acute and pilot drf toxicity testing in drug safety evaluation

... design and coordination and helped to draft the manuscript AK contributed to the development of the protocol and study instruments All the authors have been involved in drafting and revising the manuscript, ... demographic and clinical characteristics of the FESP and the control subjects were summarized in Table Age and gender distribution of the subjects and smoking habit did not differ between patients and ... an increased activity of GPx and a decreased activity of CAT in RBCs (3) a positive correlation exists between the score of SAPS and the levels of GSHt and GSHr The findings of this study indicate...

Ngày tải lên: 11/08/2014, 15:22

... Germany, Greece, Ireland, Italy, the Netherlands, Norway, Portugal, Spain, Switzerland and the UK), of which (Denmark, Germany, Spain and Switzerland) did not take part in the maintenance phase This ... law on information and liberty Population To be included, patients had to be aged 18 years or over, presenting as in- or out-patients for the treatment of acute or mixed mania, and initiating or ... ties in the previous weeks or with a partner (live -in or not live -in) Relapse was defined for patients not achieving simple remission and patients meeting one of the following relapse criteria: increase...

Ngày tải lên: 11/08/2014, 17:20

... 99 Chapter Screens in Safety and Hazard Assessment 112 Chapter Acute Toxicity Testing in Drug Safety Evaluation 130 Chapter Genotoxicity 176 Chapter Subchronic and Chronic Toxicity Studies 237 ... Drug Safety Assessment 634 Pharmacokinetics and Toxicokinetics in Drug Safety Evaluation 691 Chapter 19 Safety Pharmacology 737 Chapter 20 Evaluation of Human Tolerance and Safety in Clinical ... detailed in a later section of this chapter In vitro methods are increasingly providing new tools for use in both early screening and the understanding of mechanisms of observed toxicity in preclinical...

Ngày tải lên: 11/04/2014, 01:13

... grade toxicity during treatment Acute grade GU and GI toxicity was found in 47% and 30% of our patient group Ten patients (3%) developed grade acute GU side effects with two patients having a urinary ... dysuria and grade hematuria and urinary frequency/ urgency toxicity Furthermore, this patient suffered from Table 2: Pre-treatment complaints and acute toxicity according to the Common Toxicity ... months, continuing scoring of toxicity is needed, because an increase in GU complications has been reported after three years [27] In conclusion, a dose of 76 Gy in 35 fractions using IMRT and fiducial...

Ngày tải lên: 09/08/2014, 09:22

... parameters and acute GI toxicity or late GI toxicity free survival Acute and late GU Toxicity The PGUM and acute and late GU toxicity are summarized in Table Incidence of single symptoms (dysuria, incontinence, ... minority of patients who did not attend these visits were contacted and data were successfully retrieved Table 2: Pre-treatment gastrointestinal morbidity and gastrointestinal acute and late toxicity ... Gy), respectively Acute and late GI Toxicity Patient characteristics are summarized in Table The pretreatment GI morbidity, acute and late GI toxicity and incidence of late GI toxicity at last...

Ngày tải lên: 09/08/2014, 09:22

... created the randomization scheme by drawing treatment assignments from a blinded container The investigator administering the drug, the technicians performing testing, and the subject were blinded to ... stimulus for that pain condition from the average SUDs score obtained during and minutes after the 15-minute exposure Comparisons between pain conditions and between testing sessions within each subject ... similar in migraineurs with and without vertigo Cephalalgia 2008; 28:988 - 990 Vitkovic J, Paine M, Rance G Neuro-otological findings in patients with migraine- and nonmigraine-related dizziness...

Ngày tải lên: 26/10/2012, 09:57

... of chronic toxicity tests using naupliar and copepodite stages in addition to the acute and subchronic toxicity tests conducted in the present study CONCLUSIONS Acute and subchronic toxicity of ... (median effect concentration) in chronic toxicity tests and the acute- chronic ratio, which have not been simultaneously determined in most acute and chronic toxicity studies In the present study, the ... per female in control and acetone-control and between the values in control and test solutions (for each TBTCl concentration) in each experiment (every two days) RESULTS Acute toxicity in adult...

Ngày tải lên: 05/09/2013, 10:15

... 81 Mg2+-independent Neutral Sphingomyelinases 84 Alkaline Sphingomyelinase from the Intestinal Tract 85 Bacterial Sphingomyelinase-phospholipase C 85 Sphingomyelinase Mechanism 85 Binding of Magnesium ... Alonso Introduction and Scope Sphingomyelinases 80 Types of Sphingomyelinases 80 Acid Sphingomyelinase (aSMase) 80 Secretory Sphingomyelinase (sSMase) 81 Neutral, Mg2+-dependent Sphingomyelinases ... Ions 85 Binding of Substrate 85 Mechanism of Catalysis 86 Sphingomyelinase Assay 88 Sphingomyelinase Inhibitors 89 Sphingomyelinase–Membrane Interactions 89 Lipid Effects on Sphingomyelinase Activity...

Ngày tải lên: 17/02/2014, 05:20

... staining is brown The section is counter stained with hematoxylin (B) In situ staining of renal VT1 bound in vivo VT1 (50 lg per mouse) injected i.p and bound within the kidney was immunostained ... endothelial staining in Fabry mouse; (C, D) lung – epithelial cell staining increased in Fabry mouse; (E, F) brain microvascular endothelial staining in Fabry mouse Magnification ·16 no VT1 staining of ... three individual mice in each category are shown.) Magnification: (a–c, e–g) ·40; (d, g, i–l) ·16 * ¼ central veins, p ¼ portal veins Inserts in (a) and (b) show Kupffer cell staining, and in (d)...

Ngày tải lên: 19/02/2014, 07:20

... gasoline, or industries Lead occurs in drinking water through leaching from lead-containing pipes, faucets, and solder, which in turn can be found in plumbing of older buildings • • • Foods and ... deposition into leafy vegetables (Mushak et al 1989 as cited in AAP 1993) grinding or cutting equipment during processing Packaging Lead in packaging may contaminate food • • Bright red and yellow paints ... of gasoline in the U.S between 1976 and 1996 The major exposure pathways for workers are inhalation and ingestion of lead-bearing dust and fumes Workers in the lead smelting, refining, and manufacturing...

Ngày tải lên: 05/03/2014, 10:20

... amphetamines (including amphetamine and methamphetamine), cocaine, marijuana, narcotics (including morphine, codeine, and others), and phencyclidine Testing methodology has continually evolved now including ... specimen of choice in the drug testing industry in the USA is urine and in clinical medicine, serum In recent years, interest has grown in the use of other matrices as drug testing media Although ... analysis for drugs and chemicals including the most common drugs of abuse and also focuses on the interpretation, that is, the understanding and appreciation of the results of this testing in a medical–legal...

Ngày tải lên: 06/03/2014, 09:20

... overexpressing SMO cells further confirmed the increased SMO activity, with decreases in intracellular spermine pools and increased spermidine levels in SMO1 and SMO5 cells These changes in spermine and ... oxidation of spermine to spermidine diminishes nuclear spermine pools Because spermine has essential roles in the the protection of DNA, including free radical scavenging and DNA shielding, this reduction ... media (Mediatech, Inc., Herndon, VA, USA) containing 9% iron-supplemented fetal bovine serum (Hyclone, Logan, UT, USA) and 1% penicillin and streptomycin Beas2B cells were maintained in LHC-9 serum-free...

Ngày tải lên: 07/03/2014, 05:20

... Drug- Metabolizing Enzymes, Transporters, and Drug Drug Interactions 83 Steven W Louie and Magang Shou Experimental Models of Drug Metabolism and Disposition 151 Gang Luo, Chuang Lu, Xinxin Ding, ... Espina R, Yu L, Adedoyin A, Talaat R, Mutlib A, Scatina J Obtaining exposures of metabolites in preclinical species through plasma pooling and quantitative NMR: Addressing metabolites in safety ... via chlorination) some drugs and physiological substrates Depending on the remaining structure, the formed radical products of drugs can yield quinones, quinone imines, diimines, dimers (and other...

Ngày tải lên: 28/03/2014, 10:20

... data reported in the present study, and obtained in living cells, confirm the finding obtained in reconstituted proteoliposomes [11,12] and isolated membranes [29,30] indicating that Pgp and a bacterial ... anthracyclines, are positively charged and therefore bind to acidic groups in proteins and membranes Thus, their movement into the cell can be envisaged as a series of binding and releasing events ... is expected to handle incoming drugs more efficiently compared to drugs already present in the cell interior By contrast, in the case where drug concentrations in the cytoplasm and the cytoplasmic...

Ngày tải lên: 29/03/2014, 08:20

... polymorphisms in CYP2D6 can significantly affect the activity of the enzyme, and therefore serve as an important guideline for determining the dose of antidepressant drugs and preventing drug- induced toxicity ... experiments in which total protein bound and imported into mitochondria is present; T, trypsin-treated mitochondria in which only the protein imported into mitochondria is present In the lanes marked In , ... CYP2D6 content, ranging from a relatively high level in HL134 and 137 to a moderate level in HL136, low levels in HL132, 139 and 140, and almost undetectable levels in HL131 and 141 (Fig 1A) Densitometry...

Ngày tải lên: 29/03/2014, 23:20

... irritancy testing, immunotoxicity, target organ toxicity (including endocrine and neurotoxicity), and ecotoxicity involving the use of fish, invertebrates, and so on Within these main areas there ... Neurotoxtctty Acutelcytotoxicity testing Recent Successes and Developments in In Vitro Toxicity Testing It is refreshing to observe the momentum that is now gathering in this field (see Table 6) and the ... Types of In Vitro Aims, Toxicity Testing The general advantages and disadvantages of in vitro testing for toxicity are described in Table Validation The successful use and industrial and regulatory...

Ngày tải lên: 11/04/2014, 09:47

... pharmacokinetic evaluation Such measurements and analysis are adequate for understanding a single drug in a single species in a number of different situations since both protein binding and the resultant ... EF EM Average amount of drug in the body over a dosing interval Maximum amount of drug in the body over a dosing interval Minimum amount of drug in the body over a dosing interval Area under plasma ... organ is involved in drug clearance Within this equation Cli is the intrinsic clearance based on total drug concentrations and therefore includes drug bound to protein Lipophilic drugs bind to...

Ngày tải lên: 11/04/2014, 10:03

... of Testing Proof of Concept Testing 62 62 Network Readiness Testing 63 Design Verification Testing 63 Hardware Certification Testing 63 Network Operating System Testing Migration Plan Testing ... Explaining the different types of testing that complement decision making during the various phases of a network’s lifecycle ■ Outlining a business and technical blueprint for developing a testing ... Concept Testing 28 Network Readiness Testing 28 Network Capacity Planning and Testing Design Phase: Design and Test Activities Low-Level Design Migration Plan 29 29 29 30 Design Verification Testing...

Ngày tải lên: 30/05/2014, 23:50

... formation and maintenance of the histo-architecture Plasmonogen activator inhibitor-2 (PAI-2) Involved in the regulation and inhibition of binding between urokinase-type plasminogen activator and its ... protein for phosphoserin motifs Regulated the interactions and subcellular localization of signalling molecules γ-Catenin Forms a complex with α- and β-Catenin to Cadherins, that are involved in ... hours Silver staining Proteins were visualized using the silver staining method employing a modification of the method of Heukeshoven according to Sinha et al [15,16] Image Analysis and Spot Identification...

Ngày tải lên: 18/06/2014, 15:20

... mutation and the potential binding affinity of the amino acid motif spanning the mutation to the patient’s HLA (Table and 2) Peptides were designed based on the predicted binding affinity using the ... http://bimas.cit.nih.gov/molbio/hla_bind/ In case of a single residue point mutation (peptides and 4), the mutation was placed in the center and residues were included on each side, so that every 9-mer containing the mutation ... resulting in a change from thymine to cytosine which led to a substitution in valine to alanine at position 166 Patient had a mutation at nucleotide number 332 resulting in a change from guanine...

Ngày tải lên: 18/06/2014, 16:20