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Biomedical subjects

T Wang

Publications and source records attributed to T Wang.

At least 379 records · Page 21Linked to original sources

Effects of pravastatin on chronic rejection of rat cardiac allografts.

BACKGROUND: Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, inhibits coronary transplant vasculopathy in the clinical setting. To further delineate the immune modulatory effect of this agent, it was tested in a rat cardiac transplant model of chronic rejection. METHODS: Rat heterotopic abdominal cardiac transplants were performed using a Lewis to Fischer 344 combination. Fischer 344 recipients received a brief course of cyclosporine to decrease the incidence of acute rejection. Experimental groups were treated with either high-dose (10 mg/kg) or low-dose (5 mg/kg) pravastatin for 120 days, while a control group did not receive pravastatin. The effect of pravastatin on chronic rejection of cardiac allografts was analyzed by histology, and the expression of laminin, fibronectin, macrophages, and T cells was assessed by immunohistochemistry. RESULTS: Coronary transplant vasculopathy was inhibited in both groups of pravastatin-treated animals, as compared with controls. Immunohistochemistry revealed that control animals had degraded laminin and fibronectin which paralleled the degree of tissue necrosis. In contrast, pravastatin-treated animals had modest amounts of extracellular matrix proteins retained within intermyocytes and endothelium, a pattern seen in native cardiac tissue. The pravastatin-treated groups also had fewer graft-infiltrating macrophages, specifically within the arterial intima and perivascular areas. CONCLUSIONS: Progressive chronic vascular rejection, a leading cause of allograft failure, can be inhibited by pravastatin in a well-defined rat cardiac transplant model. Pravastatin appears to inhibit the synthesis and subsequent degradation of extracellular matrix proteins and block the infiltration of macrophages to the graft, which emphasizes that this inflammatory cell plays a major role in the pathogenesis of transplant chronic rejection.

Animals↗

Fas ligand gene transfer to renal allografts in rats: effects on allograft survival.

BACKGROUND: Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection. METHODS: The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis (RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9 x 10(9) plaque-forming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting. RESULTS: Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P < 0.05). CONCLUSIONS: (1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.

Adenoviridae↗

New capsule with tailored properties for the encapsulation of living cells.

A new capsule for the encapsulation and transplantation of pancreatic islets has been developed. Five active ingredients are involved in the capsule formation process: high viscosity sodium alginate (SA-HV), cellulose sulfate (CS), poly(methylene-co-guanidine) hydrochloride (PMCG), calcium chloride, and sodium chloride. Complexation reaction exhibits several unique features: (1) solution of SA-HV with CS represents a physical mixture of two entangled polyanions that provide both pH-sensitive (carboxylic) and permanently charged (sulfate) groups; (2) presence of CaCl2 in the cation solution ensures formation of the gelled bead after the drop of polyanion solution is immersed in the cation solution; (3) character of the polycation (PMCG), i.e., low molecular weight and unusually high charge density, combines both high mobility and reactivity; (4) presence of PMCG in cation solution, together with CaCl2, gives rise to the competitive binding of these two cations based on their diffusion and affinity towards the anion groups; and (5) NaCl provides the anti-gelling sodium ions that significantly affect the reaction of CaCl2 with the polyanion matrix, thus altering the final properties of the capsule surface, shape, and permeability. The capsule size, mechanical strength, membrane thickness, and permeability can be precisely adjusted and quantified. Detailed information on the permeability aspects is given in another paper by Brissová et al. [J. Biomed. Mater. Sci., 39, 61 (1998)]. The new features concerning capsule processing and testing are presented. We believe that the capsule characteristics can be optimized in the next step to meet the biological criteria. The initial transplantation results suggest that this capsule is biocompatible and noncytotoxic and is a promising candidate for the immunoisolation of cells such as pancreatic islets.

Animals↗

Control and measurement of permeability for design of microcapsule cell delivery system.

Transplantation of immunoisolated islets of Langerhans has been proposed as a promising approach to treating insulin-dependent diabetes mellitus. Recently, a cell delivery system based on a multicomponent microcapsule has been designed for the immunoisolation of insulin-secreting pancreatic islets. The capsule, formed by polyelectrolyte complexation of sodium alginate and cellulose sulfate with poly(methylene-co-guanidine), markedly has improved mechanical strength compared with the widely used alginate/poly(L-lysine) capsules. It also provides a flexibility for readily adjusting membrane thickness and capsule size, and, more important, the membrane permeability can be altered over a wide range of molecular sizes. To rigorously test the capsule diffusion properties, we have improved capsule permeability measurement by using two complementary methods: (1) size exclusion chromatography with dextran standards; and (2) newly developed methodology for assessing permeability to a series of biologically relevant proteins. Viability and function of rat pancreatic islets enclosed in the capsules with different permeability were tested in vitro. The insulin secretion of encapsulated islets was well preserved even though slightly delayed in comparison with a control group of free islets. We believe that the unique features of this encapsulation system together with the precise characterization of its physical parameters will enable us to find the optimal range of capsule permeability for in vitro and in vivo survival and function of encapsulated pancreatic islets.

Alginates↗

Nonaqueous capillary zone electrophoresis for separation of free fatty acids with indirect fluorescence detection.

The feasibility of combining nonaqueous capillary zone electrophoresis with indirect fluorescence detection was studied for the efficient separation and sensitive detection of ionizable hydrophobic substances which do not possess practically suitable detection properties. Medium- and long-chain free fatty acids, C6-C24, were selected as test compounds. The results showed that such a wide range of medium- and long-chain free fatty acids could be separated between any two consecutive homologs in one run and be detected at a level of about 0.01-0.02 mM in highly basic methanol/acetonitrile media containing fluorescein as coion of background electrolyte for indirect fluorescence detection.

Acetonitriles↗

Copper exposure impairs intra- and extracellular acid-base regulation during hypercapnia in the fresh water rainbow trout (Oncorhynchus mykiss).

In order to evaluate the impact of water-borne copper on acid-base regulation in fresh water rainbow trout, chronically cannulated fish were exposed to copper (0.6 mg 1(-1)), hypercapnia (water PCO2 of 6 mmHg) or a combination of copper and hypercapnia, while a fourth untreated group served as the control. Blood samples obtained at 0 h, 4 h and 24 h were analysed for acid-base status, ion concentrations and respiratory parameters. Tissue samples from caudal skeletal muscle, liver and gill filaments were examined for intracellular acid-base status, ion- and water contents, and copper concentration. Exposure to copper alone elicited a small extracellular metabolic alkalosis, no changes in arterial PO2, and a minor decrease in plasma ion concentrations. Hypercapnia alone increased arterial PCO2 from approximately 2 mmHg to 7.2 mmHg, but the extracellular respiratory acidosis present at 4 h was almost completely compensated at 24 h due to an increase in plasma bicarbonate concentration [HCO3-] from 8.1 mM to 24.4 mM. Combined exposure to hypercapnia and copper resulted in a slightly larger acidosis at 4 h, and the fish failed to restore extracellular pH at 24 h, because plasma [HCO3-] only increased to 16.3 mM. Fish exposed to hypercapnia and copper also showed a delayed recovery of intracellular pH in skeletal muscle, compared to fish exposure to hypercapnia only. Thus, copper exposure impaired both extracellular and intracellular acid-base regulation during hypercapnia. When seen in connection with only minor effects of copper on osmoregulatory and respiratory parameters, the reduced ability to regulate acid-base suggests that acid-base regulation may be one of the most copper-sensitive branchial functions.

Acid-Base Equilibrium↗

Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.

BACKGROUND: Posttransplantation lung reperfusion injury continues to be a major problem. We have shown that controlling the initial period of reperfusion limits this injury after 2 hours of warm lung ischemia. The effectiveness of this modality, however, is unknown after longer periods of cold ischemia, which more closely mimics the clinical situation. METHODS: After baseline measurements, 10 pigs had the left lung flushed with a modified Euro-Collins solution, explanted, stored at 4 degrees C for 24 hours, and transplanted into 10 other pigs. Five (group 1) underwent uncontrolled reperfusion created by removal of the vascular clamps after implantation of the new left lung, mimicking the clinical situation. The other five (group 2) underwent controlled reperfusion, which we performed by taking blood from the femoral artery, mixing it with a crystalloid solution (using a mixer heater) to make the blood hyperosmolar, alkalotic, and substrate-enriched, and pumping it through a leukocyte-depleting filter into the transplanted lung for 10 minutes at a pressure of 20 to 30 mm Hg before removing the pulmonary artery clamp. The right pulmonary artery and bronchus were then ligated, and left lung function was assessed each hour for 4 hours and compared with baseline. RESULTS: Controlled reperfusion (group 2) minimized the reperfusion injury, preserving posttransplant pulmonary compliance (92% +/- 1% versus 68% +/- 1%; p < 0.001), reducing the rise in pulmonary vascular resistance (27% +/- 2% versus 166% +/- 3%; p < 0.001), improving oxygenation (PO2, 425 +/- 14 versus 82 +/- 11 mm Hg; p < 0.001), and lowering myeloperoxidase activity (0.22 +/- 0.02 versus 0.45 +/- 0.02 deltaOD/mg protein per minute; p < 0.001) and tissue edema (83.0% +/- 0.3% versus 84.9% +/- 0.3%; p < 0.001) compared with uncontrolled reperfusion, which resulted in an injury so severe that 3 of 5 pigs died before the 4-hour measurements. CONCLUSIONS: After 24 hours of cold ischemia uncontrolled reperfusion results in a severe pulmonary reperfusion injury. This injury is almost completely avoided by controlling the composition (modified solution and white blood cell filter) and conditions (pressure) of the reperfusion. Because this experiment mimics the clinical situation, it suggests surgeons should begin to use this modality to limit reperfusion injury after lung transplantation.

Animals↗

The importance of cardioplegic infusion pressure in neonatal myocardial protection.

BACKGROUND: Cardioplegia infusion pressure is usually not directly monitored during neonatal heart operations. We hypothesize that the immature newborn heart may be damaged by even moderate elevation of cardioplegic infusion pressure, which in the absence of direct aortic monitoring may occur without the surgeon's knowledge. METHODS: Twenty neonatal piglets received cardiopulmonary bypass and the heart was protected for 70 minutes with multidose blood cardioplegia infused at an aortic root pressure of 30 to 50 mm Hg (low pressure) or 80 to 100 mm Hg (high pressure). Group 1 (n = 5, low pressure), and group 2 (n = 5, high pressure) were uninjured (nonhypoxic) hearts. Group 3 (n = 5, low pressure) and group 4 (n = 5, high pressure) first underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) before initiating cardiopulmonary bypass to produce a clinically relevant hypoxic stress before cardiac arrest. Function was assessed using pressure volume loops (expressed as a percentage of control), and coronary vascular resistance was measured with each cardioplegic infusion. RESULTS: In nonhypoxic (uninjured) hearts (groups 1 and 2) cardioplegic infusion pressure did not significantly affect systolic function (end systolic elastance, 104% versus 96%), preload recruitable stroke work (102% versus 96%) diastolic compliance (152% versus 156%), or coronary vascular resistance but did raise myocardial water (78.9% versus 80.1%; p < 0.01). Conversely, if the cardioplegic solution was infused at even a slightly higher pressure in hypoxic hearts (group 4), there was deterioration of systolic function (end systolic elastance, 28% versus 106%) (p < 0.001) and preload recruitable stroke work (31% versus 103%; p < 0.001), rise in diastolic stiffness (274% versus 153%; p < 0.001), greater myocardial edema (80.5% versus 79.6%), and marked increase in coronary vascular resistance (p < 0.001) compared to hypoxic hearts given cardioplegia at low infusion pressures (group 3), which preserved function. CONCLUSIONS: Hypoxic neonatal hearts are very sensitive to cardioplegic infusion pressures, such that even moderate elevations cause significant damage resulting in myocardial depression and vascular dysfunction. This damage is avoided by using low infusion pressures. Because small differences in infusion pressure may be difficult to determine without a direct aortic measurement, we believe it is imperative that surgeons directly monitor cardioplegia infusion pressure, especially in cyanotic patients.

Animals↗

Controlled reperfusion after lung ischemia: implications for improved function after lung transplantation.

OBJECTIVES: Despite improvements in organ preservation, reperfusion injury remains a major source of morbidity and mortality after lung transplantation. This pilot study was designed to investigate the effects of controlled reperfusion after lung ischemia. METHODS: Twenty adult pigs underwent 2 hours of warm lung ischemia by crossclamping the left bronchus and pulmonary artery. In five (group 1), the clamp was simply removed at the end of ischemia (uncontrolled reperfusion). The 15 other pigs underwent modified reperfusion using blood from the femoral artery to perfuse the lung through the pulmonary artery (pressure 40 to 50 mm Hg) for 10 minutes before removing the pulmonary artery clamp. In five (group 2), the blood was mixed with crystalloid, resulting in a substrate-enriched, hypocalcemic, hyperosmolar, alkaline solution. In five (group 3), the blood was circulated through a leukocyte-depleting filter, and the last five (group 4) underwent reperfusion with both a modified solution and white blood cell filter. Lung function was assessed 60 minutes after reperfusion, and biopsy specimens were taken. RESULTS: Controlled reperfusion with both a white blood cell filter and modified solution (group 4) completely eliminated the reperfusion injury that occurred with uncontrolled reperfusion (group 1), resulting in complete preservation of compliance (98% +/- 1% vs 77% +/- 1%; p < 0.001, and arterial/alveolar ratio (97% +/- 2% vs 27% +/- 2%; p < 0.001); no increase in pulmonary vascular resistance (106% +/- 1% vs 198% +/- 1%; p < 0.001); lowered tissue edema (82.1% +/- 0.4% vs 84.3% +/- 0.2%; p < 0.001), and myeloperoxidase activity (0.18 +/- 0.02 vs 0.35 +/- 0.02 deltaOD/min/mg protein; p < 0.001). In contrast, using either a white blood cell filter or modified solution separately improved but did not avoid the reperfusion injury, resulting in pulmonary function and tissue edema levels that were intermediate between group 1 (uncontrolled reperfusion) and group 4 (white blood cell filter and modified solution). CONCLUSION: After 2 hours of warm pulmonary ischemia, (1) a severe lung injury occurs after uncontrolled reperfusion, (2) controlled reperfusion with either a modified reperfusion solution or white blood cell filter limits, but does not avoid, a lung reperfusion injury, (3) reperfusion using both a modified reperfusate and white blood cell filter results in complete preservation of pulmonary function. We therefore believe surgeons should control the reperfusate after lung transplantation to improve postoperative pulmonary function.

Animals↗

Temperature effects on lung and blood gases in Bufo paracnemis: consequences of bimodal gas exchange.

The arterial pH decreases with rising body temperature in ectothermic vertebrates. We report on how this regulation was achieved in relation to bimodal respiration in the toad Bufo paracnemis. Gas exchange was measured for the lung and also for the whole body (skin and lung). In addition, lung gas pressures (PL(O2) and PL(CO2)) and arterial blood gases (pH and P(O2)) were measured at 17, 27 and 35 degrees C. Arterial pH fell from 7.85 at 17-7.64 at 35 degrees C. Concomitantly, PL(CO2) increased from 5.6 mmHg at 17 degrees C to 10.4 mmHg at 35 degrees C. Regardless of temperature, PL(O2) remained virtually constant at 125-126 mmHg, whereas arterial P(O2) increased significantly with rising temperature (50 mmHg at 17 degrees C; 79 mmHg at 35 degrees C). The pulmonary gas exchange ratio (RE) increased from 0.28 at 17 degrees C to 0.51 at 35 degrees C, while the ratio for whole body gas exchange (lung + skin) was close to 0.8 irrespective of temperature. Since CO2 conductance of the skin increased little with temperature, the lung eliminated a larger fraction of total CO2 output. This shift caused the increase of RE for pulmonary exchange with rising temperature, which increased PL(CO2) and contributed to a negative deltapHa/deltaT. Therefore, bimodal respiration in Bufo accounted for part of the temperature-dependent pH regulation, while the final adjustments depend on pulmonary ventilation.

Animals↗

Computed radiography versus screen-film mammography in detection of simulated microcalcifications: a receiver operating characteristic study based on phantom images.

RATIONALE AND OBJECTIVES: The authors compare a 43-micron computed radiographic system with a mammographic screen-film system for detection of simulated microcalcifications in an observer-performance study. MATERIALS AND METHODS: The task of detecting microcalcifications was simulated by imaging aluminum wire segments (200-500 microns in length; 100, 125, or 150 microns in diameter) that overlapped with tissue background structures produced by beef brisket. A total of 288 such simulations were generated and examined with both computed radiography and conventional screen-film mammography techniques. Computed radiography was performed with high-resolution plates, a 43-micron image reader, and a 43-micron laser film printer. Computed radiographic images were printed with simple contrast enhancement and compared with screen-film images in a receiver operating characteristic study in which experienced readers detected and scored the simulated microcalcifications. Observer performance was quantitated and compared by computing the area under the receiver operating characteristic curve. RESULTS: Although the resolution of the computed radiography system was better than that of commercial systems, it fell short of that of screen-film systems. For the 100-micron microcalcifications, the difference in the average area under the curve was not statistically significant, but it was significant for the larger simulated microcalcifications: the average area under the curve was 0.58 for computed radiography versus 0.76 for screen-film imaging for the 125-micron microcalcifications and 0.83 versus 1.00, respectively, for the 150-micron microcalcifications. CONCLUSION: Observer performance in the detection of small simulated microcalcifications (100-150 microns in diameter) is better with screen-film images than with high-resolution computed radiographic images.

Breast Diseases↗

Case-control study of diet and prostate cancer in China.

INTRODUCTION: A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer. However, limited epidemiologic study has never examined the role of diet in low risk populations. METHODS: A case-control study was conducted in 12 cities in China to evaluate the relationship between dietary factors and prostate cancer risk. We conducted personal interviews with 133 histopathologically confirmed prostate cancer cases diagnosed between 1989 to 1992 and 265 neighborhood controls of similar age. RESULTS: Cases were more likely than controls to consume food with high fat and from animal sources (p < 0.01). The daily fat intake and the percentage of energy from fat were statistically significantly higher among cases than among controls (p < 0.01). The adjusted odds ratio for total fat between lowest quartiles and highest quartiles was OR = 3.6 (95 percent C.I. 1.8-7.2); for saturated fat, OR = 2.9 (95 percent C.I. 1.5-5.7); and for unsaturated fat, OR = 3.3 (95 percent C.I. 1.7-6.3). DISCUSSION: The data suggest that dietary fat, both saturated and unsaturated, are associated with an increased risk for prostate cancer in a low risk population.

Adult↗

Responses of natural killer cell activity to acute laboratory stressors in healthy men at different times of day.

To assess possible diurnal variations in natural killer reactivity to acute laboratory stressors, this study investigated changes in natural killer cell activity (NKCA) during and after three stressors (mental arithmetic, speech, and the Stroop) at 3 times of the day (08:00, 12:00, and 16:00) in 30 healthy men. NKCA activity increased during mental arithmetic and speech tasks at all 3 times of the day. Change in NKCA was greatest in the afternoon. Differences in the magnitude of mood changes were also observed at the 3 times of day, parallel to immune reactivity. These findings suggest that the dynamics of stress-related NKCA are more complex than previously believed and that time of day may affect the way they are generated or interpreted.

Affect↗

Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger.

NHE3 is one of five plasma membrane Na+/H+ exchangers and is encoded by the mouse gene Slc9a3. It is expressed on apical membranes of renal proximal tubule and intestinal epithelial cells and is thought to play a major role in NaCl and HCO3- absorption. As the distribution of NHE3 overlaps with that of the NHE2 isoform in kidney and intestine, the function and relative importance of NHE3 in vivo is unclear. To analyse its physiological functions, we generated mice lacking NHE3 function. Homozygous mutant (Slc9a3-/-) mice survive, but they have slight diarrhoea and blood analysis revealed that they are mildly acidotic. HCO3- and fluid absorption are sharply reduced in proximal convoluted tubules, blood pressure is reduced and there is a severe absorptive defect in the intestine. Thus, compensatory mechanisms must limit gross perturbations of electrolyte and acid-base balance. Plasma aldosterone is increased in NHE3-deficient mice, and expression of both renin and the AE1 (Slc4a1) Cl-/HCO3- exchanger mRNAs are induced in kidney. In the colon, epithelial Na+ channel activity is increased and colonic H+,K+-ATPase mRNA is massively induced. These data show that NHE3 is the major absorptive Na+/H+ exchanger in kidney and intestine, and that lack of the exchanger impairs acid-base balance and Na+-fluid volume homeostasis.

Animals↗

Experimental models in peritoneal dialysis: a European experience.

BACKGROUND: The development of adequate animal models is important for the in vivo study of selected aspects of peritoneal dialysis (PD) that cannot be evaluated by an in vitro model, such as peritoneal membrane transport, the influence of local defense mechanisms, and for testing new osmotic agents and their biocompatibilities. METHODS: Our experience with animal models for PD, including the acute Stockholm model in non-uremic rats, the acute and chronic Amsterdam model in non-uremic rats, and the chronic Gent model in uremic rats, is described. RESULTS: The Stockholm model proved to be useful in understanding the normal physiology of peritoneal transport, and for testing new dialysis solutions and their biocompatibilities. It is a rather simple and inexpensive model, and thus is suitable for screening new solutions and additives. The Amsterdam model permits the study of chemokines and mesothelial cell regeneration in vivo, and is applied in a model of chronic peritonitis. The results of the Gent model suggest that chronic peritoneal dialysis in uremic rats is feasible for at least eight weeks. This model is, however, very laborious, time consuming, and expensive. CONCLUSION: Further improvement of the technique and increase of the dialysis dose should result in a better and more realistic model for peritoneal dialysis. It is hoped that in the future these models will be useful to test the effects of long-term intraperitoneal application of different dialysis solutions and additives in uremic animals.

Animals↗

Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume.

In the present study, we investigated (1) the effect of an increase in dialysate fill volume on peritoneal fluid and solute transport using a 1.36% glucose solution, and (2) the effect of intraperitoneal administration of hyaluronan on peritoneal transport characteristics when different fill volumes were used. A four-hour dwell study with frequent dialysate and blood sampling was performed in 26 male Sprague-Dawley rats with 131I albumin as the intraperitoneal volume marker. Each rat was injected intraperitoneally with 25 ml (group Con25, N = 6) or 40 ml (group Con40, N = 7) of 1.36% glucose dialysis solution alone or 25 ml (group HA25, N = 6) or 40 ml (Group HA40, N = 7) of 1.36% glucose dialysis solution with 0.01% hyaluronan. The peritoneal transport of fluid, glucose, urea, and total protein as well as the intraperitoneal hydrostatic pressure (IPP) with different fill volumes were evaluated. We found that IPP and peritoneal fluid absorption rate significantly increased with the increase in fill volume (P < 0.01), and therefore the net ultrafiltration volume was significantly lower in the Con40 group compared to the Con25 group despite a higher transcapillary ultrafiltration rate in the Con40 group. The addition of hyaluronan to dialysate significantly (P < 0.01) decreased the peritoneal fluid absorption rate (by 22% in HA25 vs. Con25 and by 29% in HA40 vs. Con40) and thus significantly increased the net peritoneal fluid removal. The diffusive mass transport coefficients for glucose, urea and total protein did not differ between the Con25 and Con40 groups or between the two hyaluronan groups as compared to their respective control groups. The peritoneal clearance of urea increased significantly in the high fill volume group (by 58% in Con40 vs. Con25) and in the two hyaluronan groups (by 21% in HA25 vs. Con25 and by 16% in HA40 vs. Con40). We conclude that: (1) An increase in dialysate fill volume using 1.36% glucose dialysis solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption rate, and therefore lower net ultrafiltration. (2) Intraperitoneal addition of hyaluronan significantly decreases the peritoneal fluid absorption rate, and the decreasing effect is even more marked when a high fill volume is used. (3) Small solute clearances increase markedly with increases in fill volume, and then further increase by adding hyaluronan to the dialysate due to the increase in drainage volume. Thus, intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption, and may thereby prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume.

Animals↗

Genetic evaluation by best linear unbiased prediction using marker and trait information in a multibreed population.

Genetic evaluation by best linear unbiased prediction (BLUP) requires modeling genetic means, variances, and covariances. This paper presents theory to model means, variances, and covariances in a multibreed population, given marker and breed information, in the presence of gametic disequilibrium between the marker locus (ML) and linked quantitative trait locus (MQTL). Theory and algorithms are presented to construct the matrix of conditional covariances between relatives (Gv) for the MQTL effects in a multibreed population and to obtain the inverse of Gv efficiently. Theory presented here accounts for heterogeneity of variances among pure breeds and for segregation variances between pure breeds. A numerical example was used to illustrate how the theory and algorithms can be used for genetic evaluation by BLUP using marker and trait information in a multibreed population.

Genetic Linkage↗