|
| ||
|
|
||
Chronic Studies (chronic + studies)
Selected AbstractsWhat level of effect is a no observed effect?ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2000Mark Crane Abstract The no observed effect concentration (NOEC) is currently a major summary statistic in ecotoxicity testing. Its use is heavily criticized, partly because it is a poor estimator of "safe" chemical concentrations. In this short communication, we review the limited information available on the percentage effect that corresponds with the NOEC, a value designated the ECNOEC, and calculate ECNOEC values for fish growth data. The average ECNOEC for different test protocols was found to vary widely, with values for chronic studies ranging from 10 to 34%. Individual results varied even more widely. This analysis suggests that the NOEC is neither a consistent summary statistic nor an indicator of safe concentrations of toxic chemicals. [source] No change in apoptosis in skeletal muscle exposed acutely or chronically to alcoholADDICTION BIOLOGY, Issue 1 2003AG PAICE The pathogenic mechanisms responsible for the deleterious changes in ethanol-exposed skeletal muscle are unknown, although apoptosis may be a causal process. We therefore investigated the responses of skeletal muscle to acute or chronic ethanol exposure in male Wistar rats. In acute studies, rats were dosed with ethanol (75 mmol (3.46 g)/kg BW) and killed after either 2.5 or 6 hours. In chronic studies, rats were fed ethanol as 35% of total dietary energy for 6 weeks. Apoptosis was determined by either DNA fragmentation or TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling) assays. The results showed that apoptosis was not increased in the ethanol-exposed muscle in both acute and chronic studies compared to appropriate controls. [source] The role of early neural activity in the maturation of turtle retinal functionJOURNAL OF ANATOMY, Issue 4 2001EVELYNE SERNAGOR In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials long before the eye becomes exposed to sensory experience at birth. These early bursts are synchronised between neighbouring retinal ganglion cells (RGCs), yielding unique spatiotemporal patterns: ,waves' of activity sweep across large retinal areas every few minutes. Both at retinal and extraretinal levels, these embryonic retinal waves are believed to guide the wiring of the visual system using hebbian mechanisms of synaptic strengthening. In the first part of this review, we recapitulate the evidence for a role of these embryonic spontaneous bursts of activity in shaping developing complex receptive field properties of RGCs in the turtle embryonic retina. We also discuss the role of visual experience in establishing RGC visual functions, and how spontaneous activity and visual experience interact to bring developing receptive fields to maturation. We have hypothesised that the physiological changes associated with development reflect modifications in the dendritic arbours of RGCs, the anatomical substrate of their receptive fields. We demonstrate that there is a temporal correlation between the period of receptive field expansion and that of dendritic growth. Moreover, the immature spontaneous activity contributes to dendritic growth in developing RGCs. Intracellular staining of RGCs reveals, however, that immature receptive fields only rarely show direct correlation with the layout of the corresponding dendritic tree. To investigate the possibility that not only the presence of the spontaneous activity, but even the precise spatiotemporal patterns encoded in retinal waves might contribute to the refinement of retinal neural circuitry, first we must clarify the mechanisms mediating the generation and propagation of these waves across development. In the second part of this review, we present evidence that turtle retinal waves, visualised using calcium imaging, exhibit profound changes in their spatiotemporal patterns during development. From fast waves sweeping across large retinal areas and recruiting many cells on their trajectory at early stages, waves become slower and eventually stop propagating towards hatching, when they become stationary patches of neighbouring coactive RGCs. A developmental switch from excitatory to inhibitory GABAA responses appears to mediate the modification in spontaneous activity patterns while the retina develops. Future chronic studies using specific spatiotemporal alterations of the waves will shed a new light on how the wave dynamics help in sculpting retinal receptive fields. [source] Pulmonary responses and recovery following single and repeated inhalation exposure of rats to polymeric methylene diphenyl diisocyanate aerosolsJOURNAL OF APPLIED TOXICOLOGY, Issue 6 2002Joanne D. Kilgour Abstract Acute and repeated inhalation exposures (for 28 days) to polymeric methylene diphenyl diisocyanate (PMDI) were performed in rats. Investigations were made at the end of exposures and after 3, 10 and 30 days of recovery following single acute exposures and after 30 days of recovery following 28 days of exposure. Acute exposures to 10, 30 or 100 mg m,3 PMDI produced clinical signs in all animals that were consistent with exposure to irritant aerosols. An exposure concentration-related body weight loss and increase in lung weight were seen post-exposure, with complete recovery by day 8. The time course of changes in the lung over the initial days following exposure consisted of a pattern of initial toxicity, rapid and heavy influx of inflammatory cells and soluble markers of inflammation and cell damage, increased lung surfactant, a subsequent recovery and epithelial proliferative phase and, finally, a return to the normal status quo of the lung. During these stages there was evidence for perturbation of lung surfactant homeostasis, demonstrated by increased amounts of crystalline surfactant and increased number and size of lamellar bodies within type II alveolar cells. Repeated exposure over 28 days to the less toxic concentrations of 1, 4 or 10 mg m,3 PMDI produced no clinical signs or body weight changes, but an increase in lung weight was seen in animals exposed to 10 mg m,3, which resolved following the 30-day recovery period. Other effects seen were again consistent with exposure to irritant aerosols, but were less severe than those seen in the acute study. Analysis of bronchoalveolar lavage fluid revealed similar changes to those seen in the acute study. At both 10 and 4 mg m,3 PMDI increased numbers of ,foamy' macrophages in lung lavage cell pellet correlated with the increased phospholipid content of the pellet. Changes in lung lavage parameters and electron microscopic evidence again suggested perturbations in surfactant homeostasis. Histologically, bronchiolitis and thickening of the central acinar regions was seen at 10 and 4 mg m,3, reflecting changes in cell proliferation in the terminal bronchioles and centro-acinar regions. Almost all effects seen had recovered by day 30 post-exposure. Both acute and subacute studies demonstrate rapid recovery of effects in the lung following exposure to PMDI, with no progression of these effects even at concentrations higher than those shown to produce tumours in a chronic study. These findings add weight to the hypothesis that pulmonary tumours seen following chronic exposure to PMDI are most likely due to a combination of the chronic irritant effects of repeated exposure, coupled with the presence of insoluble polyureas formed by polymerization of PMDI (found in studies reported here and previous chronic studies), and therefore acute or short-term exposures to PMDI are likely to be of little concern for long-term pulmonary health. Copyright © 2002 John Wiley & Sons, Ltd. [source] Comparison of the experience with acute and chronic electrically stimulated detrusor myoplasty,NEUROUROLOGY AND URODYNAMICS, Issue 5 2002John G. Van Savage Abstract Aims To evaluate the acute and chronic urodynamic effects of electrically stimulated detrusor myoplasty in dogs. Methods Eight female mongrel dogs were studied acutely and six dogs chronically (0 to 12 weeks postoperatively). Bladders were wrapped with the rectus abdominis muscle, keeping an intact blood supply and at least two intercostal nerves of the flap preserved. Bladders were electrically stimulated with bipolar electrodes inserted into the muscle. Urodynamics and post void residual were measured post operatively in the acute studies and every 2 weeks for 3 months in chronic studies. Results Acutely, the increase in intravesical pressure was 45±7 cm H2O, which resulted in a postvoid residual of 26±3%. In the chronic study, increases of intravesical pressure sufficient to empty the bladder during myoplasty electrical stimulation were not sustained, although detrusor compliance and flap viability were preserved. Conclusions The electrically stimulated detrusor myoplasty worked well acutely to increase vesical pressure sufficient to empty the bladder, but the chronically stimulated myoplasty did not maintain efficient bladder emptying primarily due to electrode problems. Further studies with improved electrode material and placement are required before clinical application of the electrically stimulated detrusor myoplasty can be assessed. Neurourol. Urodynam. 21:516,521, 2002. © Wiley-Liss, Inc. [source] Pharmacological studies on Indian black tea (leaf variety) in acute and chronic inflammatory conditionsPHYTOTHERAPY RESEARCH, Issue 6 2008Dilip K. Roy Abstract Infusions of Indian black tea (BTI), when administered orally, produced significant inhibition of rat paw oedema, induced with carrageenin (pre and post treatment) and arachidonic acid. BTI was also found to inhibit peritoneal capillary permeability and caused a marked reduction of lipopolysaccharide induced PGE2 generation. In these models, the observed antioedema effect was similar to that of BW755C (a dual inhibitor of cyclooxygenase and 5-lipoxygenase enzymes). BTI was found to scavenge superoxide and hydroxyl radicals, and also protected rat erythrocytes from the damaging effects of hydrogen peroxide. In chronic studies, BTI inhibited granuloma formation along with the reduction of both lipid peroxidation and hydroxyproline content (in the granuloma tissue). Significant antiarthritic activity was observed with regular administration of BTI in the Freund's adjuvant induced model of arthritis. Chronic treatment with BTI (in arthritic rats) resulted in a decrease of paw diameter and tissue lipid peroxidation, along with a restoration of GSH, catalase and superoxide dismutase levels. Copyright © 2008 John Wiley & Sons, Ltd. [source] Chronic Pharmacological and Safety Evaluation of HematideÔ, a PEGylated Peptidic Erythropoiesis-Stimulating Agent, in RodentsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009Kathryn W. Woodburn To support the safety of long-term dosing of chronic renal failure patients, a comprehensive toxicology programme was implemented including rat subchronic and chronic studies. Rats were administered 0, 0.1, 1 and 10 mg/kg of Hematide every 3 weeks for 3 months via subcutaneous injection or for 6 months via intravenous injection. The dosing period was followed by a 6-week follow-up period. The primary pharmacology of Hematide resulted in erythroid polycythemia as measured by elevated haemoglobin levels that were time- and dose-dependent. The pharmacology profiles were similar regardless of administration route. For example, for male rats at Day 90, subcutaneous dosing resulted in haemoglobin increases of 2.7, 4.5 and 6.9 g/dl for 0.1, 1 and 10 mg Hematide/kg respectively, compared to 2.8, 5.7 and 7.4 g/dl increases for intravenous dosing. Histopathological changes were related to the prolonged severe polycythemia induced in normocythemic animals administered an erythropoiesis-stimulating agent. The findings included extramedullary haematopoiesis in the spleen and liver, bone marrow hypercellularity and organ congestion. Microscopic findings were reversible, demonstrating a return towards control findings within 6 weeks following cessation of dosing. Systemic exposures, based on both area under the curve (AUC) and maximum concentration (Cmax), were substantially greater for intravenous than subcutaneous administration. No Hematide-specific antibodies were detected. In conclusion, Hematide is a potent erythropoiesis-stimulating agent, and the studies provide support for the safety of clinical development, including chronic dosing, for the treatment of anaemia associated with chronic renal failure. [source] | |||||||||||||