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Genetic and other effects on bacterial phagocytosis and killing by cultured peripheral blood monocytes of SLA-defined miniature pigs.

The influence of miniature swine major histocompatibility complex genes (SLA) upon phagocytic and bactericidal activities of peripheral blood monocytes against Salmonella typhimurium and Staphylococcus aureus was measured in vitro using cultured cells and bacterial/enzyme-dependent tetrazolium dye (MTT) reduction. Haplotype significantly influenced uptake and killing of each bacterium by monocytes of 4- and 8-week-old pigs. Cells from 4-week-old SLA ad and aa pigs were significantly better than all others at phagocytizing S. aureus and cells from dg and gg were poorest. Killing of S. aureus was highest at 4 weeks in SLA cd pigs and in dg and gg pigs at 8 weeks of age. Uptake and killing of S. typhimurium was highest in homozygous aa and cc haplotypes at 4 weeks and pigs with the c x d recombinant haplotype had highest uptake and killing of S. typhimurium at 8 weeks. Litter, but not sire, also influenced significantly the uptake and killing of S. aureus and S. typhimurium.

Animals↗

Common swine leucocyte antigen (SLA) haplotypes in NIH and Sinclair miniature swine have similar effects on the expression of an inherited melanoma.

Mixed lymphocyte culture and serological typing of NIH and Sinclair miniature swine indicate that the two herds share a common SLA haplotype. NIH haplotype a (International Haplotype H10) appears identical to Sinclair haplotype B, which has significant effects on the penetrance of Sinclair swine cutaneous malignant melanoma (SSCM). Offspring of crosses between melanoma-bearing Sinclair swine homozygous for the B haplotype and non-melanoma NIH aa swine have tumour incidence identical to Sinclair melanoma BB x Sinclair non-melanoma BB offspring. Our results provide further support for the involvement of the swine leucocyte antigen (SLA) complex in the inheritance of SSCM, and identify a new source of non-tumour animals that have all of the genes for SSCM except those at the tumour-initiator locus.

Animals↗

Effect of unilateral bite splint on mastication in the miniature pig.

Unilateral premature occlusal contacts are known to alter masticatory activity levels during clenching, but whether natural chewing is similarly affected is not known. The purpose of this study was to analyse the effects of a unilateral bite splint on mastication. Eleven experiments were carried out using three miniature pigs. Electromyography of the masticatory muscles and movements of the jaw were recorded during natural chewing before and after inserting a bite splint on the second and third deciduous premolars. In contrast to human clenching, the integrated activities of the jaw-closing muscles increased, especially on the contralateral side. The increases were mainly due to the prolongation of the burst durations. Jaw opening activity was increased as well. The frequency of mastication fell slightly and the animal preferred to chew food on the bite splint side. These results demonstrate the importance within the particular experimental conditions of the occlusal condition in regulating chewing behaviour.

Animals↗

Time series analysis of jaw muscle contraction and tissue deformation during mastication in miniature pigs.

Masticatory muscle contraction causes both jaw movement and tissue deformation during function. Natural chewing data from 25 adult miniature pigs were studied by means of time series analysis. The data set included simultaneous recordings of electromyography (EMG) from bilateral masseter (MA), zygomaticomandibularis (ZM) and lateral pterygoid muscles, bone surface strains from the left squamosal bone (SQ), condylar neck (CD) and mandibular corpus (MD), and linear deformation of the capsule of the jaw joint measured bilaterally using differential variable reluctance transducers. Pairwise comparisons were examined by calculating the cross-correlation functions. Jaw-adductor muscle activity of MA and ZM was found to be highly cross-correlated with CD and SQ strains and weakly with MD strain. No muscle's activity was strongly linked to capsular deformation of the jaw joint, nor were bone strains and capsular deformation tightly linked. Homologous muscle pairs showed the greatest synchronization of signals, but the signals themselves were not significantly more correlated than those of non-homologous muscle pairs. These results suggested that bone strains and capsular deformation are driven by different mechanical regimes. Muscle contraction and ensuing reaction forces are probably responsible for bone strains, whereas capsular deformation is more likely a product of movement.

Animals↗

The tissue distribution of Ia- and IgM-positive cells in adult and newborn miniature pigs.

Distribution of Ia- and IgM-positive cells was compared in tissues of adult and newborn miniature pigs, using indirect immunoperoxidase and immunofluorescent techniques with monoclonal antibodies. The different distribution patterns were found mainly in adult jejunum and kidney. Both IgM- and Ia-staining were ascertained in the lamina propria between the Lieberkühn crypts and in the lymphoid follicles of the jejunum. Moreover, IgM-positive cells were demonstrated in the crypts while Ia-reaction was seen in the lamina propria of the villi. In the kidney, IgM-staining was limited to the glomeruli. On the contrary, a distinct Ia-reaction was found mainly in intertubular structures. Small differences in IgM- and Ia-positive cell distribution were also noted in the mesenteric lymph nodes and in the spleen. Developmental changes of the adult distribution patterns (chiefly that of IgM-positive cells) were found in all tissues studied at 2 days of age.

Aging↗

Cytochemical localization of glycoconjugates in the secretory epithelial cells lining the prostate gland of the miniature pig.

The aim of the study was to emphasize several specific functional aspects of the mammalian prostate gland. In this connection, the subcellular localization and characterization of glycoconjugates in the secretory epithelial cells were examined that line the prostate gland of the miniature pig, using cytochemistry, including lectin-gold methods. The results verified a diversified pattern of glycoconjugates in the structures of the secretory cells. The secretory granules and the free surface coat of the plasma membrane contained several sugar moieties such as alpha-D-Man, alpha-D-Glc, alpha-L-Fuc, beta-D-Gal, GalNAc, GlcNAc and NeuAc (sialic acid), whereas the Golgi apparatus exhibited GlcNAc and sialic acid residues. In addition, the cisterns of the endoplasmic reticulum showed alpha-D-Man and alpha-D-Glc moieties. It seems likely that the secretory glycoconjugates demonstrated contribute to favourable conditions for fertilization.

Animals↗

Establishment of a pneumococcal septicemia model in the miniature swine.

Human pneumococcal septicemia, the prominent postsplenectomy complication, was as yet difficult to study in the porcine model, since this species appeared to be fairly resistant against pneumococcal infections. We have used two strains of pneumococci (serotype 1 and 6B) both of which had been isolated from patients with systemic infection and both of which were maintained in a virulent state by regular mouse passage. After challenge with 10(9) type 1 pneumococci, however, only one of the 5 pigs developed fever, none showed profound hematological alterations and each animal exhibited a rapid clearance of bacteria from peripheral blood. By contrast, challenge of 7 animals with type 6B pneumococci resulted in a slower and incomplete bacterial clearance with persistent bacteremia for up to 24 hours. All animals developed fever and a profound leukopenia with less than 5,000 leukocytes/ml and 3 of the 7 animals died after injection of type 6B pneumococci. The results show that potentially the type 6B pneumococci can be successfully employed for studies of gram positive septicemia in the miniature swine.

Animals↗

Effect of cisapride on myoelectrical activity of the gastrointestinal tract in the conscious miniature pig.

In conscious miniature pigs with electrodes implanted in the wall of the antrum pylori, duodenum, jejunum, ileum and caecum, the influence of intravenous injection of cisapride, 0.5 and 1 mg/kg, on gastrointestinal myoelectrical activity, was examined. Cisapride, 1 mg/kg, induced a delayed and sustained increase in antral myoelectrical activity. The studied intestinal segments were rather insensitive to the stimulating effect of the benzamide, since only the jejunum and the caecum revealed an increase in myoelectrical activity with the higher dose studied.

Animals↗

Effect of some gastrointestinal hormones on antral, small intestinal and caecal myoelectrical activity in the conscious miniature pig.

The effect of i.v. infusion of gastrin (CCK-4), cholecystokinin (CCK-8) and pancreatic polypeptide (PP), 20 and 200 ng/kg/min for 1 h, on gastrointestinal electrical activity and arterial pressure was studied in conscious miniature pigs. During infusion of CCK-8 a transient hypertension was observed. In the antrum, the 3 peptides provoked an increase in slow wave activity and a decrease in spike activity. In the intestine, CCK-8 induced an increase in ileal spiking activity, whereas infusion of PP resulted in an increased frequency of long spike bursts in the caecum.

Animals↗

Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine.

1. The purpose of these experiments was to use radiolabelled microspheres to measure blood flow distribution within the brain, and in particular to areas associated with motor function, maintenance of equilibrium, cardiorespiratory control, vision, hearing and smell, at rest and during exercise in miniature swine. Exercise consisted of steady-state treadmill running at intensities eliciting 70 and 100 % maximal oxygen consumption (V(O(2),max)). 2. Mean arterial pressure was elevated by 17 and 26 % above that at rest during exercise at 70 and 100 % V(O(2),max), respectively. 3. Mean brain blood flow increased 24 and 25 % at 70 and 100 % V(O(2),max), respectively. Blood flow was not locally elevated to cortical regions associated with motor and somatosensory functions during exercise, but was increased to several subcortical areas that are involved in the control of locomotion. 4. Exercise elevated perfusion and diminished vascular resistance in several regions of the brain related to the maintenance of equilibrium (vestibular nuclear area, cerebellar ventral vermis and floccular lobe), cardiorespiratory control (medulla and pons), and vision (dorsal occipital cortex, superior colliculi and lateral geniculate body). Conversely, blood flow to regions related to hearing (cochlear nuclei, inferior colliculi and temporal cortex) and smell (olfactory bulbs and rhinencephalon) were unaltered by exercise and associated with increases in vascular resistance. 5. The data indicate that blood flow increases as a function of exercise intensity to several areas of the brain associated with integrating sensory input and motor output (anterior and dorsal cerebellar vermis) and the maintenance of equilibrium (vestibular nuclei). Additionally, there was an intensity-dependent decrease of vascular resistance in the dorsal cerebellar vermis.

Animals↗

A miniaturized centrifugal pump for assist circulation.

The newly developed Nikkiso HMS-15 is a miniaturized centrifugal pump. It has an impeller diameter of only 50 mm and a priming volume of only 25 ml. A totally new approach was applied to develop this very small pump. The new pump showed comparable hemolysis with pumps twice as big (e.g., the most widely used cone-shaped centrifugal pump [index of hemolysis, 0.005]). This finding refutes the belief that the pump diameter must be sufficiently large in size. Clinical application for cardiac assist was performed for 48 h without any thrombus formation despite low heparin dosage. Also, the pump showed quite favorable blood trauma when applied as a pump for cardiopulmonary bypass during open heart surgery. The compactness, the high controllability, and the system versatility proved to be very effective for clinical application. This pump is considered very reliable for its highly optimized design.

Aged↗

Mechanical unloading with a miniaturized axial flow pump (hemopump): an experimental study.

A family of miniaturized axial flow pumps has been developed, including the Hemopump, the 14-F, and the 21-F HP, which were especially designed for cardiological use. We designed an experimental set-up to study the unloading properties of these devices in a model of regional stunning in an anesthetized, open thorax preparation in sheep. Stunning was caused by 15-min occlusion of the diagonal branch of the left anterior descending coronary artery with subsequent 90 min of reperfusion. Regional myocardial function was assessed by sonomicrometry. A control group was compared with 2 groups with either mechanical unloading during part of ischemia (Group 2) or the early phase of reperfusion (Group 3). In either unloading protocol, both Hemopumps were used. It was shown that recovery from asynchrony was significantly faster in Groups 2 and 3 if unloading was performed with the 21-F HP compared with control Group 1 and the groups using the 14-F HP (p > 0.05). Thus, mechanical unloading with the 21-F Hemopump enhances recovery from stunning whereas unloading with the 14-F HP has only minor effects on hemodynamics and no effects on recovery.

Animals↗

A comparative blinded study in miniature swine of whole blood-, hemoglobin-, platelet-, plasma-, and lymphocyte-associated acetaldehyde as markers for ethanol intake.

Blood samples were obtained from miniature swine maintained on 0, 2, or 6 g/kg/24 hr ethanol for 8 months (N = 6 in each group). Samples from drinking pigs were taken after 8 hr of ethanol abstinence and all were coded and sent for "blinded" analysis. A fluorigenic high performance liquid chromatographic assay was used to quantify whole blood-associated acetaldehyde, hemoglobin-associated acetaldehyde, plasma-associated acetaldehyde, platelet-associated acetaldehyde, and lymphocyte-associated acetaldehyde. Detectable levels of acetaldehyde were found in each sample in both drinking and nondrinking pigs. Analysis of whole blood-associated acetaldehyde was most discriminatory in distinguishing nondrinking from drinking pigs (mean 21.4 +/- 1.0 microM for nondrinkers vs. 24.6 +/- 1.5 SD for the group consuming 2 g/kg ethanol, p = 0.001). Measurements of hemoglobin-associated acetaldehyde normalized to protein concentration (250 +/- 47 nmoles/g vs. 203 +/- 33 SD, p less than 0.05 drinking vs. nondrinking pigs) and platelet-associated acetaldehyde (0.46 0.34 vs. 0.15 +/- 0.16 nmoles/3 x 10(8) platelets, p = 0.05 drinking vs. nondrinking pigs) were also useful in discriminating drinking from nondrinking animals. Analysis of plasma-associated acetaldehyde and lymphocyte-associated acetaldehyde were not useful as markers of ethanol consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Transesophageal echocardiography using cypress-miniaturized echocardiogram unit: initial clinical experience.

Transesophageal echocardiography (TEE) was introduced clinically in the United States in 1987. Recent technologic advances have resulted in the creation of a small portable hand-carried ultrasound (HCU) device that can be easily carried throughout the hospital with greater flexibility for cardiac imaging. These HCU devices have harmonic, color, and spectral Doppler (continuous/pulsed wave). Siemens Medical Solutions USA, Inc. has incorporated a TEE connector, which connects to its Cypress (highly miniaturized echocardiogram unit) and allows the performance of a TEE with this unit, which is mildly heavier than a typical HCU. We describe our initial clinical experience with this unit. The image quality is comparable to routine TEEs, with the advantages of shorter duration, portability, affordable cost, avoiding the use of high-end machine from the echo lab, availability of non-HCU units for other studies, and preventing the need for an echo technician to be involved in the procedure.

Aged↗

Laser angioplasty in miniature swine: advantages of a modified fiber tip delivery system.

Laser angioplasty using a spherical lensed fiber-tip laser delivery catheter and a 200 mum bare silica fiber tip was performed in occluded atherosclerotic iliac arteries of miniature swine. Group I consisted of 8 animals with 11 totally occluded arteries in which the bare silica fiber was used. Group II included 22 animals with occlusive lesions in 41 arteries in which the silica lens tip was used. In vivo laser angioplasty was performed in both groups using an argon ion laser delivering 2 to 3 watts of power in 1 to 5 second intervals. Successful recanalization occurred in 7/11 (64%) in group I arteries and 35/41 (85%) in group II arteries. Vascular perforation occurred in 36% (4/11) in group I compared to 10% (4/41) in group II (P less than 0.05). Mechanical perforation due to the bare fiber alone accounted for 50% of the perforations in group I and did not occur with the silica lens-tip device (group II). We conclude that the atraumatic lensed fiber is more effective in recanalizing occlusive lesions and is a safer delivery system than the bare silica fiber.

Angioplasty, Laser↗

Enhanced bone apposition around biofunctionalized sandblasted and acid-etched titanium implant surfaces. A histomorphometric study in miniature pigs.

Microrough titanium (Ti) surfaces of dental implants have demonstrated more rapid and greater bone apposition when compared with machined Ti surfaces. However, further enhancement of osteoblastic activity and bone apposition by bio-functionalizing the implant surface with a monomolecular adsorbed layer of a co-polymer - i.e., poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its derivatives (PLL-g-PEG/PEG-peptide) - has never been investigated. The aim of the present study was to examine early bone apposition to a modified sandblasted and acid-etched (SLA) surface coated with an Arg-Gly-Asp (RGD)-peptide-modified polymer (PLL-g-PEG/PEG-RGD) in the maxillae of miniature pigs, and to compare it with the standard SLA surface. Test and control implants had the same microrough topography (SLA), but differed in their surface chemistry (polymer coatings). The following surfaces were examined histomorphometrically: (i) control - SLA without coating; (ii) (PLL-g-PEG); (iii) (PLL-g-PEG/PEG-RDG) (RDG, Arg-Asp-Gly); and (iv) (PLL-g-PEG/PEG-RGD). At 2 weeks, RGD-coated implants demonstrated significantly higher percentages of bone-to-implant contact as compared with controls (61.68% vs. 43.62%; P < 0.001). It can be concluded that the (PLL-g-PEG/PEG-RGD) coatings may promote enhanced bone apposition during the early stages of bone regeneration.

Acid Etching, Dental↗

A 6-month dermal toxicity test with dithranol and butantrone in miniature swine.

Continuous topical administration of dithranol and butantrone for 6 months caused different irritation profiles in miniature swine. In paraffin wax sticks in white petrolatum, butantrone gave rise to much less initial irritation than dithranol, but after 2-3 weeks the situation had equalized. In gel formulations, butantrone was initially more irritant than dithranol. The vehicles themselves induced significant irritation. Signs of skin hyperplasia (parakeratosis and acanthosis) and inflammation were frequent histopathological findings at the end of the study, but no malignant changes were found. Dithranol and butantrone did not produce any chemical, hematological or serious histological abnormalities during the treatment, suggesting a lack of systemic toxicity. No evidence of systemic absorption was found. This long-term study did not predict delayed irritation of butantrone observed in about 1/3 of the psoriatic patients after treatment for 1-2 months.

Administration, Topical↗

Dentin formation in miniature pigs with special reference to indomethacin and orthodontic treatment.

The rate of dentin mineralization and the influence of indomethacin on the dentin mineralization rate during orthodontic treatment was determined in miniature pigs by intravital labeling with tetracycline. The results demonstrated that the dentin mineralization rate in the control animals was 3.8 microns/day, a rate corresponding to that of human teeth. Both indomethacin and orthodontics had an effect on the dentin mineralization rate, indomethacin reducing and orthodontic forces increasing it. In combination, the two factors neutralized each other.

Animals↗