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C Schelotto

Publications and source records attributed to C Schelotto.

18 recordsLinked to original sources

A biocompatibility study on peritoneal dialysis solution bags for CAPD.

Numerous factors related to the composition of peritoneal dialysis solutions (PDS) contribute to the pathogenesis of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). They include high osmolarity, low pH, and the presence of lactate, which may be responsible for stimulating the proliferation of peritoneal fibroblasts (PF) and for the toxicity on the peritoneal mesothelial cells (PMC). Similar effects could be hypothesized for the plasticizers released from the PDS bags, usually made of polyvinyl chloride (PVC), such as the acid esters of phthalic acid, particularly bis-(2-ethylhexyl) phthalate (BEHP). Recently, however, new BEHP-free bags (Clear-Flex, Bieffe, Italy) made of three layers (polyethylene, nylon, and polypropylene) have been introduced. The aim of this work is to evaluate in vitro the effects of samples of PDS contained in PVC bags (Bieffe) and in Clear-Flex bags on the proliferative capacity of peritoneal fibroblasts and peritoneal mesothelial cells, and the release of interferon gamma (IFN gamma), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) from peritoneal T lymphocytes (PTLs) and macrophages (PM phi s). Results have shown that in the presence of PDS samples contained in PVC bags, the proliferative capacity of peritoneal fibroblasts was higher than in Clear-Flexbags. There was also an increased release of IFN-gamma and IL-1 from PTLs and PM phi s (cytokines that stimulate the collagen synthesis) and a decreased release of PGE2 (cytokines which inhibit the collagen synthesis). An inhibiting action on peritoneal mesothelial cells was also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Bacterial peritonitis and beta-2 microglobulin (B2M) production by peritoneal macrophages (PM0) in CAPD patients.

To evaluate the role of bacterial peritonitis in peritoneal macrophage (PMO) Beta-2 Microglobulin (B2M) production and its relationship with PMO Interleukin-1 (IL-1) and Leukotriene B4 (LTB4) release we analyzed in 20 CAPD patients (10 with peritonitis): 1. in vivo plasma and peritoneal dialysis effluent (PDE) B2M, IL-1 and LTB4 levels; 2. in vitro B2M, IL-1 and LTB4 release by PMO. Values were compared with those seen in the plasma or with peripheral blood monocytes of 30 hemodialysis (HD) patients (10 treated with Cuprophan-CU-, 10 with Polyacrylonitrile - PAN, and 10 with Cellulose Acetate - CA). Results showed that in CAPD patients with bacterial peritonitis B2M, IL-1 and LTB4 concentrations in the PDE were significantly higher than those seen in CAPD patients without peritonitis or in the plasma of HD patients treated with PAN or CA, but were similar to those seen in HD patients treated with CU. At the same time, in vitro, PMO from CAPD patients with bacterial peritonitis produced more B2M, IL-1 and LTB4 than did PMO from CAPD patients without peritonitis or peripheral blood monocytes from HD patients treated with PAN or CA. We conclude that in CAPD patients bacterial peritonitis is able to induce PMO B2M production, probably via a cytokine-mediated process, which may be analogous to what occurs with peripheral blood monocytes of HD patients treated with CU.

Adult↗

Peritoneal dialysis fluid (PDF) C++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients.

Our previous in vitro studies have shown that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PMO) antimicrobial activity in CAPD patients. We thus evaluated in vivo in 24 CAPD patients (12 who had never had peritonitis and 12 with an overall peritonitis incidence of more than one episode per 8 patient/month), the effects of different peritoneal dialysis fluid (PDF) Ca++ concentrations (1.25, 1.75 and 2.25 mmol/L) on PMO: 1. cytoplasmic Ca++ concentration; 2. superoxide generation; 3. Leukotriene B4 (LTB4) release; 4. bacterial killing for staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PMO Ca++ levels, superoxide and LTB4 generation, and bacterial killing, such that with 2.25 mmol/L of Ca++ these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca++ - induced effects. On the contrary, with PDF Ca++ levels of 1.25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients and may be useful in the prophylaxis and therapy of peritonitis.

Adult↗

Ca++ and 1,25(OH)2D3 regulate in vitro and in vivo the response to human recombinant erythropoietin in CAPD patients.

In vitro studies indicate that the culture medium Ca++ concentration conditions the response to erythropoietin of bone marrow erythropoietic cells which also have specific receptors for 1,25(OH)2D3. We therefore evaluated in 12 anemic CAPD patients: 1) in vitro with increasing concentrations of Ca++ alone or Ca++ plus 1,25(OH)2D3 a) Ca++ in the bone marrow erythroid cell cytoplasm; b) colony (BFU-E and CFU-E) growth from bone marrow erythroid cells. 2) in vivo before and after 24 weeks of i.v. recombinant human erythropoietin (rHuEPO) therapy a) bone marrow erythroid cell cytoplasmic Ca++; b) BFU-E and CFU-E growth. Results showed that in CAPD patients, in vitro cytoplasmic Ca++ in bone marrow erythroid cells, and BFU-E and CFU-E growth were lower than in normals and the addition of Ca++ caused a dose-dependent increase; 1,25(OH)2D3) potentiated these effects; 2, in vivo rHuEPO therapy normalized the aforementioned parameters. An inverse relationship was seen between the bone marrow erythorid cell cytoplasmic Ca++ levels before therapy and the duration of therapy necessary to correct anemia. These data underline the role of Ca++ and 1,25(OH)2D3 in erythropoiesis in uremic patients and may aid the understanding of the mode of action and the degree of response to rHuEPO in CAPD patients.

Anemia↗

Bone marrow erythroid precursor Ca++ regulates the response to human recombinant erythropoietin (rHuEPO) in hemodialysis patients.

The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.

Adult↗

Ca++ and 1,25(OH)2D3 enhance peritoneal macrophage (PMPhi) antimicrobial functions in CAPD.

Ca++ has been proposed as an intracellular second messenger for the activation of immune cells. An immune regulatory role for 1,25(OH)2D3 has also been suggested. We therefore evaluated the role of Ca++ and 1,25(OH)2D3 in the depressed antibacterial functions of 8 CAPD patients with relapsing bacterial peritonitis by evaluating in vitro the effects of escalating concentrations of 1,25(OH)2D3 and/or Ca++ on: 1. peritoneal macrophage (PMO) cytoplasmic Ca++; 2. PMO superoxide generation; 3. PMO leukotriene B4 release, 4. PMO bacterial killing. Results showed a dose-dependent increase in all parameters for Ca++ concentrations from 500 to 3,000 microM while with both a CA(++)-free medium and with Ca++ concentrations of 5,000 microM of medium all the aforementioned functions were abrogated. Addition of low doses of 1,25(OH)2D3 strongly potentiated the stimulatory effect of Ca++ on cell functions, while high doses were inhibitory. These in vitro data underline the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients, and may be useful in the prophylaxis and therapy of peritonitis.

Adult↗

Effects of Ca++ and 1,25(OH)2D3 on peritoneal immune-cell cytokine release and fibroblast proliferation in CAPD patients.

We have demonstrated the role in some CAPD patients with ultrafiltration (UF) loss of an increased peritoneal lymphocyte (PLy) and macrophage (PMO) Ca++ concentration in the release of large amounts of gamma-Interferon (gamma-IFN) and Interleukin-1 (IL-1), which stimulate peritoneal fibroblast proliferation. We have also shown in vitro and in vivo that the calcium channel blocker verapamil (VPM) is able to normalize the previously high Ca++ PLy and PMO concentration and cytokine release, to decrease fibroblast proliferation, and to increase UF in only 60% of the CAPD patients with UF loss due to a cytokine-mediated hyperproliferation of peritoneal fibroblasts, while in the remaining 40% there is little improvement in UF (VPM responders and low-responders, respectively). To evaluate which mechanisms in addition to passive Ca++ influx can play a role in the Ca(++)-dependent activation of peritoneal immune-cells, we evaluated in 6 CAPD VPM low-responder patients the effects of in vitro of different doses of Ca++ and 1,25(OH)2D3 on: 1) PLy and PMO cytoplasmic Ca++ levels in the PLy and PMO cytoplasm; 2) gamma-IFN and IL-1 release by PLy and PMO; 3) peritoneal fibroblast proliferation. Results showed a direct correlation between Ca++ levels in the medium and the PLy and PMO Ca++ concentrations, IL-1 and gamma-IFN release, and peritoneal fibroblast proliferation. These effects were enhanced by the addition of low doses of 1,25(OH)2D3 to the medium, while both high 1,25(OH)2D3 doses and verapamil abrogated the Ca+(+)-induced PLy and PMO activation. These results underline the importance of both Ca++ and 1,25(OH)2D3 in peritoneal immune-cell activation and peritoneal fibroblast proliferation, and may offer a new prophylactic approach for preventing UF loss in CAPD.

Adult↗

Effect of monophosphoryl lipid A (MPLA) on peritoneal leukocyte function.

We analyzed the in vitro effects of monophosphoryl lipid A (MPLA), a nontoxic bacterial endotoxin-derived immunomodulant, on the depressed immune functions of peritoneal lymphocytes (PLy) and macrophages (PMO) of 6 CAPD patients with relapsing bacterial peritonitis. MPLA was also tested for its capacity to stimulate the peritoneal fibroblast proliferation as determined by 3H-thymidine incorporation. In vitro incubation of PLy and PMO with escalating doses of MPLA up to 5 micrograms/ml, resulted in a dose-dependent enhancement of Gamma-Interferon (Gamma-IFN) and Interleukin-2 (IL-2) production by PLy, and Interleukin-1 (IL-1) by PMO. There was also an increase in PMO bacterial killing and membrane Fc receptor number, while no change in peritoneal fibroblast proliferation was seen with any of the MPLA concentrations tested. These results suggest that the peritoneal leukocyte abnormalities observed in some high peritonitis rate CAPD patients may be reversed, to some degree, by MPLA, without directly inducing a potentially deleterious peritoneal fibrosis.

Adult↗

Cytokine-induced peritoneal fibrosis in CAPD. Effects of Ca++ and 1,25(OH)2D3.

We have demonstrated in some continuous ambulatory peritoneal dialysis (CAPD) patients with ultrafiltration (UF) loss, the role of increased peritoneal lymphocyte (PLy) and macrophage (PMO) Ca++ concentrations in the release of large amounts of gamma-interferon (gamma-IFN) and Interleukin-1 (IL-1), which stimulate peritoneal fibroblast proliferation. We have also shown in vitro and in vivo that the calcium channel blocker verapamil (VPM) is able to normalize the previously high PLy and PM0 Ca++ concentrations, and cytokine release; to decrease fibroblast proliferation; and to increase UF in 60% of the CAPD patients with UF loss due to a cytokine-mediated hyperproliferation of peritoneal fibroblasts, while in the remaining 40% there is little improvement (VPM responders and low-responders, respectively). To evaluate which mechanisms, in addition to passive Ca++ influx, can play a role in the Ca++-dependent activation of peritoneal immune cells, we evaluated the effects in vitro of different doses of Ca++ alone; with VPM; and with 1,25(OH)2D3 on: 1) PLy and PM0 cytoplasmic Ca++ levels; 2) gamma-IFN and IL-1 release by PLy and PM0; and 3) peritoneal fibroblast proliferation in six CAPD VPM low-responder patients. Results showed a direct correlation between Ca++ levels in the medium and PLy and PM0 Ca++ concentrations; IL-1 and gamma-IFN release; and peritoneal fibroblast proliferation. These effects were enhanced by the addition of low doses of 1,25(OH)2D3 to the medium, while both high 1,25(OH)2D3 doses and verapamil abrogated the Ca++-induced PLy and PM0 activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

Intraperitoneal therapy with interferon-alpha in CAPD patients with relapsing bacterial peritonitis.

In CAPD patients with relapsing bacterial peritonitis who do not benefit from intraperitoneal therapy with IgG (IgG nonresponders), the authors demonstrated that peritoneal macrophages are deficient in IgG Fc receptors (FcR) and, therefore, unable to kill bacteria, independent of the levels of the opsonic molecule IgG in the peritoneal dialysis effluent (PDE). Because previous studies showed that interferon-alpha (IFN-alpha) is able to increase in vitro the number of PM0 IgG FcR in CAPD patients with relapsing bacterial peritonitis, the authors studied the in vivo effects of IP administration of IFN-alpha (1,000 IU daily in the overnight exchange for 12 months) on: PM0 superoxide generation; PM0 bacterial killing; PM0 IgG FcR; the number of bacteria in the PM0 cytoplasm; and peritonitis relapses in these patients. By the 10th day, IFN-alpha induced a progressive rise in all of the previously depressed PM0 functions tested, the disappearance of bacteria from the PM0 cytoplasm, and no further episodes of bacterial peritonitis were detected during 12 months. These data indicate that IFN-alpha may represent a useful tool for preventing infections in CAPD patients with relapsing bacterial peritonitis.

Adult↗

Acetate free biofiltration. Effects on peripheral blood monocyte activation and cytokine release.

Acetate free biofiltration (AFB), a new hemodiafiltration (HDF) technique characterized by a buffer free dialysate and postdilution infusion of a sterile HCO3 solution, was recently proposed as an alternative to HDF performed with acetate or bicarbonate dialysate. To evaluate the effects of dialysate buffer on immune cell activation, release of interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) from peripheral blood monocytes was studied in 12 uremic patients before and after HDF with polyacrylonitrile membranes (Filtral 12, Hospal Laboratories, Bologna, Italy) and consecutive dialysis with acetate, bicarbonate, and AFB. Data were correlated with the monocyte cytoplasmic concentration of Ca++, an index of early cell activation. Levels of bacterial endotoxins in the acetate, bicarbonate, buffer free dialysate, and infusate for AFB were also determined. Results showed that release of IL-1, PGE2, and LTB4, was greater after HDF with acetate than with bicarbonate; after bicarbonate dialysis, however, TNF production was significantly higher. On the other hand, after AFB, minimal production of these cytokines was seen and TNF, in particular, was undetectable. There was a direct correlation between release of cytokines in the monocytes and cytoplasmic Ca++ content. In the bicarbonate dialysate, detectable levels of bacterial endotoxins were found, whereas the acetate, buffer free dialysate, and infusate were endotoxin free. It was concluded that acetate dialysis directly activates peripheral blood monocytes to produce IL-1, PGE2, and LTB4, whereas bicarbonate induced TNF activation occurs through endotoxins. In AFB, which uses a buffer free dialysate and sterile bicarbonate infusion, monocyte activation is negligible.

Acetates↗

Low calcium peritoneal dialysis solution. Effects on calcium metabolism and bone disease in CAPD patients.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (AI) intake. By maintaining high serum Ca2+ levels, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. To evaluate the effects of a low Ca2+ peritoneal dialysis solution (PDS; 1.25 mmol/L) on calcium metabolism, the following were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (six with high PTH levels, and high turnover bone disease [Group 1], and six with low PTH levels, and low turnover bone disease [Group 2] documented by bone biopsies): 1) serum Ca2+ and PO4 levels; 2) serum PTH levels; 3) serum AI levels; and 4) bone morphology. The follow-up was 12 months. In both groups, within the third month, there was a decrease in serum Ca2+. In Group 2, serum PTH increased, reaching the norm, and in Group 1 it further increased, exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to give oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels while stopping AI gels. This did not induce any increase in serum Ca2+, whereas serum AI fell significantly. In Group 1, to avoid a further rise of serum PTH, the low Ca2+ PDS was supplemented with calcitriol (mean 3.5 +/- 0.5 microgram/day); this was followed by a reduction in serum PTH with no increase in serum Ca2+ or PO4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Two-chamber hemodiafiltration: comparison between exogenous reinfusion (PFD) and endogenous reinfusion (HFR)].

PURPOSE: This research aimed to compare two highly efficient dialysis techniques, paired filtration dialysis (PFD) and on-line hemodiafiltration with endogenous reinfusion (HFR) to evaluate the possible differences from a clinical, rehabilitative and managerial point of view. METHODS: The study was carried out on 14 patients (aged 40-65 yrs) six patients underwent PFD and eight patients underwent HFR. Patients on PFD came from low-flux hemodialysis (HD), while patients on HFR came either from PFD (n=5) or from low-flux HD (n=3). The research was based on the evaluation of patients inverted exclamation mark parameters (depurative and biochemical, level of clinical, medical and social rehabilitation) and of management parameters (technological aspects, cost analysis and medical-legal issues). RESULTS: HFR treatment improved plasmatic albumin values (> or =4.0 g/dL) and had a lower resistance to recombinant human erythropoietin (rHuEPO) therapy (by reducing the rHuEPO doses to reach the maintenance target values of hemoglobin (Hb) although both therapies resulted in equal depurative efficiency, and improved patient rehabilitation. CONCLUSIONS: This preliminary research, which requires further confirmation, demonstrates that HFR seems to provide PFD with other positive benefits and offers the uremic patient a better life style.

Adult↗

Peritoneal macrophage beta-2 microglobulin production and bacterial peritonitis in CAPD patients.

To evaluate the role of bacterial peritonitis in peritoneal macrophage (PM) Beta-2 Microglobulin (B2M) production, and its relationship with PM Interleukin-1 (IL-1) and Leukotriene B4 (LTB4) release, the authors studied 20 CAPD patients (10 with peritonitis): 1. in vivo plasma and peritoneal dialysis effluent (PDE) B2M, IL-1, and LTB4 levels; 2. in vitro B2M, IL-1, and LTB4 release by PM. Values were compared with those seen in the plasma or with peripheral blood monocytes of 30 hemodialysis (HD) patients (10 treated with Cuprophan [CU]; 10 with Polyacrylonitrile [PAN]; and 10 with Cellulose Acetate [CA]). Results showed that in CAPD patients with bacterial peritonitis B2M, IL-1 and LTB4 concentrations in the PDE were significantly higher than those seen in CAPD patients without peritonitis, or in the plasma of HD patients treated with PAN or CA, but were similar to those seen in HD patients treated with CU. At the same time, in vitro PM from CAPD patients with bacterial peritonitis produced more B2M, IL-1, and LTB4, than did PM from CAPD patients without peritonitis, or peripheral blood monocytes from HD patients treated with PAN or CA. The authors conclude that in CAPD patients, bacterial peritonitis is able to induce PM B2M production, probably via a cytokine mediated process, which may be analogous to what occurs with peripheral blood monocytes of HD patients treated with CU.

Adult↗

Modulation of peritoneal macrophage antimicrobial activity by peritoneal dialysis fluid, Ca++, and 1,25(OH)2D3 in CAPD patients.

Previous in vitro studies showed that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients. Twenty-four CAPD patients were evaluated in vivo (12 who had never had peritonitis, and 12 with an overall peritonitis incidence of more than one episode per 8 patient/months), for the effects of different peritoneal dialysis fluids (PDF) and Ca++ concentrations (1.25, 1.75, and 2.25 mmol/L) on PM0: cytoplasmic Ca++ concentration; superoxide generation; leukotriene B4 (LTB4) release; and bacterial killing for Staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PM0 Ca++ levels, superoxide and LTB4 generation, and bacterial killing such that, with 2.25 mmol/L of Ca++, these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca(++)-induced effects. On the other hand, with PDF Ca++ levels of 1,25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PM0 antibacterial function in CAPD patients, and may be useful in determining the prophylaxis and therapy of peritonitis.

Calcitriol↗

Peritoneal dialysis solution pH and Ca2+ concentration regulate peritoneal macrophage and mesothelial cell activation.

We evaluated the in vitro effects of pH and Ca2+ concentration of peritoneal dialysis solution (PDS) on (1) the release of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8) from peritoneal macrophages (PM0) and peritoneal mesothelial cells (PMC); (2) the release of IL-6 and IL-8 by PMC; and (3) the PM0 and PMC intracellular Ca2+ concentration. Aliquots of 5 x 10(6) PM0 and PMC were incubated (2 hr, 37 degrees C) in 1 ml of physiologic growth medium (RPMI 1640) and in 1 ml of four different PDS (1.36 g/dl glucose): (1) type A PDS (pH 5.5, Ca2+ 1.75 mM), (2) type B PDS (pH 5.5, Ca2+ 1.25 mM), (3) type C PDS (bicarbonate buffered pH 7.4, Ca2+ 1.75 mmol/L, and (4) type D PDS (bicarbonate buffered pH 7.4, Ca2+ 1.25 mM); each was stimulated with S. epidermidis. Results showed that type A PDS samples induced an average 60% increase in PM0 and PMC cytoplasmic levels and in cytokine release, whereas with type B PDS samples there was a 90% decrease. Type C PDS samples did not modify the PM0 and PMC IL-6 and IL-8 production, whereas a 3-fold rise in the production of IL-1 and TNF-alpha by PM0 was seen; this was associated with an increase in PM0 and PMC Ca2+ cytoplasmic levels. When type D PDS samples were incubated, however, there was an average 40% decrease in PM0 and PMC cytoplasmic Ca2+ levels and in cytokine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗