Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery

Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.     

Hidden costs of food production: the veterinarian's role

Veterinarians who work in food-animal production and food safety help to deliver food policy by enabling farmers to supply safe, affordable food. However, existing food policy reflects a production bias and is increasingly being criticized for its hidden costs. These costs include reduced animal welfare, the inflated risk of anti-microbial resistance, and the current pandemic of human obesity and overweight. Veterinarians do not generally recognize that this is the context within which they do their work. In this article, I review this context and argue that veterinary students should be taught about it. I also argue that the profession should join with food-policy analysts, ethicists, and others who are already calling for a rethinking of food policy, so that new policy might meet the full wealth of problems and not just some.     

A slowly progressive retinopathy in the Shetland Sheepdog

Objective To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study. Procedure Ophthalmic examination including slit‐lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course‐test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark‐adapted b‐wave amplitudes. SPR1‐dogs had ophthalmoscopic signs of SPR, but normal dark‐adapted b‐wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark‐adapted b‐wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination. Results The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper‐reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b‐wave amplitudes throughout dark‐adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod–cone degeneration ( prcd )‐mutation in three dogs with SPR was negative. Conclusion Slowly progressive retinopathy is a generalized rod–cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper‐reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd‐mutation.     

Oesophageal strictures in cats associated with doxycycline therapy

Four cases of oesophageal stricture subsequent to doxycycline administration are reported. All cases were young to middle age (median age 3 years; range 1-7 years), and either domestic shorthair or domestic longhair breed. In all cases the predominant clinical sign was regurgitation, which developed at variable times after doxycycline administration. In all cases the reason for doxycycline use was treatment or prophylaxis of suspected infections (Mycoplasma haemofelis, Chlamydophila felis or Bordetella bronchiseptica), and the duration of therapy was variable. In one case the stricture was definitively diagnosed at post mortem examination, in the three other cases, definitive diagnosis was by endoscopy. Balloon dilation was successful in the three cases that were treated. This is the largest case series, to date, of oesophageal disease in cats associated with doxycycline administration. Caution should be exercised when administering oral medication to cats, especially doxycycline, and should be accompanied either by a water or food swallow.     

Pharmacokinetics and clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia

This study determined the pharmacokinetics and compared the clinical effects of xylazine and dexmedetomidine in horses recovering from isoflurane anesthesia. Six healthy horses aged 8.5 ± 3 years and weighing 462 ± 50 kg were anesthetized with isoflurane for 2 hr under standard conditions on two occasions one-week apart. In recovery, horses received 200 μg/kg xylazine or 0.875 μg/kg dexmedetomidine intravenously and were allowed to recover without assistance. These doses were selected because they have been used for postanesthetic sedation in clinical and research studies. Serial venous blood samples were collected for quantification of xylazine and dexmedetomidine, and the pharmacokinetic parameters were calculated. Two individuals blinded to treatment identity evaluated recovery quality with a visual analog scale. Times to stand were recorded. Results (mean ± SD) were compared using paired t tests or Wilcoxon signed-ranked test with p < .05 considered significant. Elimination half-lives (62.7 ± 21.8 and 30.1 ± 8 min for xylazine and dexmedetomidine, respectively) and steady-state volumes of distribution (215 ± 123 and 744 ± 403 ml/kg) were significantly different between xylazine and dexmedetomidine, whereas clearances (21.1 ± 17.3 and 48.6 ± 28.1 ml/minute/kg), times to stand (47 ± 24 and 53 ± 12 min) and recovery quality (51 ± 24 and 61 ± 22 mm VAS) were not significantly different. When used for postanesthetic sedation following isoflurane anesthesia in healthy horses, dexmedetomidine displays faster plasma kinetics but is not associated with faster recoveries compared to xylazine.     

Perioperative use of analgesics in dogs and cats by Canadian veterinarians in 2001

A random sample of 652 Canadian veterinarians was surveyed to determine perioperative use of analgesics in dogs and cats following common surgeries. The response rate was 57.8%. With the exception of taildocking in puppies, at least 85% of animals received preincisional analgesics, and 30% to 98.1% received postincisional analgesics. A similar survey was conducted in 1994; since then, analgesic usage has increased markedly, as have ratings of the pain caused by different surgeries. In 2001 most veterinarians (62%) used at least 2 classes of analgesic perioperatively. However, strong opioids, local anesthetics, and alpha-2 agonists were underused, and there was an overreliance on weak opioids (butorphanol, meperidine). Up to 12% of veterinarians did not use any analgesics. Nationally, this may have affected many animals monthly; for example, approximately 6000 dogs or cats undergoing ovariohysterectomy. Continuing education (provincial level) and review articles were considered effective ways to inform veterinarians about optimal analgesic practices.