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In this study we compared the heavy metal concentration found in different tissues and eggs of the loggerhead sea turtle and evaluated the potential ecotoxicological risk for this important species. Eighteen heavy metal elements were determined in different tissues (liver, gonads, fat, kidney, heart, brain, and spleen) of nine individuals of Caretta caretta found stranded along the coasts of Messina (Sicily, Italy) and in the shell and yolk of six eggs from the island of Linosa (Sicily, Italy). For the analysis of the heavy metals, we used the analytical procedures in accordance with the EPA 200.8 method supplemented by EPA 6020b with three replicates for each measurement. The elements analysed showed different organotropism even if the liver showed higher levels of bioaccumulation. Turtles’ tissues showed the highest values of iron in the liver, followed by zinc in the heart and arsenic in the kidney. Regarding eggs, zinc, iron, and barium were dominant in the yolk and iron, boron, and copper in the eggshell. From the analyses carried out the worrying levels of arsenic and cadmium in the kidneys and liver of C. caretta raise questions about the risk related to exposure to these non-essential elements. This study highlights the importance of multi-element biomonitoring by increasing knowledge on the biodistribution of 18 heavy metals and the related potential risks for C. caretta. We also exploring for the first time the presence of several heavy metals in the eggs and their possible implication for the survival of the species.

Objective To determine the effect of the Klox fluorescence biomodulation system (Phovia) on the healing of surgical wounds. Study design Prospective, blinded, controlled clinical trial. Sample population Healthy dogs undergoing orthopedic surgery (n = 10). Methods Half of the length of each surgical wound was treated with Phovia, and the remaining 50% was treated with saline solution on the first day after surgery and every 3 days until day 13. Wound healing of treated and control areas within each wound was evaluated via macroscopic assessment and histological and immunohistochemical analysis of treated and control wounds. Results The areas treated with Phovia achieved lower histology scores (P = .001), consistent with complete re-epithelialization, less inflammation of the dermal layer, and greater and more regular deposition of collagen. According to immunohistochemistry, expression of factor VIII, epidural growth factor, decorin, collagen III, and Ki67 was increased in treated compared with untreated tissues. Conclusion Phovia therapy improved re-epithelialization, decreased dermal inflammation, and improved matrix formation in uncomplicated cutaneous incisional wounds by regulating the expression of key biological mediators. Clinical significance Phovia may be a beneficial adjunct to promote the healing of incisional wounds.

Simple Summary Elective bilateral ovariectomy in mule mares is recommended to correct undesirable behaviour effects related to oestrus and also in order to improve work performance. This procedure is usually carried out in a standing position with a combination of sedative and analgesic drugs along with local anaesthesia of the ovarian pedicles. The aim of the study was to evaluate the effects of epidural lidocaine-xylazine in sedated standing mules undergoing elective bilateral laparoscopic ovariectomy. The findings suggest that no significant changes were found in heart rate, respiratory rate, rectal temperature with respect to baseline values. Sedation and analgesia were satisfactory in six out of the eight mules. Epidural analgesia with lidocaine-xylazine may be a good alternative to local anaesthetics infiltration of the ovarian pedicle for elective bilateral laparoscopic ovariectomy in standing mule mares, but further studies should be performed. Abstract The purpose of this study was to determine the analgesic efficacy and safety of epidural lidocaine-xylazine administration in standing mules undergoing elective bilateral laparoscopic ovariectomy in order to suppress unwanted behaviour. Eight mule mares were sedated with intramuscular 0.05 mg/kg acepromazine followed by 1.3 mg/kg of xylazine and 0.02 mg/kg of butorphanol intravenously. Sedation was maintained by a constant rate infusion of 0.6 mg/kg/h of xylazine. The paralumbar fossae were infiltrated with 30 mL of 2% lidocaine. Epidural anaesthesia was performed at the first intercoccygeal space with 0.2 mg/kg of lidocaine and 0.17 mg/kg of xylazine. After 15 min, bilateral laparoscopic ovariectomy was performed. Heart rate, respiratory rate, rectal temperature, invasive arterial blood pressure, degree of analgesia, sedation and ataxia were evaluated during surgery. The laparoscopic ovariectomy was successfully completed in all animals. Sedation and analgesia were considered satisfactory in six out of the eight mules. In conclusion, caudal epidural block allowed surgery to be easily completed in six out of eight. The animals did not show any signs of discomfort associated with nociception and were mostly calm during the procedures, however additional studies are needed to establish epidural doses of xylazine and lidocaine that result in reliable abdominal pain control in mules for standing ovariectomy.

Previously, we reported that the administration of a p62/SQSTM1-encoding plasmid demonstrates high safety and signs of clinical benefits for human cancer patients. The treatment also suppressed tumor growth and metastasis in dogs and mouse models. Here we investigated some mechanistic aspects of these effects. In mammary tumors bearing-dogs, i.m. injections of p62 plasmid reduced tumor sizes and their aggressive potential in 5 out of 6 animals, with one carcinoma switching to adenoma. The treatment increased levels of smooth muscle actin in stroma cells and type III collagen in the extracellular matrix, which correlate with a good clinical prognosis. The p62 treatment also increased the abundance of intratumoral T-cells. Because of the role of adaptive immunity cannot be tested in dogs, we compared the protective effects of the p62 plasmid against B16 melanoma in wild type C57BL/6J mice versus their SCID counterpart lacking lymphocytes. The plasmid was only protective in the wild type strain. Also, p62 plasmid amplified the anti-tumor effect of T-cell transfer from tumor-bearing animals to animals challenged with the same tumors. We conclude that the plasmid acts via re-modeling of the tumor microenvironment, making it more favorable for increased anti-cancer immunity. Thus, the p62-encoding plasmid might be a new adjuvant for cancer treatments.

Tumescent anesthesia (TUM) is a technique that was initially used to perform liposuction under local anesthesia, which consists of the injection of such large volumes of local anesthetic until to produce swelling and firmness (tumescence) of the surgical area. The aim of this study was to compare the intraoperative analgesic efficacy of lidocaine (LID) constant rate infusion (CRI), of TUM, or their combination (LID/TUM) and the postoperative pain and analgesic requirement in dogs undergoing unilateral mastectomy. Twenty-four dogs were premedicated with dexmedetomidine (3 μg/kg) and methadone (0.2 mg/kg) intravenously (IV). After induction with propofol IV to effect, dogs were randomly allocated to receive a loading dose of lidocaine (2 mg/kg) followed by a CRI of 100 μg/kg/min (Group LID) in addition to an equivalent volume of lactated Ringer’s solution instead of local TUM, a loading dose of lactated Ringer’s solution followed by a CRI of Ringer’s solution in addition to TUM (Group TUM), a loading dose of lidocaine (2 mg/kg) followed by a CRI of 100 μg/kg/min in addition to TUM (Group LID/TUM). Anesthesia was maintained with isoflurane in oxygen. Postoperative pain scores were assessed once the dogs had fully recovered from the sedative effects, and following 15, 30, 45 and 60 min. The results of the current study allow us to assert that all three treatments provided satisfactory intraoperative antinociceptive effects but administration of LID/TUM induced greater inhibition on sympathetic stimulating effect up to 60 min from recovery, thus, providing better early postoperative pain relief in dogs undergoing mastectomy.

This study aimed to investigate the morphological patterns of the genital tract after long-term treatment of deslorelin acetate in a female cat, a gonadotropin-releasing hormone agonist currently used in adult cats to obtain transient oestrus suppression. A 1-year-old Chartreux female cat was treated with 4.7 mg deslorelin acetate to suppress oestrus manifestations. The treatment was repeated for a total of × 3 every 2 years. After 8 years, the female cat came into oestrus again, but she was no more implanted, and an ovariohysterectomy was performed. Before surgery, an ultrasound examination was performed that showed a normal uterus and the presence of about 5 follicles in ovaries. Concentrations of oestradiol, progesterone, and vaginal smears were compatible with oestrus. During surgery, a very short ovarian pedicle was observed yet neither uterus nor ovaries presented appreciable alterations. At histology, the ovaries presented a juvenile appearance with numerous primordial and periovulatory follicles. The uterus showed marked endometrial hyperplasia with polypoid projection and atrophic myometrium. Based on this case report, deslorelin acetate is a powerful drug able to preserve ovarian function. However, the suppression of gonadotrophin, especially for a long period, has a detrimental atrophic effect on the target organs during treatment and, on the opposite, hyperplastic changes may occur after the restoring of normal cyclicity.

In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro‐grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti‐inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real‐time polymerase chain reaction (RT‐PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative‐inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor VIII and significantly low expression of collagen 3. These data were confirmed by RT‐PCR analysis. The study findings suggested that AAMGs obtained through mechanical disruption present a safe, efficient, and reliable technique, enhancing tendon healing., The group treated with stromal vascular fraction showed a final tendon diameter and a percentage hardness expression that were similar to the original healthy tendon.

This protocol describes a validation procedure to assess the diagnostic accuracy of a radiographic method using a simple device, specifically designed to quantify the cranial tibial translation in dogs. This protocol was used in the following publication: https://doi.org/10.1371/journal.pone.0228621 Tambella AM, Omini L, Attili AR, Vullo C, Martin S (2020) Evaluation of cranial tibial translation in dogs: Diagnostic accuracy of radiographic method using a simple device. PLoS ONE 15(2): e0228621. (ISSN: 1932-6203) (DOI: 10.1371/journal.pone.0228621)

This protocol describes a radiographic procedure to objectively quantifyin vivothe cranial tibial translation using a simple device in dogs. This protocol was used in the following publication: https://doi.org/10.1371/journal.pone.0228621 Tambella AM, Omini L, Attili AR, Vullo C, Martin S (2020) Evaluation of cranial tibial translation in dogs: Diagnostic accuracy of radiographic method using a simple device. PLoS ONE 15(2): e0228621. (ISSN: 1932-6203) (DOI: 10.1371/journal.pone.0228621)

Pig cryptorchidism is a congenital anomaly, which requires surgical intervention. Pain assessment in pig farming has some limitations and consumers are increasingly concerned about suffering linked to on-farm procedures. The PGS seems to be a promising tool for pain assessment in piglets, although it has not been investigated whether this tool is applicable to growing pigs. This study was designed to determine whether the PGS could be useful to assess pain in growing pigs undergoing on-farm cryptorchidectomy. Ten mixed-breed cryptorchid pigs were pre-medicated with azaperone and ketamine. Anesthesia was induced and maintained using IV sodium based. Pigs were filmed pre- and 6 h post-surgery to evaluate their behavior (scan sampling every minute). Besides, 36 pictures of the face expressions (18 pre- and 18 6 h post-surgery) were scored with the PGS by three treatment-blind observers. The pre-surgery pig&rsquo, s activity ratio was 59%, while it was 2% 6 h post-surgery. While the PGS inter-observer reliability was excellent (Interclass Correlation Coefficient value of 0.87), the PGS score increased significantly in pigs 6 h post-surgery (Paired sample t-test, p = 0.02). The PGS proved to be a potentially effective method to assess pain associated with cryptorchidectomy. However, further validation studies are required to validate this tool for other potentially painful procedures.

Background Canine otitis externa is a painful condition which can be challenging to treat due to difficulties in the administration of otic medication. This can be due to lack of owner compliance in the application of ear drops or due to the resentment that some dogs demonstrate when attempts are made to administer topical medication into a sensitive ear canal. The aim of the study was to assess the efficacy of a topical LED-illuminated gel (LIG) in canine otitis externa in comparison to standard of care therapy. Dogs with spontaneous otitis externa were randomly allocated in three groups: groups QW received LIG once weekly; BW received LIG twice weekly; group C received enrofloxacin and silver sulfadiazine twice daily. LIG consists of a topical application of a gel containing chromophores that, when illuminated by a LED lamp, re-emit fluorescent light which can stimulate physiological responses, promoting healing and controlling bacteria. The evaluation protocol (T0 to T5) considered clinical assessment (OTIS-3-index-scoring-system; pruritus-severity-scale; pain-severity-score; aural temperature), cytological scoring system, quali-quantitative bacteriologic assessment. Results All groups (QW, n = 21; BW, n = 23; C, n = 20) showed improvement during the study (QW: P P P − 4 for pruritus, total OTIS-3 and temperature assessments; BW: P − 4 for all clinical, cytological and bacteriologic assessments; C: P P − 4 for bacteriologic assessment). The highest clinical score reduction occurred in Group BW (P 3; P 4 and P − 4 in T5). BW reached the clinically relevant effect level at T3 (− 3.26 ± 1.21 levels), QW reached it at T4 (− 3.24 ± 0.99), C did not reach it. No differences between groups were seen in the reduction of CFU/mL (T0-T5). Conclusions All treatment groups showed a positive clinical effect. LIG administered twice-a-week was the most favourable protocol of the study. LIG may be considered beneficial in the management of canine otitis externa; it seems to be effective in controlling the clinical condition, including the signs of inflammation and local pain, the bacterial growth, and it may help increasing treatment compliance.

A hand-made, radiolucent, custom-designed device having a mobile and a non-mobile platforms was used to objectively quantify the in vivo cranial tibial translation, in order to assess the functional status of cranial-cruciate-ligament (CrCL) in dogs. The hypothesis was that changes in CrCL integrity would result in detectable changes in tibial translation. To validate the diagnostic method, data from injured (PA, n = 32), contralateral (CO, n = 32) and healthy stifles (HE, n = 32) were compared. Normalized tibial translation (ΔN) of each stifle was measured in medio-lateral radiographic projection obtained before and during standard thrust force application, in PA (43.59±12.97%), CO (20.32±6.69%) and HE (12.22±3.77%). Comparing PA with HE and CO (ΔN cut-off value: 29.73%), diagnosis could be issued with very high probability. Comparing HE with CO (ΔN cut-off value: 14.80%), high performance was obtained. The translator device could be a useful tool to objectively quantify the in vivo tibial translation in dogs with CrCL rupture, before surgery and during post-operatory follow-up.

Mules are hybrids bred from the mating of a jack donkey and a horse mare, known for their strength and resistance and still used to work in agriculture. Although they have been for long considered sterile, evidence of estrus cycle has been demonstrated together with abnormal behavior related to ovarian activity. In this study, a bilateral standing laparoscopic ovariectomy technique using the LigaSure technology was applied in 10 mare mules for treating unwanted behavioral patterns. The technique was effectively performed on these animals avoiding the risk of general anesthesia, and the use of the LigaSure technology allowed good hemostasis and reduced surgical time. Owners declared to be satisfied with the resolution of the behavior.

To investigate the ovulatory mechanisms triggered by raw semen (RS) in rabbits, we examined the expression of nerve growth factor (NGF)—a supposed ovulation-inducing factor (OIF)—and cognate receptors in anterior pituitary, ovary, and cervix as well as plasma NGF and luteinizing hormone (LH) concentrations. Six does/group were sham-inseminated with sterile saline (PBS), naturally mated (NM), inseminated with RS alone or after lumbar anesthesia (ARS), or treatment with COX inhibitors (CIRS). Immunohistochemistry revealed positive signals for NGF and receptors in all tissues. RT-PCR confirmed the presence of the target transcripts in the same tissues, except NTRK1 in the cervix. Circulating NGF concentrations rose 3- to 6-fold (P < 0.01) 15 min after semen deposition into the genital tract of NM, RS, and ARS rabbits and remained sustained thereafter. Circulating NGF was 4-fold lower (P < 0.01) in CIRS than in RS does indicating that NGF is mainly synthesized by the uterus. A concomitant rise of LH and NGF concentrations was found in 83.3%, 50.0%, and 16.7% of NM, RS, and CIRS does, respectively, but not in ARS (despite high NGF circulating levels). Seminal plasma NGF concentration was 151.9 ± 9.25 μg/mL. The ovulatory responses were 0%, 83.3%, 66.7%, 16.7%, and 0% in PBS, NM, RS, ARS, and CIRS groups, respectively. Present data confirm that, although RS may induce ovulation via endocrine mechanisms through binding to NGF receptors in the ovary, a novel OIF-mediated neural mechanism facilitates ovulation in rabbits.

Disorders of sexual development (DSDs) are common in horses and cause economic loss in horse breeding. Thus, it is important to develop methods for unambiguous and fast identification of affected horses shortly after birth, as well as those that may propagate the condition to the next generation. Genetic causes of DSDs are multivarious and still little known, and thus development of diagnostic tests requires accumulating knowledge about individual cases and their etiologies. In particular, it is necessary to perform clinical, ultrasound, surgical, histological, cytogenetic, and genetic analyses with close attention in all the affected individuals. This report describes the case of a XX/XY chimeric horse with reproductive apparatus abnormalities and a very low percentage of XY cell in blood highlighting that to avoid undiagnosed case of cell chimeras, above all when studying DSD cases, it is essential to perform both genetic and cytogenetic analyses possibly on more than one tissue.

The present research used immunohistochemistry to analyse the detection and localisation of nitric oxide synthase (NOS) isoforms in the ductuli efferentes and epididymis of prepubertal and adult alpaca. In the ductuli efferentes and epididymis of prepubertal and adult animals, nNOS and eNOS were similarly expressed in epithelial lining cells, conversely differences were observed in the immunopresence of iNOS. Our data provide evidence that NOS isoforms may have roles in reproductive functions and in the developmental processes of the excurrent duct system in the alpaca.

Previously, we reported that the administration of a p62/SQSTM1-encoding plasmid demonstrates high safety and clinical benefits for human cancer patients, having also suppressed tumor growth and metastasis in dogs and mouse models. Here we investigated the mechanistic aspects of these effects. In mammary tumors bearing-dogs, p62 plasmid i.m. injections reduced tumor volumes, and reverted tumor grade to less aggressive lesions in 5 out of 6 animals, with one carcinoma switching to benign adenoma. The treatment increased levels of alpha-SMA in stroma cells and collagen 3 in the extracellular matrix, both of which correlate with a good clinical prognosis. p62 treatment also increased the abundance of intratumoral T-cell. To test the role of adaptive immunity, we compared protective effects of the plasmid against B16 melanoma in wild type C57BL/6J mice and in the corresponding SCID strain lacking lymphocytes. The plasmid was only protective in the wild type strain. Also, p62 plasmid amplified anti-tumor effect of adoptive T-cell transfer from tumor-bearing animals to animals challenged with the same tumors. We conclude that the plasmid acts indirectly via re-modeling of the tumor microenvironment, making it more favorable for increased anti-cancer immunity. Thus, the p62-encoding plasmid might be a new adjuvant for cancer treatments. Key words: Canine breast tumors, Tumor microenvironment, Anti-cancer immunity, p62 / SQSTM1, DNA plasmid, clinical trial, extracellular matrix.

The aim of this experimental study was to evaluate the sedative and cardiorespiratory effects of alfaxalone and midazolam after intramuscular administration in pigs. Fourteen pigs, weighing 18 to 22 kg, aged between 55 and 70 days, American Society of Anaesthesiologists classification 2, affected by congenital reducible umbilical hernia, were included in the study. Alfaxalone (5 mg/kg) and midazolam (0.5 mg/kg) mixed in the same syringe were administered into the neck muscle. Pain on injection, quality of sedation and time to achieve lateral recumbency were recorded. Heart rate (HR), respiratory frequency (fR), and rectal temperature (RT) were recorded at 0 (baseline: before drug administration), 10, 15, and 20 min after the injection. Oxygen saturation of haemoglobin (SpO2), arterial blood pH, arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions and bicarbonate concentration (HCO3-) were recorded at 10, 15, and 20 min after injection. Continuous data were analysed using a repeated-measure analysis of variance (ANOVA) and aP-value < 0.05 was considered significant. Ten animals out of fourteen showed no pain on injection, whereas the remaining four exhibited mild pain. The time from the end of injection to lateral recumbency was 266 ± 40 s. The quality of sedation ranged between good to very good. No significant changes in the variables monitored were observed between the time points. In conclusion, the intramuscular administration of alfaxalone and midazolam in pigs at the doses used induced reliable and fast sedation, without pain on injection and moderate respiratory effects.

Background Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome in veterinary medicine characterized by severe intestinal dysmotility without evidence of mechanical occlusion of the intestinal lumen. The exact pathogenesis of CIPO is unknown. Case presentation A 1-year-old male Miniature Bull Terrier dog was presented with a history of chronic weight loss, regurgitation, lethargy, vomiting and diarrhea. The dog was submitted for exploratory laparotomy. A full thickness intestinal biopsy was taken and a CIPO was suspected. The clinical condition deteriorated and the dog was euthanized. At gross examination the small intestine was severely dilated. Histologically severe fibrosis of the submucosa and severe atrophy of the tunica muscularis were present in small intestine and colon. Immunohistochemical examination with a panel of antibodies for gastro-intestinal neuromuscular disease-associated antigens revealed a severely reduced expression of alpha-smooth muscle actin in the tunica muscularis. Conclusions This case report describes the gross, histological and immunohistochemical findings of CIPO affecting a 1-year-old Miniature Bull Terrier; on the basis of these findings a myopathic form of CIPO is hypothesized in this case.

Background In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value

Elongated soft palate is a common upper airway anomaly in brachycephalic dogs. The scientific literature considering this pathology in nonbrachycephalic dogs is limited. The aim of this study was to estimate the importance of the elongated soft palate in nonbrachycephalic dogs (n = 10), carrying out, at the same time, a comparison with selected brachycephalic dogs (n = 19), on the effect of carbon dioxide laser staphylectomy. The selected population had only elongated soft palates and no other disorders. The surgery was rapid and uncomplicated; no suture material was used. The comprehensive recovery was significant (P < 0.0001): 68.4% of brachycephalic dogs and 100% of nonbrachycephalic dogs had complete recovery. The incomplete recovery in older brachycephalic dogs matched a more advanced pathologic phase. This study suggests that, in the case of high respiratory tract alteration and poor exercise tolerance, it is imperative to consider in differential diagnosis the elongated soft palate in nonbrachycephalic breeds, too; their clinical signs are less severe and frequently underestimated. The surgical treatment has a favorable prognosis when the only alteration is elongated soft palate. The carbon dioxide laser has been confirmed as an useful option for staphylectomy in dogs.

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine, and dogs in some countries. Metamizole is rapidly hydrolyzed to the active primary metabolite 4-methyl-amino-antipyrine (MAA). MAA is formed in much larger amounts compared to other minor metabolites. Among the other secondary metabolites, 4-amino-antipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after administration of 25 mg/kg MT by intravenous (IV) and intramuscular (IM) routes in healthy donkeys. Six jennies were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study. Blood was collected at predetermined times within 24 hours, and plasma was analyzed by a validated HPLC UV method. Plasma concentrations of MAA after IV and IM administrations of MT were detectable from 5 minutes to 10 hours in all the donkeys. Plasma concentrations of AA were detectable from 5 minutes to 8 hours, but in smaller amounts. Cmax (P

Flupirtine (FLU) is a nonopioid analgesic drug with no antipyretic or antiphlogistic effects labeled for humans. It does not induce the side effects associated with the classical drugs used as pain relievers (Non steroidal antiinflammatory drugs and opioids) in human beings. The aim of this study was to evaluate the pharmacokinetic profiles of FLU after IV and PO administrations in healthy donkeys. Six Amiata breed adult jennies were randomly assigned to two treatment groups using an open, 2 × 2 Latin-square crossover study design. Group 1 (n = 3) received a single dose of 1 mg/kg of FLU injected IV into the jugular vein. Group 2 (n = 3) received FLU (5 mg/kg) via nasogastric tube. The washout period was 1 week. Blood samples (5 mL) were collected at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, 36, and 48 hours, and plasma was then analyzed by a validated high-performance liquid chromatography method. No adverse effects were noticed in either administration group. After IV and PO administrations, FLU was detectable in plasma for up to 24 hours. The mean elimination half-life was longer after PO (10.81 hours) than after IV (0.90 hours) administration. The clearance was fast, and the area under the plasma concentration–time curve was small, findings consistent with a low PO bioavailability of about 20%. The pharmacokinetic trend of FLU in donkeys was different from those earlier reported in cats and dogs. Further studies are needed to understand if this active ingredient may be used in donkeys.

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine, and dogs. MT is rapidly hydrolysed to the primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared to other minor metabolites, and it has been selected from the regulatory European Medicines Agency as a marker residue for MRL calculation. The aim of this research was to evaluate the pharmacokinetic profiles of MAA after 20 mg/kg MT by intravenous (IV) and intramuscular (IM) administrations in healthy sheep. Twelve sheep were randomly allocated to two equal treatment groups according to a 2 × 2 crossover study. Blood was collected at predetermined times within 36 h and plasma was analysed by a validated HPLC UV method. No behavioural changes or alterations in health parameters were observed in the IV or IM groups of animals during or after (up to 7 days) the drug administration. Plasma concentrations of MAA after IV administration of MT were detectable from 5 min to 8 h in all the sheep, they were still detectable at 10 h in two animals, and the plasma quantification of MAA was possible from 5 min to 10 h in all the animals after IM administration. The only two significantly different parameters between the groups were maximum concentration (Cmax) and time to maximum concentration (Tmax) (P

Sulpiride is an antipsychotic human drug. It is commonly used to encourage ovulation in noncycling mares and to stimulate lactation in adoptive mares. No pharmacokinetic data are available for donkeys. The aim of this study was to assess the pharmacokinetics profile of sulpiride after intravenous (IV), intramuscular (IM), and oral (PO) administrations in healthy jennies. Animals (n = 6) were treated with sulpiride, 1 mg/kg by IV, IM, and PO routes according to a randomized cross-over design (3 × 3 Latin square). Blood samples (5 mL) were collected at predetermined times and analyzed using a validated high performance liquid chromatography with fluorescence detection method. IV and IM administrations gave similar curves, but they were not bioequivalent. The IM average bioavailability was 73.5%. After PO administration, the drug plasma concentrations were low and consequently both area under the curve and bioavailability (9.4%) were low. This finding could be because of the physicochemical features of the drug. Indeed, considering that sulpiride is a weak base, existing in the ionized form at gastric and physiological pH, it is unsurprising that it is poorly absorbable, especially in equine species whose gastric pH is particularly acidic. In conclusion, injective routes are definitely preferable to PO dosing because of the very low F% via this route.

// Maria Giovanna Sabbieti 1, * , Dimitrios Agas 1, * , Melania Capitani 1 , Luigi Marchetti 1 , Antonio Concetti 1 , Cecilia Vullo 1 , Giuseppe Catone 1 , Vladimir Gabai 2 , Victor Shifrin 2 , Michael Y Sherman 3 , Alexander Shneider 2 , Franco M Venanzi 1 1 School of Biosciences and Veterinary Medicine, University of Camerino, Camerino (Italy) 2 CureLab Oncology Inc, 43 Rubury Hillway Needham MA (USA) 3 Dept. Biochem, Boston University School of Medicine, Boston MA (USA) * These authors have contributed equally to this work Correspondence to: Alexander Shneider, e-mail: ashneider@curelab.com Franco M Venanzi, e-mail: franco.venanzi@unicam.it Keywords: p62/SQSTM1, chronic inflammation, osteoporosis, immunotherapy Received: November 04, 2014 Accepted: December 09, 2014 Published: February 12, 2015 ABSTRACT We recently reported that a DNA plasmid coding p62-SQSTM1 acts as an effective anti tumor vaccine against both transplantable mouse tumors and canine spontaneous mammary neoplasms. Here we report the unexpected finding that intramuscular delivery of p62 DNA exerts a powerful anti-osteoporotic activity in a mouse model of inflammatory bone loss (i.e, ovariectomy) by combining bone-sparing and osteo-synthetic effects. Notably, the suppression of osteoporosis by p62DNA was associated with a sharp down-regulation of master inflammatory cytokines, and up-regulation of endogenous p62 protein by bone-marrow stromal cells. The present data provide a solid rational to apply p62 DNA vaccine as a safe, new therapeutic for treatment of inflammatory related bone loss diseases.

Objective To determine the efficacy of topical application of the autologous platelet gel (PG) in canine chronic protracted decubital ulcers. Study Design Prospective, randomized, blind controlled clinical trial. Animals Dogs (n = 18) with bilateral chronic wounds caused by protracted decubitus ulcers. Methods For each dog, wound side was randomized to receive either platelet gel (group PG) every 5 days for 5 dressing changes, or paraffin gauzes dressings (group C), as negative control. Wound healing and wound surfaces were compared at admission and then evaluated every 5th day, until day 25. Outcome variables were: open wound area, reduction of open wound surface compared to admission and to each preceding dressing change, time to complete epithelialization. Results Significant differences in healing process were observed at day 5 and continued throughout the entire study period (P

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083-6 h) with a Tmax at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies.

Our previous data demonstrated profound anti-tumor and anti-metastatic effects of p62 (sqstm1) DNA vaccine in rodents with various types of transplantable tumors. Testing anti-cancer medicine in dogs as an intermediary step of translational research program provides two major benefits. First, clinical data collected in target animals is required for FDA/USDA approval as a veterinary anti-cancer drug or vaccine. It is noteworthy that the veterinary community is in need of novel medicine for the prevention and treatment of canine and feline cancers. The second more important benefit of testing anti-cancer vaccines in dogs is that spontaneous tumors in dogs may provide invaluable information for human trials. Here, we evaluated the effect(s) of p62 DNA vaccine on mammary tumors of dogs. We found that p62 DNA vaccine administered i.m. decreased or stabilized growth of locally advanced lesions in absence of its overall toxic effects. The observed antitumor activity was associated with lymphocyte infiltration and tumor encapsulation via fibrotic reaction. This data justifies both human clinical trials and veterinary application of p62 DNA vaccine.

Objectives: To assess the value of the intra-articular Wallace distractor in stifle arthroscopy in the dog. Methods-Ex-vivo study: ten cadaver limbs of dogs were used to explore the stifle joints by arthroscopy each once without and once with the aid of a Wallace distractor. Radiographs and observational data were used to assess the degree of joint distraction and to evaluate any collateral intra-articular damages. In vivo study: distractor-assisted arthroscopy was thereafter performed in 12 consecutive clinical cases of dogs with cranial cruciate ligament rupture. The use of the Wallace distractor, clinical setting, time to complete joint evaluation were recorded. Results: In the cadaver study, radiographic findings showed a significant increase of the joint space after the insertion of the distractor. Visual range during arthroscopy employing the Wallace distractor increased substantially and facilitated the assessment of all visible intra-articular structures. Mean time to evaluate the femoropatellar space was 4,1 minutes, to observe cruciate ligaments 6,5 minutes and to complete joint inspection 10,1 minutes. In the clinical study, the use of Wallace distractor allowed improved arthroscopic observation of all relevant structures, without sub-patellar fat pad removal. Mean time to complete joint inspection was 28,5 minutes. Clinical significance: The use of the Wallace joint distractor may be helpful in the arthroscopic assessment of the canine stifle. It is easy to insert, it allows a considerable distraction of the joint making it easier visibility and reducing the possible need to remove the sub patellar fat pad. With its blunt pins Wallace joint distractor limits the risk of iatrogenic damage and can be easy to use even for surgeons who do not have much experience in knee arthroscopy.

SummaryA 20-month-old male Rottweiler dog was presented with the complaint of chronic right forelimb lameness that was unresponsive to conservative treatment. Physical examination allowed for the topographical identification of the source of the problem as a firm enlargement of the soft tissues that was partially movable from humeral bone and compatible with an alteration of the triceps brachii muscle. Radiographic images showed signs that were highly suggestive of myositis ossificans. Computed tomography allowed for a more accurate characterization of the lesion, to exclude involvement of the elbow joint and humeral bone, and to localize anatomically the lesion in the caput accessorium and longum of the triceps brachii muscle. Surgical excision of the ossified portion of the triceps muscle was performed. Histological examination of the excised tissue substantiated the diagnosis of myositis ossificans. A one year clinical and radiographic follow-up examination showed a complete recovery, with no evidence of complications or recurrence. Despite myositis ossificans in dogs having previously been identified in the hindlimbs, this case of myositis ossificans circumscripta of the triceps muscle suggests that it may also occur in the muscles of the forelimb.

Background: The present study aims to analyse the in vivo behaviour of nanohydroxyapatite and to assess its regenerative capacity in dogs affected by periodontal disease. Methods and findings: The dogs employed in the study were randomly subdivided into a control group and an experimental group. After clinical, instrumental and radiological examinations, all the subjects underwent dental prophylaxis and a bioptic sample was taken. A histopathological examination of the periodontal tissues, in correspondence to teeth with periodontopathy ranging between stages 2 and 3, followed. Regenerative therapy with applications of nanohydroxyapatite was administered only to the dogs of the experimental group. After a period of between 35 and 40 days, a further clinical, instrumental and radiological examination was carried out and a bioptic sample taken solely on the dogs whose histological examinations showed changes ascribable to periodontal disease. The results of the histopathological examination demonstrated that only the dogs in the experimental group, who underwent dental prophylaxis together with the administration of nanohydroxyapatite, showed clear signs of improvement with respect to their initial condition. Conclusions: In conclusion the study demonstrated that the nanohydroxyapatite represents a valid osteoconductive and osteoinductive graft product and confirmed its regenerative potential in periodontal therapy in dogs.