Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.

AIMS: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration. METHODS: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses. RESULTS: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration. CONCLUSIONS AND CLINICAL RELEVANCE: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Abbreviations: ADG: Average daily gain; Cmax: Maximum concentration; COX: Cyclooxygenase; LOD: Limit of detection; NSAID: Non-steroidal anti-inflammatory drugs; CL: Plasma clearance; T1/2el: Plasma elimination half-life; Tmax: Time to achieve Cmax; Vd: Volume of distribution.

Practices and opinions of New Zealand sheep farmers towards pain management in lambs during castration and/or tail docking.

AIMS: To collect baseline data from New Zealand sheep farmers on techniques for docking and castrating lambs, their perceptions of the level of pain lambs experience following these procedures, and their opinions about the use of pain relief. METHODS: From a voluntary cross-sectional survey of New Zealand sheep farmers, descriptive statistics were provided for quantitative study variables. Thematic analysis was performed on the free-text comments. Univariable logistic regression was used to assess factors associated with farmers indicating they would consider using a device allowing administration of pain relief simultaneously with castration and tail docking. RESULTS: There were 432 survey responses containing sufficiently complete data for analysis. Of the 340 individuals (77.5%) always or sometimes performing castration of ram lambs, 242 (72.2%) used rubber rings for complete castration, 23 (6.9%) used the short scrotum method for cryptorchid castration, and 75 (22.4%) used a combination of both methods. Of the 423 individuals (97.9%) who indicated that they always or sometimes performed tail docking, 245 (57.9%) used a hot iron only, 148 (35.0%) used a rubber ring only, 26 (5.8%) used both methods, 3 (0.7%) used a surgical knife, and 1 (0.2%) provided no response. Less than 2% of respondents always or sometimes used pain relief for these procedures. Of the 432 respondents, 139 (32.2%) and 180 (41.7%) strongly agreed that castration and tail docking do not cause sufficient pain to warrant using pain relief, respectively. Time and cost were identified as major barriers to providing pain relief. In the unadjusted logistic regression analyses, respondents who were female, had high levels of education, had been farming < 20 years, who believed lambs experienced high levels of pain following the procedures, and who believed pain lasted longer than 6 hours, were more likely to indicate willingness to use pain control devices. CONCLUSION AND CLINICAL RELEVANCE: Our results suggest very few New Zealand sheep farmers currently provide lambs with pain relief following tail docking or castration. This is likely due to the perception that the procedures are not painful enough to warrant pain relief, and concern over time and cost. This highlights the need to educate farmers about lamb pain and distress following tail docking and castration, and its negative impact on animal welfare. Farmers also need pain relief techniques and tools that can be administered simultaneously with these procedures to save time and labour cost.

A case of tail-biting on a multi-site swine operation in Ontario.

This case study describes a severe tail-biting event on a multi-site swine operation in Ontario and outlines the management strategies implemented in an attempt to control the problem. An established social order was clearly present before the tail-biting event occurred. Over 40% of tail-docked pigs in 3 of 8 grower-finisher barns were severely affected, leading to higher mortality and increased numbers of pigs re-housed in hospital pens. Environmental factors, management practices, and animal health in the barns experiencing the tail-biting event are described, including detection of the mycotoxin deoxynivalenol in corn at > 2 ppm. Changes implemented in response to tail-biting included altering the phase-feeding schedule, adding enrichment devices, and increasing surveillance. The subsequent cohort of pigs was followed through the finisher barns and did not engage in the same severity or prevalence of tail-biting as the previous cohort of pigs which experienced the tail-biting event. Key clinical message: No single factor was identified as the initiating cause for the severe tail-biting event. The subsequent cohort of pigs in 4 barns of the same operation were monitored for tail-biting from entry until market, and the incidence of tail-biting was very low.

Un cas de caudophagie dans une exploitation porcine à sites multiples en Ontario. Cette étude de cas décrit un cas grave de caudophagie dans une exploitation porcine à sites multiples en Ontario et décrit les stratégies de gestion mises en oeuvre pour tenter de limiter le problème. Un ordre social établi était clairement présent avant que l'événement de mordillage de queue ne se produise. Plus de 40 % des porcs à la queue coupée dans trois des huit élevages de type croissance-finition ont été gravement touchés, ce qui a entraîné une mortalité plus élevée et un nombre accru de porcs relogés dans des enclos hospitaliers. Les facteurs environnementaux, les pratiques de gestion et la santé animale dans les porcheries où sévissaient la caudophagie sont décrits, y compris la détection de la mycotoxine désoxynivalénol dans le maïs à > 2 ppm. Les changements mis en oeuvre en réponse à la caudophagie comprenaient la modification du calendrier d'alimentation par phases, l'ajout de dispositifs d'enrichissement et l'augmentation de la surveillance. La cohorte suivante de porcs a été suivie dans les porcheries de finition et n'a pas eu la même gravité ou prévalence de caudophagie que la cohorte précédente de porcs qui ont subi l'événement de caudophagie.Message clinique clé :Aucun facteur unique n'a été identifié comme la cause initiale de l'événement grave de caudophagie. La cohorte suivante de porcs dans quatre porcheries de la même exploitation a été surveillée pour la caudophagie depuis l'entrée jusqu'au marché, et l'incidence de la caudophagie était très faible.(Traduit par Dr Serge Messier).

The contribution of the mouse tail to thermoregulation is modest.

Understanding mouse thermal physiology informs the usefulness of mice as models of human disease. It is widely assumed that the mouse tail contributes greatly to heat loss (as it does in rat), but this has not been quantitated. We studied C57BL/6J mice after tail amputation. Tailless mice housed at 22°C did not differ from littermate controls in body weight, lean or fat content, or energy expenditure. With acute changes in ambient temperature from 19 to 39°C, tailless and control mice demonstrated similar body temperatures (Tb), metabolic rates, and heat conductances and no difference in thermoneutral point. Treatment with prazosin, an α1-adrenergic antagonist and vasodilator, increased tail temperature in control mice by up to 4.8 ± 0.8°C. Comparing prazosin treatment in tailless and control mice suggested that the tail's contribution to total heat loss was a nonsignificant 3.4%. Major heat stress produced by treatment at 30°C with CL316243, a ß3-adrenergic agonist, increased metabolic rate and Tb and, at a matched increase in metabolic rate, the tailless mice showed a 0.72 ± 0.14°C greater Tb increase and 7.6% lower whole body heat conductance. Thus, the mouse tail is a useful biomarker of vasodilation and thermoregulation, but in our experiments contributes only 5-8% of whole body heat dissipation, less than the 17% reported for rat. Heat dissipation through the tail is important under extreme scenarios such as pharmacological activation of brown adipose tissue; however, non-tail contributions to heat loss may have been underestimated in the mouse.

Modified Tail Amputation Technique in a Blue and Gold Macaw (Ara ararauna) With Uropygial Gland Adenocarcinoma.

A 33-year-old male blue and gold macaw (Ara ararauna) presented with a 5-month history of an ulcerated lesion and feather loss at the tail base. Two 4-mm biopsies obtained by the primary care veterinarian were consistent with uropygial gland adenocarcinoma. The bird was examined at the Veterinary Medical Teaching Hospital, University of California, and on physical evaluation, the dorsal and ventral surface of the tail base were devoid of feathers, ulcerated and crusted without an identifiable uropygial gland. Complete blood count, plasma biochemistry panel, whole-body radiographs, and an echocardiogram were performed before surgery. The bird was anesthetized, and a complete amputation of the tail was performed. The skin was incised with a radiofrequency electrosurgical system approximately 2 mm circumferentially cranial to the diseased tissue. The musculature was transected to the level of the vertebral column, disarticulating between the second and third caudal vertebrae and transecting the spinal cord with a no. 15 blade. Lateral vertebral processes of the second vertebra were removed with a rongeur. Coccygeus lateralis muscles and tensor fasciae latae muscles and skin were closed laterolaterally with 2 layers and 3-0 polydioxanone suture. The bird recovered uneventfully and was discharged after 6 days of hospitalization. The histopathological diagnosis was adenocarcinoma with squamous differentiation, marked scirrhous response, and superficial epithelial ulceration. It was determined that narrow margins of unaffected tissue were achieved from the pathological examination of submitted material. The bird was evaluated 24 days after surgery and again 3.5 months after surgery, without evidence of complications or recurrence. Approximately 10 days after the last reexamination, the bird was euthanatized after being found minimally responsive at home. A postmortem examination was not performed.

Short communication: A comparison of cow cleanliness, fly population, and fly avoidance behaviors among docked, switch-trimmed, and switch-intact dairy cows in 3 commercial dairy herds.

Tail docking is a controversial practice in the dairy industry. Proponents claim that tail docking keeps the udder cleaner, and therefore improves milk quality and decreases somatic cell count. Opponents of tail docking cite that it causes unnecessary pain, backed by multiple studies that demonstrate no positive benefits of tail docking and that tail docking increases aggravation from flies. The objective of this study was to evaluate and compare cow cleanliness, fly population, and fly-avoidance behaviors among cows with docked, switch-trimmed, and switch-intact tails. A total of 206 cows from 3 Kentucky dairy herds were included in the longitudinal observational study. Each farm included previously docked cows, switch-intact cows, and cows whose switches were trimmed at the initial farm visit. Researchers visited each farm every 2 wk for 8 wk to record cow cleanliness, teat cleanliness, fly population, and fly-avoidance behavior scores. No significant differences were found in cow cleanliness scores, teat cleanliness scores, fly population scores, skin twitching, or foot stomping counts among docked, switch-trimmed, or switch-intact cows. Although the fly population scores did not differ, the amount of tail swings among docked, switch-intact, and switch-trimmed cows were significantly different. The odds of exhibiting tail swinging were 2.63 times greater for docked cows than for switch-trimmed cows and 1.92 times greater than for switch-intact cows. Overall, switch trimming resulted in similar outcomes to tail docking, although neither showed improvements over intact tails.

Prevalence of Spondylosis Deformans in Tailed Versus Tail-Docked Rottweilers.

Tail docking is a routine procedure for rottweilers in the United States and Canada. A cross-sectional comparative study was conducted in tailed (n = 25) and docked (n = 39) rottweilers ≥5 yr old to compare prevalence and severity of spondylosis deformans in the lumbar spine between groups. The prevalence of spondylosis was 68.0% in tailed dogs and 76.9% in docked dogs, which was not significantly different (P = .563). Distribution of spondylosis severity did not significantly differ between tailed and docked dogs (P = .102). Logistic regression found moderate to severe spondylosis was associated with age and sex. Females were three times at greater risk than males (odds ratio 3.10, 95% confidence interval 1.060-9.08; P = .039). Risk increased 1.4 times for each additional year (odds ratio 1.43, 95% confidence interval 1.02-1.99, P = .036). Tail docking may not impact or only play a minor role in spondylosis deformans in rottweilers.

Neuromuscular control of locomotion is altered by tail autotomy in geckos.

Animal locomotion is driven by underlying axial and appendicular musculature. In order for locomotion to be effective, these muscles must be able to rapidly respond to changes in environmental and physiological demands. Although virtually unstudied, muscles must also respond to morphological changes, such as those that occur with tail autotomy in lizards. Tail autotomy in leopard geckos (Eublepharis macularius) results in a 25% loss of caudal mass and significant kinematic alterations to maintain stability. To elucidate how motor control of the locomotor muscles is modulated with these shifts, we used electromyography (EMG) to quantify patterns of in vivo muscle activity in forelimb and hindlimb muscles before and after autotomy. Forelimb muscles (biceps brachii and triceps brachii) exhibited no changes in motor recruitment, consistent with unaltered kinematics after autotomy. The amplitude of activity of propulsive muscles of the hindlimbs (caudofemoralis and gastrocnemius) was significantly reduced and coincided with decreases in the propulsive phases of femur retraction and ankle extension, respectively. The puboischiotibialis did not exhibit these changes, despite significant reductions in femur depression and knee angle, suggesting that the reduction in mass and vertical ground-reaction force by autotomy allows for the maintenance of a more sprawled and stable posture without increasing motor recruitment of the support muscles. These results highlight the significant neuromuscular shifts that occur to accommodate dramatic changes in body size and mass distribution, and illuminate the utility of tail autotomy as a system for studying the neuromuscular control of locomotion.

Macrophages modulate adult zebrafish tail fin regeneration.

Neutrophils and macrophages, as key mediators of inflammation, have defined functionally important roles in mammalian tissue repair. Although recent evidence suggests that similar cells exist in zebrafish and also migrate to sites of injury in larvae, whether these cells are functionally important for wound healing or regeneration in adult zebrafish is unknown. To begin to address these questions, we first tracked neutrophils (lyzC(+), mpo(+)) and macrophages (mpeg1(+)) in adult zebrafish following amputation of the tail fin, and detailed a migratory timecourse that revealed conserved elements of the inflammatory cell response with mammals. Next, we used transgenic zebrafish in which we could selectively ablate macrophages, which allowed us to investigate whether macrophages were required for tail fin regeneration. We identified stage-dependent functional roles of macrophages in mediating fin tissue outgrowth and bony ray patterning, in part through modulating levels of blastema proliferation. Moreover, we also sought to detail molecular regulators of inflammation in adult zebrafish and identified Wnt/ß-catenin as a signaling pathway that regulates the injury microenvironment, inflammatory cell migration and macrophage phenotype. These results provide a cellular and molecular link between components of the inflammation response and regeneration in adult zebrafish.

Electroencephalographic responses of anaesthetized pigs (Sus scrofa) to tail docking using clippers or cautery iron performed at 2 or 20 days of age.

OBJECTIVE: To compare electroencephalographic (EEG) responses of pigs to tail docking using clippers or cautery iron, performed at 2 or 20 days of age. STUDY DESIGN: Prospective, randomised controlled experimental study. ANIMALS: A total of 40 Large White x Landrace entire male pigs aged 2 (n=20) or 20 (n=20) days were randomly assigned to undergo tail docking using clippers or cautery iron. METHODS: Anaesthesia was induced and maintained with halothane delivered in oxygen. Following instrumentation, end-tidal halothane concentration was stabilised at 1.0±0.05%, and EEG recording commenced. After a 5 minute baseline period, tail docking was performed and recording continued for additional 10 minutes. EEG data were subjected to Fast Fourier transformation, yielding the summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT). Variables recorded during the baseline period were compared with those calculated at consecutive 15 second intervals following tail docking. RESULTS: Following tail docking, F50 decreased briefly but significantly in 2-day-olds, whereas 20-day-olds exhibited a sustained increase in F50 (p<0.05). Immediately after tail docking, F50 was overall lower in 2-day-olds than in 20-day-olds (p<0.05). F95 increased after docking in 20-day-olds docked using clippers (p<0.05) but did not change in 20-day-olds docked using cautery iron or in 2-day-olds docked using either method. Overall, F95 was lower in 2-day-olds than in 20-day-olds from 30 to 60 seconds after docking (p<0.05). PTOT decreased after docking in 20-day-olds (p<0.05) but did not change in 2-day-olds. Overall, PTOT was lower in 2- than in 20-day-olds during baseline and after tail docking (p<0.05). CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that tail docking using clippers is more acutely painful than docking using cautery iron and that docking within the first days of birth may be less acutely painful than docking at a later age.

Electroencephalographic assessment of oral meloxicam, topical anaesthetic cream and cautery iron for mitigating acute pain in pigs (Sus scrofa) undergoing tail docking.

OBJECTIVE: To evaluate the efficacy of oral meloxicam, topical anaesthetic cream and cautery iron in mitigating acute nociceptive responses of pigs to tail docking. STUDY DESIGN: A prospective, randomized, controlled experimental study. ANIMALS: A total of 40 healthy Large WhitexLandrace pigs aged 21±1 days, weighing 6.1±0.9 kg. METHODS: Pigs were randomly assigned to one of four treatments (n=10 per treatment): CONTROL: docked using clippers without analgesia; MEL: docked using clippers after administration of oral meloxicam; EMLA: docked using clippers after application of topical anaesthetic cream; and CAUT: docked using a cautery iron without analgesia. Anaesthesia was induced and maintained with halothane in oxygen. Following induction, end-tidal halothane was stabilized at 0.95-1.05% and electroencephalograph (EEG) recording commenced. After 5 minutes of baseline data collection, tail docking was performed and recording continued for a further 10 minutes. The EEG summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were calculated for the baseline period and for consecutive 30-second intervals following docking. RESULTS: Following docking, F50 increased and PTOT decreased significantly in CONTROL and MEL pigs. EMLA pigs exhibited no change in any variable, whilst CAUT pigs exhibited a reduction in PTOT but no change in F50. F50 was higher in control pigs than in EMLA pigs 30-60 seconds after docking (p≤0.01). PTOT was lower in CONTROL than in EMLA pigs 30-90 seconds after docking (p<0.03) and in CAUT pigs 60 seconds after docking (p=0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Prior application of EMLA cream abolished EEG indicators of nociception in pigs docked using clippers. Docking using a cautery iron without analgesia ameliorated EEG indicators of nociception, relative to using clippers without analgesia. Prior administration of EMLA cream or the use of cautery instead of clippers may reduce the acute pain experienced by pigs undergoing tail docking.

ANESTHETIC MANAGEMENT OF AN INDO-PACIFIC BOTTLENOSE DOLPHIN (TURSIOPS ADUNCUS) REQUIRING SURGICAL DEBRIDEMENT OF A TAIL ABSCESS.

This report describes the anesthetic management of a 14-yr-old, 160-kg, female Indo-Pacific bottlenose dolphin ( Tursiops aduncus ) that underwent surgical debridement for a refractory subcutaneous abscess twice within a 6-mo interval. The animal was otherwise in good physical condition at each anesthetic procedure. Following premedication with intramuscular midazolam and butorphanol, anesthesia was induced with propofol and maintained with sevoflurane by intubation. During surgery ventilation was controlled. Blood pressure was indirectly estimated using either oscillometric or pulse oximetry. Presumed hypotension was managed by adjusting the sevoflurane concentration and infusion of dopamine. During recovery, the dolphin regained adequate spontaneous respiration following intravenous administration of flumazenil and doxapram. The dolphin was extubated at 85 min and 53 min after the first and second surgeries, respectively. Successful weaning from the ventilator and initiation of spontaneous respiration was the most important complication encountered. Establishment of a reliable blood pressure measurement technique is critical to success for anesthesia in this species.

Impact of Repeated Tail Clip and Saphenous Vein Phlebotomy on Rats Used in Toxicology Studies.

Sampling blood for toxicokinetic (TK) evaluation in rodents is typically performed using a satellite group of animals to avoid depleting the blood volume and inducing an additional stressor in the main study animals. This practice does not allow for direct comparison of individual animal toxicity to exposure. These studies evaluated serial collection of twelve, 40-µl blood samples from each rat from either a tail clip or a saphenous vein bleed and its impact on toxicologic parameters over 4- and 14-day periods. The results show the feasibility of successfully collecting TK samples from main study animals, using either of the two techniques. Both procedures were amenable to execution by a single technician using dried blood spot sampling. Any changes observed in the primary markers of erythroid mass between the nonbled control rats and repeat sampled rats were minimal and the range of values often overlapped. This technique would improve the quality of data generated from toxicology studies by allowing a direct comparison of systemic exposure to toxicity while at the same time reducing the number of rats by obviating the need for satellite groups.

Cosmetic tail docking: an overview of abuse and report of an interesting case.

BACKGROUND: This paper presents an overview of the global controversies surrounding cosmetic tail docking in puppies, some observed inconsistent practices among dog breeders and Veterinarians in West Africa, and the need for the African Veterinary Profession to take a decisive position on the cosmetic docking procedure. CASE PRESENTATION: An interesting report of observed complications associated with cosmetic tail docking in a 3 week old male Boerboel is reported alongside the management of the ensuing complications. CONCLUSION: This paper highlights the still prevalent practice of cosmetic tail docking and seeks to enlighten clinicians towards stemming its abuse in Africa.

Effects of tail docking on the expression of genes related to lipid metabolism in Lanzhou fat-tailed sheep.

To evaluate stearoyl-CoA desaturase (SCD), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), and peroxisome proliferator-activated receptor (PPARγ) expression in Lanzhou fat-tailed sheep (with and without docked tails), 18 rams were randomly divided into two equal groups (docked group, LT; control group, LC). These data were also used to increase the understanding of sheep fat deposition and metabolism. All animals were harvested at the age of 18 months, and expression was determined for 10 tissues. The results indicated that the fat weight of each tissue in LT was higher than in LC (P < 0.05). SCD expression in semitendinosus, omentum majus fat (OF), subcutaneous fat, kidney fat (KF), and subcutaneous rump fat was higher in LT than in LC rams (P < 0.05). Trends (P < 0.10) associated with higher HSL expression of LC in comparison to that of LT rams in intestinal fat, OF, and KF tissues were detected. Numerically, LPL expression was the highest in KF, OF, and kidney tissues, but there were few differences (P > 0.10). PPARγexpression was greater in LT than in LC rams in liver tissues (P < 0.05), but there were few differences in other tissues. No significant differences were found with regard to the regression analysis of expression and adipose tissue weights, but the two indices exhibited the same trend. The results indicated that changes in fatty deposits may be due to the common control of docking management and the minor effects associated with the regulation of SCD, HSL, LPL, and PPARγexpression.

Whole-organ cell shape analysis reveals the developmental basis of ascidian notochord taper.

Here we use in toto imaging together with computational segmentation and analysis methods to quantify the shape of every cell at multiple stages in the development of a simple organ: the notochord of the ascidian Ciona savignyi. We find that cell shape in the intercalated notochord depends strongly on anterior-posterior (AP) position, with cells in the middle of the notochord consistently wider than cells at the anterior or posterior. This morphological feature of having a tapered notochord is present in many chordates. We find that ascidian notochord taper involves three main mechanisms: Planar Cell Polarity (PCP) pathway-independent sibling cell volume asymmetries that precede notochord cell intercalation; the developmental timing of intercalation, which proceeds from the anterior and posterior towards the middle; and the differential rates of notochord cell narrowing after intercalation. A quantitative model shows how the morphology of an entire developing organ can be controlled by this small set of cellular mechanisms.

Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole.

BACKGROUND: Appendage regeneration in amphibians is regulated by the combinatorial actions of signaling molecules. The requirement of molecules secreted from specific tissues is reflected by the observation that the whole process of regeneration can be inhibited if a certain tissue is removed from the amputated stump. Interestingly, urodeles and anurans show different tissue dependencies during tail regeneration. The spinal cord is essential for tail regeneration in urodele but not in anuran larva, whereas the notochord but not the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic hedgehog is one of the signaling molecules responsible for such phenomenon in axolotl, as hedgehog signaling is essential for overall tail regeneration and sonic hedgehog is exclusively expressed in the spinal cord. In order to know whether hedgehog signaling is involved in the molecular mechanism underlying the inconsistent tissue dependency for tail regeneration between anurans and urodeles, we investigated expression of hedgehog signal-related genes in the regenerating tail of Xenopus tadpole and examined the effect of the hedgehog signal inhibitor, cyclopamine, on the tail regeneration. RESULTS: In Xenopus, sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate. Overall regeneration was severely impaired in cyclopamine-treated tadpoles. Notochord maturation in the regenerate, including cell alignment and vacuolation, and myofiber formation were inhibited. Proliferation of spinal cord cells in the neural ampulla and of mesenchymal cells was also impaired. CONCLUSION: As in the axolotl, hedgehog signaling is required for multiple steps in tail regeneration in the Xenopus tadpole, although the location of the Shh source is quite different between the two species. This difference in Shh localization is the likely basis for the differing tissue requirement for tail regeneration between urodeles and anurans.