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PubMed1999

Saline infusion contrast intrauterine sonographic assessment of the endometrium with high-frequency, real-time miniature transducer in normal menstrual cycle: a preliminary report.

Normal endometrial texture was visualized using saline infusion contrast intrauterine sonography with a specially developed 20 MHz flexible catheter-based high-resolution, real-time miniature (2.4 mm outer diameter) ultrasound transducer in primary infertile women (n = 15) with a normal menstrual cycle. All the women had <2 years infertility duration and were studied in proliferative, and early or mid-secretory phases. Before intrauterine sonography, transvaginal sonographic assessment of the endometrium was conducted. The overall image clarity was subjectively compared between intrauterine and transvaginal sonography. Most endometrial textures in both proliferative and secretory phases were viewed more easily with intrauterine rather than transvaginal sonography, and this was especially true with an intrauterine saline infusion technique. Moreover, it was possible to obtain finer image quality of very small endometrial interfacial and internal textures with intrauterine sonography. However, the depth of penetration of the ultrasound beam is only approximately 2 cm, therefore examination of larger pathological endometrial lesions is markedly limited because of the shallow scanning range of the high-frequency transducer. Intrauterine sonography may be a valuable tool in imaging endometrial texture in normal menstrual cycle, and possibly in infertility practice, complementing and not replacing transvaginal sonography.

Computer Systems↗
PubMed2002

Miniaturization: an overview of biotechnologies for monitoring the physiology and pathophysiology of rodent animal models.

Recent advances in bioengineering technologies have made it possible to collect high-quality reproducible data quantitatively in a wide range of laboratory animal species, including rodents. Several of these technologies are incorporated into a plan called Miniaturization, which aims to design, develop, and maintain rodent animal models to study the pathophysiology and therapy of human diseases. Laser Doppler flowmetry, digital sonomicrometry, bioelectrical impedance, and microdialysis are some of the most widely used methods under the plan because they cause minimal pain and distress, reduce the number of animals used in biomedical research, and allow chronic, nonterminal assessment of physiological parameters in rodents. An overview of each of these technologies and their major applications in rodents used for biomedical research is provided.

Animals↗
PubMed1984

Intestinal metabolism of orally administered glucose and fructose in Yucatan miniature swine.

Absorption rates and metabolism of orally administered glucose and fructose were quantitated in conscious, overnight-fasted, Yucatan miniature swine. The pigs were surgically prepared, with catheters in the portal vein and a carotid artery. A continuous wave Doppler flow cuff was placed around the portal vein. Four to 7 days after surgery, arterial and portal venous blood samples were obtained in the basal state and at 15-minute intervals for 4 hours following oral administration of glucose or fructose (1.5 g/kg body weight). Absorption rates and intestinal metabolism were calculated from portal blood flow and arterio-venous concentration differences for glucose, fructose and lactate. Oral fructose administration was accompanied by a rise in intestinal lactate production, which correlated significantly with the fructose absorption rate. Intestinal lactate output during fructose absorption could account for 12% of the fructose absorbed or metabolized. A small rise in glucose output from the gut was also observed. In contrast, after oral glucose administration, only a modest rise in intestinal lactate output was noted. It could account for only 2% of the glucose absorbed or metabolized. No correlation between glucose absorption rate and intestinal lactate output was observed. These studies indicate that a significant portion of oral fructose is converted to lactate during absorption but that the major part enters the portal vein as fructose. Only minimal intestinal metabolism of ingested glucose occurs.

Administration, Oral↗
PubMed1990

The effect of chronic alcohol ingestion on free radical defense in the miniature pig.

Cellular protection from free radical reactions was measured in hepatic tissue from controls and miniature pigs fed ethanol. The activities of copper-zinc superoxide dismutase (CuZnSOD) and glutathione peroxidase were lower and the activity of manganese superoxide dismutase (MnSOD) was higher in the pigs fed ethanol than in controls. Glutathione concentration was lower in the pigs fed ethanol than in controls. Ethanol consumption did not result in increased lipid peroxidation as assessed by thiobarbituric acid-reactive substances. The ethanol-induced effects on the activities of the superoxide dismutases may be a reflection of available metals and/or a response to increased hepatic concentration of oxygen radicals. Because the protection afforded by the glutathione system was altered, pigs fed ethanol may be at risk of peroxidative damage with continued ethanol exposure.

Alcoholism↗
PubMed1991

Homoarginine labeling is suitable for determination of protein absorption in miniature pigs.

Intestinal proteolysis and absorption of dietary protein was followed using a chemical label of the lysine side-chain. Protein-bound lysine was transformed into homoarginine (HA), an amino acid that is not used for protein synthesis. Disappearance in the intestinal tract of HA originating from labeled casein and soybean isolate and appearance in peripheral blood was followed in four miniature pigs fitted with permanent T-cannulas at the proximal jejunum and ileum. Less than 0.2% of HA appeared in the digesta at the ileum when up to 13.5 mmol of HA was infused either into the jejunum or jugular vein. Several factors suggest that HA in fact traces the exogenous (dietary) protein: 1) the quick postprandial appearance of HA in plasma; 2) the high (greater than 97%) oro-ileal absorption of HA-labeled casein and soybean isolate; 3) the similarity of chymotryptic proteolysis in vitro of guanidinated and native casein; 4) the fact that only trace amounts of the marker reenter the intestinal lumen from the blood. Therefore HA-label is suitable for the differentiation of exogenous and endogenous protein in the chyme and thus the measurement of oro-ileal protein absorption and irreversible loss of endogenous protein in the chyme of the small intestine.

Animals↗
PubMed1992

The influence of dietary fiber on proliferation of intestinal mucosal cells in miniature swine may not be mediated primarily by fermentation.

Cannulated miniature pigs were used as a model for evaluating the effects of fiber-containing diets on proliferation of colonic epithelial cells. Biopsy specimens taken from the mucosa of the cecum and distal colon were incubated in [3H]thymidine and processed using autoradiography. Digesta from the cecum was analyzed for concentrations of short-chain fatty acids (SCFA), pH and volume. Cellular proliferation at both intestinal sites was influenced by the source or quantity of dietary fiber. These dietary variables also influenced SCFA concentrations and pH of cecal digesta and the volume of contents in the fermentation chamber. Cellular proliferation was not significantly correlated, however, with the quantity of water-soluble dietary fiber consumed, with SCFA concentrations or pH of the cecal digesta, or with the volume of the fermentation chamber. We suggest that the influence of dietary fiber on intestinal cell proliferation cannot be predicted from markers of the fermentation capacity of specific diets, because fiber likely influences intestinal proliferation through several interactive mechanisms, some of which include luminal factors.

Animals↗
PubMed1994

Gastric emptying regulates the kinetics of nitrogen absorption from 15N-labeled milk and 15N-labeled yogurt in miniature pigs.

Thirty-six miniature pigs divided into two groups of 18 animals were fed 15N-labeled milk or yogurt. Polyethylene glycol 4000 was added to the diets as a non-absorbable marker of the liquid phase. Animals were slaughtered 1, 2, 4, 8 and 12 h after meal ingestion, and the gastrointestinal tract was removed and divided into 10 parts. Polyethylene glycol, total nitrogen and 15N enrichment were measured in the digesta. Both the intestinal delivery of the liquid phase and the nitrogenous fraction of the chyme were delayed more in pigs fed yogurt than in pigs fed milk. No stimulatory effect of diet ingestion on endogenous nitrogen secretion was found. Both milk proteins and yogurt proteins were highly digestible: 93% of the exogenous nitrogen disappeared 12 h after feeding. The kinetics of exogenous nitrogen delivery into the intestine was correlated (r = 0.999 for milk and r = 0.974 for yogurt) with that of exogenous nitrogen absorption. These results suggest that milk proteins are rapidly absorbed after they reach the intestine. Gastric emptying is a major factor controlling the kinetics of milk nitrogen absorption.

Animals↗
PubMed1996

Dietary fish oil enhances insulin sensitivity in miniature pigs.

The effects of dietary fish oil, MaxEPA, and corn oil on insulin sensitivity were examined in male miniature pigs. The pigs (20-35 kg) received 750 g of nonpurified diet per day (160 g/kg protein, 50 g/kg fat) with the addition of either 30 g corn oil or 30 g MaxEPA, resulting in 90 g total fat per kg diet for 4-5 wk. The MaxEPA diet provided 12.6 g (n-3) polyunsaturated fatty acids per kg diet (6.7 g eicosapentaenoic acid, 4.8 g docosahexaenoic acid), 4.7 g (n-3) polyunsaturated fatty acids and 147 mg cholesterol. The corn oil diet provided 22.7 g (n-6) polyunsaturated fatty acids per kg diet and no (n-3) polyunsaturated fatty acids; cholesterol was added to equal the amount in the MaxEPA. After overnight withdrawal of food, intravenous glucose tolerance tests were conducted in conscious pigs by using previously placed jugular vein catheters. Plasma glucose responses and the areas under the plasma glucose curves were similar in seven MaxEPA- and five corn oil-fed pigs. However, the incremental areas under the insulin curves were significantly lower for the pigs fed MaxEPA. Thus values for insulin sensitivity (SI), determined with Bergman's minimal model, were significantly higher for MaxEPA than for corn oil-fed pigs, whereas the rate of glucose disappearance (KG), did not differ between the two groups. Therefore, substitution of (n-3) for (n-6) polyunsaturated fatty acids in dietary lipids is associated with enhanced insulin sensitivity in male pigs.

Animals↗
PubMed1998

Absorption of nutrients is only slightly reduced by supplementing enteral formulas with viscous fiber in miniature pigs.

Viscous polysaccharides reduce intestinal absorption of glucose and diminish postprandial hyperglycemia. However, it is unknown whether viscous fiber also inhibits absorption of nutrients under conditions of enteric feeding. Therefore, we measured the absorption rates of nutrients in miniature pigs by perfusing a 150-cm length of jejunum with 8.37 kJ/min of the three following enteral diets: an isoosmotic oligomeric diet (1670 kJ/L), a hyperosmotic oligomeric diet and an isoosmotic polymeric diet (both 3350 kJ/L). The diets were supplemented with guar gum from 0 to 4.4 g/L. With the three guar-free diets, the mean absorption rate of energy was 5.2 +/- 0.32 kJ/min, corresponding to 62% of the energy infused. Absorption rates of carbohydrate, protein, fat and energy linearly declined as concentrations of guar or the logarithm of chyme viscosity increased. Due to modulations in viscosity, the inhibitory effects of guar were significantly different among the three diets. With the isoosmotic and hyperosmotic oligomeric and the polymeric diets, the addition of 1 g guar/L diminished the absorption of energy by 9.7, 6. 6 and 3.7%, respectively. The strong inhibitory effect on nutrient absorption with the isoosmotic oligomeric diet was caused by an increase in chyme viscosity due to water absorption. With the hyperosmotic oligomeric and the polymeric diets, the chyme viscosity and thus inhibitory effects on absorption were diminished by water secretion and the concomitant infusion of pancreatic enzymes. Results indicate that the addition of small amounts of guar gum to enteral diets of high energy density exerts only small effects on absorption of nutrients.

Animals↗
PubMed1998

Dietary menhaden and corn oils and the red blood cell membrane lipid composition and fluidity in hyper- and normocholesterolemic miniature swine.

Fatty acids in the diet are readily incorporated into lipids in various tissues. However, it is not clear whether all tissues have the same level of incorporation. Second, (n-6) unsaturated fatty acids increase the fluidity of membranes, but this has not been shown for (n-3) fatty acids. In this study, we measured the incorporation of (n-6) and (n-3) fatty acids into erythrocyte membrane lipids and studied their effects on the fluidity of erythrocyte membranes. One group of female miniature swine was made hypercholesterolemic by feeding the swine cholesterol and lard for 2 mo; the other group served as controls and was fed a stock diet. Both groups were then fed either corn oil or menhaden oil or a mixture of the two for 23 additional weeks. Blood was collected at 0, 2, 4, 12 and 23 wk after initialization of the experimental diets, and fatty acid composition of phospholipids was assessed. Membrane phospholipids of pigs fed menhaden oil had elevated (n-3) fatty acids (20:5 and 22:6), and lower 18:2 than those fed corn oil. There was no difference in 20:4 content. The fatty acid changes occurred as early as 2 wk after consumption of the corn oil or menhaden oil in pigs previously fed a stock diet, but it took longer in pigs previously fed lard + cholesterol, indicating residual effects of pretreatment. Menhaden oil increased anisotropy (indicating decreased fluidity) more than corn oil for the nonpolar probe diphenylhexatriene (DPH) at earlier time points, but not at 23 wk. Erythrocyte membrane fluidity was significantly related to membrane polyunsaturate content, with (n-6) fatty acids having a greater influence than (n-3) fatty acids. A comparison of the present red blood cell fatty acid compositions with brain synaptosome fatty acid compositions for the same animals showed poor correlations for some of the fatty acids. There was no significant direct relationship between docosahexaenoate (DHA) concentrations in erythrocyte membranes with DHA concentrations in brain synaptosomes from cerebellum, forebrain and caudate nucleus.

Animals↗
PubMed2000

Plasma thyroxine and cholesterol concentrations of miniature pigs are influenced by thermally oxidized dietary lipids.

To investigate the effect of a dietary oxidized oil on thyroid hormone status and circulating cholesterol, we conducted a study with 16 male miniature pigs fed a nutritionally adequate diet with 15% of either fresh or thermoxidized oil for 35 d (n = 8/group). The thermoxidized oil was prepared by heating sunflower oil at 110 degrees C for 48 h. The fresh oil consisted of a mixture of sunflower oil and lard (94:6, v/v) which had a fatty acid composition similar to the thermoxidized oil. At the end of the study, there were no differences in body weight gains and plasma clinicochemical variables between groups, suggesting that the thermoxidized oil did not induce general toxic symptoms. However, pigs fed the thermoxidized oil had significantly higher plasma concentrations of total and free thyroxine (P < 0.05) and a tendency for a higher plasma concentration of thyroid hormone-stimulating hormone (P < 0.1) than pigs fed the fresh oil. Additionally, pigs fed the thermoxidized oil had lower concentrations of cholesterol in plasma, LDL and HDL (P < 0.05). There were significant negative correlations between the plasma concentrations of total (r = -0.29) and free thyroxine (r = -0.40) and that of cholesterol (P < 0.05), suggesting that there is a causal relationship between the changes in thyroxine concentration and the reduction of plasma cholesterol. Our results indicate that there is a close relationship between alterations of thyroid hormone status and cholesterol metabolism in pigs fed a thermoxidized oil, and dietary oxidized fats should be considered in thyroid hormone disorders.

Animals↗
PubMed2002

LiF:Mg,Cu,P 'pin worms': miniature detectors for brachytherapy dosimetry.

Dose measurements in brachytherapy 192Ir implants are often difficult due to large dose gradients and complex photon spectra. Therefore, tissue-equivalent detectors with a high spatial resolution, such as the highly promising LiF:Mg,Cu,P thermoluminescent detectors (TLDs) are required. It was the aim of the present work to ascertain if miniature LiF:Mg,Cu,P TLDs can effectively measure the dose distribution around 192Ir implants. 'Pin worm' TLDs (type MCP, diameter 0.6 mm, length 2 mm) were compared with GR-200R (SSDL, Beijing) rods cut in half. The TLDs were tested for reproducibility and energy dependence using high dose rate (HDR) and low dose rate (LDR) brachytherapy units. 192Ir measurements were performed in a tissue equivalent phantom accommodating hollow needles and catheters routinely used in brachytherapy. Pin worms had an average reproducibility of less than +/-2% (1 SD) and a detection limit of less than 10 microGy. The small dimensions of the pin worms allowed their placement within brachytherapy needles and catheters. The measured relative dose distribution was in good agreement with the predictions of a computerised treatment planning system (ADAC Pinnacle); however, limitations in the TLD energy correction did not allow for absolute dose comparison.

Brachytherapy↗
PubMed2002

Miniature thermoluminescent detectors for dosimetry in radiotherapy.

At the Institute of Nuclear Physics in Kraków (INP), in collaboration with the Centre of Oncology in Kraków, several types of miniature thermoluminescent LiF:Mg,Ti and LiF:Mg,Cu,P detectors specially designed for clinical dosimetry in radiotherapy have been developed. The detectors are manufactured in the form of solid pellets of diameter down to 1 mm and typical thickness 0.5 mm, in the form of rods with a diameter of 0.5 mm and a length of a few mm, and as two-layer detectors with a thin (in the range of 0.065 mm) active layer of high-sensitive LiF:Mg,Cu,P. All three types of newly developed detectors have already been applied in proton beam dosimetry, surface dosimetry of eye-plaque brachytherapy applicators, phantom dosimetry for vascular brachytherapy and in vivo dosimetry in interstitial brachytherapy. These detectors were found to be very useful for dose measurements in high dose gradients, where spatial resolution better than 1 mm is required.

Brachytherapy↗
PubMed2002

Characterisation of an ultra-miniature counter for microdosimetric measurements in a therapeutic 400 MeV/A carbon beam.

Single event spectra of a clinical carbon beam have been measured by an ultra-miniature tissue-equivalent proportional counter (UMC). In order to cover the energy range of the Bragg peak, the incident energy of the carbon beam was degraded by aluminium plates. Single event spectra for carbon-events incident to the UMC were analysed and selected at several carbon energies using thin scintillation counters. It was found that the dose weighted lineal energy distributions have a doublet peak structure due to incident carbon beam and fragment contributions.

Calibration↗
PubMed1986

Effects of altrenogest and exogenous gonadotropins on ovarian function and embryo recovery in swine leukocyte antigen inbred miniature swine as influenced by cystic endometrial hyperplasia.

Altrenogest (ALT), a synthetic progestogen, and exogenous gonadotropins were administered to the Swine Leukocyte Antigen (SLA) inbred miniature pig that typically has a reduced ovulation rate and small litter size. In Study 1, 15 adult female pigs were either controls (Group I, n = 5), fed 15 mg ALT/day for 14 days (Group II, n = 5), or fed ALT and treated with pregnant mare's serum gonadotropin (1200 IU, i.m.) and human chorionic gonadotropin (500 IU, i.m.) 24 h and 104 h, respectively, after ALT withdrawal (Group III, n = 5). In Study 2, three groups of pigs (I, n = 24; II, n = 11; III, n = 11) were treated similarly to those in Study 1 except that pigs in Study 2 (Groups II and III) were mated. Ovaries of all animals in both studies were examined laparoscopically or by laparotomy 5-8 days after estrus to assess ovarian activity. The uteri of Group II and III animals in Study 2 were flushed with tissue culture medium, which was evaluated for the presence and quality of embryos. No pig demonstrated estrous behavior during ALT administration. Not all animals demonstrated typical estrous behavior after ALT withdrawal. When the data from both studies were combined, 2 of 16 (12.5%) of group II and 6 of 16 (37.5%) of Group III pigs failed to demonstrate standing estrus. Following ALT withdrawal, females in Groups II and III returned to estrus in 5.6 +/- 0.3 and 5.8 +/- 0.3 days, respectively (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatic oxygen supply-uptake relationship and metabolism during anesthesia in miniature pigs.

The study evaluated the effects of different anesthetics on the hepatic oxygen supply-demand relationship and hepatic lactate uptake (HLu). Miniature pigs (n = 33), weighing 20-31 kg, were divided into five groups and accordingly anesthetized with halothane, isoflurane, enflurane (0.9%, 1.5%, and 2.2% end-expired concentrations, respectively), fentanyl (100 micrograms/kg iv bolus followed by a continuous infusion of 50 micrograms.kg-1.h-1), or sodium pentobarbital (30 mg/kg iv bolus followed by a continuous infusion at a rate of 1-2 mg.kg-1.h-1). The surgical preparation allowed the authors to induce a stepwise decrease in hepatic blood supply without congestion in the preportal tissues. Prior to induced hepatic hypoperfusion, the values of hepatic oxygen delivery (HDO2) were the greatest in the isoflurane and fentanyl groups and the smallest in the halothane group, while the values of hepatic oxygen uptake (HVO2) were the smallest in the halothane group without differences among the other four groups. During stepwise decrease in hepatic blood and oxygen supply, HLu started to decrease at higher values of hepatic oxygen delivery in the fentanyl group (HDO2 = 10 mlO2.min-1.100 g-1) than in all others (HDO2 = 6-7 mlO2.min-1.100 g-1). At values of HDO2 equal to 2-3 mlO2.min-1.100 g-1, the values of HLu became negative, signifying that the liver began to release rather than to metabolize lactate. There was a linear relationship between the values of HDO2 and hepatic venous oxygen tension or saturation (r = 0.96; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

In vitro and in vivo effects of recombinant human interleukin-2 in naive miniature swine.

Recent data in mice have shown that early administration of recombinant human interleukin-2 (rIL-2) provides significant protection from lethal graft-versus-host disease. Because of the potential clinical importance of these findings, it will be important to assess the effectiveness of this therapy in a large animal preclinical bone marrow transplantation model. We report here our initial studies of the in vitro and in vivo effects of rIL-2 in miniature swine. In vitro 4-day cultures of pig peripheral blood lymphocytes (PBL) in complete medium containing rIL-2 at 1,000 U/ml resulted in optimal proliferation and generation of lymphokine-activated killer (LAK) cells. A pig-mouse hybridoma cell line was found to be highly sensitive as a LAK cell target. Two naive pigs received 20,000 U/kg and 2 pigs received 100,000 U/kg of rIL-2 intravenously twice a day for 4 days. No clinical symptoms were seen during or after administration at the lower dose while both high dose-treated animals showed generalized erythema from days 2 to 4, and one showed mild diarrhea during this period. The disappearance of IL-2 activity from the serum showed two components: (1) an initial fast component with a half-time of approximately 10 min and (2) a slow component with a half-time of approximately 60 min. LAK cell precursors disappeared from the peripheral circulation by 6 min after rIL-2 administration and began to recover by 6 h in the low dose recipients and only after 12 h in the high dose recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

In vivo treatment with monoclonal antibodies directed against CD4 and CD8 antigens in miniature swine.

Two monoclonal antibodies (mAb) with specificities for mature T-cell subsets in miniature swine have been characterized previously. Antibody 74-12-4 recognizes the porcine CD4 accessory molecule and 76-2-11 is specific for the CD8 molecule. We have now examined the effects of in vivo administration of 74-12-4 and 76-2-11 on several parameters of transplantation immunity. No prolongation of class I disparate skin or kidney graft survival was observed in animals treated with either mAb alone or with a combination of both. In addition, in vivo treatment with these mAbs, in combination with subtherapeutic total body irradiation, failed to permit engraftment of allogenic bone marrow. These therapeutic failures were thought likely to be a consequence of the fact that 74-12-4 coats, but does not deplete, CD4 cells in vivo. Because there are numerous anti-human mAbs that likewise fail to deplete in vivo, we have used 74-12-4 as a prototype to further manipulations aimed at achieving depletion. We attempted to eliminate 74-12-4-coated cells in two animals by subsequent administration of a hyperimmune pig anti-mouse Ig serum. In both such treated animals, administration of this serum produced surprisingly rapid clearance of 74-12-4 from the circulation and caused uncoating of CD4 cells, but no significant cell elimination was detected by flow cytometry. We have also prepared an anti-porcine-CD4 immunotoxin by conjugating 74-12-4 to the ribosome inhibitory plant toxin, pokeweed antiviral protein. This immunotoxin led to significant but not complete CD4 cell depletion from the peripheral blood in four of four treated animals. Further manipulations and possibly development of new anti-porcine CD4 mAbs may therefore be required to achieve complete depletion and successful mAb-mediated modification of transplantation responses.

Animals↗