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V Panichi

Publications and source records attributed to V Panichi.

At least 37 records · Page 2Linked to original sources
PubMed1999

L-propionyl carnitine reduces toxicity correlated to cyclosporine-induced intracellular ATP concentrations.

In previous trials we proved how propionyl carnitine, an acyl carnitine characterized by its intense mitochondrial metabolic, and cardio and vasoprotective activity, could prevent the cyclosporine-induced nephrotoxicity. Subsequently we also noted how propionyl carnitine could prevent the increase in renal intracellular calcium, which is the base of many cyclosporine-induced toxic phenomena. In our trials, we used the isolated and perfused rat kidney technique to examine if with the variations of the concentration of intracellular calcium, the adenosine 5'-triphosphate concentrations also varied, and if this decrease could be corrected by administrating propionyl carnitine. The results we obtained in these experiments indicated that when propionyl carnitine was administered preventively, the concentrations of renal intracellular adenosine 5'-triphosphate which were decreased by the cyclosporine returned to their normal values and, at the same time, a decrease in the increased vascular resistance of the kidney was noted. Therefore, propionyl carnitine corrected one of the biochemical alterations which explained the pathogenesis of the renal damage induced by cyclosporine.

Adenosine Triphosphate↗
PubMed1998

Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium.

Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.

Adult↗
PubMed1998

Cytokine production in haemodiafiltration: a multicentre study.

BACKGROUND: Bacterial contamination of dialysate may enhance cytokine production in haemodialysis. We tested the hypothesis that intracellular cytokines could be enhanced in a large group of patients exposed to backfiltration of dialysate over a long period of observation. METHODS: The intracellular cytokine (interleukin-1 receptor antagonist and interleukin-1beta) concentrations in chronic uraemic patients undergoing haemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared to those found in patients treated with a modified haemodiafiltration modality without backfiltration (Group I, 16 patients), in patients shifted from one modality to the other (Group III, 27 patients) and in 10 patients on haemodialysis (Group IV) in a 1-year multicentre study. Group V comprised 10 healthy volunteers. All dialysis monitors were equipped with dialysate ultrafiltration systems. Dialysate contamination was studied by the LAL and the peripheral mononuclear cell/interleukin-1beta assays in the presence or absence of polymyxin B. RESULTS: Intracellular interleukin-1 receptor antagonist and interleukin-1beta both increased significantly (P < 0.002) but slowly (after 8 months) in Groups II vs I, and during the 4-month period in haemodiafiltration with backfiltration in Group III. The incidence of post/predialysis concentration ratio (over 1.5) increased two- to threefold in patients treated with haemodiafiltration with backfiltration with respect to haemodiafiltration without backfiltration. Results on the assays for LAL (< 0.5 E/ml) and interleukin-1beta (range 80.1-90.2 pg/5 x 10(6) cells; 70.2-81.3 pg/5 x 10(6) cells with polymyxin B) showed a moderate-to-low degree of dialysate contamination. CONCLUSIONS: Backfiltration of dialysate with moderate-to-low degree of contamination may enhance cytokine synthesis in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality and/or at reducing backfiltration is highlighted.

Adult↗
PubMed1998

Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in patients with predialytic renal failure.

Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality. Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective. In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance 22.9 +/- 9.8 ml; range 8-32 ml/min) were treated in a cross-over randomized design with oral daily calcitriol 0.5 micrograms/die (Treatment A), three oral boluses of 2 micrograms of calcitriol a week (Treatment B) and a single oral bolus of 2 micrograms of calcitriol a week (Treatment C). All treatment periods lasted three months and were followed by a wash-out period of one month. Serum iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance were measured every two weeks. Serum iPTH was also determined in a control group of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21 +/-12 ml/min) observed for three months without calcitriol treatment. Daily oral intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270 +/- 169 pg/ml to 135 +/- 76 pg/ml (p < 0.01; B) and to 165 +/- 121 pg/ml (p < 0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n.s.). No significant differences in renal function were observed during the different study periods. Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure.

Administration, Oral↗
PubMed1998

Biocompatibility evaluation of polyamide hemofiltration.

INTRODUCTION: Postdilution hemofiltration with a polyamide membrane is a renal replacement technique widely used, but very little information is available regarding the biocompatibility of this treatment. In this paper we report the results of an acute study of the biocompatibility of polyamide hemofiltration. PATIENTS AND METHODS: Complement activation such as C3a and C5a Des Arg (RIA), granulocyte degranulation like alpha 1 elastase intradialytic increase (ELISA) and the expression of high affinity membrane receptors for IL-2 (anti-TAC) were determined. Beta 2-microglobulin (RIA) intradialytic decrease, as well as its convective removal, was evaluated. The nature of protein layer adsorbed onto the polyamide membrane, at the end of the dialytic session was investigated with a new immunohistochemical technique. Cell-associated cytokine concentration (like IL-1 beta and IL-1Ra - ELISA) was determined on mononuclear cell lysates. RESULTS: A low degree of complement activation was detected with the polyamide membrane when data were adjusted for hemoconcentration and for 1 m2 of membrane surface area. An important convective removal not only of Beta 2-microglobulin (258+/-20 mg/session), but also of the activated anaphylatoxins (225+/-76 ng/ml for C3a and 22.5+/-4 ng/ml for C5a) was revealed. A marked deposition of all coagulation factors with no detectable amount of immunoglobulins and complement factors was revealed on the polyamide membrane at the end of the dialytic session. No intradialytic (for IL-1beta) (from 14. 1+/-3.0 to 13.5+/-2.9 pg/2.5 x 10(6) cell) and interdialytic (for IL-1Ra) (from 4572+/-1076 to 5408+/-615 pg/2.5 x 10(6) cell) cell-associated cytokine expression was induced by hemofiltration. DISCUSSION AND CONCLUSION: Polyamide hemofiltration is a highly biocompatible technique due to the use of a synthetic membrane with a sterile reinfusion fluid and the convective removal of the activated anaphylatoxins and Beta 2-microglobulin.

Adult↗
PubMed1996

Acute suppression of parathyroid activity during hemofiltration.

Hemofiltration (HF) induces a significant reduction in parathormone (PTH). This effect is related not only to the convective removal of PTH molecules but also to the biological suppression of parathyroid glands by plasma-ionized calcium (iCa) increase. The acute inhibitory effect on parathyroid gland activity, ionized calcium mass balance, phosphate kinetics and intact PTH (PTHi) dialytic removal during post-dilution polyamide HF were studied in 31 chronic uremic patients. HF ensures good phosphate removal (from 2.54 +/- 1.19 to 1.27 +/- 0.35 mEq/l; p < 0.01), a positive iCa mass balance (8 +/- 4 mmol/session) with a iCa plasma increase and negligible convective PTHi removal (9 +/- 2 pg/ml). Study of the PTHi profile during HF characterized two different parathyroid responses: 26/31 patients showed a physiological parathyroid gland response to the iCa increase (from 1.17 +/- 0.09 to 1.42 +/- 0.07 mmol/l; p = 0.002) with a significant PTHi decrease (from 123 +/- 111 to 35 +/- 28 pg/ml; p = 0.01) and a maximal PTH inhibition of 88%. In 5 patients, with more severe hyperparathyroidism, in spite of a comparable increase in iCa (from 1.28 +/- 0.12 to 1.46 +/- 0.08 mmol/l; p = 0.02), this physiological calcium-PTHi feedback was lost, revealing an autonomization of the gland (maximal inhibition of 45%). In our experience, study of the PTHi profile during a single HF session may represent a clinical test for the functional exploration of parathyroid glands, suggesting future (medical or surgical) clinical strategy.

Acute Disease↗
PubMed1996

Study of serum 3,5,3'-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness.

Sulfation is an important pathway of triiodothyronine (T3) metabolism. Increased serum T3 sulfate (T3S) values have been observed during fetal life and in pathological conditions such as hyperthyroidism and selenium deficiency. Similar variations have also been reported in a small number of patients with systemic non-thyroidal illness, but the underlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 28 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as controls. Both ESND and CRF patients had lower serum total T4 (TT4) and total T3 (TT3) than normal controls, while serum reverse T3 (rT3) was increased significantly in ESND (0.7 +/- 0.5 nmol/l; p < 0.001 vs. controls) but not in CRF (0.3 +/- 0.1 nmol/l). The TT3/rT3 ratio, an index of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients. Serum T4-binding globulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 +/- 32 pmol/l) and CRF (100 +/- 24 pmol/l) than in controls (50 +/- 16 pmol/l, p < 0.001). Serum T3S values showed a positive correlation with rT3 values and a negative correlation with both TT3 and FT3 values in ESND, but not in CRF. In the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 +/- 5) and in ESND (23 +/- 18) as compared to controls (10 +/- 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CRF patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent on the impaired renal excretion of T3S. Because T3S can be reconverted to T3, it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.

Adult↗
PubMed1995

Acute effects of calcitonin gene related peptide on renal haemodynamics and renin and angiotensin II secretion in patients with renal disease.

The renal haemodynamic effects and renin-angiotensin II response to calcitonin gene-related peptide (CGRP) infusion were assessed in 16 patients with moderate hypertension and renal insufficiency. CGRP lowered the systemic mean blood pressure by 13% and increased the heart rate by 25%; the glomerular filtration rate rose from 56 +/- 11 ml/min to 71 +/- 8 ml/min (p < 0.005), the renal plasma flow decreased from 369 +/- 19 ml/min to 342 +/- 25 ml/min (p < 0.002) and the filtration fraction increased from 15 +/- 0.2% to 20 +/- 0.2%. Plasma renin activity rose stepwise during the CGRP infusion from 1.28 +/- 0.5 ng/ml/h to 1.66 +/- 0.4 and 1.89 +/- 0.4 ng/ml/h (p < 0.001). Angiotensin II showed a marked increase after 10 min of infusion (91.6 +/- 47.00 pg/ml) (control value 6.01 +/- 3.09 pg/ml) and at the end (28.63 +/- 16.00 pg/ml) (p < 0.001). CGRP exerts an apparently favourable effect on renal function of patients with renal insufficiency, but the observed increase of glomerular filtration rate is obtained by an increase of intraglomerular pressure secondary to angiotensin II production.

Adult↗
PubMed1995

Protein layer on hemodialysis membranes: a new immunohistochemistry technique.

In order to investigate the nature of the protein layer deposited on hemodialysis membranes we developed a direct immunohistochemical technique using fluoresceinated antibodies to plasma membranes. Fifteen patients on regular dialytic treatment were dialyzed with CU, HE, PAN, PS and PMMA and the dialyzers analyzed at the end of a standard dialytic session. Snap frozen sections of hollow fiber devices were treated with flourescein-isothiocyante conjugated antibodies for IgG, IgA, IgM C3c, fibrinogen, factor VIII, factor XIIIa-s, antithrombin III, fibrinogen degradation products (PDF) and plasminogen. Protein deposits were evaluated by a quantitative criteria, which evaluates the intensity of fluorescence and the area of the capillary wall occupied by this fluorescence by using an image analysis software. The coagulation cascade is activated by all membranes and similar deposits of these proteins were revealed, whereas important differences in C3c deposition were found.

Adsorption↗
PubMed1995

Eliminant effects of calcitonin gene related peptide on the tubular epithelial cells in an isolated and perfused rat kidney.

The effect of the infusion of calcitonin gene related peptide (CGRP) on the renal structure and enzyme release from tubular epithelial cells was studied. This study was performed in the model of an isolated perfused kidney to avoid the systemic effects and complex hormonal and neuromediated interaction following the CGRP infusion in the intact experimental animal. After infusion of CGRP, the perfused kidney, studied by semiquantitative histology and electron microscopy, did not show any alteration at the glomerular level; however, important histological lesions were apparent at the proximal tubular level: the brush border was destroyed and the epithelial cells were markedly flattened. This structural damage to epithelial cells was confirmed by electron microscopy. The alanine amino peptidase (AAP) and N-acetyl-glucosaminidase (NAG) were significantly increased in the effluent of the perfusion system, in confirmation of the histological damage. The direct toxic effect of CGRP on the tubular epithelial cells may be related to the reabsorption and tubular transport of this substance.

Acetylglucosaminidase↗
PubMed1995

Protective effect of L-propionylcarnitine on cyclosporine-induced nephrotoxicity.

Nephrotoxicity has represented the major limitation in the use of cyclosporine A (CyA). The structural abnormalities at the level of the proximal tubular cells are necrosis, vacuolisation and lipid droplets, as well as CyA-induced glomerular afferent arteriole constriction and granular juxtaglomerular cell hyperplasia. The mode of action of vasoconstriction is not well known, but there appears to be substantial impairment of endothelial cell function leading to enhanced release of vasoconstrictors such as endothelin and thromboxane. L-propionylcarnitine (PC), one of the most potent analogues of carnitine, is able to correct and to prevent alterations in endothelial membrane permeability and it has been identified in the kidney of various animal species. To investigate a possible reduction of CyA-induced nephrotoxocity, we examined the effects of a pretreatment with PC before administering several doses of CyA in an isolated and perfused rat kidney. The histological findings showed that the perfusion with PC reduces the vasoconstrictive effect of CyA on the glomerular capillaries and preserves the tubular epithelium. The ratio of the diameter between the glomerular capillary tuft and Bowman's capsule was higher, while at the tubular level the ratio internal-diameter/diameter evaluated at the level of the basal membrane was lower in PC + CyA perfused kidneys than in only CyA perfused ones. The final value of perfusion pressure was lower in PC + CyA perfused kidneys than in only CyA perfused ones, confirming the histological findings. The release induced by CyA of alanine aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG), markers of tubular damage, was significantly reduced by pretreatment with PC. These data suggest that the pretreatment with PC reduces the CyA-induced nephrotoxicity in an isolated and perfused rat kidney.

Analysis of Variance↗
PubMed1994

Cellular expression of lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 in normal kidney structures and in renal cancer. Possible significance in immune response and in the clinicopathological correlation.

In this study we investigated the presence of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on renal cell cancer in 16 patients who underwent nephrectomy. In all cases, normal renal tissues presented ICAM-1 on the parietal epithelial cells lining Bowman's capsule while neither the visceral epithelium nor the glomerular endothelium were stained. The epithelial proximal and distal tubular cells were stained poorly (5 +/- 3 positive tubular cross sections/mm2). No renal cells were stained by the monoclonal antibody for LFA-1. In contrast, in renal cancer tissue we found 6 cases, negative for ICAM-1 and the others positive with a mean number of positive tubular cross sections of 52 +/- 37/mm2. In 10 cases staining with LFA-1 antibody was negative, while for the other cases the mean number of positive tubular cross sections was 11 +/- 8/mm2. Our results suggest that the expression of ICAM-1 and LFA-1 on the surface of malignant cells may explain the unusual clinical aspects of renal cell carcinoma, its association with the immune system, and clarify certain aspects of immunotherapy.

Carcinoma, Renal Cell↗
PubMed1994

Mechanisms of acid-base homeostasis in acetate and bicarbonate dialysis, lactate hemofiltration and hemodiafiltration.

The different mechanisms of acidosis buffering were investigated in 15 RDT patients dialyzed in cross-over with four depurative techniques: acetate dialysis (AD), bicarbonate dialysis (BD), lactate hemofiltration (LHF) and hemodiafiltration (HDF) with acetate bath and lactate reinfusion fluid. Blood pH, bicarbonate, blood gases, intraerythrocytic pH - on red cell hemolisates - anion gap, L-lactate, pyruvate, adenosinmonophosphate (ADP) and 2-3 Diphosphoglycerate (2-3 DPG) levels were evaluated. During AD the intradialytic buffering is initially achieved by the CO2 fall and later by the acetate metabolism and an important bicarbonate shift from the intra to the extracellular space. A physiological compensation is obtained during BD with bicarbonate administration and a mild ventilatory response to the pCO2 increase. In LHF the massive lactate administration, with plasma levels of 7 mmol/l, strongly alters the Central Nervous System elettroneutrality inducing a hyperventilatory response with a purely pulmonary acidosis buffering. Furthermore the lactate/pyruvate ratio rose as high as 40:1 with ADP increase and cellular energy depletion. In HDF several different mechanisms are associated: the CO2 fixation, the acetate muscular metabolism, the intra-extracellular bicarbonate shift with the pulmonary response driven by lactate Central Nervous System penetration.

2,3-Diphosphoglycerate↗
PubMed1994

Evaluation of calcitonin-gene related peptide on haemodynamics of isolated perfused rat kidney.

Outside the central nervous system, calcitonin-gene-related peptide (CGRP) plays an important role in the control of regional blood flow. The present authors studied the renal haemodynamic effects of CGRP in the model of isolated perfused rat kidney (IPRK). This experimental model avoids the complex feed-back mechanisms activated by any modification of renal perfusion pressure. It was found that the infusion of CGRP in the IPRK induced a marked decrease of perfusion pressure; this vasoactive effect is well measured by the glomerular morphometric analysis that shows a striking increase in the glomerular diameter and volume.

Animals↗