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Biomedical subjects

G Soldani

Publications and source records attributed to G Soldani.

At least 19 recordsLinked to original sources
PubMed2006

Silicone based polyurethane materials: a promising biocompatible elastomeric formulation for cardiovascular applications.

The biocompatibility of a new material for cardiovascular applications constituted by a poly(ether)urethane (PEtU) and a silicone [polydimethylsiloxane (PDMS)] was evaluated. The achieved material shows properties similar to both polyurethanes and silicones. The material was transformed into porous membranes by a spray-deposition technique. Since any material preparation and manufacturing procedure may introduce some toxicity, in vitro cytotoxicity screening tests were carried out. Human umbilical vein endothelial cells (HUVECs) and a mouse fibroblasts cell line (L929) were cultivated with extracts obtained from materials containing 10, 40 and 100% (w/w) of PDMS. The commercially available Estane 5714-F1 and Cardiothane 51 were used as controls. Extracts were incubated up to 72 hours with HUVECs and L929 cells. The cytotoxic effect was evaluated by light microscopy, cell viability (MTT reduction and neutral red uptake) and proliferation (5-bromo-2'-deoxyuridine incorporation) tests. In vivo studies were carried out using materials containing the same PDMS percentages as for in vitro experiments. The same commercial controls were used. Results obtained with cell culture studies agreed with those obtained in the in vivo experiments and showed that the material preparation and manufacturing procedure do not introduce any toxicity in the products at each PDMS concentration investigated.

Animals↗
PubMed2006

Pharmacokinetics of clomipramine and desmethylclomipramine after single-dose intravenous and oral administrations in cats.

A cross-over study was performed in six adult spayed cats to determine the pharmacokinetics of clomipramine and its metabolite, desmethylclomipramine (DCMP) after intravenous (0.25 mg/kg) and oral (0.5 mg/kg) single-dose administrations. Plasma clomipramine and DCMP were measured by high-performance liquid chromatography at regular intervals for up to 30 h. Intravenous clomipramine best fit a two-compartmental model yielding an elimination rate constant of 0.037-0.09 h(-1) from which a mean half-life of 12.3 h was calculated. Mean clomipramine AUC(0--infinity) (ngxh/mL), clearance (L/hxkg), V(ss) (L/kg) and MRT (h) values were 652.5, 0.393, 5.0, and 13.5, respectively. Compartmental modeling for clomipramine, after oral administration, and DCMP after both administrations, produced wide parameter estimates and plots of residuals indicated poor goodness of fit. Noncompartmental analysis yielded mean AUC(0--30 h) (ngxh/mL), C(max) (ng/mL) and T(max) (h) of 948.3, 87.5 and 6.2 for clomipramine, and 613.8, 34.8, and 12.8 for DCMP respectively after oral administration. Clomipramine bioavailability was 90%. The present study showed marked pharmacokinetic variability for clomipramine and DCMP through biphasic absorption and potential genetic variability in clomipramine metabolism. It was concluded that population pharmacokinetics would allow better characterization of clomipramine variability that may explain the variability in clinical response noted in cats.

Administration, Oral↗
PubMed2004

Safety of azamethiphos in eel, seabass and trout.

The safety of azamethiphos (AZA), an organophosphorous insecticide and the active ingredient of Salmosan, was evaluated in the European eel, seabass and rainbow trout. Fish were bathed in 0.1 ppm AZA for a period of 60, 120 or 240 min. After termination of each treatment fish were transferred to clean aquaria and randomly sampled over 21 days. Compared to controls, brain acetylcholinesterase (AChE) was inhibited up to 44, 56 and 62% in eels, seabass and trout, respectively, with the inhibition being significant for up to 4 days in eels and seabass and 7 days in trout. As result of the AChE depression, fish displayed motor hyperactivity and erratic jumping at the onset of treatment. Mortality was observed only in trout following exposure for 240 min. A variable correlation observed among species between the level of exposure, the reduced activity of brain AChE and the signs of toxicity suggest that brain AChE should be considered as an indicator of exposure rather than as an index of toxicity of AZA. The present data indicate that at the therapeutic dosage of 0.1 ppm AZA for 1h can be safely used in eels, seabass and trout. The extended treatment times up to 240 min were equally safe for eels and seabass but not for trout.

Acetylcholinesterase↗
PubMed2004

A new HPLC method to determine glomerular filtration rate and effective renal plasma flow in conscious dogs by single intravenous administration of iohexol and p-aminohippuric acid.

A high-performance liquid chromatography method to determine iohexol (IOX) and p-aminohippuric acid (PAH) in the plasma of dogs is evaluated according to recovery, reproducibility, and linearity utilizing a gradient pump. The mobile phase consists of 50mM sodium dihydrogen phosphate with 0.5mM tetrabutylammonium chloride, the pH is adjusted to 4.1, methanol is added to the final ratio of 90:10 (v/v), the flow rate is set at 1 mL/min, and separation is achieved with an ODS2 Luna column. The UV detector is set at 254 nm. IOX and PAH are used for evaluation of the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). The present method tested in three dogs demonstrates the accuracy in the evaluation of ERPF and GFR. Because of its precision and simplicity and low cost, it can be considered a good tool for ERPF and GFR in small animal practice.

Animals↗
PubMed2003

Effects of liquid and freeze-dried grapefruit juice on the pharmacokinetics of praziquantel and its metabolite 4'-hydroxy praziquantel in beagle dogs.

Grapefruit juice changes the pharmacokinetic parameters of a variety of drugs metabolized primarily by cytochrome P450 3A. In a three-phase crossover study, six male beagle dogs were administered 100 ml of water (control), 100 ml of commercial liquid grapefruit juice, or 10 g of freeze-dried grapefruit juice (equivalent to 100 ml of liquid grapefruit juice) with 100 ml of water, followed after 2 h by single oral dose of praziquantel (30 mg kg(-1)). After treatment, the dogs were sampled at different times. Determination of praziquantel and its metabolite 4'-hydroxy praziquantel (identified by GC/MS) was performed by HPLC. Liquid and freeze-dried grapefruit juice preadministration increased the C(max) of praziquantel about three-fold and the AUC 2.5- and 2.3-fold, respectively. The T(max) (0.75 h) was unaffected by liquid or freeze-dried grapefruit juice, while T(1/2) was 2.3- and 1.7-fold higher compared with controls. The amount of 4'-hydroxy praziquantel was also affected by both liquid and freeze-dried grapefruit juice administration: the AUC and C(max) increased four- and three-fold, respectively and the T(max) was significantly enhanced. These findings demonstrate that both freeze-dried grapefruit juice and commercial liquid grapefruit juice significantly increase plasma concentrations and T(1/2) of praziquantel in dogs.

Animals↗
PubMed2002

A comparative kinetic study of thiamphenicol in pre-ruminant lambs and calves.

Eight healthy Holstein-Friesian calves and 8 Massese lambs of either sex (10-15-days old) were used to evaluate the pharmacokinetics of thiamphenicol after intravenous (i.v.) and oral (p.o.) administration (30 mg/kg). Plasma concentrations of thiamphenicol were determined by high-performance liquid chromatography on blood samples collected over 24h following treatment. Pharmacokinetic variables of the drug were calculated for both species and after both administration routes. After intravenous administration of thiamphenicol, a rapid distribution phase was followed by a slower elimination phase and, when thiamphenicol was administered p.o., the bioavailability was about 60% in both species. The higher volume of distribution and the longer biological elimination half-lives in pre-ruminant compared with adult animals indicate that thiamphenicol distributes widely into the extravascular compartment of pre-ruminants. Interspecies differences were observed in the kinetic behaviour of thiamphenicol with respect to peak plasma concentration (C(max)), time of peak plasma concentration (T(max)), elimination half-life (T(1/2)) and total clearance (Cl(B)). In conclusion intravenous or oral administration of 30 mg/kg of thiamphenicol provides plasma concentrations higher than minimum effective concentrations inhibiting bacterial growth (MICs) against most pathogens in pre-ruminant lambs and calves.

Administration, Oral↗
PubMed2002

Light microscopy evaluation of polyurethane vascular grafts porosity by Sudan Black B staining.

In small-diameter vascular grafts, the porosity of the internal surface plays an important role because it affects initial thrombus deposition and therefore the graft's patency. As well as many other studies reported in the literature we have carried out a study of the relationship between porosity and the manufacturing parameters of polyurethane (PU) grafts by standard scanning electron microscopy (SEM) analysis. However, SEM was not completely satisfactory for evaluating the 'sponge-like' uptake of water by the graft due to the unavoidable water loss and metal coating during preparation. In fact this preparation produces artefacts of the three-dimensional porous structure. To avoid this problem we investigated the possibility of observing the graft's internal surface through a stereomicroscope after it had absorbed water. We looked into a simple staining procedure which preferentially colours the PU graft fibres with respect to the void areas. After testing different kinds of stains, we eventually found that Sudan Black B, which usually stains for all kinds of lipid, turned out to be an excellent stain for the water-loaded PU grafts when diluted with ethanol. This staining procedure, coupled with a computerized image analysis system, allowed us to evaluate the degree of void and average void size of the graft internal surface and to correlate these data with graft density and manufacturing parameters.

Azo Compounds↗
PubMed2002

Residue depletion of thiamphenicol in the sea-bass.

The residue depletion of thiamphenicol (TAP) was investigated in the sea-bass (Dicentrarchus labrax) after 5 days' treatment with medicated food at a dose of 15 or 30 mg/kg bw/day. Fish were sampled for blood and muscle + skin from 3 h until 14 days after treatment. Thiamphenicol concentrations were assayed by high performance liquid chromatography. Thiamphenicol concentrations measured 3 h after stopping treatment were 0.77 microg/mL and 0.91 (15 mg/kg dose) or 1.32 microg/mL and 1.47 microg/g (30 mg/kg dose), in plasma and muscle + skin, respectively. After a withdrawal of 3 days, plasma and tissue concentrations were: 0.08 microg/mL and 0.03 microg/g (lower dose) or 0.12 microg/mL and 0.06 microg/g (higher dose), respectively. Thiamphenicol was not detectable either in plasma or in tissues on days 7, 10 and 14 following withdrawal of the medicated food. Based on maximum residue levels (MRL) for TAP in fin fish, established at 50 microg/kg for muscle and skin in natural proportions, a withdrawal period of 5 and 6 days is proposed, after treatment at 15 or 30 mg/kg of TAP with medicated feed pellets, respectively, to avoid the presence of violative residues in the edible tissues of the sea-bass.

Administration, Oral↗
PubMed2001

Enantiopure 3-(arylmethylidene)aminoxy-2-methylpropionic acids: synthesis and antiinflammatory properties.

Some optically active 3-(arylmethylidene)aminoxy- (3a-g, 4a-g) and fluorenylideneaminoxy-2-methylpropionic acids (5, 6), were prepared as analogues of the antiinflammatory arylpropionic acids of type B, in which the aromatic group is substituted by an MAOM moiety. Some of the new compounds, tested in vivo for their antiinflammatory properties by means of the carrageenan-induced paw edema method in rats, exhibited activity indices similar to that shown in the same test by ibuprofen. Compounds 3a,b and 4a,b, for which at least one of the two enantiomers had shown an inhibition value higher than 40% in the in vivo test, were assayed for their in vitro enzymatic inhibitory activity, showing percentage inhibition values between 40 and 50% at a concentration of 10 microM against COX-2; at the same concentration, they appeared to be devoid of any activity towards COX-1. Compounds 3a,b and 4a,b also proved to possess a similar toxicity. The lack of enantioselectivity shown by compounds 3-6 was tentatively explained in terms of a conformational freedom of the enantiomers which allows their quasi-superimposition.

Animals↗
PubMed2001

Pharmacokinetics and microsomal oxidation of praziquantel and its effects on the P450 system in three-month-old lambs infested by Fasciola hepatica.

Praziquantel (PZQ) is a broadly effective trematocide and cestocide, widely employed in veterinary and human medicine. In view of several differences in both its pharmacokinetic profile in different animal species and in the cytochrome P450-dependent system between ruminant and nonruminant species, the present study was undertaken to determine the pharmacokinetics of this drug, its effects on the P450 system and the involvement of cytochrome P450 in its metabolism in 3-month-old lambs infested by Fasciola hepatica. Following both oral and i.m. administration, PZQ disposition was best described by a linear one-compartment open model with a rapid absorption and elimination. Although the PZQ dose used by the i.m. route was only half of that used by the oral route, the mean PZQ plasma concentration was higher after i.m. than after oral treatment. Oral treatment with 30 mg/kg/day of PZQ did not modify the mono-oxygenase activities tested, whilst the administration of PZQ at a dose of 60 mg/kg/day for 2 days caused a significant decrease in the P450 3A-dependent erythromycin N-demethylase and 6beta testosterone hydroxylase activities. From the incubation of microsomes from lambs not treated with PZQ, a single metabolite (PZQ 11b-OH or PZQ 1-OH) was identified by GC/MS analysis. By selective inhibition of the 3A subfamily performed with triacetyloleandromycin, the production of this metabolite declined by about 90% suggesting a prominent role of P450 3A isoforms in this oxidation. These features indicate that agents or drugs which are able to modulate P450 3A-dependent catalysis may interfere with the metabolism, bioavailability and therapeutic effects of PZQ.

Administration, Oral↗
PubMed1999

Inhibitory effect of the cannabinoid receptor agonist WIN 55,212-2 on pentagastrin-induced gastric acid secretion in the anaesthetized rat.

The effect of the cannabinoid (CB) receptor agonist WIN 55,212-2 on gastric acid secretion was studied in the anaesthetized rat after stimulation with pentagastrin. WIN 55,212-2 (0.5-2 mg/kg, i.v.) was inactive on basal secretion but caused a marked inhibition (80%) of the acid secretion stimulated by pentagastrin (10 microg/kg, i.v.). The enantiomer WIN 55,212-3 (1-3 mg/kg, i.v.) did not significantly modify basal or pentagastrin-induced acid secretion. The inhibitory effect of WIN 55,212-2 against pentagastrin was prevented by the administration of the selective cannabinoid CB1 receptor antagonists SR141716A (1 mg/kg, i.v.) and LY320135 (1 mg/kg, i.v.); by contrast, the CB2 receptor antagonist SR144528 (0.3-1 mg/kg, i.v.) was without effect. The selective CB2 receptor agonist JWH-015 (0.1-10 mg/kg, i.v.) was inactive on the increase of acid output stimulated by pentagastrin. These results suggest that the inhibitory effect of WIN 55,212-2 on pentagastrin-stimulated acid secretion in the anaesthetized rat is mediated by specific cannabinoid receptors. Moreover, the antagonism of WIN 55,212-2-induced effects by the selective CB1 receptor antagonists SR141716A and LY320135 together with the ineffectiveness of both the CB2 receptor agonist JWH-015 and the CB2 receptor antagonist SR144528 indicate that CB1 receptor subtypes are predominantly involved in the antisecretory effect of WIN 55,212-2.

Anesthesia↗
PubMed1999

Gastric antisecretory effects of compound BP 2-94: a histamine H3-receptor agonist prodrug.

Compound BP 2-94 is an orally available prodrug of the histamine H3-receptor agonist (R)-alpha-methylhistamine, which was found to produce higher plasma levels than the parent drug in humans. In the present study radioimmunoassay was carried out in dogs to investigate the generation of (R)-alpha-methylhistamine in vivo after intragastric administration of the prodrug. The effects of BP 2-94 on gastric acid secretion and on histamine, gastrin, and somatostatin release were also investigated. After intragastric administration of BP 2-94 (10 mg/kg), both the prodrug and (R)-alpha-methylhistamine were detected in plasma: plasma levels of (R)-alpha-methylhistamine decayed with a T1/2 of about 1 hr and displayed concentrations as high as 50-fold the EC50 of the drug at the H3 receptor for at least 2 hr. In conscious dogs provided with gastric fistula BP 2-94, administered at 10 and 30 mg/kg intragastrically, caused a dose-dependent inhibition (maximum reduction was about 80%) of the acid secretion stimulated by 2-deoxy-D-glucose, whereas (R)-alpha-methylhistamine (20 mg/kg, intragastrically) was ineffective. BP 2-94 (30 mg/kg, intragastrically) significantly reduced the acid secretion stimulated by bombesin, while leaving unaffected that induced by histamine. The increase in plasma gastrin levels induced by 2-deoxy-D-glucose, bombesin or a test meal was not significantly modified by BP 2-94 (30 mg/kg, intragastrically). In anesthetized dogs BP 2-94 (30 mg/kg, intragastrically) significantly reduced histamine release detected in the portal vein under bombesin infusion, whereas it did not modify gastrin and somatostatin plasma levels. These data indicate that BP 2-94 is a good prodrug of (R)-alpha-methylhistamine in the dog, causing an efficacious reduction of acid secretion induced by both 2-deoxy-D-glucose and bombesin. Moreover, the study of paracrine and hormonal mediators of acid secretion confirms that the main mechanism underlying inhibition of acid production induced by H3-receptor activation is the impairment of histamine release from gastric histaminocytes (possibly enterochromaffin-like cells).

Animals↗
PubMed1998

Comparative bioavailability of two sustained-release theophylline formulations in the dog.

The kinetics of two sustained-release theophylline formulations, Theo-Dur (Recordati, Milano, Italy) and Diffumal (Malesci, Firenze, Italy) were studied in eight beagle dogs. In a first part of the study each animal was injected intravenously with aminophylline dihydrate, Aminomal (Malesci, Firenze, Italy), in order to determine the absolute bioavailability of the two sustained-release theophylline formulations orally administered to the dogs in the second experimental phase, over a period of 9 days, following a balanced two-period cross-over design. Assays for theophylline were performed by high performance liquid chromatography and the pharmacokinetic analysis was performed using the non-compartmental method. The principle of superposition was then applied to predict multiple dose plasma concentrations from experimental single dose data. No significant differences between the two preparations were found with respect to the main pharmacokinetic parameters, showing that the two preparations are bioequivalent. The fact that the differences between experimental and predicted results were not statistically significant allows us to conclude that multiple dose steady state plasma theophylline concentration in the dog can be predicted from experimental single dose data. Furthermore, after repeated treatment, both Diffumal and Theo-Dur, given twice daily are able to maintain therapeutic (5-20 mg ml-1) plasma theophylline concentrations in the dog.

Animals↗