Search PubMed⌕ Search

Biomedical subjects

Giovanni Gambaro

Publications and source records attributed to Giovanni Gambaro.

32 records · Page 2Linked to original sources
PubMed2002

Dietary fatty acid supplementation modulates the urinary excretion of calcium and oxalate in the rat. Insight into calcium lithogenesis.

BACKGROUND: An anomalous plasma phospholipid polyunsaturated fatty acid composition has been reported in calcium nephrolithiasis, and was proposed to play a crucial role in the pathogenesis of hypercalciuria and hyperoxaluria, well-known risk factors for lithogenesis. METHODS: To confirm this hypothesis, we administered rats three different diets rich in coconut, soybean and fish oils, and evaluated their effect on plasma urinary calcium and oxalate excretion, since the quality of fatty acids represents an important factor able to influence the activity of delta-6-desaturase, the rate-limiting enzyme in the biosynthetic pathway of highly unsaturated fatty acids. RESULTS: In comparison with coconut and fish oil, dietary supplementation with soybean oil increased plasma phospholipid arachidonic acid and serum 1,25-vitamin D(3) values, as well as renal tissue calcium content and urinary excretion of sodium, oxalate and calcium. CONCLUSIONS: Our findings demonstrate that the quality of fatty acids may modify the urine excretion of calcium and oxalate, confirming our previous hypothesis of a pathogenetic link between cellular membrane phospholipid polyunsaturated fatty acid composition and calcium nephrolithiasis. In addition, our study provides new insights into the relationship between dietary, environmental factors and renal stone disease.

Animals↗
PubMed2000

Glycosaminoglycan therapy prevents TGF-beta1 overexpression and pathologic changes in renal tissue of long-term diabetic rats.

Chronic induction of the prosclerotic cytokine transforming growth factor beta (TGF-beta) has been implicated in the pathogenesis of diabetic nephropathy. In a rat model of diabetes mellitus-induced glomerulosclerosis, daily administration of a modified heparin (mH) glycosaminoglycan (GAG) preparation with low anticoagulant activity prevented glomerular and tubular matrix accumulation, as well as overexpression of TGF-beta1 mRNA and albuminuria, without obvious side effects. To elucidate the molecular mechanisms of GAG/mH inhibitory actions on TGF-beta1, studies using cultured mesangial cells were also performed. In these cells, high glucose-induced, dose-dependent increases in TGF-beta1 mRNA and bioactive TGF-beta protein expression were inhibited by GAG/mH treatment, whereas basal TGF-beta1 expression was not affected. Both the heparin-derived GAG and dermatan sulfate were effective, indicating that the heparin chemical structure is not necessary for inhibitory activity. Coincubation of GAG with active TGF-beta1 demonstrated no inhibitory effect on TGF-beta1 bioactivity, excluding a neutralizing effect of GAG on TGF-beta1 a the protein level. Furthermore, it was demonstrated that GAG inhibited phorbol myristate acetate-induced translocation of protein kinase C-alpha (PKC-alpha) and -beta1 and activation of PKC-alpha, as well as high glucose-induced activation of PKC-alpha. These results suggest that GAG inhibit TGF-beta1 overexpression at the transcriptional level, possibly via inhibition of high glucose-activated PKC. The findings indicate the potential of GAG therapy for the prevention of diabetic glomerulosclerosis by the inhibition of chronic disease-induced TGF-beta1 mRNA overexpression.

Animals↗
PubMedDate not supplied

Diuretics and dopamine for the prevention and treatment of acute renal failure: a critical reappraisal.

The efficacy of diuretics and dopamine in preventing and treating acute renal failure (ARF) is still debated, although these drugs are widely used in clinical practice. The present review addresses this debate providing an update on available data. There are very few well controlled and sufficiently large trials testing these agents in different ARF clinical settings, with either a preventive or a curative goal. Unfortunately, most findings rule out any favourable effects of diuretics, mannitol, atrial natriuretic peptides, and dopamine. In fact, at least in some clinical conditions, they can even worsen the risk of ARF or aggravate its course.

Acute Kidney Injury↗
PubMedDate not supplied

Heparin reduces glomerular infiltration and TGF-beta protein expression by macrophages in puromycin glomerulosclerosis.

BACKGROUND: In a number of experimental models of nephropathy, heparin is renoprotective because it inhibits mesangial matrix synthesis and cell proliferation; in most of these models, glomerular macrophage infiltration has a pathogenic role. We investigated the hypothesis that heparin might also be renoprotective by modulating the macrophages in various ways in the chronic puromycin glomerulosclerosis model. METHODS: We studied the effect of a 3 month course, two different dosages of a non-anticoagulant heparin by immunohistochemical evaluation of the number of macrophages (ED-1 positive cells) in glomeruli, as well as the expression and deposition of TGF-beta and latent TGF-beta binding protein in foam cells and mesangial matrix. RESULTS: The renoprotective effect of heparin in this model was confirmed by our observation of lower urine protein and albumin excretion, and a reduced glomerular sclerosis score. These effects were associated with the prevention of macrophage glomerular infiltration, and the inhibition of the TGF-beta axes in foam cells as shown by the reduction in cytoplasm immunostaining for TGF-beta and LTBP-1; heparin also reduced peri-macrophagic collagen IV deposition. CONCLUSIONS: The inhibition of TGF-beta in macrophages seems to be part of heparin general activities. The inhibitory effect of heparin on macrophage infiltration and TGF-beta synthesis in this renal disease model supports the notion that heparin and derived molecules constitute potentially useful therapeutic agents in nephropathies.

Analysis of Variance↗
PubMedDate not supplied

Renal transplantation from non-heart- beating donors: a review of the European experience.

Shortage of organs for transplantation has prompted a few centers in Europe to retrieve kidneys from non-heart-beating donors (NHBD). Indeed, it has been suggested that NHBDs could bridge the gap between supply and demand in renal transplantation. However, NHB donation still has only limited diffusion. Reluctance to accept NHBDs as a source of kidneys is due to medical, organizational and ethical reasons. The experiences, protocols and results in Europe are described in this review. The analysis of the European experience of kidney transplantation from NHBDs looks promising in term of results. Long-term outcome is very similar in the two groups notwithstanding worse short-term results. Actually, the primary non functioning of grafts is significantly worse in NHBD kidneys. However, data suggest that results could be improved by better patient selection and retrieval team organization. Delayed graft function is also much more frequent in NHBD kidneys; this poses problems in the short-term, but in the long-term does not seem to influence the outcome. The risk that efforts in NHBD programs endanger regular HBD programs because of limited organizational resources is not supported by published data. Indeed, in the experiences analysed here it appears that NHBD consistently increased the number of available kidneys and has no effect on HB donations.

Europe↗
PubMedDate not supplied

Is the simian virus SV40 associated with idiopathic focal segmental glomerulosclerosis in humans?

BACKGROUND: Glomerulosclerosis was reported in mice transgenic for the simian polyomavirus SV40 early region that contains the transforming sequences encoding the SV40 large T-antigen (TAG). This was discovered when an SV40 epidemic occurred following the use of contaminated polio vaccines during 1955-1963, and led to investigations that showed an association between SV40 infection and tumors in humans. We investigated the possible association of SV40 infection and idiopathic focal segmental glomerulosclerosis (FSGS). METHODS: The study was performed in 17 Bouin-fixed, paraffin-embedded renal biopsies from FSGS patients and 10 matched biopsies from patients with IgA glomerulonephritis; all patients had undergone polio vaccination in the early 1960s. Extracted DNA was polymerase chain reaction (PCR) amplified using SV.for3/SV.rev primers and GabE1/GabE2 primers; both sets of primers map in the region of SV40 TAG sequences, and amplify a fragment of respectively 105-bp and 135-bp. The biopsies considered were those in which the DNA was sufficiently intact to allow amplification of a fragment of 102-bp of the ApoE gene. RESULTS: Three FSGS and none of the IgA biopsies were positive for the SV.for3/SV.rev fragment. Conversely, amplification with GabE1/GabE2 primers did not lead to any specific product in either the IgA or FSGS biopsies. Restriction fragment length polymorphism and sequencing analyses revealed that the positive results obtained with the SV.for3/SV.rev primers were due to amplicons generated by multiple dimerization of forward and reverse primers. CONCLUSIONS: With the limited number of patients investigated, this study excludes the hypothesis that SV40 is associated with idiopathic FSGS.

Antigens, Polyomavirus Transforming↗
PubMedDate not supplied

Double urine circulation: importance of pores.

The authors examine a presentation to the Royal Academy of Sciences of Paris by L. Morin, French physician and meteorologist. In this communication the presence of "pores" in the stomach and the bladder, which would allow a quick elimination of the urines on the occasion of an abundant fluid intake.

France↗
PubMedDate not supplied

Crystals, Randall's plaques and renal stones: do bone and atherosclerosis teach us something?

The pathogenesis of calcium-oxalate (CaOx) renal stones is still debated and a number of issues needs to be clarified. In particular, it is difficult to combine the intraluminal physical-chemical imbalance and fixed particle theory with the evidence that CaOx stones actually form and grow on Randall's plaque in the renal pelvis. On the basis of recent findings in renal stone research, and data from the biology of ectopic calcification, the hypothesis is advanced that abnormal pre-urine CaOx supersaturation triggers inflammation in the long Henle's loop cells at tip forceps level. This in turn induces differentiation of these cells toward the osteogenic lineage, determining the synthesis of typical bone osteoid proteins (osteopontin, osteocalcin, BMP-2, etc) and hydroxyapatite mineralization of the Henle's basement membrane (beneath the differentiating cells) which precedes Randal's plaque formation. This may constitute a further, still unexplored example of epithelial-mesenchymal-differentiation in the kidney.

Animals↗
PubMedDate not supplied

Silent chronic kidney disease epidemic seen from Europe: designing strategies for clinical management of the early stages.

Given the alarming predictions of the potentially devastating future epidemic of end-stage renal disease (ESRD), further knowledge is still urgently needed on this topic. The real dimensions of the problem are still unclear. It is difficult to compare Europe and the USA because different criteria are used in data collection and not much information is available, but the epidemic of silent chronic kidney disease seems to be more widespread in the States than in Europe, and more severe in terms of cardiovascular mortality. Defining early chronic renal insufficiency carrying a definite risk of ESRD is not easy, particularly for chronic renal conditions in which the clinical picture is still faint and the renal dysfunction minimal. It is also hard to say which tools are most suitable for diagnosing such renal disorders (renal filtration indexes vs. composite indexes of renal damage, e.g. the NKF's CKD stages). Furthermore, it is still not clear which strategies best identify subjects with these conditions (screening vs. early interception; general population vs. high-risk groups), how effective therapeutic approaches are, which subject categories benefit from early diagnosis and intervention, and how clinical measures should be structured (multidisciplinary case management-based approaches vs. general practitioner-oriented approaches). These issues are discussed in this paper.

Chronic Disease↗
PubMedDate not supplied

A validated model of disease progression in IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the general population. There is accumulating evidence that immunosuppressive treatment is efficacious in IgAN. However, it is critical to define appropriate indicators for this therapy especially in the wake of potentially deleterious side effects to immunosuppressives. METHODS: This study retrospectively reviewed IgAN cases collected since 1981 to identify clinical and/or histological parameters for disease progression; 310 patients with biopsy proven IgAN, diagnosed from January 1981 to March 2004, were included. RESULTS: We defined a clinical prognostic index (CPI) using multivariate analysis, which incorporated these clinical/ histological parameters. Semiquantitative scores were assigned as follows: 2 points if creatinine (Cr) was >1.4 mg/dL, 1 point if proteinuria was >1 g/24 hr, 1 point if a patient was affected by hypertension, and 1 point if a patient was older than 30 yrs. Dividing our population into two groups (scores 0-2 = low CPI group; scores 3-5 = high CPI group), we demonstrated a significantly different 10-yr renal survival rate; in the low CPI group, renal survival since time of biopsy at 10 yrs was 91.7%; in the high CPI group the renal survival at 10 yrs was 35%. We validated the CPI in an independent sample from Verona (validation group) and demonstrated similar results for the CPI. CONCLUSIONS: The CPI is convenient to use for defining the risk of disease progression.

Adolescent↗
PubMedDate not supplied

Henoch-Schönlein purpura and Crohn's disease in a family.

A 16-year-old female who underwent an appendicectomy had terminal segmental ileitis, and developed Henoch-Schonlein purpura (HSP) a few days later. Her brother had suffered from post-infection HSP, while her mother has suffered from Crohn's disease. Human leukocyte antigen (HLA) typing in the patient disclosed the DRB1*11 allele, which has been reported to be associated with HSP, but the brother proved negative, suggesting that this allele was irrelevant to the HSP pathogenesis. The patient and the other relatives did not disclose HLA DRB1*01, which is the only class II phenotype reported to be associated with both diseases. While this case report lends support to the idea that the earlier observation of concomitant Crohn's disease and HSP in the same patients is no chance association, it suggests that if the two pathological conditions share a common genetic background, this does not seem to be related to class II HLA phenotypes. Other, as yet unknown genes could be involved.

Adolescent↗