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Biomedical subjects

S Carozzi

Publications and source records attributed to S Carozzi.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1988

Interferon-gamma (IFN-gamma) as in vitro enhancing factor of peritoneal macrophage defective bactericidal activity during continuous ambulatory peritoneal dialysis (CAPD).

Interferon-gamma (IFN-gamma) can be considered a primary factor required in vitro and in vivo for inducing endocellular lysis of microorganisms by peritoneal macrophages (PM luminal diameter), an essential activity in continuous ambulatory peritoneal dialysis (CAPD) patients that prevents bacterial peritonitis. In 22 uremic patients treated with CAPD we analyzed: (1) the amount of IFN-gamma released by elicited peritoneal lymphocytes (PL); (2) oxidative metabolism and microbicidal activity by elicited PM luminal diameter; (3) immunoglobulin G (IgG) Fc-receptor expression on PM luminal diameter membrane; (4) the effect on PM luminal diameter hydrogen peroxide (H2O2) generation, bactericidal activity, and IgG Fc-receptor expression exerted in vitro by human recombinant IFN-gamma (rIFN-gamma). Results demonstrate that IFN-gamma release by elicited PL is lower in some CAPD patients with high peritonitis incidence (HPI) than in healthy donors or in CAPD patients with low peritonitis incidence (LPI). Simultaneously, PM luminal diameter from CAPD patients with HPI are characterized by a decreased ability to generate oxygen metabolites, to kill bacteria, and by a lack in IgG Fc-receptor expression; these defects were completely cured after being treated with rIFN-gamma. These results show that the IFN-gamma treatment in vitro could strengthen PM luminal diameter phagocytosis, oxygen metabolite generation, and bacterial killing in CAPD patients with HPI, and suggest that IFN-gamma may be considered a possible therapy in vivo for these patients.

Adult↗
PubMed1988

Immunologic patterns in CAPD patients with peritonitis.

Alterations of peritoneal defense mechanisms, i.e. opsonization, phagocytosis, and bacterial killing, may be responsible for the high peritonitis rate in a subgroup of CAPD patients. Peritonitis incidence and in vitro bacterial opsonization has been shown to depend on IgG concentrations in the dialysate and on the ability of macrophages to produce fibronectin. Additionally, a high peritonitis incidence is associated with decreased bactericidal activity of macrophages; thus infective organisms may survive intracellularly despite intact phagocytosis. In some CAPD patients a disturbance in lymphokine and monokine release may be responsible for the reduced ability of their macrophages to kill bacteria.

Blood Bactericidal Activity↗
PubMed1988

Peritonitis prevention in CAPD.

In 12 CAPD patients with frequent peritonitis episodes (1.6 vs 0.5/year in controls), low IgG concentrations in the effluent and reduced opsonic capacity of the dialysate were observed. Intermittent intraperitoneal IgG (dosage: 12 g/3 weeks, duration: 24 months) increased the opsonic capacity for Staphylococcus epidermidis of the effluent 3-fold, while the peritonitis rate fell to 0.2/year. During the treatment interval the effluent IgG levels and opsonic capacity of the dialysate were initially high and fell progressively thereafter. However, even at trough levels it still remained higher than in controls. Interleukin-1 levels increased 2.5-fold from the third to the eighth day. In those patients with lower clinical response, IgG levels and opsonic capacity of the dialysate were only transiently elevated; their macrophages were shown to be deficient in Fc-receptors. Intraperitoneal human recombinant interferon-alpha was able to improve Fc-receptor expression, oxygen metabolite generation of macrophages and bactericidal capacity of the dialysate in these patients. In conclusion, an unusually high peritonitis rate in CAPD patients may be treated by intraperitoneal IgG-application; in poor responders intraperitoneal interferon should be considered.

Humans↗
PubMed1987

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↗
PubMed1987

Identification of autoreactive lymphocytotoxic antibodies in sensitised dialysis and kidney transplant patients.

Autoreactive lymphocytotoxic antibodies, which have been found in sensitised dialysis patients, are generally not considered to be harmful to a renal allograft. In this work the presence of such autoreactive antibodies was investigated in the following groups of sensitised endstage renal disease patients: (a) dialysis patients waiting for a first kidney transplant, (b) kidney transplanted patients, and (c) dialysis patients with a previous failed graft. Only sera from the above patients which showed high reactivity (greater than 30%) against peripheral blood lymphocytes of a random cell panel (R-PBL), were screened for the presence of autoreactive lymphocytotoxic antibodies, by testing at different temperatures against autologous T lymphoblasts (PHA-ATL) and EBV-induced autologous B lymphoblasts (EBV-ABL). The results showed that both blood transfusions, and viral infections such as cytomegalovirus (CMV), correlated with the presence of autoreactive antibodies, and that in addition, by using PHA-ATL and/or EBV-ABL as absorbing reagents, it was possible to remove the antibodies. These absorption procedures allowed the identification of the presence of autoreactive antibodies alone or in combination with other alloantibodies.

Adolescent↗
PubMed1987

Monocyte-macrophage mediated suppression of erythropoiesis in renal anaemia.

To investigate monocyte-macrophages and their secretions in the pathogenesis of renal anaemia we studied the following in 12 uraemic patients and in 12 normal subjects: 1. in vitro proliferation of erythroid progenitors (BFU-e) from uraemic and normal peripheral whole mononuclear cells; 2. effects of monocyte-depletion of uraemic or normal whole mononuclear cells on proliferation of BFU-e; 3. effects of adding uraemic or normal peritoneal macrophages (PM0) to peripheral blood normal non-adherent mononuclear cells; and 4. Interleukin-1 (IL-1) and prostaglandin E2 (PGE2) concentrations in supernatants of uraemic and normal PM0. BFU-e growth from uraemic whole mononuclear cells is lower than that of normal whole mononuclear cells. The removal of monocytes induces an increase in BFU-e development in uraemic patients, but a decrease in normal subjects. The addition of uraemic PM0 to normal nonadherent mononuclear cells causes a decrease in BFU-e formation, compared to values incubating normal PM0. PGE2 release in supernatants of uraemic PM0 is greater than in supernatants of normal PM0, and IL-1 activity is less with uraemic PM0 than that with normal PM0. In Conclusion we found that uraemic monocyte-macrophages have a suppressive effect on BFU-e development in vitro which can be mediated by abnormal release of secretory products.

Adult↗
PubMed1986

Suppressor resident peritoneal macrophages and peritonitis incidence in continuous ambulatory peritoneal dialysis.

Our study was designed to see if peritoneal macrophages (PM) of continuous ambulatory peritoneal dialysis (CAPD) uremic patients, by weakening local defense, could contribute to an increase of peritonitis incidence. Coincubation of nonadherent control responding cells (NACRC) and PM from normal subjects or CAPD patients with low peritonitis incidence (LPI) did not modify blastogenic response of cells to PHA. Coincubation of NACRC and PM from CAPD patients with high peritonitis incidence (HPI) produced noticeable decrease in blastogenic response; these PM, unable to produce normal amounts of Interleukin-1 (IL-1), released large amounts of prostaglandin E2 (PGE2). CAPD patients with LPI and normal subjects produced both substances in similar amounts. PM of CAPD patients with HPI were less able to kill bacteria than those from normal subjects and CAPD patients with LPI, showing a stronger suppressor effect on local defense. This suppressor activity correlated directly to PGE2 release and inversely to IL-1 production. We can hypothesize that in some uremic patients, subpopulations of macrophages growing in response to local stimuli produce humoral substances, negatively affecting cellular-mediated defense and favoring elevated bacterial expansion in peritoneum.

Adult↗