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Definitive Test (definitive + test)
Selected AbstractsWeathering and aging of 2,4,6-trinitrotoluene in soil increases toxicity to potworm Enchytraeus crypticusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2005Roman G. Kuperman Abstract Energetic materials are employed in a wide range of commercial and military activities and often are released into the environment. Scientifically based ecological soil-screening levels (Eco-SSLs) are needed to identify contaminant explosive levels in soil that present an acceptable ecological risk. Insufficient information for 2,4,6-trinitrotoluene (TNT) to generate Eco-SSLs for soil invertebrates necessitated toxicity testing. We adapted the standardized Enchytraeid Reproduction Test and selected Enchytraeus crypticus for these studies. Tests were conducted in Sassafras sandy loam soil, which supports relatively high bioavailability of TNT. Weathering and aging procedures for TNT amended to test soil were incorporated into the study design to produce toxicity data that better reflect the soil exposure conditions in the field compared with toxicity in freshly amended soils. This included exposing hydrated TNT-amended soils in open glass containers in the greenhouse to alternating wetting and drying cycles. Definitive tests showed that toxicity for E. crypticus adult survival and juvenile production was increased significantly in weathered and aged soil treatments compared with toxicity in freshly amended soil based on 95% confidence intervals. The median effect concentration and 20% effective concentration for reproduction were 98 and 77 mg/kg, respectively, for TNT freshly amended into soil and 48 and 37 mg/kg, respectively, for weathered and aged TNT soil treatments. These findings of increased toxicity to E. crypticus in weathered and aged TNT soil treatments compared with exposures in freshly amended soils show that future investigations should include a weathering and aging component to generate toxicity data that provide more complete information on ecotoxicological effects of energetic contaminants in soil. [source] Pigmentation development in hatchery-reared flatfishesJOURNAL OF FISH BIOLOGY, Issue 5 2000J. A. Bolker Malpigmentation is common in hatchery-reared flatfishes, decreasing the market value of whole fish, and increasing the risk of predation for juveniles released to enhance wild stocks. Pigmentation development in flatfishes occurs in two phases. First, during embryonic and larval stages pigment cells differentiate on both sides of the body. Second, at metamorphosis larval melanophores disappear, and adult melanophores differentiate on the ocular but not on the blind side. Malpigmentation seems to result from disruptions of the second phase, and may take the form of albinism on the ocular side or darkening of the blind side. Both types of aberration may be related to aspects of the hatchery environment such as lighting, substratum, and diet. Larval nutrition appears to be a key factor and enrichment of larval diets with fatty acids and Vitamin A can greatly reduce malpigmentation rates; however, levels suffcient to prevent pigmentation defects frequently cause other abnormalities. Two developmental explanations for albinism have been proposed. The first is that differentiation of ocular-side skin follows the normal blind-side pathway and adult melanophores therefore fail to develop on the ocular side. The second hypothesis suggests that dietary deficiencies inhibit retinal development and the resulting visual defects lead to failure of a hormonal signal required for melanophore differentiation. These hypotheses may well be complementary; as yet neither has been thoroughly tested. Definitive tests will require a combination of manipulative techniques such as tissue transplantation and cell culture with nutritional, behavioural and hormonal assays. Such integrative studies will further the understanding both of normal pigmentation development and of the environmental factors that contribute to high rates of albinism in hatchery-reared flatfish. [source] Development of an ex vivo model for the study of microbial infection in human teethINTERNATIONAL ENDODONTIC JOURNAL, Issue 5 2007B. Patel Aims, (1) To infect human teeth artificially to mimic root canal and dentine infection, using the Constant Depth Film Fermenter (CDFF); (2) To verify the similarity of the infections to those found, in vivo, using culture and microscopy (SEM, LM and TEM). Methodology, Human teeth [n = 38 and n = 28, for phases I (preliminary) and II (definitive), respectively] were infected within the CDFF for a period of 28 days and at pre-selected time points were removed, externally decontaminated using validated protocols and subjected to either culture-dependent or microscopy protocols. The condition of the teeth was varied in phase I to establish the feasibility of the approach and identify optimal conditions. This informed the selection of optimal conditions for definitive test in phase II. For culture-dependent analysis in this phase, a dentine filing sample was obtained from the apical 5 mm of the root canal and cultured anaerobically to allow isolation of individual strains. Bacterial DNA was extracted from purified isolates, the 16S rRNA genes amplified by PCR and the amplicons sequenced for identity using sequence databases. Teeth assigned for microscopy were post-fixed in 3% gluteraldehyde after removal from the CDFF and then subjected to appropriate protocols prior to microscopic evaluation of the infection. Results, All three microscopy techniques and culture-dependent analysis confirmed infection of the human teeth using the CDFF, with root canal infections visually resembling closely those seen in vivo. Furthermore, partial 16S rRNA gene sequencing of DNA from cultured isolates confirmed a selective number of 7,9 genera/species in the apical portion of two teeth each at 7 and 28 days; these taxa are also commonly recovered from teeth with apical periodontitis, in vivo. There were no objective measures other than speciation and topographical evaluation to compare the artificial and real (in vivo) infections. Conclusions, The proposed ex vivo model has the potential for development into an investigative tool for studying the dynamics of bacterial ecology in infected root canals, both before and after treatment. Its advantage is the ability to control both the abiotic and biotic factors. There is a need for the development of objective measures to compare artificial and real bacterial biofilms. [source] Total estradiol levels in migrant and British-born British Pakistani women: Investigating early life influences on ovarian functionAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2009Tessa M. Pollard The purpose of this study was to test the hypothesis that women who grow up in energetically stressed environments have later menarche and lower total estradiol levels during their reproductive years than do women who grow up in less energetically stressed environments. We assessed total estradiol in a serum sample taken 9,11 days after the start of the menstrual cycle in 26 women who grew up in Pakistan and migrated to the UK as adults, in 28 British-born British Pakistani women, and in 25 British-born women of European origin. Women who grew up in Pakistan reported a later menarche than women who grew up in the UK. However, we found no significant differences between the groups in total estradiol level. Thus our findings do not support the hypothesis that estradiol levels are partially determined during early life. However, having considered our findings in relation to those of other studies, we conclude that new methodological approaches are needed to provide a more definitive test of the hypothesis. Am. J. Hum. Biol. 2009. © 2008 Wiley-Liss, Inc. [source] Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Maria V. Papadopoulou The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source] Absence of Borrelia burgdorferi DNA in cutaneous B-cell lymphomas from the United StatesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2001Gary S. Wood Background: An association between Borrelia burgdorferi and cutaneous B-cell lymphoma (CBCL) has been made in several European countries. The evidence in favor of such an association has recently been based on more definitive tests for the pathogenetic role of B. burgdorferi in CBCL, including positive cultures or polymerase chain reaction (PCR) amplification of borrelial DNA from lesional skin. However, there is only one report of B. burgdorferi in four North American cases of B-cell lymphoma. Methods: We retrieved 38 cases of primary and secondary CBCL from different geographic regions of the United States. Two separate techniques were used to detect borrelial DNA by PCR, a nested PCR method to amplify a B. burgdorferi -specific gene as well as a borrelial chromosomal Ly-1 clone amplification method. Southern blot hybridization was used for confirmation of the PCR results. Results: No B. burgdorferi -specific DNA was detected in any of the 38 CBCL cases, whereas detectable PCR products were obtained with our positive controls. Conclusions: Our findings, in light of previous studies, suggest that B. burgdorferi plays a minimal role in the development or pathogenesis of CBCL in the United States. The findings also suggest that the geographic variations in the clinical manifestations of B. burgdorferi are indeed real and may be secondary to the genetic and phenotypic differences between B. burgdorferi strains present in Europe and North America. [source] | |||||||||||||