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Biomedical subjects

G Piccoli

Publications and source records attributed to G Piccoli.

At least 145 records · Page 8Linked to original sources

Phenotypic and functional analysis of circulating phagocytic cells in IgA nephropathy patients.

We analysed the possible mechanisms responsible for the functional abnormalities reported on phagocyte cell function in IgA nephropathy patients. The oxidative metabolism by the superoxide anion ferricytochrome C reduction test on monocytes and the chemiluminescence response on neutrophils was examined in 32 patients. Moreover the expression of cell membrane structures involved in immune response and phagocytosis (i.e. Fc receptors and HLA class II antigens) was evaluated cytofluorimetrically using specific monoclonal antibodies. Our own results did not show striking differences in oxidative potential and phenotype of patients' phagocyte cells as compared with healthy controls. However a HLA class II-associated structure was found to be quantitatively more expressed in patients' monocytes than in normal controls (P less than 0.005). These findings suggest that the defective phagocyte system function reported in IgA nephropathy patients is not simply due to a loss of cell surface receptors, nor to abnormalities in intracellular metabolic pathways implying oxygen consumption. The increase in expression of some HLA class II structures, often associated with the presence of circulating IgA immune complexes, probably reflects a protracted immunological stimulation.

Adolescent↗

CAPD in a large population: a 7-year experience.

In this report we evaluate the results obtained with CAPD in uremic patients in Piedmont, a Northern Italian region (4.4 million inhabitants) during the last 7 years. Data are gathered from the computerized records of the regional dialysis and transplantation registry, which collects information on 3,567 pts, 2,243 of which entered since Jan. 1981 and 1,808 alive at Dec. 1987. Among these, 193 (11%) were on CAPD, a figure almost constant in the last 7 years. However CAPD diffusion is not uniform among the 20 centers of the region, ranging from 0 to 49.5% of the patients on dialysis. CAPD is particularly employed in the elderly (47.5% of the patients being older than 60 years and 19.5% over 70). This treatment was the first choice in 16% of the patients admitted to dialysis between 1981-87; this figure reaches 33% for the diabetics. High drop out rates still represent a major problem, in a 6 year follow up 66% of the patients being transferred to another dialysis treatment. Peritonitis is the main cause of drop out (22%), while loss of peritoneal membrane efficiency accounts for 7%, patient's choice 14%, catheter complications 14%, inability to cope 8%, clinical problems 20% and other reasons 15%. Drop out rate is not influenced by the presence of high risk condition or age. Survival curves show no significant difference for CAPD in comparison to hemodialysis in all the age groups considered. This epidemiological survey, based on a global 522 pts experience extended over a 7 year period, indicates that CAPD is a competitive mode of treatment in chronic uremia.

Acetates↗

Gluten-induced experimental IgA glomerulopathy.

The effect of alimentary gluten and of its lectin-like fraction gliadin in inducing IgA mesangial deposits in BALB/c mice was investigated. In the pilot study G1 (4 mice), G2 (4 mice) and G3 (6 mice) received ovalbumin, human gamma-globulins, and crude gluten, respectively. The antigens, 1 mg/ml, were given in drinking water for 14 weeks. G4 (20 mice) were fed with standard mouse fodder. Gluten, as well as other alimentary antigens, induced IgA mesangial deposits with intense IgA staining in each animal, however a positive IgA staining was also observed in 10 of 20 adult controls. Antigliadin IgA antibodies were detected in renal tissue eluates from gluten-immunized mice but were found in eluates from control animals too. IgA deposits and antigliadin IgA in renal tissue were also observed in 3 of 7 adult mice (G7) fed for 30 weeks with standard fodder, then for 1 month with a protein-free diet supplemented with 20% amino acids. Conversely, there were no IgA mesangial deposits or IgA anti-gliadin antibodies in renal eluates of 1- or 2-week-old mice (G5 and G6). For the definitive protocol, 4-week-old BALB/c mice were selected and fed with basal glutenfree diet. G8 (14 mice) did not receive any alimentary immunogen in the drinking water, whereas G9 (15 mice) and G10 (15 mice) received ovalbumin and gliadin, respectively. G11 (15 mice) had standard gluten-containing diet. IgA deposits semiquantified by immunofluorescence scores were found to be significantly greater in G9 and G10 than in G8 (Student' t-test p1 less than 0.003, Mann-Whitney test p2 less than 0.001 and p1 less than 0.01, p2 less than 0.007, respectively), and in G11 than in G8 (p1 and p2 less than 0.05). The presence of positive IgA staining (greater than or equal to 2/6 scores) was significantly less frequent in G8 in comparison to G9 (chi-square test p3 less than 0.002), G10 (p3 less than 0.02) and G11 (p3 less than 0.04). Total serum IgA were significantly higher in orally immunized G9 and G10 than in G8 control mice (p1 less than 0.005, p2 less than 0.002). Anti-gliadin IgA in circulation as well as in renal deposit eluates were significantly increased in gluten-eating mice (G10 and G11) as compared with the gluten-free control group G8. These observations indicate that gliadin does induce IgA immune deposits in BALB/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hexokinase microheterogeneity in rabbit red blood cells and its behaviour during reticulocytes maturation.

Hexokinase in rabbit reticulocytes is present in two molecular forms (hexokinase Ia and Ib) separable by ion-exchange chromatography on DE-52 columns. By the use of ion-exchange HPLC we have been able to show that the isozymic form we previously called hexokinase Ia can be resolved into two peaks of activity one of which is (Ia) soluble, the other (Ia*) particulate. Hexokinase Ia* can be solubilized by detergents like saponine and Triton X-100 and disappears during 'in vivo' reticulocytes maturation. This new hexokinase microheterogeneity is not caused by different oxidized forms of the enzyme nor influenced by the presence of proteolytic inhibitors during lysate preparation.

Animals↗

Single kidney function: effect of acute protein and water loading on microalbuminuria.

The hyperfiltration induced by an acute response to an oral protein and water load was investigated to ascertain whether it can modify the urinary albumin excretion (UAE) in the microalbuminuric range by further increasing the glomerular filter permeability. To this end, six patients with a single kidney selected as having microalbuminuria on a regular diet without the clinical or laboratory data of overt renal disease and eight healthy subjects received a short-term protein and water load (150 g of meat-derived protein and 1 liter of water). In patients with one kidney, mean basal UAE values were significantly higher than in control subjects (p less than 0.006), whereas endogenous creatinine clearance values were only slightly lower (p greater than 0.05). One hour after the protein and water load, an abrupt increase in microalbuminuria levels was found in patients with one kidney and mean UAE values were significantly higher than in control subjects (p less than 0.002), whereas mean creatinine clearance values were significantly lower in patients than in control subjects (p less than 0.01). High UAE (p less than 0.002) and low creatinine clearance (p less than 0.002) values were maintained over the following four hours in patients with one kidney. These data suggest that in the single kidney with reduced renal functional reserve, an oral protein and water load magnifies the pre-existing loss of glomerular permselective properties due to chronic hyperfiltration as manifested by a further increase in microalbuminuria.

Adult↗

Erythrocyte Na,K pump activity and arterial hypertension in uremic dialyzed patients.

We have evaluated in 26 uremic patients [21 on hemodialysis, 5 on continuous ambulatory peritoneal dialysis (CAPD)], 11 normotensive, and 15 hypertensive (MAP greater than 110 mm Hg) patients the following properties: a) erythrocyte (RBC) Na concentration [Nai] and ouabain-sensitive and -resistant Na effluxes; b) the effect of uremic sera on ouabain-sensitive Na efflux in normal RBC; c) serum digoxin-like immunoreactivity; d) cardiac index and total peripheral resistance. In 19 healthy subjects a) and c) were also evaluated. RBC Na,K pump activity was lower in uremic patients than in normal subjects (P less than 0.0005), and lower in hypertensive (P less than 0.02) than in normotensive patients. Serum from uremic patients inhibited ouabain-sensitive Na efflux in normal RBC, the inhibition being correlated with both the rate constant for ouabain-sensitive Na efflux (r = -0.67; P less than 0.005) and [Nai] (r = 0.43; P less than 0.05) of RBC of patients from whom the serum was obtained. Inhibition of ouabain-sensitive Na efflux was significantly higher with serum from hypertensive than from normotensive patients (P less than 0.05). Serum digoxin-like immunoreactivity was present in all uremic patients (0.402 +/- 0.054 ng/ml in normotensive and 0.428 +/- 0.040 ng/ml in hypertensive, P = ns), while it was not detectable in normal subjects. Hypertensive patients had peripheral resistance significantly higher than normotensive (P less than 0.05), while cardiac index was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Pathogenesis of arterial hypertension in chronic uraemia: the role of reduced Na,K-ATPase activity.

In 38 uraemic dialysed patients (17 normotensive, 21 hypertensive) we measured (1) erythrocyte sodium concentration [Nai] and ouabain-sensitive sodium efflux, and (2) arterial pressure, cardiac index and total peripheral resistance. Erythrocyte Na-K pump activity was lower in hypertensive than in normotensive patients (P less than 0.02). Hypertensive patients had significantly higher peripheral resistance than normotensive patients (P less than 0.05), while the cardiac index was similar in both groups. Inverse correlations were found between the rate constant for ouabain-sensitive sodium efflux in erythrocytes and both systolic and diastolic pressure (r = -0.43 and r = -0.45, respectively; P less than 0.01) and total peripheral resistance (r = -0.76; P less than 0.0001). Our data suggest that reduced sodium transport by the Na-K pump plays a role in the pathogenesis of arterial hypertension in patients with chronic uraemia.

Blood Pressure↗

Microalbuminuria in single kidney patients: relationship with protein intake.

Experimental models have shown that the reduction in renal mass induces an increase in glomerular filtration rate of the remnant nephrons, leading to proteinuria and glomerular sclerosis. Since the presence of microalbuminuria - increased urinary albumin excretion (UAE) undetectable by routine assays - can be an early sign of this phenomenon, UAE in the normo- and microalbuminuric range was measured in 24 single kidney patients with negative Albustix. Nephrectomy had been performed in 22 cases 1 to 28 years before, mostly because of renal lithiasis. Patients were selected as being normotensive, normoglycemic and free of recurrent urinary infections or stones. On regular diet (mean protein intake 1.2 g/kg/day), UAE mean values were significantly higher in single kidney patients than in 20 controls both in supine position during overnight rest (clinostatism) (37.71 +/- 56.32 vs 2.56 +/- 2.27 micrograms/min, p less than 0.001) and in erect position during moderate physical effort (orthostatism) (67.31 +/- 86.12 vs 4.59 +/- 5.73 micrograms/min, p less than 0.004). Microalbuminuria was observed in 18/24 single kidney patients in clinostatism and 15/24 in orthostatism. A subgroup of 14 patients was also studied on different protein dietetic regimens. After one month on a 0.6 g/kg/day protein containing diet, UAE mean levels significantly decreased in comparison to those found on regular diet (clinostatism: 26.15 +/- 35.93 vs 49.24 +/- 70.29 micrograms/min, p less than 0.02; orthostatism: 31.73 +/- 46.97 vs 68.92 +/- 83.53 micrograms/min, p less than 0.001). One month after a 1.6 g/kg/day protein diet UAE mean values significantly increased (clinostatism 83.99 +/- 88.04 micrograms/min, p less than 0.001; orthostatism: 117.19 +/- 116.12 micrograms/min, p less than 0.001). Our data indicate that microalbuminuria, detectable in the majority of patients with a single kidney, can be modulated by different protein intakes.

Adult↗

Quantitative and functional analysis of IgG Fc receptor molecules in polymorphonuclear leukocytes and monocyte macrophages in patients with essential mixed cryoglobulinaemia.

In order to gain insight into the role of IgG Fc receptors in essential mixed cryoglobulinaemia (EMC), we analyzed quantitatively the expression of such molecules on polymorphonuclear leukocytes (PMN) and assessed them, functionally, on PMN, tissue macrophages and circulating monocytes in 6 HLA-B8-, DR3-negative patients with EMC and glomerulonephritis. The Fc receptors expressed on PMN surface, as estimated by using AB 8.28 monoclonal antibody to PMN Fc receptor and 125I-labelled rabbit F(ab')2 fragments to mouse IgG as detecting system, were found to be quantitatively normal in EMC patients, whereas PMN Fc- receptor-mediated phagocytosis was reduced. Moreover, the patients were found to have prolonged macrophage clearance of IgG-sensitized autologous erythrocytes and reduced kinetics of ingestion of IgG-coated material by circulating monocytes. This impairment of Fc receptor function may play a remarkable role in the tissue localization of immune material in this disease.

Adult↗

Mediterranean diet and primary IgA nephropathy.

Since IgA nephropathy can be experimentally induced by alimentary antigens, mechanisms of oral immunization might be supposed also in human primary IgA nephropathy (PIgAGN). IgA immune complexes (IgAIC) are thought to play a major role in PIgAGN, hence this parameter was monitored in six PIgAGN patients subjected to diets excluding gluten, meat or eggs respectively and selected as having persistent urinary activity and high IgAIC levels. On gluten-free diet IgAIC significantly decreased over 3 different periods of 10 days (Student's t-test p 1 less than 0.03, Rank-Signed test p 2 less than 0.02), 1 month (p 1 less than 0.007, p 2 less than 0.02) and 6 months (p 1 less than 0.05, p 2 less than 0.02). IgAIC significantly increased again on a gluten containing diet over 1 month (p 1 less than 0.008, p 2 less than 0.04) and 3 months (p 1 less than 0.02, p 2 less than 0.04). After 6 months on a gluten-free diet, all patients had normal IgAIC values and decreased IgA2 subclass-IgAIC, in agreement with the hypothesis of withdrawal of an antigen challenging the mucosal immune system. These data indicate a relationship between a gluten-containing diet and high levels of IgAIC in PIgAGN patients, suggesting that dietetic factors might play a role in the different geographical distribution of this nephropathy.

Adult↗