ABSTRACT
PURPOSE: To evaluate the safety and effectiveness of diamond burr debridement (DBD) for the treatment of calcific band keratopathy (CBK) in horses. METHODS: Medical records from horses with CBK were reviewed over a period of 4 years. Diagnosis of CBK was based on slit-lamp examination findings, and DBD was performed on standing sedated horses. Follow-up was obtained by clinical reevaluation of the treated eyes or a telephone survey with the referring veterinarian. RESULTS: Twenty-two horses of different ages (median: 11 years; range: 5-23) representing 24 CBK-affected eyes (14 left eyes and 10 right eyes) were included in the study. The patients had a medical history of chronic and recurrent uveitis, which required repeated long-term treatments with various combinations of ophthalmic corticosteroids. DBD alone cleared the cornea in 22 affected eyes (92%), but it was combined with blade scraping in two cases with thick calcium plaques. The postoperative medication included a topical antibiotic, atropine drops, and oral flunixin meglumine. Corneal healing was achieved in 21 eyes (87%), 5-21 days (median time 13 days) postoperatively. The three remaining horses were lost to follow-up. Recurrence occurred in 5 of the 21 (24%) reexamined eyes, 3-12.5 weeks (median 8 weeks) postoperatively, and required a second DBD. Four of the 21 eyes ended up being enucleated due to sequelae of uveitis. The main limitations of the study include those inherent to all retrospective clinical data collections. CONCLUSION: Mechanical DBD can readily and safely clear the cornea in horses with CBK, but recurrence of calcium deposition is possible.
ABSTRACT
The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.
Subject(s)
Cattle Diseases , Encephalopathy, Bovine Spongiform , Prion Diseases , Prions , Scrapie , Sheep Diseases , Swine Diseases , Sheep , Female , Cattle , Animals , Swine , Prion Diseases/veterinary , Brain/metabolismABSTRACT
PURPOSE: To evaluate the clinical course and outcome of canine spontaneous chronic corneal epithelial defects (SCCEDs) treated with a combination of cotton-tip epithelial debridement (ED) and corneal thermal cautery (CTC), with or without diamond burr debridement (DBD). METHODS: Retrospective medical record review was used to identify dogs treated for SCCEDs at the Veterinary School of Toulouse between 2001 and 2021. The variables identified included signalment, history, clinical findings, previous treatments, and outcomes. Surgery was performed under manual restraint after topical anesthesia of the cornea. The outcome endpoints included healing, clearing of the cornea and complications. RESULTS: Seventy-seven dogs (89 eyes) from 28 different breeds fulfilled the inclusion criteria. The mean age was 8.78 years. The overall success rate after one procedure was 65.1% with a mean healing time of 15.4 days, but 21 eyes lost to follow-up after the initial treatment, were not included in calculations. There was no significant effect of age, eye, brachycephalic conformation and previous treatments. No significant differences in healing rates were found between groups that received DBD or not. Fifteen eyes (22.7%) underwent a second procedure. Complications (corneal pigmentation, uveitis, corneal bullae, and corneal infection) were observed in 15 cases (22%), with only two cases of complicating melting ulcer. CONCLUSIONS: CTC is a safe and effective treatment for SCCEDs in dogs and can be performed without general anesthesia. Additional DBD does not bring any significant value to CTC in SCCEDs. CTC could be interesting in cases where other procedures are less desirable.
Subject(s)
Corneal Diseases , Dog Diseases , Dogs , Animals , Retrospective Studies , Corneal Diseases/surgery , Corneal Diseases/veterinary , Debridement/veterinary , Debridement/methods , Dog Diseases/surgery , Cornea/surgery , Cautery/veterinaryABSTRACT
A 6-year-old miniature Shetland pony mare was referred for evaluation of a left corneal mass, which developed from the healing tissue of a corneal traumatic ulceration that had occurred 4 weeks previously. On gross examination, a spherical, smooth-surfaced, and pink-colored lesion of about 1 cm in diameter was protruding from the left palpebral fissure. Ophthalmic examination revealed that it was attached to the scar tissue of the cornea, and that one corpora nigra was adherent to the posterior face of corneal wounded area, without sign of uveitis. The remainder of the ophthalmic examination was unremarkable. The mass was excised, and cryotherapy was used as an adjunctive therapy. Histopathology of the resected mass was consistent with a pyogenic granuloma on the basis of radially oriented proliferating capillaries, embedded in immature granulation tissue containing an infiltrate of neutrophils, plasma cells and eosinophils. There were no histological features of malignancy. 2 months after surgery, the ventral part of the fibrotic corneal scar was slightly raised by a pink tissue, suggesting possible recurrence of the initial lesion. A second cryotherapy was performed over the leukoma area. No recurrence has been noted for a follow-up period of more than 25 months. Pyogenic granuloma is a benign proliferative fibrovascular response that typically develops after trauma or surgery. Corneal involvement is rare in humans, and to the authors' knowledge has never been documented in veterinary ophthalmology.
Subject(s)
Corneal Diseases , Corneal Injuries , Corneal Ulcer , Granuloma, Pyogenic , Horse Diseases , Horses , Humans , Animals , Female , Granuloma, Pyogenic/etiology , Granuloma, Pyogenic/veterinary , Granuloma, Pyogenic/pathology , Corneal Diseases/etiology , Corneal Diseases/therapy , Corneal Diseases/veterinary , Cornea/pathology , Corneal Injuries/veterinary , Corneal Injuries/pathology , Corneal Ulcer/etiology , Corneal Ulcer/therapy , Corneal Ulcer/veterinary , Wound Healing , Horse Diseases/etiology , Horse Diseases/therapy , Horse Diseases/pathologyABSTRACT
A preclinical study was performed to investigate the efficacy and safety of a new viral inactivated, devitalized, freeze-dried and gamma-sterilized human umbilical cord amniotic membrane (lhUC-AM) for the treatment of deep scleral and corneal defects with or without perforation. Firstly, lhUC-AM was investigated on experimental deep sclerectomy in rabbit eyes (n = 12) and compared to autograft (n = 4) on cross section histology. Secondly, lhUC-AM was studied on a selected series of uncontrolled cases of corneal defects (n = 18) with or without perforation, in dogs and cats. lhUC-AM tolerance, reconstruction of the deep corneal lesion and recovery of the structural aspect of the tissue were followed post-surgery. In experimental deep sclerectomy, histology showed that the lhUC-AM was well tolerated and degraded completely in 45 days while allowing an overall quality and kinetic of scleral regeneration, similar to autograft. In the clinical situations, lhUC-AM was well tolerated, with ocular inflammatory signs quickly decreasing after surgery. Mean follow-up was 16.40 ± 11.43 months. In 15 out of 18 cases, lhUC-AM allowed ocular surface wound healing. The ocular surface was fully reconstructed three months after surgery. This study suggests a good safety and efficacy profile of lhUC-AM in the treatment of deep corneal or scleral defect in animals. This new tissue should now facilitate the treatment of severe ocular surface diseases in humans.
ABSTRACT
OBJECTIVE: The aim of this retrospective study was to review the clinical data and outcomes of patients that suffered ectopic cilium (EC). ANIMALS STUDIED: One hundred and twelve dogs from multiple private practices in France, with a clinical diagnosis of EC were included in the study. RESULTS: The mean age of affected dogs was 2.3 years. There were 64 females and 48 males. The most represented breeds were the Shi Tzu, the French Bulldog, the English Bulldog and the Chihuahua. Eleven dogs were affected bilaterally. The upper eyelid was implicated in 93.5% of the cases, with the median portion being the most affected. No statistical difference was observed between the right and the left eye. EC were associated with distichiasis in 50% of the cases. Pigmentation of the conjunctiva at the point of exit of the EC was present in 58% of the cases. EC were short in 75% and long in 25% of the cases. Corneal complications were statistically associated with short EC. The corneal lesions associated with EC were keratitis (94%), corneal granuloma (0.8%), corneal fibrosis (2.7%), corneal degeneration (0.8%), superficial corneal ulcer (68.7%), deep corneal ulcer (8%) and perforating corneal ulcer (0.8%). The surgeries which consisted of the removal of the hair follicle was successful in 88.4% of the cases. CONCLUSION: EC is a rare condition which can be treated successfully by the removal of the hair follicles. It must be suspected in cases of corneal lesions unresponsive to medical treatment.
Subject(s)
Corneal Ulcer , Dog Diseases , Animals , Cilia/pathology , Conjunctiva/pathology , Corneal Ulcer/veterinary , Dog Diseases/surgery , Dogs , Female , Male , Retrospective StudiesABSTRACT
OBJECTIVES: The aim of this multicentre retrospective study was to review the clinical data, outcomes and histopathological features of cats that had been treated for ocular surface dermoids. METHODS: Thirteen cats from various private practices in France with a clinical diagnosis of ocular surface dermoid were included in the study. RESULTS: The mean age of the study population at the time of diagnosis was 5 months. There were nine males and four females. Three different breeds were domestic shorthair (n = 7), Birman (n = 4) and Havana Brown (n = 2). Two of the four Birmans were related (same sire). The two Havana Browns were also related (same sire). All of the dermoids were unilateral. Five of the dermoids were strictly conjunctival. Four affected both the conjunctiva and the cornea. Three affected both the conjunctiva and the eyelid, and one was strictly corneal. They were located in various positions: temporal (n = 9), inferonasal (n = 1), dorsonasal (n = 1) and dorsotemporal (n = 1). The last dermoid was heterogeneous and involved the nasal, dorsal and temporal quadrants. Concurrent eye diseases were observed in five patients: four cats exhibited associated eyelid agenesis and one cat exhibited persistent iris-to-iris pupillary membranes. Ten dermoids were surgically excised with no recurrences. Surgery was not performed for three cats: one cat died a few days after diagnosis and two cats were lost to follow-up after initial presentation. CONCLUSIONS AND RELEVANCE: Ocular surface dermoids are a rare condition in cats that can be treated successfully by surgical excision. Although our study reports only a small number of cases, the observation of ocular surface dermoids in two related cats in two different breeds indicates that genetic transmission is likely.
Subject(s)
Cat Diseases , Dermoid Cyst , Animals , Cat Diseases/surgery , Cats , Conjunctiva/surgery , Dermoid Cyst/pathology , Dermoid Cyst/surgery , Dermoid Cyst/veterinary , Eyelids/pathology , Female , France/epidemiology , Male , Retrospective StudiesABSTRACT
OBJECTIVE: To evaluate the use of autologous lamellar keratoplasty for the treatment of feline corneal sequestrum (FCS). PROCEDURE: The medical records of cats diagnosed with FCS that underwent autologous lamellar keratoplasty between 2012 and 2020 with a minimum of 2 months of follow-up were reviewed. After keratectomy of FCS, a button adjacent to the corneal limbus was harvested on the same eye and sutured to the recipient bed. A nictitating membrane flap was left in place until the first recheck except for one patient. Postoperative treatment with topical and systemic antibiotics and systemic nonsteroidal anti-inflammatory medications was prescribed. Follow-up examinations were carried out 2 weeks, 1 month and 2 months post-operatively and consisted of a complete ophthalmic examination. RESULTS: A total of 35 cats (35 eyes) were included. The median follow-up time was 3.2 months (range, 2-59 months). Brachycephalic cats were overrepresented (85.7%). The mean graft size was 6.5 mm (range, 6-9 mm). Minor complications consisting of melting and partial integration of the graft occurred in 2/35 eyes (5.7%). Recurrence was observed in 1/35 eyes (2.9%) and was managed by a superficial keratectomy. A good visual outcome was achieved in all eyes, and a faint or mild corneal opacification occurred in 15/35 (42.9%). CONCLUSIONS: Autologous lamellar keratoplasty is an effective treatment for FCS, providing good tectonic support to the affected cornea and resulting in good visual and cosmetic outcomes. These results should be verified in future prospective studies that include a larger number of cases and longer-term follow-up.
Subject(s)
Cat Diseases/surgery , Corneal Diseases/veterinary , Corneal Transplantation/veterinary , Animals , Cats , Corneal Diseases/surgery , Corneal Transplantation/adverse effects , Female , Male , Retrospective Studies , Tomography, Optical/veterinary , Transplantation, Autologous/veterinaryABSTRACT
Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. In this study, we characterized the prion strains responsible for hGH-iCJD cases originating from UK (n = 11) and France (n = 11) using human PrP expressing mouse models. The cases included PRNP MM, MV and VV genotypes from both countries. UK and French sporadic CJD (sCJD) cases were included as controls. The prion strains identified following inoculation with hGH-iCJD homogenates corresponded to the two most frequently observed sCJD prion strains (M1CJD and V2CJD). However, in clear contradiction to the initial hypothesis, the prion strains that were identified in the UK and the French hGH-iCJD cases were not radically different. In the vast majority of the cases originating from both countries, the V2CJD strain or a mixture of M1CJD + V2CJD strains were identified. These data strongly support the contention that the differences in the epidemiological and genetic profiles observed in the UK and France hGH-iCJD cohorts cannot be attributed only to the transmission of different prion strains.
Subject(s)
Creutzfeldt-Jakob Syndrome/epidemiology , Creutzfeldt-Jakob Syndrome/pathology , Encephalopathy, Bovine Spongiform/epidemiology , Encephalopathy, Bovine Spongiform/pathology , Human Growth Hormone/adverse effects , PrPSc Proteins/adverse effects , Adult , Animals , Cohort Studies , Creutzfeldt-Jakob Syndrome/transmission , Encephalopathy, Bovine Spongiform/transmission , Female , France/epidemiology , Human Growth Hormone/administration & dosage , Humans , Male , Mice , Mice, Transgenic , Middle Aged , PrPSc Proteins/administration & dosage , PrPSc Proteins/isolation & purification , United Kingdom/epidemiologyABSTRACT
BACKGROUND: Conjunctivitis in atopic dogs has already been described yet is rarely observed, and likely underdiagnosed in practice. OBJECTIVES: To assay various cytokines in tears and conjunctivae from atopic and normal dogs, and to compare canine atopic dermatitis-associated conjunctivitis with controls. ANIMALS: Ten atopic and ten normal client-owned dogs. METHODS AND MATERIALS: Ocular surfaces were sampled bilaterally in a prospective study, using two different methods. Tear samples were obtained with a sterile swab previously moistened with saline solution (method A). Conjunctival impressions were obtained with a conjunctival impression device (method B). For each sample, the concentrations of a panel of 13 cytokines were measured by multiplex analyses. CADESI-4, pruritus (PS) and conjunctival (CS) scores were determined. RESULTS: Among the measured cytokines, only granulocyte-macrophage colony-stimulating factor (GM-CSF), keratinocyte-derived chemokine (KC)-like and interleukin (IL)-8 were above the limit of quantification in most samples. Absolute amounts of each cytokine were always higher in samples obtained with method A than with method B. GM-CSF amounts were lower in atopic dogs (method A, P=0.02; method B, P=0.0005). KC levels were higher in atopic dogs, yet the differences were not significant. IL-8 amounts were higher in atopic dogs (method A, P=0.0003; method B, P=0.006). CONCLUSIONS AND CLINICAL RELEVANCE: Regardless of the method, these preliminary results suggest an overexpression of IL-8 in conjunctivae and tears of atopic dogs despite subtle conjunctival symptoms. As IL-8 is commonly found in many inflammatory conditions, further studies are needed to determine its specificity in atopic conjunctivitis.
Subject(s)
Conjunctivitis, Allergic , Dog Diseases , Animals , Conjunctivitis, Allergic/diagnosis , Conjunctivitis, Allergic/veterinary , Cytokines , Dog Diseases/diagnosis , Dogs , Pilot Projects , Prospective Studies , TearsABSTRACT
Glial vulnerability to prions is assessed in murine Creutzfeldt-Jakob disease (CJD) using the tg340 mouse line expressing four-fold human PrP M129 levels on a mouse PrP null background at different days following intracerebral inoculation of sCJD MM1 brain tissues homogenates. The mRNA expression of several astrocyte markers, including glial fibrillary acidic protein (gfap), aquaporin-4 (aqp4), solute carrier family 16, member 4 (mct4), mitochondrial pyruvate carrier 1 (mpc1) and solute carrier family 1, member 2 (glial high-affinity glutamate transporter, slc1a2) increases at 120 and 180 dpi. In contrast, the mRNA expression of oligodendrocyte and myelin markers oligodendrocyte transcription factor 1 (olig1), olig2, neural/glial antigen 2 (cspg), solute carrier family 16, member 1 (mct1), myelin basic protein (mbp), myelin oligodendrocyte glycoprotein (mog) and proteolipid protein 1 (plp1) is preserved. Yet, myelin regulatory factor (myrf) mRNA is increased at 180 dpi. In the striatum, a non-significant increase in the number of GFAP-positive astrocytes and Iba1-immunoreactive microglia occurs at 160 dpi; a significant increase in the number of astrocytes and microglia, and a significant reduction in the number of Olig2-immunoreactive oligodendrocytes occur at 180 dpi. A decrease of MBP, but not PLP1, immunoreactivity is also observed in the striatal fascicles. These observations confirm the vulnerability and the reactive responses of astrocytes, together with the microgliosis at middle stages of prion diseases. More importantly, these findings show oligodendrocyte vulnerability and myelin alterations at advanced stages of murine CJD. They confirm oligodendrocyte involvement in the pathogenesis of CJD.
Subject(s)
Creutzfeldt-Jakob Syndrome , Prion Diseases , Animals , Astrocytes , Creutzfeldt-Jakob Syndrome/genetics , Mice , Myelin Sheath , OligodendrogliaABSTRACT
Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrPC) and transgenic PrPC from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called "interference," is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrPC, bovine and murine PrPC, or murine and porcine PrPC These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrPC from two different species. Our results indicate interference with the infection process, manifested as extended survival times and reduced attack rates. The interference with the infectious process was reduced or absent when the potentiality interfering PrPC species was efficiently converted by the inoculated agent. However, the propagation of the endogenous murine PrPSc was favored, allowing us to speculate that host-specific factors may disturb the interference caused by the coexpression of an exogenous second PrPCIMPORTANCE Prion propagation can be interfered with by the expression of a second prion protein in the host. In the present study, we investigated prion propagation in a host expressing two different prion protein genes. Our findings indicate that the ability of the second prion protein to interfere with prion propagation is related to the transmissibility of the prion in the host expressing only the interfering prion protein. The interference detected occurs in a prion strain-dependent manner. Interestingly, a bias favoring the propagation of the murine PrP allele has been observed. These results open the door to future studies in order to determine the role of host factors other than the PrP amino acid sequence in the interference in prion propagation.
Subject(s)
Alleles , Host-Pathogen Interactions/genetics , PrPC Proteins/genetics , PrPSc Proteins/genetics , PrPSc Proteins/metabolism , Prions/genetics , Prions/physiology , Amino Acid Sequence , Animals , Cattle/genetics , Disease Models, Animal , Mice , Mice, Transgenic , PrPC Proteins/metabolism , Scrapie , Swine/geneticsABSTRACT
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrPSc in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.
Subject(s)
Creutzfeldt-Jakob Syndrome/transmission , PrPSc Proteins , Adult , Aged , Aged, 80 and over , Animals , Female , Humans , Male , Mice , Middle AgedABSTRACT
This report describes the clinical features, histopathology, and surgical treatment of a case of conjunctival calcification in a 5-month-old female English Setter, referred with a history of recurrent conjunctivitis in the right eye (OD). The ophthalmic findings were limited to multifocal white plaques embedded in a markedly inflamed conjunctiva of the eyelids and the anterior nictitating membrane OD. Calcification was suspected. The blood cell count, blood chemical profile, and urinalysis were within normal limits, and long-bone radiographs appeared normal. After removal of the affected area by means of a large conjunctivectomy, cryopreserved canine amniotic membrane (AM) was transplanted to fill in the defect. Multifocal ectopic calcium deposits in the conjunctival lamina propria were confirmed histopathologically. The postoperative healing was uneventful, and no recurrence was observed during a follow-up period of five years. Conjunctival mineralization is uncommon in canine ophthalmology, and the cause remained undetermined in the present case, for which AM transplantation was able to promote conjunctival healing after a large surgical excision.
Subject(s)
Amnion/transplantation , Calcinosis/veterinary , Conjunctival Diseases/veterinary , Dog Diseases/surgery , Animals , Calcinosis/surgery , Combined Modality Therapy , Conjunctival Diseases/surgery , Dogs , FemaleABSTRACT
Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently classified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K-digested abnormal prion protein (PrPres) isoform identified by Western blotting (type 1 or type 2). Converging evidence led to the view that MM/MV1, VV/MV2, and VV1 and MM2 sCJD cases are caused by distinct prion strains. However, in a significant proportion of sCJD patients, both type 1 and type 2 PrPres were reported to accumulate in the brain, which raised questions about the diversity of sCJD prion strains and the coexistence of two prion strains in the same patient. In this study, a panel of sCJD brain isolates (n = 29) that displayed either a single or mixed type 1/type 2 PrPres were transmitted into human-PrP-expressing mice (tgHu). These bioassays demonstrated that two distinct prion strains (M1CJD and V2CJD) were associated with the development of sCJD in MM1/MV1 and VV2/MV2 patients. However, in about 35% of the investigated VV and MV cases, transmission results were consistent with the presence of both M1CJD and V2CJD strains, including in patients who displayed a "pure" type 1 or type 2 PrPres The use of a highly sensitive prion in vitro amplification technique that specifically probes the V2CJD strain revealed the presence of the V2CJD prion in more than 80% of the investigated isolates, including isolates that propagated as a pure M1CJD strain in tgHu. These results demonstrate that at least two sCJD prion strains can be present in a single patient.IMPORTANCE sCJD occurrence is currently assumed to result from spontaneous and stochastic formation of a misfolded PrP nucleus in the brains of affected patients. This original nucleus then recruits and converts nascent PrPC into PrPSc, leading to the propagation of prions in the patient's brain. Our study demonstrates the coexistence of two prion strains in the brains of a majority of the 23 sCJD patients investigated. The relative proportion of these sCJD strains varied both between patients and between brain areas in a single patient. These findings strongly support the view that the replication of an sCJD prion strain in the brain of a patient can result in the propagation of different prion strain subpopulations. Beyond its conceptual importance for our understanding of prion strain properties and evolution, the sCJD strain mixture phenomenon and its frequency among patients have important implications for the development of therapeutic strategies for prion diseases.
Subject(s)
Creutzfeldt-Jakob Syndrome/transmission , Genetic Variation , Prions/genetics , Animals , Biological Assay , Brain/pathology , Cell Line , Codon , Female , Humans , Methionine/genetics , Mice , PrPSc Proteins/genetics , Prions/classification , Protein Isoforms , Valine/geneticsABSTRACT
Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet129, TgMet/Val129, and TgVal129. L-type BSE showed a higher zoonotic potential in TgMet129 mice than classical BSE, whereas Val129-PrP variant was a strong molecular protector against L-type BSE prions, even in heterozygosis. H-type BSE could not be transmitted to any of the mice. We also adapted 1 H- and 1 L-type BSE isolate to sheep-PrP transgenic mice and inoculated them into human-PrP transgenic mice. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
Subject(s)
Encephalopathy, Bovine Spongiform , Prion Diseases , Prions , Animals , Brain/metabolism , Cattle , Europe , Mice , Mice, Transgenic , Prions/genetics , Prions/metabolism , SheepABSTRACT
OBJECTIVE: To assess the degree and duration of corneal anesthesia induced by topical application of 2% lidocaine gel to the healthy canine eye. ANIMALS: Nineteen adult Beagles free of ocular abnormalities. PROCEDURES: Baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. The 2% lidocaine gel (0.1 mL) was applied to one eye, randomly assigned, and the same volume of a lubricant gel was applied to the opposite eye. The CTT measurements were repeated bilaterally within 1 minute, after drug application, and every 5 minutes, until the baseline corneal sensitivity was restored. The potential for local adverse effects was evaluated. RESULTS: Complete desensitization of the cornea (CTT = 0) was achieved one minute after lidocaine gel application and was maintained during 25.3 ± 12.5 minutes. Overall, the corneal sensitivity was significantly decreased for 58.4 ± 16.6 minutes compared with baseline level. Minor and reversible punctate epithelial erosions of the cornea were observed in the two treatment groups and were attributed to the anesthetic effect and the aesthesiometry procedure. CONCLUSIONS: In the current study, the 2% lidocaine gel provided a sustained, deep and well-tolerated corneal anesthesia in ophthalmically normal dogs.
Subject(s)
Anesthetics, Local/pharmacology , Cornea/drug effects , Dogs/physiology , Lidocaine/pharmacology , Anesthetics, Local/administration & dosage , Animals , Female , Gels , Lidocaine/administration & dosage , Male , Ophthalmic SolutionsABSTRACT
Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE.
ABSTRACT
An 18-month-old Arabian-English filly resident in southwest France was referred for evaluation of a conjunctival mass in the right eye (OD). A pink, solid, and mobile nodular formation, measuring approximately 1.2 × 0.8 cm was found under the superior nasal bulbar conjunctiva during an ophthalmic examination that was otherwise normal. The mass was surgically removed using a standing procedure. Cytological examination of fine-needle aspirates from the mass revealed a mixed eosinophilic-lymphocytic inflammation. Histological examination confirmed the dense and diffuse eosinophilic-lymphocytic infiltrate of the mass, and it revealed several cross sections of a parasitic nematode. The morphometric diagnosis identified an immature form of a filarial worm, and molecular analysis of the mitochondrial cytochrome c oxydase subunit 1 (cox1) and 12S rRNA gene sequences led to further identification of the specimen as Setaria equina. Microfilaremia was not observed on fresh blood smears. There have been no signs of local recurrence after 18 months, nor any evidence of intraocular involvement. To the authors' knowledge, this is the first documented case of subconjunctival setariasis due to S equina in a horse.
Subject(s)
Conjunctiva/parasitology , Conjunctival Diseases/veterinary , Horse Diseases/parasitology , Nematode Infections/veterinary , Setaria Nematode/isolation & purification , Animals , Conjunctiva/pathology , Conjunctiva/surgery , Conjunctival Diseases/parasitology , Conjunctival Diseases/pathology , Conjunctival Diseases/surgery , Female , Horse Diseases/pathology , Horses , Nematode Infections/parasitology , Nematode Infections/pathology , Nematode Infections/surgery , Phylogeny , Setaria Nematode/geneticsABSTRACT
OBJECTIVE: To describe the phenotype of canine macular corneal dystrophy (MCD) including the clinical presentation, multimodal ocular imaging, histopathology, and ultrastructural analysis in ten Labrador Retrievers. PROCEDURE: Multicentered data collection. RESULTS: Labrador Retrievers affected by MCD were presented between the age of 4.5 and 6 years of age with a history of cloudy eyes and/or visual impairment. Findings on ophthalmic examination included a diffuse haze of the corneal stroma and multiple, well-demarcated, off-white to yellow-brown, punctate corneal opacities heterogeneous in size. Corneal vascularization developed in most dogs as the disease progressed. Disease progression was associated with increased density of the corneal haze as well as increased number and size of the focal opacities and dogs developed significant visual impairment. Spectral domain-optical coherence tomography revealed multifocal hyper-reflective regions within the stroma. In vivo confocal microscopy revealed marked alterations in reflectivity throughout the entire stroma. Normal keratocytes could not be identified in affected areas. Histopathology showed stromal collagen fibers separated by acidophilic granular material on hematoxylin and eosin stain. The material stained with periodic acid-Schiff and colloidal iron stain but not with Masson trichrome stain, confirming the accumulation of glycosaminoglycans. On electron microscopic ultrastructural examination, keratocytes presented with vacuolated rough endoplasmic reticulum and multiple electron dense cytoplasmic inclusions. In areas keratocytes appeared ruptured, with cell organelles and proteinaceous material grouped together between collagen fibers. CONCLUSION: MCD in Labrador Retrievers has similarities with the human counterpart of the condition and is an important differential diagnosis in dogs with corneal disease.