Ingesta-associated choledocholithiasis in horses: 2 cases and literature review.

Equine ingesta-associated choledocholithiasis is a rare cause of morbidity and mortality. We describe here the clinical, gross, histologic, and microbiologic features of this condition in 2 horses and compare the features to 2 previous cases. Case 1 was a 4-y-old Thoroughbred mare with colic. Case 2 was an 18-y-old American Paint Horse mare with colic, chronic weight loss, and inappropriate mentation. Both had elevated biochemical markers of hepatocellular injury and cholestasis and were euthanized given a poor prognosis. Case 1 had a well-formed 5-cm choledocholith surrounding a piece of hay, and had chronic neutrophilic cholangiohepatitis, bridging fibrosis, and extrahepatic obstruction. Case 2 had an ill-formed choledocholith with occasional hay fragments, wood stick, and twigs, and had regionally extensive hepatocellular necrosis with mild neutrophilic cholangiohepatitis and bridging fibrosis. Enterococcus casseliflavus and Escherichia coli were isolated in both cases; Clostridium spp. were also isolated from case 2. All 4 reported cases had increased activity of cholestatic enzymes, hyperbilirubinemia, portal inflammation, and bridging fibrosis. Colic, pyrexia, leukocytosis with neutrophilia, and elevated hepatocellular enzyme activity were documented in 3 cases. Foreign material in all 4 cases was plant origin (choledochophytolithiasis), including hay (n = 2), sticks/twigs (n = 2), and grass awns (n = 1). Ingesta-associated choledocholithiasis may be considered as a cause of colic, pyrexia, and elevated cholestatic biomarkers in horses.

Effects of Δ9-Tetrahydrocannabinol and the Aminoalkylindole K2/Spice Constituent JWH-073 on Cardiac Tissue and Mesenteric Vascular Reactivity.

Background: Although use of Cannabis sativa is not associated with serious adverse effects, recreational use of aminoalkylindole (AAI) cannabinoid receptor agonists found in K2/Spice herbal blends has been reported to cause adverse cardiovascular events, including angina, arrhythmia, changes in blood pressure, ischemic stroke, and myocardial infarction. Δ9-Tetrahydrocannabinol (Δ9-THC) is the primary CB1 agonist found in cannabis and JWH-073 is one of the AAI CB1 agonists found in K2/Spice brands sold to the public. Methods: This study used in vitro, in vivo, and ex vivo approaches to investigate potential differences on cardiac tissue and vascular effects betweenJWH-073 and Δ9-THC. Male C57BL/6 mice were treated with JWH-073 or Δ9-THC and cardiac injury was assessed by histology. Effects of JWH-073 and Δ9-THC on H9C2 cell viability and ex vivo mesenteric vascular reactivity were also determined. Results: JWH-073 or Δ9-THC induced typical cannabinoid effects of antinociception and hypothermia but did not promote death of cardiac myocytes. No differences in cell viability were observed in cultured H9C2 cardiac myocytes after 24 h of treatment. In isolated mesenteric arteries from drug-naive animals, JWH-073 produced significantly greater maximal relaxation (96%±2% vs. 73%±5%, p<0.05) and significantly greater inhibition of phenylephrine-mediated maximal contraction (Control 174%±11%KMAX) compared with Δ9-THC (50%±17% vs. 119%±16%KMAX, p<0.05). Discussion: These findings suggest that neither cannabinoid at the concentrations/dose studied caused cardiac cell death, but JWH-073 has the potential for greater vascular adverse events than Δ9-THC through an increased vasodilatory effect.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

The Use of 3D Printers in Medical Education with a Focus on Bone Pathology.

The purpose of this study was to determine the feasibility and effectiveness of incorporating three-dimensional (3D)-printed models into pathology lectures. 3D models of an osteochondroma and an osteosarcoma were printed from a digital model and MRI, respectively, using both stereolithographic and fused-deposition modeling printing techniques. First year medical students with no prior instruction on bone tumors were randomized into two groups: a control group with 2D images and an experimental group with 3D models. The students viewed a pre-recorded lecture about bone tumors, supplemented with handling either 2D images or 3D models of an osteochondroma and osteosarcoma. Performance on pre- and post-activity assessments was compared to evaluate educational effectiveness. Printing 3D models of bone tumors was relatively simple and inexpensive. Assessment data showed that although both groups had improved performance and greater confidence post-lecture, those that handled the 3D models had a more favorable experience than those with the 2D images. This study demonstrates 3D-printed models can be incorporated into a pathology lecture and can positively influence teaching-learning outcomes.

Evaluating the Use of Mixed Reality to Teach Gross and Microscopic Respiratory Anatomy.

Advances in technology often evolve into instructional platforms. This study evaluated the applicability of mixed reality (MR) in anatomy instruction. First-year medical students were randomized into a control group using a cadaver and light microscopes, or an experimental group using HoloLens, to complete a learning activity on gross and microscopic respiratory anatomy. Compared with the control group, the experimental group reached an equivalent score on the post-activity knowledge assessment, performed better on follow-up assessment, had consistently higher perceived understanding, and rated the activity higher. Findings suggest MR is an effective teaching tool and provides a favorable learning experience.

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.

Introduction: Synthetic cannabinoids (SCs) are commonly found in preparations used as recreational drugs. Although severe adverse health effects are not generally associated with cannabis use, a rising number of studies document seizures and even death after SC use. In this study, a mouse model is used to investigate the hypothesis that SCs are more toxic than Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis. Materials and Methods: Beginning with the SCs, JWH-073 and AM-2201, dose-response curves were generated to find the dose of each drug that was similarly efficacious to 50 mg/kg THC. Mice were given daily intraperitoneal (IP) injections of vehicle, 50 mg/kg THC, 30 mg/kg JWH-073, or 1 mg/kg AM-2201 until tolerance to the antinociceptive and hypothermic effects was complete, and then were assessed for spontaneous and antagonist-precipitated withdrawal and potential organ damage. No differences in tolerance were noted, but AM-2201 showed more rearing in the spontaneous and antagonist-precipitated withdrawal phases than either vehicle or the other two drug treatments. Histopathological examination of these mice revealed no drug-induced lesions. In a subsequent set of experiments, various doses of THC, methanandamide (mAEA), and of a variety of SCs (HU-210, CP55940, JWH-073, AM-2201, and PB-22) were given IP, and convulsions and change in body temperature were quantified. Discussion: The treatments yielded varying numbers of convulsions and a range of changes in body temperature. JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, mAEA, or cannabidiol (CBD) (the latter two producing none). HU-210, CP55940, JWH-073, and mAEA produced greater hypothermia than THC or CBD. Convulsions and hypothermia induced by several agonists were prevented by pretreatment with a CB1 antagonist, but not a CB2 antagonist. Conclusions: In agreement with human studies and case reports, this study found that SCs generally produced more seizures than THC. Of particular significance was the finding that mAEA produced far greater hypothermia than THC (similar to most SCs), but unlike the SCs and THC, produced no seizures.

Gold Nanoparticle Toxicity in Mice and Rats: Species Differences.

Nanotoxicity studies are greatly needed to advance nanomedical technologies into clinical practice. We assessed the toxic effects of a single intravenous exposure to commercially available gold nanoparticles (GNPs) in mice and rats. Fifteen-nm GNPs were purchased and independently characterized. Animals were exposed to either 1,000 mg GNPs/kg body weight (GNP group) or phosphate-buffered saline. Subsets of animals were euthanized and samples collected at 1, 7, 14, 21, and 28 days postexposure. Independent characterization demonstrated that the physicochemical properties of the purchased GNPs were in good agreement with the information provided by the supplier. Mice exposed to GNPs developed granulomas in the liver and transiently increased serum levels of the pro-inflammatory cytokine interleukin-18. No such alterations were found in rats. While there was no fatality in mice post-GNP exposure, a number of the rats died within hours of GNP administration. Differences in GNP biodistribution and excretion were also detected between the two species, with rats having a higher relative accumulation of GNPs in spleen and greater fecal excretion. In conclusion, GNPs have the ability to incite a robust macrophage response in mice, and there are important species-specific differences in their biodistribution, excretion, and potential for toxicity.

Mitigating or exacerbating effects of maternal-fetal programming of female mice through the food choice environment.

Humans live, eat, and become overweight/obese in complex surroundings where there are many available food choices. Prenatal exposure to poor food choices predisposes offspring to increased negative health risks, including obesity. Many animal experiments have analyzed intergenerational body weight parameters in an environment without food choices, which may not be directly translatable to the human food environment. In this study, offspring from mothers with a defined high-fat diet (HFD) or low-fat diet (LFD) were arbitrarily assigned to either an exclusively LFD or HFD or to a diet where they have a choice between LFD and HFD (choice diet). Offspring displayed negative outcomes of increased body weight, body fat, serum leptin, and blood glucose levels when given the choice diet compared with offspring on the LFD. Conversely, improved energy expenditure was found for offspring given the choice diet compared with offspring from HFD dams given LFD. In addition, maternal diet-specific influences on offspring metabolic parameters were identified, especially in offspring from HFD dams, including positive outcomes of reduced leptin in LFD offspring, reduced corticosterone and cholesterol levels in HFD offspring, and increased exercise levels in choice offspring, as well as the negative outcome of increased calorie intake in LFD offspring from HFD dams. This defined model can now be used as the basis for future studies to characterize the cycle of inter- and intragenerational obesity and whether more realistic diet environments, especially those including choice, can mitigate phenotype.

Current thoughts on maternal nutrition and fetal programming of the metabolic syndrome.

Chronic diseases such as type 2 diabetes and cardiovascular disease are the leading cause of death and disability worldwide. Although the metabolic syndrome has been defined in various ways, the ultimate importance of recognizing this combination of disorders is that it helps identify individuals at high risk for both type 2 diabetes and cardiovascular disease. Evidence from observational and experimental studies links adverse exposures in early life, particularly relating to nutrition, to chronic disease susceptibility in adulthood. Such studies provide the foundation and framework for the relatively new field of developmental origins of health and disease (DOHaD). Although great strides have been made in identifying the putative concepts and mechanisms relating specific exposures in early life to the risk of developing chronic diseases in adulthood, a complete picture remains obscure. To date, the main focus of the field has been on perinatal undernutrition and specific nutrient deficiencies; however, the current global health crisis of overweight and obesity demands that perinatal overnutrition and specific nutrient excesses be examined. This paper assembles current thoughts on the concepts and mechanisms behind the DOHaD as they relate to maternal nutrition, and highlights specific contributions made by macro- and micronutrients.

Concurrent nasal adenocarcinoma and rhinosporidiosis in a cat.

A 10-year-old, neutered, male Domestic Shorthair cat was presented to the teaching hospital for labored breathing, anorexia, and weight loss of several months duration. External examination revealed distortion of the bridge of the nose and pink fleshy polyps protruding from each nostril. The cat was euthanized and submitted for postmortem examination. In addition to the external findings, the nasal cavity had extensive bone and cartilage loss and contained a tan firm mass in the caudal region of the nasal cavity near the cribriform plate. On histologic examination, the mass was a nasal adenocarcinoma, and the polyps were composed of hyperplastic nasal epithelium and submucosal stroma that contained sporangia consistent with Rhinosporidium seeberi.

Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model.

Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na) were blended with PAA(-) Na(+) and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of -0.7 (+/-0.2), and incorporated approximately 20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 microg g(-1) or single dosage of 15 microg g(-1) in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 microg g(-1) revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.