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Kinds of Agents Used Selected AbstractsSoluble human p55 and p75 tumor necrosis factor receptors reverse spontaneous arthritis in transgenic mice expressing transmembrane tumor necrosis factor ,ARTHRITIS & RHEUMATISM, Issue 9 2006Carl K. Edwards III Objective The roles of the transmembrane and secreted forms of tumor necrosis factor , (TNF,) in rheumatoid arthritis (RA) remain unclear. Agents used to inhibit TNF, have shown varying efficacy in RA patients, suggesting that anti-TNF, agents possess dissimilar mechanisms of action, including the ability to neutralize transmembrane (tmTNF,) and secreted TNF,. In this study, TNF,-knockout (TNF,-KO) mice that were genetically altered to express elevated levels of tmTNF, were constructed to further understand the roles of the 17-kd secreted, trimeric, and 26-kd transmembrane forms of TNF,. Methods A speed-congenic mating scheme was used to generate 3 unique strains of mice: 1) transgenic tmTgA86 mice overexpressing 26-kd tmTNF, and also secreting 17-kd trimeric TNF, (tmTNF,-transgenic), 2) TNF,,/, mice (TNF,-KO), and 3) transgenic mice overexpressing tmTNF, backcrossed to TNF,-KO mice (tmTNF,-transgenic/TNF,-KO). Mice were treated with phosphate buffered saline (as vehicle control), dexamethasone (as positive control), or modified recombinant human soluble TNF receptor (sTNFR) p55 or p75, and were assessed clinically and histopathologically for signs of inflammation and development of arthritis. Results The tmTNF,-transgenic/TNF,-KO mice were born with crinkled tails and spinal deformities similar to those in ankylosing spondylitis. By 2,4 weeks, these mice developed symmetric inflammatory arthritis, characterized by tissue swelling, pannus formation, and bone deformities. The tmTNF,-transgenic mice also developed spontaneous-onset arthritis, but at a slower rate (100% incidence by 10,12 weeks). Clinical and histologic progression of arthritis in the tmTNF,-transgenic/TNF,-KO mice was reduced by treatment with dexamethasone or with the p55 or p75 sTNFR (69% and 63% reduction in total histologic score, respectively). Conclusion These data show that arthritis is sufficiently initiated and maintained in tmTNF,-transgenic/TNF,-KO mice, and that it can be neutralized by recombinant human p55 or p75 sTNFR, resulting in amelioration of the biologic and subsequent histologic destructive effects of tmTNF,. [source] Quantitative assessment of human serum high-abundance protein depletionELECTROPHORESIS, Issue 21 2008Rene Stempfer Abstract The aim of this study is to quantify the effectivity of the depletion of human high-abundance serum and plasma proteins for improved protein identification and disease marker candidate discovery and to assess the risk of concomitant removal of relevant marker proteins. 2-DE and bottom-up shotgun MS combining 2-D capillary chromatography with MS/MS were applied in parallel for the analysis of fractions resulting from the depletion procedure. For many proteins the factors of enrichment by the depletion were obvious allowing their enhanced detection and identification upon high-abundance protein depletion. Nano-liquid chromatography linked MS allowed the efficient identification of several low-abundant proteins that were not identified on the 2-DE gels. Resolving the fractions that were eluted from the matrix upon depletion indicated unspecific binding of disease relevant proteins in plasma samples from acute myocardial infarction patients. The unspecific binding to the depletion matrix of inflammatory markers spiked into the serum was found to depend on the type of capturing agent used. Polyclonal avian antibodies (IgY) displayed the least unspecific binding due to the high immunogenicity of mammalian proteins in avian hosts. [source] Effect of temperature on development, overwintering and establishment potential of Franklinothrips vespiformis in the UKENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 2 2007Eleni Larentzaki Abstract This study investigated the effect of temperature on the development and overwintering potential of the predatory thrips Franklinothrips vespiformis (Crawford) (Thysanoptera: Aeolothripidae), a biological control agent used against glasshouse pests in continental Europe and Israel. Developmental rates increased linearly with rearing temperatures. It was estimated that 304.9 degree days, above a lower threshold temperature of 11.9 °C, were required for F. vespiformis to complete development from egg to adult eclosion. The effect of low temperatures (,5, 0, and 5 °C) was examined on adult female and larval survival. Subsequent reproductive and developmental attributes of survivors were also investigated. Lethal time experiments indicated that larval stages are more cold tolerant than adult F. vespiformis females. Surviving larvae increased their developmental times to adults with decreasing temperature and increasing exposure periods and second instars were significantly more successful than first instars in reaching adulthood. Surviving adult females decreased their oviposition rate with decreasing temperature and increasing exposure periods, and exposures to low temperatures affected the number of viable eggs produced. The results are discussed in the context of overwintering and establishment potential of F. vespiformis in the UK in the event of introducing the predatory thrips as a biological control agent against glasshouse pests. [source] Effective management of adverse effects while on oral chemotherapy: implications for nursing practiceEUROPEAN JOURNAL OF CANCER CARE, Issue 2010K. HARROLD rn, bsc ( hons ), chemotherapy, iv access clinical nurse specialist HARROLD K. (2010) European Journal of Cancer Care19, 12,20 Effective management of adverse effects while on oral chemotherapy: implications for nursing practice The publication of guidelines by the United Kingdom National Patient Safety Agency and the National Confidential Enquiry into Patient Outcome and Death which looked into deaths within 30 days of systemic anticancer therapy and the more recent position statement from the United Kingdom Oncology Nursing Society have all highlighted the need for an improvement in the care and management of patients receiving oral chemotherapy. While it is essential that patients are aware of the rationale behind dose interruption and modification if they are to effectively deal with toxicities and complications that may arise, they also require access to a clear line of communication in order to facilitate early intervention. The value of pre treatment patient education and ongoing support for these patients has already been extensively documented and while a multidisciplinary team approach in this is vital, nurses are ideally placed to take a leading role in these two aspects of treatment management. This article aims to detail and review current best management practices for the most commonly reported toxicities associated with capecitabine, an oral chemotherapeutic agent used in the management of patients with colorectal cancer. Only if both the patient and the health care professional supporting them are aware of best management practices will the impact of toxicities be minimised and treatment outcomes optimised. [source] A research on used quantity of ground resistance reduction agent for ground systemsEUROPEAN TRANSACTIONS ON ELECTRICAL POWER, Issue 4 2010Li-Hsiung Chen Abstract The ground resistance reduction agent can be used to decrease ground resistance for high soil resistivity. The ground resistance decreases and the ground resistance reduction rate increases with increasing quantity of ground resistance reduction agent used. However, the ground resistance reduction effect will display the saturation phenomenon when the quantity of ground resistance reduction agent used increases to a certain level. This research discusses the quantity of ground resistance reduction agent used for ground rod. The used quantity of ground resistance reduction agent should be avoided in saturated areas to maximize the efficiency of ground resistance reduction agent use. Copyright © 2009 John Wiley & Sons, Ltd. [source] Inhibition of human vascular endothelial cells proliferation by terbinafineINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Pei-Yin Ho Abstract We have demonstrated previously that terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, suppresses proliferation of various cultured human cancer cells in vitro and in vivo by inhibiting DNA synthesis and activating apoptosis. In our study, we further demonstrated that TB at a range of concentrations (0,120 ,M) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). Terbinafine was not cytotoxic at a concentration of 120 ,M, indicating that it may have an inhibitory effect on the cell proliferation in HUVEC. The TB-induced inhibition of cell growth rate is reversible. [3H]thymidine incorporation revealed that TB reduced the [3H]thymidine incorporation into HUVEC during the S-phase of the cell-cycle. Western blot analysis demonstrated that the protein levels of cyclin A, but not cyclins B, D1, D3, E, CDK2 and CDK4, decreased after TB treatment. The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Pretreatment of HUVEC with a p21 specific antisense oligonucleotide reversed the TB-induced inhibition of [3H]thymidine incorporation. Taken together, these results suggest an involvement of the p21-associated signaling pathway in the TB-induced antiproliferation in HUVEC. Capillary-like tube formation and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of TB. These findings demonstrate for the first time that TB can inhibit the angiogenesis. © 2004 Wiley-Liss, Inc. [source] Asthma Pharmacotherapy Prescribing in the Ambulatory Population of the United States: Evidence of Nonadherence to National Guidelines and Implications for Elderly PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2008Prakash Navaratnam MPH OBJECTIVES: To examine the level of physician adherence to the Expert Panel Report 2 (EPR-2) pharmacotherapy guidelines of the asthma population, specifically in the elderly ambulatory patient population of the United States. DESIGN: Retrospective cross-sectional study using a national survey. SETTING: National Ambulatory Medical Care Survey data of U.S. elderly patients from 1998 through 2004. PARTICIPANTS: The weighted population sample size was 82,020,318 patients. There were 1,540 observations in this study (preweighted sample size) and 96 strata, with 446 population sampling units (PSUs). There were 11,868,340 patients that were elderly, and they accounted for 14.5% of the overall population sampled. MEASUREMENTS: Specific patient demographic variables, physician demographic variables, and information about asthma medications prescribed were extracted from the data set and analyzed. Descriptive statistics for the patient demographic, physician demographic, and asthma pharmacotherapy variables were generated. A series of logistic regression models were created, with the choice of asthma pharmacotherapy agent used as the dependent variable and patient and physician demographic variables as the independent variables. RESULTS: A major finding was that physicians were not adherent to the National Asthma Education and Prevention Program EPR-2 asthma pharmacotherapy guidelines. Another finding was that, although elderly patients (aged ,65) were exposed to more-stable patterns of care, they were less likely to be prescribed controller medications, long-acting bronchodilators (LABAs), combinations of inhaled corticosteroids and LABAs, and short-acting beta agonists than patients aged 35 to 64. CONCLUSION: A more-concerted effort needs to be undertaken to improve physician adherence to the EPR-2 guidelines, especially in prescribing asthma pharmacotherapy to elderly patients. [source] Bleaching Agents with Varying Concentrations of Carbamide and/or Hydrogen Peroxides: Effect on Dental Microhardness and RoughnessJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 6 2008JULIANA JENDIROBA FARAONI-ROMANO DDS ABSTRACT Purpose:, To evaluate the effect of low and highly concentrated bleaching agents on microhardness and surface roughness of bovine enamel and root dentin. Methods:, According to a randomized complete block design, 100 specimens of each substrate were assigned into five groups to be treated with bleaching agents containing carbamide peroxide (CP) at 10% (CP10); hydrogen peroxide (HP) at 7.5% (HP7.5) or 38% (HP38), or the combination of 18% of HP and 22% of CP (HP18/CP22), for 3 weeks. The control group was left untreated. Specimens were immersed in artificial saliva between bleaching treatments. Knoop surface microhardness (SMH) and average surface roughness (Ra) were measured at baseline and post-bleaching conditions. Results:, For enamel, there were differences between bleaching treatments for both SMH and Ra measurements (p = 0.4009 and p = 0.7650, respectively). SMH significantly increased (p < 0.0001), whereas Ra decreased (p = 0.0207) from baseline to post-bleaching condition. For root dentin, the group treated with CP10 exhibited the significantly highest SMH value differing from those groups bleached with HP18/CP22, HP7.5, which did not differ from each other. Application of HP38 resulted in intermediate SMH values. No significant differences were found for Ra (p = 0.5975). Comparing the baseline and post-bleaching conditions, a decrease was observed in SMH (p < 0.0001) and an increase in Ra (p = 0.0063). Conclusion:, Bleaching agents with varying concentrations of CP and/or HP are capable of causing mineral loss in root dentin. Enamel does not perform in such bleaching agent-dependent fashion when one considers either hardness or surface roughness evaluations. CLINICAL SIGNIFICANCE Bleaching did not alter the enamel microhardness and surface roughness, but in root dentin, microhardness seems to be dependent on the bleaching agent used. [source] Physico-chemical characterisation of 99mTc-tin fluoride colloid agent used for labelling white cellsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 6 2006Chris Tsopelas Abstract 99mTc,tin fluoride colloid is an agent used to label leucocytes, for the imaging and diagnosis of inflammatory conditions including Crohn's disease. Despite previous investigations, this radiolabelling agent is still poorly characterised. The aim of this work was to examine the process of formation and stability of 99mTc,tin fluoride colloid using mass spectrometry, membrane filtration and atomic absorption spectrophotometric techniques. Tin-oxide bonds in tin clusters were identified in the stannous fluoride reagent vial by mass spectrometry. From radioactive particle size distribution experiments, the facile disruption of radiocolloid particles with excess oxygen gas contrasted to the partial hydrolysis of Sn(II) during the formation process. Under the standard conditions, 10% of particles were determined as 1,3 µm, and this population coordinated 96% of the 99mTc added. Colloid particle formation and the reduction of 99mTc-pertechnetate is discussed. Sodium fluoride may optimise 1,3 µm radioactive particle size, by regulating particle growth. 99mTc,tin fluoride colloid is affected by positive or negative charge, as either Al, Mo ions or solid membranes, resulting in either coagulation and/or deflocculation of the particles. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis of 3,4,3 LI 1,2 HOPO labelled with 14CJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2001R. Burgada Abstract 3,4,3 LI 1,2 HOPO 1 or LIHOPO (1,5,10,14-tetra (1-hydroxy-2-pyridone-6-oyl)-1,5,10,14-tetraazatetradecane.) is a decorporation agent used against actinides. It was synthesised labelled with carbon 14 with a view to metabolism studies. [6,9- 14C]-LIHOPO 2 was obtained in two radioactive steps through a very convenient synthesis in 50% radioactive yield from commercially available [1,4- 14C]-spermine, hydrochloride and 1-benzyloxy-6-oxo-1,6-dihydropyridine-2-carbonyl chloride 7. The synthesis of 7 is also described. Copyright © 2001 John Wiley & Sons, Ltd. [source] Focal nodular hyperplasia: Central scar enhancement pattern using gadoxetate disodiumJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Adib R. Karam MD Abstract Purpose: To illustrate the unusual enhancement pattern of the focal nodular hyperplasia central scar using Gadoxetate Disodium. Materials and Methods: Over a 10-month period, six patients, with a total of seven focal nodular hyperplasia lesions with typical central scar, had MRI of the liver using Gadoxetate Disodium (Eovist, Bayer HealthCare Pharmaceuticals Inc., Wayne, NJ). Four of the six patients had a prior Gadobenate Dimeglumine (Multihance, Bracco Diagnostics Inc., Princeton, NJ) -enhanced MRI of the liver performed within the previous year. The dynamic enhancement pattern of the central scar on the 10 liver MRIs was independently analyzed by two abdominal imaging radiologists who were blinded to the contrast agent used. Results: On the Gadoxetate Disodium-enhanced MRIs and during the arterial phase, 1-min, 2-min, and 3-min delay, none of the central scars demonstrated enhancement. However, all four of the lesions that were previously scanned using Gadobenate Dimeglumine demonstrated typical enhancement after a 3-min delay. Conclusion: On Gadoxetate Disodium-enhanced MRIs of the liver, the central scar of focal nodular hyperplasia lesions does not typically demonstrate delayed enhancement. J. Magn. Reson. Imaging 2010;32:341,344. © 2010 Wiley-Liss, Inc. [source] Chemical Agent Simulant Release from Clothing Following Vapor ExposureACADEMIC EMERGENCY MEDICINE, Issue 2 2010Robert J. Feldman MD ACADEMIC EMERGENCY MEDICINE 2010; 17:1,4 © 2010 by the Society for Academic Emergency Medicine Abstract Objectives:, Most ambulatory victims of a terrorist chemical attack will have exposure to vapor only. The study objective was to measure the duration of chemical vapor release from various types of clothing. Methods:, A chemical agent was simulated using methyl salicylate (MeS), which has similar physical properties to sulfur mustard and was the agent used in the U.S. Army's Man-In-Simulant Test (MIST). Vapor concentration was measured with a Smiths Detection Advanced Portable Detector (APD)-2000 unit. The clothing items were exposed to vapor for 1 hour in a sealed cabinet; vapor concentration was measured at the start and end of each exposure. Clothing was then removed and assessed every 5 minutes with the APD-2000, using a uniform sweep pattern, until readings remained 0. Results:, Concentration and duration of vapor release from clothing varied with clothing composition and construction. Lightweight cotton shirts and jeans had the least trapped vapor; down outerwear, the most. Vapor concentration near the clothing often increased for several minutes after the clothing was removed from the contaminated environment. Compression of thick outerwear released additional vapor. Mean times to reach 0 ranged from 7 minutes for jeans to 42 minutes for down jackets. Conclusions:, This simulation model of chemical vapor release demonstrates persistent presence of simulant vapor over time. This implies that chemical vapor may be released from the victims' clothing after they are evacuated from the site of exposure, resulting in additional exposure of victims and emergency responders. Insulated outerwear can release additional vapor when handled. If a patient has just moved to a vapor screening point, immediate assessment before additional vapor can be released from the clothing can lead to a false-negative assessment of contamination. [source] Extracts of various species of Epilobium inhibit proliferation of human prostate cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2003Annabella Vitalone This study examined whether various species of Epilobium, a phytotherapeutic agent used in folk medicine as a treatment for benign prostatic hyperplasia, may have an antiproliferative effect in PZ-HPV-7 human prostatic epithelial cells in-vitro. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) test, [methyl- 3H]thymidine incorporation into DNA and flow cytometry analysis were used to evaluate cell proliferation. Ethanolic extracts of E. spicatum, E. rosmarinifolium and E. tetragonum inhibited DNA synthesis in PZ-HPV-7 cells. While at high concentrations all extracts were cytotoxic, DNA synthesis was also decreased at levels that caused no or little cytotoxicity. Treatment of cells with Epilobium extracts did not result in a formation of DNA fragments (evaluated by the TUNEL assay) or chromatin condensation (assessed by Hoechst staining). Flow cytometry analysis indicated that Epilobium extracts inhibit the progression of the cell cycle from the G0/G1 phase. These results suggest that extracts of Epilobium inhibit proliferation of human PZ-HPV-7 cells in-vitro by affecting progression of the cell cycle. This study provides some initial biological plausibility for the use of Epilobium extracts in benign prostatic hyperplasia. [source] INTERACTIONS OF THE MIX-LINKED ,-(1,3)/,-(1,4)- d -XYLANS IN THE CELL WALLS OF PALMARIA PALMATA (RHODOPHYTA),JOURNAL OF PHYCOLOGY, Issue 1 2003Estelle Deniaud Algal cell wall mechanical properties, crucial for biological functions and commercial applications, rely on interactions in macromolecular assemblies. In an effort to better understand the interactions of the matrix-phase ,-(1,3)/(1,4)- d -xylan in the edible seaweed Palmaria palmata ((L.) O. Kuntze, Rhodophyta, Palmariales), sequential extractions by saline, alkaline, and chaotropic solutions were done. The chemical composition and structure and the physicochemical properties of the isolated xylan revealed that it was partly acidic, probably due to the presence of sulfate (up to 5%) and phosphate groups (up to 4%). Although such acidity suggested ionic interactions of xylan in the cell walls, the high yields of polysaccharide extracted by alkali and particularly by 8 M urea and 4.5 M guanidium thiocyanate demonstrated that it was mainly hydrogen bonded in the cell wall. H-bonds did not appear to be related to the mean proportions of ,-(1,3) and ,-(1,4)- d -xylose linkages because these did not differ between extracts of increasing alkalinity. However, the decreasing molar weight and intrinsic viscosity of extracts obtained by alkaline solution containing a reducing agent used to prevent polysaccharide degradation suggested the presence of an alkali-labile component in the xylan. These results are discussed with regard to the role of potential wall proteins as a means of control of these interactions. [source] Synthesis, properties, and sulfonation of novel dendritic multiblock copoly(ether-sulfone)JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2008Sumiko Matsumura Abstract Multiblock copoly(ether-sulfone)s (PESs) bearing anchor units for the construction of dendritic blocks were synthesized by two-step reactions: (1) synthesis of PES block with both phenoxide end-groups; (2) chain extension and end-capping of the block by use of excess novel hexafunctional agent, hexakis(4-(4-fluorophenylsulfonyl)phenyl)benzene. The optimum average block length (n) and amount (x) of the hexafunctional agent used for the synthesis of high-molecular-weight PES without crosslinking were n = 26 and x = 2.6 equiv, respectively. The dendritic blocks in the PES were constructed by the aromatic nucleophilic substitution reaction of the activated aromatic fluoride groups on the anchor units using 4-tritylbenzenethiol. The clean substitution of the fluoride groups in the PES was confirmed by 1H NMR and 19F NMR. Three sulfonic acid groups were introduced on the pendant phenyl rings of the trityl groups in the PES by the reaction with chlorosulfonic acid. This is the first example of a dendritic PES bearing clusters of sulfonic acid groups only on the dendritic blocks. Cast films of presulfonated dendritic PES were strong and flexible, however, the membranes of sulfonated dendritic PES were brittle so that the conductivity measurements were not performed. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6365,6375, 2008 [source] Effects of Tooth Preparation Burs and Luting Cement Types on the Marginal Fit of Extracoronal RestorationsJOURNAL OF PROSTHODONTICS, Issue 2 2009Mohamed F. Ayad BDS Abstract Purpose: Although surface roughness of axial walls could contribute to precision of a cast restoration, it is unclear how the roughness of tooth preparation affects marginal fit of the restoration in clinical practice. The purpose of this study was to describe the morphologic features of dentin surfaces prepared by common rotary instruments of similar shapes and to determine their effects on the marginal fit for complete cast crowns. Materials and Methods: Ninety crowns were cast for standardized complete crown tooth preparations. Diamond, tungsten carbide finishing, and crosscut carbide burs of similar shape were used (N = 30). The crowns in each group were subdivided into three groups (n = 10) for use with different luting cements: zinc phosphate cement (Fleck's), glass ionomer cement (Ketac-Cem), and adhesive resin cement (Panavia 21). Marginal fit was measured with a light microscope in a plane parallel to the tooth surface before and after cementation between four pairs of index indentations placed at equal distances around the circumference of each specimen. Difference among groups was tested for statistical significance with analysis of variance (ANOVA) followed by Ryan-Einot-Gabriel-Welsch Multiple Range Test (,= 0.05). Results: Analysis of measurements disclosed a statistically significant difference for burs used to finish tooth preparations (p < 0.001); however, luting cement measurements were not significantly different (p= 0.152). Also, the interaction effect was not significantly different (p= 0.685). For zinc phosphate cement, the highest marginal discrepancy value (100 ± 106 ,m) was for tooth preparations refined with carbide burs, and the lowest discrepancy value (36 ± 30 ,m) was for tooth preparations refined with finishing burs. For glass ionomer cement, the highest marginal discrepancy value (61 ± 47 ,m) was for tooth preparations refined with carbide burs, and the lowest discrepancy value (33 ± 40 ,m) was for tooth preparations refined with finishing burs. For adhesive resin cement, the highest marginal discrepancy value (88 ± 81 ,m) was for tooth preparations refined with carbide burs, and the lowest discrepancy value (19 ± 17 ,m) was for tooth preparations refined with finishing burs. Conclusions: Marginal fit of complete cast crowns is influenced by tooth preparation surface characteristics, regardless of the type of luting agent used for cementation. Tooth preparations refined with finishing burs may favor the placement of restorations with the smallest marginal discrepancies, regardless of the type of cement used. [source] The pharmacokinetics and safety of porfimer after repeated administration 30,45 days apart to patients undergoing photodynamic therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. P. Pereira Summary Background, Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. Aim, To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30,45 days apart in patients undergoing photodynamic therapy. Methods, Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3,5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. Results, Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. Conclusion, Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days. [source] Clinical evaluation of a new formulation of propofol in a medium-chain and long-chain triglycerides emulsion in dogsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007J. I. REDONDO GARCÍA Propofol formulated in a mixed medium-chain and long-chain triglycerides emulsion has been recently introduced for clinical use as an alternative to the conventional long-chain triglycerides formulation. This prospective multicentric study evaluated the clinical effectiveness and the complications associated with the use of this new formulation of propofol in dogs. Forty-six Spanish veterinary clinics participated in this study. A total of 541 anaesthesias (118 ASA I, 290 ASA II, 101 ASA III and 32 ASA IV) performed for various diagnostic and therapeutic purposes were evaluated. The anaesthetic protocol was not controlled, with the exception that propofol had to be used at least for induction of anaesthesia. The induction dose of propofol and the incidence of anaesthetic complications throughout the procedure were recorded. A chi-square test compared the incidence of complications according to the maintenance agent used (propofol vs. inhalatory anaesthesia), anaesthetic risk (ASA classification) and the reason for the anaesthesia. The patients premedicated with ,2 agonists needed lower doses (mean ± SD, 2.9 ± 1.3 mg/kg i.v.) than the animals premedicated with phenothiazines (3.9 ± 1.4 mg/kg i.v.) or benzodiazepines (4.0 ± 1.4 mg/kg i.v.). The most frequent complications were difficult endotracheal intubation (1.3%), postinduction apnoea (11.3%), cyanosis (0.6%), bradypnoea (2.6%), tachypnoea (2.8%), bradycardia (2%), tachycardia (2.6%), hypotension (0.2%), shock (0.2%), vomiting (4.6%), epileptiform seizures (2.8%), premature awakening (7.4%) and delayed recovery (0.9%). There were no cases of pain on injection or aspiration pneumonia. Three dogs died (0.55%), one during induction and two during recovery from anaesthesia. This study demonstrates that the new formulation of propofol is an useful and effective drug to induce general anaesthesia in dogs. [source] Influence of Coupling Agents on Melt Flow Behavior of Natural Fiber CompositesMACROMOLECULAR MATERIALS & ENGINEERING, Issue 5 2007Velichko Hristov Abstract The influence of coupling agents on the melt rheological properties of natural fiber composites has been investigated in this work using capillary and rotational rheometers. Scanning electron microscopy was also employed to supplement the rheological data. It was found that molecular weight and molecular weight distribution of the polymer matrix and coupling agent characteristics influence the filler wetting and the melt flow properties of the filled composites. Generally, low molecular weight and narrow molecular weight distribution polyethylene matrix provides relatively larger increase of the viscosity of the composites. Coupling agents tend to increase the resistance to shearing, but wall slip effects may interfere with the measured values, especially at very high filler loadings. Entrance pressure loss in capillaries is also influenced by polymer matrix and coupling agent used. [source] Measuring the arterial input function with gradient echo sequencesMAGNETIC RESONANCE IN MEDICINE, Issue 6 2003Matthias J.P. van Osch Abstract The measurement of the arterial input function by use of gradient echo sequences was investigated by in vitro and in vivo experiments. First, calibration curves representing the influence of the concentration of Gd-DTPA on both the phase and the amplitude of the MR signal were measured in human blood by means of a slow-infusion experiment. The results showed a linear increase in the phase velocity and a quadratic increase in ,R as a function of the Gd-DTPA concentration. Next, the resultant calibration curves were incorporated in a partial volume correction algorithm for the arterial input function determination. The algorithm was tested in a phantom experiment and was found to substantially improve the accuracy of the concentration measurement. Finally, the reproducibility of the arterial input function measurement was estimated in 16 patients by considering the input function of the left and the right sides as replicate measurements. This in vivo study showed that the reproducibility of the arterial input function determination using gradient echo sequences is improved by employing a partial volume correction algorithm based on the calibration curve for the contrast agent used. Magn Reson Med 49:1067,1076, 2003. © 2003 Wiley-Liss, Inc. [source] Living related small bowel transplantation in children: 3-dimensional computed tomography donor evaluationPEDIATRIC TRANSPLANTATION, Issue 1 2004Fabrizio Panaro Abstract:, The evaluation of the small bowel vascular anatomy of living small bowel donors (LSBD) is usually performed with conventional angiography (CA). Recently, angio computed tomography (CT) has become a valid study of the vascular anatomy for kidney and liver living donors. We studied the applicability of angio CT with 3-D reconstruction (3-D-ACT) in the evaluation of LSBD. Potential LSBDs for pediatric transplant underwent both CA and 3-D-ACT to evaluate the anatomy of the distal branches of the superior mesenteric artery and vein. Angio-CT was performed with General Electric Lightspeed Scanner. The 3-D reconstruction was performed on the TeraRecon workstation. Adverse reactions, contrast dosage, test duration, invasiveness, hospital-stay, patient discomforts and accuracy were evaluated. Four potential donors (four female; mean age: 30.5 yr; mean BMI: 28.4) underwent both tests. Adverse reactions correlated to contrast agent used (90 mL CA, 150 mL 3-D-ACT) were not reported. CA required a hospitalization of 6 h as opposed to immediate discharge after the 3-D-ACT. The CA required the placement of transfemoral catheter and therefore greater patient discomfort than with 3-D-ACT. The 3-D-ACT arterial images were rated as equivalent to CA, however, 3-D-ACT venous images were rated better than the CA in all cases. CT-angiography with 3-D reconstruction is an acceptable method for vascular evaluation. When compared with routine angiography, it is less invasive, better tolerated and faster, but does require a significantly greater volume of venous contrast. 3-D-ACT also offers a better evaluation of the venous phase, and thus may become the test of choice to evaluate the vascular anatomies of LSBD candidates. [source] Flame retarding effects of nanoclay on wood,fiber compositesPOLYMER ENGINEERING & SCIENCE, Issue 3 2007G. Guo This research article focuses on investigating the effects of nanoclay particles on the flame retarding characteristics of wood,fiber/plastic composites (WPC) using ASTM D635. The processing aspects of nanocomposites with WPC are presented. The processing techniques for controlling the degree of exfoliation and the cost aspect are also described. It turns out that the coupling agent used for wood,fibers is also effective for the exfoliation of clay, and therefore, no additional cost is required. This research indicates that the structure of nanocomposites (i.e., the degree of exfoliation) and the clay content used have a large impact on the flame retardancy of WPC. The flame retardancy is investigated as a function of these parameters. Based on this, a cost-effective way to improve flame retardancy of WPC is presented. POLYM. ENG. SCI., 47:308,313, 2007. © 2007 Society of Plastics Engineers. [source] Acute Hepatitis Associated with Treatment of Peyronie's Disease with Potassium Para-Aminobenzoate (Potaba)THE JOURNAL OF SEXUAL MEDICINE, Issue 12 2008Joey Roy ABSTRACT Introduction., Potassium para-aminobenzoate is an agent used in the treatment of sclerotic diseases including Peyronie's disease of the penis. It has been reported that this medication may have been responsible for cases of acute liver injury. Aim., To inform clinicians of the possibility of an adverse drug event associated with the oral intake of potassium para-aminobenzoate by reporting an additional case and compiling information from previous reports. Methods., The affected patient's medical records were diligently reviewed; all available and relevant information pertaining to this adverse event is reported. Similar case reports were analyzed and compared, and relevant information was compiled in this report. Results., The patient enjoyed a full biochemical recovery from his hepatitis 4 months after discontinuation of potassium para-aminobenzoate. Conclusion., To date, the oral use of potassium para-aminobenzoate has been reported to be linked to acute liver injury in six individuals. Appropriate management of this adverse drug event is the immediate discontinuation of the offending drug and general patient support measures. Roy J, and Carrier S. Acute hepatitis associated with treatment of Peyronie's disease with potassium para-aminobenzoate (Potaba). J Sex Med **;**:**,**. [source] CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008D. D. Bloom Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source] Scanning electron microscopy evaluation of the hard tissue barrier after pulp capping with calcium hydroxide, mineral trioxide aggregate (MTA) or ProRoot MTAAUSTRALIAN ENDODONTIC JOURNAL, Issue 2 2009Eduardo Galia Reston dds Abstract The aim of this study was to investigate the morphology and localisation of calcium hydroxide- and mineral trioxide aggregate (MTA)-induced hard tissue barriers after pulpotomy in dogs' teeth. Pulpotomies were performed on maxillary and mandibular premolars of five dogs. The teeth were assigned into three groups according to the pulp-capping agent used. The pulpal wounds were capped with calcium hydroxide (Ca(OH)2, control), MTA or ProRoot MTA, and the cavities were restored with amalgam. After a 90-day follow-up period, the dogs were euthanised and the teeth were examined under scanning electron microscopy (SEM). An image-processing and analysis software was used to delimit the perimeters of the root canal area and the hard tissue barrier to determine the percentage of root canal obliteration. SEM data were used to assess the morphology, localisation and extension of the reparative hard tissue barriers. ProRoot MTA was statistically different from MTA and Ca(OH)2 (P < 0.05) regarding tissue barrier morphology. Localisation data showed that ProRoot MTA was significantly different from Ca(OH)2 (P < 0.05) and similar to MTA (P > 0.01; P > 0.05). No statistically significant difference (P > 0.01; P > 0.05) was observed between MTA and Ca(OH)2. A larger number of complete (centroperipheral) hard tissue barriers with predominance of dentinal tubules was observed to the ProRoot MTA when compared with the Ca(OH)2 group. [source] A Prospective Observational Study of the Effect of Etomidate on Septic Patient Mortality and Length of StayACADEMIC EMERGENCY MEDICINE, Issue 1 2009Karis L. Tekwani MD Abstract Objectives:, Etomidate is known to cause adrenal suppression after single-bolus administration. Some studies suggest that when etomidate is used as an induction agent for intubation of septic patients in the emergency department (ED), this adrenal suppression leads to increased mortality, vasopressor requirements, and length of hospital stay. The authors sought to determine differences in the in-hospital mortality and hospital length of stay (LOS) between septic patients given etomidate and patients given alternative or no induction agents for rapid-sequence intubation in our ED. Methods:, This was a nonrandomized, prospective observational study of all patients meeting sepsis criteria who were intubated in an ED over a 9-month period. Times of patient presentation, intubation, admission, discharge, and/or death were recorded, as well as the intubation agent used, if any, and corticosteroid use. The authors also recorded relevant laboratory and demographic variables to determine severity of illness using the Mortality in Emergency Department Sepsis (MEDS) score. Mortality and survivor LOS between the patients given etomidate and those given alternative or no induction agents were compared. Results:, A total of 106 patients with sepsis were intubated over the study period. Of these, 74 patients received etomidate, while 32 patients received ketamine, benzodiazepines, propofol, or no induction agents. Age in years (median = 78; interquartile range [IQR] = 67 to 83), gender (45% male), MEDS score (median = 13; IQR = 10 to 15), and receipt of supplemental corticosteroids (56%) were statistically similar between the two groups. In-hospital mortality of patients given etomidate (38%; 95% confidence interval [CI] = 28% to 49%) was similar to those receiving alternatives (44%; 95% CI = 28% to 61%). Surviving patients had a median hospital LOS after receiving etomidate of 10 days compared to those receiving alternatives (7.5 days; p = 0.08). Conclusions:, No statistically significant increase in hospital LOS or mortality in patients given etomidate for rapid-sequence intubation was found. Suggestions that the use of etomidate for intubation in the ED be abandoned are not supported by these data. [source] Utility-Based Optimization of Combination Therapy Using Ordinal Toxicity and Efficacy in Phase I/II TrialsBIOMETRICS, Issue 2 2010Nadine Houede Summary An outcome-adaptive Bayesian design is proposed for choosing the optimal dose pair of a chemotherapeutic agent and a biological agent used in combination in a phase I/II clinical trial. Patient outcome is characterized as a vector of two ordinal variables accounting for toxicity and treatment efficacy. A generalization of the Aranda-Ordaz model (1981,,Biometrika,68, 357,363) is used for the marginal outcome probabilities as functions of a dose pair, and a Gaussian copula is assumed to obtain joint distributions. Numerical utilities of all elementary patient outcomes, allowing the possibility that efficacy is inevaluable due to severe toxicity, are obtained using an elicitation method aimed to establish consensus among the physicians planning the trial. For each successive patient cohort, a dose pair is chosen to maximize the posterior mean utility. The method is illustrated by a trial in bladder cancer, including simulation studies of the method's sensitivity to prior parameters, the numerical utilities, correlation between the outcomes, sample size, cohort size, and starting dose pair. [source] Fluorescence enhancement of warfarin induced by interaction with ,-cyclodextrinBIOTECHNOLOGY PROGRESS, Issue 4 2009Jacob M. Vasquez Abstract Warfarin is the most common agent used for control and prevention of venous as well as arterial thromboembolism (blood clots). In aqueous media, warfarin forms inclusion complexes with a family of cyclic oligosaccharides, ,, ,, ,-cyclodextrins (CD). The formation of these complexes results in enhancement of the fluorescence of warfarin. Such spectroscopic changes offer a venue for the development of bioanalytical methodologies for warfarin quantification in biological liquids. We characterized the photophysical properties of warfarin in solvents with varying polarity and viscosity. The fluorescence quantum yield of warfarin correlated: (1) strongly with the solvent viscosity (R = 0.979) and (2) weakly with the solvent polarity (R = 0.118). These findings indicate that it is the change of the viscosity, rather than polarity, of the microenvironment that causes the fluorescence enhancement of warfarin upon binding to ,-CD. Utilizing the observed fluorescence enhancement in fluorescence titration measurements, the binding constants of warfarin to ,-CD were obtained (2.6 × 102 M,1,3.7 × 102 M,1). Using multivariable linear analysis, we extracted the stoichiometry of warfarin-,-CD interaction (1:1). © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Zheng Jiao WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? , Sirolimus is an immunosuppressive agent used for the prophylaxis of renal allograft rejection. , Several conventional pharmacokinetic and population pharmacokinetic studies have been conducted to assess the pharmacokinetic characteristics of sirolimus in White or African-American recipients. WHAT THIS STUDY ADDS? , The population pharmacokinetics of sirolimus in Chinese adult renal transplant recipients was characterized for the first time. , New drug,drug interactions between herbal medicines and sirolimus were identified as the covariates on sirolimus clearance. AIMS This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients. METHODS Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of ciclosporin dose reduction and ciclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with ciclosporin, sirolimus and corticosteroids during the first 3 months followed by either ciclosporin dose reduction or ciclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations (C0) from 112 patients were used to develop a population pharmacokinetic model using the nonmem program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, ciclosporin daily dose, ciclosporin C0 as well as other commonly used co-medications were explored. RESULTS The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 10.1 l h,1 (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or ciclosporin C0. Moreover, CL/F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates from nonmem. CONCLUSIONS These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients. [source] DNA ligase IV is a potential molecular target in ACNU sensitivityCANCER SCIENCE, Issue 8 2010Natsuko Kondo Nimustine (ACNU) is a chloroethylating agent which was the most active chemotherapy agent used for patients with high-grade gliomas until the introduction of temozolomide, which became the standard of care for patients with newly diagnosed glioblastomas in Japan. Since temozolomide was established as the standard first-line therapy for glioblastoma multiforme (GBM), ACNU has been employed as a salvage chemotherapy agent for recurrent GBM in combination with other drugs. The acting molecular mechanism in ACNU has yet to be elucidated. ACNU is a cross-linking agent which induces DNA double-strand breaks (DSBs). The work described here was intended to clarify details in repair pathways which are active in the repair of DNA DSBs induced by ACNU. DSBs are repaired through the homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways. Cultured mouse embryonic fibroblasts were used which have deficiencies in DNA DSB repair genes which are involved in HR repair (X-ray repair cross-complementing group 2 [XRCC2] and radiation sensitive mutant 54 [Rad54]), and in NHEJ repair (DNA ligase IV [Lig4]). Cellular sensitivity to ACNU treatment was evaluated with colony forming assays. The most effective molecular target which correlated with ACNU cell sensitivity was Lig4. In addition, it was found that Lig4 small-interference RNA (siRNA) efficiently enhanced cell lethality which was induced by ACNU in human glioblastoma A172 cells. These findings suggest that the down-regulation of Lig4 might provide a useful tool which can be used to increase cell sensitivity in response to ACNU chemotherapy. (Cancer Sci 2010) [source] | |||||||||||||||||||||||||||||||||||||||||||