Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum

OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.     

Cyclooxygenase (COX) inhibitors and the intestine

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.     

Basic mammalian bone anatomy and healing.

The goal of any method of fracture repair should be the early return to function of the patient with minimum postoperative morbidity. This is accomplished most optimally by having a basic understanding of the biology of bone healing and by being familiar with the musculoskeletal system of the species before attempting fracture repair. Applying the fundamental principles of mammalian bone anatomy and physiology to the bird ensures the best prognosis possible and minimizes postoperative complications in the avian patient.     

Extrapituitary and Pituitary Pathological Findings in Horses with Pituitary Pars Intermedia Dysfunction: A Retrospective Study

The objective of this study was to describe the histopathologic changes observed in extrapituitary organs as well as the pituitary glands of horses with pituitary pars intermedia dysfunction (PPID). Adrenal gland, thyroid gland, liver, lung, kidney, heart, and pituitary gland from 32 horses with clinical and histologic evidence of PPID and 20 control horses were reviewed histologically. Ten of the control horses were aged animals (≥15 years), allowing those changes attributed to age to be identified. In addition to previously reported changes in adrenal gland and liver, an association was established between PPID and several extrapituitary histopathologic changes, namely bronchiolitis, proliferative glomerulopathy, and myocardial lipofuscinosis and fibrosis. The potential biologic significance of these changes is discussed and, although the retrospective design of the current study precludes establishment of causal relationships between the observed extrapituitary changes and PPID, these findings suggest that further investigations are warranted.     

Evaluation of azathioprine on lesion severity and lymphocyte blastogenesis in dogs with perianal fistulas

Fourteen dogs with perianal fistulas were entered into a prospective clinical study to investigate the effects of long-term azathioprine on clinical outcome and to determine if the clinical results correlated with lymphocyte blastogenesis tests. Complete remission of perianal fistulas was seen in eight (57%) of 14 dogs; partial remission occurred in one (7%) dog; and no response was detected in five (36%) dogs. The results of lymphocyte blastogenesis assays did not correlate with therapeutic response.     

Crude protein and essential amino acid requirements in chicks during the first week posthatch

1. This study examined optimal lysine and sulphur amino acid supply in the first week posthatch in broilers and the relationship between essential amino acids and dietary crude protein during the first week posthatch on performance at 7 d and through marketing. 2. The optimal supply during the 7 d posthatch using a 230 g/kg crude protein diet for sulphur amino acids was 9.1 and for lysine was 10.3-10.8 g/kg with maximal body weight (BW) or feed efficiency as the criteria. 3. Feeding diets with crude protein content ranging from 200 to 260 g/kg with either constant amounts of essential amino acids at different crude protein levels or constant ratios of essential amino acids to crude protein resulted in enhanced performance at 7 but not at 4 d with high protein intake and proportionally increased essential amino acids. 4. Performance on diets with crude protein ranging from 160 to 280 g/kg, with constant ratios of essential amino acid to crude protein, was much enhanced with the high crude protein diets at 7 d. All chicks were transferred to standard diets after 7 d and the BW advantage due to the balanced amino acid-high crude protein diet remained through marketing. 5. Thus increasing essential amino acids in a constant ratio to crude protein enhanced performance during the 7 d posthatch.     

Functional development and intestinal absorption in the young poult

1. Absorption, secretion of digestive enzymes and intestinal morphology were determined in poults from hatching to 19 d. 2. Oleic acid was approximately 80% absorbed at hatch and this changed little with age and was not influenced by fasting. In contrast, glucose and methionine were 48 to 56% absorbed at hatch and this increased to 75 to 80% at 4 d; however, this increase in absorption was inhibited by fasting. Percentage absorption of protein did not change between 5 and 19 d, whereas absolute uptake of fat and protein and net secretion of digestive enzymes and fatty acids and N to the duodenum increased with age and body weight (BW). 3. The length and diameter and villus size in the small intestines increased rapidly after hatch whereas the number of villi per cross section did not change with age. Duodenum and ileum surface area reached a plateau after 11 d whereas jejunal surface area continued to increase until 19 d. Duodenal and ileal surface area were not related to BW, but jejunal surface area was significantly correlated. 4. While the major part of the absorption occurred in the duodenum and upper jejunum, uptake of both protein and fat increased in the distal segments of the small intestine with age. Overall absorption of both fat and protein was correlated with BW. 5. It appears that in the posthatch poult intestinal surface area is not a limiting factor in growth, which was correlated with digestive secretions, fat and protein uptake.     

Cystic thyroid and parathyroid lesions in cats

Reports of cystic thyroid and parathyroid masses in cats are uncommon. Herein, the authors describe a series of four cats with cystic ventral cervical lesions, among them thyroid cyst (n=1), thyroid cystadenoma (n=2), and parathyroid adenocarcinoma (n=1). Presentations ranged from completely asymptomatic cervical swellings to signs related to local compression of adjacent structures (e.g., trachea). Ultrasonographic evaluation was helpful in localization of the mass in two cases. Hormone analysis and concentration of cystic fluid were performed in one cat. Surgical excision was performed successfully in three cases. Histopathological examination was performed in all four cases. Long-term prognosis was excellent for those cases in which follow-up was available.     

Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.     

Putative transmission of Mycobacterium tuberculosis infection from a human to a dog

A 3.5-year-old Yorkshire Terrier was evaluated for anorexia and vomiting; infection with Mycobacterium tuberculosis was diagnosed by use of histology, bacteriologic culture, and polymerase chain reaction (PCR) assay on various tissues. The dog was living with a human with an established M. tuberculosis infection. Findings were unique in that diagnosis of M. tuberculosis infection was obtained via PCR techniques, and isolates from the owner and dog were matched via restriction fragment length polymorphism fingerprinting. Dogs infected with M. tuberculosis from humans are most commonly infected via the respiratory tract. Clinical signs in dogs are variable and depend on the integrity of the immune system and the degree of dissemination. Diagnosis can often be obtained through histopathology and bacteriologic culture; additional diagnostic techniques are also available. Treatment of a dog with confirmed M. tuberculosis infection is controversial, and at least 6 months of multidrug treatment is required.