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Testing Protocol (testing + protocol)
Selected AbstractsA novel amphibian tier 2 testing protocol: A 30-week exposure of Xenopus tropicalis to the antiandrogen flutamideENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2007Paul L. Knechtges Abstract In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis. [source] Prediction of onset of crystallization in amorphous pharmaceutical systems: Phenobarbital, nifedipine/PVP, and phenobarbital/PVPJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010Vincent Caron Abstract The aim of this work is to determine if a stability testing protocol based on the correlations between crystallization onset and relaxation time above the glass transition temperature (Tg) can be used to predict the crystallization onsets in amorphous pharmaceutical systems well below their Tg. This procedure assumes that the coupling between crystallization onset and molecular mobility is the same above and below Tg. The stability testing protocol has been applied to phenobarbital, phenobarbital/polyvinylpyrrolidone (PVP) (95/5, w/w), and nifedipine/PVP (95/5, w/w). Crystallization onsets have been detected by polarized light microscopy examination of amorphous films; molecular mobility has been determined by dielectric relaxation spectroscopy above Tg and by both isothermal calorimetry and modulated differential scanning calorimetry below Tg. We find that small amounts of PVP significantly retard re-crystallization. This dramatic effect of PVP is not related to mobility, so this approach applies, at best, to extrapolation of high temperature data on a given formulation to low temperatures. Variation in molecular mobility at these concentrations of PVP is not the dominant factor in determining variation in propensity for re-crystallization from glassy systems; we suggest surface interactions between PVP and nuclei and/or small crystals slowing growth control variation in crystallization kinetics between formulations. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3887,3900, 2010 [source] A critical assessment of the ICH guideline on photostability testing of new drug substances and products (Q1B): Recommendation for revisionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2010Steven W. Baertschi Abstract The ICH guideline on photostability (ICH Topic Q1B) was published in November 1996 and has been implemented in all three regions (US, EU, and Japan). The guideline describes a useful basic protocol for testing of new drug substances and associated drug products for manufacturing, storage, and distribution, but it does not cover the photostability of drugs under conditions of patient use. The pharmaceutical industry now has considerable experience in designing and carrying out photostability studies within the context of this guideline, and issues have been identified that would benefit from the revision process. The purpose of this commentary is to accomplish the following: (i) highlight issues proposed for consideration in the ICH revision process, (ii) offer a rationale for why these issues may compromise the design of a testing protocol and/or the results of the testing program, and (iii) provide recommendations for clarification of the guideline. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2934,2940, 2010 [source] An evaluation of the robustness of the Tanaka characterization protocol for reversed-phase liquid chromatography columnsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 16 2005Patrik Petersson Abstract The robustness of the popular ,Tanaka' LC column characterization protocol has been evaluated by the statistical tools of reduced factorial design, multiple linear regression and principal component analysis. These have shown that in order to obtain reliable and reproducible results, it is especially important to control the methanol content, the temperature and, in the case of the total ion-exchange capacity test (,B/P pH 7.6), the pH of the mobile phase. In particular, the hydrophobicity tests (kPB and ,) are sensitive to small changes in methanol content. Provided that the operating parameters for the Tanaka column characterization protocol are controlled within the following experimental limits, i. e. methanol content ±0.5% v/v, temperature ±3°C, pH ±0.10 and buffer concentration ±2.0 mM, it is feasible to distinguish between RP materials that possess selectivity differences larger than their batch-to-batch reproducibility. These experimental requirements can be easily met by current LC instrumentation. Hence, the validity of the Tanaka testing protocol for characterizing columns has been verified. [source] Comparison of the quality of some Croatian and German wheat varieties according to the German standard protocolMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2003Ljiljana Unbehend Abstract Ten Croatian and five German wheat varieties were tested. They were carried out using the German standard testing protocol. The results demonstrated that the quality of the Croatian wheat varieties could be ranged in A,C quality groups according to the German testing protocol. Croatian wheat varieties were comparable in many parameters (protein content, hardness, water absorption, dough handling properties and volume yield) with chosen German wheat varieties. Some differences were found in falling number, sedimentation value, flour yield, and ash value number. [source] Clinical Predictors of Defibrillation Thresholds with an Active Pectoral Pulse Generator Lead SystemPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2002DENICE M. HODGSON HODGSON, D.M., et al.: Clinical Predictors of Defibrillation Thresholds with an Active Pectoral Pulse Generator Lead System. Active pectoral pulse generators are used routinely for initial ICD placement because they reduce DFTs and simplify the implantation procedure. Despite the common use of these systems, little is known regarding the clinical predictors of defibrillation efficacy with active pulse generator lead configurations. Such predictors would be helpful to identify patients likely to require higher output devices or more complicated implantations. This was a prospective evaluation of DFT using a uniform testing protocol in 102 consecutive patients with an active pectoral can and dual coil transvenous lead. For each patient, the DFT was measured with a step-down protocol. In addition, 34 parameters were assessed including standard clinical echocardiographic and radiographic measures. Multivariate stepwise regression analysis was performed to identify independent predictors of the DFT. The mean DFT was 9.3 ± 4.6 J and 93% (95/102) of patients had a DFT , 15 J. The QRS duration, interventricular septum thickness, left ventricular mass, and mass index were significant but weak (R < 0.3) univariate predictors of DFT. The left ventricular mass was the only independent predictor by multivariate analysis, but this parameter accounted for < 5% of the variability of DFT measured (adjusted R2= 0.047, P = 0.017). The authors concluded that an acceptable DFT (< 15 J) is observed in > 90% of patients with this dual coil and active pectoral can lead system. Clinical factors are of limited use for predicting DFTs and identifying those patients who will have high thresholds. [source] Rapid prenatal diagnosis of common trisomies: discordant results between QF-PCR analysis and karyotype analysis on long-term culture for a case of trisomy 18 detected in CVSPRENATAL DIAGNOSIS, Issue 12 2006S. K. Allen Abstract Objectives QF-PCR analysis can be used as a rapid test to diagnose primary trisomy in prenatal samples. Mosaicism in CVS detected by QF-PCR has previously been reported; however, no case has so far been reported in which the QF-PCR result was completely discrepant to that of the karyotype analysis from a long-term culture. Methods A CVS, referred because of a high serum screening risk of 1:10 for Down Syndrome and 1:110 for Edwards Syndrome, was tested by QF-PCR analysis and chromosome analysis of cultured cells. Subsequent analyses were carried out on a follow-up amniotic fluid sample and foetal tissue samples. Results Conflicting results were obtained between QF-PCR analysis on two independent fronds from the chorionic villi and chromosome analysis on cultured CVS. Cytogenetic and molecular analysis on a subsequent amniotic fluid sample indicated trisomy 18 with no evidence of mosaicism. Analysis of follow-up tissue confirmed trisomy in a foetal skin sample and mosaicism for trisomy 18 in four placental sites tested. Conclusion We report here an apparently normal CVS QF-PCR result that was completely discrepant with the trisomy 18 positive karyotype result on long-term culture. This has important implications regarding our current testing protocol. Copyright © 2006 John Wiley & Sons, Ltd. [source] Most proteinase3- and myeloperoxidase-antineutrophil cytoplasmic antibodies enzyme-linked immunosorbent assays perform less well in treated small-vessel vasculitis than in active diseaseAPMIS, Issue 2009JUDY SAVIGE Antineutrophil cytoplasmic antibodies (ANCA) levels have been thought to follow disease activity, with levels being high at presentation, declining with treatment and increasing just before relapse. However, we have shown that ANCA often persist for many years in patients with clinically inactive Wegener's granulomatosis. ANCA assays are less sensitive for treated disease than for active disease, and the levels in treated patients produce different results in different assay systems. ANCA often persist for years without relapse, and the risk of relapse probably depend on levels that are critical for any individual patient. The capture enzyme-linked immunosorbent assays may be more sensitive in detecting early relapse. Relapse is more common when ANCA levels are high but, although elevated, ANCA levels are lower in relapse than at presentation. Standardized ANCA levels for the definitions of remission and relapse may not be possible, and the optimal ANCA testing protocol for treated disease remains unclear. [source] Phytotoxicity assay for seed production using Brassica rapa L.INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 4 2010David Olszyk Abstract Although pesticide drift can affect crop yield adversely, current plant testing protocols emphasize only the potential impacts on vegetative plant growth. The present study was conducted to determine whether a plant species with a short life cycle, such as Brassica rapa L. Wisconsin Fast Plants®, can be used to indicate potential effects on seed production of herbicides applied at relatively low levels (e.g., low field application rates [FAR]). The effects of ,0.1,×,FAR of aminopyralid, cloransulam, glyphosate, primisulfuron, or sulfometuron applied 14 d after emergence (DAE), were evaluated for B. rapa grown in mineral soil in pots under greenhouse conditions. Effects were expressed as the effective concentration of the herbicide producing a 25% reduction in a response (EC25) based on nonlinear regression. Brassica rapa seed dry weight was reduced by sulfometuron at an EC25 of 0.00014,×,a field application rate (FAR) of 53,g active ingredient (a.i.) ha,1, primisulfuron at 0.008 (experiment 1) or 0.0050 (experiment 2),×,FAR of 40,g,a.i.,ha,1, cloransulam at 0.022,×,FAR of 18,g,a.i.,ha,1, glyphosate at 0.0399,×,FAR of 834,g,a.i.,ha,1, and by aminopyralid at 0.005,×,FAR of 123,g,a.i.,ha,1, but only for 1 of 2 experiments. Reduced seed production occurred at less than the FAR that reduced shoot dry weight with sulfometuron and primisulfuron, whereas neither aminopyralid, cloransulam, nor glyphosate affected shoot dry weight. A short life cycle form of B. rapa could be used to indicate reduced seed production with plants grown only 1 week longer (,35,DAE) than as the current vegetative vigor test for nontarget herbicide effects on plants. Integr Environ Assess Manag 2010;6:725,734. © 2010 SETAC [source] Role of thermodynamic, molecular, and kinetic factors in crystallization from the amorphous stateJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Chandan Bhugra Abstract Though there is an advantage in using the higher solubility amorphous state in cases where low solubility limits absorption, physical instability poses a significant barrier limiting its use in solid oral dosage forms. Unlike chemical instability, where useful accelerated stability testing protocols are common, no methodology has been established to predict physical instability. Therefore, an understanding of the factors affecting crystallization from the amorphous state is not only important from a scientific perspective but also has practical applications. Crystallization from the amorphous matrix has been linked to the molecular mobility in the amorphous matrix and recent research has focused on developing the link between these two fundamental properties of glass forming materials. Although researchers have been actively working in this area for some time, there is no current review describing the present state of understanding of crystallization from the amorphous state. The purpose of this review therefore is to examine the roles of different factors such as molecular mobility, thermodynamic factors, and the implication of different processing condition, in crystallization from the amorphous state. We believe an increased understanding of the relative contributions of molecular mobility and processing conditions are vital to increased usage of the amorphous state in solid oral dosage forms. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1329,1349, 2008 [source] Ecotoxicity testing of chemicals with particular reference to pesticidesPEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2006Colin H Walker Abstract Ecotoxicity tests are performed on vertebrates and invertebrates for the environmental risk assessment of pesticides and other chemicals and for a variety of ecotoxicological studies in the laboratory and in the field. Existing practices and strategies in ecotoxicity testing are reviewed, including an account of current requirements of the European Commission for the testing of pesticides and the recent REACH (Registration, Evaluation, Authorisation and Restrictions of Chemicals) proposals for industrial chemicals. Criticisms of existing practices have been made on both scientific and ethical grounds, and these are considered before dealing with the question of possible alternative methods and strategies both for environmental risk assessment and for ecotoxicological studies more generally. New approaches from an ecological point of view are compared with recent developments in laboratory-based methods such as toxicity tests, biomarker assays and bioassays. With regard to the development of new strategies for risk assessment, it is suggested that full consideration should be given to the findings of earlier long-term studies of pollution, which identified mechanisms of action by which environmental chemicals can cause natural populations to decline. Neurotoxicity and endocrine disruption are two cases in point, and biomarker assays for them could have an important role in testing new chemicals suspected of having these properties. In a concluding discussion, possible ways of improving testing protocols are discussed, having regard for current issues in the field of environmental risk assessment as exemplified by the debate over the REACH proposals. The importance of flexibility and the roles of ecologists and ecotoxicologists are stressed in the context of environmental risk assessment. Copyright © 2006 Society of Chemical Industry [source] Use of Intradermal Dilutional Testing and Skin Prick Testing: Clinical Relevance and Cost EfficiencyTHE LARYNGOSCOPE, Issue 9 2006Dr. Merritt Seshul MD, FAAOA Abstract Objectives/Hypothesis: The objective was to determine the agreement of the positive results from a multiple skin prick test (SPT) device with the ability to determine a definable endpoint through intradermal dilutional testing (IDT) to compare semiquantitatively the degree of positivity of SPT results with quantitative results from IDT and to analyze the cost of immunotherapy based on SPT compared with IDT guided by SPT. Study Design: Retrospective review of clinical data (random accrual). Methods: One hundred thirty-four patients underwent allergy screening using a multiple SPT device. Antigens testing positive by skin prick device were tested using IDT on a separate day. Antigens testing negative by SPT were not evaluated by IDT. Regional allergy testing practice patterns were determined, and a cost analysis using Medicare rates was performed Results: There was good agreement between an antigen testing positive by SPT and the determination of a definable endpoint (93.33%, n = 1,334 antigens). The degree of positivity from the SPT correlated poorly with the final endpoint concentration (r = 0.40, P < .0001). Blended testing techniques were similar in cost when compared with several commonly used allergy testing protocols. Conclusions: Antigens which show reactivity to a multiple SPT device usually have a treatable endpoint that is independent of the degree of positivity of the SPT result. IDT is an important step in the determination of the strongest starting dose of immunotherapy that may be safely administered. Initiating immunotherapy in this manner may potentially create significant health care savings by shortening the time required for a patient to reach their individual maximally tolerated dose. The use of a relatively large screening panel is cost effective and does not increase the average number of antigens treated by immunotherapy. Blended allergy testing techniques that include IDT in their protocol are comparable in cost with commonly used allergy testing protocols. [source] Longitudinal study of the spread of ovine Johne's disease in a sheep flock in southeastern New South WalesAUSTRALIAN VETERINARY JOURNAL, Issue 4 2005L RAST Objective The aim of this study was to apply whole flock testing over time to determine the prevalence, distribution and spread of infection in a recently infected flock, with a view to planning intervention strategies for disease control. Procedure Serology, pooled faecal culture (PFC) and histology were used to determine the distribution and persistence of infection in a sheep flock in south east New South Wales between 1997 and 2002. Partial flock testing was done up to June 2000, after which annual whole flock testing, using PFC was performed. Results Faecal shedding of M a paratuberculosis was not detected in home-bred sheep until 7 years after the introduction of infected sheep in 1993. For at least 7 years there was clustering of infection and shedding within two age groups only. The infected groups appeared to have been exposed to infection (mycobacterial contamination) at an early age (< 12 months) and commenced shedding at 5 years of age or older. Groups that were exposed to contamination as adults did not shed detectable amounts of M a paratuberculosis during the study period. Conclusion Clustering of detectable infection in age groups of sheep that were exposed as lambs was a feature on this farm, providing indirect evidence of finite duration of survival of M a paratuberculosis on pasture and the influence of age on the susceptibility of sheep to develop detectable M a paratuberculosis infection. Spread of infection occurred very slowly and was probably related to the long incubation period (exposure to shedding interval) of 5 years observed on this farm. The findings suggest that partial flock culling, selective grazing management and vaccination could lead to a reduction in mycobacterial contamination on farm to a level at which patent infection no longer occurs. Better understanding of disease spread within flocks over time through flock profiling using PFC will help in devising surveillance strategies (including testing protocols for market assurance testing) to detect infected flocks where there has been clustering and slow spread of infection. [source] Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2CANCER, Issue 1 2005A clinic-based series Abstract BACKGROUND Although BRCA1 and BRCA2 were identified in 1994 and 1995, respectively, to the authors' knowledge the optimal management of women with BRCA -associated breast carcinoma remains incompletely defined. The current study evaluates the appropriateness of breast-conserving therapy (BCT) in women with BRCA mutations. METHODS Between May 1992 and October 2003, 87 female participants in genetic testing protocols were identified who 1) were found to have deleterious germline BRCA mutations and 2) reported a history of invasive breast carcinoma that was treated with wide local excision and radiation therapy. Clinical records were reviewed and follow-up was updated. RESULTS The 87 subjects underwent BCT for 95 invasive breast tumors (8 women received BCT for metachronous bilateral tumors). In all 95 treated breasts, the 5-year and 10-year probabilities of metachronous ipsilateral breast carcinoma (MIBC) were 11.2% and 13.6%, respectively. Among the 87 subjects, the 5-year and 10-year probabilities of metachronous contralateral breast carcinoma (CBC) after treatment of the index tumor were 11.9% and 37.6%. No clinical factors were identified that were associated with either MIBC or CBC, including the use of tamoxifen or chemotherapy. CONCLUSIONS Women with BRCA -associated breast carcinoma who undergo BCT appear to have risks of MIBC that are similar to those reported for young women without known mutations. The indications for unilateral mastectomy in this group of women should be the same as those for women with nonhereditary carcinoma. However, significant risks of CBC and possibly late MIBC may prompt the serious consideration of bilateral mastectomy as a preventive measure. Cancer 2005. © 2004 American Cancer Society. [source] | ||||||||||||||||