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Biomedical subjects

G Gaja

Publications and source records attributed to G Gaja.

At least 37 records · Page 2Linked to original sources
PubMed1991

Prostacyclin release from endothelial cells, induced by defibrotide treatment, favours the function of grafted rat hearts and kidneys.

Defibrotide, a single-stranded DNA fraction obtained from mammalian lungs and able to increase prostacyclin production by endothelial cells, has been shown to be efficient in protecting rat organs (heart, kidney and liver) from ischaemic damage. We studied the efficacy of the drug in preserving the function of rat heart and kidney submitted to isotransplantation. Defibrotide was administered to donor Wistar rats at the dose of 32 mg/kg in 1.5 ml of saline. Heart and kidney were isolated and cold-preserved in buffered phosphate medium and continuously infused with defibrotide (32 mg/h) through the innominate or renal artery. Recipient Wistar rats were treated with defibrotide before and after transplantation at the dose of 32 mg/kg/day. Controls were treated with the vehicle of the drug. The function of isografted organs was evaluated at 12 and 24 h and at 2, 4 and 7 days from grafting. Heart function was evaluated by studying creatinine phosphokinase (CPK) and lactic dehydrogenase (LDH) activities of myocardial tissue. Renal function was evaluated by studying serum creatinine and urea levels of kidney-grafted rats. CPK and LDH activities were found to be significantly higher in defibrotide-treated rats than in controls. Creatinine and urea levels remained significantly lower in defibrotide-treated rats than in the controls. The results of the present work indicate that defibrotide treatment is useful to maintain the functionality of grafted hearts and kidneys.

Animals↗
PubMed1990

Prevention of impaired liver metabolism due to ischemia in rats. Efficacy of defibrotide administration.

The effect of defibrotide treatment in protecting liver metabolism from ischemic damage was studied. The drug was administered to male Wistar rats as a bolus (30 mg/kg body weight) at the beginning of 60 min ischemia and then continuously during 60 min of postischemic reperfusion at a dose of 30 mg/kg body weight. This dose was previously identified as useful to protect against myocardial ischemia induced in the cat. ATP and ADP intrahepatic levels were significantly higher in drug-treated rats than in untreated animals. The liver cytoplasmic NAD+/NADH ratio in defibrotide-treated rats was no different from that observed in sham-operated rats. The mitochondrial NAD+/NADH ratio in the liver was also improved by defibrotide treatment. Our data suggest that defibrotide may exert protective activity on hepatocytes useful for inducing a rapid restoration of their metabolism. Such a restoration is possibly related to improvement of microcirculation through an increase in prostaglandin I2 production or oxygen delivery due to drug administration.

Adenine Nucleotides↗
PubMed1989

Increased cAMP levels in lymphocytes of allografted rats: possible relationship to delayed graft rejection.

We studied the levels of nucleotides in peripheral blood and in spleen lymphocytes obtained from allografted rats. Four types of allografts were performed by using ACI rats (RT1a) as donors and Lewis rats (RT1l) as recipients: heart, pancreas, kidney and liver. Ungrafted Lewis rats were used as controls. Rejection time without immunosuppression occurred at 6.7 +/- 0.25 days from transplant in heart-allografted, at 7.3 +/- 0.25 days in pancreas-grafted, at 6.8 +/- 0.24 days in kidney-grafted, and at 20 +/- 3 days in liver-grafted rats. Biochemical assays on lymphocytes were performed on the 7th day after operation by measuring the intracellular content of APT, ADP, AMP, cAMP, NAD+ and NADH. Our results showed that the prolonged survival of allografts in liver-grafted rats correlated with the higher content of cAMP in their lymphocytes than in those of controls. In addition, ATP and ADP levels in lymphocytes from heart-and pancreas-allografted rats were significantly lower than those of lymphocytes from liver-allografted rats.

Adenine Nucleotides↗
PubMed1989

Defibrotide, a stimulator of prostacyclin (PGI2) production, prevents the effects of ischaemic damage.

Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, has been demonstrated to exert profibrinolytic and antithrombotic activity through stimulation of vascular prostacyclin (PGI2) production. We studied the effect of defibrotide administration in protecting liver and heart from ischaemic and postischaemic reperfusion damage. Defibrotide was administered as an i.v. bolus (30 mg/kg) at the beginning of liver ischaemia and at the same dose continuously during 60 min of postischaemic reperfusion. ATP levels were significantly improved in livers of defibrotide-treated rats as compared to those obtained in livers of rats treated with vehicle of the drug. Intrahepatic cytoplasmic and mitochondrial NAD+/NADH ratios were higher in defibrotide-treated than in vehicle-treated animals. The hearts, isolated from rats according to the transplantation procedure, were subjected to different times of warm + cold ischaemia. During ischaemia, the hearts were perfused continuously with 60 mg/kg of defibrotide or vehicle of the drug. The loss of creatine phosphokinase and lactate dehydrogenase activities due to an increased ischaemia time was limited in defibrotide-perfused hearts. Intracardiac ATP and ADP levels were significantly higher in defibrotide-treated organs than in controls. Our results demonstrate the efficacy of defibrotide in protecting liver and heart from ischaemia.

Animals↗
PubMed1988

Metabolic function of grafted liver in rats.

We studied the metabolic variations in grafted livers at different times after transplant by measuring the hepatic energy and redox states. Five groups of rats were studied: control ungrafted Wistar (RT1y) rats (group 1), ungrafted Wistar rats with ligature of the hepatic artery (group 2), isografted Wistar rats (group 3), allografted Wistar rats with livers from ACI (RT1a) donors (group 4, long-term surviving rat strain combination), and allografted Wistar rats with livers from BN (RT1n) rats (group 5, rejector rats). The metabolism of grafted livers was studied for 7 days in groups 2 and 3, for 2 months in group 4, and at the time of rejection in group 5. Adenine nucleotide levels (ATP, ADP, AMP) were significantly impaired at 24 hr and at 48 hr from grafting in isografted and in allografted livers, and the reestablishment of normal values began at the 7th day from grafting. Cytoplasmic NAD+/NADH ratios were lowered at 24 hr from grafting in isografted and in allografted livers. Mitochondrial NAD+/NADH ratios were lowered at 24 hr in isografted livers and at 24 hr and 48 hr from grafting in allografted livers. The metabolic studies performed for 2 months revealed a significant correlation between well-maintained metabolic functions and transplant survival. On the contrary, an important energy loss was evidenced in livers of group 5, at the time of rejection.

Adenine Nucleotides↗
PubMed1985

Effect of cyclosporine and aminophylline on streptozotocin-induced diabetes in rats.

Diabetes induced in rats by multiple low doses of streptozotocin is thought to mimic type 1 disease in man. We tested the effect of concomitant treatment with immunomodulator drugs in this diabetic experimental model. Administration of cyclosporine resulted in a rapid appearance of hyperglycemia, perhaps by a potentiation of the direct cytotoxic action of streptozotocin on beta cells. By contrast, aminophylline administration protected the animals from the diabetogenic action of streptozotocin. Concomitant treatment with aminophylline and cyclosporine failed to protect the rats from the hyperglycemia induced by streptozotocin.

Aminophylline↗
PubMed1984

Nucleotide metabolism in spleen and peripheral blood lymphocytes during theophylline treatment.

The in vivo effect of theophylline on lymphocyte nucleotide metabolism was investigated. Rat peripheral blood lymphocytes presented more elevated levels of adenosine 5'-triphosphate (ATP) and cyclic adenosine 3',5'-monophosphate (cAMP) than shown by spleen lymphocytes. A continuous (15 days) daily oral treatment of the rats with aminophylline increased intralymphocytic cAMp content in peripheral blood (by 14 times) and in spleen lymphocytes (by 4 times), whereas ATP content was not significantly changed. NAD+ and NADH levels and NAD+/NADH ratios appeared higher in peripheral blood than in spleen cells, and were not influenced by aminophylline treatment. These results may be explained by assuming the existence of a different distribution of lymphocyte subpopulations and of a different sensitivity of the same to aminophylline treatment. The studies of nucleotide variation in peripheral blood lymphocytes incubated at 37 degrees C in anoxic conditions (N2+CO2, 95:5) revealed an impairment of ATP production and a well-preserved redox state.

Adenosine Triphosphate↗