Beneficial immunosuppressive effect of combined use of FK 506 and cyclosporine assessed by proliferative responses of cloned human T cells.
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Cell Survival↗
Biomedical subjects
M Imanishi
Publications and source records attributed to M Imanishi.
[Experimental studies on the mode of action of cyclosporine and FK506 assessed by proliferation response of human cloned T lymphocytes].
We applied cloned human T lymphocytes established in our laboratory to evaluate the mode of action of Cyclosporine (CsA) and FK506. Phenotypic and functional analysis led us to conclude that HTL403 was a helper T cell clone and HTL805 a cytotoxic one. Susceptibility of HTL-403 to the immunosuppressants demonstrated that alloantigen-driven proliferative response can recover to the rIL2-driven level by the addition of rIL2 at higher concentration of the agents. Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. FK506 showed remarkable suppressive effect on the proliferative response of HTL-805 even at a considerably low concentration, while CsA suppressed such a response dose-dependently. We concluded that FK506 can be used to reverse ongoing acute rejection as well as to prevent acute rejection.
Cell Division↗
Aspirin injection test to predict angioplasty outcome in unilateral renovascular hypertension: preliminary report.
We examined the usefulness of aspirin DL-lysine for prediction of the outcome of renal artery angioplasty in renovascular hypertension. The study was carried out in eight hypertensive patients with unilateral renal artery stenosis: six were free from azotemia and two had slight azotemia. Before and 30 min after an intravenous injection of aspirin DL-lysine (18 mg/kg), renal venous and abdominal aortic plasma was sampled and assayed for prostaglandin E2 and plasma renin activity. Blood pressure and heart rate were serially measured at this time. Renal angioplasty was later performed and was technically successful in all patients. In the six patients without azotemia, aspirin inhibited renal prostaglandin E2 synthesis and suppressed renin release from the ischemic kidney, resulting in lowered blood pressure. Renal angioplasty caused plasma renin activity to become normal and lowered high blood pressure. The reduction in blood pressure by angioplasty was correlated with the responses of blood pressure and renin release to aspirin. However, in the two patients with azotemia, aspirin neither suppressed renin release nor lowered blood pressure. Their hypertension was not reduced by the angioplasty. These results indicate that an aspirin injection test could be useful for prediction of the outcome of angioplasty in unilateral renovascular hypertension.
Adult↗
Renal and femoral vascular responses to endothelin-1 in dogs: role of prostaglandins.
Vascular responses to endothelin were examined with special reference to prostaglandins (PGs). Intrarenal infusion of endothelin (ET)-1 (1-5 ng/kg/min) to dogs caused a transient increase followed by a sustained decrease in renal blood flow, with no change in blood pressure or heart rate. Renal secretion rates of PGE2 and I2 (determined as 6-keto PGF1 alpha) were increased with ET, dose-dependently, and the intrarenal infusion of ET (5 ng/kg/min) elevated the systemic arterial concentration of 6-keto PGF1 alpha from 26 +/- 5 to 83 +/- 14 pg/ml. Because this increase in PG secretion was not affected by the platelet activating factor antagonist, CV 6209, it is unlikely that ET-induced renal PG production was platelet activating factor-mediated. Pretreatment with aspirin abolished completely the increased PG secretion elicited by ET and potentiated the ET-induced reduction renal blood flow. Intrafemoral infusion of ET (5 ng/kg/min) also induced an initial increase followed by a gradual decrease in femoral blood flow, without any increase in PG secretion from the hindlimb. Aspirin had no effects on the femoral hemodynamic action of ET. In addition, initial transient increases in either renal or femoral blood flow by endothelin were not affected by aspirin. Thus, the ET-induced production of renal PGs counteracts the renal vasoconstrictor action of ET, an event in marked contrast to the lack of any apparent involvement of PGs in the femoral hemodynamic action of ET. The ET-induced transient vasodilation shows no apparent relation to the cyclooxygenase products.
6-Ketoprostaglandin F1 alpha↗
Effects of nifedipine SR and enalapril on office, home and ambulatory blood pressure in "white-coat" systemic hypertension.
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Adult↗
Mechanisms of intracellular pH regulation in the hamster inner medullary collecting duct perfused in vitro.
To examine the mechanisms of H+ transport in the mid-inner medullary collecting duct of hamsters, we measured the intracellular pH (pHi) in the in vitro perfused tubules by microscopic fluorometry using 2',7'-bis(carboxyethyl)-carboxyfluorescein (BCECF) as a fluorescent probe. In the basal condition, pHi was 6.74 +/- 0.04 (n = 45) in HCO3(-)-free modified Ringer solution. Either elimination of Na+ from the bath or addition of amiloride (1 mM) to the bath produced a reversible fall in pHi. After acid loading with 25 mM NH4Cl, pHi spontaneously recovered with an initial recovery rate of 0.096 +/- 0.012 (n = 23) pH unit/min. In the absence of ambient Na+, after removal of NH+4, the pHi remained low (5.95 +/- 0.10, n = 8) and showed no signs of recovery. Subsequent restoration of Na+ only in the lumen had no effect on pHi. However, when Na+ in the bath was returned to the control level, pHi recovered completely Amiloride (1 mM) in the bath completely inhibited the Na(-)-dependent pHi recovery. Furthermore, elimination of Na+ from the bath, but not from the lumen, decreased pHi from 6.97 +/- 0.07 to 6.44 +/- 0.05 (n = 12) in the HCO3-/Ringer solution or 6.70 +/- 0.03 to 6.02 +/- 0.5 pH unit/min in the presence of CO2/HCO3-, whereas it did not recover in the absence of CO2/HCO3-.(ABSTRACT TRUNCATED AT 250 WORDS)
Amiloride↗
Possible role of renal prostaglandin E2 in natriuresis associated with supraventricular tachycardia.
We investigated the possible role of renal prostaglandin (PG) E2 in natriuresis associated with supraventricular tachycardia (SVT). In five female patients with paroxysmal tachycardia, SVT was artificially induced and then stopped 60 min later. Before, during, and after SVT, plasma levels of arginine vasopressin and atrial natriuretic peptide (ANP) and the urinary excretion of sodium and PGE2 were measured. Polyuria was observed during SVT. However, natriuresis did not occur until immediately after the termination of SVT. During SVT, the plasma levels of arginine vasopressin tended to decrease. When SVT was terminated, the vasopressin levels increased significantly (p less than 0.01). Urinary excretion of PGE2 tended to decrease during SVT and then increased significantly (p less than 0.01) after SVT ended. Urinary excretion of sodium was correlated (r = 0.699, p less than 0.001) with the urinary excretion of PGE2. Plasma ANP increased during SVT, but there was no correlation with urinary sodium excretion. These results suggest that renal PGE2, the biosynthesis of which may be stimulated by a increase in plasma vasopressin, is an important factor contributing to the natriuresis observed after the end of SVT.
Adult↗
Sodium sensitive and sodium retaining hypertension.
The differences between sodium sensitive and sodium retaining hypertension were theoretically considered using a water tank model of body fluid volume-blood pressure regulation. If an outlet valve is attached to a tank with a base area corresponding to the reciprocal of total peripheral resistance (TPR) and water is poured into this tank at a rate corresponding to the amount of Na+ intake, then equilibrium should be achieved at a certain water level, volume and output from the outlet, which represent mean arterial pressure (MAP), cardiac output (CO) and urinary Na+ excretion. The height of the outlet from the tank bottom and the size cross-sectional area, of the outlet correspond to the x-intercept and slope of the renal function (pressure-natriuresis) curve, respectively. In both nonsodium sensitive hypertension, due to the shift of the curve toward a higher blood pressure level (elevated height of the outlet) without change in the slope (size of the outlet), and sodium sensitive hypertension, due to the depressed slope of the curve (reduced outlet size), not only MAP (water level) but also CO (water volume) are increased, resulting in sodium retaining hypertension, if TPR (reciprocal of base area) remained unchanged, while CO is relatively unchanged, resulting in nonsodium retaining hypertension, if TPR is elevated. Thus, the MAP and its sensitivity to sodium intake is determined by the renal function curve. Since body fluid volume is determined by both the renal function curve and TPR, however, changes in TPR during the development of hypertension is a major factor in determining whether or not the body fluid volume has to change only a small amount or a large amount. Therefore, the sodium sensitivity of blood pressure and sodium retention must be considered separately.
Blood Pressure↗
Normalization of increased sodium sensitivity by maintenance hemodialysis.
Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/- 1.3 mm Hg/L) in patients (n = 10) whose BP was still high.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of endothelin on renal hemodynamics and renal function in anesthetized dogs.
Porcine endothelin was infused directly into the renal artery of anesthetized dogs to evaluate the renal action of endothelin. Endothelin (0.2 to 5.0 ng/kg/min) elicited a dose-dependent reduction in the renal blood blow with no changes in systemic blood pressure. Endothelin infusion (0.2 ng/kg/min) decreased the renal blood flow by 30% and urinary sodium excretion by 50% without any changes in the glomerular filtration rate. However, higher doses did reduce glomerular filtration rate. These data suggest that endothelin preferentially constricts efferent arterioles and that endothelin may enhance the renal reabsorption of sodium.
Animals↗
A comparison of lisinopril with enalapril by monitoring plasma angiotensin II levels in humans.
The present study was designed to examine and compare the acute effects of lisinopril (20 mg) and enalapril (10 mg) after a single oral administration on the inhibition of the renin-angiotensin system (RAS) in eight normal subjects. Serum concentration of lisinopril and enalaprilat, an active metabolite of enalapril, reached the respective maximal levels at 6 and 4 hr after administration of the drugs. At 24 hr, the serum concentration of lisinopril was higher than that of enalapril; thus the rate of disappearance of lisinopril was retarded, in comparison to that of enalapril. The reduction of serum angiotensin I converting enzyme (ACE) activity was consistent with the pattern of increase of concentration of the drugs in the serum. However, with these two drugs, the concentration of plasma ANG II was decreased in a similar manner, and it returned to the pretreatment level within 24 hr. Thus, there was no significant difference in ANG II levels throughout the 24 hr-study between the lisinopril and enalapril treatment. The results indicate that a single administration of 20 mg lisinopril and 10 mg enalapril show similar potency for lowering the circulating ANG II level, although lisinopril exerts a more sustained inhibition of serum ACE activity. The measurement of ANG II provides useful informations for evaluating the efficacy of ACE inhibitors for the inhibition of circulatory RAS.
Administration, Oral↗
[Urinary FDP D-dimer and E fragments in renal transplantation].
Both D-dimer and E fragments in urinary FDP were determined in renal transplantation patients. Urinary D-dimer fragments increased in 14 out of 20 acute rejections (70.0%) and in 6 out of 18 chronic rejections (33.3%). Urinary E fragments increased in 8 out of 9 acute rejections (88.9%) and in 4 out of 5 chronic rejections (80.0%). It is suggested that urinary FDP-E fragment is a better indicator to detect or predict rejection than the whole Urinary FDP. The appearance of D-dimer in the urine indicates intravascular coagulation in glomeruli followed by a secondary fibrinolysis in the course of the rejection reaction. The urinary D-dimer/FDP ratio which was used as the indicator of fibrinolytic activity in glomeruli was obtained in various conditions of renal transplants. The ratios were relatively high in the urines from well functioning grafts. This ratio deteriorated at the onset of rejection crisis and tended to go upward during the course of the recovery when the rejection was reversible. In the cases of irreversible acute rejection and chronic rejection, these ratios remained at a low level. D-dimer/FDP ratio might be useful indicator to predict the reversibility of rejection and the prognosis of renal allograft. Furthermore, these findings suggest that fibrinolytic and thrombolytic therapy by the tissue-type plasminogen activator (t-PA) along with immunosuppressive drugs might be more effective for the treatment of these rejections.
Fibrin Fibrinogen Degradation Products↗
[Management of hypertension after renal transplantation].
We report the clinical result of our management for post-transplant hypertension in 47 renal allograft recipients who were followed up for more than one year after transplantation. Hypertension developed in 4 (26.7%) out of 15 cases who were treated with conventional immunosuppressive therapy (Group I) and 18 (56.3%) out of 32 cases treated with CsA (Group II). In group I, all the 6 patients who had been nephrectomized their original kidney at the time of transplantation did not develop hypertension. And the blood pressure before transplantation had a marked effect on post-transplant blood pressure. In group II, there were many recipients who had become hypertensive after transplantation though most of them became normotensive with dose reduction of immunosuppressants. Ten normotensive patients before transplantation who had not developed hypertension retained their normal blood pressure throughout the course without any antihypertensive medication. We could find no correlation between graft function and blood pressure, although recipients with poor graft function had a tendency to be hypertensive. A satisfactory fall in blood pressure in the patients treated with CsA was observed when the immunosuppressive regimen was changed to triple therapy to reduce the dose of CsA. The recorded blood pressure were 174.0 +/- 19.0/105.2 +/- 16.5 mmHg after transplantation and 145.2 +/- 15.7/78.4 +/- 17.1 mmHg at the latest follow-up. We performed original nephrectomy in 6 patients whose blood pressure could not have been controlled by the antihypertensive medication. All the venous sampling studies showed that increased renin secretion was confined to original kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[The effects of thromboxane A2 synthetase inhibitor on chronic rejection of kidney transplantation].
There has been no useful treatments for chronic vascular rejection (CVR) after kidney transplantation until now. Recently, however, some reports have suggested that the thromboxane A2 synthetase inhibitor, OKY-046, is useful in reducing proteinuria in nephrotic syndrome and preventing progression of CVR. Five patients with CVR (serum creatinine range: 1.7-2.6 mg/dl) were treated with OKY-046 for over one year and the effect of OKY-046 was evaluated. One patient developed acute rejection and another renal hypertension during this study. Except for the cases of acute rejection and renal hypertension, serum creatinine slightly decreased in 1 case and remained unchanged in 2 cases. Urinary excretion of protein and thromboxane B2 decreased significantly but prostaglandin E2 did not change in the treatment of the deterioration with OKY-046. We concluded that OKY-046 was effective in preventing graft function and decreasing urinary protein excretion in kidney transplant recipients with CVR.
Acrylates↗
[Clinical studies on hyperuricemia and gout after transplantation].
We performed renal transplantation on 67 patients (living 37, cadaver 30) between November 1975 and December 1987. Twenty-seven of the 67 patients had hyperuricemia (serum uric acid: male greater than or equal to 8.0 mg/dl, female greater than or equal to 7.0 mg/dl) and 2 of them had episodes of gout. However, there was no correlation between serum creatinine and uric acid in 27 hyperuricemic patients. Twelve of 27 hyperuricemic patients were treated with either allopurinol or benzbromarone. These therapies were effective for 9 of them and serum uric acid level controlled well. One of 2 gouty patients developed gout 4 years after cadaveric renal transplantation. She was treated with anodyne and benzbromarone for gout. These treatments were effective and she has been in good condition. We consider it necessary to treat hyperuricemia after renal transplantation and to control serum uric acid well.
Adult↗
[Interaction between phenobarbital and ciclosporin following renal transplantation: a case report].
We report a case of decreased ciclosporin (CsA) trough level due to the interaction with phenobarbital after living renal transplantation in a 15-year-old male. Two other cases prescribed valproate sodium as an anticonvulsant, showed no change in the plasma CsA levels. Therefore, it is necessary to recognize the drug interaction with CsA, and appropriate drug should be chosen in clinical renal transplantation.
Adolescent↗
Endothelin stimulates the renal production of prostaglandin E2 and I2 in anesthetized dogs.
The infusion of endothelin into the renal artery of anesthetized dogs (5 ng/kg per min) decreased the renal blood flow without changing the blood pressure, indicating that endothelin caused renal vasoconstriction. The renal secretion rate of prostaglandin E2 and I2 markedly increased and these increases were abolished by pretreatment with aspirin. Furthermore, the renal vasoconstrictor effect of endothelin was potentiated by aspirin, suggesting a role of prostaglandins in the renal action of endothelin.
Anesthesia↗
Removal of intracellular waste products by hemofiltration.
Because the total amount of waste products removed by hemofiltration can be measured exactly, it was divided into two components, that removed from the extracellular compartment and that removed from the intracellular compartment, using inulin as a marker for extracellular fluid in five uremic patients treated with hemofiltration in the postdilution mode. The amount removed from the extracellular compartment as a proportion to the total amount removed from the whole body by hemofiltration was 86.5% +/- 10.6% for guanidinosuccinic acid, 69.1% +/- 15.6% for sodium, 59.4% +/- 3.3% for uric acid, 56.4% +/- 2.1% for inorganic phosphate, 45.6% +/- 5.3% for creatinine, 43.1% +/- 7.2% for potassium, 42.9% +/- 3.1% for guanidinoacetic acid, 42.5% +/- 7.5% for methylguanidine, 37.2% +/- 8.4% for chloride, 36.3% +/- 2.8% for urea, and 6.9% +/- 2.9% for glucose. These results show that extracellular substances such as sodium and guanidinosuccinic acid were removed mainly from the extracellular compartment. On the other hand, glucose was removed only from the intracellular compartment, since blood glucose level is regulated. Although uric acid, inorganic phosphate, creatinine, potassium, guanidinoacetic acid, and methylguanidine are intracellular substances, they accumulated also in the extracellular fluid in renal failure, and were removed from both compartments, intracellular as well as extracellular, by hemofiltration.
Body Fluids↗