Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor     

Jane C.F. Chang  Paul Ciaccio  Patricia Schroeder  Lindsay Wright  Russell Westwood  Anna-Lena Berg 《Journal of toxicologic pathology》2014,27(1):31-42

AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT_1B) receptor, was explored as a potential treatment for depression. To support clinical trials, repeat dose toxicity studies in rats and dogs were conducted. Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86 days. Extensive pathologic changes were seen in all animals in retina epithelium (inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung, kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues. Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and pathology study showed that the concentration of AZD3783 in the brain was approximately 4 times higher than in the plasma after 4 weeks of dosing, however, they were similar in all regions examined, and did not correlate with areas with pathologic findings. Our findings with AZD3783 in dogs have not been reported previously with other CNS compounds that effect through serotonergic pharmacology.  相似文献   

The effect of slaughtering procedures on blood spotting in rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar)     

Bjorn Roth  Ole Johan Torrissen  Erik Slinde 《Aquaculture (Amsterdam, Netherlands)》2005,250(3-4):796-803

Rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) were submitted for various slaughter and bleeding procedures to see what effect this would have on blood drainage of the muscles. Results show that the bleeding method is of less importance, while it is the timing that is important. No significant difference in bloodspotting was observed between fish that were bled live by a gill cut or percussive killed and bled by gutting. Most of the drainage of blood in the fish muscle seems to occur within the first hours postmortem, so rigor mortis is of little importance. The visual appearance of the fillet was influenced by number and size of the bloodstains. Colour measurements with Hunter L*, a*, b* did not reveal this. We conclude that a gill cut is not necessarily to obtain bleeding, so the industry can omit this phase and go directly to gutting.  相似文献   

Compensatory Growth of Pond-reared Hybrid Striped Bass, Morone chrysops × Morone saxatilis, Fingerlings     

Marc J.  Turano Russell J.  Borski Harry V.  Daniels 《Journal of the World Aquaculture Society》2007,38(2):250-261

Compensatory growth (CG) or “catch‐up growth” is a period of super‐accelerated growth following a period of suboptimal conditions (i.e., lack of prey availability or overwintering). Little is known about the CG response in pond‐raised fish and whether hybrid striped bass (HSB), Morone chrysops × Morone saxatilis, might exhibit the rapid growth states or improvements in other production characteristics that may accompany the response. To evaluate the potential for CG in HSB culture, a 16‐wk growth trial in twelve 0.1‐ha earthen ponds was conducted. Approximately 2850 fish (mean weight ± SD = 3.2 g ± 1.1) were stocked into ponds and subjected to one of four cyclic feeding regimens. Treatment regimens included a control (0 wk, fed twice daily to apparent satiation) and cycles of 1, 2, or 4 wk of feed deprivation, followed by 1, 2, or 4 wk of feeding to apparent satiation. Fish in the 4‐wk feeding regimen were offered feed twice during the feed‐deprivation period (once every other week). Growth, specific growth rate (SGR), hepatosomatic index (HSI), intraperitoneal fat ratio, and condition factor (CF) were measured every other week, while overall growth, feed efficiency (FE) (FE = [weight gain/feed fed] × 100), and survival were calculated at the trial termination. The effect of these feeding regimens on water quality was examined by monitoring pH, turbidity, total ammonia nitrogen, nitrite–nitrogen, nitrate–nitrogen, soluble reactive phosphorus, and chlorophyll a weekly; total nitrogen and phosphorous biweekly; and dissolved oxygen and temperature twice daily. Cyclic feeding elicited CG; fish subjected to the 2‐wk regimen had a significantly higher SGR than 0‐wk controls during all but the final refeeding period. FE was higher for all fish in the cyclic regimens, although only FE for fish in the 2‐wk regimen was statistically greater (40%) than the controls. HSI was the most responsive measure and significantly decreased in the 2‐ and 4‐wk treatments during feed‐deprivation period and overcompensated during the refeeding period. CF also varied with feeding cycle and proved to be an effective nonlethal measure of predicting a CG response. No statistical differences in water quality parameters were observed. These data suggest that CG can be effectively induced in pond‐raised HSB and that the increase in FE warrants further research for practical application. Future pond studies with fingerling HSB fish should be conducted with emphasis on feed‐deprivation periods of 2 wk and refeeding periods of at least twice that of the feed‐deprivation period.  相似文献   

Treatment of the early life stages of scallop (Pecten maximus) with antimicrobial agents; searching for an alternative to chloramphenicol     

Lise Torkildsen  Rosie Coyne  Ole Bent Samuelsen  Thorolf Magnesen  Øivind Bergh 《Aquaculture International》2002,10(5):399-409

High mortality rates are often observed in rearing the early stages of the great scallop, Pecten maximus. The addition of antibacterial agents has been necessary to improve larval survival. However, as one antibacterial agent, chloramphenicol, is banned in Norway and Europe the aim of this study is to investigate alternative antibacterial agents. The therapeutic agents investigated in this study were florfenicol, oxytetracycline, oxolinic acid, neomycin and Pyceze. The mean minimum inhibitory concentration (MIC) values were determined for oxytetracycline, oxolinic acid and Pyceze against bacteria isolated from scallop larvae. Two types of treatment regime were investigated on an intermediate scale (20 L). One regime involved continuous exposure of scallop larvae to the therapeutic agent while the other involved a short exposure lasting two hours. All intermediate scale treatments were performed in parallel to large-scale production (800 L) treatment with chloramphenicol. Of the therapeutants investigated, oxolinic acid was the most effective, although only at high concentrations. The short exposure of two hours was ineffective for all therapeutics.  相似文献   

Inclusion of a commercial poultry by-product meal as a protein replacement of fish meal in practical diets for African catfish Clarias gariepinus (Burchell 1822)     

A A Abdel-Warith  P M Russell  & S J Davies 《Aquaculture Research》2001,32(S1):296-305

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The efficacy of a single intraperitoneal injection of either flumequine or oxytetracycline hydrochloride in prevention of outbreaks of atypical Aeromonas salmonicida infection in goldsinny wrasse, Ctenolabrus rupestris L., following stress.     

Ole Bent Samuelsen  Arne Ervik  Lise Torkildsen  Øivind Bergh 《Aquaculture International》2002,10(3):257-264

In this investigation, the efficacy of a single intraperitonealinjection of either flumequine or oxytetracycline hydrochloride to preventoutbreak of atypical Aeromonas salmonicida infection ingoldsinny wrasse, Ctenolabrus rupestris, following stresswas studied. Six groups of goldsinny wrasse, each of 50 individuals, weretreated with an intraperitoneal injection of either propylene glycol : saline(50 : 50), 200 mg kg^–1 of oxytetracycline or 50mg kg^–1 of flumequine dissolved in propyleneglycol : saline (50 : 50). Three days following medication the fish in allgroups were stressed by an intraperitoneal injection of prednisolone acetate(0.05 ml) and a rise in seawater temperature from 9 to 11°C. Mortality was observed daily for 21 days. Flumequine wasthe more effective with a mean cumulative mortality of 5% compared tooxytetracycline with 54%. The mean cumulative mortality in the unmedicatedcontrol groups was 84%. Bacterial examination of kidneys from dead fishconfirmed the presence of atypical A. salmonicida as theprobable cause of death. Minimum inhibitory concentration (MIC) values forflumequine and oxytetracycline against the isolated A.salmonicida were determined to 0.13 gml^–1, and 2.0 g ml^–1,respectively.  相似文献   

The minimum dietary requirement of vitamin C in Atlantic salmon (Salmo salar) fry using Ca ascorbate-2-monophosphate as dietary source     

Kjartan Sandnes  Ole Torrissen  Rune Waagbø 《Fish physiology and biochemistry》1992,10(4):315-319

The minimum dietary vitamin C requirement for optimal growth and normal development in Atlantic salmon (Salmo salar) fry at the onset of feeding was studied, using Ca ascorbate-2-monophosphate (AP) as dietary source. The requirement was established by means of a feeding study lasting for 23 weeks from the beginning of feeding. The practical diets used were supplemented with AP at levels of 0, 10, 20, 40, 80 and 160 mg ascorbic acid (AA) equivalents/kg. Growth, mortality, hydroxyproline content in skin and backbone, and AA in liver were recorded to evaluate the results. The results suggest that the minimum dietary requirement for optimal growth and normal development is in the range of 10–20 mg AA equivalents/kg dry diet during the period studied.  相似文献   

Remedies for pseudoreplication   总被引：1，自引：0，他引：1  

Russell B. Millar  Marti J. Anderson 《Fisheries Research》2004,70(2-3):397-407

Pseudoreplication is the failure of a statistical analysis to properly incorporate the true structure of randomness present in the data. It has been well documented and studied in the ecological literature but has received little attention in the fisheries literature. Avoiding pseudoreplication in analyses of fisheries data can be difficult due to the complexity of the statistical procedures required. However, recent developments in statistical methodology are decreasing the extent to which pseudoreplication has to be tolerated. Seven examples are given here, beginning with simple design-based remedies and progressing to more challenging examples including the model-based remedies of mixed-effects modelling, generalized linear mixed models, state-space models, and geostatistics.  相似文献   

Accumulation of aluminum on atlantic salmon eggs during the incubation period     

Yngve Ulgenes  Ole J. Torrissen 《Aquacultural Engineering》1989,8(6):369-380

Groups of rainbow trout Onchorhyncus mykiss eggs were incubated in duplicate trays with PVC screens and the original aluminum screens. During the incubation period, aluminum bound to sediments was deposited on the eggs and in the whole hatching system.

The pH of the inlet water to the hatching system with PVC screen was experimentally lowered by adding sulphuric acid. Buffering of the outlet water was observed at pH lower than 5, and at pH 4·5 and lower, an increased aluminum concentration in the outlet water was recorded.

These experiments show that aluminum accumulated on eggs and in the hatching system during periods with neutral water represents a serious threat to the survival of eggs and fry of salmonids if pH drops below 5·0, even for a few hours. In sensitive lakes and rivers, pH drops below 5·0 are common during heavy rain or during the snow melting period.  相似文献   

Multifactorial resistance to transpermethrin in field-collected strains of the tobacco budworm Heliothis virescens F.     

Russell A. Nicholson  Thomas A. Miller 《Pest management science》1985,16(6):561-570

The penetration, degradation and excretion of [³H]transpermethrin were examined in susceptible and field-collected pyrethroid-resistant strains of the tobacco budworm Heliothis virescens. No consistent differences in labelled materials excreted or recovered in cuticle rinses were found between the resistant (R) and susceptible (S) larvae. Considerably lower levels of the parent compound were present internally in R compared with S larvae after 24h (P <0.01), clearly identifying a metabolic resistance mechanism in Meloland and Westmorland larvae. Moderate levels of absorbed permethrin accompanied by an absence of poisoning symptoms were observed in certain individuals of both R strains, suggesting a second resistance mechanism. Neurobioassays of R larvae showed a consistently lower sensitivity of the neuromuscular system to pyrethroids when compared with the S larvae, thus confirming the indication from metabolic studies of the additional (site-insensitive) mechanism. Toxicity values suggest a cross-resistance to other pyrethroids.  相似文献