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Objective— Hypercholesterolemia and hypertension are associated with aortic valve stenosis (AVS) in humans. We have examined aortic valve function, structure, and gene expression in hypercholesterolemic/hypertensive mice. Approach and Results— Control, hypertensive, hypercholesterolemic ( Apoe −/− ), and hypercholesterolemic/hypertensive mice were studied. Severe aortic stenosis (echocardiography) occurred only in hypercholesterolemic/hypertensive mice. There was minimal calcification of the aortic valve. Several structural changes were identified at the base of the valve. The intercusp raphe (or seam between leaflets) was longer in hypercholesterolemic/hypertensive mice than in other mice, and collagen fibers at the base of the leaflets were reoriented to form a mesh. In hypercholesterolemic/hypertensive mice, the cusps were asymmetrical, which may contribute to changes that produce AVS. RNA sequencing was used to identify molecular targets during the developmental phase of stenosis. Genes related to the structure of the valve were identified, which differentially expressed before fibrotic AVS developed. Both RNA and protein of a profibrotic molecule, plasminogen activator inhibitor 1, were increased greatly in hypercholesterolemic/hypertensive mice. Conclusions— Hypercholesterolemic/hypertensive mice are the first model of fibrotic AVS. Hypercholesterolemic/hypertensive mice develop severe AVS in the absence of significant calcification, a feature that resembles AVS in children and some adults. Structural changes at the base of the valve leaflets include lengthening of the raphe, remodeling of collagen, and asymmetry of the leaflets. Genes were identified that may contribute to the development of fibrotic AVS.

Antimicrobial therapy continues to be important in reducing losses due to pneumonic forms of Mycoplasma bovis disease in beef and dairy calves. Although M. bovis diseases have been documented as frequent and economically important in the United States, there are no published reports on the antimicrobial activity of approved compounds against US strains. In this study, the authors report on the activity of 9 different antimicrobials against 223 recently recovered isolates of M. bovis. These isolates represent accessions from 5 geographic regions of the United States and were grouped by 4 tissues of origin (milk, respiratory, joint, or ear and eye). A broth microdilution test was used to determine minimum inhibitory concentration (MIC) values by reading redox changes detected in broth with alamarBlue (resazurin) indicator. For each antimicrobial, the median, MIC50, MIC90, mode, and range were calculated, and the values used for comparisons. In the absence of accepted breakpoint values, published MIC cutoff values for animal mycoplasmas as well as Clinical Laboratory Standards Institute interpretive criteria were used as a reference to define in vitro activity. The MIC values from active antimicrobials were found to distribute independently of region of origin of the isolates or of tissue of origin. Enrofloxacin, florfenicol, and spectinomycin were found to be active compounds in vitro. Oxytetracycline and chlortetracycline were active against more than half of the isolates. Very few isolates were inhibited by tilmicosin and none by erythromycin, ampicillin, or ceftiofur. The antimicrobial profiles determined for these US strains were remarkably similar to those reported for European isolates. However, unlike in Europe, there appears to be no diversity of profiles when US isolates are grouped by region or tissue of origin.

This survey was undertaken to determine the relative frequency of agents that are currently associated with neonatal diarrhea in swine, including Clostridium difficile and porcine reproductive and respiratory syndrome virus (PRRSV). The subjects for this study were the first 100 live 1–7-day-old piglets submitted to the Iowa State University Veterinary Diagnostic Laboratory with a clinical signalment of diarrhea, beginning on January 1, 2000. The evaluation of each pig included bacterial culture of a section of ileum, 2 sections of jejunum, and a single section of colon; a fluorescent antibody test (FAT) or immunohistochemistry (IHC) for transmissible gastroenteritis virus (TGEV); ELISA's for rotavirus and C. difficile toxins; IHC for PRRSV; and microscopic examination of ileum, midjejunum, spiral colon, liver, spleen, and lung. Survey results demonstrate a decline in the relative number of diagnoses of TGEV, Escherichia coli, and Clostridium perfringens type C compared with retrospective data. The combined case frequency rate for these 3 pathogens dropped from 70% in 1988 to 21% in 2000. This survey also demonstrated the emergence of C. difficile as an important pathogen of neonatal swine. Clostridium difficle toxin was detected in the colon contents of 29% of the piglets, and at least 1 toxin-positive animal was identified in 55% of the cases. All 29 C. difficile toxin-positive piglets had mesocolonic edema, and colitis was observed in 21 of 29 toxin-positive animals. PRRSV-positive macrophages were detected in the lamina propria of intestinal villi by IHC in 10 piglets with diarrhea. In 6 of these cases, PRRSV was the only pathogen detected. Gross and microscopic lung lesions were not a reliable indicator of PRRSV infection in these neonatal pigs with diarrhea. The addition of tests for C. difficile and PRRSV to a routine neonatal diarrhea diagnostic protocol resulted in a significant increase in the diagnostic success rate on both individual animal and case bases.