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Biomedical subjects

N Perico

Publications and source records attributed to N Perico.

137 records · Page 8Linked to original sources
PubMed1986

Effect of short-term cyclosporine administration in rats on renin-angiotensin and thromboxane A2: possible relevance to the reduction in glomerular filtration rate.

A short-term treatment with Cyclosporine A (CyA) induces a decrease in glomerular filtration rate (GFR), promptly reversible after withdrawal of the drug. Several lines of evidence are now available as to indicate that this phenomenon is dependent on a hemodynamic perturbation resulting in a renal vasoconstriction. With the present work we have examined the relationship between the reduction in GFR which follows a short-term administration of CyA in rats and the biochemical changes in renin-angiotensin system and renal arachidonic acid metabolism. Our results show that CyA administration (25 mg/kg/day) for 45 days stimulates renin-angiotensin system with an increase in plasma renin activity. These changes are not accompanied by a parallel increase in the renal synthesis of vasodilatory prostaglandin E2 and prostacyclin as it occurs in other conditions of renin-angiotensin stimulation. At variance glomerular synthesis and urinary excretion of thromboxane A2 (TxA2) are increased progressively during CyA treatment. These changes in renal Tx precede the increase in serum creatinine and the decrease in GFR thus indicating that TxA2 might be an additional factor potentiating the effect of angiotensin II on glomerular hemodynamics. In conclusion the early reduction in GFR which follows daily administration of CyA in rats might be the result of a synergic action of angiotensin II and TxA2 on vascular tone and mesangial contraction which is not modulated by an increase in glomerular vasodilatory prostaglandins. If this explanation may be applied to early reduction in GFR observed in humans treated with CyA before tubular toxicity develops needs to be investigated further.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Heparin for hemodialysis: practical guidelines for administration and monitoring.

Anticoagulation of extracorporeal circuit still represents a major problem for hemodialysis units. Uraemic patients are at risk of hemorrhages, so anticoagulant could increase such a risk. On the other hand clotting of extracorporeal circuit may complicate inadequate heparin administration or hemostatic activation by the foreign surfaces. In this article we propose a simple standard for heparin administration and monitoring which allows the theoretical best anticoagulation for extracorporeal circuit. Our data also indicate that the effect of our proposed schedule is not influenced by the type of membrane or dialyser used.

Adult↗
PubMedDate not supplied

[Functional loss of the transplanted kidney: immunological and non-immunological factors].

During the past few years, the short-term graft survival after kidney transplantation has improved dramatically, a phenomenon not paralleled by an increase in the long-term graft survival. This is due to the progressive renal injury and dysfunction known as chronic transplant nephropathy or 'chronic rejection', a process that involves both immune and non-immune factors. Immunological factors include T- and B-cell recognition of alloantigens, cytomegalovirus infection, and endothelial cell activation followed by vascular smooth cells proliferation. Among nonimmune mechanisms, proteinuria and hypertension play a relevant role. Moreover, the reduced number of functioning nephrons may trigger an inflammatory process that, eventually, contributes to the loss of the graft. Several studies have documented the efficacy of blocking the renin-angiotensin system (RAS) in reducing proteinuria and preventing renal function deterioration in experimental models of chronic rejection. Early results are promising. However, available clinical trials are rather limited in terms of number of patients enrolled, consequently they cannot be considered definitive. Since several pathogenetic factors are involved in the progression of chronic transplant nephropathy, a multidrug approach with specific immunosuppressants and RAS-blocking drugs has been proposed to control/prevent chronic injury and progressive renal deterioration. Preliminary results in experimental models are promising. Data from prospective clinical trials are, however, mandatory to confirm the efficacy of a polypharmacological strategy in preventing chronic rejection.

B-Lymphocytes↗
PubMedDate not supplied

[Transplants].

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Humans↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibition and calcium channel blockade both normalize early hyperfiltration in experimental diabetes, but only the former prevents late renal structural damage.

We studied the potential renoprotective properties of a calcium channel blocker in moderately hyperglycemic diabetic rats both in the early phase of the disease and in the very long term, and compared such an effect with that of an angiotensin-I-converting enzyme (ACE) inhibitor. Three groups of diabetic rats, one receiving no therapy except insulin and the remaining two receiving insulin and the ACE inhibitor enalapril or the calcium blocker lacidipine and one group of nondiabetic control rats were followed for 4-6 weeks. Both antihypertensive drugs lowered systolic blood pressure comparably. At the end of the observation period, untreated diabetic rats exhibited elevation of glomerular filtration rate and renal plasma flow. Both enalapril and lacidipine treatment completely prevented whole-kidney hyperfiltration and hyperperfusion. Four additional groups of rats, similarly treated, were followed for 1 year. A comparable control of systolic blood pressure and blood glucose level was achieved with the two antihypertensive regimens throughout the whole study period. At 12 months, the average kidney weight was elevated to similar values in all diabetic groups relative to control rats. Untreated diabetic rats had progressive proteinuria and developed glomerulosclerosis. Enalapril markedly limited the development of proteinuria. By contrast, urinary protein excretion in diabetic rats given lacidipine markedly increased with time, and values were as high as those in untreated diabetic animals. Similarly, only enalapril was effective in limiting glomerular injury. These results indicate that ACE inhibition but not calcium channel blockade has a favorable effect in preventing renal disease progression in diabetic rats and suggest that the various antihypertensive regimens are not equally beneficial in protecting against diabetic glomerulopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Studies of privileged sites and organ transplantation.

Extensive research has been carried out in the last years to try to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. Ideally, one would hope to achieve a state of donor-specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals, and even in humans increasing data are available that tolerance is achieved in some patients years after transplantation. The interest in donor-specific transplant tolerance has been renewed by the recent observations that in the rat the thymus is an immunologically privileged site into which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection induced donor-specific unresponsiveness, which allowed survival of a second donor-strain islet cell allograft transplanted into an extrathymic site. Findings on cellular allograft have been extended to vascularized organ allografts. Recent experiments documented that in the rat intrathymic injection of donor cells allows subsequent renal graft to survive indefinitely. Unresponsiveness to rat kidney graft is donor but not tissue specific and evidence is presented here that the thymus has a central role in such a phenomenon. Hopefully, these studies will open new perspectives in transplantation promoting indefinite graft survival without the complications of long-term immunosuppressants.

Animals↗
PubMedDate not supplied

Intrathymic transplantation of donor cells allows a stabilized, incompatible renal transplant to survive indefinitely after cyclosporine withdrawal.

Recent experiments have shown that exposure of maturing rat thymocytes to donor cells induces a condition of donor-specific unresponsiveness in the recipient that allows indefinite survival of a subsequent kidney transplant without the need for long-term immunosuppressants. Here, studies were performed in Lewis (RT1(1)) rats to determine whether (a) the process of unresponsiveness to kidney allograft induced by intrathymic donor cell inoculation occurred also with a noninbred strain of donor animals, and (b) this technique could allow the elimination of the need for daily immunosuppressive therapy in animals already transplanted with an incompatible kidney. Kidneys from noninbred Sprague-Dawley rats transplanted in incompatible Lewis (RT1(1)) rats, previously injected intrathymically with cells from the same donor, survived indefinitely. Intrathymic inoculation of donor cells into Lewis rats allowed a stabilized, incompatible renal allograft from Brown-Norway (RT1n) rats to survive indefinitely after discontinuation of immunosuppressive treatment with cyclosporine. These findings provide an approach for renal transplantation without immunosuppressive therapy and a potential strategy to overcome side effects related to the use of immunosuppressants in animals already transplanted.

Animals↗