[Pidotimod causes apoptotic cell death and inhibits the proliferative activity of YAC-1 tumor cells in vitro].
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Adjuvants, Immunologic↗
Biomedical subjects
G Coppi
Publications and source records attributed to G Coppi.
Immunopharmacology of Pidotimod: effect on natural killer cell activity and thymocyte cell death.
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Animals↗
Activity of the new immunostimulant PGT/1A against experimental bacterial infections.
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Adjuvants, Immunologic↗
Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death.
Experiments were performed to analyze the possible effect of the immunomodulating agent Pidotimod (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid) on mouse Natural Killer (NK) cell activity and glucocorticoid hormone(GCH)-induced thymocyte apoptosis. The results indicate that in vivo treatment with Pidotimod (200 mg/Kg ip for 5 days) causes a significant increase in NK activity and in vitro treatment produces a significant reduction of dexamethasone-induced thymocyte apoptosis. This inhibition appears to be dose-dependent and is also evident against TPA or Ca(++)ionophore-induced apoptosis.
Adjuvants, Immunologic↗
Inhibitory effect of theophylline, theophylline-7-acetic acid, ambroxol and ambroxol-theophylline-7-acetate on rat lung cAMP phosphodiesterase isoenzymes.
It is assumed that theophylline (THEO) and its xanthinic derivatives inhibit lung phosphodiesterase (PDE) and block adenosine receptors in the induction of bronchodilatation. Since the theophyllinic compound ambroxol-theophylline-7-acetic acid (ATA) has been shown in vivo to be a sound bronchodilator, this paper compares the action of ambroxol-theophylline-7-acetate (ATA), its two components, theophylline-7-acetic acid (TAA) and ambroxol (AMB), and theophylline (THEO) on the hydrolytic activity of three rat-lung cAMP PDE (types I, III and IV) and on striatal adenosine receptors. THEO inhibited all three isoenzymes with equal intensity, whereas ATA was as powerful but inhibited types III and IV only, on which AMB and TAA also showed lower effects. Lastly, unlike THEO, ATA and its two components were unable to antagonize adenosine receptors. Taken as a whole, these results suggest that the bronchodilating activity of ATA is the result of specific inhibition of particular forms of PDE and is thus more specific than that of THEO alone.
3',5'-Cyclic-AMP Phosphodiesterases↗
ACTH fragments reverse experimental haemorrhagic shock in rats.
Hypovolemic shock was produced in rats by withdrawing about 50% of estimated total blood volume. Following mean arterial pressure stabilization in the range of 25-27 mmHg, the rats were given intravenous ACTH (1-4) (4-9) (4-10) (5-10) (1-10) in comparison with ACTH (1-24). The ACTH fragments, administered within 5 min after shock induction, promptly and dose-dependently improved mean arterial pressure and survival of rats; the ACTH (1-10) showed an activity similar to that of ACTH (1-24) whereas the other fragments were less active.
Adrenocorticotropic Hormone↗
Activity and tolerability of tetridamine vaginal lavage in rats and women.
Tetridamine (2-methyl-3-methylamino-4,5,6,7-tetrahydroindazole) is a well known analgesic and anti-inflammatory drug. Here the activity and the tolerability of a new 0.134% tetridamine formulation in rats and women, are reported. Anti-inflammatory and analgesic tests were performed in Sprague-Dawley rats with carrageenin oedema; topical application of 0.134% tetridamine solution showed a marked reduction of paw swelling (-54.4%) and pain sensibility (-81.0%). A 28 days vaginal tolerability study performed on Sprague-Dawley rats with tetridamine lavage (0.2 ml/rat/day) showed, in comparison with control group, no changes in haematology, coagulation, clinical biochemistry and in histological examinations of uterus and vagina. Clinical studies (4 open and 1 double-blind) were performed on 93 women suffering from vulvovaginitis and cervicitis by treatment of 0.134% tetridamine vaginal lavage, two times daily, for 7 days. Tetridamine lavage reduced or eliminated all inflammation symptoms like burning, leucorrhea, etc. and resulted very well tolerated. From these pharmacotoxicological and clinical results we can conclude that tetridamine vaginal lavage is a new formulation with high activity and good tolerability.
Adult↗
[Dihydroergocristine. A review of pharmacology and toxicology].
A pharmacological and toxicological review of dihydroergocristine (DHEC, CAS 17479-19-5) is reported. Dihydroergocristine exercises a double agonistic/antagonistic activity on dopaminergic and adrenergic receptors; it also shows a non competitive antagonistic effect on serotonin receptors. The central effects of DHEC depend on the initial cerebrovascular resistance. DHEC exercises an inhibiting effect on the anaerobic glycolysis and on aerobic oxidation processes. It increases the cerebral blood flow and the oxygen consumption of the brain. Dihydroergocristine protects the brain against the metabolic effects of ischaemia by acting at a cellular level. In age-related modifications of the cerebral enzymatic antioxidant system DHEC increases the reduced glutathione. DHEC exercises a vasoregulating amphoteric action which depends on the initial tonus: it is hypotensive in hypertensive and normotensive animals but it is hypertensive in hypotensive animals. The results of acute and chronic toxicity in rats, dogs and monkeys, of teratogenesis and fertility in rats and rabbits and of mutagenic tests show that DHEC is a non toxic and well tolerated drug.
Animals↗
[The pharmacokinetics of dihydroergocristine after intravenous and oral administration in rats].
The pharmacokinetic properties of dihydroergocristine (DHEC, CAS 17479-19-5) were investigated in rats using a specific radioimmunoassay technique specific for non-metabolized drugs. DHEC, administered intravenously at the dose of 6 mg/kg, showed a plasma profile conforming to an open two-compartment pharmacokinetic model with a long terminal half-life (t1/2 = 13.6 h). DHEC kinetics after oral administration (6 mg/kg) showed two peaks. The first peak (C = 37 micrograms/l) occurred at the first collection point (0.5 h) indicating a quick absorption of the drug. The second peak (C = 34 micrograms/l) occurred at 2 h and may be considered an indication of an enterohepatic cycle. A long terminal half-life (t1/2 = 18.1 h) was observed. An extensive biotransformation of DHEC was indicated by an almost complete absence of unchanged drug in the urine and a high systemic clearance (2.65 l.h-1 x kg-1). A large volume of distribution (52 l.kg-1) was calculated.
Administration, Oral↗
[The pharmacokinetics of dihydroergocristine in free-will subjects after oral administration of three formulations].
This paper reports the pharmacokinetics of three dihydroergocristine (DHEC, CAS 17479-19-5) oral formulations in six volunteers. In a randomized crossover trial the volunteers received 6 mg of the drug (1 tablet of 6 mg; 3 ml of drops containing 2 mg/ml; 1 single-dose bottle containing 6 mg); radioimmunoassay was used for the determination of the unchanged drug plasma levels. DHEC shows a plasma profile according to a 3-compartment pharmacokinetic model with a long half-life and high distribution volume. The analysis of AUC0-infinity, Cmax, tmax, and other pharmacokinetic parameters shows that the three formulations investigated are practically bioequivalent.
Administration, Oral↗
HPLC method for pharmacokinetic studies on ciclopirox olamine in rabbits after intravenous and intravaginal administrations.
This paper reports a HPLC method to detect unchanged and glucuronide derivatives of ciclopirox olamine (a substituted 2-pyridone antimycotic) and gives pharmacokinetics in rabbits after i.v. and intravaginal administration. The HPLC method utilizes a RP 18 reverse phase column, a mobile phase of water and acetonitrile (60/40), a flux of 1 ml/min and wavelength of 304 nm. For the determination of free ciclopirox the plasma drug is methylated with dimethyl sulphate, extracted with n-exane, purified on Adsorbex CN and injected into the column. For the determination of total (free and glucuronide derivatives) ciclopirox the plasma is previously hydrolized with beta-glucuronidase before the application of the above procedure. In rabbits the drug is administered at 15 mg/kg for both routes; the t1/2 elim is 2.1 hours, the total clearance/F is 0.73 1.h-1 and the distribution volume/F is 2.2 1. Ciclopirox olamine, after intravaginal administration, shows low absorption (about 2%) and is mainly transformed into glucuronide derivatives.
Administration, Intravaginal↗
Simple high-performance liquid chromatographic method for the determination of PGT/1A, a new immunostimulating drug, in biological fluids.
This paper describes a simple high-performance liquid chromatographic method for the determination of PGT/1A (3-L-pyroglutamyl-L-thiazolidine-4-carboxylic acid), a new immunostimulating drug, in plasma and urine. The column was packed with LiChrospher-NH2 (5 microns), the mobile phase was 0.02 M monobasic potassium phosphate (pH 3.2 with concentrated phosphoric acid)-acetonitrile (25:75, v/v), the flow-rate was 1.2 ml/min, the detection wavelength was 210 nm and the apparatus was a Varian Model 5000. Plasma (1 ml) was added to 1.2 ml of acetonitrile and the supernatant injected; the urine was diluted 1:5. The retention time of PGT/1A was 9.4 min in plasma and 9.9 min in urine. The method was validated for recovery, accuracy and reproducibility. The results after intravenous injection in twelve volunteers are also given.
Acetonitriles↗
Pharmacokinetics of alpha-dihydroergokryptine in monkeys after oral administration.
The pharmacokinetic profile of a single dose (6 mg/kg) of alpha-dihydroergokryptine (alpha-DHEK) was established after oral administration in monkeys using a radio-immunoassay technique for non-metabolized drug. alpha-DHEK showed a plasma profile according to an open three-compartment pharmacokinetic model with a long half-life (mean = 5.787 h). The disposition of alpha-DHEK involves a fast absorption, a slow distribution phase and a slow elimination phase. alpha-DHEK showed an high total clearance and distribution volume; the drug is largely metabolized, as concluded from the very low urinary excretion.
Administration, Oral↗
Pharmacokinetics of alpha-dihydroergocryptine in rats after intravenous and oral administration.
The pharmacokinetic properties of alpha-dihydroergocryptine methanesulphonate (alpha-DHEK, CAS 19467-62-0) were investigated in rat using a radioimmunoassay technique for nonmetabolized drug. alpha-DHEK, intravenously administered at the dose of 6 mg/kg, showed a plasma profile according to an open 3-compartment pharmacokinetic model with a long half-life (about 7.56 h). The kinetics of alpha-DHEK after oral administration (6 mg/kg) showed two peaks; the second peak at 8 h was probably due to an enterohepatic cycle. The disposition of alpha-DHEK consisted in a fast absorption and a slow elimination (t1/2el about 6.78 h). The alpha-DHEK was largely metabolized as results from the complex metabolite profile in body fluids and from very low urinary elimination of unchanged drug.
Administration, Oral↗
[Protective action of some compounds against the toxicity of acetaldehyde, acrolein and formaldehyde in the rat].
The Authors report the protective activity of some compounds against the toxicity of acetaldehyde, acrolein and formaldehyde in the rat. The compounds were orally administered 30 min before and 5 hours after the toxicant aldehyde administration (acetaldehyde 2150 mg/kg os; acrolein 75 mg/kg os; formaldehyde 950 mg/kg os). L-cysteine and L-ascorbic acid showed a good protective activity against the three toxicant aldehydes. Cysteamine, BHT and propyl gallate showed activity against acetaldehyde and formaldehyde. Quercetin was active only against acetaldehyde whereas alpha-tocopherol was inactive.
Acetaldehyde↗
The effect of the cross-linking time period upon the drug release and the dynamic swelling of gelatin microspheres.
The cross-linking time period affected both the swelling and release processes of cross-linked gelatin microspheres. In the dynamic swelling procedure, the combination of both phenomena of microparticle swelling and drug diffusion produced at first the increase and then the decrease of the diameter of a loaded microsphere. The increase of the cross-linking time period produced the shift of the penetrant transport from anomalous to super-case II kinetics. This behaviour could justify the decrease of the diffusion component of the drug release as the cross-linking time period increased.
Aminophylline↗
The thyrotropin releasing hormone analogue, RGH 2202, reverses experimental haemorrhagic shock in rats.
Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 22-23 mm Hg, the rats were given an i.v. bolus injection of L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202) to be compared with thyrotropin-releasing hormone (TRH). RGH-2202, administered within 5 min following shock induction, dose dependently improved the mean arterial pressure and survival of the rats. The activity of RGH-2202 was superior to that of TRH after i.v. administration; both drugs showed a lower activity after i.m. administration.
Animals↗
[Synthesis of gallic acid derivatives with L-thiazolidin-4-carboxylic acid and study on their antiradical and antitoxic activity].
The authors report the synthesis of three new derivatives of gallic acid with L-thiazolidine-4-carboxylic acid. The new compounds were tested for radical scavenger activity against doxorubicin toxicity in mice and for antitoxic activity against acetaldehyde and formaldehyde toxicities in rats. Unlike the utilized standards, the new compounds show no activity.
Acetaldehyde↗