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Biomedical subjects

L Faccini

Publications and source records attributed to L Faccini.

At least 19 recordsLinked to original sources

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

Angiotensin-Converting Enzyme Inhibitors↗

Albumin permeability in isolated glomeruli in incipient experimental diabetes mellitus.

AIMS/HYPOTHESIS: The pre-clinical phase of diabetic nephropathy is characterised by increased glomerular filtration rate and episodes of microalbuminuria. The cause of the microalbuminuria has been variably ascribed to alterations of the size or charge selective barriers of the glomerulus or both or as a consequence of the haemodynamic changes. Our aim was to investigate very early albumin permeability alterations in isolated glomeruli which were not subject to perfusion pressure. METHODS: Isolated glomeruli were studied from 120 male Wistar rats, divided into three groups: streptozotocin-treated, streptozotocin-treated with insulin pellet implants, and controls. From each group ten animals were killed at 7, 14, 28, and 56 days after induction. Study variables included blood pressure, proteinuria, iopamidol clearance, albumin permeability and glomerular area. Subsequently, albumin permeability, proteinuria, and iopamidol clearance were determined in an additional group of 40 diabetic animals studied at 24, 72, 96, and 120 h after induction. RESULTS: Albumin permeability increased steadily from induction in streptozotocin-treated animals, reaching a plateau at approximately 120 h. Glomerular filtration rate was shown to increase significantly at approximately 7 days and proteinuria correlated with it. Glomerular hypertrophy was observed both in streptozotocin-treated animals and in streptozotocin-treated rats with insulin pellet implants. Strict blood glucose control delayed the appearance of the permeability defect in isolated glomeruli and inhibited the increase in glomerular filtration in intact animals. It did not prevent glomerular hypertrophy. CONCLUSION/INTERPRETATION: An albumin permeability defect exists early in isolated non-perfused glomeruli from streptozotocin-treated rats and seems to be independent of glomerular filtration rate alterations.

Animals↗

Interferon versus steroids in patients with hepatitis C virus-associated cryoglobulinaemic glomerulonephritis.

BACKGROUND/AIMS: The association between mixed cryoglobulinaemia, cryoglobulinaemic glomerulonephritis, and chronic hepatitis C virus infection has recently been described. The renal disease had usually been treated with immunosuppressive therapy, but, given the presence of viral infection, this therapy is no longer recommended. In this study, we compare steroid vs interferon therapy in a group of patients affected by hepatitis C virus-positive cryoglobulinaemic glomerulonephritis in the stationary phase. PATIENTS/METHODS: The diagnosis of cryoglobulinaemic glomerulonephritis was made bearing in mind standard criteria. Patients were randomly assigned to 2 groups receiving oral prednisone 0.2 mg/kg/die for 6 months (6 patients, group A) or lymphoblastoid interferon 3 MU, three times a week for 6 months [7 patients, group B). Hepatitis C virus-RNA was determined by reverse transcription-polymerase chain reaction and hepatitis C virus genotype according to Okamoto. Hepatitis C virus-RNA quantitation was performed by competitive polymerase chain reaction. RESULTS; The 2 groups were comparable in terms of age and severity of kidney failure. All genotypes of hepatitis C virus were found with a prevalence of Type 1b. In group A, 4 patients showed a partial response; in group B, 1 patient achieved complete remission, 4 a partial response, 2 patients in both groups showed no response. At the end of the treatment, all patients in both groups relapsed. Only 1 patient in group B became hepatitis C virus-RNA negative, and recovered from cryoglobulinaemic glomerulonephritis. CONCLUSIONS: Interferon seems to be an effective drug in the treatment of cryoglobulinaemic glomerulonephritis, but dosage and length of treatment still need to be addressed by large multicentre studies.

Aged↗

Social problem-solving deficits and hopelessness, depression, and suicidal risk in college students and psychiatric inpatients.

The Social Problem-Solving Inventory-Revised was used to examine the relations between problem-solving abilities and hopelessness, depression, and suicidal risk in three different samples: undergraduate college students, general psychiatric inpatients, and suicidal psychiatric inpatients. A similar pattern of results was found in both college students and psychiatric patients: a negative problem orientation was most highly correlated with all three criterion variables, followed by either a positive problem orientation or an avoidance problem-solving style. Rational problem-solving skills emerged as an important predictor variable in the suicidal psychiatric sample. Support was found for a prediction model of suicidal risk that includes problem-solving deficits and hopelessness, with partial support being found for including depression in the model as well.

Adolescent↗

Effects of a dimeric vs a monomeric nonionic contrast medium on renal function in patients with mild to moderate renal insufficiency: a double-blind, randomized clinical trial.

The efficacy and safety of nonionic dimeric contrast media in subjects with impaired renal function is largely unknown. The present study was aimed at determining the risk of tubular nephrotoxicity in patients with mild to moderate renal insufficiency who underwent intravenous urography (IVU) with the nonionic dimeric contrast agent iodixanol (Visipaque, Nycomed Imaging, Oslo, Norway). In a double-blind protocol 64 patients (55 males; mean age 68.3 years) with serum creatinine between 135 and 265 micromol/l who were to undergo IVU were randomized to receive iodixanol (a nonionic dimer) or iopromide (a nonionic monomer), 600 mg I/kg b. w. Renal function was evaluated before and 1 h, 6 h, 24 h, 48 h and 7 days after IVU with analysis of serum creatinine, urinary enzymes alanylaminopeptidase and N-acetyl-beta-glucosaminidase, and urinary microproteins alpha-1-microglobulin and albumin. Renal function remained stable in both contrast medium groups during the follow-up period. No statistically significant differences were observed between the monomer and the dimer in terms of urinary enzyme and microprotein excretion or serum creatinine. Transient radiocontrast-induced nephropathy developed in 1 patient who had received iodixanol. The administration of the nonionic dimeric contrast medium iodixanol, or of the nonionic monomer iopromide, entailed a low nephrotoxic potential in patients with mild to moderate renal insufficiency undergoing excretory urography.

Acetylglucosaminidase↗

Relationship between whole-body protein turnover and serum creatinine in chronically uremic patients.

To investigate the relationship between decline in renal function and alterations of protein metabolism we determined the rate of whole-body protein turnover in a group of 15 postabsorptive chronically uremic patients (9 males and 6 females) with different levels of serum creatinine concentrations (average 5.7 +/- 0.4 (SE) mg x dl(-1); range 3.3-9.1). Patients' age and body mass index were 53 +/- 4 years (range 26-73) and 24.7 +/- 0.6 kg/m2 (range 20.3-28.7), respectively. Nutritional status (plasma albumin 3.6 +/- 0.4 g x dl[-1]) and acid-base equilibrium (arterial pH 7.38 +/- 0.01) were fairly controlled by therapy. Whole-body leucine rate of appearance (Ra), an index of whole-body protein turnover, was assessed using a stable isotope technique. L-[1-(13)C]leucine was continuously infused and plasma [1-(13)C]alpha-ketoisocaproic acid enrichment was determined in steady-state conditions as a marker of the intracellular leucine enrichment. The average leucine Rawas 2.03 +/- 0.13 micromol x kg(-1) x min(-1) (range 1.29-3.19). Using simple linear regression analysis, the coefficient of correlation between the individual values of serum creatinine concentration and leucine Ra was 0.59 (n = 15; p = 0.02). Leucine Ra did not significantly correlate with blood pH or plasma albumin. In conclusion, we found a positive linear relationship between the values of plasma creatinine concentration and the rate of whole-body protein degradation. This correlation suggests that the progression of renal insufficiency is associated with accelerated rates of turnover of body proteins.

Adult↗

Mechanisms of malnutrition in uremia.

The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.

Adult↗

Dose effect of nitrendipine on urinary enzymes and microproteins following non-ionic radiocontrast administration.

BACKGROUND: Although calcium-channel antagonists have been proposed as prophylaxis to prevent radiocontrast-induced nephropathy, the dose and dose interval to achieve a protective effect have not been quantified in humans. METHODS: In a randomized, double-blind protocol we studied urinary enzyme and microprotein excretion in 121 outpatients (mean age 65.3 +/- 9.3 years, 62% male) with normal renal function who were to undergo digital subtraction arteriography with iohexol or iopentol. The subjects were treated with a single dose of placebo (group 1) or nitrendipine 10 mg (group 2) or 20 mg (group 3) p.o. 1 h before the procedure. Blood and urine samples were collected 1 h before, 1 h after, and 24 h after contrast administration. Study variables included contrast volume and serum creatinine, and urinary creatinine, osmolality, albumin, alanylamino-peptidase (AAP, a brush border enzyme), N-acetyl-beta-glucosaminidase (NAG, a lysosomal enzyme), and alpha-1-microglobulin (alpha-1-micro, a filtered microprotein). RESULTS: Serum values of creatinine remained unchanged during the study period. Albuminuria was not affected by contrast administration, whereas AAP, NAG, and alpha-1-micro increased significantly, all except AAP returning to baseline at 24 h. Pretreatment with nitrendipine did not reduce enzyme excretion, although AAP levels were lower in general in the group assigned to the 20-mg dose. Acute renal failure, defined as a 50% increase of serum creatinine 24 h after radiocontrast administration, was found in eight patients: four from group 1 (8.3%), three from group 2 (6.5%), and one from group 3 (3.7%). CONCLUSIONS: Neither the course of enzyme excretion nor the incidence of acute renal failure following radiocontrast administration were affected by single doses of calcium antagonists. AAP levels were lower in general in subjects taking the 20-mg dose of nitrendipine. This study also indicates that a single low or normal dose of nitrendipine per os is not effective prophylaxis before radiocontrast administration. The designs of future studies investigating the "nephroprotective' effect of calcium-channel antagonists per os should incorporate (1) the use of repeated doses to saturate hepatic metabolic pathways, and (2) the control of confounding variables in the measurement of urinary enzymes.

Acetylglucosaminidase↗

[An atypical presentation of a case of Horton's giant-cell arteritis].

Horton giant cell arteritis can present with an atypical clinical picture that often resembles other diseases. In the case described below, the patient initially demonstrated clinical and laboratory evidence of a Candida albicans sepsis, and therefore we started antimycotic treatment with amphotericin B. Because of an adverse reaction to that drug, we added parenteral steroids before every administration of the antimycotic which led to an unexpected improvement of symptoms. This result caused us to reconsider some clinical aspects that could have been interpreted also as vasculitis, in particular for a giant cell arteritis: throbbing temporal headache, diffuse weakness, important rise in ESR, myoarthralgias. We performed a biopsy of the temporal artery that confirmed our diagnosis.

Amphotericin B↗

Involvement of the renin angiotensin system in the pathogenesis of postexercise proteinuria.

Proteinuria after strenuous exercise is common in healthy subjects. The pathophysiologic mechanism of postexercise proteinuria (PEP) is not clear, although the phenomenon has long been known and many explanatory theories have been proposed. It is widely recognized that angiotensin II may increase filtration of protein through the glomerular membrane, and that its concentration in plasma increases during exercise. The aim of this study was to evaluate possible involvement of angiotensin II in the pathogenesis of PEP. Of 25 young volunteers who performed maximal aerobic exercise, eight showed PEP. The exercise was repeated after an interval of at least one week, now 90 minutes after administration of captopril (25 mg). Captopril did not affect the achieved work load of the maximal blood pressure and heart rate during the exercise, but PEP was not found. As it was possible to prevent PEP by administering an angiotensin-converting enzyme inhibitor, the study supports the theory that the renin angiotensin system is involved in the pathogenesis of PEP.

Adult↗

Intraglomerular metastases. A possibly maldiagnosed entity.

Intraglomerular metastases are rare. We observed a case of lung cancer which gave rise to liver metastases and to exclusively intraglomerular kidney metastases, mimicking angio-endotheliomatosis. Differential diagnosis and histological features of the lesion are discussed.

Adenocarcinoma↗

Effect of intravenous supplementation of a new essential amino acid formulation in hemodialysis patients.

Protein energy undernutrition (PEU) and abnormalities of amino acid (AA) metabolism are common in maintenance hemodialysis patients (MHP). A new EAA formulation (BS695), enriched with valine and threonine, containing some histidine, and low in phenylalanine and methionine was recently developed. We randomly supplemented 11 MHP with this solution (treated group, TG) and 10 MHP with a standard AA solution containing both essential and non-essential AA (control group, CG). Both groups received 3.65 g of nitrogen, i.v. three times per week during hemodialysis for six months. During treatment, dietary intake remained stable in both groups. Before treatment, after three and six months of treatment, and six months after the end of treatment, we determined routine blood chemistries, anthropometry, serum protein levels (albumin, transferrin), delayed cutaneous sensitivity (Multi-test), protein catabolic rate (PCR), plasma AA content and motor nerve conduction velocity (MNCV). Before treatment PEU, predominantly of marasmic type, was common. After treatment anthropometry and immune response were unchanged in both groups; PCR increased more in CG than in TG; serum albumin levels decreased significantly only in CG; MNCV improved in TG and worsened in CG. These preliminary results suggest that this new EAA formulation may have beneficial effects on some nutrition related abnormalities of MHP. Better results might occur with long-term AA supplementation, particularly if it is associated with a higher energy intake.

Amino Acids, Essential↗

Contrast agent nephrotoxicity: comparison of ionic and nonionic contrast agents.

The effects on glomerular and proximal tubular function of an ionic contrast agent (sodium meglumine diatrizoate) and a nonionic agent (iopamidol) were compared in 34 patients with normal renal function. The patients received large doses (2.5 ml/kg body weight) of contrast material for IV digital subtraction angiography. Urine samples, collected before, immediately after, and on the first and third days after digital subtraction angiography, were analyzed for albumin, alanil-aminopeptidase, alpha-glucosidase, and beta-2-microglobulin. The changes noted were mild and of short duration with both contrast agents, despite the high dose given. These results suggest that, at least as far as renal toxicity is measured by these tests is concerned, ionic monomers can be safely used instead of more expensive nonionic media in procedures, such as digital subtraction angiography, that require high doses of contrast material.

Adult↗