-
Blood May 1986Platelet transport towards the vessel wall is influenced by the hematocrit, red blood cell (RBC) size, and shape. Recent in vitro studies have indicated that RBC... (Clinical Trial)
Clinical Trial
Increased red blood cell deformability due to isoxsuprine administration decreases platelet adherence in a perfusion chamber: a double-blind cross-over study in patients with intermittent claudication.
Platelet transport towards the vessel wall is influenced by the hematocrit, red blood cell (RBC) size, and shape. Recent in vitro studies have indicated that RBC deformability may also influence platelet transport. The observation that isoxsuprine, a known vasodilating drug, caused increased RBC deformability in vitro and decreased platelet transport in vitro prompted us to study the effects of this drug in vivo. The study was performed in a double-blind cross-over study of isoxsuprine v placebo in ten patients with peripheral arterial insufficiency. RBC deformability was estimated from viscosity measurements using the blood viscosity equation of Dintenfass and expressed as T value. Platelet transport was studied in an annular perfusion chamber according to Baumgartner. Human umbilical arteries were used as blood vessels. Perfusion studies were performed with whole blood or with RBCs of the patients mixed with normal platelets and plasma at a standardized hematocrit and platelet count. An increase in RBC deformability concomitant with a decrease in platelet adherence was observed in patients on isoxsuprine with a drop in T value of approximately 0.06 (from 0.91 toward 0.86), and a concomitant decrease in platelet adherence of 20% to 40%. These observations differed significantly from the results in the placebo group and showed a significant group-period interaction at the cross-over of medication (analysis of variance). The effects on platelet adherence were observed at high vessel wall shear rate (1,800 s-1) with perfusates consisting of patients' RBCs and donor plasma and platelets at standardized hematocrit and platelet count. No differences were observed under these conditions at a shear rate of 300 s-1. When whole blood of patients was used, nonsignificant effect was observed at shear rates of 300 s-1 and 1,800 s-1. This was probably caused by the added noise due to variations in hematocrit and platelet number. These data demonstrate that isoxsuprine increases RBC deformability, and they suggest the possibility of decreasing platelet-vessel wall interaction in vivo by manipulation of RBC deformability.
Topics: Adult; Aged; Blood Platelets; Blood Viscosity; Cell Adhesion; Clinical Trials as Topic; Double-Blind Method; Erythrocyte Deformability; Hematocrit; Humans; Intermittent Claudication; Isoxsuprine; Male; Mathematics; Middle Aged; Perfusion; Platelet Aggregation; Platelet Count
PubMed: 3516258
DOI: No ID Found -
Blood Dec 1984Hematocrit and red cell size are important factors for the transport of blood platelets toward subendothelium in flowing blood. We report that red cell deformability...
Hematocrit and red cell size are important factors for the transport of blood platelets toward subendothelium in flowing blood. We report that red cell deformability also influences platelet transport. Red cell deformability was estimated with Couette-flow viscosimetry at a shear rate of 130 s-1 and expressed as a 'T' factor--a dimensionless parameter relating the relative viscosity and the hematocrit derived from the relationship: T = (1 - mu -0.4 rel)/H, where mu rel is the relative viscosity and H is the hematocrit. The normal value of T was within a narrow range (0.91 +/- 0.02). Treatment of normal red cells with isoxsuprine and chlorpromazine caused decreased rigidity and decreased T. Cholesterol loading and treatment with diamide increased rigidity and increased T. In vitro perfusion experiments in an annular perfusion system with everted human umbilical arteries were performed with perfusates to which such treated red blood cells were added to investigate their influence on platelet adherence to artery subendothelium. Platelet adherence was well correlated with red cell rigidity, with increased adherence at increased rigidity and vice versa. A change in T of 0.10 corresponded to a change in platelet adherence of approximately 50%. These effects were more pronounced at a wall shear rate of 1,800 s-1 than at 300 s-1.
Topics: Blood Platelets; Blood Vessels; Blood Viscosity; Chlorpromazine; Diamide; Erythrocyte Deformability; Erythrocyte Indices; Hematocrit; Humans; Isoxsuprine
PubMed: 6498337
DOI: No ID Found -
Ayu 2017Premature contraction of the uterus is the very first sign of premature labour, which is followed by progressive changes in cervix such as effacement and dilatation....
Premature contraction of the uterus is the very first sign of premature labour, which is followed by progressive changes in cervix such as effacement and dilatation. Four or more uterine contractions with or without pain per hour is a major biophysical predictor of preterm labour. According to the WHO statistics, every year, an estimated 15 million babies are born preterm and this number is rising. Although tocolytic agents are used to suppress premature contractions and prevent preterm labour, it is not proven to be efficacious in preventing preterm birth or reducing neonatal mortality or morbidity. As per Ayurveda, (preterm labour) results due to the malfunctioning of (a type of which is responsible for the excretory action). (medicated enema therapy) is considered the best for managing the deranged . is also indicated in (routine antenatal care) after completion of seven months of pregnancy. In this present case study, (medicated enema prepared along with milk) was administered in a 28 year old second gravida patient of 33 weeks gestation with premature contractions, wherein isoxsuprine hydrochloride proved to be ineffective. Per-rectal with 450 ml administered for 2 consecutive days was found to be effective in preventing the uterine contractions and further advancement to preterm labour. The drugs in possess antioxytocic and vasodilating properties which may effectively curtailed the progress of premature contractions.
PubMed: 30254396
DOI: 10.4103/ayu.AYU_200_17 -
Japanese Journal of Pharmacology Dec 1984Ritodrine hydrochloride (ritodrine) has been effectively prescribed for the prevention of premature labor. The present study was carried out to investigate the mode of...
Ritodrine hydrochloride (ritodrine) has been effectively prescribed for the prevention of premature labor. The present study was carried out to investigate the mode of action of ritodrine on the uterus and heart in comparison with those of isoxsuprine and isoproterenol. 1) Ritodrine (10(-8)-10(-6) M) suppressed the spontaneous motility of pregnant rat uterus and showed positive chronotropic action at the doses of 10(-6)-10(-4) M in guinea-pig atria. 2) In the Ca2+-free, K+-rich Tyrode solution, ritodrine suppressed the Ca2+ induced contracture of pregnant rat uterus, while it potentiated the carbachol induced contraction. 3) Ritodrine increased the amount of cyclic AMP in the uterus but not in heart. This action of ritodrine was suppressed by pretreatment with propranolol (10(-6) M). 4) These results suggest that ritodrine causes actions through activation of cyclic AMP production, as in the case of isoproterenol, and it acts more selectively on beta 2-adrenoceptors than on beta 1-adrenoceptors.
Topics: Adrenergic beta-Agonists; Animals; Calcium; Carbachol; Cyclic AMP; Female; Guinea Pigs; Heart Rate; In Vitro Techniques; Isoproterenol; Isoxsuprine; Myocardium; Pregnancy; Propanolamines; Rats; Rats, Inbred Strains; Ritodrine; Uterine Contraction; Uterus; Verapamil
PubMed: 6151996
DOI: 10.1254/jjp.36.477 -
Food Additives & Contaminants. Part A,... Jan 2017Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine....
Bovine teeth as a novel matrix for the control of the food chain: liquid chromatography-tandem mass spectrometry detection of treatments with prednisolone, dexamethasone, estradiol, nandrolone and seven β-agonists.
Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine. Pharmacological principles such as esterification may be applied to facilitate the administration of veterinary drugs and increase drug half-life. Prednisolone, whose therapeutic administration is regulated for food producing animals in the EU, is available in its acetate form as well as nandrolone, a banned anabolic steroid, which may be obtained as nandrolone phenylpropionate and estradiol as a benzoyl ester. While the distribution and accumulation of lipophilic and hydrophilic substances in human teeth have been well documented, studies on residues in bovine teeth are lacking. We hypothesised that analysis of bovine teeth could be used to detect both regulated and banned veterinary drugs. Steroids may be illegally used as growth promoters in food producing animals, alone or combined with β2-agonists; therefore, we developed, and validated, in accordance with the Commission Decision 2002/657/EC, two analytical confirmatory LC-MS/MS methods to detect these classes of compounds following a unique liquid extraction procedure. Finally, we analysed teeth from three male Friesian veal calves treated with intramuscular estradiol benzoate, oral prednisolone acetate or intramuscular nandrolone phenylpropionate in combination with oral ractopamine, respectively, and from seven bovines from the food chain. Teeth from treated animals were positive for their respective drugs, with the exception of nandrolone phenylpropionate. One sample from a food chain bovine was positive for isoxsuprine, one of the seven β2-agonists studied. Non-esterified forms of the steroids were not found. These results demonstrate that bovine teeth are a suitable matrix for the determination of pseudoendogenous substances or illicit administration of veterinary drugs.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Cattle; Chromatography, Liquid; Dexamethasone; Estradiol; Food Chain; Nandrolone; Prednisolone; Tandem Mass Spectrometry
PubMed: 27845609
DOI: 10.1080/19440049.2016.1252469 -
Analytica Chimica Acta Apr 2007The number of substances with beta-agonistic activity, illegally introduced in meat production or in sports doping as anabolic or beta-blocking agents is increasing....
Solubilisation and binding characteristics of a recombinant beta2-adrenergic receptor expressed in the membrane of Escherichia coli for the multianalyte detection of beta-agonists and antagonists residues in food-producing animals.
The number of substances with beta-agonistic activity, illegally introduced in meat production or in sports doping as anabolic or beta-blocking agents is increasing. Analytical methods suited for their multianalyte detection are thus necessary. In this perspective, receptor assays were developed. The research activities undertaken in this study describe the solubilisation of a recombinant human beta(2)-adrenergic receptor produced in the inner membrane of genetically modified Escherichia coli, using the detergent n-dodecyl-beta-d-maltoside. Its potential to detect the presence of beta-agonists or beta-blockers in biological samples was evaluated. The solubilised beta(2)-adrenergic receptor retained its binding affinity in a radio-receptor assay based on the competition for the binding to receptors between a ligand (beta-agonist or antagonist) and the radioligand [(125)I]iodocyanopindolol. The IC(50) values ranged from 5+/-1 x 10(-8) M (clenbuterol) to 8+/-2 x 10(-6) M (isoxsuprine) for the beta-agonists tested and from 1.5+/-0.2 x 10(-10) M (carazolol) to 1.2+/-0.2 x 10(-5) M (metoprolol) for the beta-blockers tested. It was shown to have a lower limit of detection than a radio-receptor assay using the solubilised beta(2)-adrenoceptor expressed in a mammalian cell line. The solubilised recombinant human beta(2)-adrenoreceptor expressed in E. coli would be a useful tool to develop non radioactive multianalyte screening methods.
Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Escherichia coli; Protein Binding; Receptors, Adrenergic, beta-2; Recombinant Proteins; Reference Standards; Solubility
PubMed: 17418176
DOI: 10.1016/j.aca.2007.02.057 -
The Tohoku Journal of Experimental... Feb 1981The stimulating effect of some drugs on the ripening of the uterine cervix in rats was studied by measuring the wet weight of the uterine cervix and by both light and...
The stimulating effect of some drugs on the ripening of the uterine cervix in rats was studied by measuring the wet weight of the uterine cervix and by both light and electron microscopy in nonpregnant castrated and pregnant conditions. Since the light and electron microscopic findings after estrogen (E) administration to castrated rats were similar to those found in the uterine cervix of rats at the end of pregnancy, it was concluded that E (E2 greater than or equal to E3 greater than or equal to E1) plays a major role in the ripening mechanism. It was also found that DHA-S, progesterone and relaxin had stimulating effects on cervical ripening. Oxytocin and PG (PGE2 greater than PGF2 alpha) showed the ripening activity only in pregnant condition. Moreover, oxytocin, PGE2 and PGF2 alpha potentiated the estrogen action. The effects on the increase in wet weight of the uterine cervix and microscopic findings due to DHA-S were different from E in castrated rats. It is therefore postulated that the effect of DHA-S might be mainly due to the secondary increase in E converted from DHA-S in the ovary and, in addition, to a direct effect of this medicament on the uterine cervix. There was essentially no difference in ultrastructure between the cervix of control (nonpregnant, castrated or pregnant) rats and that of rats treated with HCG, isoxsuprine hydrochloride, dihydroergotoxine, diazepam or n-butylscopolammonium bromide.
Topics: Animals; Castration; Cervix Uteri; Estrogens; Female; Microscopy, Electron, Scanning; Organ Size; Pregnancy; Prostaglandins; Pyrones; Rats
PubMed: 7268763
DOI: 10.1620/tjem.133.205 -
British Journal of Clinical Pharmacology Mar 19781 Following the observation that lymphocyte beta-adrenoceptor responsiveness was not depressed in asthmatics treated only with non-adrenergic drugs we have explored the...
1 Following the observation that lymphocyte beta-adrenoceptor responsiveness was not depressed in asthmatics treated only with non-adrenergic drugs we have explored the effects of prolonged exposure to beta-adrenoceptor agonists in normal subjects. 2 Treatment with oral salbutamol (12-16 mg/kg/day for 10 days), or with inhaled salbutamol (3000 microgram/day for 8-10 days) resulted in a significant reduction in lymphocyte beta-adrenoceptor responsiveness. 3 A 48 h infusion of isoxsuprine (10 mg/h) resulted in a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 4 Prolonged elevation of endogenous catecholamines caused by phaeochromocytoma was also associated with a marked depression of lymphocyte beta-adrenoceptor responsiveness (P less than 0.001). 5 There was no evidence that an increase in phosphodiesterase activity could explain the reduced cyclic AMP response. 6 It is concluded that diminished beta-adrenoceptor response occurs as a response to prolonged exposure to beta-adrenoceptor agonists. It is likely that the diminished response seen in asthmatic subjects can be explained on a similar basis and does not indicate an inherent cellular defect. 7 The possible clinical significance of such changes in asthmatics are discussed.
Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adrenal Gland Neoplasms; Albuterol; Cyclic AMP; Humans; In Vitro Techniques; Isoproterenol; Isoxsuprine; Lymphocytes; Pheochromocytoma; Prostaglandins E; Receptors, Adrenergic; Receptors, Adrenergic, beta
PubMed: 207293
DOI: 10.1111/j.1365-2125.1978.tb01623.x -
British Journal of Pharmacology Nov 1976
Topics: Animals; Guinea Pigs; In Vitro Techniques; Isoxsuprine; Muscle Contraction; Myocardial Contraction; Trachea
PubMed: 990617
DOI: No ID Found -
Japanese Journal of Pharmacology Jun 1970
Topics: Action Potentials; Amino Alcohols; Animals; Atropine; Cocaine; Depression, Chemical; Female; Guinea Pigs; Heart Atria; In Vitro Techniques; Male; Membrane Potentials; Norepinephrine; Potassium; Propranolol; Rats; Reserpine; Sodium; Vasodilator Agents
PubMed: 5311557
DOI: 10.1254/jjp.20.179