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Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine.

Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), apolipoproteins (apo) B, C-III, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals, exhibiting TC > or = 250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL-C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25%), LDL-C (-27%), lathosterol (-40%), apoB (-22%), apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (-12%) and apoA-I (-11%) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoA-I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC, LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swine is similar to that observed in humans, although the drugs is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.

Animals↗

Mechanism of decreased forward stroke volume in children and swine with ventricular septal defect and failure to thrive.

Children with ventricular septal defect (VSD) often demonstrate failure to thrive (FTT). Such patients usually have reduced systemic cardiac output which has been postulated as a cause for their growth retardation. This study was conducted to ascertain the mechanism of the reduced cardiac output in children with VSD and FTT and also in a porcine model of VSD. Forward stroke volume was reduced in VSD-FTT children, 31 +/- 8 ml/m2, compared to normal children, 49 +/- 15 ml/m2 (P less than 0.05), but was not reduced in children with VSD and normal growth and development (41 +/- 16 ml/m2). Forward stroke volume was also reduced in swine with VSD compared to controls. Contractility assessed by mean velocity of circumferential shortening (Vcf) corrected for afterload was similar in normals and VSD-FTT children. Contractile performance was also similar in normal and VSD swine. Afterload assessed as systolic stress was similar in FTT-VSD children and normal subjects. Preload assessed as end-diastolic stress was increased in the VSD-FTT group. End-diastolic volume was not larger in the VSD-FTT group. We conclude that the reduced stroke volume seen in VSD-FTT children and VSD-swine was not due to reduced contractility, increased afterload or reduced preload. The reduced stroke volume may have been due to failure of end-diastolic volume to increase adequately.

Animals↗

Articular cartilage blood vessels in swine osteochondrosis.

Perfusion studies in swine with early lesions of osteochondrosis demonstrated that lamellar areas of chondrocyte necrosis within reserve zones of growth areas occurred only in regions of nonperfused articular cartilage. Articular cartilage with a similar anatomical location was perfused in some animals. Occasionally, nonperfused articular cartilage showed vascular alterations within cartilage canals without evidence of significant perivascular or lamellar necrosis. By light microscopy, some vessels within or adjacent to nonperfused articular cartilage had normal morphology; however, ultrastructural abnormalities were found in some vessels of all cartilage canals adjacent to necrotic cartilage lamella. Minimal alterations were in the few cartilage canal vessels that appeared normal by light microscopy, and the surrounding chondrocytes showed only minimal alterations. Early cartilage canal alterations were seen in the endothelium of cartilage canal capillaries, and ultrastructural changes in these vessels were similar to those described with experimentally induced, direct vascular injury. Vascular injury was followed by leakage of plasma and cells into the interstitial space of the cartilage canal. Necrosis of the vessel wall and interstitial tissue caused the cartilage canals to appear empty or to be filled with fibrin-like material. Although the vascular changes could be considered as part of the normal process of cartilage maturation and cartilage canal chondrification, observations suggest that in domestic swine the attendant cartilage necrosis and chondrolysis is exuberant. It is suggested that alterations in cartilage canal vessels play a major role in the pathogenesis of articular cartilage lesions that are found in osteochondrosis of swine.

Animals↗

Comparison of GN Hajna and tetrathionate as initial enrichment for salmonellae recovery from swine lymph nodes and cecal contents collected at slaughter.

An epidemiologic survey was conducted to determine the prevalence of salmonellae in swine from 5 farms of an integrated swine operation. The purpose of this study was to evaluate the recovery efficiencies for salmonellae from swine lymph nodes and cecal contents when GN Hajna and tetrathionate were compared as initial enrichments. Salmonellae were isolated from 61% of 645 pigs at slaughter; 324 positive cultures were from lymph nodes, and 224 were from cecal contents. Frequently, pigs had salmonellae isolated from both the lymph nodes and cecal contents. Total isolations, regardless of source, were similar for GN Hajna (247) and tetrathionate (301). There was no difference (P > 0.05) in the number of isolations from lymph nodes when GN Hajna enrichment was compared with tetrathionate enrichment (174 vs. 150). However, there was a significant (P < 0.05) advantage of utilizing tetrathionate when compared with GN Hajna for isolations from cecal contents (151 vs. 73).

Abattoirs↗

African swine fever virus infection of skin-derived dendritic cells in vitro causes interference with subsequent foot-and-mouth disease virus infection.

Highly purified skin-derived dendritic cells (SDDCs) isolated from swine skin by a simple novel method were cultured for 24 hours before independent or sequential inoculation with African swine fever virus (ASFV) and foot-and-mouth disease virus (FMDV). By avidin-biotin immunohistochemical staining, ASFV antigen was detected in 50% of SDDCs as early as 1.5 hours postinfection (HPI) and in 80% by 3 HPI when cytopathic effect was noted. Cell lysis was detected with FMDV infection as early as 8 HPI; immunostaining for FMDV antigen was found in 10% of the cells. African swine fever virus replication was detected by transmission electron microscopy in a high percentage of SDDCs by 11 HPI. Sequential infection with FMDV 3 hours after ASFV inoculation blocked FMDV infection. These findings demonstrate that both ASFV and FMDV infect dendritic cells of Langerhans cell type in vitro and ASFV interferes with FMDV infection.

African Swine Fever Virus↗

A limited interval of delayed modest hypothermia for ischemic brain resuscitation is not beneficial in neonatal swine.

This investigation determined if a short interval of modest hypothermia (1 h) initiated 30 min after brain ischemia provided neuroprotection. The rationale for the time and duration of brain cooling reflects the likelihood that the implementation of neuroprotective strategies will occur at an interval shortly after ischemia, and that long-term maintenance of normothermia is a cornerstone of neonatal stabilization. Studies were performed in 22 ventilated neonatal mini-swine in a superconducting magnet to obtain 31P magnetic resonance spectra. After a control period all animals underwent 15 min of global brain ischemia and were maintained normothermic for the first 30 min post-ischemia. In one group of 11 swine normothermia was continued. In the other group of 11 swine, modest hypothermia was initiated at 30 min post-ischemia, continued for 1 h and followed by resumption of normothermia. Animals were subsequently weaned from ventiltor support, removed from the magnet, and underwent neurobehavioral and histologic assessment at 72 h post-ischemia. Both groups had similar severity of ischemia, as indicated by identical changes in arterial blood pressure and pH, alterations in brain beta-nucleotide triphosphate (% of control where control = 100%, 32 +/- 28 vs 27 +/- 26% for normothermic and hypothermic groups, respectively), and the extent of intraischemic brain acidosis (6.13 +/- 0.19 vs 6.14 +/- 0.14 for normothermic and hypothermic groups, respectively). In both groups the distribution of stages of encephalopathy were the same: 1 normal and 10 abnormal (4 mild, 2 moderate, and 4 severe) normothermic, and, 3 normal and 8 abnormal (4 mild, 2 moderate, and 2 severe) hypothermic animals. There was no difference in the extent of neuronal injury between groups. We conclude that a 1-h interval of modest hypothermia initiated at 30 min post-ischemia does not confer neuroprotection.

Animals↗

Immunization of rabbits against Pasteurella multocida using a commercial swine vaccine.

Elaboration of heat-labile toxin (PMT) is an important virulence factor in some isolates of Pasteurella multocida from rabbits. Previously, we reported that immunization with inactivated PMT (IPMT) stimulated protective immunity to challenges from PMT. To test the hypothesis that immunization with a commercial swine vaccine containing IPMT stimulates similar protective immunity, groups of five rabbits were inoculated twice intramuscularly (i.m.), 10 days apart, with 0.5 ml of sterile saline or a commercial swine P. multocida bacterin-toxoid (BT). In addition, a group was inoculated intranasally with 5 microg of IPMT. Serum and nasal lavage samples were taken on days 0, 7, 14 and 21 after initial immunization and assayed by ELISA for anti-PMT antibody. Serum IgG and nasal lavage IgA were detectable by day 14 in BT and IPMT-immunized rabbits, but not in the saline controls. Groups of similarly inoculated rabbits were then challenged intranasally with 28 microg of PMT 21 days after initial immunization, and necropsied 7 days later, along with control challenged and non-challenged rabbits. Histological lesion severity was graded on a numerical scale. Non-immunized and saline, challenged controls developed more severe pneumonia, pleuritis, nasal turbinate atrophy and testicular atrophy than IPMT and BT-immunized rabbits. The results confirm the hypothesis that immunization with a commercial swine P. multocida BT confers protective immunity in rabbits against challenges from PMT.

Animals↗

Detection of antibodies against porcine reproductive and respiratory syndrome (PRRS) virus in swine sera by enzyme-linked immunosorbent assay.

We developed an enzyme-linked immunosorbent assay (ELISA) to detect antibodies against PRRS virus in swine sera. The ELISA antigen was prepared from MARC-145 cells infected with PRRS virus. The results from serial serum samples from experimentally infected and random swine indicated that the ELISA was more sensitive than indirect fluorescent and immunoperoxidase monolayer assays. Since the ELISA enables many sera to be simultaneously and rapidly tested, it was useful for detection antibodies against PRRS virus in swine sera.

Animals↗

Early epithelial invasion by Salmonella enterica serovar Typhimurium DT104 in the swine ileum.

Salmonella enterica serovar Typhimurium is an important intestinal pathogen in swine. This study was performed to document the early cellular invasion of Salmonella serovar Typhimurium in swine ileum. Ileal gut-loops were surgically prepared in ten 4- to 5-week-old mixed-breed pigs and inoculated for 0-60 minutes. Loops were harvested and prepared for both scanning and transmission electron microscopy (SEM and TEM, respectively). Preferential bacterial adherence to microfold cells (M cells) was seen within 5 minutes, and by 10 minutes bacterial invasion of the apical membrane was seen in M cells, goblet cells, and enterocytes. This multicellular invasion was observed throughout the course of infection. In addition, SEM revealed a specific affinity of Salmonella serovar Typhimurium to sites of cell extrusion. Using TEM, bacteria in these areas were focused in the crevices formed by the extruding cell and the adjacent cells and in the cytoplasm immediately beneath the extruding cell. Our results suggest that early cellular invasion by Salmonella serovar Typhimurium is nonspecific and rapid in swine. Furthermore, the combination of SEM and TEM data suggests that Salmonella serovar Typhimurium may use sites of cell extrusion as an additional mechanism for early invasion.

Animals↗

[Göttingen miniature swine as a model for diet-induced atherosclerosis].

Twenty-four Göttingen Miniature Swine/csk, in order to evaluate their potential usefulness as a model for experimental atherosclerosis studies, were fed diets of three types, a high-fat plus high cholesterol diet, a high-fat diet, and a commercial diet. Each group consisted of 4 males and 4 females. Swine fed the experimental diet were investigated by gross, microscopic and serum biochemical examination on the 1st, 3rd, 6th and 9th month after start of experimentation. Lesions of atherosclerosis were observed in the high-fat plus high-cholesterol diet group. After a month on the experimental diet, intimal thickening was detected in the abdominal aorta just above the origin of internal iliac artery, left coronary artery and ascending aorta by microscopic examination. Thereafter, on the 9th month after the start, there was more extensive and severe atherosclerosis. These lesions were classified into two types by the difference in the histologic architecture of arterial wall. One was fatty streaks that were in thoracic aorta belonging to the elastic type and the other was fibrous plaques that were in abdominal aorta and iliac artery and so on, belong to the transitional or muscular type. High-fat plus high-cholesterol diet feeding led to elevated serum cholesterol and beta-lipoprotein levels, and had an effect on several kinds of metabolism. All of the swine fed high-fat or commercial diet had little gross, microscopic lesions and had no change in serum cholesterol and beta-lipoprotein levels. Hypercholesterolemia and hyper-beta-lipoproteinemia had a close relation to the development and acceleration of atherosclerosis. It was possible to show that the diet induced atherosclerosis was similar in quality to that observed in humans, and that the Göttingen miniature swine was a suitable animal for the study of atherosclerosis.

Animals↗

[Tuberculosis lymphadenitis in slaughtered swine from the State of São Paulo, Brazil: microscopic histopathology and demonstration of mycobacteria].

INTRODUCTION: As the occurrence of tuberculosis lymphadenitis in swine constitutes a public health risk, especially in immunosuppressed individuals, the distribution of tuberculoid lesions and the presence of microbacteria in lymph nodes and hepatic and muscular tissue in swine for slaughter, in the State of S. Paulo, SP (Brazil), in the period from 1993 to 1994, were studied. MATERIAL E METHOD: Tuberculous lesions in 60 carcasses of swine, slaughtered at abattoirs during the period 1993-1994, were studied. When macroscopic lesions were observed, a representative sampling of lymph nodes, hepatic and muscular tissues (masseter and diaphragm) were examined using histopathological and microbacterial isolation techniques. RESULTS: The macroscopic lesions were found predominantly in mesenteric lymph nodes. The MAI Complex (M.avium-intracellulare) was isolated mainly in the carcass group that showed lesions and was not found in the control group. Microorganisms of the MAI Complex were not isolated from hepatic and muscular tissues. CONCLUSION: No clear relationship between the type of mycobacteria isolated and the macroscopic lesions observed during the carcass inspection was found.

Animals↗

Effect of free gingival grafts on naturally-occurring recession in miniature swine.

Miniature swine exhibit naturally-occurring, progressive recession on facial surfaces of the permanent mandibular incisors. The purpose of this study was to determine whether placing a free gingival graft to augment the width of keratinized gingiva of mandibular incisors in miniature swine would prevent or retard recession at the grafted site compared to an untreated contralateral control site. In 8 litter-mate miniature swine, free gingival grafts were placed on the facial surface of the permanent central and lateral incisors on one side of the mandible. The contralateral mandibular incisors did not receive any treatment and served as controls. Clinical measurements, including eruption, recession, pocket depth, attachment level, and keratinized gingival width were obtained preoperatively, 2 to 3 weeks after surgery to assess the success of gingival augmentation, and 3, 6, and 9 months postoperatively. Eight grafted sites were successful and showed significant augmentation of the keratinized gingival width, with a mean increase of 5.8 +/- 0.7 mm, while 6 grafts failed and showed a slight decrease in the mean width of -0.4 +/- 0.5 from the preoperative to postoperative examination. All sites showed significant recession during the experimental period. Successful sites showed no statistically significant or clinically major difference in the rate or amount of recession than contralateral control sites. By 9 months, the average increase in recession from the baseline examination was 2.8 +/- 1.5 mm for successfully grafted sites and 2.6 +/- 1.3 mm for contralateral controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Yucatan miniature swine as a model for the study of human diabetes mellitus.

Two lines of Yucatan miniature swine have been developed by genetic selection for decreased and increased glucose clearance during an i.v. glucose tolerance test. The decreased glucose clearance is due to low peripheral insulin levels usually from a decrease in insulin secretion. In two pigs the decreased peripheral insulin resulted from increased hepatic uptake of insulin. During gestation and lactation, an increased insulin resistance and a diabetic-like state occurs in some animals. When fed a low fiber diet that contains 40% of calories from saturated fat (a typical American diet), Yucatan swine become more glucose intolerant. Seven to ten animals on the diet from the glucose intolerant line showed a glucose tolerance curve that would have been classified as diabetic if they were humans utilizing both intravenous and oral glucose tolerance tests. Miniature swine from this line are available to interested researchers.

Animals↗

Failure of genetically selected miniature swine to model NIDDM.

Ten young adult miniature swine from a line reported to be genetically selected for glucose intolerance and eight normal controls were obtained from Colorado State University. They were consecutively exposed to 4 mo of a high-fiber, low-fat standard swine diet; 4 mo of a high-sucrose, high-fat, low-fiber diabetogenic diet; and 4 mo of excess diabetogenic diet for obesification. Results of oral glucose tolerance and intravenous insulin tolerance tests conducted at the end of each regimen were compared. Hyperglycemia was not observed in any animals after any manipulation. Insulin sensitivity was also not influenced by diet. We conclude that F7 low-K miniature swine from this colony fail to model human non-insulin-dependent diabetes.

Animals↗

Use of real-time reverse transcriptase polymerase chain reaction assay and cell culture methods for detection of swine influenza A viruses.

OBJECTIVE: To evaluate sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay performed on pooled nasal swab specimens, compared with virus isolation performed on individual nasal swab specimens by use of 2 cell culture lines for detection of swine influenza A viruses. SAMPLE POPULATION: 900 nasal swab specimens obtained from pigs at an abattoir and 62 nasal swab specimens submitted for diagnostic testing. PROCEDURES: Primers were chosen to amplify a conserved portion of the influenza virus matrix gene. Assay sensitivity was initially determined by testing serial dilutions of various subtypes of swine influenza viruses. Sensitivity and specificity were confirmed by use of nasal swab specimens with or without addition of known concentrations of influenza virus and further validated by testing nasal swab specimens obtained through an abattoir surveillance program or submitted for diagnostic testing. Aliquots of specimens were pooled in sets of 10, and results of real-time RT-PCR assays were compared with results of virus isolation of individual specimens in Madin Darby canine kidney (MDCK) and mink lung (Mv1Lu) cells. RESULTS: Real-time RT-PCR assay was highly specific (100%) and sensitive (88% to 100%). Among the 16 viruses isolated, 3 grew only in Mv1Lu cells and 3 grew only in MDCK cells. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that real-time RT-PCR assay is a fast and accurate test for screening numerous nasal swab specimens for swine influenza virus. Some viruses were isolated in only MDCK or Mv1Lu cells, indicating that use of >1 cell line may be required to isolate a broad range of influenza A viruses.

Animals↗

Analysis of the 1998 outbreak of leptospirosis in Missouri in humans exposed to infected swine.

OBJECTIVE: To determine the extent of leptospirosis in persons exposed to infected swine, confirm the source of disease, define risk factors for infection, and identify means for preventing additional infections during an outbreak in Missouri in 1998. DESIGN: Cross-sectional study. SAMPLE POPULATION: 240 people and 1,700 pigs. PROCEDURE: An epidemiologic investigation was conducted of people exposed to infected pigs from the University of Missouri-Columbia swine herd. The investigation included review of health of the pigs, a cross-sectional study of the people handling the pigs, serologic testing of human and porcine sera, and risk-factor analysis for leptospirosis within the human population. RESULTS: Serologic testing of samples collected at the time of the investigation indicated that 59% of the pigs had titers to leptospires, denoting exposure. Of the 240 people in the exposed study population, 163 (68%) were interviewed, and of these, 110 (67%) submitted a blood sample. Nine (8%) cases of leptospirosis were confirmed by serologic testing. Risk factors associated with leptospirosis included smoking (odds ratio [OR], 14.4; 95% confidence interval [CI], 1.39 to 137.74) and drinking beverages (OR, 5.1; 95% CI, 1.04 to 24.30) while working with infected pigs. Washing hands after work was protective (OR, 0.2; 95% CI, 0.03 to 0.81). CONCLUSIONS AND CLINICAL RELEVANCE: Leptospirosis is a risk for swine producers and slaughterhouse workers, and may be prevented through appropriate hygiene, sanitation, and animal husbandry. It is essential to educate people working with animals or animal tissues about measures for reducing the risk of exposure to zoonotic pathogens.

Abattoirs↗

Occurrence of Salmonella serotype Typhimurium DT104 on a commercial swine farm before, during, and after depopulation and repopulation.

OBJECTIVE: To determine whether depopulation-repopulation could be used to eradicate Salmonella serotype Typhimurium DT104 from a commercial swine farm in the midwestern United States. DESIGN: Observational study SAMPLE POPULATION: A commercial swine farm undergoing depopulation-repopulation to eliminate porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae. PROCEDURE: Pooled fecal samples, tissue samples, and serum samples were collected from pigs on the farm before and after depopulation-repopulation. When there were no pigs on the farm, environmental swab specimens were collected for bacterial culture. Serum was analyzed for anti-Salmonella antibodies with an indirect ELISA. Salmonella isolates obtained by bacterial culture of fecal, tissue, and environmental samples were characterized by means of serotyping, phage typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. RESULTS: 167 Salmonella isolates representing 9 serotypes were recovered from the farm. Results of PFGE and antimicrobial susceptibility testing suggested that S. Typhimurium DT104 strain was not eradicated from the farm. However, seroprevalence of anti-Salmonella antibodies and the percentage of pooled fecal samples positive for Salmonella spp were significantly decreased following repopulation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that depopulation-repopulation in conjunction with stringent cleaning and disinfection, attention to biosecurity procedures, control of other diseases, and changes in feed management may reduce the occurrence of, but likely will not eliminate, Salmonella spp in commercial swine herds.

Animal Husbandry↗

Conception failure in swine: importance of the sex ratio of a female's birth litter and tests of other factors.

Failure of gilts and sows to conceive when they are mated is a potentially serious economic cost for swine producers. In Exp. 1, we determined that anogenital distance of newborn gilts is related to the proportion of males in the litter (P < .001). Gilts from litters with more males have larger anogenital distances (mean = 8.0 +/- .2 mm); those from litters with low proportions of males have smaller anogenital distances (mean = 5.7 +/- .1 mm). In Exp. 2, we examined the effect of birth litter sex ratio of sows and gilts on reproductive performance using a 13-yr database of breeding and litter data. Gilts that failed to become pregnant on the first breeding attempt came from litters with significantly higher proportions of males than gilts that successfully conceived on the first breeding attempt. Overall, female swine were significantly more likely to exhibit lower rates of successful breeding during their first four breeding attempts if they had been born in a male-biased litter. These results have implications for swine producers deciding which gilts to keep and which to market. Given the higher probability of reproductive problems for gilts from litters of 12 or more pigs with 67% or more males, these females should likely become market hogs. Sow's age, mode of insemination, and the number of insemination attempts at an estrus period, but not season, can affect successful breeding.

Age Factors↗