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PubMed1990

Excretion and tissue distribution of 14C-labelled 8-methoxypsoralen in beagle dogs and miniature pigs.

Male beagle dogs and miniature swine were given 14C-labelled 8-methoxypsoralen (8-MOP) as a single oral dose (10 mg/kg body weight). In dogs, there appeared to be wide variability in 8-MOP absorption as indicated by the broad range of percentages of radioactivity recovered from urine and faeces over a 4-day period (3.6-24.7% in urine; 47.3-94.9% in faeces); mean recovery values were 13.6% in the urine and 68.6% in the faeces. In pigs, considerable variability in absorption was also evident, but not to the extent of that seen in dogs. Based on the fraction of the dose recovered in the urine, the absorption of 8-MOP was greater in pigs; the proportion of the dose recovered in urine over a 7-day period ranged from 25.8 to 57.8%. Faecal recovery ranged from 15.4 to 49.0% of the dose. Mean recovery values in pigs were 45.4% in urine and 35.6% in faeces. Most of the 8-MOP was cleared from the bodies of dogs and pigs in a few days, and little 8-MOP residue was sequestered in any of the tissues examined in either species. Small amounts of an 8-MOP-related substance remained in the liver and blood for as long as 4 days in dogs and 7 days in pigs.

Animals↗
PubMed1988

Examination of minoxidil-induced acute cardiotoxicity in miniature swine.

Minoxidil, a vasodilating antihypertensive agent, was given orally in doses of 1, 3 or 10 mg/kg to miniature swine on 2 consecutive days. Mean arterial pressure decreased and heart rate increased most consistently after the 10 mg/kg dose. However, all 3 doses of minoxidil induced myocardial hemorrhages and/or left ventricular papillary muscle necrosis within 24 h after the second dose. Necrosis, characterized by hypercontraction of muscle cells and myofibrillar damage, occurred in 1 of 8 pigs given 1 mg/kg, 3 of 13 given 3 mg/kg and 7 of 14 given 10 mg/kg of minoxidil. The pharmacological effects of minoxidil, hypotension and reflex tachycardia, probably led to ischemia and necrosis in left ventricular papillary muscles. Gross hemorrhages involving the left atrium and to a lesser extent the left ventricle were found in 4 of 8 pigs given 1 mg/kg, 9 of 13 given 3 mg/kg and 11 of 14 given 10 mg/kg of minoxidil. The atrial lesions were manifested grossly by diffuse redness and microscopically by interstitial edema, extravasation of erythrocytes and infiltration of areas around small arteries and arterioles with acute and chronic inflammatory cells. The hemmorhagic areas were concentrated along the epicardial surfaces, and to a lesser extent along the endocardial surfaces. Atrial lesions induced by minoxidil preferentially involve the left atrium in pigs and the right atrium in dogs. These differences may be related to the anatomic patterns of coronary circulation in the 2 species.

Administration, Oral↗
PubMed1984

A diabetes insipidus-like syndrome in the intact Yucatan miniature boar following implantation of desoxycorticosterone-acetate (DOCA).

A syndrome of polydipsia and polyuria is described in the intact adult Yucatan miniature boar following implantation of silicone rubber strips impregnated with desoxycorticosterone-acetate (DOCA). Water intake was significantly greater than control 5 days post-DOCA. Urine output was significantly greater than control 7 days post-DOCA, and urine osmolality was significantly decreased 8 days post-DOCA. Serum potassium was significantly less than control 24 hr post-DOCA, and serum sodium was consistently and significantly greater than control by 1 week post-DOCA. As suggested in the dog, the increase in water turnover following DOCA administration in the pig is initiated by an increased thirst followed by an increase in urine output.

Animals↗
PubMed1990

Relationship of hypokalemia to metabolic alkalosis in the intact Yucatan miniature boar following implantation of deoxycorticosterone-acetate (DOCA) or d-aldosterone.

1. Normo-kalemic Yucatan miniature boars were implanted with deoxycorticosterone-acetate (DOCA) or d-aldosterone (Aldo) to evaluate the relationship of hypokalemia to the pathogenesis of metabolic alkalosis following mineralocorticoid administration. 2. Serum potassium was significantly less than control within 24 hr, serum bicarbonate significantly elevated within 4 days and pH 1-2 days later with no significant differences between DOCA and Aldo. 3. These data demonstrate that pre-existing potassium deficits are not required for the development of alkalosis with mineralocorticoid administration, DOCA and Aldo are equally effective, co-existing hypokalemia is necessary in the genesis, and perhaps maintenance, of metabolic alkalosis with excess mineralocorticoids, and hypokalemia is not a consequence of the alkalosis.

Aldosterone↗
PubMed1991

Effect of dietary fat on biliary lipids composition of gallbladder bile in miniature swine (Sus scrofa).

1. Weaning animals (34 days old) were fed for 6 months with four diets that differed only in the quantity and quality of fat sources (control group 3.2% (w/w), lard-fed group 7.6% (w/w), olive-oil-fed group 10.4% (w/w), and sunflower-oil-fed group 10.5% (w/w). Samples were collected and assessed after animals were killed at 6 months of age. 2. Our results show that the quality of fat did not alter biliary lipids composition of the gallbladder bile composition in miniature swine after 6 months adaptation to the diet, except for a significant increase of the phospholipid concentration in the lard-fed group with regard to the control group. 3. The highest and lowest bile cholesterol saturation indices were observed in sunflower and lard-fed groups, respectively showing in all cases saturation indices far from the saturation point.

Adaptation, Physiological↗
PubMedDate not supplied

Effects of adaptation to diets enriched with saturated, monounsaturated and polyunsaturated fats on lipid and serum fatty acid levels in miniature swine (Sus scrofa).

A total of 37 miniature swine (Sus scrofa) was fed with three diets of 9% fat content, differing only in the quality of the fat source (sunflower oil, olive oil and lard fat). Three groups of animals were fed for a 3 month period, and three other groups were fed for a 12 month period. After the two experimental periods, the influence of the diet on serum lipids and serum fatty acids was studied. In the short term, the serum cholesterol level was higher in the lard group, but with time, it undergoes a significant increase in the sunflower group, due to increases both in HDL-C and in LDL-C. In the olive oil group, LDL-C hardly varies with time, while HDL-C tends to decrease. In the lard group, LDL-C increases and HDL-C decreases. The atherogenic index is, in the long term, lower in the lard group and higher in the polyunsaturated fat group. The fatty acid composition of serum lipids in the long term shows a greater saturation index (SI) for the sunflower group and lard group, an increase in monounsaturated fatty acids in the olive oil group, and a higher percentage of linoleic acid in the sunflower group.

Adaptation, Physiological↗
PubMed1994

Heart and liver fatty acid composition and vitamin E content in miniature swine fed diets containing corn and menhaden oils.

Female miniature swine, 4-11 yr, were fed 15% fat diets containing n-3 and/or n-6 polyunsaturated fat for 6 months, at 1.95 g fat/kg body weight. Liver lipids from menhaden oil-fed minipigs were elevated in the n-3 fatty acids: 20:5, 22:5 and 22:6, but heart lipids only in 20:5 and 22:6. Liver cell plasma membrane was elevated in 20:5, 22:5 and 22:6 and lowered in the n-6 acids 18:2 and 20:4 in menhaden oil-fed animals, to a greater extent than in the total tissue lipids. Liver alpha-tocopherol tended to decrease upon feeding menhaden oil, but heart alpha-tocopherol concentrations were not affected.

Animals↗
PubMed1991

Detection of 19-nortestosterone and its urinary metabolites in miniature pigs by gas chromatography-mass spectrometry.

The metabolism of 19-nortestosterone was investigated in a miniature non-castrated male pig (boar), in a castrated pig (barrow) and in a female pig (sow). Urine samples were taken before and at regular intervals after the injection of 100 mg of Laurabolin (nortestosterone laurate). The sample clean-up consists in preliminary solid-phase extraction, followed by high-performance liquid chromatographic purification and fractionation. Finally, gas chromatography-mass spectrometry is used to identify the 19-nortestosterone metabolites.

Animals↗
PubMed1993

Inhibitory effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury in hypercholesterolemic miniature pigs.

OBJECTIVES: The present study aimed to clarify the effects of heparin, aspirin and ketanserin on coronary artery vasoconstriction after arterial balloon injury. BACKGROUND: The mechanisms of coronary artery vasoconstriction after coronary angioplasty are not well understood. METHODS: After being fed a cholesterol-rich diet for 1 month, 71 Göttingen miniature pigs were randomly allotted to five groups: 16 pigs with no pretreatment (group A); 21 pigs pretreated with heparin, 3,000 U (group B); 13 pigs pretreated with aspirin, 50 mg/day orally for 2 days (group C); 11 pigs pretreated with ketanserin, 1 mg/kg body weight (group D); 10 pigs pretreated with aspirin, 50 mg/day for 2 days, heparin, 6,000 U and ketanserin, 1 mg/kg (group E). After this pretreatment, the left anterior descending or the left circumflex coronary artery, or both, was denuded by a 2F balloon catheter. RESULTS: The coronary vasoconstriction at the injured sites reached a peak level 6 min after the arterial injury and subsided within 30 min. The coronary vasoconstriction at the injured site 6 min after arterial injury was 56 +/- 5% in group A, which was significantly greater than that in group B (28 +/- 6%, p < 0.01), group C (25 +/- 5%, p < 0.01), group D (26 +/- 7%, p < 0.01) or group E (24 +/- 5%, p < 0.01), whereas there was no significant difference in the coronary vasoconstriction among the latter four groups. CONCLUSION: These results suggest that serotonin released from aggregating platelets plays a major part in the platelet-dependent coronary artery vasoconstriction after arterial injury.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Chronic ethanol consumption alters transbilayer distribution of phosphatidylcholine in erythrocytes of Sinclair (S-1) miniature swine.

Effects of chronic ethanol consumption on transbilayer distribution of phospholipids in the exofacial and cytofacial leaflets of erythrocytes from chronic ethanol-consuming Sinclair (S-1) miniature swine were examined. Phosphatidylcholine (PC) was predominantly located in the exofacial leaflet and phosphatidylethanolamine (PE) and phosphatidylserine (PS) located primarily in the cytofacial leaflet. Chronic ethanol consumption significantly increased PC content in the exofacial leaflet without changing bulk membrane PC composition. Ethanol-induced changes in PC distribution were specific for PC and not detected in PE or PS. There was also a significant decrease in sphingomyelin in the ethanol group. Sphingomyelin is primarily an exofacial phospholipid. The specific ethanol-induced changes in the exofacial leaflet are consistent with recent studies showing that the exofacial membrane leaflet is more susceptible to effects of ethanol as compared to the cytofacial leaflet. Such specificity of action provides a new way of viewing how ethanol alters membrane structure and function.

Animals↗
PubMed1991

The Yucatan miniature swine as an in vivo model for screening skin depigmentation.

The usefulness of the Yucatan miniature pig as a screen for skin dipigmenting activity by topical application was evaluated with standard compounds. This is a naturally occurring breed of swine with light brown to dark brown skin that is relatively hairless. The skin morphology, including the pattern of pigment distribution, in this breed of swine closely resembles the human skin. Test compounds examined in this study included the three standard compounds with known clinical depigmenting activity, hydroquinone (HQ), 4-hydroxyanisole (4HA) and tert-butyl catechol (TBC), each at a 5% concentration. Test materials in 25 microliters of propylene glycol/ethanol (50:50) were applied topically twice daily, 7 days a week for 90 days to test sites on each side of the dorsal mid-line. Test sites were graded weekly for variation in pigmentation and local irritation. After 90 days of test material application, skin biopsies of the test sites were taken for histological evaluation. Topical application of HQ, 4HA and TBC promoted marked skin depigmentation which was substantiated by reductions of pigment and melanocytes observed on microscopic examination. While both HQ and TBC produced marked local irritation, 4HA was only mildly irritating. These results suggest that the Yucatan pig, could be a potentially useful model for screening compounds with skin depigmenting activity.

Animals↗
PubMed2005

K-band EPR dosimetry: small-field beam profile determination with miniature alanine dosimeter.

The use of small-size alanine dosimeters presents a challenge because the signal intensity is less than the spectrometer sensitivity. K-band (24 GHz) EPR spectrometer seems to be a good compromise between size and sensitivity of the sample. Miniature alanine pellets were evaluated for small-field radiation dosimetry. Dosimeters of DL-alanine/PVC with dimensions of 1.5 mm diameter and 2.5 mm length with 5 mg mass were developed. These dosimeters were irradiated with 10 MV X-rays in the dose range 0.05-60 Gy and the first harmonic (1h) spectra were recorded. Microwave power, frequency and amplitude of modulation were optimized to obtain the best signal-to-noise ratio (S/N). For beam profile determination, a group of 25 dosimeters were placed in an acrylic device with dimensions of (7.5 x 2.5 x 1)cm3 and irradiated with a (3 x 3)cm2 10 MV X-rays beam field size. The dose at the central region of the beam was 20 Gy at a depth of 2.2 cm (build up for acrylic). The acrylic device was oriented perpendicular to the beam axis and to the gantry rotation axis. For the purposes of comparison of the spatial resolution, the beam profile was also determined with a radiographic film and 2 mm aperture optical densitometer; in this case the dose was 1 cGy. The results showed a similar spatial resolution for both types of dosimeters. The dispersion in dose reading was larger for alanine in comparison with the film, but alanine dosimeters can be read faster and more directly than film over a wide dose range.

Alanine↗
PubMed2005

Growth of miniature pig parotid cells on biomaterials in vitro.

Both Sjögren's syndrome and therapeutic irradiation for head and neck cancer lead to irreversible damage of the parenchyma of the salivary glands. This report describes an attempt to grow miniature pig (minipig) parotid gland cells on artificial films and tubular scaffolds with the ultimate intention of developing bio-engineered replacement tissue. Minipig parotid cells were isolated and cultured. The growth and structural and physiological features of the cells which were cultured on films and porous tubular scaffolds made from poly(ethylene glycol)-terephthalate (PEGT)/poly(butylene terephthalate) (PBT) were examined. By 9 days, the parotid cells on the films and the tubular scaffolds formed continuous monolayers. The secretory granules and nuclei of the cultured acinar cells remained polarised. Desmosomes, gap junctions and tight-like junctions were still present between the apical regions of adjacent cells. Amylase activity decreased during the culture period but was still evident in the medium after 10 days of culture. In conclusion, minipig parotid cells are well-maintained in vitro on both a flat surface and a three-dimensional (3D) scaffold. The addition of a Matrigel coating to the surface of synthetic materials aids cell growth and maintenance of a morphology that more closely resembles normal epithelium.

Animals↗
PubMed2005

The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs.

Previously, we have shown, in vivo, that the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe decreases hepatic apolipoprotein (apo) B secretion into plasma. To test the hypothesis that avasimibe modulates postprandial triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg) containing retinol was given to 9 control miniature pigs and to 9 animals after 28 days treatment with avasimibe (10 mg/kg/day, n=5; 25 mg/kg/day, n=4). The kinetic parameters for plasma retinyl palmitate (RP) metabolism were determined by multi-compartmental modeling using SAAM II. Avasimibe decreased the 2-h TRL (d<1.006 g/mL; S(f)>20) triglyceride concentrations by 34%. The TRL triglyceride 0-12 h area under the curve (AUC) was decreased by 21%. In contrast, avasimibe had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma, however, the TRL RP 0-12 h AUC was decreased by 17%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate (FCR) was increased 1.4-fold with avasimibe. The TRL RP FCR was negatively correlated with very low density lipoprotein (VLDL) apoB production rate measured in the fasting state (r=-0.504). No significant changes in total intestinal lipid concentrations were observed. Thus, although avasimibe had no effect on intestinal TRL secretion, plasma TRL clearance was significantly increased; an effect that may relate to a decreased competition with hepatic VLDL for removal processes.

Acetamides↗
PubMed2006

Analysis of nuclear reprogramming in cloned miniature pig embryos by expression of Oct-4 and Oct-4 related genes.

Xenotransplantation is a rapidly expanding field of research and cloned miniature pigs have been considered as a model animal for it. However, the efficiency of somatic cell nuclear transfer (SCNT) is extremely low, with most clones resulting in early lethality and several kinds of aberrant development. A possible explanation for the developmental failure of SCNT embryos is insufficient reprogramming of the somatic cell nucleus by the oocyte. In order to test this, we analyzed the reprogramming capacity of differentiated fibroblast cell nuclei and embryonic germ cell nuclei with Oct-4 and Oct-4 related genes (Ndp5211, Dppa2, Dppa3, and Dppa5), which are important for embryonic development, Hand1 and GATA-4, which are important for placental development, as molecular markers using RT-PCR. The Oct-4 expression level was significantly lower (P<0.05) in cloned hatched blastocysts derived from fibroblasts and many of fibroblast-derived clones failed to reactivate at least one of the tested genes, while most of the germ cell clones and control embryos correctly expressed these genes. In conclusion, our results suggest that the reprogramming of fibroblast-derived cloned embryos is highly aberrant and this improper reprogramming could be one reason of the early lethality and post-implantation anomalies of somatic cell-derived clones.

Animals↗
PubMed2005

Liquid-based hybridization assay with real-time detection in miniaturized array platforms.

An assay for the fluorescent detection of short oligonucleotide probe hybridization in miniaturized high-density array platforms is presented. It combines hybridization in solution with real-time fluorescent detection, which involves measurement of fluorescence increase by means of an induced fluorescence resonance energy transfer. The feasibility of this approach using DNA or RNA as a target, and short DNA- as well as LNA (locked nucleic acid)-modified oligonucleotides as probes is shown. The presented approach could potentially contribute to a significant increase in the throughput of large-scale genomic applications, such as oligofingerprinting and genotyping, and also reduce material consumption.

Computer Systems↗
PubMed2005

Electrochemical determination of gamma-glutamyl transpeptidase activity and its application to a miniaturized analysis system.

A novel method to determine the activity of gamma-glutamyl transpeptidase (gamma-GTP) was developed. gamma-l-glutamyl-l-glutamate and glycyl-glycine were used as the substrates for gamma-GTP. l-glutamate produced by the enzymatic reaction was measured with an amperometric l-glutamate sensor. Following the mixing of the substrate solution and a sample solution, the current generated on the l-glutamate sensor continued to increase at a constant rate. The method was used to construct a miniaturized analysis system for the determination of gamma-GTP activity. The system consisted of the l-glutamate sensor formed on a glass substrate and a polydimethylsiloxane (PDMS) flow channel. Since the l-glutamate concentration in the solution increased as the solution was mobilized through the flow channel, a constant current increase was observed. The relation between the slope of the response curve and the activity of gamma-GTP was linear between 35 U l(-1) and 659 U l(-1). The rate analysis in the micro flow channel minimized the influence of interferents. The reproducibility of the output of the micro system was found to be good with a relative standard deviation (R.S.D.) of 5.6% at 659 U l(-1). The activities of gamma-GTP in human serum samples were also determined and compared with values obtained with a conventional spectroscopic method. The values obtained by the two methods were consistent with a correlation coefficient of 0.953.

Biomarkers↗
PubMed2006

A biofilm enhanced miniature microbial fuel cell using Shewanella oneidensis DSP10 and oxygen reduction cathodes.

A miniature-microbial fuel cell (mini-MFC, chamber volume: 1.2 mL) was used to monitor biofilm development from a pure culture of Shewanella oneidensis DSP10 on graphite felt (GF) under minimal nutrient conditions. ESEM evidence of biofilm formation on GF is supported by substantial power density (per device cross-section) from the mini-MFC when using an acellular minimal media anolyte (1500 mW/m2). These experiments demonstrate that power density per volume for a biofilm flow reactor MFC should be calculated using the anode chamber volume alone (250W/m3), rather than with the full anolyte volume. Two oxygen reduction cathodes (uncoated GF or a Pt/vulcanized carbon coating on GF) were also compared to a cathode using uncoated GF and a 50mM ferricyanide catholyte solution. The Pt/C-GF (2-4% Pt by mass) electrodes with liquid cultures of DSP10 produced one order of magnitude larger power density (150W/m3) than bare graphite felt (12W/m3) in this design. These advances are some of the required modifications to enable the mini-MFC to be used in real-time, long-term environmental power generating situations.

Bioelectric Energy Sources↗