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Biomedical subjects

P Jablonski

Publications and source records attributed to P Jablonski.

At least 19 recordsLinked to original sources
PubMed2003

The thermodynamic water retention capacity of solutions and gels.

The thermodynamic water retention capacity (WRC) has been defined and applied to different heterogeneous phase equilibria. This definition includes others known from the literature for testing heterogeneous systems. For the type of a real solution it is shown that at constant values of temperature and pressure the WRC is related to the difference of the chemical potential of water between the original state and the state after having applied a constraint. The dependence of WRC on concentration of a solute is predicted to be described by an e-function which has been experimentally confirmed in the literature.

Models, Theoretical↗
PubMed2002

Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation.

The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin.

Activity Cycles↗
PubMed2001

Heart preservation with celsior solution improved by the addition of nitroglycerine.

BACKGROUND: Preservation of rat hearts was extended to 16 hr when nitroglycerine (NTG) was added to colloid-free University of Wisconsin solution (MUW). This study examined the effectiveness of Celsior solution (CEL) and whether adding NTG to CEL would improve and extend cardiac preservation. METHODS: Two studies were conducted: (a) 9-hr preservation with either CEL or MUW, (b) 16-hr preservation with CEL, CEL+NTG, or MUW+NTG. Rat heart isografts were flushed and stored at 0 degrees C before heterotopic transplantation with an indwelling externalized intraventricular balloon-tipped catheter. One and 7 days after transplantation, quantitative functional studies were performed. RESULTS: After 9-hr preservation, all (6/6) grafts preserved with MUW beat for 7 days, whereas only 1/6 hearts preserved with CEL continued to beat. After 16-hr preservation, 6/10 CEL+NTG hearts beat for 7 days compared with 7/8 MUW+NTG hearts; none of the hearts preserved with CEL survived. Function was similar in CEL+NTG and MUW+NTG groups on day 1 (left ventricular developed pressure (LVDP): CEL+NTG=64+/-16, MUW+NTG=104+/-16 mmHg; maximum dP/dt: CEL+ NTG=2024+/-551, MUW+NTG=3582+/-513 mmHg/sec) and day 7: (LVDP: CEL+NTG=126+/-25, MUW+NTG=177+/-24 mmHg; maximum dP/dt: CEL+NTG=3835+/-848, MUW+ NTG=5639+/-670 mmHg/sec). Function in both groups improved significantly (P<0.05) on day 7 compared with day 1. CONCLUSIONS: Celsior was not as effective as MUW for rat heart preservation. The addition of NTG to both CEL and MUW provided similar effective preservation for 16 hr. NTG should be added routinely to both solutions.

Adenosine↗
PubMed2001

Influence of buprenorphine analgesia on post-operative recovery in two strains of rats.

The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control group received a second injection 9 h later. Behavioural observations by three independent observers provided no information in assessing pain in this model. All rats lost weight, consumed less food and water after surgery. On the first day, both SD and DA rats receiving buprenorphine lost less weight than untreated control groups. Using weight loss as an efficacy criterion, low-dose buprenorphine, given once or twice, provided effective analgesia in SD rats. A higher single dose provided no additional benefit and a second dose was detrimental, reducing body weight and food intake. In DA rats, the high dose, given twice, appeared to be more effective than the lower dose. All DA cage cohorts consumed < 10% pre-operative food despite buprenorphine treatment, suggesting a higher dosage may be necessary. However, all SD and 80% DA rats who received no buprenorphine gained body weight on the second day, whereas most of the buprenorphine-treated rats continued to lose weight for another 2 days, despite increased food consumption by both strains. Buprenorphine may adversely affect intestinal function over a number of days due to its enterohepatic circulation; this effect may be more severe in DA rats. Adverse metabolic effects of buprenorphine and other opioids may preclude their use in the future if it can be shown that non-steroidal anti-inflammatory drugs (NSAIDs) provide equally effective analgesia.

Age Factors↗
PubMed2000

Liver preservation: a comparison of celsior to colloid-free University of Wisconsin solution.

INTRODUCTION: Celsior (CEL) was formulated specifically for heart preservation. Recently some preliminary reports have suggested that CEL is also effective for liver preservation. In this study liver preservation with CEL was compared to colloid-free University of Wisconsin solution (MUW). METHODS: Arterialized rat liver isografts were flushed and stored for 24 hr at 0 degrees C in CEL or MUW before orthotopic transplantation. Plasma albumin, bilirubin, glucose, aspartate aminotransferase, and alkaline phosphatase were measured 1, 2, 3, 7, 14, 21, and 28 days after surgery. RESULTS: All recipients of MUW-preserved livers survived, none of the recipients of CEL-preserved grafts lived beyond 3 days. On day 1, AST was raised in all rats but rats receiving CEL-preserved liver grafts were also markedly hypoglycemic, hypoalbuminemic and had elevated alkaline phosphatase. CONCLUSION: Celsior is not an effective solution for long-term liver preservation in its present composition.

Adenosine↗
PubMed2000

Functional, histological, and inflammatory changes in chronically rejecting small bowel transplants.

Our aim was to develop a model of chronic rejection (CR) in small bowel allografts, and to study the changes occurring in these grafts. Small bowel transplantation was performed using the DA to AS rat strain combination. Short-term (5 mg/kg intramuscular, from days -2 to +9), or long-term cyclosporin treatment (5 mg/kg, 3 times a week until day 50) was given to prevent acute rejection. Controls were untreated allografts, DA isografts with and without cyclosporin, and normal DA and AS rats. They were followed for 50 and 100 days after transplantation. Recipients of a syngeneic graft lost weight during the first week after transplantation, but started to regain weight and kept growing thereafter. Histology showed normal bowel architecture with normal mesenteric lymph nodes and Peyers patches. Vigorous acute rejection occurred in the untreated allografts. Animals had persistent weight loss, and were killed between 6-13 days after transplantation. No clinical signs of graft-versus-host disease were seen. Histology showed end-stage acute rejection. In both cyclosporin-treated allografted groups the postoperative course was as in the isografted animals. However, all animals had histologic signs of CR by 50 and 100 days after transplantation. Changes were most prominent in the mesentery. Serositis with increased vascularity, inflammation with sclerosis, and patchy myointimal proliferation with endothelialitis of the mesenteric vessels were found. Changes in the bowel were patchy and included some thickening of the muscle coat, crypt hyperplasia, scattered necrotic cells in the crypts, slight blunting of villi and loss of goblet cells. Infiltrating cells in the mesentery and bowel consisted mainly of CD 4+ cells, CD 8- T-cells and monocytes/macrophages. Lactulose-mannitol urinary excretion ratio was significantly increased in short-term cyclosporin treated allografts at days 50 and 100 posttransplant. Serum albumin levels were significantly lowered in this group at both time points examined. We developed two models in which CR occurs after small bowel transplantation. Long-term cyclosporin treatment delayed the development of CR, since functional abnormalities were only seen in the animals that were treated with short-term cyclosporin.

Animals↗
PubMed2000

Insulin receptor and insulin receptor substrate-I in rat retinae.

Insulin receptor substrate-I (IRS-I) is a major cytosolic substrate of the insulin receptor Expression of insulin receptor and IRS-I, and the distribution of these components of the insulin-signalling pathway, were investigated in rat retinae. Insulin receptor and IRS-I were located in retinal sections with anti-insulin receptor and anti-IRS-I antibodies. Reverse transcription-polymerase chain reaction (RT-PCR) of retinal mRNA was performed with primers specific for insulin receptor and IRS-I gene sequences. Immunohistochemistry demonstrated distinct but closely associated staining patterns for insulin receptor and IRS-I throughout rat retinae. The RT-PCR product from rat retinal insulin receptor mRNA corresponded to the high affinity insulin receptor isoform. The RT-PCR product for retinal IRS-I mRNA agreed with that predicted from the gene sequence. The expression of IRS- I and insulin receptors indicates a signalling mechanism by which insulin can influence retinal metabolism or function.

Animals↗
PubMed1999

Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

Animals↗
PubMed1999

Increased expression of basic fibroblast growth factor during chronic rejection in intestinal transplants is associated with macrophage infiltrates.

Long-term survival of intestinal transplants is hampered by chronic rejection (CR). Since transplants with CR demonstrate fibrotic changes, the cytokine basic fibroblast growth factor (bFGF) may be involved in the tissue remodelling of chronic intestinal rejection. The aim of this study was to investigate the bFGF gene and protein expression and distribution in chronically rejecting intestinal allografts. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination. Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA. bFGF gene expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) of the ileum RNA and was standardized against Glyceraldehyde-3-phosphate-dehydrogenase (GAP-DH) expression. bFGF protein was determined using immunohistochemistry. To identify the bFGF-positive cell type, sequential sections were stained for cell markers. Allografts showed histological features of CR, whereas isografts preserved normal architecture. bFGF gene expression was present in normal ileum and significantly upregulated in allografts. Immunohistochemical staining showed a significant increase in bFGF protein compared to isografts. Most bFGF-positive cells were localized in the submucosa and muscularis, particularly around the neural plexus. bFGF-positive cells appeared to be ED-2-positive macrophages, strongly suggesting that the site of bFGF production is the activated macrophage. This study demonstrates increased bFGF mRNA and protein in chronically rejecting intestinal allografts that appear to be produced by macrophages.

Animals↗
PubMed1999

Improved cardiac preservation by the addition of nitroglycerine to colloid-free University of Wisconsin solution (MUW).

BACKGROUND: This study examines whether the addition of nitroglycerine, a known coronary vasodilator and nitric oxide donor, to colloid-free University of Wisconsin solution will improve and extend cardiac preservation. METHODS: Rat hearts were flushed and stored in colloid-free University of Wisconsin solution with or without the addition of nitroglycerine for 12, 16 or 20 hours at 0 degrees C before heterotopic transplantation with an indwelling externalized intraventricular balloon-tipped catheter. One and 7 days after transplantation of the heart the catheter was connected to a pressure transducer and quantitative functional studies were performed. RESULTS: After 12 hours preservation with nitroglycerine in colloid-free University of Wisconsin solution 6/6 grafts continued to beat for 7 days compared to 3/6 without nitroglycerine. After 16 hours preservation the addition of nitroglycerine 5/7 hearts continued to beat for 7 days compared to 0/6 without nitroglycerine (p < .05). Only 1/6 hearts beat for 7 days after 20 hours preservation with nitroglycerine. On Days 1 and 7, the left ventricular developed pressure (LVDP), contractility (max dP/dt) and rate of relaxation (peak -dP/dt) of 12 hour preserved hearts was better (p < .05) when nitroglycerine was present. The function of hearts preserved with the addition of nitroglycerine was similar after 12 and 16 hours preservation. CONCLUSION: Nitroglycerine is a valuable additive to colloid-free University of Wisconsin solution, extending effective preservation of the rat heart to 16 hours and significantly improving left ventricular function after 12 and 16 hours preservation. The addition of nitroglycerine, however, did not extend preservation to 20 hours.

Adenosine↗
PubMed1999

EGF and TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Long-term survival of small bowel transplants is hampered by chronic rejection. Epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) have opposing, regulatory roles in normal intestinal physiology and may be involved in the pathogenesis of chronic intestinal rejection. Our aim was to investigate the expression of EGF and TGF-beta1 in chronically rejecting small bowel transplants. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination; Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA rats. PreproEGF and TGF-beta1 gene expression was evaluated by northern blot analysis of the ileum RNA and standardized against glyceraldehyde-3-phosphate-dehydrogenase expression. Allografts demonstrated functional impairment and histological features of chronic rejection, whereas isografts appeared normal. Allografts demonstrated a significant reduction of EGF mRNA when compared to DA isografts. No significant changes were detected in TGF-beta1 expression in either allogeneic or syngeneic grafts. In conclusion, this study demonstrates reduced preproEGF and preserved TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Analysis of Variance↗
PubMed1999

The return of glomerular-filtered albumin to the rat renal vein.

BACKGROUND: Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high, and this has been confirmed in studies in which albumin uptake by the tubules has been inhibited. Therefore, there must be a high-capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. METHODS: This study identifies the presence of glomerular-filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium-labeled albumin into the renal artery in vivo and in the isolated perfused kidney. RESULTS: The postglomerular filtered albumin is returned to the blood supply by a high-capacity pathway that transports this albumin at a rate of 1830 +/- 292 micrograms/min.rat kidney (N = 14, mean +/- SEM). This pathway has been identified under physiological conditions in vivo and in the isolated perfused kidney. The pathway is specific for albumin, as it does not occur for horseradish peroxidase. The pathway is inhibited in a nonfiltering kidney. The pathway is also inhibited by ammonium chloride (an agent that inhibits tubular protein uptake but does not alter glomerular size selectivity) and by albumin peptides (which compete for the tubular albumin receptor). CONCLUSIONS: The high-capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.

Albumins↗
PubMed1998

Studies in a modified auxiliary abdominal rat heart transplantation model: preservation with colloid-free University of Wisconsin solution.

BACKGROUND: Current clinical heart preservation is still limited to 6 hours. A suitable heart transplantation model to rapidly screen the effectiveness of new solutions is essential. This study examines a new screening test-a modification of the conventional abdominal rat heart transplantation model that overcomes its serious limitation of lack of quantitative evaluation of function. METHODS: Rat hearts, with an externalized intraventricular balloon-tipped catheter, were transplanted immediately (controls) or flushed and stored in colloid-free University of Wisconsin solution in ice for 6, 9, or 12 hours before transplantation. One and 7 days later this catheter was connected to a pressure transducer and a calibrated syringe. Heart rate, maximum developed pressure, and maximum rate of left ventricular pressure rise were determined. Grafts were prepared for histologic study on day 7. RESULTS: All preserved hearts commenced beating within 2 minutes (controls beat within 20 seconds). On day 1 the heart rate and chamber stiffness (deltaP/deltat) were similar in all groups. The 9- and 12-hour-preserved hearts had significantly (p < 0.05) diminished developed pressure and contractility. On day 7 contractility and developed pressure improved in 9- and 12-hour-preserved grafts. There was extensive muscular atrophy and necrosis, with extensive cellular infiltrate in the 9- and 12-hour-preserved grafts; other grafts showed no damage. CONCLUSION: This quantitative model provides an ischemia-related gradation of function and greater discrimination than conventional methods. It has refuted previous studies suggesting effective preservation for 20 hours and demonstrated that functional testing is essential in evaluating preservation regimens.

Adenosine↗
PubMed1998

Modified technique of abdominal heart transplantation in the rat.

BACKGROUND: A rapid, reproducible screening model is essential for evaluation of novel preservation regimens. This study describes a modification of the abdominal rat heart transplantation model reducing anastomosis time and allowing quantitative assessment for 7 days. METHODS: Hearts, obtained from inbred Dark Agouti rats, were arrested and stored in cold colloid-free University of Wisconsin solution until transplantation. The Dark Agouti recipient underwent a left nephrectomy. The donor left common carotid artery was anastomosed to the recipient left renal artery with a "sleeve" anastomosis. The "cuffed" donor left pulmonary artery was inserted into the left renal vein. Study 1 examined continuing viability by daily palpation and morphologic study by examination of hematoxylin and eosin-stained sections on days 4 or 90. Study 2 examined quantitative assessment of cardiac function in the anesthetized recipient. The model was further modified by introducing an externalized, fluid-filled, balloon-tipped catheter into the left ventricle. RESULTS: The new technique allowed vascular anastomoses to be completed in 5 to 12 minutes, minimizing rewarming of the graft. Most (25 of 28) grafts beat for 90 days, and 80% of these showed normal structure. There was evidence of myocyte damage or arteriosclerosis in 5 of 25 at 90 days and in 4 of 17 at 4 days. Cardiac function parameters were similar in consecutive runs and did not change between days 1 and 7. CONCLUSION: This abdominal rat heart transplant model is quick and easy to perform, minimizes warm ischemia, and is suitable for both short- and long-term studies. Quantitative parameters, assessed by use of an in situ intraventricular balloon-tipped catheter, are reproducible and maintained for 7 days.

Animals↗
PubMed1996

Comparison of UW solution and St. Thomas' solution in the rat: importance of potassium concentration.

BACKGROUND: University of Wisconsin solution (UW) is in limited clinical use for heart transplantation, but there are doubts about its efficacy and concerns about the effect of its high K+ concentration on endothelium. St. Thomas' solution with or without aspartate is widely used and is of proven efficacy. METHODS: Using a modified (starch-free) variant of UW (MUW) we studied: (1) recovery of function with UW compared with aspartate-containing St. Thomas' solution; (2) effect of elevation of K+ in St. Thomas' solution to the level in UW; and (3) effect of reduction of K+ in UW and addition of Ca2+ or aspartate. Isolated rat hearts underwent 7 hours of arrest at 1 degrees C using MUW with or without 20 mmol/L aspartate or using aspartate-containing St. Thomas' solution. RESULTS: Functional recovery with MUW (51.8% +/- 2.5%) was superior to that with aspartate-containing St. Thomas' solution (37.1% +/- 4.3%; p < 0.01). Addition of aspartate to MUW had no effect. During 6 hours of arrest, lowering the K+ in MUW from 125 mmol/L to 20 mmol/L reduced functional recovery from 59.9% +/- 4.2% to 42.3% +/- 4.3% (p < 0.01). The addition of 1 mmol/L Ca2+ had no effect. Elevation of K+ in St. Thomas' solution produced more rapid arrest but no improvement in recovery. CONCLUSIONS: The protective effect of starch-free UW is greater (+13%) than that of aspartate-enriched St. Thomas' solution. Reduction of K+ in UW to lessen possible deleterious effects would decrease its protective effect by about 30% to a level comparable with that of St. Thomas' solution.

Animals↗
PubMed1996

The effects of insulin on the electroretinogram of bovine retina in vitro.

PURPOSE: This study investigates the role of insulin in retinal function by examining the effects of insulin on the a- and b-waves of the electroretinogram (ERG) recorded from an in vitro bovine retina eye-cup preparation. METHODS: Bovine eyes were enucleated immediately after exsanguination, hemisected to form an eye cup, and transported to the laboratory in oxygenated medium. Eye cups were then transferred to a perfusion system that provided constant superfusion of oxygenated perfusate solution to the retina, enabling it to remain in a functional state in vitro. The ERG was recorded, as the retinal response to photic stimulation, from electrodes mounted within the perfusion system. The effects of insulin on the ERG were investigated by adding insulin to the perfusate solution. RESULTS: Application of insulin to the in vitro retina preparation decreased the amplitudes of the a- and b-waves of the ERG in a dose dependent manner with a maximal effect at doses of 0.1 U/ml and above. These effects were reversible. CONCLUSION: The reduction of ERG amplitudes may result from the hyperpolarising effect of insulin reported in other tissues. The findings suggest that insulin may have a regulatory role in retinal activity; however extrapolation of these results to the intact organism is dependent on the presence of insulin in retina.

Animals↗
PubMed1995

The effect of ureteric stenting on the function and morphology of long-term rat renal allografts.

In the development of a reliable model for chronic rejection in rat renal allografts, the effect of modifying the ureteric anastomosis was tested. Rats, tolerized by pretreatment with two donor blood transfusions under Cyclosporin A, received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.

Animals↗