Chronic Epilepsy and Mossy Fiber Sprouting Following Organophosphate-Induced Status Epilepticus in Rats.

Organophosphate (OP) compounds are highly toxic and include pesticides and chemical warfare nerve agents. OP exposure inhibits the acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-induced SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). In male Sprague-Dawley rats, we assessed hippocampal pathology and chronic SRS following SE induced by administration of OP agents paraoxon (2 mg/kg, s.c.), diisopropyl fluorophosphate (4 mg/kg, s.c.), or O-isopropyl methylphosphonofluoridate (GB; sarin) (2 mg/kg, s.c.), immediately followed by atropine and 2-PAM. At 1-hour post-OP-induced SE onset, midazolam was administered to control SE. Approximately 6 months after OP-induced SE, SRS were evaluated using video and electroencephalography monitoring. Histopathology was conducted using hematoxylin and eosin (H&E), while silver sulfide (Timm) staining was used to assess mossy fiber sprouting (MFS). Across all the OP agents, over 60% of rats that survived OP-induced SE developed chronic SRS. H&E staining revealed a significant hippocampal neuronal loss, while Timm staining revealed extensive MFS within the inner molecular region of the dentate gyrus. This study demonstrates that OP-induced SE is associated with hippocampal neuronal loss, extensive MFS, and the development of SRS, all hallmarks of chronic epilepsy. SIGNIFICANCE STATEMENT: Models of organophosphate (OP)-induced SE offer a unique resource to identify molecular mechanisms contributing to neuropathology and the development of chronic OP morbidities. These models could allow the screening of targeted therapeutics for efficacious treatment strategies for OP toxicities.

Pulsed-field gel electrophoresis patterns and antimicrobial susceptibility phenotypes for coagulase-positive staphylococcal isolates from pustules and carriage sites in dogs with superficial bacterial folliculitis.

OBJECTIVE: To determine whether coagulase-positive staphylococcal isolates that are genotypically the same strain obtained from pustules and carriage sites of individual dogs with superficial bacterial folliculitis have the same antimicrobial susceptibility phenotype. ANIMALS: 40 dogs with superficial bacterial folliculitis. PROCEDURES: Samples were obtained from 3 pustules and 3 carriage sites (ie, anus, nonlesional axillary skin, and nasal mucosa) for bacterial culture, morphologic identification, Gram staining, catalase and coagulase testing, antimicrobial susceptibility testing, speciation, and pulsed-field gel electrophoresis (PFGE). RESULTS: 223 isolates from pustules and carriage sites were included. Seventeen susceptibility phenotypes were found among isolates. One hundred twenty-eight (100%) isolates from pustules and 95 (100%) isolates from carriage sites were susceptible to cephalothin; 128 (100%) isolates from pustules and 94 (98.9%) isolates from carriage sites were susceptible to amoxicillin-clavulanic acid; 114 (89.1%) isolates from pustules and 82 (86.3%) isolates from carriage sites were susceptible to erythromycin and lincomycin hydrochloride; and 103 (80.5%) isolates from pustules and 70 (73.7%) isolates from carriage sites were susceptible to trimethoprim-sulfamethoxazole. In 37 of 39 (94.9%) dogs, isolates with the same PFGE pattern from multiple pustules had the same susceptibility phenotype. In 21 of 33 (63.6%) dogs, isolates from multiple carriage sites with the same PFGE pattern had the same susceptibility phenotype. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with superficial bacterial folliculitis, most coagulase-positive staphylococcal isolates from pustules that are genotypically the same strain will have the same susceptibility phenotype and treatment may be based on empiric antimicrobial selection or susceptibility testing of 1 lesional isolate.

Genotypic relatedness of staphylococcal strains isolated from pustules and carriage sites in dogs with superficial bacterial folliculitis.

OBJECTIVE: To determine whether staphylococcal isolates cultured from pustules and carriage sites in dogs with superficial bacterial folliculitis were genotypically the same strain by use of pulsed-field gel electrophoresis (PFGE). ANIMALS: 40 dogs with superficial bacterial folliculitis. PROCEDURES: Samples were obtained from 3 pustules and 3 carriage sites (anus, axillary skin, and nasal mucosa). Bacterial culture, morphologic identification, Gram staining, catalase and coagulase tests, speciation, and PFGE were performed. RESULTS: Of 246 isolates, 203 were Staphylococcus intermedius, 5 were Staphylococcus aureus, 15 were Staphylococcusspp, and 22 were coagulase-negative staphylococcal isolates. No dog had an isolate with the same PFGE pattern as an isolate from another dog. Coagulase-positive isolates from multiple pustules and multiple carriage sites had the same PFGE pattern in 37 of 39 (94.9%) and 22 of 39 (56.4%) dogs, respectively. Coagulase-positive staphylococcal isolates from at least 1 pustule had the same PFGE pattern as an isolate from at least 1 carriage site in 34 of 36 (94.4%) dogs. Ninety-seven of 116 (83.6%) coagulase-positive staphylococcal isolates from pustules had the same PFGE pattern as an isolate from at least 1 carriage site. Sixty-nine of 91 (75.8%) coagulase-positive staphylococcal isolates from carriage sites had the same PFGE pattern as an isolate from at least 1 pustule. CONCLUSIONS AND CLINICAL RELEVANCE: Coagulasepositive staphylococcal strains were heterogeneous among dogs with superficial bacterial folliculitis. In individual dogs, strains from multiple pustules were genotypically the same, and strains from pustules were genotypically the same as strains from carriage sites.

Comparison of pulse administration versus once daily administration of itraconazole for the treatment of Malassezia pachydermatis dermatitis and otitis in dogs.

UNLABELLED: OBJECTIVE To compare clinical efficacy of pulse administration with itraconazole versus once daily administration for the treatment of cutaneous and otic M pachydermatis infection in dogs. DESIGN: Randomized controlled trial. ANIMALS: 20 dogs. PROCEDURE: Dogs were treated with itraconazole orally (n = 10/group), using a pulse administration regimen (5 mg/kg [2.3 mg/lb], PO, q 24 h for 2 consecutive days per week for 3 weeks) or once daily administration (5 mg/kg, PO, q 24 h for 21 days). No other treatment was permitted. On days 0 and 21, clinical severity of cutaneous and otic disease was assessed, and samples were collected for cytologic examination and yeast culture. Cytology (sum of the mean number of yeast organisms per oil immersion field for affected sites) and culture (mean of the score for extent of yeast growth for samples from affected sites) scores were calculated. RESULTS: For dogs in both treatment groups, clinical severity of cutaneous and otic disease was significantly decreased by day 21, but decrease in severity was not significantly different between groups. Similarly, skin cytology, skin culture, and ear culture scores were significantly decreased on day 21, compared with day 0, for both groups, but decreases were not significantly different between groups except that dogs in the pulse administration group had a significantly greater decrease in ear culture scores than did dogs in the daily administration group. However, when cytology scores only for ear samples were analyzed, day 21 score was not significantly decreased, compared with day 0 score, for either group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that both pulse administration and once daily administration of itraconazole were efficacious in the treatment of M pachydermatis cutaneous infection in dogs. However, adjunctive treatment may be needed in dogs with M pachydermatis otitis.