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Biomedical subjects

F Berti

Publications and source records attributed to F Berti.

At least 91 records · Page 5Linked to original sources

Defibrotide has antiischemic activity in perfused rabbit hearts, preventing tissue Ca++ overloading.

Defibrotide (D), a polydeoxyribonucleotide obtained from mammalian lungs, reduced the ischemic contracture due to low perfusion (0.2 ml/min) of the isovolumic left heart of the rabbit and abolished the irregularity of the rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). D stimulated the release of PG-like material. Indomethacin infusion completely prevented both the antiischemic activity of D and its ability to increase the generation of prostaglandins in the rabbit heart. Measurement by atomic absorption spectroscopy of calcium content in ischemic heart tissue and its mitochondrial fraction indicated that the ischemic procedure significantly increased tissue calcium content in both. D, Prostacyclin (PGI2) and Nifedipine protected the heart from ischemic ventricular contracture and prevented accumulation of calcium in the heart. The effect of D on preventing Ca++ overload was completely abolished by indomethacin infusion. The results indicate that the beneficial effects of Defibrotide in experimental ischemia are primarily due to a release of Prostaglandin E2 (PGE2) and PGI2, which in turn may inhibit the detrimental effects of calcium overload in myocytes and mitochondria.

Animals↗

Protective activity of inhaled frusemide against immunological respiratory changes and mediator release in guinea-pigs.

The antianaphylactic activity of inhaled frusemide was studied in ovalbumin-sensitized guinea-pigs. The exposure of the animals to frusemide aerosol (1% solution for 20 min) attenuated the respiratory response to ovalbumin challenge (aerosol 1% solution) and was associated with a significant reduction of blood histamine (70%; P less than 0.01) and thromboxane-B2 (35%; P less than 0.01) compared to control animals. Similar results were obtained in isolated lungs perfused via the trachea excised from ovalbumin-sensitized guinea-pigs exposed to frusemide aerosol (1% solution for 20 min). In this series of experiments frusemide significantly prevented the increase in tracheal perfusion pressure (45%; P less than 0.01) and the concomitant release into the pulmonary effluent of both histamine (75%; P less than 0.01) and thromboxane-B2 (39%; P less than 0.01). In another series of experiments, frusemide (1 x 10(-4) M) significantly reduced the immune release of histamine from mast cells of ovalbumin-sensitized rats. The inhibitory activity of frusemide was in the same range of potency (66%; P less than 0.01) as that of disodium cromoglycate (1 x 10(-4) M). These data taken together indicate that frusemide when given by inhalation prevents histamine release secondary to antigen-antibody reaction.

Administration, Inhalation↗

Determination of zeranol and beta-zearalanol in calf urine by immunoaffinity extraction and gas chromatography-mass spectrometry after repeated administration of zeranol.

A method for the determination of zeranol and its metabolite beta-zearalanol in bovine urine is described. It has been applied to samples from calves given multiple subcutaneous doses of zeranol. Samples were extracted with immunoaffinity columns containing antibodies raised against zeranol and were analysed by gas chromatography-mass spectrometry. The immunoaffinity columns were prepared by coupling immunoglobulin G fractions obtained from rabbit antisera with a Sepharose matrix. The immunizing agent was carboxybutylzeranol coupled to bovine serum albumin. Gas chromatography-mass spectrometry was performed in the negative-ion chemical ionization mode, after derivatization of the compounds to their pentafluorobenzyl ethers, and allowed detection of analytes with a sensitivity of 0.01 ppb in spiked urine. The derivatization method and the gas chromatographic determination were also applied to the similar compounds zearalanone, zearalenone and beta-zearalenol. A synthesis of dideuterated zeranol and beta-zearalanol by isotopic exchange is described. These deuterated analogues had an isotopic purity of more than 99% and were used for quantitation of zeranol and beta-zearalanol by isotope dilution mass spectrometry. The recoveries of zeranol and beta-zearalanol, using the immunoaffinity columns, were determined after extraction from spiked urine and were 84 and 64%, respectively. The urines of treated calves were collected for several days after treatments and were analysed after hydrolysis with beta-glucuronidase and arylsulphatase. The samples showed variable but generally decreasing concentrations of zeranol and beta-zearalanol. The levels of beta-zearalanol ranged from less than 0.01 to 98 ppb and were 1.2-3.2 times higher than those of zeranol.

Animals↗

Effects of defibrotide on prostacyclin release from isolated rabbit kidneys and protection from post-ischemic acute renal failure in vivo.

We evaluated whether defibrotide, a single-stranded polydeoxyribonucleotide that enhances prostacyclin (PGI2) release from various isolated organs, could also release PGI2 from the rabbit kidney and prove effective against renal ischemic injury. Isolated perfused kidneys responded to defibrotide (100, 250 and 500 micrograms ml-1 min-1) with a dose-dependent release of immunoreactive 6-keto-PGF1 alpha (4-fold increase at highest dose), which was prevented by indomethacin pre-treatment. In vivo, venous blood withdrawn from heparinized rabbits (and representative of renal outflow) was conveyed over a collagen matrix, onto which platelets adhered and aggregated. Recording the weight increase of the matrix was used as a bioassay to follow the time-course of released PGI2. We observed that renal outflowing blood from defibrotide treated animals (50 mgKg-1 i.v.) displayed lower (P less than 0.05 versus controls) platelet activation, consistent with enhanced PGI2 release from the kidneys. Furthermore, the duration of this effect was longer lasting than that predicted from the known plasma half-life of the drug. After transient (30 min) occlusion of the renal arteries, glomerular filtration rate (GFR) dropped by about 50% (P less than 0.01) during the first reperfusion hour in control animals, with only mild recovery having occurred 4 h later. Defibrotide (16 mgKg-1 bolus + 16 mgKg-1h-1, i.v.) could not antagonize the initial impairment (40% GFR reduction), but allowed full recovery at the end of the observation period (P less than 0.05 vs controls). Indomethacin, instead, caused a dramatic reduction of GFR (70%) during early reperfusion, with no subsequent recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Pathophysiology of coronary vasomotor tone.

The Authors focus the great importance of the endothelium-dependent relaxation in normal and diseased human coronary arteries. The impairment or loss of this powerful dilator process, that is multifactorial and related to the stage of development of the endothelial damage seems to be, beyond all doubt, implicated with vasospasm and thrombosis. Furthermore the response of coronary smooth muscles to vasoconstrictors, particularly to serotonin, may be augmented. These vasoconstrictors may be present in larger amount at the site of the rupture of atheromatous plaque, following platelet deposition and aggregation that trigger the release of platelet-derived products such as ADP, 5-HT and eicosanoids. The recognition and the increasing knowledge on the relationship between endothelial-relaxing mechanism dysfunction and coronary heart disease is certainly leading to new hope for a more rational therapeutical intervention.

Animals↗

Immune release of histamine and other lipid mediators from guinea-pig isolated kidney: antagonism by BN-52021.

The ability of a specific PAF-receptor antagonist, BN-52021, to control the release of mediators of anaphylaxis from actively sensitized (ovalbumin) guinea-pig has been investigated "in vitro". BN-52021 perfused through the kidney at different molar concentrations (1 x 10(-4)-1 x 10(-5)-1 x 10(-6] prior to antigen challenge neither modified the basal values of perfusion pressure nor stimulated mediator release from the organ. On the contrary, the compound antagonized in a concentration dependent way both vasoconstriction of the renal vessels and the increase in the perfusate of histamine, TXB2 and SRS-A due to antigenic shock. The antagonistic activity of BN-52021 was very consistent at 1 x 10(-4) M at which concentration the immunological release of histamine and TXB2 was reduced by 75%. The beneficial effect of BN-52021 in experimental anaphylaxis of the kidney may have some therapeutic implications principally in those pathological conditions where an abnormal increase of renal histamine and other mediators may compromise the haemodynamic function of this organ.

Animals↗

Defibrotide, by enhancing prostacyclin generation, prevents endothelin-1 induced contraction in human saphenous veins.

Spirals of human saphenous veins (HSV), mounted in a 5 ml organ bath containing Krebs-Henseleit solution (37 degrees C), when kept in contact with defibrotide (100-200 ug/ml) for 15 min, enhance (2 and 3 fold) their own basal release of 6-keto-PGF 1 alpha (61 +/- 1.3 pg/mg w.t. n = 12). The phenomenon was long lasting upon repeated washing and sensitive to indomethacin (1 ug/ml). Endothelin-1 (ET-1, 20-40 ng) induced a sustained contraction of HSV and concomitantly released from the venous tissue a proportional amount of 6-keto-PGF 1 alpha. Indomethacin (1 ug/ml), by inhibiting cyclo-oxygenase enzyme, potentiated the contractile activity of ET-1 in HSV whereas exogenous PGE2 (20 ng/ml) considerably reduced the tension developed by the peptide on this venous tissue. Defibrotide (200 ug/ml), by releasing 6-keto-PGF 1 alpha, and other vasoactive prostaglandins, antagonized the contractile effect ET-1 (20 ng) in HSV. This data indicates that the eicosanoid metabolism is involved in the modulation of the potent vasoconstrictor effect of ET-1 in HSV and that PGI2-releaser, such as defibrotide, may have therapeutical value against immoderate changes of venous tone.

6-Ketoprostaglandin F1 alpha↗

Prevention of antigen-induced early obstructive reaction by inhaled furosemide in (atopic) subjects with asthma and (actively sensitized) guinea pigs.

The present study was undertaken to determine the effect of furosemide on antigen-induced bronchoconstriction. Ten patients with stable asthma (eight men and two women), aged 17 to 48 years, were challenged with the same dose of allergen (Dermatophagoides pteronissinus, Parietaria, and grass mix) that had induced an FEV1 fall of at least 20% in a preliminary study on two occasions: immediately after placebo and furosemide (approximately 28 mg) administered by inhalation in random order and double-blind. Furosemide did not demonstrate any direct bronchodilator effect but markedly attenuated allergen-induced bronchoconstriction. The mean (95% confidence interval) maximum fall in FEV1 was 31.5% (40.2% to 22.8%) after placebo and 8.4% (11.8% to 4.9%) after furosemide administration. Furosemide, administered by aerosol to anesthetized guinea pigs actively sensitized to ovalbumin, dose dependently protected the animals from anaphylactic reaction. Infusion of furosemide (10 mg/kg for 10 minutes) failed to protect the animals from the anaphylactic response. In nonsensitized guinea pigs, the cardiovascular and pulmonary changes induced by histamine (10 micrograms/kg intravenously [i.v.]), leukotriene C4 (1 micrograms/kg i.v.), and platelet-activating factor (0.1 microgram/kg i.v.) were not modified by aerosol administration of furosemide (10 mg/ml for 10 minutes). In conclusion, inhaled furosemide induces a clear-cut protection against immediate obstructive reaction caused by areoallergerns and ovalbumin, both in subjects with asthma and actively sensitized guinea pigs, respectively.

Administration, Inhalation↗

Oesophageal cancer treated by photodynamic therapy alone or followed by radiation therapy.

Photodynamic therapy (PDT) with porphyrins and red light is receiving increasing attention in the management of malignant tumours. At present PDT is primarily indicated for the treatment of superficial or early-stage lesions. At the Department of Radiotherapy and the First Institute of Surgery in Padova (Italy) more than 150 cases of tumours of different types have been treated using this technique. This paper briefly describes 21 cases of superficial oesophageal cancer. A complete response was observed in 11 of 21 cases. Radiation therapy appeared to be very effective as a salvage treatment of non-response patients.

Antineoplastic Agents↗

Production and biologic interactions of prostacyclin and platelet-activating factor in acute myocardial ischemia in the perfused rabbit heart.

This study showed that the 1-O-hexadecyl form of platelet-activating factor (PAF) is released along with 6-keto-prostacyclin1 alpha (6-keto-PGF1 alpha) in the perfusates of ischemic-isolated rabbit heart. During the early phase of the reperfusion, the release of PAF and 6-keto-PGF1 alpha was particularly increased (PAF, from 5.4 +/- 1.2 to 19.7 +/- 2.0 ng/min; 6-keto-PGF1 alpha, from 2.3 +/- 0.1 to 27.4 +/- 1.8 ng/min) and this event was coupled with the characteristic mechanical alterations of myocardial performance and perfusion pressure (PP). These changes were effectively antagonized by pretreatment of the hearts with both prostacyclin (PGI2, 20 ng/ml) and the PGI2-releaser defibrotide (400 micrograms/ml). The protecting activity observed with PGI2 was paralleled by a reduction in the rate of PAF release during reperfusion (from 19.7 +/- 2.0 to 6.8 +/- 0.2 ng/min). In defibrotide-treated preparations, inhibition of PAF formation was associated with a pronounced stimulation of 6-keto-PGF1 alpha generation, which was particularly marked on reperfusion (from 27.4 +/- 1.8 to 197.5 +/- 8.2 ng/min). Indomethacin (1 microgram/ml) ablated the antiischemic effect of defibrotide but did not potentiate the rate of formation of PAF despite inhibition of 6-keto-PGF1 alpha biosynthesis. From these results, we conclude that in a model of severe myocardial ischemia, in which the major determinants of cardiac performance are under control, generation of PAF and PGI2 appears to play an important biologic role in determination of the severity of myocardial ischemic damage.

Animals↗

Antianaphylactic and antihistaminic activity of the non-steroidal anti-inflammatory compound nimesulide in guinea-pig.

Nimesulide (4-nitro-2-phenoxymethane sulfonanilide, Aulin, Mesulid) is a non-steroidal anti-inflammatory compound which shows antihistaminic activity and inhibits the immune release of histamine. The antihistaminic activity of this compound is specific for H1-receptor and has been demonstrated on isolated strips of guinea-pig trachea and on histamine-induced multiphasic inotropic response in left atria of guinea pig electrically driven. The effect of nimesulide is of non competitive type and, at the concentration of 1 x 10(-5) mol/l, is nearly 2 time less potent than pyrilamine (mepyramine) at 1 x 10(-6) mol/l. Nimesulide (1.6 mumol/kg i.v.) inhibits both bronchoconstriction (69%) and TXB2 formation (93%) induced by histamine (0.05 mumol/kg i.v.) in anaesthetized guinea-pigs. In contrast indomethacin (1.6 mumol/kg i.v.) decreases the generation of TXB2 (89%) without affecting the enhancement in tracheal insufflation pressure induced by histamine. In actively sensitized guinea-pigs both nimesulide and indomethacin protect the animals from deadly anaphylactic crisis. The rise in tracheal pressure induced by the antigenic challenge is inhibited of 80% and 63% respectively by nimesulide and indomethacin (6.4 mumol/kg i.v.). At this dose the two compounds reduced of 90% approximately the immunological release of TXB2 in the circulation. The release of histamine, induced by the anaphylactic reaction caused in perfused lungs obtained from actively sensitized guinea-pigs, is lessened by nimesulide (EC50 = 3.06; fid. lim. 2.59-3.63 mumol/l) and potentiated by indomethacin (EC50 = 0.89; fid. lim. 0.67-1.17 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Physiological cost of apple-farming activities.

Seventeen agricultural male workers, aged between 21 and 56 years, were investigated in the field during six different job-activities of apple-farming: pruning, weeding, hand and mechanical spraying, mowing and picking. Pulmonary ventilation and oxygen consumption were recorded for short periods by Oxylog, while heart rate was monitored for more than 24 hours by Holter's method. The farmers also rated the work intensity according to Borg's RPE scale. Pulmonary ventilation ranged on average between 13 and 30 1/min and oxygen consumption between 500 and 1300 ml/min, with a relative aerobic cost between 15 and 40%, in the different work activities. Heart rate varied on average between 80 and 94 beats/min with a relative cardiac cost between 20 and 30%. The physiological criteria (oxygen uptake and cardiac response) and the subjective rating of fatigue gave a substantially similar evaluation of the work strain, 'moderate-heavy' for mowing, weeding and picking, 'moderate' for pruning and hand spraying, 'light' for mechanical spraying of pesticides. On the whole, apple-farming can be evaluated as 'moderate' intensity, thanks to the mechanisation implemented in reducing the work-load and the work-time of many job activities.

Journal Article↗

Antisecretory activity of 6-aminoindazole in rats.

Administration of 6-aminoindazole (6-AIN) and 5-aminoindazole (5-AIN) to rats depressed gastric acid secretion, both basal and carbachol-stimulated. 6-AIN proved to be more active than 5-AIN in decreasing the stimulated secretory process. The antisecretory activity of 6-AIN appears to be partially an antihistamine effect, since this compound antagonized the stimulatory action of betazole on isolated guinea pig auricle. The antisecretory activity of 6-AIN is probably associated with an antimuscarinic effect, since the molecule decreased carbachol-stimulated gastric acid secretion in rats and depressed neostigmine-stimulated motility of duodenum and colon in the anaesthetized cat. It also lessened the hypertonus of isolated guinea-pig trachea caused by pilocarpine. The antisecretory effects of 6-AIN also appear to be associated with myolytic activity, since it decreased the spontaneous motility of duodenum and colon in anaesthetized cats and the spontaneous myoactivity of isolated jejunum of the rabbit. It depressed the contractions of isolated guinea-pig ileum caused by histamine and decreased the spasmogenic effects of barium chloride on isolated guinea-pig gall bladder. These results suggest that 6-AIN probably depresses gastric acid secretion by interfering with both histamine and acetylcholine receptors and with other receptors involved in the secretory process.

Animals↗