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F Ciani

Publications and source records attributed to F Ciani.

At least 19 recordsLinked to original sources
PubMed2006

Lectin-like oxidized-LDL receptor-1 (LOX-1) polymorphisms influence cardiovascular events rate during statin treatment.

BACKGROUND: Oxidized-LDL (ox-LDL) are involved in atherothrombosis by induction of endothelial dysfunction and thrombosis. The specific receptor lectin-like oxidized-LDL receptor-1 (LOX-1) is expressed in endothelial cells, monocytes and platelets. LOX-1 gene allelic variants (3'UTR/T) have been related with cardiovascular events and reduced anti-platelet activity induced by statins. OBJECTIVES: To detect whether LOX-1 polymorphisms could affect statins effectiveness in cardiovascular prevention. PATIENTS/METHODS: The present was a retrospective study performed in 751 white hypercholesterolemic subjects treated with increasing doses of atorvastatin (n=382, 247 male, 135 female) or simvastatin (n=369, 244 male, 125 female) up to 4 years, whose LDL target was 3.36 mmol/L according to the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATPIII). Single nucleotide polymorphism were evaluated by allelic discrimination assays (PCR), lipid profile by enzymatic-colorimetric methods and C-reactive protein (CRP) by a nephelometric technique. RESULTS: Twenty-three non-ST elevation (NSTEMI) and eleven ST-elevation myocardial infarction (STEMI) were encountered in the observational period without differences between treatments (p=0.175) and sex (p=0.139). Each symptomatic subject (10 reaching the appropriate LDL target and 24 with still undesirable LDL) had the 3'UTR/T allelic variant (adjusted O.R. 4.63, 95% C.I. 3.46-6.70, p<0.0001). Among patients not reaching LDL target the C allele resulted protective with respect to T carriers (p<0.00001). Also, similar changes of CRP resulted in different event rate between T and C carriers (p<0.001) in the whole cohort. CONCLUSIONS: In the studied population LOX-1 genetic variants influence cardiovascular risk reduction induced by statins also in patients not reaching the LDL target. The previously described LOX-1-related antithrombotic actions of both statins employed could have a specific role in what observed, suggesting a genetic influence in statins LDL-lowering partially related actions.

Aged↗
PubMed2006

Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems.

Rhesus monkey embryonic stem cells (ESCs) (R366.4), cultured on a three-dimensional (3D) collagen matrix with or without human neonatal foreskin fibroblasts (HPI.1) as feeder cells, or embedded in the collagen matrix, formed complex tubular or spherical gland-like structures and differentiated into phenotypes characteristic of neural, epithelial and endothelial lineages. Here, we analysed the production of endogenous extracellular matrix (ECM) proteins, cell-cell adhesion molecules, cell-surface receptors, lectins and their glycoligands, by differentiating ESCs, forming a micro-environment, a niche, able to positively influence cell behaviour. The expression of some of these molecules was modulated by HPI.1 cells while others were unaffected. We hypothesized that both soluble factors and the niche itself were critical in directing growth and/or differentiation of ESCs in this 3D environment. Creating such an appropriate experimental 3D micro-environment, further modified by ESCs and modulated by exogenous soluble factors, may constitute a template for adequate culture systems in developmental biology studies concerning differentiation of stem cells.

Animals↗
PubMed2006

Genetic and biochemical approach to early prenatal diagnosis in a family with mut methylmalonic aciduria.

Genetic and biochemical prenatal diagnosis was performed at 11 weeks of gestation in a family with a proband affected by mut methylmalonic aciduria (MMA) and homozygotes for the MUT gene c.643G>A (p.Gly215Ser) mutation. Both chorionic villus and amniotic fluid samples were used. The presence of high levels of methylmalonic acid and propionylcarnitine determined by gas chromatography/mass spectrometry and LC/MS/MS analysis, respectively, and the identification of the p.Gly215Ser at a homozygous level in foetal DNA allowed a certain, rapid and early diagnosis. To our knowledge, this is the first mut MMA prenatal diagnosis carried out by genetic and biochemical approach.

Amino Acid Metabolism, Inborn Errors↗
PubMed2002

Clinical findings and biochemical and molecular analysis of four patients with holocarboxylase synthetase deficiency.

Holocarboxylase synthetase (HLCS) deficiency (HLCSD) is a rare autosomal recessive disorder of biotin metabolism. HLCS catalyzes the biotinylation of the four human biotin-dependent carboxylases. Using the newly available human genomic sequence, we report the map of HLCS genomic structure and the predicted exon/intron boundaries. Moreover, the molecular studies of four patients (two Italians, one Iranian, and one Australian) affected by HLCS deficiency are here reported. The clinical findings, the age of onset, and response to biotin treatment differed between our patients. The diagnosis was made by organic acid analysis and confirmed by enzymatic analysis in three patients. Six mutations in the HLCS gene were identified, including two novel (N511K and G582R) and four known missense mutations (L216R, R508W, V550M, and G581S). Five of the mutations are localized within the HLCS biotin-binding domain, whereas the L216R amino acid change is located in the N-terminal region outside of the putative biotin-binding domain. This mutation, previously reported in a heterozygous state, was detected for the first time in a patient with homozygous status. The patient's severe clinical phenotype and partial responsiveness to biotin support a genotype-phenotype correlation through the involvement of residues of the N-terminal region in a substrate specificity recognition or regulation of the HLCS enzyme.

Acidosis↗
PubMed2002

Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia.

Hyperphenylalaninemia (HPA), due to a deficiency of phenylalanine hydroxylase (PAH) enzyme, is caused by mutations in the PAH gene. Molecular analysis in 23 Italian patients with PAH deficiency identified two novel (P281R, L287V) and 20 previously described genetic lesions in the PAH gene. The detection of the A403V amino acid substitution in combination with null mutations in patients with BH4-responsive PAH deficiency leads us to correlate it with BH4 responsiveness.

DNA Mutational Analysis↗
PubMed2002

Two new mutations in children affected by partial biotinidase deficiency ascertained by newborn screening.

Mutation analysis performed on DNA from 6 Italian patients with partial biotinidase deficiency ascertained by newborn screening allowed the identification of two new mutations, c1211C > T (T404I) and a single base deletion c594delC. All patients were compound heterozygous for the D444H amino acid substitution showing that this mutation is also common in Italian patients affected by partial biotinidase deficiency.

Amidohydrolases↗
PubMed2001

Lectin-binding patterns in the olfactory system of the lizard, Physignathus lesueurii.

Lectin binding histochemistry was performed on the olfactory system of Physignathus lesueurii to investigate the distribution and density of defined carbohydrate terminals on the cell-surface glycoproteins of the olfactory and vomeronasal receptor cells and their terminals in the olfactory bulbs. The lectin staining patterns indicate that the vomeronasal and olfactory receptor cells are characterized by glycoconjugates containing alpha-D-galactose and N-acetyl-D-glucosamine terminal residues. The presence of specific glycoproteins, whose terminal sugars are detected by lectin binding, might be related to the chemoreception and transduction of the odorous message into a nervous signal or to the histogenesis and development of the olfactory system. The olfactory and vomeronasal receptor cells are vertebrate neurons that undergo a continual cycle of proliferation not only during development but also in mature animals.

Animals↗
PubMed2000

Lymphocyte mRNA analysis of the ornithine transcarbamylase gene in Italian OTCD male patients and manifesting carriers: identification of novel mutations.

A new simple, non-invasive method using ornithine transcarbamylase (OTC) mRNA isolated from peripheral blood (PBL) or lymphoblastoid cell lines has been performed. This approach based on reverse transcription and nested PCR to obtain a double strand PBL OTC cDNA allowed the identification of genetic lesions in five Italian families affected by OTC deficiency (OTCD). In the PBL OTC mRNA two new mutations, T262K and W265L, have been detected in three unrelated male OTCD patients with mild symptoms. One known mutation, T264A, has been identified in one manifesting carrier. The known mutation E310X, detected on genomic DNA of another manifesting carrier, failed to be detected in her PBL OTC mRNA because of the presence of a STOP codon. All mutations have been confirmed in the patients' and their relatives' genomic DNA. In three patients the mutations have also been confirmed in the mRNA isolated from frozen liver biopsy. The T262K amino acid substitution has been detected in a male's PBL OTC mRNA at homozygous state while a heterozygous pattern has been detected at the genomic DNA level, suggesting that the patient is a somatic mosaic for this mutation. Here we show that PBL OTC mRNA analysis is useful to detect genetic lesions in male and female OTCD patients.

Cell Line, Transformed↗
PubMed2000

Lectin cytochemical localisation of glycoconjugates in the olfactory system of the lizards Lacerta viridis and Podarcis sicula.

To investigate the presence of defined carbohydrate moieties on the cell surface of the olfactory and vomeronasal receptor cells and the projections of the latter into the olfactory bulbs, a lectin binding study was performed on the olfactory system of the lizards: Lacerta viridis and Podarcis sicula. Both lizards showed a high lectin binding for N-acetyl-glucosamine in the sensory neurons. The lectin binding patterns in Lacerta indicated that the main olfactory system possessed a moderate density of N-acetyl-galactosamine residues and detectable levels of galactose ones. The vomeronasal system on the other hand contained a high density of N-acetyl-galactosamine moieties and a moderate density of glucosamine ones. In Podarcis the main olfactory system and vomeronasal organ contained respectively detectable and moderate levels of galactose residues. The expression of specific glycoconjugates may be associated with outgrowth, guidance and fasciculation of olfactory and vomeronasal axons.

Acetylglucosamine↗
PubMed2000

Prolonged exclusive breast-feeding from vegan mother causing an acute onset of isolated methylmalonic aciduria due to a mild mutase deficiency.

We describe a case of methylmalonic aciduria (MMA) occurred in a 22-month-old boy whose diet was exclusively based upon breast-feeding from a mother following a long-lasting strict vegetarian diet. Clinical picture showed a dramatic onset, with a profound drowsiness associated with a severe metabolic acidosis, hyperammonemia, macrocytic anemia, ketonuria, and massive methylmalonic aciduria without homocystinuria. Both symptoms and biochemical findings quickly improved thanks to prompt vitamin B(12)parenteral therapy. Biochemical and enzymatic findings allowed a diagnosis of mild mutase deficiency, which only and inadequate dietary B(12)contribution might have revealed. Our case highlights the risk of a prolonged strictly vegetarian diet of lactating mother for providing inadequate amounts of some nutrients to the breast-fed baby. Moreover, such a dietary behaviour could dramatically unmask otherwise clinically unapparent metabolic defects in the baby.

Adult↗
PubMed2000

Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women.

OBJECTIVE: The aim of our randomized, controlled trial was to verify the effect of folic acid supplementation on homocysteine levels in postmenopausal women. STUDY DESIGN: Thirty-six women were divided randomly into 2 groups as follows: a placebo group (n = 18) and a group receiving 500 microg folic acid per day for 4 weeks (n = 18). To assess concentrations of plasma homocysteine, venous blood samples were taken on enrollment and after 4 weeks of treatment. RESULTS: Mean plasma homocysteine levels were 10.9 +/- 2.7 micromol/L in the placebo group and 7.8 +/- 2.35 micromol/L (P <.01) in the group receiving 500 microg folic acid per day for 4 weeks. The thirds (referred to as tertiles) of women with the highest baseline homocysteine plasma levels showed the greatest reduction in homocysteine, with a mean decrease of 4.35 micromol/L (32%; P <.01), in comparison with a decrease of 3.35 micromol/L (29%; P <.01) in the middle tertile and 1.3 micromol/L (22.4%; P =.09) in the lower tertile. CONCLUSIONS: The results show that low doses of folic acid are associated with a significant reduction in plasma concentrations of homocysteine. The highest initial levels of homocysteine showed the most important reduction after therapy.

Cardiovascular Diseases↗
PubMed2000

Lethal late onset cblB methylmalonic aciduria.

OBJECTIVE: To alert the physicians to the possibility of a late-onset inborn error of metabolism in an apparently previously healthy patient with acute clinical presentation. DESIGN: Case report. SETTING: Pediatric unit and general intensive care unit. PATIENT: An apparently previously healthy 12-yr-old female presented acutely with vomiting, fever, bronchopneumonia, and progressive loss of consciousness associated with ketoacidosis, hyperglycemia, and hyperammonemia. She died 3 days later with a diagnosis of insulin-dependent diabetes mellitus. INTERVENTIONS: Intravenous hydration, glucose and insulin, mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Organic acid analysis on a postmortem sample of aqueous humor revealed high levels of methylmalonic acid. Enzymatic studies on cultured fibroblasts were consistent with the diagnosis of cblB methylmalonic aciduria. CONCLUSIONS: The diagnosis of cblB methylmalonic aciduria was made in a postmortem patient who died with a misdiagnosis of insulin-dependent diabetes mellitus. Unclear biochemical findings and positive family history should strongly lead to suspicion of an inborn error of metabolism in an apparently previously healthy critically ill patient.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Inhibition of neutral endopeptidase potentiates the effects of atrial natriuretic peptide on acute cyclosporin-induced nephrotoxicity.

BACKGROUND: The use of cyclosporin A (CyA) is limited by its significant nephrotoxicity. Atrial natriuretic peptide (ANP) has been shown to ameliorate the reduction in glomerular filtration rate (GFR) induced by CyA, but its effect is transient. One explanation may be the rapid breakdown of this hormone by neutral endopeptidase (NEP) which is highly active in the kidney. In the present study, we examined the effect of the NEP inhibitor thiorphan on the acute fall in GFR induced by CyA. METHODS: After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg.kg(-1), i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 microg.kg(-1) i.v. as bolus and a maintenance infusion of 1 microg. kg(-1).min(-1)); (3) thiorphan alone (5 mg.kg(-1) i.v. as bolus and a maintenance infusion of 0.5 mg.kg(-1). min(-1)); (4) ANP plus thiorphan (as in 2 and 3), and (5) an infusion of 0.9% saline, increased from 1.2 to 3 ml.h(-1). The GFR was measured as the clearance of (3)H-methoxyinulin (ml.min(-1).100 g(-1) body weight). RESULTS: The data show: (1) the GFR fell from 1.06 +/- 0.15 to 0.59 +/- 0.09 ml.min(-1).100 g(-1) (p < 0.01) 60 min after CyA and remained depressed for at least 2 h; (2) ANP caused a marked initial rise in GFR from 0.49 +/- 0.07 to 1.23 +/- 0.18 ml.min(-1).100 g(-1) (p < 0.005 vs. CyA) which declined rapidly to the value seen after CyA injection alone, despite continuing ANP infusion; (3) thiorphan caused a modest, but significant increase in GFR within 15 min from 0.48 +/- 0.04 to 0.69 +/- 0.10 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which was sustained during infusion and for at least 30 min after stopping infusion; (4) ANP plus thiorphan produced a marked increase in GFR from 0.58 +/- 0.09 to 1.39 +/- 0.44 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which then decreased, but remained above the post-CyA injection value, until infusion of both drugs ended; (5) more than doubling the saline infusion rate per se had no significant effect on the GFR response to CyA. The blood pressure decreased significantly during ANP infusion, but more so when combined with thiorphan. CONCLUSION: These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance, and prolong, the vasodilator and diuretic effects of ANP.

Acute Disease↗
PubMed2000

[Protagonists of natural delivery].

In an attempt to re-humanize such natural event as giving birth, several, maternity wards have proposed alternative solutions. Since 1985 the obstetric-paediatric staff in Poggibonsi (Siena) has been using a special natural (active) room to this purpose. In this report we wish to understand the motivations which lead couples to decide to give birth in the active birth room. From daily contact with persons involved in this type of birth it has been possible to reach various conclusions regarding the persons most deeply involved in the event. The need of intimacy in a unique moment such as giving birth the almost total absence of medical intervention, the possibility of immediate and continuous contact with her baby, and also the reassuring presence of her family represent the main reasons for womans' choicfe in this matter. Even through the father cannot personally participate in the emotions of pregnancy and birth, he takes part by choosing to be as close as possible to his partner and child through his continuous and attentive presence. The mid-wife, that in this situation is far from the doctor's supervision is the person preferred by the woman giving birth because she too is a woman and because of her professional capacities, and she is therefore extremely reassuring. Last, the child-nurse represent the friend who affectionately and materially supports the mother and the family, especially concerning breast-feeding and care of the newborn baby.

Fathers↗
PubMed1999

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group.

OBJECTIVES: The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol. BACKGROUND: Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement. METHODS: Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction < or =40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142+/-44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74+/-23 mg/day). RESULTS: At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume -8+/-7 vs. +7+/-6 ml/m2, p = 0.053; end-systolic volume -7+/-5 vs. +6+/-4 ml/m2, p = 0.047), an improvement in LV ejection fraction (+7+/-3% vs. -1+/-2%, p = 0.045), a reduction in ventricular ectopic beats (-12+/-9 vs. +62+/-50 n/h, p = 0.05) and couplets (-0.5+/-0.4 vs. +1.5+/-0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (-0.6+/-0.6 vs. +1.3+/-0.5 ml/kg/min, p = 0.03). CONCLUSIONS: In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.

Adrenergic beta-Antagonists↗
PubMed1999

Lectin characterization of the olfactory system in brachiopterygian fish.

Lectin binding was performed on the olfactory system of Polypterus and Erpetoichthys, the living genera of the subclass of Brachiopterygii. The lectin histochemical patterns and the Western-blot analysis indicate that the receptor cells of the olfactory mucosa are characterized by high density of specific glycoconjugate residues. The presence of glycoproteins, whose terminal sugars are detected by lectin binding, might be related to the reception of an odor stimulus and its transduction into a nervous signal or to the histogenesis of the olfactory system.

Animals↗
PubMed1998

A decrease in renal medullary tonicity stimulates anion transport in Henle's loop of rat kidneys.

To investigate the effect of reduction in renal medulla osmolality on loop of Henle (LOH) net bicarbonate reabsorption, clearance and microperfusion experiments were performed on Sprague-Dawley rats. The decrease of renal medulla osmolality was induced by intravenous infusion of either a large dose of mannitol (mannitol protocol) or a hypotonic solution (hypotonic protocol) delivered at a rate to match the sodium and bicarbonate load of the control period. During the mannitol protocol, clearance data demonstrated a rise in glomerular filtration rate (GFR), renal plasma flow, urine pH, and fractional bicarbonate excretion. On the contrary, microperfusion experiments, performed in the absence of mannitol in the tubular perfusate, revealed a significant increase both in the absolute and fractional LOH bicarbonate transport. During the hypotonic protocol, there was a decrease in GFR, associated with an increase in fractional excretion of bicarbonate. In the microperfusion experiments, hypotonic saline, similar to mannitol, stimulated absolute and fractional LOH bicarbonate transport. Net reabsorption of chloride, measured under the same experimental conditions, was also found to be activated. Therefore, the intravenous infusion of hypotonic solution affected the LOH transepithelial net reabsorption of both bicarbonate and chloride. We hypothesize that the increase in the transport rate of these two anions, along the same segment and in similar experimental conditions, may be mediated, at least in part, by decreased medullary tonicity, which is one factor common both to hypertonic mannitol and hypotonic saline infusion.

Animals↗