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Biomedical subjects

M G Nasini

Publications and source records attributed to M G Nasini.

At least 19 recordsLinked to original sources
PubMed1997

Peritoneal dialysis effluent, cytokine levels, and peritoneal mesothelial cell viability in CAPD: a possible relationship.

Recent studies have emphasized the role of peritoneal mesothelial cell (PMC) in peritoneal immune defense mechanisms in continuous ambulatory peritoneal dialysis (CAPD). The aim of this study was to evaluate a possible relationship between peritoneal dialysis effluent (PDE), cytokine (Cy) levels, and PMC viability and their impact on peritonitis morbidity. Fifteen patients initiating CAPD for end-stage renal failure participated in the study. The following parameters were evaluated: (1) the levels of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and interleukin-8 (IL-8) in PDE samples taken 7 days after initiating CAPD, at the end of the first, third, and sixth month of CAPD (determined by a solid phase enzyme amplified sensitivity immunoassay EASIA); (2) peritoneal mesothelial cell viability [determined by the release of lactate dehydrogenase (LDH) and by trypan blue extrusion test] by isolating and culturing peritoneal mesothelial cells at the moment of the placement of the peritoneal catheter and at the sixth month of CAPD; (3) peritonitis incidence during the 24 months after starting CAPD. At the first month of CAPD in all patients there was a slight increase in PDE IL-1 beta and TNF-alpha levels, while other Cy were almost undetectable. Time course studies showed that in 10 patients (Group I) there was a significant increase in PDE levels of IL-6, IL-8, and INF-gamma (p < 0.0005) in comparison to other Cy and a good PMC viability. In the other 5 patients (Group II) there were higher PDE levels of IL-1 beta and TNF-alpha (p < 0.0005). This was associated with a marked reduction in PMC viability determined by the release of LDH and by the trypan blue extrusion test. During the 24 months after starting CAPD, incidence of peritonitis was one episode per 24 patient-months in Group I and one episode per 9.2 patient-months in Group II. Our results show that from the beginning of CAPD there are distinct patterns of Cy in the PDE that correlate with a different PMC viability and peritonitis morbidity. Thus the analysis of the above-mentioned parameters may be useful in the early identification of the risk of peritonitis, thus allowing preventive measures.

Cell Survival↗
PubMed1995

Two years of experience with a new device system: a multicenter study.

Peritonitis is a crucial complication of peritoneal dialysis. Over the last few years, new device systems have been developed to reduce episodes of peritonitis caused by exogenous contamination. Remarkable improvement has been obtained by modifying the original connection between the catheter and the bag with the introduction of the Y-set. The aims of this study were to test the reliability and simple use of a double-bag system without disinfectant in-line (Gemini, Gambro) and to evaluate the incidence of peritonitis in a 2-year period of follow-up. In a group of 167 patients, enrolled in 14 dialysis units in Italy, with a follow-up of 2433 patient-months, we observed 82 episodes of peritonitis in 52 patients, with a cumulative incidence of 1 episode every 29.7 patient-months. At 12 months the percentage of patients peritonitis-free was 69.7%, and at 24 months it was 62.8%. The training to complete the bag exchange, assessed by patient and nursing staff, was defined as "easy" in 61% of the cases and "difficult" in only 12% of the cases. The percentage of patients requiring a partner was 23%. For patients this device system presents easy handling in terms of the bag exchange, and it may prevent peritonitis.

Adult↗
PubMed1993

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↗
PubMed1993

Ca2+ concentration in the peritoneal dialysis solution regulates peritoneal fibroblast proliferation and peritoneal macrophage and lymphocyte cytokine release.

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), because it reduces ultrafiltration capacity. Since studies in vitro have demonstrated that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, we evaluated in 8 uremic patients at the start of CAPD and in 4 control patients the effects in vitro of different peritoneal dialysis solution Ca concentrations (1, 1.25, 1.75, and 2 mmol/L) on peritoneal fibroblast (PF) proliferation, peritoneal macrophages (PM phi), and peritoneal lymphocyte (PLy) release of interleukin-1 (II-1) and interferon-gamma (IFN-gamma) (cytokines which are known to induce PF proliferation), and cytoplasmic Ca2+ concentration in PF, PM phi, and PLy. Results showed that in both the uremic and control patients, increasing the dose of Ca2+ in the medium induced a dose-dependent increase in PF proliferation and the release of IL-1 and IFN-gamma from PM phi and PLy. Meanwhile, the cytoplasmic parameters PF, PM phi, and PLy Ca2+ in the uremic patients were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients the use of a physiological Ca peritoneal dialysis solution (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma thus preventing peritoneal sclerosis.

Calcium↗
PubMed1993

Low- and high-turnover bone disease in continuous ambulatory peritoneal dialysis: effects of low-Ca2+ peritoneal dialysis solution.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.

Administration, Oral↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

Effect of monophosphoryl lipid A on the in vitro function of peritoneal leukocytes from uremic patients on continuous ambulatory peritoneal dialysis.

We analyzed the effects of monophosphoryl lipid A (MPL), a relatively nontoxic immunostimulant derived from bacterial endotoxin, on the depressed in vitro immune function of leukocytes derived from six patients undergoing continuous ambulatory peritoneal dialysis and who had histories of recurrent bacterial peritonitis. MPL was also tested for its capacity to stimulate the proliferation of peritoneal fibroblasts, as determined by [3H]thymidine incorporation. In vitro incubation of peritoneal lymphocytes and macrophages (PM phi) with increasing amounts of MPL, up to 5 micrograms/ml, resulted in a dose-dependent enhancement of gamma interferon and interleukin-2 production by peritoneal lymphocytes and interleukin-1 release by PM phi. In vitro incubation of PM phi with MPL also resulted in an increase of PM phi bacterial killing and membrane Fc receptor number, although no change in peritoneal fibroblast proliferation was seen with any of the MPL concentrations tested. These results suggest that the peritoneal leukocyte dysfunction observed in patients undergoing continuous ambulatory peritoneal dialysis and who have high rates of peritonitis may be alleviated, to some degree, by MPL, without directly inducing a potentially deleterious fibrotic lesion.

Adult↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗