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Biomedical subjects

O Santoni

Publications and source records attributed to O Santoni.

At least 19 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↗

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↗

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↗

[Comparison between immunofluorescent aspects of chronic HBsAG+, HBAG-hepatitis and some cases of chronic toxic-dismetabolic liver diseases].

In the study the aspects noticed on hepatic biopsies by I.F. in HBsAg+ and HBsAg- chronic hepatitis and in some cases of hepatitis on dismetabolic basis in Wilson's disease are compared. Great differences occurred between HBsAg+, HBsAg- and the Hepatitis in Wilson disease. In fact in the first case reactivity is often present due to immunological phenomena (presence of IgG immunocomplexes and autoantibodies) while in Wilson's disease these aspects are not found confirming the hypothesis that in the latter case is a question of an exclusively toxic damage.

Biopsy↗

[Evaluation of functional periodicity of the pituitary gland by harmonic analysis.--IV) Circadian prolactin secretion in women with breast cancer].

Secretory periodicity of prolactin (PRL) is preserved in women with breast cancer in spontaneous or surgical menopause. Hormone titres occurring during the day may be occasionally significantly higher in respect to the ones observe in normal controls at the same hours. The periodicity features calculated by the Fourier's method show however normal indices, namely mesor (mean PRL titres in the 24 hours) phase, amplitude and frequency of oscillations.

Adult↗

[Evaluation of pituitary functional periodicity by harmonic analysis. I) Circadian somatotropin secretion in acromegaly].

STH circadian secretion has been investigated in 11 acromegalic patients. The physiological STH nocturnal surge is not present in acromegaly, but when data are evaluated by Fourier's cosines analysis, a rhythmicity is however found also in acromegaly. The characteristics of harmonics, namely periodicity, amplitudes and phases, are largely different in respect to pattern of normal subjects, where the rhythmicity is represented by an harmonics with 24-hour periodicity.

Acromegaly↗

[Evaluation of pituitary functional periodicity by harmonic analysis. II) Circadian prolactin secretion in acromegaly].

PRL levels over 24 hours have been studied in 9 acromegalic patients (4 men and 4 women). Hormone levels were found significantly higher than age and sex matched normal subjects in 4 cases (2 males and 2 females). PRL and STH levels were significantly correlated in men, but not in women. A 24-hour periodicity of PRL secretion was found in 4 cases, however in 2 of them the phase was anticipated in respect to the control group. In 4 of the remaining subjects the hormone secretion is made up by a succession of episodes with higher frequency than in the control group. Only in one case no significant periodicity of secretion was observed.

Acromegaly↗

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↗

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↗