tests were performed on 52 samples; 126 in the hemodilution group (42 for each native, diluted 1/2, and diluted 1/4 samples) and 20 in the hemoconcentration group (10 for each native and 10% concentrated samples). Hematocrit in the tested samples ranged from 9.8% to 57.6% while hemoglobin levels ranged from 3.2 to 20.1 g/dL. The phenotype profile detected with the MDmulticard using the simplified protocol resulted in 22 A, seven B, 20 O, and three AB, of which nine were D- and five were Kell positive. No discrepancies were found with respect to the results obtained with the reference method. The simplified protocol for MDmulticard use could be considered a reliable method for blood typing in extreme environment or emergency situations, worsened by red blood cell dilution or concentration. © 2017 AABB.

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...

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.

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...

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).

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)

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.

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.

Naxos disease in an Arab family is not caused by the Pk2157del2 mutation; evidance for exclusion of the plakoglobin gene

International Nuclear Information System (INIS)

Stuhmann, M.; El-Harith, A.; Bukhari, Iqbal A.

2004-01-01

Nax os disease is a rare hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy. This study aims to determine whether Naxos disease in a Saudi Arab family is caused by the Pk2157del2 mutation that was identified in Greek families from Naxos Island where the disease had originally been described. This study was undertaken at King Fahad Hospital of the University, Al-Khobar, and the Medical University of Hannover, in the spring of 2003. Naxos disease has been encountered in a 2-year-old girl and her 30-year-old aunt of a Saudi Arab family. Deoxyribonucleic acid samples of this family were analyzed by polymerase chain-reaction (PCR) amplification of the respective region of the plakoglobin gene, and direct nucleotide sequencing of the PCR-products. Segregation analysis was performed employing the newly detected IVS11+22G/A polymorphism. Molecular genetic analysis of the DNA sample of the child diagnosed with Naxos disease showed absence of the Pk2157del2 mutation. In addition, the segregation analysis revealed heterozygosity for IVS11+22G/A in the affected girl. Absence of the Pk2157del2 frameshift in the affected child proved that Naxos disease in this Saudi Arab family is not caused by the same mutation that was identified in the Greek families. Furthermore, heterozygosity for the IVS11+22G/A polymorphism provided evidence for exclusion of the plakoglobin gene in this consanguineous family. (author)

Decontamination of Bacillus subtilis Spores in a Sealed Package Using a Non-thermal Plasma System

Science.gov (United States)

Keener, Kevin M.; Jensen, J. L.; Valdramidis, V. P.; Byrne, E.; Connolly, J.; Mosnier, J. P.; Cullen, P. J.

The safety of packaged food and medical devices is a major concern to consumers and government officials. Recent inventions (PK-1 and PK-2) based on the principles of non-thermal, atmospheric plasma has shown significant reduction in bacterial contamination inside a sealed package. The objective of this study was to evaluate the PK-1 and PK-2 systems in the reduction of Bacillus subtilis spores using packages containing air or modified atmosphere (MA) gas (65% O2/30% CO2/5% N2). The experimental design consisted of the following parameters: (1) two voltage conditions: 13.5 kV with 1.0 cm electrode gap (PK-1) and 80 kV with 4.5 cm electrode gap (PK-2), (2) two treatment conditions: inside and outside the field of ionization, (3) PK-1 and PK-2 optimized treatment times: 300 and 120 s, respectively, and (4) two package gas types: air and modified atmosphere (MA) gas (65% O2/30% CO2/5% N2). Measurements included: (1) bacterial reductions of Bacillus subtilis var. niger (B. atrophaeus), (2) ozone, nitrous oxides (NOx), and carbon monoxide concentrations, and (3) relative humidity. Bacillus subtilis (1.7 × 106/strip) were loaded into sterile uncovered petri dishes and treated with ionization generated in packages using air or MA gas blend. Samples were treated for 300 s (PK-1) or 120 s (PK-2) and stored at room ­temperature for 24 h. Results documented relative humidity (RH) ranged from 20% to 30%. After 300 s of PK-1 treatment (13.5 kV/44 W/1.0 cm gap), ozone concentrations were 6,000 ppm (air) and 7,500 ppm (MA). After 120 s of PK-2 treatment (80 kV/150 W/4.5 cm), ozone concentrations were 7,500 ppm (air) and 12,000 ppm (MA). Ozone and NOx concentrations were non-detect (ND) after 24 h. PK-1 carbon monoxide levels were package ionization process.

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

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

Development and validation of a dried blood spot assay for the quantification of ribavirin using liquid chromatography coupled to mass spectrometry

Science.gov (United States)

Jimmerson, Leah C.; Zheng, Jia-Hua; Bushman, Lane R.; MacBrayne, Christine E.; Anderson, Peter L.; Kiser, Jennifer J.

2014-01-01

Efficient, inexpensive and sensitive assays for the measurement of drugs are of interest for pharmacokinetic and pharmacodynamics (PK-PD) analysis. Dried blood spots (DBS) are a unique bioanaltyical matrix with the potential to fulfill this interest for the measurement of numerous analytes. Here we describe the development and validation of a reversed-phase high performance liquid chromatographic (LC), tandem mass spectrometry (MS/MS) assay for the determination of ribavirin (RBV) in DBS. A 3mm punch from spotted and dried whole blood was extracted in methanol utilizing isotopically labeled internal standard for LC-MS/MS analysis. Validation was performed over a range of 0.05 μg/mL to 10.0 μg/mL and the method was shown to be precise (coefficient of variation ≤ 15%) and accurate (within ±15% of control). These acceptance criteria were met for hematocrit ranges of 20-54%, for center versus edge punches and for spot volumes from 10-60 μL. RBV was stable for up to 140 days at room temperature and −20°C as well as for three freeze/thaw cycles. Correlation of RBV in DBS versus in plasma yielded r2 ≥ 0.98 demonstrating that DBS can be used as an alternative to plasma for PK-PD studies in human subjects. PMID:24291608

Potentiometric investigations of molecular heteroconjugation equilibria of substituted phenol+n-butylamine systems in dimethyl sulfoxide

International Nuclear Information System (INIS)

Czaja, MaIgorzata; Baginska, Katarzyna; Kozak, Anna; Makowski, Mariusz; Chmurzynski, Lech

2005-01-01

Molecular heteroconjugation constants, K BHA DMSO and K AHB DMSO , expressed as their logarithms, have been determined by potentiometric titration for eleven substituted phenol+n-butylamine systems in a polar protophilic aprotic solvent, dimethyl sulfoxide (DMSO). An increasing tendency towards molecular heteroconjugation in these systems without proton transfer has been found with increasing pK a DMSO (HA), i.e., with decreasing phenol acidity. Moreover, a linear correlation has been established between the determined lgK BHA DMSO values and pK a DMSO (HA). Furthermore, overall stability constants, lgK o DMSO , could be correlated linearly with pK a DMSO (HA) values

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.

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.

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

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.

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.

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.

Determining the pk(a) of N,N-dimethylsphingosine and the flip-flop rate of related compounds with deuterium nuclear magnetic resonance

International Nuclear Information System (INIS)

Lau, Bienca

1995-01-01

Deuterium nuclear magnetic resonance ( 2 H-NMR) spectroscopy was applied to determine the pk(a) of the protein kinase C (PKC) inhibitor, N,N-dimethylsphingosine (DMS), when bound to 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. The quadrupolar splittings from deuterium labels at the α- and the β-positions of the POPC headgroup responded in a manner indicative of a positive surface charge density at pH 7.0. Conversely, at pH 10.0 DMS had virtually no influence on either quadrupolar splitting, an effect attributed to titration of the dimethylamino group of DMS to its neutral form. A DMS titration curve was obtained by quantifying the charge in the quadrupolar splittings as a function of pH. Simulation of this curve yielded a pk(a) of 8.8 of membrane-bound DMS. Using a similar approach, the dynamic process of flip-flop was examined in two DMS analogues. We discuss here the quantitative and the qualitative aspects as well as the limitations of this application. (author)

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.

[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.

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)

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).

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.

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.

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....

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.

Effects of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 on amygdaloid kindled seizures and the anticonvulsant efficacy of diazepam.

Science.gov (United States)

Albertson, T E; Walby, W F

1986-11-01

The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied. When diazepam (3 mg/kg) was injected 15 min before or after a second injection of the vehicle control DMSO (0.25 ml/kg), a significant reduction in the duration of afterdischarge and seizure rank, elicited by a suprathreshold stimulation in amygdaloid-kindled rats, occurred. When either CGS 8216 (10 mg/kg) or RO 15-1788 (10 mg/kg) were given 15 min before diazepam (3 mg/kg) prior to stimulation, the anticonvulsant properties of diazepam were blocked. When RO 15-1788 (10 mg/kg) was given 15 min after diazepam, antagonism of the anticonvulsant effects on diazepam was shown. However, when either CGS-8216 (10 mg/kg) or PK-11195 (10 and 60 mg/kg) were given 15 min after diazepam (3 mg/kg), the anticonvulsant properties of diazepam were not blocked. The anticonvulsant effects of diazepam were reversed when CGS-8216 (10 mg/kg) was given 5 min after diazepam (3 mg/kg) or when a larger dose (30 mg/kg) was given at the same 15 min interval.(ABSTRACT TRUNCATED AT 250 WORDS)

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...

Pharmacokinetic-pharmacodynamic modeling of the antihypertensive interaction between azilsartan medoxomil and chlorthalidone in spontaneously hypertensive rats.

Science.gov (United States)

Kumar Puttrevu, Santosh; Ramakrishna, Rachumallu; Bhateria, Manisha; Jain, Moon; Hanif, Kashif; Bhatta, Rabi Sankar

2017-05-01

A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the time course of blood pressure following oral administration of azilsartan medoxomil (AZM) and/or chlorthalidone (CLT) in spontaneously hypertensive (SH) rats. The drug concentration and pharmacological effects, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tail-cuff manometry, respectively. Sequential PK-PD analysis was performed, wherein the plasma concentration-time data was modeled by one compartmental analysis. Subsequently PD parameters were calculated to describe the time-concentration-response relationship using indirect response (IDR) PK-PD model. The combination of AZ and CLT had greater BP lowering effect compared to AZ or CLT alone, despite of no pharmacokinetic interaction between two drugs. These findings suggest synergistic antihypertensive pharmacodynamic interaction between AZ and CLT noncompetitively, which was simulated by inhibitory function of AZ and stimulatory function of CLT after concomitant administration of the two drugs. The present model was able to capture the turnover of blood pressure adequately at different time points at two different dose levels. The current PK-PD model was successfully utilized in the simulation of PD effect at a dose combination of 0.5 and 2.5 mg/kg for AZ and CLT, respectively. The developed preclinical PK-PD model may provide guidance in the optimization of dose ratio of individual drugs in the combined pharmacotherapy of AZ and CLT at clinical situations.

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

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.

Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites.

Science.gov (United States)

Allgayer, H; Sonnenbichler, J; Kruis, W; Paumgartner, G

1985-01-01

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).

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 ...

Addition of ash and PK with or without N on a peatland in southern Sweden. Effects on tree growth and needle element concentrate; Tillfoersel av aska och PK med eller utan N paa en torvmark i soedra Sverige. Effekter paa traedtillvaext och aemneshalter i barr

Energy Technology Data Exchange (ETDEWEB)

Sikstroem, Ulf (Forestry Research Inst. of Sweden, Uppsala (Sweden))

2008-04-15

In Sweden, about 1.3 million tonnes of ash are produced annually. Out of that amount, 150 000 - 300 000 tonnes have been estimated to originate from forest fuels, i.e. ashes that potentially can be brought back to the forest. Apart from being a compensatory measure after intensive forest harvest (e.g. including tops and branches), the ash may be used to increase the tree growth on peat soils (ash fertilization). On peat soils, tree growth is generally increased after addition of ash or phosphorous (P) and potassium (K) fertilizers. However, in some cases also nitrogen (N) addition is required. On sparsely stocked mires, fertilization may promote the regeneration as well as increase the growth of the trees. Sufficient drainage and supply of plant-available N are some prerequisites for increasing tree growth by PK-addition. In 1982, Skogforsk established a field experiment (168 Perstorp) located in the province of Scania in a sparsely stocked Pinus Sylvestris (L.) sapling stand on a ditched mire where different nutrient regimes were tested. The experiment had a randomized block design including four blocks and seven treatments. Ash and different dozes of P (raw phosphate) and K (potassium chloride), with or without simultaneous N addition, were included as well as un untreated control. The aim of the present study was to evaluate the effects on tree growth and needle elemental concentrations 26 years after treatment. The addition of similar dozes of P (approx. 40 kg P/ha), as ash (2.5 tonnes/ha) or as PK-fertilizer rendered similar growth responses. The increase in stem-wood growth was in the order of 1,6 - 1,9 m3/ha/yr during the 26-year period. The N-addition had no additional effect. On the control plots, the growth was more or less negligible (approx. 0,04 m3sk/ha/yr). On average, the high dozes of raw-phosphate and potassium chloride (40 kg P/ha and 80 kg K/ha) gave a higher growth increase than the low dozes (20 kg P/ha and 40 kg K/ha), although this effect was

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.

Laparoscopic subtotal hysterectomy using the plasma kinetic and lap loop systems: an alternative approach in the surgical management of women with uterine fibroids.

Science.gov (United States)

Erian, John; El-Shawarby, Salem A; Hassan, Mohsen; Wissa, Ihab; Chandakas, Stefanos; Hill, Nicholas

2008-03-01

To evaluate the safety and applicability of laparoscopic subtotal hysterectomy (LSH) using the plasma kinetic (PK) and lap loop systems as an alternative surgical approach in the management of uterine fibroids in women who have completed their families. Sixty-two consecutive LSH were performed during this prospective study from March 2003 to March 2005 at Princess Royal University Hospital, Kent, UK. All study patients had menorrhagia resistant to at least one form of therapy, with a mean duration of symptoms of 3.5 years. In addition, four patients had previous myomectomy. The mean number of fibroids removed was 2.7. The mean weight of the uterus was 141.9 g. The mean operative time was 46.8 min, and the mean blood loss was 126.6 mL. The overall perioperative complication rate was 4.8% with no visceral injury, or return to theatre. At follow-up, all patients were satisfied with surgery. The study describes the first application of the PK and Lap Loop systems in LSH for the surgical management of uterine fibroids in women in whom fertility is not an issue, and its findings suggest that this minimally invasive technique is a safe, and valid alternative. Larger adequately-powered studies are however still required.

Optimalisasi Pengelolaan dan Pemanfaatan Aset Tanah dan Bangunan Perguruan Tinggi Negeri (PTN yang Melaksanakan Pengelolaan Keuangan Badan Layanan Umum (PK BLU0 dalam Rangka Meningkatkan Pelayanan Pendidikan

Directory of Open Access Journals (Sweden)

Dewi Kania Sugiharti

2014-08-01

Full Text Available Abstrak Perguruan Tinggi Negeri Pengelolaan Keuangan Badan Layanan Umum (PTN-PK BLU merupakan instansi pemerintah yang diberi kewenangan untuk melakukan pengelolaan keuangan badan layanan umum, dengan tujuan untuk meningkatkan pelayanan bidang pendidikan kepada masyarakat dalam rangka mencerdaskan kehidupan bangsa. Fleksibilitas dalam pengelolaan keuangan PTNPKBLU berdasarkan prinsip ekonomi dan produktivitas, serta penerapan praktik bisnis yang sehat. Berdasarkan PP Nomor 23 Tahun 2005 dan PP Nomor 6 Tahun 2006 sebagaimana telah diubah dengan PP Nomor 38 Tahun 2008, fleksibilitas tersebut hanya berlaku dalam pengelolaan keuangan. Tanah dan bangunan yang berada dalam penguasaan PTNPKBLU, wajib dipergunakan sesuai dengan tugas pokok dan fungsi PTNPKBLU tersebut. Secara normatif, tidak ada ketentuan yang memberikan wewenang kepada kuasa pengguna barang untuk memanfaatkannya untuk tujuan lain. Aturan memberi peluang untuk mendayagunakan barang milik negara yang tidak dipergunakan sesuai dengan tugas pokok dan fungsi, yaitu dalam bentuk sewa, pinjam pakai, kerja sama pemanfaatan, dan bangun serah guna/bangun guna serah dengan tidak mengubah status kepemilikan, namun pemanfaatan tersebut hanya dapat dilakukan oleh pengelola barang, bukan oleh kuasa pengguna barang. Dalam hal ini, kuasa pengguna barang milik negara hanya berwenang dan bertanggung jawab untuk menyerahkan tanah dan/atau bangunan yang tidak dimanfaatkan untuk kepentingan penyelenggaraan tugas pokok dan fungsi kantor yang dipimpinnya tersebut, kepada pengguna barang. Abstract State University implementing PK BLU is a government agency with the right to use Pengelolaan Keuangan Badan Layanan Umum (PK BLU to better increase educational service in order to improve the intellectual life of the people of Indonesia. Flexibility in a State University implementing PK BLU has to be based on economic principles, productivity, and fairness. Based on Government Regulation 23/2005 and Government

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.

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.

Genetic prion disease: no role for the immune system in disease pathogenesis?

Science.gov (United States)

Friedman-Levi, Yael; Binyamin, Orli; Frid, Kati; Ovadia, Haim; Gabizon, Ruth

2014-08-01

Prion diseases, which can manifest by transmissible, sporadic or genetic etiologies, share several common features, such as a fatal neurodegenerative outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in the CNS. In infectious prion diseases, such as scrapie in mice, prions first replicate in immune organs, then invade the CNS via ascending peripheral tracts, finally causing death. Accelerated neuroinvasion and death occurs when activated prion-infected immune cells infiltrate into the CNS, as is the case for scrapie-infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS inflammatory insult. To establish whether the immune system plays such a central role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated nor aggravated prion disease manifestation. Concomitantly, we present evidence that PK-resistant PrP forms were absent from CNS immune infiltrates, and most surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages and stages of disease. These results imply that the mechanism of genetic prion disease differs widely from that of the infectious presentation, and that the conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS. If the absence of pathogenic PrP forms form immune organs is also true for gCJD patients, it may suggest their blood is devoid of prion infectivity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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 ...

[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.

Study of the production of $\\Lambda_b^0$ and $\\overline{B}^0$ hadrons in $pp$ collisions and first measurement of the $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ branching fraction

CERN Document Server

Aaij, R.; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Buchanan, Emma; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fohl, Klaus; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Ninci, Daniele; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zucchelli, Stefano

2016-01-27

The product of the $\\Lambda_b^0$ ($\\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ ($\\overline{B}^0\\rightarrow J/\\psi\\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\\rm T}<20~{\\rm GeV}/c$ and $2.0 < y < 4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\\sqrt{s}=7~{\\rm TeV}$ in 2011 and $\\sqrt{s}=8~{\\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\\Lambda_B^0}/f_d$, the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ is measured to be \\begin{equation*} \\mathcal{B}(\\Lambda_b^0\\rightarrow J/\\psi pK^-)= (3.04\\pm0.04\\pm0.06\\pm0.33^{+0.43}_{-0.27})\\times10^{-4}, \\end{equation*} where the first uncertainty is st...

[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.

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.

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.

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".

Widespread Dependence of Backup NHEJ on Growth State: Ramifications for the Use of DNA-PK Inhibitors

International Nuclear Information System (INIS)

Singh, Satyendra K.; Wu Wenqi; Zhang Lihua; Klammer, Holger; Wang Minli; Iliakis, George

2011-01-01

Purpose: The backup pathway of nonhomologous end joining (B-NHEJ) enables cells to process DNA double-strand breaks (DSBs) when the DNA-PK-dependent pathway of NHEJ (D-NHEJ) is compromised. Our previous results show marked reduction in the activity of B-NHEJ when LIG4 -/- mouse embryo fibroblasts (MEFs) cease to grow and enter a plateau phase. The dependence of B-NHEJ on growth state is substantially stronger than that of D-NHEJ and points to regulatory mechanisms or processing determinants that require elucidation. Because the different D-NHEJ mutants show phenotypes distinct in their details, it is necessary to characterize the dependence of their DSB repair capacity on growth state and to explore species-specific responses. Methods and Materials: DSB repair was measured in cells of different genetic background from various species using pulsed-field gel electrophoresis, or the formation of γ-H2AX foci, at different stages of growth. Results: Using pulsed-field gel electrophoresis, we report a marked reduction of B-NHEJ during the plateau phase of growth in KU and XRCC4, mouse or Chinese hamster, mutants. Notably, this reduction is only marginal in DNA-PKcs-deficient cells. However, reduced B-NHEJ is also observed in repair proficient, plateau-phase cells after treatment with DNA-PK inhibitors. The reduction of B-NHEJ activity in the plateau phase of growth does not derive from the reduced expression of participating proteins, is detectable by γ-H2AX foci analysis, and leads to enhanced cell killing. Conclusions: These results further document the marked dependence on growth state of an essential DSB repair pathway and show the general nature of the effect. Molecular characterization of the mechanism underlying this response will help to optimize the administration of DNA repair inhibitors as adjuvants in radiation therapy.

Estimating the arterial input function from dynamic contrast-enhanced MRI data with compensation for flow enhancement (II): Applications in spine diagnostics and assessment of crohn's disease

NARCIS (Netherlands)

van Schie, Jeroen J. N.; Lavini, Cristina; van Vliet, Lucas J.; Kramer, Gem; Pieters-van den Bos, Indra; Marcus, J. T.; Stoker, Jaap; Vos, Frans M.

2017-01-01

Pharmacokinetic (PK) models can describe microvascular density and integrity. An essential component of PK models is the arterial input function (AIF) representing the time-dependent concentration of contrast agent (CA) in the blood plasma supplied to a tissue. To evaluate a novel method for

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

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

Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects.

Science.gov (United States)

Vu, Thuy; Ma, Peiming; Chen, Jiyun Sunny; de Hoon, Jan; Van Hecken, Anne; Yan, Lucy; Wu, Liviawati Sutjandra; Hamilton, Lisa; Vargas, Gabriel

2017-09-01

Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.

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.

A physiologically-based recirculatory meta-model for nasal fentanyl in man

DEFF Research Database (Denmark)

Upton, RN; Foster, DJR; Christrup, Lona Louring

2012-01-01

Pharmacokinetic (PK) and pharmacodynamic (PD) data were available from a study of a nasal delivery system for the opioid analgesic fentanyl, together with data on the kinetics of fentanyl in arterial blood in man, and in the lung and brain of sheep. Our aim was to reconcile these data using a phy...

Population pharmacokinetics of nalmefene in healthy subjects and its relation to μ-opioid receptor occupancy.

Science.gov (United States)

Kyhl, Lars-Erik Broksoe; Li, Shen; Faerch, Kirstine Ullitz; Soegaard, Birgitte; Larsen, Frank; Areberg, Johan

2016-02-01

The aims of this study were to develop a population pharmacokinetic (PK) model to describe the PK of nalmefene in healthy subjects and to relate the exposure of nalmefene to the μ-opioid receptor occupancy by simulations in the target population. Data from nine phase I studies (243 subjects) with extensive blood sampling were pooled and used for the population PK model building. Data from four other phase I studies (85 subjects) were pooled and used as an external validation dataset. Eight subjects from an imaging study contributed occupancy data and the pharmacokinetic/pharmacodynamic (PK/PD) relationship was modelled. Combining the population PK model and the PK/PD relationship enabled simulations to predict μ-opioid occupancy. A two compartment model with first order absorption best described the nalmefene PK data. The typical subject in the population was estimated to have a systemic clearance of 60.4 l h(-1) and a central volume of distribution of 266 l. Absolute oral bioavailability was estimated to 41% without food intake and with food about 53%. Simulation of the μ-opioid receptor occupancy shows that the 95% confidence bound is within or above 60-90% occupancy for up to 22-24 h after a single dose of 20 mg nalmefene. A robust population PK model for nalmefene was developed. Based on the concentration-occupancy model the μ-opioid receptor occupancy after a single 20 mg dose of nalmefene is predicted to be above the target therapeutic occupancy for about 24 h in about 95% of the target population. © 2015 The British Pharmacological Society.

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...

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.

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

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

Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

Science.gov (United States)

Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

2008-05-01

Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

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.

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.

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

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.

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

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.

Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC-TQ/MS

Directory of Open Access Journals (Sweden)

Yi Jin

2017-10-01

Full Text Available The compatibility between Danggui (Angelicae Sinensis Radix and Honghua (Carthami Flos is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae.

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.

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.

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...

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...

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.

Pharmacokinetics of enrofloxacin HCl-2H2O (ENRO-C) in dogs and PK/PD Monte Carlo simulations against Leptospira sp.

Science.gov (United States)

Sumano, Hector; Ocampo, Luis; Tapia, Graciela; Mendoza, C de Jesus; Gutierrez, Lilia

2018-04-12

Pharmacokinetics/pharmacodynamics (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H 2 O (Enro-C), as well as Monte Carlo simulations based on composite MIC 50 and MIC 90 vs. Leptospira sp., were carried out in dogs after their IM and oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high performance liquid chromatography (HPLC). Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1.6 ± 0.12 µg/mL and 7.6 ± 0.93 µg/mL after IM administration. Area under the plasma vs. time concentrations in 24 h (AUC 0-24 ) were 8.02 µg/mL/h and 36.2 µg/mL/h for Enro-R oral and Enro-C oral , respectively, and 8.55 ± 0.85 µg/mL/h and 56.4 ± 6.21 µg/mL/h after IM administration of these drugs. Only PK/PD ratios and Monte Carlo simulations obtained with Enro-C, anticipate that its IM administration to dogs will result in therapeutic concentrations to treat leptospirosis. This is the first time enrofloxacin has been recommended to treat this disease in dogs.

[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.

The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

International Nuclear Information System (INIS)

Pajonk, Frank; Ophoven, Arndt van; Weissenberger, Christian; McBride, William H

2005-01-01

By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132

Virtual blood bank

Directory of Open Access Journals (Sweden)

Kit Fai Wong

2011-01-01

Full Text Available Virtual blood bank is the computer-controlled, electronically linked information management system that allows online ordering and real-time, remote delivery of blood for transfusion. It connects the site of testing to the point of care at a remote site in a real-time fashion with networked computers thus maintaining the integrity of immunohematology test results. It has taken the advantages of information and communication technologies to ensure the accuracy of patient, specimen and blood component identification and to enhance personnel traceability and system security. The built-in logics and process constraints in the design of the virtual blood bank can guide the selection of appropriate blood and minimize transfusion risk. The quality of blood inventory is ascertained and monitored, and an audit trail for critical procedures in the transfusion process is provided by the paperless system. Thus, the virtual blood bank can help ensure that the right patient receives the right amount of the right blood component at the right time.

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.

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.

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 ...

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.

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.

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.

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 ...

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

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...

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.

Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria

Directory of Open Access Journals (Sweden)

Lindegardh Niklas

2011-07-01

Full Text Available Abstract Background Currently, population pharmacokinetic (PK studies of anti-malarial drugs are designed primarily by the logistical and ethical constraints of taking blood samples from patients, and the statistical models that are fitted to the data are not formally considered. This could lead to imprecise estimates of the target PK parameters, and/or designs insufficient to estimate all of the parameters. Optimal design methodology has been developed to determine blood sampling schedules that will yield precise parameter estimates within the practical constraints of sampling the study populations. In this work optimal design methods were used to determine sampling designs for typical future population PK studies of dihydroartemisinin, the principal biologically active metabolite of oral artesunate. Methods Optimal designs were derived using freely available software and were based on appropriate structural PK models from an analysis of data or the literature and key sampling constraints identified in a questionnaire sent to active malaria researchers (3-4 samples per patient, at least 15 minutes between samples. The derived optimal designs were then evaluated via simulation-estimation. Results The derived optimal sampling windows were 17 to 29 minutes, 30 to 57 minutes, 2.5 to 3.7 hours and 5.8 to 6.6 hours for non-pregnant adults; 16 to 29 minutes, 31 minutes to 1 hour, 2.0 to 3.4 hours and 5.5 to 6.6 hours for designs with non-pregnant adults and children and 35 to 59 minutes, 1.2 to 3.4 hours, 3.4 to 4.9 hours and 6.0 to 8.0 hours for pregnant women. The optimal designs resulted in acceptable precision of the PK parameters. Conclusions The proposed sampling designs in this paper are robust and efficient and should be considered in future PK studies of oral artesunate where only three or four blood samples can be collected.

Insulin aspart pharmacokinetics: an assessment of its variability and underlying mechanisms.

Science.gov (United States)

Rasmussen, Christian Hove; Røge, Rikke Meldgaard; Ma, Zhulin; Thomsen, Maria; Thorisdottir, Rannveig Linda; Chen, Jian-Wen; Mosekilde, Erik; Colding-Jørgensen, Morten

2014-10-01

Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control post-prandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between and within individuals. The present article identifies the main physiological mechanisms that govern the PK of IAsp following subcutaneous administration and quantifies them in terms of their contribution to the overall variability. CT scanning data from Thomsen et al. (2012) are used to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic distribution and elimination (Pørksen et al., 1997; Sjöstrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b) are analyzed in the nonlinear mixed effects software Monolix® to determine the presence and effects of the mechanisms described in this article. The distribution of IAsp in the subcutaneous depot show an initial dilution of approximately a factor of two in a single experiment. Injected insulin hexamers exist in a chemical equilibrium with monomers and dimers, which depends strongly on the degree of dilution in subcutis, the presence of auxiliary substances, and a variety of other factors. Sensitivity to the initial dilution in subcutis can thus be a cause of some of the variability. Temporal variations in the PK are explained by variations in the subcutaneous blood flow. IAsp antibodies are found to be a large contributor to the variability of total insulin PK in a study by Chen et al. (2005), since only

DNA-PK dependent targeting of DNA-ends to a protein complex assembled on matrix attachment region DNA sequences

International Nuclear Information System (INIS)

Mauldin, S.K.; Getts, R.C.; Perez, M.L.; DiRienzo, S.; Stamato, T.D.

2003-01-01

Full text: We find that nuclear protein extracts from mammalian cells contain an activity that allows DNA ends to associate with circular pUC18 plasmid DNA. This activity requires the catalytic subunit of DNA-PK (DNA-PKcs) and Ku since it was not observed in mutants lacking Ku or DNA-PKcs but was observed when purified Ku/DNA-PKcs was added to these mutant extracts. Competition experiments between pUC18 and pUC18 plasmids containing various nuclear matrix attachment region (MAR) sequences suggest that DNA ends preferentially associate with plasmids containing MAR DNA sequences. At a 1:5 mass ratio of MAR to pUC18, approximately equal amounts of DNA end binding to the two plasmids were observed, while at a 1:1 ratio no pUC18 end-binding was observed. Calculation of relative binding activities indicates that DNA-end binding activities to MAR sequences was 7 to 21 fold higher than pUC18. Western analysis of proteins bound to pUC18 and MAR plasmids indicates that XRCC4, DNA ligase IV, scaffold attachment factor A, topoisomerase II, and poly(ADP-ribose) polymerase preferentially associate with the MAR plasmid in the absence or presence of DNA ends. In contrast, Ku and DNA-PKcs were found on the MAR plasmid only in the presence of DNA ends. After electroporation of a 32P-labeled DNA probe into human cells and cell fractionation, 87% of the total intercellular radioactivity remained in nuclei after a 0.5M NaCl extraction suggesting the probe was strongly bound in the nucleus. The above observations raise the possibility that DNA-PK targets DNA-ends to a repair and/or DNA damage signaling complex which is assembled on MAR sites in the nucleus

[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.

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

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.

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

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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.

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

Collision Based Blood Cell Distribution of the Blood Flow

Science.gov (United States)

Cinar, Yildirim

2003-11-01

Introduction: The goal of the study is the determination of the energy transferring process between colliding masses and the application of the results to the distribution of the cell, velocity and kinetic energy in arterial blood flow. Methods: Mathematical methods and models were used to explain the collision between two moving systems, and the distribution of linear momentum, rectilinear velocity, and kinetic energy in a collision. Results: According to decrease of mass of the second system, the velocity and momentum of constant mass of the first system are decreased, and linearly decreasing mass of the second system captures a larger amount of the kinetic energy and the rectilinear velocity of the collision system on a logarithmic scale. Discussion: The cause of concentration of blood cells at the center of blood flow an artery is not explained by Bernoulli principle alone but the kinetic energy and velocity distribution due to collision between the big mass of the arterial wall and the small mass of blood cells must be considered as well.

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.)

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.

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

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)

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)

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

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...

Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep.

Science.gov (United States)

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Hayashi, Hisamitsu; Onuki, Reiko; Hofmann, Alan F; Sugiyama, Yuichi

2006-03-01

Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.

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.

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.

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.

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

Science.gov (United States)

Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

2017-10-01

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of immunohematologic routine methods using the new erythrocyte-magnetized technology on the QWALYS 2 system.

Science.gov (United States)

Schoenfeld, Helge; Bulling, Katia; von Heymann, Christian; Neuner, Bruno; Kalus, Ulrich; Kiesewetter, Holger; Pruss, Axel

2009-07-01

QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte-magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps. Overall 499 blood samples were tested with our routine blood bank methods for ABO/D grouping, 313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200), and 478 samples for ABS (gel centrifugation technique, DiaMed). All samples were tested in parallel with the EMT. In 496 of 499 samples (99.4%), a complete concordance between the observed (QWALYS 2) and the expected results for ABO/D grouping was found. One sample with a weak A in an AB blood group and 2 samples with a weak D were not detected by the QWALYS system. Rh phenotyping and K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were negative in both and 15 samples showed the same antibody specificity in both. Three immunoglobulin M antibodies were as expected negative in EMT and positive by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One autoantibody was found by EMT only. The EMT is reliably suited to ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect immunoglobulin G red blood cell alloantibodies as well. The rate of false-positive reactions in ABS due to lipemic and fibrinic samples needs to be reduced.

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.

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.

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

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.

Hsp27, Hsp70, and metallothionein in MDCK and LLC-PK1 renal epithelial cells: effects of prolonged exposure to cadmium

International Nuclear Information System (INIS)

Bonham, Rita T.; Fine, Michael R.; Pollock, Fiona M.; Shelden, Eric A.

2003-01-01

Cadmium is a widely distributed industrial and environmental toxin. The principal target organ of chronic sublethal cadmium exposure is the kidney. In renal epithelial cells, acute high-dose cadmium exposure induces differential expression of proteins, including heat shock proteins. However, few studies have examined heat shock protein expression in cells after prolonged exposure to cadmium at sublethal concentrations. Here, we assayed total cell protein, neutral red uptake, cell death, and levels of metallothionein and heat shock proteins Hsp27 and inducible Hsp70 in cultures of MDCK and LLC-PK1 renal epithelial cells treated with cadmium for 3 days. Treatment with cadmium at concentrations equal to or greater than 10 μM (LLC-PK1) or 25 μM (MDCK) reduced measures of cell vitality and induced cell death. However, a concentration-dependent increase in Hsp27 was detected in both cell types treated with as little as 5 μM cadmium. Accumulation of Hsp70 was correlated only with cadmium treatment at concentrations also causing cell death. Metallothionein was maximally detected in cells treated with cadmium at concentrations that did not reduce cell vitality, and further increases were not detected at greater concentrations. These results reveal that heat shock proteins accumulate in renal epithelial cells during prolonged cadmium exposure, that cadmium induces differential expression of heat shock protein in epithelial cells, and that protein expression patterns in epithelial cells are specific to the cadmium concentration and degree of cellular injury. A potential role for Hsp27 in the cellular response to sublethal cadmium-induced injury is also implicated by our results

Aliphatic semisynthetic amino terminal variants of myoglobin: enrichment with carbon-13, determination and interpretation of terminal pK values and motions

International Nuclear Information System (INIS)

Busch, M.R.

1985-01-01

The synthesis of a series of myoglobins substituted in the amino terminal residue to provide variation in the aliphatic nature of the side chain and enrichment in 13 C was accomplished by semisynthetic methods. The replacements of valine, the native first residue, included 13 C enriched glycine, alanine, valine, leucine, and isoleucine. The products were extensively characterized and found to be virtually indistinguishable by most physical methods. 13 C NMR spectroscopy showed significant differences in the amino terminal pK value, ranging from 7.72 for myoglobin to 7.15 for myoglobin. Consideration of the electrostatic effects of the charge array indicated a balance of interactions at this site not significantly altered by variations in the side chain. By examination of the crystal structure, consideration of earlier work regarding the interactions of the side chain of Leu-2, and data regarding the motions of the terminal residue, it was concluded that the interaction of the side chain of the first residue with the hydrophobic cluster formed primarily by close contact of invariant residues Leu-2 and Leu-137 was the primary cause for the reduction in the terminal pK values seen for the larger aliphatics. By restricting the freedom of the residue, this interaction limits the available hydration volume, and consequently favors the unprotonated form of the amine. The concurrent observation of both functional elements in the series of α amino terminal residues brings out the interrelated consequences for the two categories of solvent interactions controlling structural and functional properties in a graded way

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

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

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.

Genetic diversity and natural selection in the rhoptry-associated protein 1 (RAP-1) of recent Plasmodium knowlesi clinical isolates from Malaysia.

Science.gov (United States)

Rawa, Mira Syahfriena Amir; Fong, Mun-Yik; Lau, Yee-Ling

2016-02-05

The Plasmodium rhoptry-associated protein 1 (RAP-1) plays a role in the formation of the parasitophorous vacuole following the parasite's invasion of red blood cells. Although there is some evidence that the protein is recognized by the host's immune system, study of Plasmodium falciparum RAP-1 (PfRAP-1) suggests that it is not under immune pressure. A previous study on five old (1953-1962) P. knowlesi strains suggested that RAP-1 has limited genetic polymorphism and might be under negative selection. In the present study, 30 recent P. knowlesi isolates were studied to obtain a better insight into the polymorphism and natural selection of PkRAP-1. Blood samples from 30 knowlesi malaria patients were used. These samples were collected between 2010 and 2014. The PkRAP-1 gene, which contains two exons, was amplified by PCR, cloned into Escherichia coli and sequenced. Genetic diversity and phylogenetic analyses were performed using MEGA6 and DnaSP ver. 5.10.00 programs. Thirty PkRAP-1 sequences were obtained. The nucleotide diversity (π) of exons 1, 2 and the total coding region (0.00915, 0.01353 and 0.01298, respectively) were higher than those of the old strains. Further analysis revealed a lower rate of non-synonymous (dN) than synonymous (dS) mutations, suggesting negative (purifying) selection of PkRAP-1. Tajima's D test and Fu and Li's D test values were not significant. At the amino acid level, 22 haplotypes were established with haplotype H7 having the highest frequency (7/34, 20.5 %). In the phylogenetic analysis, two distinct haplotype groups were observed. The first group contained the majority of the haplotypes, whereas the second had fewer haplotypes. The present study found higher genetic polymorphism in the PkRAP-1 gene than the polymorphism level reported in a previous study. This observation may stem from the difference in sample size between the present (n = 30) and the previous (n = 5) study. Synonymous and non-synonymous mutation analysis indicated

Current concepts in blood glucose monitoring.

Science.gov (United States)

Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

2013-12-01

Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

Current concepts in blood glucose monitoring

Science.gov (United States)

Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

2013-01-01

Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus. PMID:24910827

Current concepts in blood glucose monitoring

Directory of Open Access Journals (Sweden)

Kranti Shreesh Khadilkar

2013-01-01

Full Text Available Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG and continuous glucose monitoring system (CGMS. It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

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

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.

Automated processing of whole blood units: operational value and in vitro quality of final blood components.

Science.gov (United States)

Jurado, Marisa; Algora, Manuel; Garcia-Sanchez, Félix; Vico, Santiago; Rodriguez, Eva; Perez, Sonia; Barbolla, Luz

2012-01-01

The Community Transfusion Centre in Madrid currently processes whole blood using a conventional procedure (Compomat, Fresenius) followed by automated processing of buffy coats with the OrbiSac system (CaridianBCT). The Atreus 3C system (CaridianBCT) automates the production of red blood cells, plasma and an interim platelet unit from a whole blood unit. Interim platelet unit are pooled to produce a transfusable platelet unit. In this study the Atreus 3C system was evaluated and compared to the routine method with regards to product quality and operational value. Over a 5-week period 810 whole blood units were processed using the Atreus 3C system. The attributes of the automated process were compared to those of the routine method by assessing productivity, space, equipment and staffing requirements. The data obtained were evaluated in order to estimate the impact of implementing the Atreus 3C system in the routine setting of the blood centre. Yield and in vitro quality of the final blood components processed with the two systems were evaluated and compared. The Atreus 3C system enabled higher throughput while requiring less space and employee time by decreasing the amount of equipment and processing time per unit of whole blood processed. Whole blood units processed on the Atreus 3C system gave a higher platelet yield, a similar amount of red blood cells and a smaller volume of plasma. These results support the conclusion that the Atreus 3C system produces blood components meeting quality requirements while providing a high operational efficiency. Implementation of the Atreus 3C system could result in a large organisational improvement.

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

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.

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

Current concepts in blood glucose monitoring

OpenAIRE

Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

2013-01-01

Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on t...

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.

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

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 ...

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.

A potentiometric study of (acid+base) equilibria in substituted 4-nitropyridine N-oxide systems in methanol and dimethyl sulfoxide

International Nuclear Information System (INIS)

Gurzynski, Lukasz; Puszko, Aniela; Makowski, Mariusz; Chmurzynski, Lech

2007-01-01

The acid dissociation constants for cationic acids conjugated with 4-nitropyridine N-oxides have been determined using potentiometric titration method. The measurements in the systems of thirteen 4-nitropyridine N-oxide derivatives were carried out in the polar amphiprotic methanol (MeOH) and in the aprotic protophilic dimethyl sulfoxide (DMSO). Likewise as in the polar aprotic protophobic solvents (acetonitrile, acetone) it was found that in MeOH for all N-oxides studied the pK a values were readily determinable, whereas in DMSO the pK a values were hardly determinable or indeterminable by using the potentiometric method. In addition, just like in our previous investigations it was revealed that the sequence of the pK a values of the cationic acids in methanol is the same as in the water and the values are lower than those determined in acetonitrile and acetone. Also, it was found that the phenomenon of cationic homoconjugation equilibria was not present in the systems involving 4-nitropyridine N-oxide derivatives in both solvents used. Furthermore, protonation energies, ΔE prot , and Gibbs free enthalpies, ΔG prot , in vacuo have been compared with acid dissociation constants (expressed as pK a MeOH values) of the protonated N-oxides determined by potentiometric titration in methanol to establish a correlation between these magnitudes

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.

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...

[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis].

Science.gov (United States)

Morales-León, Felipe; von Plessing-Rossel, Carlos; Villa-Zapata, Lorenzo; Fernández-Rocca, Pola; Sanhueza-Sanhueza, Cindy; Bello-Toledo, Helia; Mella-Montecinos, Sergio

2015-04-01

Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

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 ...

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.

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.

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

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...

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.

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.

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.

Proyecto del paso superior sobre la carretera M-503 y accesos. Enlace con Villanueva del Pardillo en el P.K. 3+290 (Madrid)

OpenAIRE

Alonso Placín, Alba

2009-01-01

El presente Proyecto tiene por objeto definir y valorar las obras necesarias para la construcción del paso superior sobre la carretera M-503 en el PK 3+290, entre el tramo comprendido entre la M-50 y la M-600, así como los accesos correspondientes desde las glorietas colindantes. La carretera sobre la que discurre el paso superior objeto de proyecto tiene previsto un desdoblamiento para soportar más capacidad, con lo cual se harán referencias en ciertos casos, a esta nueva c...

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.

The Clinical Pharmacokinetics and Pharmacodynamics of Warfarin When Combined with Compound Danshen: A Case Study for Combined Treatment of Coronary Heart Diseases with Atrial Fibrillation

Directory of Open Access Journals (Sweden)

Chunxiao Lv

2017-11-01

Full Text Available Warfarin is used as anticoagulant and Compound Danshen prescription (CDP is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs with atrial fibrillation (AF. Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP on the pharmacokinetics (PK and pharmacodynamics (PD profiles of warfarin was investigated in patients. The dose and blood concentrations of warfarin, the four indicators of blood coagulation, prothrombin time, activated partial thromboplatin time, thrombin time, fibrinogen, and international normalized ratio value were compared when with and without CDDP treatment. The population PK (PPK and PPK-PD models were established to assess patient demographics, genetic polymorphisms and CDDP as covariates. And the Seattle Angina Questionnaire was used to evaluate clinical efficacy, and the bleeding risk of combination was analyzed. The results indicated that CDDP had little influence on PK and PD profiles of warfarin in most patients and the combination of CCDP and warfarin would be a promising alternative regime for CHD with AF patients. The study was registered on China Clinical Trial Registry with number ChiCTR-ONRC-13003523.

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

Bottlenecks of blood processing in Uganda

NARCIS (Netherlands)

Kajja, I.; Kyeyune, D.; Bimenya, G. S.; Sibinga, C. T. S.

2010-01-01

Aim: To identify where and why delays occur in Uganda blood banks. Background: The timely provision and supply of safe and efficacious blood components to hospitals depends on sound systems in the processing blood banks. Poorly managed systems lead to apparent blood shortages in hospitals and

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 ...

Blood component fractionation: manual versus automatic procedures.

Science.gov (United States)

Pasqualetti, Daniela; Ghirardini, Alessandro; Cristina Arista, Maria; Vaglio, Stefania; Fakeri, Azis; Waldman, Alan A; Girelli, Gabriella

2004-02-01

Over the last few years, quality system requirements have been introduced for blood components. The necessary compliance with standard productions will have a considerable impact on Blood Banks. The introduction of automated methods is the most satisfactory means to meet these requirements for blood component preparation. A new device has been developed to automate the fractionation of blood into components. We evaluated the efficacy of this instrument as compared to manual methods. A total of 218 units of blood have been collected, into several different commercial blood bag systems (77 into standard quadruple bag systems, 141 into bag systems with integrated in line filters), and used to evaluate the universality of the instrument. Whole blood units were processed using the Top/Top system and the Compomat G4 (Fresenius HemoCare). A separate program protocol was developed for each kind of bag. Use of the Compomat G4 resulted in a statistically significant (pblood components, and has been shown adaptable to use with different blood bag systems.

Distribution of cyclosporine A in ocular tissues after topical administration of cyclosporine A cationic emulsions to pigmented rabbits.

Science.gov (United States)

Daull, Philippe; Lallemand, Frédéric; Philips, Betty; Lambert, Grégory; Buggage, Ronald; Garrigue, Jean-Sébastien

2013-03-01

The aim of this study was to compare the ocular and systemic distribution of cyclosporine A (CsA) in rabbits after the instillation of preservative-free CsA cationic and anionic emulsions. For the single-dose pharmacokinetic (PK) study, rabbits were instilled with 50 μL of the test material. For the multiple-dose PK study, rabbits were instilled twice daily with Restasis or once daily with NOVA22007 for 10 days. At each time point, the cornea, conjunctiva, and whole blood were harvested for CsA quantification. Ocular and systemic distribution were determined after 4 times daily instillations with 50 μL of 3H-CsA cationic and anionic emulsions for 7 days. Restasis was used as a reference in all studies. Single-dose PK data demonstrated that NOVA22007 0.1% and 0.05% delivered higher CsA concentrations to the cornea than Restasis [concentration maximum (C max): 2692, 1372, and 748 ng/g, respectively] and have a better exposition (area under the curve). Conjunctival Cmax values were 1914, 696, and 849 ng/g and area under the curve values were 3984, 2796, and 2515 ng/g · h, for either dose of the cationic emulsions and Restasis, respectively. The multiple-dose PK and the 3H-CsA distribution data demonstrated that the systemic distribution after repeated instillations was low and comparable for all emulsions. These data demonstrate that the CsA cationic emulsions were more effective than Restasis at delivering CsA to target tissues, thus confirming the potential advantage of cationic emulsions over anionic emulsions as vehicle for ocular drug delivery for the treatment of ocular surface diseases.

Linearity analysis and comparison study on the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients

Directory of Open Access Journals (Sweden)

Jianing Chen

2016-03-01

Full Text Available The epoc® blood analysis system (Epocal Inc., Ottawa, Ontario, Canada is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc® system was evaluated in a tertiary hospital, see related research article “Analytical evaluation of the epoc® point-of-care blood analysis system in cardiopulmonary bypass patients” [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc® meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.

Serotonin and Blood Pressure Regulation

Science.gov (United States)

Morrison, Shaun F.; Davis, Robert Patrick; Barman, Susan M.

2012-01-01

5-Hydroxytryptamine (5-HT; serotonin) was discovered more than 60 years ago as a substance isolated from blood. The neural effects of 5-HT have been well investigated and understood, thanks in part to the pharmacological tools available to dissect the serotonergic system and the development of the frequently prescribed selective serotonin-reuptake inhibitors. By contrast, our understanding of the role of 5-HT in the control and modification of blood pressure pales in comparison. Here we focus on the role of 5-HT in systemic blood pressure control. This review provides an in-depth study of the function and pharmacology of 5-HT in those tissues that can modify blood pressure (blood, vasculature, heart, adrenal gland, kidney, brain), with a focus on the autonomic nervous system that includes mechanisms of action and pharmacology of 5-HT within each system. We compare the change in blood pressure produced in different species by short- and long-term administration of 5-HT or selective serotonin receptor agonists. To further our understanding of the mechanisms through which 5-HT modifies blood pressure, we also describe the blood pressure effects of commonly used drugs that modify the actions of 5-HT. The pharmacology and physiological actions of 5-HT in modifying blood pressure are important, given its involvement in circulatory shock, orthostatic hypotension, serotonin syndrome and hypertension. PMID:22407614

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.

Blood pressure and blood flow variation during postural change from sitting to standing: model development and validation

DEFF Research Database (Denmark)

Olufsen, M.S.; Ottesen, Johnny T.; Tran, H.T.

2005-01-01

Short-term cardiovascular responses to postural change from sitting to standing involve complex interactions between the autonomic nervous system, which regulates blood pressure, and cerebral autoregulation, which maintains cerebral perfusion. We present a mathematical model that can predict...... dynamic changes in beat-to-beat arterial blood pressure and middle cerebral artery blood flow velocity during postural change from sitting to standing. Our cardiovascular model utilizes 11 compartments to describe blood pressure, blood flow, compliance, and resistance in the heart and systemic circulation....... To include dynamics due to the pulsatile nature of blood pressure and blood flow, resistances in the large systemic arteries are modeled using nonlinear functions of pressure. A physiologically based submodel is used to describe effects of gravity on venous blood pooling during postural change. Two types...

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)

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

Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA- 714, and 11C-PK11195 in a Rat Model of Acute Neuro-inflammation

International Nuclear Information System (INIS)

Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B.; Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B.; Chauveau, F.; Boutin, H.; James, M.; Kassiou, M.; Kassiou, M.

2009-01-01

Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, 11 C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and 18 F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: 11 C-DPA-713 and 18 F-DPA-714, as well as the classic radioligand 11 C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: 11 C-DPA-713 and 18 F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, 18 F-DPA-714 performed better than 11 C-DPA-713 and 11 C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: 18 F-DPA-714 appears to be an attractive alternative to 11 C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with 18 F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. 18 F-DPA-714 will be further evaluated in longitudinal studies of neuro-inflammatory conditions such as are encountered in stroke or neuro

Time-to-detection of bacteria and yeast with the BACTEC FX versus BacT/Alert Virtuo blood culture systems.

Science.gov (United States)

Somily, Ali Mohammed; Habib, Hanan Ahmed; Torchyan, Armen Albert; Sayyed, Samina B; Absar, Muhammed; Al-Aqeel, Rima; Binkhamis, A Khalifa

2018-01-01

Bloodstream infections are associated with high rates of morbidity and mortality. Rapid detection of bloodstream infections is important in achieving better patient outcomes. Compare the time-to-detection (TTD) of the new BacT/Alert Virtuo and the BACTEC FX automated blood culture systems. Prospective simulated comparison of two instruments using seeded samples. Medical microbiology laboratory. Blood culture bottles were seeded in triplicate with each of the standard ATCC strains of aerobes, anaerobes and yeast. TTD was calculated as the length of time from the beginning of culture incubation to the detection of bacterial growth. TTD for the various tested organisms on the two microbial detection systems. The 99 bottles of seeded blood cultures incubated in each of the blood culture systems included 21 anaerobic, 39 aerobic and 39 pediatric bottles. The BacT/Alert Virtuo system exhibited significantly shorter TTD for 72.7 % of the tested organisms compared to BACTEC FX system with a median difference in mean TTD of 2.1 hours (interquartile range: 1.5-3.5 hours). The BACTEC FX system was faster in 15.2% (5/33) of microorganisms, with a median difference in mean TTD of 25.9 hours (IQR: 9.1-29.2 hours). TTD was significantly shorter for most of the microorganisms tested on the new BacT/Alert Virtuo system compared to the BACTEC FX system. Use of simulated cultures to assess TTD may not precisely represent clinical blood cultures. None.

Development and evaluation of diclofenac sodium thermorevesible subcutaneous drug delivery system.

Science.gov (United States)

Nasir, Fazli; Iqbal, Zafar; Khan, Jamshaid A; Khan, Abad; Khuda, Fazli; Ahmad, Lateef; Khan, Amirzada; Khan, Abbas; Dayoo, Abdullah; Roohullah

2012-12-15

The objective of current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for diclofenac sodium. The poloxamer 407, methyl cellulose, hydroxypropyl methyl cellulose and polyethylene glycol were used alone and in combination in different ratios to design the delivery system. The physical properties like Tsol-gel, viscosity, clarity of solution and gel were evaluated. The in vitro release of the drug delivery system was evaluated using membrane less method and the drug release kinetics and mechanism was predicted by applying various mathematical models to the in vitro dissolution data. Rabbits were used as in vivo model following subcutaneous injection to predict various pharmacokinetics parameters by applying Pk-Summit software. The in vitro and in vivo data revealed that the system consisting of the poloxamer 407 in concentration of 20% (DP20) was the most capable formulation for extending the drug release and maintaining therapeutic blood level of DS for longer duration (144 h). The data obtained for drug content after autoclaving the solutions indicate that autoclaving results in 6% degradation of DS. The data also suggested that the studied polymers poloxamer, MC and PG are good candidate to extend the drug release possessing a unique thermoreversible property. Copyright © 2012 Elsevier B.V. All rights reserved.

Simple intake and pharmacokinetic modeling to characterize exposure of Americans to perfluoroctanoic acid, PFOA.

Science.gov (United States)

Lorber, Matthew; Egeghy, Peter P

2011-10-01

Models for assessing intakes of perfluorooctanoic acid, PFOA, are described and applied. One model is based on exposure media concentrations and contact rates. This model is applied to general population exposures for adults and 2-year old children. The other model is a simple one-compartment, first-order pharmacokinetic (PK) model. Parameters for this model include a rate of elimination of PFOA and a blood volume of distribution. The model was applied to data from the National Health and Nutritional Examination Survey, NHANES, to backcalculate intakes. The central tendency intake estimate for adults and children based on exposure media concentrations and contact rates were 70 and 26 ng/day, respectively. The central tendency adult intake derived from NHANES data was 56 and 37 ng/day for males and females, respectively. Variability and uncertainty discussions regarding the intake modeling focus on lack of data on direct exposure to PFOA used in consumer products, precursor compounds, and food. Discussions regarding PK modeling focus on the range of blood measurements in NHANES, the appropriateness of the simple PK model, and the uncertainties associated with model parameters. Using the PK model, the 10th and 95th percentile long-term average adult intakes of PFOA are 15 and 130 ng/day.

Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

International Nuclear Information System (INIS)

Akabani, G.; Poston, J.W. Sr.

1992-01-01

At present, absorbed dose calculations for radionuclides in the human circulatory system use relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, Monte Carlo calculations were performed using the code Electron Gamma Shower (EGS4). Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessel sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was or cross fire between blood vessels was assumed. Results are useful in assessing the doses to blood and blood vessel walls for different nuclear medicine procedures

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.

Blood and Blood Components: From Similarities to Differences

Directory of Open Access Journals (Sweden)

Olivier Garraud

2018-04-01

Full Text Available Blood transfusion is made possible because, in most countries and organizations, altruistic individuals voluntarily, anonymously, and generously donate (without compensation either whole blood or separated components that are then processed and distributed by professionals, prior to being allocated to recipients in need. Being part of modern medicine, blood transfusion uses so-called standard blood components when relative to cellular fractions and fresh plasma. However, as will be discussed in this paper, strictly speaking, such so-called labile blood components are not completely standard. Furthermore, the prevalent system based on voluntary, non-remunerated blood donation is not yet universal and, despite claims by the World Health Organization that 100% of blood collection will be derived from altruistic donations by 2020 (postponed to 2025, many obstacles may hinder this ambition, especially when relative to the collection of the enormous amount of plasma destined for fractionation into plasma derivative or drugs. Finally, country organizations also vary due to the economy, sociology, politics, and epidemiology. This paper then, discusses the particulars (of which ethical considerations of blood transfusion diversity and the consequences for donors, patients, and society.

Blood and Blood Components: From Similarities to Differences

Science.gov (United States)

Garraud, Olivier; Tissot, Jean-Daniel

2018-01-01

Blood transfusion is made possible because, in most countries and organizations, altruistic individuals voluntarily, anonymously, and generously donate (without compensation) either whole blood or separated components that are then processed and distributed by professionals, prior to being allocated to recipients in need. Being part of modern medicine, blood transfusion uses so-called standard blood components when relative to cellular fractions and fresh plasma. However, as will be discussed in this paper, strictly speaking, such so-called labile blood components are not completely standard. Furthermore, the prevalent system based on voluntary, non-remunerated blood donation is not yet universal and, despite claims by the World Health Organization that 100% of blood collection will be derived from altruistic donations by 2020 (postponed to 2025), many obstacles may hinder this ambition, especially when relative to the collection of the enormous amount of plasma destined for fractionation into plasma derivative or drugs. Finally, country organizations also vary due to the economy, sociology, politics, and epidemiology. This paper then, discusses the particulars (of which ethical considerations) of blood transfusion diversity and the consequences for donors, patients, and society. PMID:29686986

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

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.

On-chip sample preparation for complete blood count from raw blood.

Science.gov (United States)

Nguyen, John; Wei, Yuan; Zheng, Yi; Wang, Chen; Sun, Yu

2015-03-21

This paper describes a monolithic microfluidic device capable of on-chip sample preparation for both RBC and WBC measurements from whole blood. For the first time, on-chip sample processing (e.g. dilution, lysis, and filtration) and downstream single cell measurement were fully integrated to enable sample preparation and single cell analysis from whole blood on a single device. The device consists of two parallel sub-systems that perform sample processing and electrical measurements for measuring RBC and WBC parameters. The system provides a modular environment capable of handling solutions of various viscosities by adjusting the length of channels and precisely controlling mixing ratios, and features a new 'offset' filter configuration for increased duration of device operation. RBC concentration, mean corpuscular volume (MCV), cell distribution width, WBC concentration and differential are determined by electrical impedance measurement. Experimental characterization of over 100,000 cells from 10 patient blood samples validated the system's capability for performing on-chip raw blood processing and measurement.

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.

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

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

Effect of blood glucose level on acute stress response of grass carp Ctenopharyngodon idella.

Science.gov (United States)

Jiang, Danli; Wu, Yubo; Huang, Di; Ren, Xing; Wang, Yan

2017-10-01

Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g -1 body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level. Handling resulted in increase of plasma levels of cortisol, glucose, and lactate and plasma lactic dehydrogenase (LDH) activity and decrease of liver glycogen content. At 1 h post-stress, the plasma cortisol level was lower in the stressed fish injected with glucose at 0.5 mg g -1 BM than the stressed fish injected with glucose at 0, 0.2, and 1.0 mg g -1 BM. No significant differences were found in the activities of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in the liver between the stressed and unstressed fish, regardless of the dose of glucose injection. At 1 h post-stress, the liver glucose-6-phosphatase (G6Pase) activity was higher in the fish without glucose injection than in the fish injected with glucose. This study reveals that blood glucose level can affect stress response of grass carp by modulating cortisol release and glucose homeostasis through glycogen metabolism and gluconeogenesis in the liver.

Absorbed dose calculations to blood and blood vessels for internally deposited radionuclides

International Nuclear Information System (INIS)

Akabani, G.; Poston, J.W.

1991-05-01

At present, absorbed dose calculations for radionuclides in the human circulatory system used relatively simple models and are restricted in their applications. To determine absorbed doses to the blood and to the surface of the blood vessel wall, EGS4 Monte Carlo calculations were performed. Absorbed doses were calculated for the blood and the blood vessel wall (lumen) for different blood vessels sizes. The radionuclides chosen for this study were those commonly used in nuclear medicine. No diffusion of the radionuclide into the blood vessel was assumed nor cross fire between vessel was assumed. Results are useful in assessing the dose in blood and blood vessel walls for different nuclear medicine procedures. 6 refs., 6 figs., 5 tabs

Study of the production of A0 b and B0 hadrons in pp collisions and first measurement of the ∧ o b !J= pK.. branching fraction

NARCIS (Netherlands)

Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.; 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.; Everse, LA; Anderlini, L.; Anderson, J.; Andreassi, G.; Andreotti, M.; Andrews, J.E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; d'Argent, P.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Bel, L. J.; Bellee, V.; Belloli, N.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Bettler, M-O.; Van Beuzekom, Martin; Bien, A.; Bifani, S.; Billoir, P.; Bird, T.D.; Birnkraut, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Buchanan, E.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Campora Perez, D.; 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.; Cauet, Ch; Cavallero, G.; Cenci, R.; Charles, M.; Charpentier, Ph; Chefdeville, M.; Chen, S.; Cheung, S-F.; Chiapolini, N.; Chrzaszcz, M.; 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.; Collazuol, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Cunliffe, S.; Currie, C.R.; D'Ambrosio, C.; Dall'Occo, E.; Dalseno, J.; David, P. N.Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; de Miranda, J. M.; Paula, L.E.; De Simone, P.; Dean, C-T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déleáge, N.; Demmer, M.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Ruscio, F.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T. M.; Falabella, A.; Färber, C.; Farley, N.; Farry, S.; Fay, R.; Ferguson, D.; Fernandez Albor, V.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fohl, K.; Fol, P.; Fontana, Mark; Fontanelli, F.; Forty, R.; De Aguiar Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garciá Pardinãs, J.; Garra Tico, J.; Garrido, L.; Gascon, D.; Carvalho-Gaspar, M.; Gauld, Rhorry; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T. J.; Ghez, Ph; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.Q.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu; Gys, T.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Humair, T.; Hussain, N.; Hutchcroft, D. E.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kecke, M.; Kelsey, M. H.; Kenyon, I. R.; Kenzie, M.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.M.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Kozeiha, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G. D.; Lai, A.; Lambert, D.M.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T. E.; Lazzeroni, C.; Le Gac, R.; Van Leerdam, J.; Lees, J. P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, S.C.; Lionetto, F.; Liu, B.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Manning, P.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli-Boneschi, F.; Martinez-Santos, D.; Martinez-Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurin, B.; Mazurov, A.; McCann, M.; McCarthy, J.; Mcnab, A.; McNulty, R.; Meadows, B. T.; Meier, F.; Meissner, M.; Melnychuk, D.; Merk, M.; Michielin, E.; Milanes, D. A.; Minard, M. N.; Mitzel, D. S.; Molina Rodriguez, J.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Müller, D.; Müller, J.; Müller, Karl; von Müller, L.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Ninci, D.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, C. J.G.; Osorio Rodrigues, B.; Otalora Goicochea, J. M.; Otto, E.A.; Owen, R.P.; Oyanguren, A.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L.L.; Pappenheimer, C.; Parkes, C.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pearce, D.A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Piucci, A.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, M. E.; Price, J.D.; Prisciandaro, J.; Pritchard, C.A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, Y.W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redi, F.; Reichert, S.; Reid, M.; dos Reis, A. C.; Ricciardi, S.; Richards, Jennifer S; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Rodrigues, A. B.; Rodrigues, L.E.T.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz Valls, P.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; 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.; Schiller, M.; Schindler, R. H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schubiger, M.; Schune, M. H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, E.; Smith, I. T.; Smith, J; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; de Souza, D.K.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefkova, S.; Steinkamp, O.; Stenyakin, O.; Stevenson-Moore, P.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; Van Tilburg, J.; Tisserand, V.; Tobin, M. N.; Todd, Jim; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Tran, N.T.M.T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, M.J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Volkov, V.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; De Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, John; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M.P.; Williams, M.; Williams, T.; Wilson, James F; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.J.; Wyllie, K.; Xie, Y.; Xu, Z.; Yang, Z.; Yu, J.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zucchelli, S.

2016-01-01

The product of the Λ0 b (B0) differential production cross-section and the branching fraction of the decay Λ0 bJ= pK.. (B0!J= K Λ (892)0) is measured as a function of the beauty hadron transverse momentum, pT, and rapidity, y. The kinematic region of the measurements is pT >20 GeV=c and 2:0>y>4:5.

Population Pharmacokinetic Model for Vancomycin Used in Open Heart Surgery: Model-Based Evaluation of Standard Dosing Regimens.

Science.gov (United States)

Alqahtani, Saeed A; Alsultan, Abdullah S; Alqattan, Hussain M; Eldemerdash, Ahmed; Albacker, Turki B

2018-04-23

The purpose of this study was to investigate the population pharmacokinetics of vancomycin in patients undergoing open heart surgery. In this observational pharmacokinetic study, multiple blood samples were drawn over a 48-h period of intravenous vancomycin in patients who were undergoing open heart surgery. Blood samples were analysed using the Architect i4000SR Immunoassay Analyzer. Population pharmacokinetic models were developed using Monolix 4.4 software. Pharmacokinetic-pharmacodynamic (PK-PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. One-hundred and sixty-eight blood samples were analysed from 28 patients. The pharmacokinetics of vancomycin was best described by a two-compartment model with between-subject variability in CL, V of the central compartment, and V of the peripheral compartment. CL and central compartment V of vancomycin were related to CL CR , body weight, and albumin concentration. Dosing simulations showed that standard dosing regimens of 1 and 1.5 g failed to achieve the PK-PD target of AUC 0--24 /MIC > 400 for an MIC of 1 mg/L, while high weight-based dosing regimens were able to achieve the PK-PD target. In summary, administration of standard doses of 1 and 1.5 g of vancomycin two times daily provided inadequate antibiotic prophylaxis in patients undergoing open heart surgery. The same findings were obtained when 15 mg/kg and 20 mg/kg doses of vancomycin were administered. Achieving the PK-PD target required higher doses (25 mg/kg and 30 mg/kg) of vancomycin. Copyright © 2018 American Society for Microbiology.

In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

Science.gov (United States)

Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

2018-05-01

Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

Quality indicators for discarding blood in the National Blood Center, Kuala Lumpur

Directory of Open Access Journals (Sweden)

Mohammed Morish

2012-01-01

Full Text Available Background and Objective: The implementation of quality system and continuous evaluation of all activities of the Blood Transfusion Services (BTS can help to achieve the maximum quantity and quality of safe blood. Optimizing blood collection and processing would reduce the rate of discard and improve the efficiency of the BTS. The objective of this study is to determine the rate of discard of blood and blood component and identify its reasons at the National Blood Centre (NBC, Kuala Lumpur, during the year of 2007 in order to introduce appropriate intervention. Study Designs and Methods: Data on the number of discarded whole blood units and its components, reasons for discard, and the number of blood components processed as well as the number of collected blood units were obtained from the Blood Bank Information System - NBC database. These were analyzed. Results: The total number of blood units collected in 2007 was 171169 from which 390636 units of components were prepared. The total number of discarded whole blood units and its components was 8968 (2.3%. Platelet concentrate recorded the highest of discard at 6% (3909 followed by whole blood at 3.7% (647, fresh frozen plasma (FFP at 2.5% (2839, and cryoprecipitate at 2% (620. The rate of discarded packed red blood cells RBCs, plasma aphaeresis, and PLT aphaeresis was less than 1% at 0.6% (902, 0.6% (37, and 0.29% (14, respectively. RBC contamination of PLT and plasma were the major cause of discard at 40% (3558. Other causes include leakage (26% - 2306, lipemia (25% - 2208, and underweight (4% - 353. Conclusion: Good donor selection, training and evaluation of the staff, as well as implementation of automation will help to improve processes and output of BTS. This would reduce discard of blood components and wastage caused by non conformance.

Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space

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Peterson, Amanda; Risin, Semyon A.; Ramesh, Govindarajan T.; Dasgupta, Amitava; Risin, Diana

2008-01-01

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less

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.

Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake

OpenAIRE

Gardiner, JV; Bataveljic, A; Patel, NA; Bewick, GA; Roy, D; Campbell, D; Greenwood, HC; Murphy, KG; Hameed, S; Jethwa, PH; Ebling, FJP; Vickers, SP; Cheetham, S; Ghatei, MA; Bloom, SR

2009-01-01

OBJECTIVE Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanis...

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.

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.

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.

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

Science.gov (United States)

Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-03-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

A study of the blood flow restriction pressure of a tourniquet system to facilitate development of a system that can prevent musculoskeletal complications.

Science.gov (United States)

Maeda, Hiroyuki; Iwase, Hideaki; Kanda, Akio; Morohashi, Itaru; Kaneko, Kazuo; Maeda, Mutsuhiro; Kakinuma, Yuki; Takei, Yusuke; Amemiya, Shota; Mitsui, Kazuyuki

2017-01-01

After an emergency or disaster, subsequent trauma can cause severe bleeding and this can often prove fatal, so promptly stopping that bleeding is crucial to preventing avoidable trauma deaths. A tourniquet is often used to restrict blood flow to an extremity. In operation and hospital, the tourniquet systems currently in use are pneumatically actuated by an air compressor, so they must have a steady power supply. These devices have several drawbacks: they vibrate and are noisy since they are pneumatically actuated and they are far from portable since they are large and heavy. Presumably, the drawbacks of pneumatic tourniquets could be overcome by developing a small, lightweight, vibration-free, quiet, and battery-powered tourniquet system. The current study built a small, vibration-free electrohydrodynamic (EHD) pump and then used that pump to restrict blood flow to the leg of rats in an experiment. This study explored the optimal conditions for effective restriction of blood flow by assessing biochemical and musculoskeletal complications following the restriction of blood flow, and this study also examined whether or not an EHD pump could be used to actuate a tourniquet system. A tourniquet cuff (width 12 mm × length 150 mm, material: polyolefin) was placed on the thigh of Wistar rats and pressure was applied for 2 hours by a device that uses EHD phenomena to generate pressure (an EHD pump). Animals were divided into four groups based on how much compressive pressure was applied with a tourniquet: 40 kPa (300 mm Hg, n = 13), 30 kPa (225 mm Hg, n = 12), 20 kPa (150 mm Hg, n = 15), or 0 kPa (controls, n = 25). Tissue oxygen saturation (regional oxygen saturation, denoted here as rSO 2 ) was measured to assess the restriction of blood flow. To assess behavior once blood flow resumed, animal activity was monitored for third day and the amount of movement was counted with digital counters. Body weight was measured before and after the behavioral experiment, and

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.

Role of blood culture systems in the evaluation of epidemiological features of coagulase-negative staphylococcal bloodstream infection in critically ill patients.

Science.gov (United States)

Oud, L; Krimerman, S; Salam, N; Srugo, I

1999-12-01

The impact of blood culture systems on the detection of coagulase-negative staphylococcal bloodstream infections in critically ill patients prior to and following the introduction of the Bactec 9240 blood culture system (Becton Dickinson Diagnostic Instrument Systems, USA), which replaced the Bactec NR 730 (Becton Dickinson Diagnostic Instrument Systems), was investigated over a 3-year period. Following the introduction of the new culture system, the incidence of bloodstream infections doubled (P<0.001). Patient demographics, severity of illness, and mortality remained unchanged, while the annual standardized mortality ratio decreased significantly. These data suggest that blood culture systems may have a major impact on the perceived incidence of coagulase-negative staphylococcal bloodstream infections in this population.

Blood donors and factors impacting the blood donation decision: motives for donating blood in Turkish sample.

Science.gov (United States)

Karacan, Eda; Cengiz Seval, Guldane; Aktan, Zeynep; Ayli, Meltem; Palabiyikoglu, Refia

2013-12-01

Donations in Turkey are insufficient to cover the high transfusion needs arising from large numbers of thalassemia and sickle cell anemia patients and increasing demands for blood due to advanced surgery and cancer treatment. The most acceptable means to get blood is voluntary blood donation and the blood donor system in Turkey mostly depends on a combination of voluntary and involuntary donors. The main aim of this study is to explore the motivations of Turkish voluntary blood donors toward blood donation and to determine predictors of blood donation motivation. A cross-sectional sample survey of active blood donors in Ankara, Turkey was conducted. The sample consisted of 189 male volunteer blood donor adults. Donors filled in a self-administered questionnaire including the measures of demographic information, empathetic concern, altruism, social responsibility and blood donation motivation questionnaire during donation. Factor analysis of Blood Donation Motivation Measure with varimax rotation revealed a three-factor solution named as "values and moral duty", "positive feelings and esteem" and "self-benefit and external reasons". The results with regression analyses showed that only social responsibility had an significant effect independent of age, income, and education on blood donation motivation. These result reflects that blood donation motivation not only linked to a high degree of altruistic reasons, but also to a combination of some self-regarding motives. Additionally, feelings of empathy or altruism may be less strong at the time the decision to help, other factors may have a larger influence on helping decisions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Medium pressure boiler water chemistry optimization using neutralizing amines mixture reagent AMINAT™ PK-2 at CEPP “Borovichi Refractories Plant” of JSC “BKO”

Science.gov (United States)

Guseva, O. V.; Butakova, M. V.; Orlov, K. A.; Vinogradov, S. V.; Pavlenko, L. S.

2017-11-01

An overview of the neutralizing amine based reagent AMINAT PK-2 usage for water chemistry of steam boilers for medium pressure boiler was given. Long term experiment showed that new reagent allows to decrease corrosion rate comparing with old water chemistry based on ammonia only. Two dosage schemes in different cycle places discussed. Scheme with two points on injection showed better results. Results of corrosion rates experiments and photos of tubes inner surfaces are presented. Based on fuel savings due to reducing scale formation the total annual economy for last year was 5.1 million Russian roubles.

Blood irradiation: Rationale and technique

International Nuclear Information System (INIS)

Lewis, M.C.

1990-01-01

Upon request by the local American Red Cross, the Savannah Regional Center for Cancer Care irradiates whole blood or blood components to prevent post-transfusion graft-versus-host reaction in patients who have severely depressed immune systems. The rationale for blood irradiation, the total absorbed dose, the type of patients who require irradiated blood, and the regulations that apply to irradiated blood are presented. A method of irradiating blood using a linear accelerator is described

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.