Biomedical subjects

M Carini

Publications and source records attributed to M Carini.

At least 55 records · Page 3Linked to original sources

PubMed1996

Adaptive morphological changes of the intestinal mucosa in orthotopic ileal bladder. Short-term and long-term evaluation.

The morphology of the mucosa of orthotopic ileal bladders in place for 3 months to 4 years was studied in biopsies obtained at random from 12 patients. A mucosal flattening, a reorganization of the lining epithelium and a disappearance of the fenestrated areas of blood capillaries were found. Enterocytes progressively stratified and acquired poorly differentiated features, along with loss of microvilli, reduction of the apical fuzzy glycocalyx and enlargement of intercellular spaces. Goblet cells at short-term evaluation were actively involved in mucous synthesis and secretion. Metabolic acidosis was slight both in short-term postoperative periods-under alkaline therapy- and in long-term postoperative periods-when therapy was suspended. It can be concluded that, firstly, urine contact determines in such reservoirs a condition of acute irritation and, secondly, environmental changes induce the ileal mucosa to develop a new phenotype probably better suited to a protective rather than absorptive function.

Aged↗

PubMed1995

Identification of flavonoid metabolites after oral administration to rats of a Ginkgo biloba extract.

An extract of Ginkgo biloba leaves (EGb) was administered by gastric probe to Wistar female rats, and urine and faeces samples were collected for 5 days and whole blood samples were withdrawn every 30 min for 6 h. After purification with SPE C18 cartridges, the samples were analysed by reversed-phase LC-diode array detection (LC-DAD) for residual flavonoid glycosides, aglycones and metabolites. No glycosides or aglycones were detected in urine, faeces or blood and extensive degradation of EGb flavonoids within 24 h was detected. Among the seven different phenylalkyl acids detected by LC-DAD, 3,4-dihydroxyphenylacetic acid (I), hippuric acid (II), 3-hydroxyphenylacetic acid (III), homovanillic acid (IV) and benzoic acid (VII) were directly confirmed by on-line mass spectrometry using an electrospray interface (ES-MS). Peaks V and VI needed to be collected and separately examined and they were found to be 3-(4-hydrophenyl)propionic acid and 3-(3-hydrophenyl)propionic acid, respectively. As further evidence, the identity of metabolites I, II, III, IV, V and VII was confirmed by co-chromatography with authentic standards.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Characterization of cisplatin-glutathione adducts by liquid chromatography-mass spectrometry. Evidence for their formation in vitro but not in vivo after concomitant administration of cisplatin and glutathione to rats anc cancer patients.

After incubation of equimolar amounts of cisplatin (CDDP) and glutathione (GSH) in phosphate buffer pH 7.4 at 37 degrees C, we detected two CDDP-GSH adducts whose structures, characterized by LC-MS, corresponded to cis-[Pt(NH3)2Cl(SG)] and cis-([Pt(NH3)2Cl]2(mu-SG))+. The latter is a new CDDP-GSH adduct, which was postulated but never structurally characterized so far. Rats and patients were given a 15-min intravenous infusion of CDDP (10 mg/kg to rats and 25 mg/m2 to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m2 to patients as a 15-min infusion). After the administrations, CDDP-GSH adducts were absent in rat and human plasma ultrafiltrates. The discrepancy between in vitro and in vivo findings can be explained based on pharmacokinetic considerations.

Animals↗

PubMed1995

Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency.

Triterpene and steroid saponins and sapogenins of medicinal plants (Aesculus hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be effective for the treatment/prevention of venous insufficiency. In this work we evaluated the inhibitory effects of these plant constituents on the activity of elastase and hyaluronidase, the enzyme systems involved in the turnover of the main components of the perivascular amorphous substance. The results evidence that for Hedera helix L., the sapogenins only non-competitively inhibit hyaluronidase activity in a dose-dependent fashion, showing comparable IC50 values (hederagenin IC50 = 280.4 microM; oleanolic acid IC50 = 300.2 microM); both the saponins hederacoside C and alpha-hederin are very weak inhibitors. The same behaviour is observed for serine protease porcine pancreatic elastase: the glycosides are devoid of inhibitory action, while genins are potent competitive inhibitors (oleanolic acid IC50 = 5.1 microM; hederagenin IC50 = 40.6 microM). Constituents from Aesculus hippocastanum L. show inhibitory effects only on hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 = 149.9 microM), less to its genin escinol (IC50 = 1.65 mM). By contrast, ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity, exhibit remarkable anti-elastase activity (IC50 = 119.9 microM; competitive inhibition). The mechanism of elastase inhibition by triterpene and steroid aglycones, with a nitroanilide derivative as substrate, is discussed.

Animals↗

PubMed1995

Determination of sunscreen agents by micellar electrokinetic chromatography.

The separation of UV-A and UV-B sunscreens by micellar electrokinetic chromatography has been studied. The optimized method, which involves the presence of an anionic surfactant (sodium dodecyl sulphate) and an organic modifier in the background electrolyte, was applied to determine these sunscreens in cosmetic products. Identification was achieved by "on-line" UV spectra. Recovery was in the range of 88-92% and the lower limit of detection was 0.15 mg ml-1.

Cinnamates↗

PubMed1995

Echinacoside and caffeoyl conjugates protect collagen from free radical-induced degradation: a potential use of Echinacea extracts in the prevention of skin photodamage.

The protective effect of caffeoyl derivatives (echinacoside, chlorogenic acid, chicoric acid, cynarine, and caffeic acid, typical constituents of Echinacea species) on the free radical-induced degradation of Type III collagen has been investigated. The macromolecule was exposed to a flux of oxygen radicals (superoxide anion and hydroxyl radical) generated by the xanthine/xanthine oxidase/Fe2+/EDTA system and its degradation assessed qualitatively by SDS-PAGE and quantitatively as the amount of soluble peptides (according to the 4-hydroxyproline method) released from native collagen after oxidative stress. The SDS-PAGE pattern of native collagen is markedly modified by free radical attack, with formation of a great number of peptide fragments with molecular masses below 97 kDa: in the presence of microM concentrations of echinacoside, there is a complete recovery of the native profile. Collagen degradation was, in fact, dose-dependently inhibited by all the compounds, with the following order of potency: echinacoside approximately chicoric acid > cynarine approximately caffeic acid > chlorogenic acid, with IC50 ranging from 15 to 90 microM. These results indicate that this representative class of polyphenols of Echinacea species protects collagen from free radical damage through a scavenging effect on reactive oxygen species and/or C-, N-, S-centered secondary radicals, and provide an indication for the topical use of extracts from Echinacea species for the prevention/treatment of photodamage of the skin by UVA/UVB radiation, in which oxidative stress plays a crucial role.

Caffeic Acids↗

PubMed1995

Differential inhibition of superoxide, hydroxyl and peroxyl radicals by nimesulide and its main metabolite 4-hydroxynimesulide.

The superoxide and hydroxyl radical scavenging activities of nimesulide (CAS 51803-78-2) and its main metabolite 4-hydroxynimesulide (CAS 109032-22-6) were investigated by Electron Spin Resonance (ESR) spectroscopy, with the spin trapping technique. Hydroxynimesulide is a good scavenger of both O2 degrees- (IC50 = 40 mumol/l) and HO degree (IC50 = 54.8 mumol/l) radicals, and its high reactivity towards HO degree was confirmed by the rate constant for reaction with HO degree (K = 8.9 x 10(10) mol-1 l s-1) determined by competition kinetic studies with 5,5-dimethyl-l-pyrroline-N-oxide. Nimesulide, which has been shown by ESR to be inactive as a superoxide quencher, has a rate constant of reaction with HO degree slightly greater than that of its metabolite (3.3 x 10(11) mol-1 l s-1). In the HO degree-induced peroxidation of phosphatidylcholine (PC) liposomes, both compounds act as potent preventive antioxidants, but the HO degree entrapping capacity of the parent drug was again greater than that of hydroxynimesulide (IC50 2.12 vs 3.84 mumol/l). The metabolite is also a potent scavenger of the peroxyl radical (ROO degree) in the propagation phase of PC peroxidation (marker conjugated dienes), with an IC50 = 2.67 mumol/l; at 5 mumol/l it induces a lag time in the decomposition of PC hydroperoxides (PC-OOH) into aldehydic products of 40 h longer than in the controls (markers: conjugated dienes and total carbonyl functions). In PC liposomes, in the presence of preformed PC-OOH, the metabolite prevents PC peroxidation stimulated by 5 mumol/l Fe2+, via the Fenton reaction (marker: conjugated dienes), at the micromolar level (IC50 = 17 mumol/l) through an anti-free radical activity and a free iron chelating mechanism. Hydroxynimesulide in fact interacts with Fe2+ ions, giving rise to a strong complex, with a stability constant (log K) estimated to be around 8/9. In addition, hydroxynimesulide efficiently protects ex vivo synovial fluid lipids from the oxidative stress induced by Fe2+/ascorbate, already at 10 mumol/l (marker: thiobarbituric acid reactive substances). These results provide evidence for strong antioxidant and iron-chelating properties of 4-hydroxynimesulide, which can act synergistically with the specific HO degree scavenging activity of the parent drug in preventing and limiting in vivo the free radical-mediated tissue damage in both acute and chronic inflammatory situations.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1994

Second stage reconfiguration of Camey I ileal bladder improves its urodynamic and clinical characteristics.

Second stage reconfiguration of Camey I neobladder with intact ileal loop was performed in 3 patients due to poor functional results and associated complications requiring reintervention. Neoblasdder capacity increased from a mean volume of 240 to 593 mL, maximum endoluminal pressure decreased from a mean value of 86 to 29 mm water, and night-time incontinence uniformly disappeared. Loop detubularization and reconfiguration, therefore, results in marked improvement of the clinical and urodynamic characteristics of Camey I ileal neobladder.

Aged↗

PubMed1994

Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action.

The scavenging by procyanidines (polyphenol oligomers from Vitis vinifera seeds, CAS 85594-37-2) of reactive oxygen species (ROS) involved in the onset (HO degrees) and the maintenance of microvascular injury (lipid radicals R degrees, RO degrees, ROO degrees) has been studied in phosphatidylcholine liposomes (PCL), using two different models of free radical generation: a) iron-promoted and b) ultrasound-induced lipid peroxidation. In a) lipid peroxidation was assessed by determination of thiobarbituric acid-reactive substances (TBARS); in b) by determination of conjugated dienes, formation of breakdown carbonyl products (as 2,4-dinitrophenylhydrazones) and loss of native phosphatidylcholine. In the iron-promoted (Fenton-driven) model, procyanidines had a remarkable, dose-dependent antilipoperoxidant activity (IC50 = 2.5 mumol/l), more than one order of magnitude greater than that of the monomeric unit catechin (IC50 = 50 mumol/l), activity which is due, at least in part, to their metal-chelating properties. In the more specific model b), which discriminates between the initiator (hydroxyl radical from water sonolysis) and the propagator species of lipid peroxidation (the peroxyl radical, from autooxidation of C-centered radicals), procyanidines are highly effective in preventing conjugated diene formation in both the induction (IC50 = 0.1 mumol/l) and propagation (IC50 = 0.05 mumol/l) phases (the scavenging effect of alpha-tocopherol was weaker, with IC50 of 1.5 and 1.25 mumol/l). In addition, procyanidines at 0.5 mumol/l markedly delayed the onset of the breakdown phase (48 h), totally inhibiting during this time the formation of degradation products (the lag-time induced by alpha-tocopherol was only of 24 h at 10 mumol/l concentration). The HO degrees entrapping capacity of these compounds was further confirmed by UV studies and by electron spin resonance (ESR) spectroscopy, using DMPO as spin trapper: procyanidines markedly reduced, in a dose-dependent fashion, the signal intensity of the DMPO-OH radical spin adduct (100% inhibition at 40 mumol/l). The results of the second part of this study show that procyanidines, in addition to free radical scavenging action, strongly and non-competitively, inhibit xanthine oxidase activity, the enzyme which triggers the oxy radical cascade (IC50 = 2.4 mumol/l). In addition procyanidines non-competitively inhibit the activities of the proteolytic enzymes collagenase (IC50 = 38 mumol/l) and elastase (IC50 = 4.24 mumol/l) and of the glycosidases hyaluronidase and beta-glucuronidase (IC50 = 80 mumol/l and 1.1 mumol/l), involved in the turnover of the main structural components of the extravascular matrix collagen, elastin and hyaluronic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Biflavonoids↗

PubMed1993

Antioxidant activity of nimesulide and its main metabolites.

The antioxidant activity of nimesulide and its main metabolites, 4'-hydroxynimesulide (M1) and 2-(4'-hydroxyphenoxy)-4-N-acetylamino-methansulfonanilide (M2), was investigated using 2 in vitro models: NADPH-supported lipid peroxidation in rat liver microsomes (marker MDA formation) and xanthine/xanthine oxidase, iron-promoted depolymerisation of hyaluronic acid, determined by gel permeation chromatographic analysis (marker molecular weight distribution). In the lipid peroxidation model, all the compounds inhibited MDA formation in a concentration-dependent manner, although with different potencies; the maximum scavenging effect was observed for M1 [50% inhibitory concentration (IC50) = 30 mumol/L; M2 IC50 = 0.5 mmol/L; nimesulide = 0.8 mmol/L]. Nimesulide was more active than its metabolites in preventing OH-induced depolymerisation of hyaluronic acid, with a 50% effective concentration of approximately 230 mumol/L, which was fairly comparable to that of tenoxicam. This protective effect was due to the OH.-entrapping capacity of the drug, which, in the Fenton-driven model, is easily converted, via OH. attack, to M1 and putatively to 2-hydroxy-4-nitro-methansulfonanilide.

Animals↗

PubMed1993

Antioxidant profile of nimesulide, indomethacin and diclofenac in phosphatidylcholine liposomes (PCL) as membrane model.

An in vitro assay based on the oxidation of phosphatidylcholine liposomes (PCL) with which we can distinguish the anti-HO zero activity from the antilipoperoxidant (R zero, ROO zero, RO zero) has been developed for testing the free-radical-scavenging ability of antiinflammatory drugs. PCL were exposed to a flux of hydroxyl radicals generated by water sonolysis for different periods, and the spontaneous lipid peroxidative phenomenon (propagation and breakdown phases) was followed for the subsequent 24 hours. Lipid peroxidation was assayed by simultaneous measurements of a) conjugated dienes, by UV spectroscopy (absorbance and second derivative at 233 nm), b) loss of lipid substrate (PC), by HPLC, and c) breakdown products (total carbonyl functions as 2,4-dinitrophenylhydrazones). Diclofenac, nimesulide and indomethacin, added to PCL at the starting of the different stages of lipid peroxidation, were tested for their overall and specific anti-radical properties. All the drugs exhibited a remarkable scavenging activity against oxy and lipid radicals, determined as percent inhibition of the formation of conjugated dienes, at concentrations easily attainable in vivo (IC50:diclofenac 2.5 microM, nimesulide 4.92 microM, indomethacin 6.85 microM), diclofenac being the most effective in quenching the R zero and ROO degree species responsible for the propagation phase. By contrast, the antioxidant activity of nimesulide and indomethacin, less potent as alkyl and peroxyl radical scavengers, is due to their ability to restrain the induction phase of the radical chain reaction mediated by hydroxyl radicals (IC50:nimesulide 1.85 microM, indomethacin 3.57 microM).

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1993

Direct characterization of caffeoyl esters with antihyaluronidase activity in crude extracts from Echinacea angustifolia roots by fast atom bombardment tandem mass spectrometry.

Fast atom bombardment (FAB-MS) and fast atom bombardment tandem mass spectrometry (FAB-MS/MS) techniques (negative ions) have been successfully applied for identification of the constituents responsible for the antihyaluronidase activity of Echinacea angustifolia roots, whose extracts are widely employed for the adjuvant therapy of chronic inflammatory diseases. Crude extracts from different solvents were tested for antihyaluronidase activity, and those with the greatest inhibitory action (the ethylacetate, butylacetate and chloroform fractions, IC50 0.44, 0.50 e 0.62 mg/ml) were directly analyzed by MS. Full scan mass spectra produced intense molecular anions: collisional activation of these resulted in tandem mass spectra rich in significant product ions. Four main caffeoyl conjugates were detected and identified by tandem mass spectrometry (daughter and parent ion mode): 2,3-O-dicaffeoyltartaric acid (chicoric acid) and 5-O-dicaffeoylquinic acid (cynarine) and 2-O-caffeoyltartaric acid (caffaric acid) in the ethylacetate fraction. Among these caffeoyl conjugates, chicoric and caftaric acids had the greatest antihyaluronidase activity: IC50 = 0.42 and 0.61 mM, while the IC50 of cynarine and chlorogenic acid were 1.85 and 2.25 mM.

Acetates↗

PubMed1993

Modified urethro-ileal anastomosis in the Studer ileal bladder.

Studer ileal bladder substitute is a low pressure reservoir anastomosed to the membranous urethra. Suitable length of mesentery is necessary to allow the ileal loop to reach the urethral stump. However, reconfiguration by double folding of the detubularized ileal segment tends to move the inferior portion of the pouch away from the membranous urethra making more difficult, if not impossible, the ileo-urethral anastomosis. In order to avoid this technical limitation, we suggest a reconfiguration of the lowest portion of the pouch into the shape of a 5-cm-long funnel, which permits the loop to approach the urethral stump and therefore facilitates the ileo-urethral anastomosis. This technique has been successfully employed in 10 patients. Eight of them have clinical, radiological and urodynamic follow-up.

Adult↗

PubMed1993

Efficacy of glutathione for treatment of fascioliasis. An investigation in the experimentally infested rat.

Liver fluke infection (Fasciola hepatica) depresses the drug-metabolizing capacity of the hepatic mixed function oxidase (MFO) and glucuronosyltransferase (GT) enzyme systems, throughout a free radicals mediated lipid peroxidation process. Glutathione (GSH, CAS 70-18-8) administered chronically (100 mg/kg i.p. once daily for 40 days) to experimentally infested rats from the onset to the maximal development of the infection (40th day), greatly reduced the damage to membrane lipids of the liver tissue (primary event of the disease), as judged by malonic dialdehyde (MDA) content (decreased by 80%) and diene conjugation absorption (delta E 1% value falls from 1.94 to 0.67). As a consequence, serum glutamate-oxaloacetate (GOT) and glutamate-pyruvate (GPT) transaminases levels, liver GSH and phospholipid (PL) contents, cytochrome P-450, NADPH-cytochrome-P-450 reductase and some typical cytochrome P-450-dependent activities (p-nitroanisole O-demethylase, aniline hydroxylase, as well as UDP-glucuronosyltransferase (GT) activity, all markedly affected in the acute stage of the disease, tend to recover to the control values. The efficacy of GSH in preventing the impairment of the hepatic drug metabolizing capacity was also demonstrated by using as substrate the widely employed flukicidal agent nitroxinil (3-iodo-4-hydroxy-5-nitrobenzonitrile). The in vitro cytochrome P-450-dependent nitroxinil detoxification (reduction to 3-iodo-4-hydroxy-5-aminobenzonitrile), drastically impaired in infested animals (-80%), is markedly restored (3-fold increase) in GSH-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

PubMed1992

Application of collisionally activated decomposition mass-analysed ion kinetic energy spectrometry to a survey of sheep milk for benzimidazole residues in relation to withdrawal periods.

A collisional spectroscopy procedure for simultaneous detection of five widely employed benzimidazole anthelmintics (laevamisole, thiabendazole, mebendazole, fenbendazole, febantel) in sheep milk was developed. The method which involves injection of crude milk extracts and selection and collision of the most abundant ionic species (M+. or fragments) obtained under electron impact ionization, is highly suitable for multi-residue analysis because of its sensitivity (limits of detection in the range of 0.6-2.8 p.p.b) and its rapidity (more than five samples per hour can be processed). The collisional approach was applied successfully for monitoring of anthelmintic residues in sheep milk.

Animals↗

PubMed1992

Retroperitoneal germ cell tumor in postmenopausal woman.

A fifty-four-year-old woman presented with right renal colic and three months later a retroperitoneal tumor was diagnosed. After explorative laparotomy with biopsy, which showed a germ cell tumor, the patient received external beam radiotherapy, but died of metastatic diffusion nine months later. We believe this is a rare occurrence of a germ cell tumor in a postmenopausal woman.

Biopsy↗

PubMed1992

Orthotopic ileal bladder: clinical, urodynamic and metabolic evaluation.

Since January 1985, orthotopic ileal bladder substitution after radical cystectomy was performed in 64 male patients. The Camey I procedure was performed in 35 patients (group 1) and the Studer procedure in 29 (group 2). Clinical, metabolic and urodynamic evaluation was performed at regular intervals with a mean follow-up of 27 months for group 1 and 13.6 months for group 2. Patients with a Camey I bladder reconstruction presented smaller capacity and higher intraluminal pressure resulting in shorter voiding intervals and a practically uniform presence of enuresis, as opposed to those reconstructed with the Studer procedure. The incidence of ureteral reflux was also higher in group 1. Metabolic studies in both groups revealed a slight metabolic acidosis which was treated with oral alkalinization. It is concluded that detubularization of the terminal ileum creates a more favorable low-pressure reservoir.

Adult↗

PubMed1992

[Observations on the natural history of heart failure. Changes due to the therapeutic use of captopril].

The purpose of this research was a retrospective evaluation of the mortality rate in 138 patients, considered after the first hospitalisation due to heart failure. After 5 years, the mortality rate was higher in the 54 patients with dilatative cardiomyopathy (74.3%), compared to the 44 patients with coronary heart disease (54.5%), while the 40 patients with valvular heart disease showed a lower mortality (37.5%). The mortality rate was higher in patients admitted in higher NYHA class. The primary aim of this research was to assess the effects of captopril on mortality in 101 treated patients, compared to 37 non treated patients, both receiving conventional treatment for heart failure. Between the 2 groups, the mortality rate showed lower percentage values for patients treated with captopril, with significant difference (p less than 0.01) at controls carried out every 12 months, until 5 years. Progressive heart failure was the greater cause of death in both groups, while the deaths classified as due to arrhythmia without pump failure were less frequent. Deaths due to reinfarction in patients with coronary heart disease showed lesser percentage values in patients treated with captopril. This research demonstrated the high mortality rate affecting a group of patients after the first hospitalisation due to heart failure. The addition of captopril to conventional treatment for heart failure significantly reduced mortality.

Age Factors↗