Gastroprotectants in small animal veterinary practice – a review of the evidence. Part 1: cyto‐protective drugs

Diverse drugs with presumed cytoprotective effect have been used therapeutically in small animal veterinary practice for various gastro‐intestinal conditions such as oesophagitis, gastric ulceration, gastritis or chronic gastro‐enteropathies. Their efficacy has been doubted in human medicine, raising similar questions in the veterinary field. The aim of this review was to assess the current evidence on the efficacy and safety of these drugs in dogs and cats. Through a systematic review of the literature, we identified 37 articles on the use of misoprostol, sucralfate and other gastroprotectants in dogs and cats. There was evidence to support use of misoprostol in the prevention of aspirin‐induced gastroduodenal mucosal injury in dogs, and for use of sucralfate in the prevention of acid‐induced oesophagitis in cats. However, the overall quality of evidence supporting the use of these drugs in small animal patients was poor. In contrast, there was evidence of important adverse effects, especially drug interaction and gastro‐intestinal signs. We therefore recommend prescribing these drugs with caution until further well‐conducted studies reveal a useful gastroprotectant effect.     

Variation in E(rns) viral glycoprotein associated with failure of immunohistochemistry and commercial antigen capture ELISA to detect a field strain of bovine viral diarrhea virus

Bovine viral diarrhea virus (BVDV) affects cattle populations causing clinical signs that range from subclinical immunosuppression to severe reproductive and respiratory problems. Detection and removal of persistently infected (PI) calves is the single most important factor for control and eradication of BVDV. Current testing strategies to detect PI calves rely heavily on immunohistochemistry (IHC) and a commercially available antigen capture ELISA (ACE) assay. These viral assays depend on 1 or 2 monoclonal antibodies which target the E(rns) glycoprotein of BVDV. The sensitivity and specificity of these two tests have been reported previously. The purpose of this research was to characterize a strain of BVDV (AU501) that was undetectable using IHC and ACE based on a single monoclonal antibody, but was consistently detected in samples from a Holstein steer using virus isolation and PCR testing. Sequencing of this AU501 viral isolate revealed a unique mutation in the portion of the genome coding for the E(rns) glycoprotein. This unique field strain of BVDV demonstrates the risk of relying on a single monoclonal antibody for detection of BVDV. Multiple testing strategies, including polyclonal or pooled monoclonal antibodies that detect more than one viral glycoprotein may be necessary to detect all PI calves and facilitate eradication of BVDV.     

Leptin in horses: tissue localization and relationship between peripheral concentrations of leptin and body condition

Obesity has been a major concern in the horse industry for many years, and the recent discovery of leptin and leptin receptors in numerous nonequine species has provided a basis for new approaches to study this problem in equine. The objectives were to: 1) clone a partial sequence ofthe equine leptin and leptin receptor genes so as to enable the design of primers for RT-PCR determination of leptin and leptin receptor gene presence and distribution in tissues, 2) develop a radioimmunoassay to quantify peripheral concentrations of leptin in equine, 3) determine if peripheral concentrations of leptin correlate with body condition scores in equine, and 4) determine if changing body condition scores would influence peripheral concentrations of leptin in equine. In Experiment 1, equine leptin (GenBank accession number AF179275) and the long-form of the equine leptin receptor (GenBank accession number AF139663) genes were partially sequenced. Equine leptin receptor mRNA was detected in liver, lung, testis, ovary, choroid plexus, hypothalamus, and subcutaneous adipose tissues using RT-PCR. In Experiment 2, 71 horses were categorized by gender, age, and body condition score and blood samples were collected. Sera were assayed for leptin using a heterologous leptin radioimmunoassay developed for equine sera. Serum concentrations of leptin increased in horses with body condition score (1 = thin to 9 = fat; r = 0.64; P = 0.0001). Furthermore, serum concentrations of leptin were greater in geldings and stallions than in mares (P = 0.0002), and tended to increase with age of the animal (P = 0.08). In Experiment 3, blood samples, body weights, and body condition scores were collected every 14 d from 18 pony mares assigned to gain or lose weight over a 14-wk interval based on initial body condition score. Although statistical changes (P = 0.001) in body condition scores were achieved, congruent statistical changes in peripheral concentrations of leptin were not observed, likely due to the small range of change that occurred. Nonetheless, serum concentrations of leptin tended to be greater in fat-restricted mares than in thin-supplemented mares (P = 0.09). We conclude that leptin and leptin receptors are present in equine tissues and that peripheral concentrations of leptin reflect a significant influence of fat mass in equine.     

Effect of intravenous infusion of recombinant ovine leptin on feed intake and serum concentrations of GH, LH, insulin, IGF-1, cortisol, and thyroxine in growing prepubertal ewe lambs

In sheep, serum concentrations of leptin change congruently with increases or decreases in nutritional status, while intracerebroventricular infusions of leptin dramatically suppress feed intake in well-fed lambs, and may also increase growth hormone (GH), and/or luteinizing hormone (LH) in undernourished lambs. The objective of the present study was to determine the effects of peripherally delivered ovine leptin, via intravenous infusions, on feed intake and serum concentrations of GH, LH, insulin, IGF-1, cortisol, and thyroxine. Twelve ewe lambs weighing 29.4 +/- 0.7 kg were infused intravenously with a linearly increasing dose of leptin or saline (n = 6 per group) for 10 days, reaching a maximum dose delivered of 0.5mg/h on day 10. Feed intake was assessed twice daily, and blood samples were collected every 10 min for 6 h on days 0, 2, 5, 8, and 10. Serum concentrations of leptin increased in leptin-treated lambs by day 2 (P = 0.05), and continued to increase to concentrations 9-fold greater than saline-infused lambs by day 10 (P < 0.001). Despite the substantial increase in serum leptin, feed intake did not differ between leptin and saline-infused lambs except on day 3.5 (P = 0.01). Furthermore, intravenous infusions of leptin did not significantly influence serum concentrations of insulin, cortisol, IGF-1, thyroxine, LH, or GH. Collectively, these observations contrast with the potent hypophagic effects of leptin when delivered intracerebroventricularly into well-fed lambs. The reasons for the disparate response of lambs treated intravenously with leptin, versus that reported for lambs treated intracerebroventricularly with leptin are not known, but may provide insight into the mechanism(s) of leptin resistance.     

Expression of vascular endothelial growth factor in canine oral malignant melanoma

Serum, plasma and tissue expression of vascular endothelial growth factor (VEGF) was measured in 20 dogs previously diagnosed histologically with oral melanoma. The concentrations of VEGF in serum and plasma were significantly higher in dogs with melanoma than in a control population (P ≤ 0.002). Concentrations of VEGF in the serum and plasma of dogs with melanoma were highly correlated (r = 0.867). Ninety‐five per cent of melanoma tissues expressed VEGF. Two staining patterns were detected: diffuse and granular cytoplasmic staining. High blood concentrations of VEGF were correlated to a shorter survival time in dogs receiving definitive therapy (P = 0.002). Survival times were significantly longer in dogs receiving definitive therapy versus palliative therapy (median 496 versus 97 days, P = 0.007). Blood concentrations of VEGF were associated with stage (P < 0.05). Dogs with oral melanoma have increased serum, plasma and tissue concentrations of VEGF. Increased expression of VEGF may be a reasonable target for future therapy of canine oral melanoma.     

Ocular metastasis of a vaccine-associated fibrosarcoma in a cat

A 6‐year‐old, neutered male domestic shorthair cat was evaluated for a recurrent vaccine‐associated fibrosarcoma. The cat had three excisions of the tumour prior to presentation and was referred for radiation therapy. Ten months following treatment with radiation therapy, the cat was presented again for a cloudy appearance to the eye. An exenteration was performed, and biopsy revealed fibrosarcoma. At the same time, two discrete pulmonary nodules were identified on thoracic radiographs. Two doses of doxorubicin (20 mg/m²) and cyclophosphamide (100 mg/m²) were administered intravenously 3 weeks apart. Despite treatment, the pulmonary nodule doubled in size. This case represents the first antemortem report of ocular metastasis of a vaccine‐associated sarcoma and supports the highly aggressive nature of these tumours.     

Cation-ratio and accelerator radiocarbon dating of rock varnish on mojave artifacts and landforms

The first accelerator radiocarbon dates of rock varnishes are reported along with potassium/argon ages of lava flows and conventional radiocarbon dates of pluvial lake shorelines, in an empirical calibration of rock varnish K(+) + Ca(2+)/Ti(4+) ratios with age in the Mojave Desert, eastern California. This calibration was used to determine the cation-ratio dates of 167 artifacts. Although cation-ratio dating is an experimental method, some dates suggest human occupation of the Mojave Desert in the late Pleistocene.     

Immunoglobulin structure: variation in the sequence of Bence Jones proteins

Analysis of the amino acid sequence of one Bence Jones protein is almost comtplete. Many points of interchange occur in the amino terminal. portion of the molecule relative to partial-sequence data for other proteins. Most, but not all, are, compartible with one-step mutations. Such structural variation in immunoglobulin light chains may result from many related genes.