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Biomedical subjects

A Giacomello

Publications and source records attributed to A Giacomello.

At least 19 recordsLinked to original sources
PubMed2004

Potential role of mycophenolate mofetil in the management of neuroblastoma patients.

In human neuroblastoma cell lines (LAN5, SHEP and IMR32), mycophenolic acid (MPA) at concentrations (10(-7)-10(-6) M) readily attainable during immunosuppressive therapy with mycophenolate mofetil (Cellcept), induces guanine nucleotide depletion leading to cell cycle arrest and apoptosis through a p53 mediated pathway (up-regulation of p53, p21 and bax and down-regulation of bcl-2 and survivin). MPA-induced apoptosis is also associated to a marked decrease of p27 protein. In the same cell lines MPA, at lower concentrations (50 nM), corresponding to the plasma levels of the active free drug during Cellcept therapy, induces differentiation toward the neuronal phenotype by causing a partial chronic guanine nucleotide depletion. MPA-induced differentiation is not associated to p27 accumulation as occurs using retinoic acid. At a fixed concentration of MPA a higher percentage of apoptotic or differentiated cells is obtained when non dialysed serum substitutes for the dialysed one, due to the higher hypoxanthine concentration in the former (about 10 microM) leading to competition on HPRT-mediated salvage of guanine. At hypoxanthine or oxypurinol concentrations higher than 1 microM (up to 100 microM) no further enhancement of MPA effects was obtained, in agreement with the recently described safety of the allopurinol-mycophenolate mofetil combination in the treatment of hyperuricemia of kidney transplant recipients. The apoptotic effects of MPA do not appear to be significantly increased by the UDP-glucuronosyltransferase inhibitor niflumic acid.

Allopurinol↗
PubMed2004

Cyclic nucleotides and neuroblastoma differentiation.

We have shown that intracellular cGMP levels increase during retinoic acid- and mycophenolic acid-induced neuroblastoma differentiation and that a 6 days treatment with 1 mM dbcGMP lead LAN5 cell to elaborate a network of neuritic processes suggesting an involvement of cGMP in neuroblastoma differentiation. We have also investigated the effects of some specific inhibitors of phosphodiesterases (PDE1, PDE3, PDE4 and PDE5) on human neuroblastoma (LAN5 and SHEP) growth and differentiation. After six days of incubation in the presence of each specific inhibitor at 10 x IC50 levels a cytostatic and differentiating effect was only observed with the PDE5 inhibitors Zaprinast and MY-5445. The cytostatic effect of these compounds increased increasing their concentrations far above their IC50 levels for PDE5, suggesting that these compounds could act by interfering with other molecular events than direct cGMP-PDE inhibition. No appreciable effect was observed using Dipyridamole, another specific PDE5 inhibitor.

Cell Differentiation↗
PubMed1997

Relation between serum triglyceride level, serum urate concentration, and fractional urate excretion.

The relations between serum urate levels and age, serum cholesterol, creatinine, glucose, and triglyceride concentrations were studied in 930 men and 298 premenopausal and 478 postmenopausal women, taking into account the renal handling of uric acid. All subjects were outpatients, and statistical evaluation was performed on cases corresponding to the central 95th percentile of the biochemical variables measured. An alternative analysis excluding subjects with serum glucose or creatinine levels outside the normal range was also performed. In men, premenopausal and postmenopausal women, and their normoglycemic normocreatininemic subsets, serum triglyceride level was positively correlated with serum urate concentration and inversely correlated with fractional urate excretion in both simple and multiple linear regression analysis. In men and postmenopausal women, there was also a strong positive independent association between serum urate and creatinine levels. This association was significant also in the normoglycemic normocreatininemic subset of men, but it was insignificant in normoglycemic normocreatininemic postmenopausal women. In this large cross-sectional study, a negative correlation between serum triglyceride concentration and renal uric acid excretion has been demonstrated.

Adult↗
PubMed1996

Hypoxanthine and xanthine levels in human aqueous humor from cataractous eyes.

Purine nucleotide degradation products have been determined by HPLC in aqueous humor obtained during cataract surgery and from plasma of 22 patients (12 women). Uric acid, cytosine, guanosine monophosphate, uracyl, guanine, adenosine, adenosine monophosphate, thymine, adenine, inosine, cyclic guanosine monophosphate, hypoxanthine and xanthine were evaluated. Uric acid and the last two were the only compounds detectable in measurable amounts in aqueous humor and in plasma of all patients. Aqueous humor xanthine levels were not significantly different from plasma; aqueous humor hypoxanthine concentrations were lower than those of xanthine and than plasma oxypurine levels. In 8 patients, treated with allopurinol, oxypurinol concentrations in aqueous humor and in plasma were comparable suggesting that oxypurines are transported through the blood-aqueous humor barrier.

Aqueous Humor↗
PubMed1993

Angiotensin-converting enzyme activator from purified human neutrophils.

An endogenous ACE activator has been revealed. Neutrophil-enriched human leucocyte preparations released in isotonic media a relatively thermostable factor, capable of increasing the angiotensin-converting enzyme activity 1.6-2.0-fold. Activator would not pass through a 30 kDa cutoff membrane. Data on the presence of the activator in vivo were obtained in studies of protein-free serum fractions of patients with a hereditary CI-esterase inhibitor deficiency. It was suggested that the neutrophil-released ACE activator could have a role in the modulation of the inflammatory response.

Adult↗
PubMed1992

[Normovolemic induced hemodilution. Behavior of various hemodynamic indices].

Changes in mixed venous oxygen saturation of hemoglobin (SvO2), heart rate (HR), cardiac index, (SI) were measured in 20 patients undergoing major orthopedic surgery (rachis and pelvis bone resections for tumours: mean-lasting 8 hours), to estimate the safety limits during isovolemic hemodilution. Up to Hb 8 g%, in all patients, a cardiac index improvement (+41%) was found, and this was mainly caused by an increase in stroke index (+31%). For 16 patients at Hb 6 g%, this improvement was present only in 44% and declined during further hemodilution. In all cases, CI was moderately lower than baseline value (-18%) this was caused by an important increase in HR (= 55%) partially compensating for by the fall in SI (-57%). The Authors conclude that, in patients under general anaesthesia, isovolemic hemodilution is safe up to Hb 8 g%. Below this value the left ventricular performance rapidly declines.

Adult↗