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Biomedical subjects

P Rigotti

Publications and source records attributed to P Rigotti.

At least 55 records · Page 3Linked to original sources
PubMed1995

Reduced fibrinolytic potential one year after kidney transplantation. Relationship to long-term steroid treatment.

Thromboembolic complications constitute an important risk in renal transplant patients, in whom a hypercoagulable state is associated with immunosuppressive treatment, and the presence of hypercoagulability and hypofibrinolysis specifically with cyclosporine. Hypercorticism secondary to steroid treatment has been associated with a thrombophilic state and the presence of a reduced fibrinolytic potential in particular. The aims of this study were to first evaluate the fibrinolytic potential by the venous occlusion (VO) test in 19 renal transplant (RT) patients, and then compare these findings with those obtained in similar groups of normal subjects and patients with Cushing's disease. The following tests were carried out before and after the VO test: euglobulin lysis time and t-PA and PAI-1 activities and antigen. Compared with normal controls, RT and Cushing's patients both showed a similar significant increase in PAI-1 activity and concentration. The VO test revealed a similar impairment in fibrinolytic potential in both the RT and Cushing groups. High and pathological PAI-1 levels before and after the VO test were consistent with a defective fibrinolytic potential due to the inhibitory effect of PAI-1 on plasminogen activation. A hypofibrinolytic state was found in 68.4% of RT patients. Our results suggest that an imbalance in the fibrinolytic system is a typical feature of RT patients one year after transplantation. Steroids appear to be the immunosuppressive drug mainly involved in determining thromboembolic risk after renal transplantation.

Adult↗
PubMed1993

Functional and morphological effects of defibrotide on renal ischemia.

Defibrotide (Df) has been reported to protect various organs from ischemic damage. The aim of this study was to evaluate the effect of Df on renal function and morphology after warm kidney ischemia. Divided into two groups, 14 pigs underwent bilateral renal clamping for 90 min. One group (7 pigs) was treated with Df (32 mg/kg per h) for 6 h, whereas the control group received 5000 IU of heparin. Serum levels of blood urea nitrogen (BUN) and creatinine measured for 6 days were significantly higher in the control group (peak 26.8 +/- 16.7 vs 11.0 +/- 2.9 mmol/l and 501.2 +/- 351.4 vs 230.2 +/- 68.0 mumol/l P < 0.05). Renal biopsy evidenced a lesser extent of tubular and endothelial damage in Df-treated animals. In conclusion, Df provided relevant protection against renal ischemic injury.

Animals↗
PubMed1993

Immunosuppressive effects of defibrotide.

The effect of defibrotide (DF) alone or in combination with CsA was examined using in vitro proliferation assays with human PBLs and in vivo heterotopic heart allografts in rats. DF alone (12.5-50 mg/ml) inhibited in vitro PBL proliferation more effectively after PHA (50-56%) or OKT3 (50-95%), than after alloantigenic (25-30%), stimulation. Furthermore, the combination of DF (1-4 mg/ml) with CsA (10-40 ng/ml) caused an 85.2-86.8% reduction in proliferative responses after OKT3 stimulation. Median-effect analysis documented that the combination index for DF and CsA was consistently lower than 0.3 at various concentration ratios of the 2 agents. Combination index values below 1.0 reflect drug synergism; those equal to 1.0 show additive, and above 1.0, antagonistic, interactions. Daily intraperitoneal injections of DF (150 mg/kg) failed to prolong the survival of Buffalo (RT-1b) heart allografts in Wistar-Furth (RT-1u) recipients, namely mean survival times of 7.0 +/- 0.7 days with, vs. 6.5 +/- 0.5 days without, DF treatment. Similarly, intravenous or intra-arterial infusion of DF (280 mg/kg) delivered directly into the heart allograft by a 7-day osmotic pump was ineffective. However, a course of local, but not systemic, DF (280 mg/kg) combined with a 14-day i.v. administration of a subtherapeutic dose of CsA (1 mg/kg) significantly prolonged heart allograft survival to 22.8 +/- 5.0 days (P < 0.001). Thus, in vitro DF is immunosuppressive alone at high concentrations, and in combination with CsA at low concentrations. Continuous infusion of DF into the graft combined with systemic administration of CsA prolonged transplant survival in vivo. These findings suggest that high tissue levels of DF potentiate the immunosuppressive effects of CsA.

Animals↗
PubMed1993

Transplantation of warm ischemia damaged kidneys: an experimental study in pigs.

This study evaluated renal function and histological and oxidative injury in transplanted kidneys harvested after prolonged warm ischemia in pigs. In 8 donor pigs, kidneys were perfused in situ 120 min after cardiac arrest. One of each pair of kidneys was used for histological and biochemical studies while the other was transplanted into a recipient undergoing bilateral nephrectomy. In 6 cases, renal function was satisfactory 14 days after transplantation. Histologically, a reversible acute tubular necrosis was observed with partial recovery at the 14th postoperative day. A moderate oxidation was revealed by decreased glutathione and increased malondialdehyde levels. In spite of this ischemic injury, these findings suggest that kidneys harvested after prolonged warm ischemia can still recover after transplantation, and that non-heart-beating donors may be considered as an alternative organ source for kidney transplantation.

Animals↗
PubMed1992

Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro.

A significant loss of human cytochrome P-450 was observed during the anaerobic incubation of NADPH-reduced human liver microsomes obtained from surgical samples, in presence of carbon tetrachloride or halothane. In order to prevent any interference in the classical spectrum of cytochrome P-450 with CO, the method of Johannesen & DePierre (1978) was modified to obtain cytochrome P-450 determination. The enzyme inactivation reaction showed pseudo-first order kinetics and was accompanied by destruction of the haem tetrapyrrolic structure, as indicated by a significant loss of its porphyrin fluorescence. Values of about 200 and 700 were calculated for the partition ratio between metabolic turnover of the substrate and enzyme inactivation during reductive incubation of one of these microsomal preparations with limiting concentrations of CCl4 and halothane, respectively. The results indicate that human liver cytochrome P-450 can be inactivated reductively in vitro by CCl4 and halothane reactive metabolites and suggest that a suicide type of mechanism, similar to that which was recently demonstrated to occur, for both substrates, with rat liver microsomes (Manno et al. 1988a & 1991), may also be involved in the inactivation of the human enzyme(s).

Animals↗
PubMed1991

Effects of defibrotide on renal function and urinary prostanoid excretion in ciclosporin-treated rats.

Defibrotide (DF) has been proposed as a new antithrombotic agent in renal transplantation. Because it was also found to increase prostacyclin synthesis, a reduction in ciclosporin (CS) nephrotoxicity could be supposed. To ascertain this hypothesis, renal function and urinary prostanoids were evaluated in four groups of rats after 10 days of oral treatment (doses in mg/kg/day): CS 50 (group A), CS 50 + DF 400 (group B), DF 400 (group C) and controls (group D). Compared to controls, creatinine clearance (CCR) was significantly lower in groups A and B (In CCr: A = 6.62 +/- 0.28, B = 6.83 +/- 0.24 vs. 8.17 +/- 0.13 microliters/min, p less than 0.01), whereas it did not change in group C (8.03 +/- 0.24 microliters/min). The urinary excretion of prostaglandin E2 (PGE2) was significantly (p less than 0.05) higher in group A (In PGE2: 3.98 +/- 0.98 nmol/mol Cr) and more evidently in groups B and C (6.89 +/- 0.38 and 6.01 +/- 0.32 nmol/mol Cr, respectively) compared to controls (1.43 +/- 0.45 nmol/mol Cr). The urinary excretion of 6-keto-PGF1 alpha and of thromboxane B2 (TxB2) were higher only in groups A and B (ln 6-keto-PGF1 alpha and ln TxB2: A = 6.45 +/- 0.22 and 4.97 +/- 0.20, B = 7.06 +/- 0.31 and 5.43 +/- 0.41 vs. group D = 5.53 +/- 0.22 and 3.79 +/- 0.42 nmol/mol Cr; p less than 0.05). The 6-keto-PGF1 alpha/Tx molar ratio was not significantly affected, although a trend for a reduction in the ratio was found in the treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Liver resection. A comparison using the Nd-YAG laser, an ultrasonic surgical aspirator, or blunt dissection.

Before gaining wide acceptance, possible surgical tools should be compared with the standard ones. This study, therefore, compared the Nd-YAG laser and the CUSA with the standard blunt dissection technique for liver resection in 24 dogs (8 in each group). Using a noncontact technique, the Nd-YAG laser was used for cutting as well as coagulation. The Nd-YAG laser or the CUSA reduced the resection time, with the laser being the faster of the two, and was accompanied by a probable but not significant decrease in perioperative blood loss. The CUSA delineated the blood vessels and bile ducts and gave superior control. It also caused significantly less tissue damage on light and electron microscopic examination than the other two methods. Cultures taken 1 week after operation showed that the risk of bacterial infection correlated well with the extent of tissue necrosis and was significantly greater after use of the Nd-YAG laser than after use of the CUSA. The numbers of animals are small and the conclusions should be tempered by caution, but it appears that the CUSA, but not the Nd-YAG laser, may improve the results of elective liver resection.

Animals↗
PubMed1985

Effect of hyperammonemia and methionine sulfoximine on the kinetic parameters of blood-brain transport of leucine and phenylalanine.

The activity of the blood-brain neutral amino acid transport system is increased in rats infused with ammonium salts or rendered hyperammonemic by a portacaval anastomosis. This effect may be due to a direct action of ammonia or to some metabolic consequence of high ammonia levels, such as increased brain glutamine synthesis. To test these possibilities we evaluated the kinetic parameters of blood-brain transport of leucine and phenylalanine in control rats, in rats after continuous 24 h infusion of ammonium salts (NH4+ = 2.5 mmol X kg-1 X h-1), and in rats treated with methionine sulfoximine, an inhibitor of glutamine synthetase, before infusion of ammonium salts. In ammonia-infused rats without methionine sulfoximine treatment, the KD and Vmax of phenylalanine transport were increased, respectively, about 170% and 80% compared to controls, whereas the Km and Vmax of leucine transport were increased, respectively, about 100% and 200%. Electron microscopy demonstrated marked swelling of astrocytic processes around brain capillaries of ammonia-infused rats; however, capillary permeability to horseradish peroxidase apparently was not increased by ammonia infusion. Administration of methionine sulfoximine before ammonia infusion inhibited glutamine synthesis and prevented the changes in transport of leucine and phenylalanine, but apparently did not reverse the perivascular swelling. These results suggest that the ammonia-induced increase in the activity of transport of large neutral amino acids across the blood-brain barrier requires glutamine synthesis in brain, and is not a direct effect of ammonia.

Ammonia↗
PubMed1985

Methionine sulfoximine prevents the accumulation of large neutral amino acids in brain of portacaval-shunted rats.

Portal-systemic shunting and hyperammonemia lead to an accumulation of the large neutral amino acids in brain and apparently alter transport of neutral amino acids across the blood-brain barrier. It has been proposed that portal-systemic shunting leads to a high brain concentration of glutamine, a product of cerebral ammonia detoxification, and thereby affects the transport of other neutral amino acids across the blood-brain barrier. To test this hypothesis, rats with a portacaval shunt were treated with L-methionine-dl-sulfoximine (MSO), an inhibitor of glutamine synthesis. Treatment with MSO resulted in lower concentrations of the neutral amino acids in brain of portacaval-shunted rats and a higher brain ammonia concentration, compared with untreated shunted rats. These results suggest that the accumulation of neutral amino acids in brain after portacaval shunt depends on the increased synthesis of glutamine in brain.

Amino Acids↗
PubMed1985

Are urinary enzymes useful markers of kidney damage in obstructive jaundice? An experimental study on Sprague-Dawley rats.

To evaluate the reliability of urinary enzymes as markers of renal tubular damage in obstructive jaundice, research was carried out on 26 Sprague-Dawley rats submitted to bile duct ligation and on 16 sham-operated rats. The fractional clearances of lysozyme (CfrLYS) and of malto-dehydrogenase (CfrMDH)-indices of tubular function-and the fractional excretions of gamma-glutamyltransferase (UfrGGT) and of alpha-glucosidase (UfrAGL)-indices of tubular anatomic damage - were measured 5, 10, 20 and 30 days after operation. Creatinine clearance, urinary sodium excretion, urinary potassium excretion, proteinuria, plasma bilirubin and bile acids were also measured. Kidneys were taken for histology. All rats submitted to common bile duct ligation had high levels of bilirubin and bile acids; proximal tubules were damaged and the extent of the lesions increased with time. However, creatinine clearance, urinary sodium excretion, proteinuria, CfrMDH and UfrAGL gave no indication of renal lesions, whereas CfrLYS and UfrGGT were significantly higher 20 and 30 days after bile duct ligation, respectively. These findings show that CfrLYS and UfrGGT could be useful tests for renal tubular lesions in jaundice.

Animals↗