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PubMed1994

Totally implantable total artificial heart and ventricular assist device with multipurpose miniature electromechanical energy system.

A multipurpose miniature electromechanical energy system has been developed to yield a compact, efficient, durable, and biocompatible total artificial heart (TAH) and ventricular assist device (VAD). Associated controller-driver electronics were recently miniaturized and converted into hybrid circuits. The hybrid controller consists of a microprocessor and controller, motor driver, Hall sensor, and commutation circuit hybrids. The sizing study demonstrated that all these components can be incorporated in the pumping unit of the TAH and VAD, particularly in the centerpiece of the TAH and the motor housing of the VAD. Both TAH and VAD pumping units will start when their power line is connected to either the internal power pack or the external battery unit. As a redundant driving and diagnostic port, an emergency port was newly added and will be placed in subcutaneous location. In case of system failure, the skin will be cut down, and an external motor drive or a pneumatic driver will be connected to this port to run the TAH. This will minimize the circulatory arrest time. Overall efficiency of the TAH without the transcutaneous energy transmission system was 14-18% to deliver pump outputs of 4-9 L/min against the right and left afterload pressures of 25 and 100 mm Hg. The internal power requirement ranged from 6 to 13 W. The rechargeable batteries such as NiCd or NiMH with 1 AH capacity can run the TAH for 30-45 min. The external power requirement, when TETS efficiency of 75% was assumed, ranged from 8 to 18 W. The accelerated endurance test in the 42 degrees C saline bath demonstrated stable performance over 4 months. Long-term endurance and chronic animal studies will continue toward a system with 5 years durability by the year 2000.

Animals↗
PubMed1994

Characterization of cutaneous antigen presentation in partially inbred miniature swine.

MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (APC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8-4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function, EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coated petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 x 10(7) TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous APC which are able to induce cutaneous immunity in a matter similar to Langerhans cells in murine or human skin.

Animals↗
PubMed2002

Miniaturization of fluorescence microscopes using fibre optics.

In both medical research and diagnostics characterization of biological tissue on the cellular level relies on high-resolution optical microscopy. In most cases, however, tissue is excised for microscopic investigation, in part because conventional microscopes are bulky instruments. Imaging of cells in the intact living organism has been difficult. Over the last decade several groups have developed miniature confocal microscopes that use fibre optics to deliver light to the specimen and to measure either reflected or excited fluorescence light. In addition, two-photon excitation recently has been employed in a small portable 'fibrescope'. A potential clinical application of these microscope probes is their endoscopic use for optical biopsy of inner organs or guidance of conventional biopsy. As a mobile research tool they may permit imaging of neuronal activity in the brain of awake, behaving animals. Here, we review technological approaches to build miniaturized fluorescence microscopes and discuss their potential applications.

Animals↗
PubMedDate not supplied

Toward a miniaturized fundus camera.

Retinopathy of prematurity (ROP) describes a pathological development of the retina in prematurely born children. In order to prevent severe permanent damage to the eye and enable timely treatment, the fundus of the eye in such children has to be examined according to established procedures. For these examinations, our miniaturized fundus camera is intended to allow the acquisition of wide-angle digital pictures of the fundus for on-line or off-line diagnosis and documentation. We designed two prototypes of a miniaturized fundus camera, one with graded refractive index (GRIN)-based optics, the other with conventional optics. Two different modes of illumination were compared: transscleral and transpupillary. In both systems, the size and weight of the camera were minimized. The prototypes were tested on young rabbits. The experiments led to the conclusion that the combination of conventional optics with transpupillary illumination yields the best results in terms of overall image quality.

Animals↗
PubMed1996

Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the beginning of each meal, and for the following 2 weeks they received itraconazole orally combined with intravenous administration of rifampin at 10 mg/kg/day. Coadministration of rifampin resulted in an 18-fold decrease in the maximum concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2) to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration-time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin affects itraconazole kinetics considerably at steady state in this miniature-pig model, probably by inducing hepatic metabolism of itraconazole.

Animals↗
PubMed2004

Effects of a synthetic progestogen, altrenogest, on oestrus synchronisation and fertility in miniature pigs.

Groups of six, six and eight miniature gilts, respectively, received 5, 10 or 15 mg/day of altrenogest for 18 days, and the numbers of corpora lutea and residual follicles were counted approximately 14 days after the treatment by an exploratory laparotomy. They were compared with the numbers in a control group of eight gilts which were examined six to eight days after oestrus. The interval between the last dose of altrenogest and the onset of oestrus increased with the dose of altrenogest, and was significantly longer after the treatments with 10 or 15 mg/day than after 5 mg/day (P < 0.01). Significantly more corpora lutea were observed in the gilts receiving 5 or 10 mg/day of altrenogest than in the control gilts (P < 0.1). Groups of six, seven and six miniature gilts that had respectively received 5, 10 or 15 mg/day of altrenogest were artificially inseminated; four, six and five of the gilts in these groups farrowed, and their mean (sd) litter sizes were 5.5 (2.4), 6.8 (1.2) and 5.0 (2.3), respectively. All six of a group of control gilts farrowed and their mean litter size was 5.8 (1.2).

Animals↗
PubMed1987

Distribution of blood flow in muscles of miniature swine during exercise.

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.

Animals↗
PubMed1989

Exercise training increases coronary transport reserve in miniature swine.

Female yucatan miniature swine were trained on a treadmill (ET) or were cage confined (C) for 16-22 wk. The ET pigs had increased exercise tolerance, heart weight-to-body weight ratio, and skeletal muscle oxidative capacity. After anesthesia the left anterior descending coronary artery was cannulated and pump perfused with blood while aortic, central venous, and coronary perfusion pressures, electrocardiogram, heart rate, and coronary blood flow were monitored. Capillary permeability-surface area product (PS) for EDTA was determined with the single-injection indicator-diffusion method by use of an organ model based on the Sangren-Sheppard equations for capillary transport. Coronary blood flow (CBF) and PS were compared before and during maximal adenosine vasodilation with coronary perfusion pressures at 120 mmHg. Results indicate that there were no differences in base-line CBF or PS between C and ET groups. alpha-Receptor blockade with phentolamine and/or prazosin, before adenosine vasodilation, produced increases in PS in C pigs but had little effect in ET pigs. During maximal vasodilation with adenosine, ET pigs had greater CBF (447 +/- 24 vs. 366 +/- 27 ml.min-1.100 g-1) and greater PS (83 +/- 9 vs. 55 +/- 7 ml.min-1.100 g-1) than the C group. It is concluded that ET induces an increased coronary transport capacity in miniature swine that includes a 22% increase in blood flow capacity and a 51% increase in capillary exchange capacity.

Animals↗
PubMed1997

Skeletal muscle biochemical adaptations to exercise training in miniature swine.

The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16-20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 +/- 1.1 mumol.min-1.g-1; Trn, 23.9 +/- 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 +/- 6%; Trn, 10 +/- 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 +/- 2; Trn, 22 +/- 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

Adaptation, Physiological↗
PubMed1998

Sleep apnea in obese miniature pigs.

We postulated that three extremely obese Yucatan miniature pigs would have more sleep apnea than three nonobese Yucatan miniature pigs. Pigs were studied with the use of electroencephalograms, inductance plethysmography, oximetry, expired nasal CO2, or thermistors. All of the obese pigs, but none of the nonobese pigs, had both sleep apnea (8.5, 10.3, and 97.0 in obese pigs vs. O apnea + hypopnea/h in all nonobese pigs; P < 0.05) and oxyhemoglobin desaturation episodes during sleep [9.4 +/- 3.0 vs. 0 + 0.53 (SD) mean desaturation episodes/h in obese pigs vs. nonobese pigs, respectively; P < 0.05]. Two of the extremely obese pigs had obstructive sleep apnea, whereas the third obese pig had central sleep apnea. We conclude that sleep apnea occurs in extremely obese Yucatan minipigs and suggest that this animal can be used as a model for sleep apnea in obesity.

Animals↗
PubMed1999

Clinical application of intrauterine sonography with high-frequency, real-time miniature transducer in gynecologic disorders. Preliminary report.

Our purpose was to determine whether intrauterine sonography with high-frequency, real-time miniature transducer (20 MHz) is useful for the diagnosis of gynecologic disorders. The study consisted of 37 women: 8 normal volunteers, 2 with molar pregnancy, 4 fibromyoma, 4 endometrial polyp, 1 intrauterine adhesion, 1 septate uterus, 5 atypical hyperplasia, 8 endometrial cancer, and 4 with cervical cancer. Comparison of diagnostic efficacy for gynecologic disorders between transvaginal and intrauterine sonography was made. The probe was easily introduced into the endometrial cavity in all patients. No notable complications were encountered. In subjects with a normal uterus, higher resolution for endometrial texture was obtained with intrauterine sonography than with transvaginal scanning. In patients with molar pregnancy, typical vesicular echoes were clearly identified. In patients with fibromyoma, myoma nodules were not clearly visualized because of poor attenuation of ultrasound. In subjects with endometrial polyp, intrauterine adhesion, and septate uterus, intrauterine lesions were clearly identified. In patients with atypical hyperplasia, high echogenicity of the endometrium was characterized. Myometrial invasion of the endometrial cancer was estimated correctly in 6 of 8 patients (75%). Intrauterine sonography could clearly detect early cervical invasion of the cervical cancer in all 4 patients, but transvaginal sonography could not do it. Intrauterine sonography with a high-frequency, real-time miniature transducer might be a useful diagnostic modality in gynecologic disorders, especially in the evaluation of early cervical cancer, endometrial cancer, and possibly in infertility practice.

Adult↗
PubMed1992

Dietary fish oil plus lovastatin decreases both VLDL and LDL apo B production in miniature pigs.

Our previous apolipoprotein (apo) B kinetic studies of miniature pigs fed fish oil (Maxepa) demonstrated that very low density lipoprotein (VLDL) apo B concentrations were markedly reduced but that low density lipoprotein (LDL) concentrations were only modestly lowered because of a threefold increase in the conversion of VLDL apo B to LDL. In the present study, the effect of Maxepa plus lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on apo B metabolism was assessed. Miniature pigs (n = 6) were simultaneously injected with autologous 131I-VLDL and 125I-LDL after a diet of pig chow supplemented with 30 g/day of Maxepa and again after the addition of lovastatin, 30 mg/day. Kinetic data were analyzed by compartmental analysis with use of the CONSAM program. Compared with Maxepa alone, the addition of lovastatin reduced VLDL apo B concentrations by 21% (p less than 0.003) because of reduced VLDL apo B production (26%, p less than 0.005), as the fractional clearance rate was not affected. Conversion of VLDL apo B to LDL was reduced by 48% (p less than 0.005), and the direct removal of VLDL apo B from plasma was reduced by 25% (p less than 0.01). Maxepa plus lovastatin reduced LDL apo B concentrations by 44% (p less than 0.004). This was due to a 38% (p less than 0.002) decrease in LDL production, which was primarily derived from VLDL. The LDL apo B fractional catabolic rate was not significantly changed. Thus, a combination of Maxepa and lovastatin reduces both VLDL and LDL apo B concentrations, primarily by decreasing production rates.

Animals↗
PubMed1991

Chemical sympathectomy alters the development of hypertension in miniature swine.

To determine if the neurotoxin 6-hydroxydopamine could be used to chemically sympathectomize neonatal miniature swine, eight newborn swine were treated with 6-hydroxydopamine beginning on the first day after birth and continuing at regular intervals for the next 6 months. Six littermates served as controls and received vehicle injections. A significant reduction in the pressor response to intravenous tyramine (95%) and in the tissue norepinephrine content of the kidneys, left ventricle, and gastrocnemius muscle (more than 93%) provided evidence for an effective long-term sympathectomy in the 6-hydroxydopamine-treated animals. In addition, the blood pressure response of these young, chemically sympathectomized swine to chronic deoxycorticosterone acetate treatment was evaluated. Mean arterial pressure before deoxycorticosterone was similar in the 6-hydroxydopamine-treated (116 +/- 2 mm Hg) and control (125 +/- 5 mm Hg) groups. One week after deoxycorticosterone, mean arterial pressure had risen significantly by 20-22 mm Hg in both groups. Blood pressure continued to increase in the control group, reaching a value of 163 +/- 6 mm Hg by the third week after treatment. In contrast, mean arterial pressure in the 6-hydroxydopamine group did not increase further during weeks 2 and 3 after deoxycorticosterone. In conclusion, chronic treatment of neonatal swine with 6-hydroxydopamine produced an animal model with an effective, general, peripheral sympathectomy. The significant attenuation of the hypertensive response in these sympathectomized animals lends further support to the hypothesis that an intact sympathetic nervous system is necessary for the full expression of deoxycorticosterone hypertension in miniature swine.

Animals↗
PubMed1984

Effect of ketone bodies on glucose production and utilization in the miniature pig.

The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-beta-OH-butyrate (Na-DL-beta-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, alpha-amino-N, and free fatty acids (FFA) were all reduced. Infusion of Na-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and alpha-amino-N increased. Infusing different amounts of Na-DL-beta-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed. Prevention of the Na-DL-beta-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 mumol/kg X min) did not prevent hypoglycemia. Infusion of Na-DL-beta-OHB plus insulin (0.4 mU/kg X min) showed no additive effect on the inhibition of Ra. Ketones did not inhibit the insulin-stimulated metabolic clearance rate (MCR) for glucose. Infusion of somatostatin (0.2 micrograms/kg X min) initially decreased plasma glucose, Ra, and Rd, which was followed by an increase in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-beta-OHB, hypoglycemia and the reduced Ra were maintained. In the anaesthetized 24-h starved miniature pig, Na-DL-beta-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and alpha-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, alpha-amino-N, and FFA were decreased, while ketone body utilization increased. Repeated infusion of Na-DL-beta-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary N-excretion accelerated. To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone body-induced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in R(a), glucose utilization declines during ketone infusion. (d)The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

3-Hydroxybutyric Acid↗
PubMed1997

Reaction strains on the condylar neck during mastication and maximum muscle stimulation in different condylar positions: an experimental study in the miniature pig.

Most researchers agree that the primate temporomandibular joint (TMJ) is loaded compressively during function and that condylar position must play a role in mediating such loads. However, the precise nature of that role remains unclear. Using a pig model in this study, we attempted to analyze strain on the neck of the condyle during normal mastication and during simulated function in different condylar positions. Miniature three-element rosette strain gauges were bonded to the lateral surface of the condylar neck in 4 female miniature pigs (one per condyle). Measurements of strain were made during normal mastication and with the pigs under general anesthesia during maximum stimulation of the masseter and temporalis muscles in each of five condylar positions--centric occlusion, centric relation, anterior, relaxed and wide open--established through use of acrylic splints. Condylar position was evaluated by superimposition of lateral and dorsoventral cephalograms, with measurement of horizontal and vertical changes in location of implants placed on the zygomatic arch. As in primates, the TMJ was found to be load-bearing during mastication, with compressive strain oriented approximately perpendicular to the occlusal plane. In 3 pigs, strain was higher during balancing than during working function. During stimulation, the TMJ reaction strains were significantly lower with the condyles in the anterior position compared with the other positions, and the compressive strain was directed more anteriorly along the neck of the condyle in that position.

Analysis of Variance↗
PubMedDate not supplied

Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes.

Although young infants are at greater risk for total parenteral nutrition (TPN)-related liver disease than adults, previous studies on the effect of the TPN energy source on the development of hepatic steatosis have been carried out in adult rats and adult humans. We studied the effect of a glucose and a glucose/fat TPN energy regimen on hepatic chemical composition and the development of steatosis in newborn miniature pigs. Twenty miniature pigs were randomized at 10 days of age to receive a TPN regimen which utilized either glucose (group A) or glucose/fat (group B) as the non-nitrogen energy source. After 8 days, blood was drawn for insulin, glucagon, SGPT, albumin, and bilirubin determinations. Samples of liver were obtained at 9 days. Plasma insulin levels were significantly higher and glucagon levels lower in group A piglets than in those in group B. Normal values were obtained for SGPT, albumin, and bilirubin, and no differences were found between groups. Chemical analysis of the livers revealed no differences between groups in the concentrations of glycogen, fat, protein, DNA, and RNA. Group A animals had significantly higher concentrations of water than group B (group A: 0.75 +/- 0.01 liter/kg; group B: 0.74 +/- 0.01; p less than 0.03). A significant correlation was found in group B between the plasma insulin/glucagon ratio and the hepatic glycogen concentration (r = 0.73, p less than 0.05). Group A animals had fat vacuoles in centrilobular hepatocytes, in contrast with group B animals who had visible fat only in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Total parenteral nutrition energy composition affects small intestinal disaccharidase activity in the newborn miniature pig.

Total parenteral nutrition (TPN) decreases disaccharidase activity in the small intestine of humans and miniature piglets. The possibility, however, that specific components of TPN (eg, the energy mix) will increase disaccharidase activity has largely been unexplored. The identification of such components would be particularly useful in the treatment of premature infants with immature gastrointestinal tracts and patients with small intestinal mucosal disease associated with decreased disaccharidase activity. To determine whether the TPN energy composition affects small intestinal disaccharidase activity, 7-day-old miniature piglet littermates were randomized to receive TPN containing either glucose (group G) or glucose and fat (group G/F) as the nonnitrogen energy source(s). The TPN regimens were isonitrogenous and isoenergetic. The piglets were not allowed oral intake during the 7 days they were maintained on TPN. At 14 days of age the piglets were killed and the small intestines analyzed for weight, protein, DNA, and disaccharidase activity. Body weight was similar between groups at both the beginning and end of the study. The TPN regimen did not affect small intestinal weight of protein and DNA content. However, jejunal and ileal sucrase and ileal maltase activities (mumol/min.kg body wt +/- SD) were greater in group G than those in group G/F (28 +/- 9 vs 19 +/- 11, p = 0.04; 13 +/- 7 vs 7 +/- 4, p = 0.037; and 31 +/- 8 vs 19 +/- 10, p = 0.0088, respectively). No differences in lactase activity were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

High-density miniaturized thermal shift assays as a general strategy for drug discovery.

More general and universally applicable drug discovery assay technologies are needed in order to keep pace with the recent advances in combinatorial chemistry and genomics-based target generation. Ligand-induced conformational stabilization of proteins is a well-understood phenomenon in which substrates, inhibitors, cofactors, and even other proteins provide enhanced stability to proteins on binding. This phenomenon is based on the energetic coupling of the ligand-binding and protein-melting reactions. In an attempt to harness these biophysical properties for drug discovery, fully automated instrumentation was designed and implemented to perform miniaturized fluorescence-based thermal shift assays in a microplate format for the high throughput screening of compound libraries. Validation of this process and instrumentation was achieved by investigating ligand binding to more than 100 protein targets. The general applicability of the thermal shift screening strategy was found to be an important advantage because it circumvents the need to design and retool new assays with each new therapeutic target. Moreover, the miniaturized thermal shift assay methodology does not require any prior knowledge of a therapeutic target's function, making it ideally suited for the quantitative high throughput drug screening and evaluation of targets derived from genomics.

Estrogen Receptor alpha↗