High-grade mucoepidermoid carcinoma of the salivary gland in a bull.

Salivary gland neoplasia is uncommon in veterinary species and has rarely been reported in cattle. Adenocarcinoma, squamous cell carcinoma, and pleomorphic carcinoma have been described in the parotid gland of dairy cows. Here we describe a case of high-grade mucoepidermoid carcinoma in a bull. The bull had a chronic history of caudal mandibular soft tissue swelling. Postmortem examination revealed a 30 × 30-cm mass with a caseonecrotic center, hemorrhage and necrosis of the ipsilateral cervical musculature, osteolysis of the right paracondylar process of the skull and right horn base, pulmonary nodules, and enlarged tracheobronchial lymph nodes. Histology of the mass, lungs, and lymph nodes revealed an invasive neoplasm composed of epithelial cells arranged in nests and ductular structures supported by a spindle cell stroma, with frequent central necrosis. Immunohistochemistry revealed that epithelial cells were diffusely positive for pancytokeratin and p63 with multifocal vimentin positivity; stromal cells were diffusely positive for vimentin and α-SMA. A salivary gland mucoepidermoid carcinoma was diagnosed based on these findings. Although rare, salivary gland neoplasia should be considered a differential diagnosis for mandibular masses in cattle.

CSF from a puppy with a cerebral vascular hamartoma.

A 9-week-old puppy with refractory seizures and a dome-shaped head presented to the Mississippi State College of Veterinary Medicine Specialty Center for suspected hydrocephalus. Computerized tomography (CT) findings included transtentorial herniation and an intra-axial mass with dystrophic mineralization. Cerebrospinal fluid analysis revealed an increased nucleated cell count of 1100/µl (RI < 5/µl), erythrocyte count of 2.2 × 106 /µl, and markedly increased microprotein of 1939 mg/dl (RI < 30 mg/dl). On cytologic examination of the CSF, numerous erythrophagocytic, and hemosiderin-laden macrophages were observed, which indicated chronic active hemorrhage. Many neutrophils, macrophages, and lymphocytes that contained numerous intracytoplasmic, pleomorphic, bright yellow crystals were observed. Considering the ongoing hemorrhage, the crystals were presumed to be hematoidin. A biopsy with histopathology was performed on the intra-axial mass, and the results were consistent with a vascular hamartoma. We speculate that the formation of these crystals was related to the ongoing hemorrhage associated with the vascular hamartoma. Identification of these crystals may be useful to aid in the identification of chronic hemorrhage associated with vascular malformations or lesions within the central nervous system.

Biodistribution and toxicity of orally administered poly (lactic-co-glycolic) acid nanoparticles to F344 rats for 21 days.

AIM: Quantify the biodistribution and assess the toxicity of PLGA (poly-lactic-co-glycolic acid) and surface-modified PLGA chitosan (PLGA/Chi) nanoparticles (NPs) orally administered for 7, 14 and 21 days to F344 rats. MATERIALS & METHODS: Fluorescent NPs were tracked in F344 rat tissues, and toxicity was evaluated by alkaline phosphatase and alanine transaminase levels, and by histologic examination of tissue samples. RESULTS: Biodistribution of PLGA and PLGA/Chi were similar, with highest amounts found in the intestine and liver. Alkaline phosphatase increased significantly in treated rats. Mild histological differences were detected in the intestine and liver. CONCLUSION: PLGA and PLGA/Chi NPs behaved similarly presenting minimal toxicity in the liver and intestine, but not in kidney, lung and brain.

Feeding by Amblyomma maculatum (Acari: Ixodidae) enhances Rickettsia parkeri (Rickettsiales: Rickettsiaceae) infection in the skin.

Rickettsia parkeri Luckman (Rickettsiales: Rickettsiaceae), a member of the spotted fever group of Rickettsia, is the tick-borne causative agent of a newly recognized, eschar-associated rickettsiosis. Because of its relatively recent designation as a pathogen, few studies have examined the pathogenesis of transmission of R. parkeri to the vertebrate host. To further elucidate the role of tick feeding in rickettsial infection of vertebrates, nymphal Amblyomma maculatum Koch (Acari: Ixodidae) were fed on C3H/HeJ mice intradermally inoculated with R. parkeri (Portsmouth strain). The ticks were allowed to feed to repletion, at which time samples were taken for histopathology, immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) for rickettsial quantification, and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of Itgax, Mcp1, and Il1beta. The group of mice that received intradermal inoculation of R. parkeri with tick feeding displayed significant increases in rickettsial load and IHC staining, but not in cytokine expression, when compared with the group of mice that received intradermal inoculation of R. parkeri without tick feeding. Tick feeding alone was associated with histopathologic changes in the skin, but these changes, and particularly vascular pathology, were more pronounced in the skin of mice inoculated previously with R. parkeri and followed by tick feeding. The marked differences in IHC staining and qPCR for the R. parkeri with tick feeding group strongly suggest an important role for tick feeding in the early establishment of rickettsial infection in the skin.

Carprofen-induced oxidative stress in mitochondria of the colonic mucosa of the dog.

The purpose of the study was to compare the conductance and mannitol permeability of canine colonic mucosa in response to carprofen or 2,4-dinitrophenol (DNP) with or without tempol pretreatment. Ten colonic mucosa sections per dog were mounted in Ussing chambers. Treatments were done in duplicate. Mucosa was exposed to carprofen (200 µg/mL) or DNP (0.25 mM), both with and without tempol (1 mM) pretreatment. Conductance was calculated every 15 min for 240 min. Mannitol flux was calculated over 3 consecutive 60-minute periods. Histology or electron microscopy was done after exposure. Conductance over time, mannitol flux, frequency of histologic categories, and electron microscopic changes were analyzed for treatment effects. The mean ± standard deviation (SD) conductance over time for carprofen or DNP-treated colons was not significantly different from control regardless of tempol pretreatment. Period 3 mannitol fluxes for carprofen and DNP-treated colon were not significantly different, but were greater than control. Period 3 mannitol flux for tempol + carprofen was significantly less than tempol + DNP-treated colon. Sloughing of cells and erosions were seen in the mucosa of carprofen-treated colon. Mitochondrial damage was seen more often in carprofen-treated than DNP-treated or control colon. Tempol pretreatment resulted in more ruptured mitochondria in the carprofen-treated colon; however, other mitochondrial changes were not significantly affected by tempol pretreatment in either carprofen or DNP treated colon. Treatment with carprofen or DNP increased the mannitol flux, but pretreatment with tempol mitigated the carprofen effect. It is apparent that structural mitochondrial damage occurs in the canine colonic mucosa after carprofen and DNP exposure.

L'objectif de la présente étude était de comparer la conductance et la perméabilité au mannitol de la muqueuse du côlon de chien en réponse au carprofène ou au 2,4-dinitrophénol (DNP) avec ou sans prétraitement au tempol. Dix sections de muqueuse du côlon par chien furent montées dans des chambres d'Ussing. Les traitements furent effectués en duplicata. La muqueuse fut exposée à du carprofène (200 µg/mL) ou du DNP (0,25 mM), chacun avec ou sans prétraitement (1 mM) au tempol. La conductance fut calculée à des intervalles de 15 minutes pour 240 minutes. Le flux de mannitol fut calculé sur trois périodes consécutives de 60 minutes. Un examen histologique ou par microscopie électronique fut effectué après l'exposition. La conductance dans le temps, le flux de mannitol, la fréquence des catégories histologiques, et les changements en microscopie électronique furent analysés pour les effets de traitement. La moyenne ± l'écart-type de la conductance dans le temps des côlons traités avec du carprofène ou du DNP n'était pas significativement différente des côlons témoins indépendamment d'un prétraitement au tempol. Les flux de mannitol à la période 3 pour les côlons traités avec du carprofène ou du DNP n'étaient pas significativement différents l'un de l'autre, mais étaient plus élevés que pour les témoins. Le flux de mannitol pour la période 3 pour le traitement tempol + carprofène était significativement moindre que celui des côlons traités avec DNP + tempol. La perte de cellules et des érosions furent observées dans la muqueuse des côlons traités avec du carprofène. Des dommages aux mitochondries ont été vus plus souvent dans les côlons traités avec du carprofène que ceux traités avec du DNP ou les témoins. Le prétraitement au tempol a résulté en plus de mitochondries rupturées dans les côlons traités avec du carprofène; toutefois, les autres dommages mitochondriaux n'étaient pas significativement affectés par un prétraitement au tempol autant pour les côlons traités avec du carprofène que du DNP. Un traitement avec du carprofène ou du DNP augmenta le flux de mannitol, mais le prétraitement avec du tempol a réduit l'effet du carprofène. Il est évident que des dommages mitochondriaux structuraux se produisent dans la muqueuse du côlon de chien suite à une exposition à du carprofrène ou du DNP.(Traduit par Docteur Serge Messier).

Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The radiotelemetry devices enabled real-time acquisition of core body temperatures and changes in heart rates and electrocardiogram intervals for 28 consecutive days without the need to constantly manipulate the animals. Blood specimens were also collected from all animals for 14 days after tick bite, and spirochete densities were assessed by quantitative polymerase chain reaction. The complexity of disease caused by relapsing-fever spirochetes was demonstrated in the nonhuman primates monitored in real time. The animals experienced prolonged episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns and repolarization of the heart were also observed. This is the first report of the characterizing disease progression with continuous monitoring in an animal model of relapsing fever due to Borrelia infection.

Sequence analysis and serological responses against Borrelia turicatae BipA, a putative species-specific antigen.

BACKGROUND: Relapsing fever spirochetes are global yet neglected pathogens causing recurrent febrile episodes, chills, nausea, vomiting, and pregnancy complications. Given these nonspecific clinical manifestations, improving diagnostic assays for relapsing fever spirochetes will allow for identification of endemic foci and expedite proper treatment. Previously, an antigen designated the Borrelia immunogenic protein A (BipA) was identified in the North American species Borrelia hermsii. Thus far, BipA appears unique to relapsing fever spirochetes. The antigen remains unidentified outside of these pathogens, while interspecies amino acid identity for BipA in relapsing fever spirochetes is only 24-36%. The current study investigated the immunogenicity of BipA in Borrelia turicatae, a species distributed in the southern United States and Latin America. METHODOLOGY/PRINCIPAL FINDINGS: bipA was amplified from six isolates of Borrelia turicatae, and sequence analysis demonstrated that the gene is conserved among isolates. A tick transmission system was developed for B. turicatae in mice and a canine, two likely vertebrate hosts, which enabled the evaluation of serological responses against recombinant BipA (rBipA). These studies indicated that BipA is antigenic in both animal systems after infection by tick bite, yet serum antibodies failed to bind to B. hermsii rBipA at a detectable level. Moreover, mice continued to generate an antibody response against BipA one year after the initial infection, further demonstrating the protein's potential toward identifying endemic foci for B. turicatae. CONCLUSIONS/SIGNIFICANCE: These initial studies support the hypothesis that BipA is a spirochete antigen unique to a relapsing fever Borrelia species, and could be used to improve efforts for identifying B. turicatae endemic regions.

Clenbuterol toxicosis in three Quarter Horse racehorses after administration of a compounded product.

CASE DESCRIPTION: 3 Quarter Horse racehorses were examined for suspected clenbuterol overdose 12 to 24 hours after administration by mouth of a compounded clenbuterol product. CLINICAL FINDINGS: All horses developed sinus tachycardia, muscle tremors, hyperhidrosis, and colic. Abnormalities on serum biochemical analysis included hyperglycemia, azotemia, and high creatine kinase activity. The presence of clenbuterol in the serum of all 3 horses and in the product administered was confirmed and quantified by use of liquid chromatography-electrospray tandem mass spectrometry. TREATMENT AND OUTCOME: Propranolol (0.01 mg/kg [0.005 mg/lb], IV) was administered to all 3 horses for antagonism of ß-adrenergic effects and caused a transient decrease in heart rate in all patients. All horses also received crystalloid fluids IV and other supportive treatment measures. Two horses were euthanatized (2 and 4 days after admission) because of complications. One horse recovered and was discharged 4 days after admission to the hospital. In the 2 nonsurviving horses, skeletal and cardiac muscle necrosis was evident at necropsy, and tissue clenbuterol concentrations were highest in the liver. CLINICAL RELEVANCE: Clenbuterol is a ß(2)-adrenergic receptor agonist licensed for veterinary use as a bronchodilator. At doses ≥ 10² µg/kg (4.5 µg/lb), in excess of those normally prescribed, ß-adrenergic stimulation by clenbuterol may cause sustained tachycardia, muscle tremors, hyperglycemia, and cardiac and skeletal muscle necrosis. Laminitis, acute renal failure, rhabdomyolysis, and cardiomyopathy were fatal complications associated with clenbuterol overdose in 2 horses in the present report. At the dose administered, propranolol was effective for short-term control of sinus tachycardia, but it did not alleviate all clinical signs in patients in the present report. These cases demonstrated the risks associated with the use of nonprescribed compounded medications for which the ingredients may be unknown.

TLR7 and TLR9 trigger distinct neuroinflammatory responses in the CNS.

Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in direct toxicity in the central nervous system (CNS). In the present study, we examined the potential of the TLR7 agonist imiquimod and the TLR9 agonist cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) to induce neuroinflammation after intracerebroventricular inoculation. CpG-ODN induced a more robust inflammatory response than did imiquimod after inoculation into the CNS, with higher levels of several proinflammatory cytokines and chemokines. The increase in cytokines and chemokines correlated with breakdown of the blood-cerebrospinal fluid barrier and recruitment of peripheral cells to the CNS in CpG-ODN-inoculated mice. In contrast, TLR7 agonists induced a strong interferon ß response in the CNS but only low levels of other cytokines. The difference in response to these agonists was not due to differences in distribution or longevity of the agonists but rather was correlated with cytokine production by choroid plexus cells. These results indicate that despite the high similarity of TLR7 and TLR9 in binding nucleic acids and inducing similar downstream signaling, the neuroinflammation response induced by these receptors differs dramatically due, at least in part, to activation of cells in the choroid plexus.

In vitro effect of carprofen and meloxicam on the conductance and permeability to mannitol and the histologic appearance of the gastric mucosa of dogs.

OBJECTIVE: To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa. SAMPLE: Gastric mucosa from 6 mature mixed-breed dogs. PROCEDURES: Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400µg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80µg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects. RESULTS: For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections. CONCLUSIONS AND CLINICAL RELEVANCE: In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 µg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.

Late onset of cerebellar abiotrophy in a boxer dog.

Cerebellar abiotrophy is a degenerative disorder of the central nervous system and has been reported in humans and animals. This case report documents clinical, histopathological, and immunohistochemical findings of cerebellar abiotrophy in an adult Boxer dog. A 3.5-year-old, female, tan Boxer dog presented with a six-week history of left-sided head tilt. Neurological examination and additional diagnostics during her three subsequent visits over 4.5 months revealed worsening of neurological signs including marked head pressing, severe proprioceptive deficits in all the four limbs, loss of menace response and palpebral reflex in the left eye, and a gradual seizure lasting one hour at her last visit. Based on the immunohistochemical staining for glial fibrillary acidic protein and histopathological examination of cerebellum, cerebellar cortical abiotrophy was diagnosed. This is the first reported case of cerebellar abiotrophy in a Boxer dog to our knowledge.

Evaluation of chondrocyte death in canine osteochondral explants exposed to a 0.5% solution of bupivacaine.

OBJECTIVE: To evaluate chondrocyte death in canine articular cartilage exposed in vitro to bupivacaine with and without methylparaben and to compare viability for cartilage with intact or mechanically debrided surfaces. SAMPLE POPULATION: Both glenohumeral joints from 10 adult canine cadavers. PROCEDURES: 10 osteochondral cores were harvested from each of the 20 humeral heads; synovium and 1 core from each joint were examined to verify joint health, and the other 9 cores were exposed to canine chondrocyte culture medium (CCCM), a 0.5% solution of bupivacaine, or 0.5% solution of bupivacaine with methylparaben for 5, 15, or 30 minutes. RESULTS: For the superficial zone of surface-intact chondrocytes, bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 5 minutes (47.7%) than did bupivacaine (23.6%) or CCCM (25.4%). Bupivacaine (53.8%) and bupivacaine with methylparaben (62.5%) caused a significantly higher percentage of chondrocyte death at 30 minutes than did CCCM (20.0%). For the superficial zone of chondrocytes with debrided surfaces, bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 30 minutes (59%) than it did at 5 minutes (37.7%). Bupivacaine with methylparaben caused a significantly higher percentage of chondrocyte death at 30 minutes (59.0%) than did CCCM (28.9%). For middle and deep zones of chondrocytes, treatment solution and surface debridement had minimal effects on percentage of chondrocyte death. CONCLUSIONS AND CLINICAL RELEVANCE: Bupivacaine and bupivacaine with methylparaben were cytotoxic to canine articular chondrocytes in vitro. Intra-articular administration of bupivacaine is not recommended for clinical use until additional studies are conducted.

Neuropeptide Y has a protective role during murine retrovirus-induced neurological disease.

Viral infections in the central nervous system (CNS) can lead to neurological disease either directly by infection of neurons or indirectly through activation of glial cells and production of neurotoxic molecules. Understanding the effects of virus-mediated insults on neuronal responses and neurotrophic support is important in elucidating the underlying mechanisms of viral diseases of the CNS. In the current study, we examined the expression of neurotrophin- and neurotransmitter-related genes during infection of mice with neurovirulent polytropic retrovirus. In this model, virus-induced neuropathogenesis is indirect, as the virus predominantly infects macrophages and microglia and does not productively infect neurons or astrocytes. Virus infection is associated with glial cell activation and the production of proinflammatory cytokines in the CNS. In the current study, we identified increased expression of neuropeptide Y (NPY), a pleiotropic growth factor which can regulate both immune cells and neuronal cells, as a correlate with neurovirulent virus infection. Increased levels of Npy mRNA were consistently associated with neurological disease in multiple strains of mice and were induced only by neurovirulent, not avirulent, virus infection. NPY protein expression was primarily detected in neurons near areas of virus-infected cells. Interestingly, mice deficient in NPY developed neurological disease at a faster rate than wild-type mice, indicating a protective role for NPY. Analysis of NPY-deficient mice indicated that NPY may have multiple mechanisms by which it influences virus-induced neurological disease, including regulating the entry of virus-infected cells into the CNS.

Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans.

The ability of the pathogenic fungus Candida albicans to cause disease requires rapid adaptation to changes in the host environment and to an evolving host immune response. The identification of 'virulence factors' using in vitro characterization of mutant strains has traditionally relied on a common set of phenotypic and biochemical assays (most often performed at 30 degrees C) and the subsequent correlation with their corresponding virulence in mouse models of disease. Utilizing a panel of isogenic mutants for the multifunctional signal-modulating 14-3-3 protein (Bmh1p), we have found that specific mutations affect a variety of different pathways currently associated with virulence, including those involved with the formation of filaments, as well as interaction with host immune cells. Surprisingly, our studies revealed that deficiencies in many of these pathways do not always correlate with virulence in a mouse model of disseminated infection. Mutations within the binding pocket of Bmh1p that affect the ability of the protein to efficiently bind ligand had varying effects on the results of a number of in vitro and in vivo assays. The capability, in vitro, to filament in embedment conditions, and to filament and form chlamydospores under microaerophilic conditions on cornmeal agar, does not correlate with virulence. It is likely that only a subset of hyphal signalling pathways is actually required for the establishment of infection in the disseminated mouse model. Most importantly, our results suggest that the delayed onset of log-phase [corrected] growth in vitro at 37 degrees C, and not at 30 degrees C, results in an inability of these mutants to rapidly adjust to environmental changes in vivo and may be responsible for their increased clearance and reduced virulence. It is critical, therefore, that future in vitro studies of putative virulence factors in C. albicans include careful characterization at physiological temperatures.

Pathophysiologic effects of phenylbutazone on the right dorsal colon in horses.

OBJECTIVE: To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC). ANIMALS: 12 healthy adult horses. PROCEDURES: A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E(2) (PGE(2)) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance. RESULTS: Data from 8 horses were analyzed. Plasma albumin concentrations decreased significantly from days 10 to 21 during phenylbutazone treatment, compared with results during the same days for the control treatment. Phenylbutazone treatment caused neutropenia (< 3.0 x 10(3) cells/microL). No other clinical or hematologic abnormalities were detected for phenylbutazone or control treatments. Two horses developed colitis while receiving phenylbutazone. No significant differences were detected in the RDC between phenylbutazone and control treatments for MPO activity, MDA and PGE(2) concentrations, and histologic evidence of inflammation. Arterial blood flow in the RDC was significantly increased during phenylbutazone treatment, compared with values for the control treatment. Differences were identified in VFA production during phenylbutazone treatment, compared with the control treatment, with a decrease in acetic acid concentrations over time. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.

Effects of carprofen on the integrity and barrier function of canine colonic mucosa.

OBJECTIVE: To measure effects of carprofen on conductance and permeability to mannitol and histologic appearance in canine colonic mucosa. SAMPLE POPULATION: Colonic mucosa from 13 mature mixed-breed dogs. Procedures-Sections of mucosa from the transverse colon and proximal and distal portions of the descending colon were obtained immediately after dogs were euthanized. Sections were mounted in Ussing chambers. Carprofen (400 microg/mL) was added to the bathing solution for treated sections. Conductance was calculated at 15-minute intervals for 240 minutes. Flux of mannitol was calculated for three 1-hour periods. Histologic examination of sections was performed after experiments concluded. Conductance was graphed against time for each chamber, and area under each curve was calculated. Conductance X time, flux of mannitol, and frequency distribution of histologic findings were analyzed for an effect of region and carprofen. RESULTS: Carprofen significantly increased mean conductance X time, compared with values for control (untreated) sections for all regions of colon. Carprofen significantly increased mean flux of mannitol from period 1 to period 2 and from period 2 to period 3 for all regions of colon. Carprofen caused a significant proportion of sections to have severe sloughing of cells and erosions involving >or= 10% of the epithelium, compared with control sections. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen increased in vitro conductance and permeability to mannitol in canine colonic mucosa. Carprofen resulted in sloughing of cells and erosion of the colonic mucosa. These findings suggested that carprofen can compromise the integrity and barrier function of the colonic mucosa of dogs.

Ligand up-regulation does not correlate with a role for CCR1 in pathogenesis in a mouse model of non-lymphocyte-mediated neurological disease.

CCR1 ligands, including CCL3, CCL5, and CCL7, are up-regulated in a number of neurological disorders in humans and animal models. CCR1 is expressed by multiple cell types in the central nervous system (CNS), suggesting that receptor signaling by neuronal cell types may influence pathogenesis. In the current study, the authors used a mouse model of retrovirus infection to study the contribution of CCR1 to neuropathogenesis in the absence of lymphocyte recruitment to the CNS. In this model, infection of neonatal mice with the neurovirulent retrovirus Fr98 results in increased expression of proinflammatory chemokines in the CNS, activation of glial cells, and development of severe neurological disease. Surprisingly, no difference in neuropathogenesis was observed between CCR1-sufficient and CCR1-deficient mice following infection with the neuropathogenic virus Fr98. CCR1 was also not necessary for control of virus replication in the brain or virus-induced activation of astroglia. Additionally, CCR1 deficiency did not affect the up-regulation of its ligands, CCL3, CCL5, or CCL7. Thus, CCR1 did not appear to have a notable role in Fr98-induced pathogenesis, despite the correlation between ligand expression and disease development. This suggests that in the absence of inflammation, CCR1 may have a very limited role in neuropathogenesis.