Salmonella Enteritidis Fatal Septicemia with Meningoencephalitis in a Tiger (Panthera tigris) Cub.

A 15-day-old, female, captive Panthera tigris cub was hospitalized after developing severe hyperthermia, depression, and lack of appetite. The clinical condition rapidly worsened, and the tiger cub died in 72 h after the onset of neurological symptoms, septic shock, and multiple organ dysfunction syndrome. The postmortem main gross findings consisted of a severe and diffuse bilateral fibrino-suppurative meningoencephalitis and ventriculitis, mild fibrinous and sero-hemorrhagic polyserositis and cystitis, severe pulmonary edema, and hemorrhages. Microscopically, the meninges, ependyma, and choroid plexuses were diffusely expanded by abundant infiltration of neutrophils and macrophages, with multifocal fibrinous exudation. Histiocytic interstitial pneumonia, fibrinous and neutrophilic polyserositis, and pyelocystitis were also observed. Vascular thrombosis with multifocal vasculitis and vascular necrosis were frequently observed. Aerobic and anaerobic cultures performed on the brain, lungs, intestine, kidneys, and in pericardial effusion reported the presence of Salmonella enterica subsp. enterica serovar Enteritidis. Environmental and nutritional contamination were identified as putative sources of infections. To the best of the authors' knowledge, this is the first report of Salmonella Enteritidis septicemia with meningoencephalitis in a tiger cub, which highlights the need to further investigate the cause of acute perinatal death to reduce the risk of infectious disease outbreaks.

Efficacy of Intra-Operative Topical Wound Anaesthesia to Mitigate Piglet Castration Pain-A Large, Multi-Centred Field Trial.

Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical local anaesthetic and antiseptic formulation instilled to the wound during surgery, is a newly evolving on-farm method to mitigate castration pain. To investigate the efficacy of Tri-Solfen®, instilled to the wound during the procedure, to alleviate subsequent castration-related pain in neonatal piglets, we performed a large, negatively controlled, randomised field trial in two commercial pig farms in Europe. Piglets (173) were enrolled and randomised to undergo castration with or without Tri-Solfen®, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Efficacy was investigated by measuring pain-induced motor and vocal responses during the subsequent procedure and post-operative pain-related behaviour in treated versus untreated piglets. There was a significant reduction in nociceptive motor and vocal response during castration and in the post-operative pain-related behaviour response in Tri-Solfen®-treated compared to untreated piglets, in the first 30 min following castration. Although not addressing pain of skin incision, Tri-Solfen® is effective to mitigate subsequent acute castration-related pain in piglets under commercial production conditions.

Computational Models for the Mechanical Investigation of Stomach Tissues and Structure.

Bariatric surgery is performed on obese people aiming at reducing the capacity of the stomach and/or the absorbing capability of the gastrointestinal tract. A more reliable and effective approach to bariatric surgery may integrate different expertise, in the areas of surgery, physiology and biomechanics, availing of a strong cooperation between clinicians and engineers. This work aimed at developing a computational model of the stomach, as a computational tool for the physio-mechanical investigation of stomach functionality and the planning of bariatric procedures. In this sense, coupled experimental and numerical activities were developed. Experimental investigations on pig and piglet stomachs aimed at providing information about stomach geometrical configuration and structural behavior. The computational model was defined starting from the analysis of data from histo-morphometric investigations and mechanical tests. A fiber-reinforced visco-hyperelastic constitutive model was developed to interpret the mechanical response of stomach tissues; constitutive parameters were identified considering mechanical tests at both tissue and structure levels. Computational analyses were performed to investigate the pressure-volume behavior of the stomach. The developed model satisfactorily interpreted results from experimental activities, suggesting its reliability. Furthermore, the model was exploited to investigate stress and strain fields within gastric tissues, as the stimuli for mechanoreceptors that interact with the central nervous system leading to the feeling of satiety. In this respect, the developed computational model may be employed to evaluate the influence of bariatric intervention on the stimulation of mechanoreceptors, and the following meal induced satiety.

Effect of three opioid-based analgesic protocols on the perioperative autonomic-mediated cardiovascular response in sheep.

Few reports evaluate the clinical effects of opioids in sheep during experimental surgical procedures. Catecholamine-mediated haemodynamic changes resulting from surgical noxious stimulation are blunted by opioids. The aim of this study was to evaluate the efficacy of three opioid-based analgesic protocols in avoiding a 20% increase in heart rate (HR) and/or mean arterial blood pressure (MAP) during experimental intervertebral disk nucleotomy in sheep. Eighteen female Brogna sheep were anaesthetized with propofol and maintained with a fixed end-tidal isoflurane concentration of 1.5 ± 0.1%. Sheep were assigned to one of three groups that intravenously received methadone 0.3 mg/kg (group M), fentanyl 2 µg/kg followed by 10 µg/kg/h (group F), or buprenorphine 10 µg/kg and 30 minutes later ketamine 1 mg/kg followed by 5 mg/kg/h (group BK). Intravenous fentanyl at 2 µg/kg would have been used for rescue analgesia in case HR and/or MAP had increased. During surgery, HR and MAP values did not increase over 20% in all groups. All animals maintained the percentage change between -4 and 7% for both variables; only one sheep in group BK had an increase in MAP superior to 20% after ketamine administration before surgical stimulation. In group M, HR decreased over time and in group BK, MAP tended to increase during surgery. All the opioid-based protocols tested were able to control the cardiovascular response to noxious stimulation in sheep undergoing spinal surgery, although ketamine may have represented a confounding factor.

Neuromuscular blockade of atracurium in permissive hypercapnic versus normocapnic swine undergoing laparoscopy.

Neuromuscular blocking agents (NMBAs) are commonly used in experimental laparoscopy in swine undergoing carbon dioxide pneumoperitoneum. Hypercapnia may be present and may prolong NMBAs' pharmacologic activity. The aim of this study is to evaluate the effect of permissive hypercapnia on the neuromuscular blockade of atracurium in swine. Six Large White swine weighing 30.5 ± 1.6 kg were sedated with intramuscular ketamine and medetomidine, after which anaesthesia was induced with propofol and maintained with sevoflurane. Atracurium 0.4 mg/kg was administered intravenously and the neuromuscular block monitored by acceleromyography during normocapnic and hypercapnic conditions (PaCO2 range 35-45 mmHg and 60-70 mmHg, respectively). Onset time and time to reach a train of four ratio (TOFR) of 0.7 and 0.9 were recorded. Cardiorespiratory parameters, electrolytes and acid-base status were measured under both conditions. Onset time was similar between the two conditions. Time to reach a TOFR of 0.7 and 0.9 (duration of the neuromuscular block) was longer in hypercapnic compared to normocapnic animals being 1325 ± 300 vs 855 ±111 (p = 0.002) and 1823 ± 434 vs 1218 ± 210 seconds (p = 0.005), respectively. Three hypercapnic swine had a TOF count of 2 and 1 instead of a count of 4 with fade. Permissive hypercapnia was associated with a decrease in pH from 7.444 ± 0.039 to 7.257 ± 0.025 (p < 0.001). No differences were observed for heart rate, end-tidal concentration of sevoflurane, body temperature and arterial haemoglobin saturation. Nonetheless, hypercapnic swine had a statistically significant increase in mean arterial pressure (p = 0.020) and plasma potassium concentration (p = 0.003). The values of PaCO2 achieved during hypercapnia were well tolerated in swine undergoing CO2 pneumoperitoneum for laparoscopy. Permissive hypercapnia increased the duration of the atracurium effect and caused an increase in the intensity of the neuromuscular block in few swine.

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies.

Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used. By the transpedicular approach, a 2 mm tunnel was drilled to the NP through the EP. A partial-nucleotomy was performed. The tunnel was sealed using a polyurethane scaffold. Lumbar discs were assigned to different groups: L1-2: nucleotomy; L2-3: EP tunnel; L3-4: nucleotomy + EP repair; L4-5: EP tunnel + repair; L5-6: control. X-Ray and MRI were performed at 0, 1, 3, and 6 months after surgery. Disc height and MRI indexes were calculated. Macro- and micro-morphology were analyzed. Pfirrmann and Thompson grades were assigned. The treated discs exhibited a progressive decrease in NP signal intensity and MRI index, displaying specific grades of degeneration based on the surgical treatment. According to Pfirrmann and Thompson grades different procedures were staged as: EP tunnel + repair: grade-II; EP tunnel: grade-III, nucleotomy + EP repair: grade-IV; nucleotomy: grade-V. A new stepwise model of IDD to study and test safety and efficacy of novel strategies for NP regeneration has been characterized. The different degrees of IDD have been observed similar to Pfirrmann and Thompson grading system. The intact AF allows for loading studies and eliminating the need for AF closure. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2460-2468, 2018.

Endodontic treatment of canine teeth in a cynomolgus monkey ( Macaca fascicularis).

A case of bilateral superior canine tooth pulp necrosis in an 18-year-old male Macaca fascicularis is described . A skull computed tomography scan was performed to confirm the diagnostic suspicion. A successful bilateral endodontic treatment with coronotomy was performed using rotary nickel-titanium instruments. Post-operative dental radiographs confirmed the correct positioning of the sealant. A rapid and excellent clinical recovery was obtained after each surgery. This innovative approach may contribute to improving the quality of root canal treatments provided to non-human primates.

Cardiovascular effects and intraoperative pharmacokinetics of tramadol in sheep undergoing spinal surgery.

OBJECTIVE: To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation. STUDY DESIGN: Prospective randomized controlled study. ANIMALS: A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. METHODS: Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg-1). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography. RESULTS: Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia.

A biomechanical approach to the analysis of methods and procedures of bariatric surgery.

Bariatric surgery includes a variety of procedures that are performed on obese people and aim at decreasing the intake of food and calories. This goal is usually pursued by reducing stomach capacity and/or absorbing capability. Adjustable gastric banding is the most common and successful operation. In general, bariatric surgical procedures are effective, but are often associated with major complications. Surgical procedure and post-surgical conformation of the stomach are usually defined on clinical and surgical basis only. Instead, the optimal configuration should be identified by analyzing the mechanical functionality of the stomach and the surrounding structures, and the relationship between food intake, nutrient adsorption, mechanical stimulation of stomach wall and feeling of satiety. A novel approach to bariatric surgery is required, integrating competences in the areas of biomechanics, physiology and surgery, based on a strong interaction between engineers and clinicians. Preliminary results from coupled experimental and computational investigations are here reported. The analyses aim to develop computational tools for the investigation of stomach mechanical functionality in pre- and post-surgical conformations.

Effects of opioids on proximal renal tubular cells undergoing ATP depletion.

This study investigated the effect of morphine, fentanyl, butorphanol and buprenorphine on viability and caspase-3 activity in renal proximal tubular cells exposed to opioids for 2 h before or 12 h after chemical anoxia. Cell viability decreased regardless the treatment although intracellular ATP content was elevated in morphine and fentanyl pre-treated cells at 12 h. Anoxia increased caspase activity but this effect was significantly reduced in cells treated before or after with morphine, fentanyl and in cell treated with butorphanol for 12 h. No influence of buprenorphine was detected. Morphine, fentanyl and butorphanol might have protective effects during kidney ischemia.

Clinicopathological findings in non-human primate recipients of porcine renal xenografts: quantitative and qualitative evaluation of proteinuria.

BACKGROUND: Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. Only limited data have been reported about clinicopathological findings in primate recipients of life-supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired graft survival. The detection of low molecular weight proteins of tubular origin is considered an early method for predicting potential graft rejection. In this study, the presence and the significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function was supported only by the transplanted organ. METHODS: Eight bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) were transplanted with a single kidney from α1,3-galactosyltransferase gene-knockout (GTKO) pigs transgenic for human CD39, CD55, CD59, and α1,2-fucosyltransferase. In addition to hematological and biochemical analyses, quantitative and qualitative analysis of proteinuria was evaluated by urinary protein-to-creatinine ratio (UPC ratio) and sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE), respectively. RESULTS: The main hematological and biochemical changes recorded after transplantation were a progressive anemia and a severe and progressive decrease in total proteins. In urine samples, the UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation, but bands consistent with mixed (i.e., tubular and glomerular) proteinuria were observed in all samples collected post-transplantation. CONCLUSIONS: The study of clinicopathological changes in cynomolgus monkey renal xenograft recipients provides a valid help in monitoring the health conditions in the post-transplant period. Moreover, the evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey renal xenograft recipients may be considered a valid, inexpensive, and less time-consuming method than more sophisticated techniques in monitoring proteinuria. Proteinuria and presence of low molecular weight (LMW) proteins were consistently found in urine after transplantation, independent of fluctuations in renal function.