Plasma pharmacokinetics and muscle residue dynamics of mebendazole in Carassius auratus

Mebendazole is approved for use in aquatic animals and is widely used in Chinese aquaculture. We developed a pharmacokinetic and residue analysis for mebendazole levels in the goldfish (Carassius auratus). Plasma and muscle samples of C. auratus were taken after oral administration of 10 mg/kg mebendazole. The maximal drug plasma concentration of 0.55 mg/L was achieved at 48 hr and then declined with the elimination half‐life (T_1/2β) of 7.99 hr. Administration of 10 mg/kg by oral gavage for 5 successive days resulted in a peak mebendazole concentration of 0.70 mg/kg in muscle at 96 hr after the last dose. The drug was then eliminated at a relatively slow rate from muscle with T_1/2β of 68.41 hr. There was no detectable mebendazole in any muscle samples at 24 days postadministration. The AUC_last in plasma and muscle was 19.42 and 105.33 mg hr/L, respectively. These data provide information for dosage recommendations and withdrawal time determinations for mebendazole use in aquariums.     

Induction of Gynogenesis and Androgenesis in Goldfish Carassius auratus (var. oranda)

Chromosome engineering was used to develop lines that expressed the stable phenotypic characteristics of goldfish, Carassius auratus (var. oranda). To obtain androgenetic individuals, carp eggs were irradiated and fertilized with sperm from goldfish bearing telescopic eyes. The fertilized eggs were divided into four groups and three of them were subjected to heat-shock treatment at 42°C for 2.0 min at 34, 37 and 40 min after fertilization. All groups exhibited low viability of embryos and after hatching the embryos were severely deformed on the head, yolk sac and tail and exhibited 100% mortality, within 2 days after hatching. To obtain gynogenetic individuals, a thin layer of carp milt was subjected to ultraviolet irradiation for 26 min to neutralize its genetic material and used to fertilize a mixture of eggs derived from three different variations of C. auratus individuals with characteristics such as round fat body, triple tail, red and black colour and telescopic eyes. The fertilized eggs were divided into six groups and five of them were subjected to heat-shock treatment at 39.5°C for 2.5 min at 15 (group 2), 20 (group 3), 30 (group 5) and 45 (group 6) min after fertilization. The percentage of fertilized eggs that survived ranged from 20 to 50% and the percentage of larval survival in groups 2–5 was 22–28% with lower levels in groups 1 and 6, ranging from 10–12%. However, 40–60% of the larvae exhibited severe deformities on the head, yolk sac and tail, whereas the rest developed normally. Fish with the typical oranda phenotype were observed in all the groups and about 1% of the fish were characterized by a triple tail but there was no fish with telescopic eyes. The results indicate that gynogenetic individual goldfish can be produced but that the induction of androgenesis requires further improvement of the techniques.     

Optimization Protocol for Storage of Goldfish (Carassius auratus) Embryos in Chilled State

A series of five experiments were conducted to explore suitable conditions for storing of goldfish embryos in a chilled state. The factors studied were embryo stage, storage temperature, physiological saline solutions and goldfish artificial coelomic fluid (GFACF) medium, antibiotics (penicillin and streptomycin), antioxidants (vitamin E, vitamin C), buffer (Hepes, Tris) and BSA (bovine serum albumin). First, goldfish embryos at eight developmental stages were incubated in aerated and dechlorinated tap water at 0°C for 24 h. Result shows that early developmental stages were most sensitive to chilling. Heartbeat‐stage goldfish embryos were chilled at 0, 4 or 8°C for up to 72 h in water, and chilled storage was possible only for up to 18, 24 and 48 h at 0, 4 and 8°C, respectively, without a decrease in viability. Chilling of goldfish embryos at 8°C in GFACF medium and Dettlaff's solution instead of water and other physiological saline solutions prolonged their viability (p < 0.01). Nevertheless, viability of chilled embryos in GFACF medium was slightly, but non‐significantly, higher than in Dettlaff's solution. Supplementation of the GFACF medium with antibiotics, Hepes or BSA increased the viability of chilled embryos, but the tested vitamin E analogue Trolox, vitamin C or Tris concentration had no effect on embryo viability. The outcome of this series of experiments shows that heartbeat‐stage goldfish embryos could be chilled for 60 h in GFACF supplemented with 25 mm Hepes, 100 U/ml penicillin, 10 μg/l streptomycin and 1 g/l BSA in such a way that embryonic development does not proceed, and viability is not lost.     

Bilateral intraocular malignant neuroectodermal tumors in a telescope goldfish (Carassius auratus)

A 5‐year‐old male telescope goldfish (Carassius auratus) developed buphthalmia of the left eye. An enucleation was performed and a diagnosis of a neuroectodermal tumor was made on histological examination. Although the fish initially recovered, it was killed 49 days postsurgery due to a severe decline in its condition. On histological evaluation of postmortem tissue samples, it was determined that the fish also had a neuroectodermal tumor of the right eye with local invasion of the brain. On immunohistochemistry, the neoplastic cells were positive for S‐100. To the authors’ knowledge, this is the first published case of naturally occurring bilateral intraocular neuroectodermal tumors in a fish.     

Immersion anaesthesia in goldfish (Carassius auratus) with three concentrations of alfaxalone

Objective

To evaluate the anaesthetic effects of three different alfaxalone doses to induce anaesthesia in goldfish.

Conjunctival habronemiasis in a square‐lipped rhinoceros (Ceratotherium simum)

A captive female square‐lipped rhinoceros born in 1993 had been showing intermittent signs of bilateral conjunctivitis and conjunctival proliferation since 1998. Periodic improvement was noted, especially in winter, but overall the condition had deteriorated over the years. Treatment with various topical, intralesional, and systemic antibiotics and glucocorticosteroids was largely ineffective, as were repeated dewormings. No primary cause for these lesions was found in biopsies taken in 2000 and 2006, although a severe infiltrate of numerous eosinophils was observed in the latter. As the condition worsened, secondary corneal changes were noted, and eventually vision was lost due to proliferative conjunctival tissue. Aggressive resection of the proliferating tissue in 2013 restored vision and submitted biopsies yielded a diagnosis of severe allergic conjunctivitis, eosinophilic granuloma, and habronematid (Habronema or Draschia) larval infection. As no other rhinoceros in the herd was affected, including two calves born to the patient who were in close contact with their mother, it was concluded the presentation was most likely due to a hypersensitivity reaction to the dead or dying larvae. Fly repellent is now regularly applied around the eye of this rhinoceros, and a protective face mask has been fitted. Ongoing periodic relapses are treated with oral ivermectin, topical antibiotics, and steroids.     

Comparatively examining of the apelin‐13 levels in the Capoeta trutta (Heckel, 1843) and Cyprinus carpio (Linnaeus, 1758)

Apelin is a recently discovered peptide produced by several tissues in the various vertebrates and fish. Apelin has been suggested to have role in regulation of many diverse physiological functions including food intake, energy homoeostasis, immunity, osmoregulation and reproduction. In this study, apelin‐13 levels in the blood serum of Cyprinus carpio and Capoetta trutta were determined. Then the results were compared between two species and sexes of each species. Apelin‐13 level was analysed using the enzyme‐linked immunoassay (ELISA) kit (Rat apelin‐13 ELISA kit, catalog no: CSB‐E14367r). Apelin‐13 level in the blood serum of C. trutta was significantly higher than those of the C. carpio (p < 0.05). However, its levels were observed to be no significant difference (p > 0.05) that compared to between sexes of each species. There was a significant negative correlation (r = ?0.829, p = 0.0001) between the apelin‐13 level and body weight of C. carpio. However, no significant correlation (r = ?0.022, p = 0.924) between the apelin‐13 level and weight of C. trutta observed.     

Canine spinal meningiomas and nerve sheath tumours in 34 dogs (2008‐2016): Distribution and long‐term outcome based upon histopathology and treatment modality

The purpose of this retrospective, multicentre case series was to describe the outcome following surgery and/or radiation of spinal meningiomas and nerve sheath tumours (NSTs) based upon treatment modality, with a specific aim to evaluate the survival times and time to recurrence following treatment for each histopathological diagnosis. Our hypothesis was that the addition of radiation therapy modalities to treatment will yield longer time to recurrence of clinical signs and survival time. Thirty‐four dogs met the inclusion criteria of histopathologically diagnosed extramedullary spinal meningioma or NST. Sixteen extramedullary spinal meningiomas and 18 NSTs were diagnosed. A diagnosis of meningioma was associated with a significantly longer survival time compared with NSTs, with median survival times (MST) of 508 days (95% confidence interval [CI]: 66‐881) vs 187 days (95% CI: 76‐433; P = .02). Dogs (seven) treated with stereotactic radiation therapy (SRT) for recurrence after surgery alone or SRT alone as their initial treatment gained an additional 125 to 346 days survival time.     

The efficacy of alfaxalone for immersion anesthesia in koi carp (Cyprinus carpio)

ObjectiveTo characterize the physiologic and behavioral effects of a single induction dose and two maintenance doses of alfaxalone delivered by water immersion in the anesthesia of koi (Cyprinus carpio).Study designProspective, within-subject complete crossover design.AnimalsSix adult koi (Cyprinus carpio) with a median body weight of 344.5 g (range 292.0–405.0 g).MethodsKoi were immersed in water containing 10 mg L^?1 alfaxalone until immobile and then maintained with alfaxalone at either 1 or 2.5 mg L^?1 via a recirculating water system. Times for anesthetic induction and recovery periods were recorded. Physiologic and blood gas parameters were evaluated before, during and after the anesthetic trial. Response to noxious stimuli was also assessed.ResultsMedian anesthesia induction time for all fish was 5.4 minutes. Median recovery time was 11.8 and 26.4 minutes in the 1.0 and 2.5 mg L^?1 doses, respectively, which were significantly different (p = 0.04). Cessation of opercular movement occurred in 0/6 and 4/6 fish exposed to 1.0 and 2.5 mg L^?1 dose respectively. No difference was observed in median heart rate over the duration of the anesthetic events. Response to noxious stimulation was 4/6 and 0/6 in the 1.0 and 2.5 mg L^?1 doses respectively. Oxygenation and ventilation did not change during the experiment, but there was a significant decrease in blood pH along with an increase in blood lactate concentration.Conclusion and clinical relevanceAdministration of alfaxalone, via water immersion, as an induction and maintenance anesthesia agent provided rapid and reliable anesthesia of koi with no mortality. The maintenance dose of 2.5 mg L^?1 was sufficient to prevent response to noxious stimuli but was associated with a clinically relevant depression in opercular rate.     

Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink (Neovison vison)

Antimicrobial agents are used extensively off‐label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild‐type E. coli and S. delphini infections in mink.     

异育银鲫幼鱼饲料中血球蛋白粉与鱼粉的适宜比例

本研究分别以豆油和磷酸二氢钙平衡饲料总油脂和总磷水平,以血球蛋白粉和鱼粉交叉组合平衡总氮水平,在等氮等油脂等磷条件下研究血球蛋白粉替代鱼粉对异育银鲫幼鱼生长性能的影响,探讨以饲料原料优化组合来实现血球蛋白粉对鱼粉替代的可行性.将初始平均体重为(18.40±1.07)g的异育银鲫幼鱼270尾随机分为6组,每组设3个重复,...     

Development of a minimum-anesthetic-concentration depression model to study the effects of various analgesics in goldfish (Carassius auratus)

Teleost fish demonstrate the neurophysiologic capacity to experience pain and analgesia. A common model for assessing analgesic effect is the reduction of minimum anesthetic concentration (MAC). The present study adapted the model of MAC depression to evaluate the analgesic effects of morphine, butorphanol, medetomidine, and ketoprofen in goldfish (Carassius auratus). MAC was determined by an up-down method of sequential population sampling, anesthetizing fish with tricaine methanesulfonate (MS-222) in concentration increments of 10 parts per million (ppm), and using intramuscular needle insertion as a supramaximal noxious stimulus. Baseline MAC was determined in triplicate at the beginning (MACi) and conclusion (MACe) of the experiment (approximately 60 days). For drug trials, MAC was redetermined 1 hr after administration of morphine (10, 20, 40 mg/kg i.m.), butorphanol (0.1, 0.2, 0.4 mg/kg i.m.), medetomidine (0.01, 0.015, 0.025 mg/kg i.m.), ketoprofen (0.5, 1.0, 2.0 mg/kg i.m.), or saline control. Each drug/dose was tested in random order with a > 6-day washout period. MACi and MACf were 163 and 182 ppm, respectively, and were significantly different from each other (P = 0.02). All doses of morphine and ketoprofen decreased MAC below MACi. The highest dose of medetomidine decreased MAC below MACi. The lowest dose of butorphanol decreased MAC below MACi, but higher doses increased MAC above MACf. The authors conclude that MAC determination in fish using MS-222 was feasible and reproducible in the short term. The fact that MAC increased over time and/or exposure may limit the usefulness of MS-222 in MAC depression studies. Morphine and ketoprofen decrease anesthetic needs in goldfish and may provide analgesia.