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Plasma Proteins (plasma + protein)
Kinds of Plasma Proteins Terms modified by Plasma Proteins Selected AbstractsPORCINE PLASMA PROTEINS AS GEL ENHANCER IN BIGEYE SNAPPER (PRIACANTHUS TAYENUS) SURIMIJOURNAL OF FOOD BIOCHEMISTRY, Issue 4 2001SOOTTAWAT BENJAKUL ABSTRACT Cohn's fraction I-S from porcine plasma showed the highest transglutaminase activity, compared to fractions I. 11+III, IV, IV-l. The optimum temperature for incorporating monodancylcadaverine into dimethylated casein was 45C. Plasma transglutaminase in fraction I-S was activated by calcium chloride but was inhibited by N-ethylmaleimide, ethylenediaminetetraacetic acid, and ammonium chloride. The addition of fraction I-S into bigeye snapper surimi resulted in a substantial increase in gel breaking force and deformation, particularly in the presence of calcium chloride and thrombin. No changes in whiteness and water holding capacity were observed in surimi gel with the addition of 0,0.5% of fraction I-S. Fraction I-S was found to catalyze nondisulfide covalent cross-linking of myosin heavy chain. The combination of endogenous and plasma transglutaminase enhanced surimi gelation. [source] Porcine Plasma Proteins as a Surimi Protease Inhibitor: Effects on Actomyosin GelationJOURNAL OF FOOD SCIENCE, Issue 4 2000W. Visessanguan ABSTRACT Effect of porcine plasma proteins (PPP) on thermal gelation of actomyosin in the presence and absence of fish proteinase was studied using a dynamic rheological test. Substantial decreases in development rate and magnitude of gel modulus were observed by the addition of proteinase to actomyosin gels. PPP was effective in protecting a myosin-heavy chain from proteolytic degradation, however, PPP itself interfered with the formation of actomyosin gel. Lower gel modulus was observed with actomyosin gels developed with higher concentrations of PPP added. Overall, PPP reversed the loss of gel modulus by the proteinase, however, the recovered gel modulus was only as high as those containing PPP only. These results implicated that, although PPP may revert autolytic activity in surimi, it interfaces with actomyosin gelation. [source] Reproductive Development of Santa Inęs Rams During the First Year of Life: Body and Testis Growth, Testosterone Concentrations, Sperm Parameters, Age at Puberty and Seminal Plasma ProteinsREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2010CEA Souza Contents We have investigated the reproductive development of the tropically adapted Santa Inęs ram, the most common hair sheep in Brazil. From 8 to 48 weeks of age, 16 animals were evaluated for body and testis growth, semen parameters, testosterone concentrations and seminal plasma proteins, using two-dimensional SDS-PAGE. Animals were weaned at 30 days and kept in feedlots thereafter, receiving hay, concentrate (18% of crude protein) and mineral supplement. Body weight increased from 12.3 ± 0.7 to 54.3 ± 1.6 kg between 8 and 48 weeks (p < 0.05), but changes in thoracic perimeter and scrotal circumference were non-significant after 36 weeks (p > 0.05). The percentage of motile sperm increased slowly until 23 weeks and more rapidly after that age, but significant changes in progressive motility occurred after 25 weeks. Presence of abnormal sperm related inversely to age. Most significant changes in sperm concentration occurred between 38 and 44 weeks (0.38 ± 0.05 to 1.14 ± 0.24 × 109 cells/ml, p < 0.05) and testosterone reached its highest concentrations at 42 weeks, decreasing afterwards. Rams reached puberty at 28.2 ± 0.8 weeks. The number of protein spots on seminal plasma gels was similar from 15 to 18 weeks (45 and 47 spots; p > 0.05), increased until 24 weeks (141 spots) and 28 weeks (170 spots; p < 0.05) and remained without significant (p > 0.05) changes from 28 to 48 weeks (186 ± 10 spots). Furthermore, the intensity of selected spots on 2D maps increased (p < 0.05) between 15 and 28 weeks, which preceded or coincided with the main developmental changes in sperm motility and percentage of defective sperm in the ejaculates. These results will support future studies designed to characterize specific seminal plasma proteins whose expression relate to the development of testis, epididymis and accessory sex glands. [source] Influences of dietary fatty acid profile on growth, body composition and blood chemistry in juvenile fat cod (Hexagrammos otakii Jordan et Starks)AQUACULTURE NUTRITION, Issue 1 2009S.-M. LEE Abstract This study was conducted to investigate the influence of dietary lipid source and n-3 highly unsaturated fatty acids (n-3 HUFA) level on growth, body composition and blood chemistry of juvenile fat cod. Triplicate groups of fish (13.2 ± 0.54 g) were fed the diets containing different n-3 HUFA levels (0,30 g kg,1) adjusted by either lauric acid or different proportions of corn oil, linseed oil and squid liver oil at 100 g kg,1 of total lipid level. Survival was not affected by dietary fatty acids composition. Weight gain, feed efficiency and protein efficiency ratio (PER) of fish fed the diets containing squid liver oil were significantly (P < 0.05) higher than those fed the diets containing lauric acid, corn oil or linseed oil as the sole lipid source. Weight gain, feed efficiency and PER of fish increased with increasing dietary n-3 HUFA level up to 12,16 g kg,1, but the values decreased in fish fed the diet containing 30 g kg,1 n-3 HUFA. The result of second-order polynomial regression showed that the maximum weight gain and feed efficiency could be attained at 17 g kg,1 n-3 HUFA. Plasma protein, glucose and cholesterol contents were not affected by dietary fatty acids composition. However, plasma triglyceride content in fish fed the diet containing lauric acid as the sole lipid source was significantly (P < 0.05) lower than that of fish fed the other diets. Lipid content of fish fed the diets containing each of lauric acid or corn oil was lower than that of fish fed the diets containing linseed oil or squid liver oil only. Fatty acid composition of polar and neutral lipid fractions in the whole body of fat cod fed the diets containing various levels of n-3 HUFA were reflected by dietary fatty acids compositions. The contents of n-3 HUFA in polar and neutral lipids of fish increased with an increase in dietary n-3 HUFA level. These results indicate that dietary n-3 HUFA are essential and the diet containing 12,17 g kg,1 n-3 HUFA is optimal for growth and efficient feed utilization of juvenile fat cod, however, excessive n-3 HUFA supplement may impair the growth of fish. [source] Simple determination of pirfenidone in rat plasma via high-performance liquid chromatographyBIOMEDICAL CHROMATOGRAPHY, Issue 12 2006Yongsheng Wang Abstract A simple, rapid and reliable high-performance liquid chromatographic method was developed and validated for the determination of pirfenidone and its major metabolites in rat plasma. Plasma proteins were precipitated with perchloric acid (10%, v/v) and the supernatant after centrifugation was determined using high-performance liquid chromatography. The analysis was carried out on a Lichrospher C18 column (250 × 4.6 mm i.d., 5 µm). The mobile phase consisted of acetonitrile,water containing 0.2% acetic acid (23:77, v/v) at a flow-rate of 1 mL/min. The eluant was detected at 310 nm. The calibration curves were linear over a concentration range from 0.15 to 76.67 µg/mL. The accuracy (relative error) of the assay ranged from -2.6 to 7.9% and the precision (coefficient of variation) was less than 4.5%. The established method has been successfully applied to a pharmacokinetic study of pirfenidone following a single oral dose to rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Liquid chromatography with electrospray ionization mass spectrometry method for the assay of glucosamine sulfate in human plasma: validation and application to a pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 3 2006Tao-Min Huang Abstract A liquid chromatography,electrospray ionization mass spectrometry (LC,ESI,MS) method was developed and validated for the assay of glucosamine sulfate in human plasma. Plasma proteins were precipitated by acetonitrile, followed by vortex mixing and centrifugation. The supernatant was transferred and derivatized with phenyl iso-thiocyanate in acetonitrile at 60°C for 40 min. Chromatographic separation was performed on a C18 column (Inertsil ODS-3 150 × 2.1 mm i.d., 5 µm, JP) with a mobile phase gradient consisting of 0.2% acetic acid (aqueous) and methanol at a flow-rate of 0.3 mL/min. MS detection using electrospray ionization (ESI) as an interface was used in single ion monitoring mode to determine positive ions at m/z 297. This method was shown to be selective and sensitive for glucosamine sulfate. The limit of detection was 35 ng/mL for glucosamine sulfate in plasma and the linear range was 0.1,20 µg/mL in plasma with a correlation coefficient (r) of 0.9991. The relative standard deviations (RSDs) of intra-day and inter-day assays were 8.7,11.4 and 9.8,12.6%, respectively. Extraction recoveries of glucosamine sulfate in plasma were greater than 73%. This method proved to be simple, reproducible and feasible for pharmacokinetic studies of glucosamine sulfate in healthy volunteers after a single oral administration (1500 mg). The pharmacokinetic parameters and relative bioavailabilities were investigated for both domestic glucosamine sulfate tablet and capsule preparations compared with an imported capsule product. Copyright © 2005 John Wiley & Sons, Ltd. [source] Pregnancy-associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy,a prospective follow-up studyDIABETIC MEDICINE, Issue 12 2007A. S. Astrup Abstract Aim Pregnancy-associated plasma protein A (PAPP-A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP-A in a large cohort of Type 1 diabetic patients. Methods In a prospective observational follow-up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0,10.3) years. PAPP-A was determined at baseline. Results In patients with diabetic nephropathy, plasma PAPP-A was elevated 3.6 (0.4,51.1) mIU/l [median (range)] vs. 2.1 (0.4,46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP-A threshold of 10 mIU/l has been suggested. Thirty-seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP-A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP-A was above the threshold 2.1 (95% CI 1.13,3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP-A was significantly predictive of all-cause mortality [P = 0.008; 2.43 (1.26,4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP-A for all-cause mortality was attenuated (P = 0.064). Conclusion We find PAPP-A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP-A was no longer significant. [source] Detection of C Reactive Protein (CRP) in Serum by an Electrochemical Aptamer-Based Sandwich AssayELECTROANALYSIS, Issue 11 2009Sonia Centi Abstract A disposable electrochemical assay involving magnetic particles and carbon-based screen-printed electrodes (SPCEs) was developed for the detection of C Reactive Protein (CRP). CRP is a plasma protein and is among the most expressed proteins in acute phase inflammation cases, being a known biomarker for inflammatory states. The assay was based on a sandwich format in which a RNA aptamer was coupled to a monoclonal antibody and alkaline phosphatase (AP) was used as enzymatic label. After the sandwich assay, the modified magnetic beads were captured by a magnet on the surface of a graphite working electrode and the electrochemical detection was thus achieved through the addition of the AP substrate (,-naphthyl-phosphate) and ,-naphthol produced during the enzymatic reaction was detected using differential pulse voltammetry (DPV). The parameters influencing the different steps of the assay were optimized in order to reach the best sensitivity and specificity. With the optimized conditions, the assay was applied to the analysis of CRP free serum and serum samples. [source] Influence of dietary 2,4,6-trinitrotoluene exposure in the northern bobwhite (Colinus virginianus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2002Robert M. Gogal Jr. Abstract The risk to wildlife from exposure to the explosive, 2,4,6-trinitrotoluene (TNT) has been a concern at numerous military installations where it has been found in the soil. To date, no published data are available describing effects of TNT exposure in an avian species. Subchronic dietary exposure to TNT was therefore evaluated in a species of management concern at military installations, the northern bobwhite (Colinus virginianus). Adult male and female quail (n = 5/sex/dose) were given commercial feed containing 3,000, 1,500, 750, and 100 mg/kg TNT for 90 d following the determination of an acute lethal dose and a 14-d range finding study. Dietary TNT intake caused a dose-dependent decrease in total red blood cell counts, packed cell volume, total plasma protein, blood prolymphocytes, and blood lymphocytes. An increased trend in late apoptotic/necrotic blood leukocytic cells was also observed in TNT-exposed birds, as was hemosiderosis in the liver. With the exception of hemosiderosis, these trends were statistically significant yet of questionable biological significance. Since treatment-related responses in this preliminary study were variable, a conservative interpretation is suggested. However, since these treatments had concentrations that were a log-fold or more than doses in similar studies using mammals, these data suggest that northern bobwhite are less sensitive to oral exposures of TNT than mammals. [source] Effects of pre- and postnatal polychlorinated biphenyl exposure on metabolic rate and thyroid hormones of white-footed mice,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2001John B. French Jr. Abstract Energy budgets have proven to be a valuable tool for predicting life history from physiological data in terrestrial vertebrates, yet these concepts have not been applied to the physiological effects of contaminants. Contaminants might affect energy budgets by imposing an additional metabolic cost or by reducing the overall amount of energy taken in; either process will reduce the energy available for production (i.e., growth or reproduction). This study examined whole animal energetic effects of polychlorinated biphenyl (PCB) exposure in white-footed mice (Peromyscus leucopus). Exposure to PCBs is known to reduce concentrations of plasma thyroid hormones, and thyroid hormones exert strong control over the rate of energy metabolism in mammals. Peromyscus leucopus that were proven breeders were fed PCBs in their food at 0, 10, and 25 ppm. Through lactation, offspring were exposed to PCB from conception and were maintained on the maternal diet to adulthood. No effects were seen on energy metabolism (O2 consumption, measured in adulthood) or on growth, but there were large dose-dependent decreases in thyroid hormone concentrations, particularly T4. The apparent disparity in our data between unchanged metabolic rates and 50% reductions in T4 concentrations can be rationalized by noting that free T3 (the fraction not bound to plasma protein) in treated mice was not significantly different from controls and that metabolism is most strongly influenced by free T3. Overall, this study did not demonstrate any energetic consequences of PCB exposure in P. leucopus at dietary concentrations up to 25 ppm. [source] Use of ristocetin cofactor activity in the management of von Willebrand diseaseHAEMOPHILIA, Issue 2001B.M. Ewenstein von Willebrand disease (vWD), the most common of the hereditary bleeding disorders, arises from quantitative or qualitative defects in von Willebrand factor (vWF). vWF is a multimeric plasma protein that plays a key role in primary and secondary haemostasis. In the current classification scheme, vWD is divided into six subtypes that are based on the nature of the vWF defect. Therapeutic strategies depend on the accurate identification of these subtypes. In most clinical situations, desmopressin is effective treatment for the great majority of patients with mild (type 1) disease, while replacement therapy with factor VIII/vWF concentrates that contain high levels of vWF activity is required for most type 2 and nearly all type 3 vWD patients. Several factor VIII/vWF replacement products are available, one of which (Humate P) has been approved for the treatment of vWD by the US Food and Drug Administration. Preliminary results of recent studies support the hypothesis that treatment with factor VIII/vWF concentrates based upon the content of vWF activity as reflected in the ristocetin cofactor assay is practicable, safe and efficacious. The establishment of optimal treatment regimens with respect to dose intensity and duration will require further study. [source] Influence of dietary amino acid profiles on growth performance and body composition of juvenile grouper Epinephelus coioidesJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2008Z. Luo Summary A feeding experiment was conducted to investigate the effects of dietary amino acid (AA) profiles on growth performance and body composition of juvenile grouper Epinephelus coioides (initial mean weight: 68.1 ± 1.0 g, mean ± SD). Five diets contained 30% fishmeal, 12% soy protein concentrate and 20% crystalline amino acids (CAAs); the control diet contained 54% fishmeal and 17% soy protein concentrate as intact protein sources. CAAs were added to the five diets to simulate the AA pattern found in white fishmeal protein (WFP), brown fishmeal protein (BFP), hen egg protein (HEP), grouper E. coioides juvenile protein (GJP) and red sea bream egg protein (REP), respectively. The highest WG and SGR were obtained in fish fed the control diet, followed by fish fed the diets with AA profiles of WFP and GJP. Fish fed the diets with AA profiles of BFP, REP and HEP showed relatively poor growth performance. Feed utilization showed a similar trend in growth parameters. Protein content of whole body among these treatments showed no significant differences (P > 0.05), but lipid content of whole body showed the highest value in the control group (P < 0.05). Dietary AA profiles significantly influenced plasma protein, cholesterol, triacylglycerol and glucose concentrations (P < 0.05). Dietary AA profiles significantly influenced the condition factor, hepatosomatic index and intraperitoneal fat ratio (P < 0.05). [source] First-trimester Down syndrome screening in women younger than 35 years old and cost-effectiveness analysis in Taiwan populationJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 5 2009Ching-Yu Chou MD Summary Objectives, Outcome of the first-trimester Down syndrome screening in younger population was less reported before. We present the outcome of this screening in Taiwanese women younger than 35 years old. We also test whether or not the first-trimester Down syndrome screening of women <35 years of age and women >35 years old routinely receiving amniocentesis is cost-effective compared with all pregnant women screened with this test in the setting of increased maternal age. Methods, From 1999 to 2007, the first-trimester Down syndrome screening including nuchal thickness, pregnancy-associated plasma protein A and free ,-hCG are provided to 10 811 singleton women <35 years of age with the cut-off of 1/270. A cost-effectiveness analysis of young women receiving this screening and older women undergo amniocentesis versus all women undergo this screening was performed in Taiwan population from 1987 to 2006, in which advanced age pregnancies increased from 2.8% to 11.6% of total pregnancies. Results, Detection rates of trisomy 21, trisomy 18, Turner syndrome and other chromosome anormalies in women <35 years of age are 87.5% (14/16), 50% (2/4), 80% (8/10) and 63% (12/19), respectively, with a false-positive rate of 5.5% (590/10 811). As advanced age pregnancies reached 11.6%, the average cost per one case averted for all women screened ranged from $77 204 to $98 421, while the cost ranged from $99 647 to $116 433 for only women <35 years of age receiving this screening. Conclusions, In an aging population, the first-trimester Down syndrome screening should be implemented for all pregnant women when it is available. [source] Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the ratJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2001François-xavier Mathy Abstract The objective of this study was to validate subcutaneous (sc) microdialysis sampling to study flurbiprofen pharmacokinetics and plasma protein binding in the awake freely moving rat. A linear microdialysis probe was manufactured using a Hemophane® hollow fiber which was tested in vitro and in vivo for the recovery of flurbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. In both cases, conventional blood sampling and sc microdialysis sampling were simultaneously performed. The microdialysates were analyzed on-line by high-pressure liquid chromatography. Naproxen, which was shown to have a similar in vivo loss by retrodialysis as flurbiprofen (71.5,±,0.9% and 71.0,±,0.8% respectively, n,=,3), was used to continuously monitor probe recovery. Concentration-dependent protein binding of flurbiprofen was demonstrated in vivo based on experiments with a simultaneous sc microdialysis and blood sampling. Values of unbound fraction were similar to those reported previously by intravenous microdialysis sampling, demonstrating that the sc unbound concentrations are very similar to those in the central compartment. There was no significant difference among pharmacokinetic parameters (AUC, CL, t1/2z, Vd) for total or unbound flurbiprofen determined after intraperitoneal and intravenous administration. Subcutaneous microdialysis is a simple yet powerful tool to study the pharmacokinetics and the in vivo plasma protein binding of flurbiprofen in the awake unrestrained rat. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1897,1906, 2001 [source] Texture and colour properties of proteins recovered from whole gutted silver carp (Hypophthalmichthys molitrix) using isoelectric solubilisation/precipitationJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 2 2009Latif Taskaya Abstract BACKGROUND: According to an FAO report, carp are the cheapest and by far the most commonly consumed fish in the world. Carp have minimal growth requirements, yet rapid growth rates. Although carp are generally considered unsuitable for human consumption in the USA, they have rapidly started populating major bodies of fresh water in the USA to the extent that commercial processing becomes of interest. However, typical mechanical means of meat recovery from carp are impractical owing to the bony nature of the carp carcass. Therefore the aim of the present study was to devise processing strategies to recover fish meat from carp that could be used in the development of human food products. RESULTS: Isoelectric solubilisation/precipitation at acidic and basic pH values was applied to whole gutted silver carp. Depending on the solubilisation pH, protein and fat recovery yields were approximately 420,660 and 800,950 g kg,1 respectively. The process effectively removed impurities such as bones, scales, skin, fins, etc. from whole gutted carp. The proteins were concentrated to approximately 900 g kg,1, while the fat was reduced by 970,990 g kg,1. Functional additives (potato starch, beef plasma protein, transglutaminase and polyphosphate) improved (P < 0.05) the texture of carp protein-based gels such that it was generally comparable to the texture of Alaska pollock surimi gels. Although titanium dioxide improved (P < 0.05) the whiteness of carp gels, it was lower (P < 0.05) than the whiteness of Alaska pollock surimi gels. CONCLUSION: Isoelectric solublisation/precipitation allows protein and lipid recovery from whole gutted carp. However, if the proteins are used as a gelling ingredient in fish food products, functional additives are recommended. Copyright © 2008 Society of Chemical Industry [source] Plasminogen on the surfaces of fibrin clots prevents adhesion of leukocytes and plateletsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2010V. K. LISHKO Summary.,Background and Objectives: Although leukocytes and platelets adhere to fibrin with alacrity in vitro, these cells do not readily accumulate on the surfaces of fibrin clots in vivo. The difference in the capacity of blood cell integrins to adhere to fibrin in vivo and in vitro is striking and implies the existence of a physiologic antiadhesive mechanism. The surfaces of fibrin clots in the circulation are continually exposed to plasma proteins, several of which can bind fibrin and influence cell adhesion. Recently, we have demonstrated that adsorption of soluble fibrinogen on the surface of a fibrin clot results in its deposition as a soft multilayer matrix, which prevents attachment of blood cells. In the present study, we demonstrate that another plasma protein, plasminogen, which is known to accumulate in the superficial layer of fibrin, exerts an antiadhesive effect. Results: After being coated with plasminogen, the surfaces of fibrin clots became essentially non-adhesive for U937 monocytic cells, blood monocytes, and platelets. The data revealed that activation of fibrin-bound plasminogen by the plasminogen-activating system assembled on adherent cells resulted in the generation of plasmin, which decomposed the superficial fibrin layer, resulting in cell detachment under flow. The surfaces generated after the initial cell adhesion remained non-adhesive for subsequent attachment of leukocytes and platelets. Conclusion: We propose that the limited degradation of fibrin by plasmin generated by adherent cells loosens the fibers on the clot surface, producing a mechanically unstable substrate that is unable to support firm integrin-mediated cell adhesion. [source] Characterization of fibronectin assembly by platelets adherent to adsorbed laminin-111JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006J. CHO Summary.,Background: Various types of laminin (LN) are ubiquitous components of basement membrane and exposed to blood upon localized damage of vascular endothelial cells. Fibronectin is a plasma protein that is insolubilized into fibrils in a regulated fashion by, for example, lysophosphatidic acid (LPA)-stimulated fibroblasts or platelets spread on supportive adhesive ligands. Objective: To study assembly of plasma fibronectin by LPA-activated platelets adherent to LN-111 via ,6,1 integrin. Results: Platelets adherent to LN-111-bound plasma fibronectin or its N-terminal 70 kD fragment in fibrillar arrays at the periphery of spread platelets under static but not shear conditions. Formation of fibronectin arrays under static conditions was inhibited by co-incubation with the N-terminal 70 kD fragment or with a 49-amino acid peptide that binds to the N-terminal region of fibronectin. Approximately 7000 fibronectin dimers bound per adherent platelet with a Kd of 50 nm. Bound 70 kD fragment was readily solubilized with deoxycholate (DOC), whereas bound fibronectin became progressively insoluble. Bound 70 kD fragment became resistant to DOC extraction after treatment with a cell-impermeable, reducible crosslinker. Crosslinked 70 kD fragment was found in a high molecular weight complex. As with fibroblasts, signaling molecules modulating actin cytoskeletal organization controlled expression of binding sites for the N-terminal 70 kD region of fibronectin on adherent platelets. Conclusions: These results indicate that platelets adherent to LN-111 via ,6,1 support subsequent assembly of fibronectin, but possibly only under conditions of intermittent or stagnant blood flow. [source] Severe blunt trauma in dogs: 235 cases (1997,2003)JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 6 2009Stephen A. Simpson DVM Abstract Objective , To evaluate population characteristics, injuries, emergency diagnostic testing, and outcome of dogs with blunt trauma requiring intensive care in an urban hospital. Design , Retrospective study 1997,2003. Setting , All data obtained from the University of Pennsylvania , Matthew J. Ryan Veterinary Hospital. Animals , Dogs admitted to the intensive care unit for treatment following blunt trauma. Interventions , None. Measurements and Main results , Of the 235 dogs that met inclusion criteria, 206 (88%) survived and 29 (12%) did not survive. Blunt vehicular trauma accounted for 91.1% of cases. Mild hyperglycemia and hyperlactatemia was common in both survivors and nonsurvivors. The chest was the most common region traumatized and the prevalence of polytrauma was 72.3%. Initial weight, vital signs, PCV, total plasma protein, BUN, glucose, lactate, acid-base status, and electrolytes did not differ between survivors and nonsurvivors. Nonsurvivors were significantly more likely to have had head trauma (P=0.008), cranium fractures (P<0.001), recumbency at admission (P<0.001), development of hematochezia (P<0.001), clinical suspicion of acute respiratory distress syndrome (P<0.001), disseminated intravascular coagulation (P<0.001), multiorgan dysfunction syndrome (P<0.001), development of pneumonia (P<0.001), positive-pressure ventilation (P<0.001), vasopressor use (P<0.001), and cardiopulmonary arrest (P<0.001). Conclusions , Outcome of severe blunt trauma in dogs treated with intensive care is very good. Despite the high survival rate, several features associated with poor outcome were identified. Neither admission lactate nor glucose was able to predict outcome. [source] Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activityJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010R. A. HUANG Huang, R. A., Letendre, L. T., Banav, N., Fischer, J., Somerville, B. Pharmacokinetics of gamithromycin in cattle with comparison of plasma and lung tissue concentrations and plasma antibacterial activity. J. vet. Pharmacol. Therap.33, 227,237. The pharmacokinetics (PK) and dose proportionality of gamithromycin (ZACTRAN®), a novel azalide, after a single intravenous (i.v.) dose of 3 mg/kg or subcutaneous (s.c.) injection at 3, 6 and 9 mg/kg body weight were studied in 13 male castrate and 13 female Angus cattle. Following i.v. administration, the mean area under the curve extrapolated to infinity (AUCinf) was 4.28 ± 0.536 ,g·h/mL, and mean elimination half-life (t1/2) was 44.9 ± 4.67 h, with a large volume of distribution (Vss) of 24.9 ± 2.99 L/kg and a high clearance rate (Clobs) of 712 ± 95.7 mL/h/kg. For cattle treated with s.c. injection of 3, 6 or 9 mg/kg, mean AUCinf values were 4.55 ± 0.690, 9.42 ± 1.11 and 12.2 ± 1.13 ,g·h/mL, respectively, and the mean elimination half-lives (t1/2) were 51.2 ± 6.10, 50.8 ± 3.80 and 58.5 ± 5.50 h. Gamithromycin was well absorbed and fully bioavailable (97.6,112%) after s.c. administration. No statistically significant (, = 0.05) gender differences in the AUCInf or elimination half-life values were observed. Dose proportionality was established based on AUCInf over the range of 0.5 to 1.5 times of the recommended dosage of 6 mg/kg of body weight. Further investigations were conducted to assess plasma PK, lung/plasma concentration ratios and plasma antibacterial activity using 36 cattle. The average maximum gamithromycin concentration measured in whole lung homogenate was 18 500 ng/g at first sampling time of 1 day (,24 h) after treatment. The ratios of lung to plasma concentration were 265, 410, 329 and 247 at 1, 5, 10 and 15 days postdose. The lung AUCinf was 194 times higher than the corresponding plasma AUCinf. The apparent elimination half-life for gamithromycin in lung was 90.4 h (,4 days). Antibacterial activity was observed with plasma collected at 6 h postdose with a corresponding average gamithromycin plasma concentration of 261 ng/mL. In vitro plasma protein binding in bovine plasma was determined to be 26.0 ± 0.60% bound over a range of 0.1,3.0 ,g/mL of gamithromycin. The dose proportionality of AUC, high bioavailability, rapid and extensive distribution to lung tissue and low level of plasma protein binding are beneficial PK parameters for an antimicrobial drug used for the treatment and prevention of bovine respiratory disease. [source] Preclinical pharmacology of robenacoxib: a novel selective inhibitor of cyclooxygenase-2JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2009J. N. KING This manuscript reports the results of preclinical studies in the rat with robenacoxib, a novel selective cyclooxygenase (COX)-2 inhibitor. Robenacoxib selectively inhibited COX-2 in vitro as evidenced from COX-1:COX-2 IC50 ratios of 27:1 in purified enzyme preparations and >967:1 in isolated cell assays. Binding to COX-1 was rapid and readily reversible (dissociation t1/2 << 1 min), whilst COX-2 binding was slowly reversible (t1/2 = 25 min). In vivo, robenacoxib inhibited PGE2 production (an index of COX-2 inhibition) in lipopolysaccharide (LPS)-stimulated air pouches (ID50 0.3 mg/kg) and for at least 24 h in zymosan-induced inflammatory exudate (at 2 mg/kg). Robenacoxib was COX-1 sparing, as it inhibited serum TxB2 synthesis ex vivo (an index of COX-1 inhibition) only at very high doses (100 mg/kg but not at 2,30 mg/kg). Robenacoxib inhibited carrageenan-induced paw oedema (ID50 0.40,0.48 mg/kg), LPS-induced fever (ID50 1.1 mg/kg) and Randall,Selitto pain (10 mg/kg). Robenacoxib was highly bound to plasma protein (99.9% at 50 ng/mL in vitro). After intravenous dosing, clearance was 2.4 mL/min/kg and volume of distribution at steady-state was 306 mL/kg. Robenacoxib was preferentially distributed into inflammatory exudate; the AUC for exudate was 2.9 times higher than for blood and the MRT in exudate (15.9 h) was three times longer than in blood (5.3 h). Robenacoxib produced significantly less gastric ulceration and intestinal permeability as compared with the reference nonsteroidal anti-inflammatory drug (NSAID), diclofenac, and did not inhibit PGE2 or 6-keto PGF1, concentrations in the stomach and ileum at 30 mg/kg. Robenacoxib also had no relevant effects on kidney function at 30 mg/kg. In summary, results of preclinical studies in rats studies suggest that robenacoxib has an attractive pharmacological profile for potential use in the intended target species, cats and dogs. [source] Prediction of adverse pregnancy outcomes by combinations of first and second trimester biochemistry markers used in the routine prenatal screening of Down syndromePRENATAL DIAGNOSIS, Issue 5 2010Tianhua Huang Abstract Objective To investigate the associations between four defined adverse pregnancy outcomes and levels of first and second trimester maternal serum markers focusing in particular on how well combinations of markers predict these adverse outcomes. Methods This was a retrospective review of associations between first and second trimester serum markers and adverse pregnancy outcomes among 141 698 women who underwent prenatal screening for Down syndrome in Ontario, Canada. Detection rates (DR), false positive rates (FPR), and odds ratios were estimated using both single and combinations of markers for the adverse outcomes defined. Results Women with decreased second trimester unconjugated oestriol (uE3), deceased first trimester maternal serum pregnancy-associated plasma protein A (PAPP-A), increased second trimester serum alpha fetoprotein (AFP), or increased second trimester total human chorionic gonadotrophin (hCG) were at greater risk of developing adverse pregnancy outcomes. At a 5% FPR, combinations of these markers predicted at best 33.3% of fetal loss and 31.5% of preterm births (PTB) before 32 weeks of gestation. Conclusion There are significant associations between the levels of first and second trimester serum markers and adverse obstetric outcomes. However, even combinations of these markers can only predict adverse obstetric outcomes with modest accuracy. Copyright © 2010 John Wiley & Sons, Ltd. [source] Association offirst-trimester low PAPP-A levels with preterm birth,,PRENATAL DIAGNOSIS, Issue 4 2010Katherine R. Goetzinger Abstract Objective To determine the association of, and predictive ability of, pregnancy-associated plasma protein A (PAPP-A), free ,-human chorionic gonadotrophin (,-hCG), and nuchal translucency (NT) with preterm birth (PTB). Methods A 5-year retrospective cohort study of women who underwent first-trimester combined screening was performed. Maternal medical, antepartum, and pregnancy outcome data were obtained. PAPP-A and ,-hCG were converted to multiples of the median (MoM), and primary exposure was defined as ,10th percentile MoM for PAPP-A. Secondary exposures were defined as , 90th percentile MoM for ,-hCG and NT values of , 20 and 25 mm. The primary outcome was PTB before 35 weeks and the secondary outcome was PTB before 32 weeks. Univariate, bivariate, multivariate, and receiver,operator analyses were used. Results Of the 2231 patients meeting inclusion criteria with complete outcome data available, 222 had a PAPP-A level ,10th percentile MoM. Abnormally low PAPP-A was associated with an increased risk for PTB < 35 weeks [adjusted odds ratio (aOR) 2.0, 1.0,3.8] and < 32 weeks (aOR 2.7, 1.1,6.4), even after adjusting for prior PTB, tobacco exposure, chronic hypertension, and body mass index. PAPP-A ,10th percentile was not sufficiently predictive of PTB < 35 weeks (area under curve = 0.63, 95% CI 0.53,0.72). Neither abnormally high ,-hCG nor increased NT was associated with an increased risk for PTB. Conclusions PAPP-A ,10th percentile is associated with an increased risk for PTB, but is not sufficiently predictive to be used clinically. Copyright © 2010 John Wiley & Sons, Ltd. [source] Effect of maternal smoking on prenatal screening for Down syndrome and trisomy 18 in the first trimester of pregnancyPRENATAL DIAGNOSIS, Issue 3 2008Pierre Miron Abstract Objectives To assess the impact of maternal smoking on first-trimester prenatal screening results for Down syndrome and trisomy 18. Methods Data on maternal smoking status, maternal age, gestational dating, levels of free beta-human chorionic gonadotrophin (,-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal blood and fetal nuchal translucency (NT) thickness were analyzed from a cohort of 53 114 women. Statistical analyses were carried out for crude and adjusted comparisons between smoking and nonsmoking groups. Results In women who smoked during the first trimester of pregnancy, PAPP-A and free ,-hCG levels from dried blood were significantly decreased (p < 0.001) and fetal NT thickness was significantly increased (p < 0.001). For an overall risk assessment combining maternal age and biochemical and ultrasound markers, no significant changes for Down syndrome were found with smoking, but significant increases in average risk as well as in positive rates were found for trisomy 18 (p < 0.001). A potential association between maternal smoking and trisomy 18 remains to be clarified. Conclusion Adjustment for smoking is recommended in first-trimester prenatal screening for trisomy 18 and probably not warranted for Down syndrome because of the cancelling effects of decreased free ,-hCG and increased NT. Further research is required to demonstrate a biological association between maternal smoking and trisomy 18. Copyright © 2008 John Wiley & Sons, Ltd. [source] First-trimester combined screening for Down syndrome: prediction of low birth weight, small for gestational age and pre-term delivery in a cohort of non-selected womenPRENATAL DIAGNOSIS, Issue 3 2008Kasper Pihl Abstract Objective To establish the relationship between the first-trimester screening markers [pregnancy-associated plasma protein A (PAPP-A), free human chorionic gonadotrophin-, (,-hCG), nuchal translucency (NT)], the Down syndrome (DS) risk estimate, and the adverse outcomes such as low birth weight, small for gestational age (SGA) and pre-term delivery. Methods A retrospective cohort study including 1734 non-selected singleton pregnancies consecutively enrolled into the programme of first-trimester combined screening for DS in a 12-month period at a single centre. Data from the Prenatal Patient Registry in ASTRAIA were combined with the Danish National Newborn Screening Registry and Danish Birth Registry. Results There was a significant relation between low PAPP-A MoM, low ,-hCG MoM, increased risk estimate for DS and low birth weight and SGA. Low PAPP-A MoM and increased NT showed a significant relation to pre-term and spontaneous pre-term delivery. Low PAPP-A MoM showed a significant relation to early pre-term delivery. Conclusion First-trimester screening markers exhibited a significant relation to low birth weight, SGA and to some extent, to pre-term and early pre-term delivery. The screening performance of individual markers was poor. Copyright © 2008 John Wiley & Sons, Ltd. [source] Contingent screening for Down syndrome,results from the FaSTER trialPRENATAL DIAGNOSIS, Issue 2 2008Howard S. Cuckle Abstract Objective Comparison of contingent, step-wise and integrated screening policies. Methods Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free ,-human chorionic gonadotrophin (hCG) at 11,13 weeks, and classified positive (>1 in 30), borderline (1 in 30,1500) or negative. Borderline risks were recalculated using ,-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15,18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. Results There were 86 Down syndrome and 32 269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. Conclusion As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing. Copyright © 2008 John Wiley & Sons, Ltd. [source] Maternal weight and ethnic adjustment within a first-trimester Down syndrome and trisomy 18 screening programPRENATAL DIAGNOSIS, Issue 8 2005David A. Krantz Abstract Objective(s) To estimate weight and ethnic group correction factors for first-trimester screening markers. Methods Ethnic-specific median MoM free beta hCG and pregnancy associated plasma protein A (PAPP-A) and delta nuchal translucency values were calculated for cohorts of maternal weight (20 lb each) using data from 51 206 patients undergoing first-trimester screening. False-positive rates for Down syndrome and trisomy 18 were evaluated both prior to and after weight and ethnicity adjustment. Results Free beta hCG and PAPP-A significantly decreased with increasing maternal weight while nuchal translucency increased by a clinically insignificant amount. For free beta hCG the regression formula indicated that after accounting for maternal weight MoM values were 16% higher for African Americans, 6% higher for Asians and 9% lower for Hispanics compared to Caucasians (p < 0.001, p = 0.001, p < 0.001, respectively) but there was no significant difference for Asian Indians. For PAPP-A, MoM values were 35% higher for African Americans (p < 0.001) but were not significantly different for the other ethnic groups compared to Caucasians. Down syndrome false-positive rates did not vary with maternal weight prior to (p = 0.291) or after weight adjustment of biochemistry (p = 0.054). Trisomy 18 false-positive rates varied significantly with weight both before (OR = 1.455 per 20-pound increase, p < 0.001) and after (OR = 1.066 per 20-pound increase, p = 0.01) weight adjustment of biochemistry; however, the odds ratio was greatly reduced after weight adjustment. Conclusion(s) The first-trimester screening markers, free beta hCG, PAPP-A and nuchal translucency vary with maternal weight and ethnicity. Adjustment of free beta hCG and PAPP-A is indicated but adjustment of nuchal translucency results may not be necessary. Copyright © 2005 John Wiley & Sons, Ltd. [source] Maternal serum human chorionic gonadotrophin and pregnancy-associated plasma protein A in twin pregnancies in the first trimesterPRENATAL DIAGNOSIS, Issue 3 2002Marko Niemimaa Abstract Objectives To determine the levels of free ,-human chorionic gonadotrophin (,-hCG) and pregnancy-associated plasma protein A (PAPP-A) in twin pregnancies in the first trimester. Methods Serum samples were obtained from 67 pregnant women with twin pregnancies and maternal serum free ,-hCG and PAPP-A concentrations were compared with those of 4279 singleton controls between the 8th and 13th weeks of gestation. Results The geometric means of chromosomally normal twin pregnancies were 1.85 MoM for free ,-hCG and 2.36 MoM for PAPP-A. There were no cases affected by Down syndrome in either group. Conclusion Twin pregnancies secrete more PAPP-A than expected on the basis of singleton controls whereas free ,-hCG production is not increased. The results of the present study can be used to establish normal reference values when introducing first trimester Down syndrome screening in prenatal care. Copyright © 2002 John Wiley & Sons, Ltd. [source] The first trimester ,combined test' for the detection of Down syndrome pregnancies in 4939 unselected pregnanciesPRENATAL DIAGNOSIS, Issue 3 2002K. Schuchter Abstract The high detection rate (DR) for Down syndrome (DS) pregnancies which can be achieved by measuring fetal nuchal translucency (NT) early in pregnancy can be improved by combining it with placental hormones [pregnancy-associated plasma protein A (PAPP-A) and free ,-human chorionic gonadotrophin (f,-hCG)] and maternal age (,combined test'). In this study we wanted to assess the DR using the ,combined test' in an unselected population of self-referred pregnant women at a false-positive rate (FPR) of about 5%. NT, PAPP-A, f,-hCG and maternal age were measured in all women with singleton pregnancies who booked for delivery in our hospital from 1 December 1997 to 31 April 2000 and who were between 10 and 13 completed weeks of gestation [crown,rump length (CRL) 35,70,mm]. The specific DS risk was calculated using the computer program Alpha Version 5aa (Logical Medical Systems, London, UK). A total of 4939 women were tested. Out of 14 DS pregnancies that occurred during this period of time, 12 were detected with the test. A total of 246 women had a false-positive test result in a non-DS pregnancy (FPR 5.0%). This makes the ,combined test' by far the best test for the detection of DS pregnancies in a low-risk population. The constant increase in maternal age at the time of delivery can also lead to an improved DR if a simple age-dependant protocol for DS detection is used, but only at the price of a much higher number of amniocenteses and subsequent abortions. The DR for DS can be increased much more markedly using the ,combined test' with a FPR that still remains at the level as it was in the early 1970s. Copyright © 2002 John Wiley & Sons, Ltd. [source] Cutaneous polyarteritis nodosa: A report of 16 cases with clinical and histopathological analysis and a review of the published workTHE JOURNAL OF DERMATOLOGY, Issue 1 2010Naoko ISHIGURO Abstract Sixteen cases of cutaneous polyarteritis nodosa referred to our Department from 1985 to 2003 were studied clinically and histopathologically. Laboratory data, treatments and clinical courses were also evaluated retrospectively. All cases had nodules and/or indurated erythemas on their lower extremities. All cases showed necrotizing vasculitis of small muscular arteries in the subcutaneous tissues and/or occlusion of those arteries histopathologically. Fifteen cases also had accumulation of plasma protein in vessels of the dermis and subcutaneous tissues. Laboratory data showed high activity of platelets and coagulation in some cases. Eleven cases had been effectively treated with non-steroidal anti-inflammatory drugs. Eight cases were observed for at least 5 years (the longest for ,19 years) and had good prognoses and no systemic involvement. Cutaneous polyarteritis nodosa seems to be a benign disease, and differs from systemic polyarteritis nodosa although their histopathological features are common. Cutaneous polyarteritis nodosa might involve local dysfunction of the circulation from the dermis to the subcutaneous area. A review of the published work shows that the cause(s) of most cases of cutaneous polyarteritis nodosa is unknown, that no controlled trials for treatment of cutaneous polyarteritis nodosa compared to polyarteritis nodosa have been reported, and that no definitively effective therapy for cutaneous polyarteritis nodosa has been established. [source] ORIGINAL ARTICLE: Murine Monoclonal Antibody 26 Raised Against Tetanus Toxoid Cross-Reacts with ,2 -Glycoprotein I: Its Characteristics and Role in Molecular MimicryAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Aleksandra Inic-Kanada Problem, Studies on experimental antiphospholipid syndrome (APS) models proved that molecular mimicry between plasma protein ,2 -glycoprotein I (,2GPI) and structure within micro-organisms or their products, might be a cause for experimental APS. Considering the heterogeneity of polyclonal antiphospholipid antibodies (aPLs), it is important to define the precise characteristics of pathogenic aPLs. To avoid the influence of polyclonality and to further analyse the connection between molecular mimicry and APS, we produced monoclonal antibodies (MAbs) against tetanus toxoid (TTd) and tested their reactivity against ,2GPI. Method of study, In this report, we analysed the characteristics of MAb26 raised against TTd and cross-reactive with ,2GPI: its binding properties in various in vitro immunoassays, its specific interactions with surface epitopes expressed on apoptotic cells and its role in vivo. Results, We have demonstrated that MAb26: (i) binds ,2GPI being immobilized on an appropriate surface: irradiated polystyrene plates, non-irradiated plates pre-coated with anionic phospholipids and polyvinylidene fluoride membrane; (ii) binds specifically to apoptotic but not to viable cells and the binding is ,2GPI-dependent; and (iii) induces a pathologic pregnancy outcome when passively injected into BALB/c mice. Conclusion, This study concluded that certain subpopulations of antibodies raised against TTd and cross-reactive with ,2GPI, because of the molecular mimicry mechanism, could have pathologic potential. [source] | |||||||||||||||||||