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Biomedical subjects

M G Nasini

Publications and source records attributed to M G Nasini.

35 records · Page 2Linked to original sources

Intraperitoneal immunoglobulin (IG) treatment in prophylaxis of bacterial peritonitis in CAPD.

To evaluate peritoneal immunological defences and to find a possible cure for alterations in the mechanism, we studied the capacity of peritoneal dialysis effluent (PDE) to opsonize bacteria and the phagocytic activity of peritoneal macrophages (PM). Subjects were 40 uremic patients followed for a mean period of 36 months and 40 normal women who underwent laparoscopy (Controls). Opsonic capacity for S.epidermidis of undiluted PDE from CAPD patients with low peritonitis occurrence (LPI) proved similar to that of 10% control serum. It was, however, noticeably inferior when patients were of high peritonitis incidence (HPI). In these cases IgG concentration in PDE was lower than in patients of LPI. A significant correlation was revealed between opsonization capacity for bacteria and IgG concentration values in PDE. We found inverse correlation between opsonic capacity of PDE and number of episodes of peritonitis. Phagocytic capacity of PM from CAPD patients was similar to that of control PM when microorganisms were preopsonized by control serum. Intraperitoneal Immunoglobulin treatment raised PDE opsonization capacity and lowered peritonitis incidence in patients of previously HPI, thus demonstrating the importance of abnormal organization in CAPD peritonitis and the possibility of preventing infections by intraperitoneal Immunoglobulin treatment. These prevention results do not occur with intravenous Immunoglobulin treatment.

Bacterial Infections↗

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↗

Peritoneal dialysis solution calcium concentration regulates peritoneal fibroblast proliferation in CAPD.

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), by reducing ultrafiltration capacity. Since studies in vitro have shown that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, eight uremics and four controls at the start of CAPD were evaluated for the in vitro effects of different peritoneal dialysis solution (PDS) Ca2+ concentrations (1, 1.25, 1.75, and 2 mmol/L) on: 1) peritoneal fibroblast (PF) proliferation; 2) peritoneal macrophage (PM) and peritoneal lymphocyte (PL) release of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma)--cytokines that are known to induce PF proliferation; and 3) cytoplasmic Ca2+ concentrations in PF, PM, and PL. Results showed that in both the uremics and controls, increasing the dose of Ca2+ in the medium induced a dose-dependent rise in PF proliferation, and in the release of IL-1 and IFN-gamma from PM and PL. Meanwhile, the cytoplasmic Ca2+ concentration of PF, PM, and PL also increased. With a PDS containing 1 mmol/L of Ca2+ in the uremics, these parameters 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 low Ca2+ PDS (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma from PM and PL, thereby preventing peritoneal sclerosis.

Calcium↗

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↗

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↗

Intraperitoneal verapamil therapy in CAPD patients with peritoneal hypopermeability. Effects on ultrafiltration.

We found higher peritoneal lymphocyte (PLy) and macrophage (PM0) Ca++ concentrations in CAPD patients with low peritoneal ultrafiltration (UF), than in normal UF patients, as well as the release of greater amounts of lymphomonokines such as interferon-gamma and interleukin-1, which stimulate peritoneal fibroblast proliferation. Since Ca++ is essential in immune-cell activation and lymphomonokine production, the authors analyzed the effects of intraperitoneal (IP) verapamil therapy in 16 CAPD patients with UF loss. The areas studied included: 1) PLy and PM0 Ca++ concentration, 2) peritoneal dialysis effluent (PDE) lymphomonokine levels, 3) peritoneal glucose absorption, 4) UF volume, and 5) peritoneal morphology. In the 10 low UF patients who showed normal glucose absorption and increased peritoneal fibroblast proliferation, of verapamil therapy increased UF volume, decreased the amount of peritoneal fibroblast proliferation, and normalized the previously high PLy and PM0 Ca++ concentrations and PDE lymphomonokine levels. Conversely, UF was not improved by IP verapamil in the six low UF patients showing high glucose absorption and prevalent mesothelial alterations. In conclusion, IP verapamil can be considered a suitable therapy for increasing UF volume in CAPD patients with peritoneal hypopermeability due to a lymphomonokine-mediated hyperproliferation of peritoneal fibroblasts.

Calcium↗

Response of CAPD patients with a high incidence of peritonitis to intraperitoneal immunoglobulin therapy.

This study has demonstrated that in the majority of high-peritonitis-incidence (PI) CAPD patients the defective opsonic activity levels in the peritoneal dialysis effluent (PDE) are restored for 3 weeks by a 12 g IP injection of immunoglobulins (Ig). Further studies showed that in a minority of high-PI CAPD patients who also had low PDE IgG and opsonic activity levels, IP Ig therapy did not significantly reduce the PI. To evaluate this phenomenon we utilized this therapy in 20 high-PI CAPD patients undergoing IP Ig therapy for an average of 24 months daily for 3 weeks (12 g every 3 weeks) and analyzed: 1) PDE IgG levels; 2) PDE opsonic activity; 3) peritoneal macrophage (PM0) membrane-bound IgG; 4) PDE Interleukin-1 (IL-1) levels; 5) PM0 membrane Fc receptor number. The results showed that in the 15 patients in whom Ig therapy reduced PI, there were long-lasting increases in the PDE IgG, opsonic activity and IL-1 levels, as well as a normal PM0 Fc receptor number and PM0 reversibly bound infused Ig. Conversely, the five patients in whom the IP Ig did not reduce the PI showed only transient increases in PDE IgG and opsonic activity levels, no PDE IL-1 increase, and the PM0 were deficient in Fc receptors and, therefore, unable to take up the infused Ig. We conclude that in high-PI CAPD patients there are different peritoneal immune defense abnormalities and that their identification is, therefore, important for the correct choice of therapy to improve these defects.

Adult↗

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↗

Low Ca2+ dialysate. Effects on bone metabolism in the course of paired filtration dialysis.

To evaluate the 1-year effects of PFD performed with low Ca2+ dialysate (1 mmol/l) on calcium metabolism and on bone disease, the authors studied in eight patients who were previously treated with PFD performed with standard Ca2+ dialysate (1.75 mmol/l). On samples from these subjects, the following were evaluated: 1) serum Ca2+ and PO4 levels, 2) serum PTH levels, 3) serum Al levels, and 4) bone morphology. All the patients were hypercalcemic, four with high serum PTH levels (high turnover bone disease, group 1) and four with low serum PTH levels (low turnover bone disease, group 2). In both groups, a decrease in serum Ca2+ and an increase in serum PTH was observed within the third month. In group 2, PTH levels reached the normal range. Because serum Ca2+ levels decreased to normal in both groups, it was possible to administer oral CaCO3 (10.5 +/- 2 g/day) to control serum PO4 and to stop Al gels. This did not induce any increase in serum Ca2+, whereas serum Al fell significantly. In group 1, to prevent a further rise in PTH, patients were treated with intravenous calcitriol (5 +/- 2 micrograms/week). This induced a reduction in the serum PTH without increasing serum Ca2+ or PO4. Within 12 months, an improvement in bone morphology was seen in both groups. It is concluded that the use of low Ca2+ dialysate corrects hypercalcemia in patients with PFD treated with high oral doses of CaCO3, and improves low turnover bone disease. The combination of low Ca2+ dialysate and intravenous calcitriol also improves high turnover bone disease.

Adult↗

Recombinant human erythropoietin resistance in hemodialysis. Effects of paired filtration dialysis.

A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.

Adult↗