bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of 17β-oestradiol or testosterone on the response to S-warfarin in castrated male rats
Authors: Winn M J , Park B K 
Published: April 2011

Abstract
The effects of castration alone, or followed by administration of 17β-oestradiol or testosterone, on the action of S-warfarin have been investigated in male Wistar rats castrated at 4 weeks of age. Six to 10 weeks later, blood samples were taken before, and at 24 h and 7 days after onset of administration of either 17β-oestradiol (50 to 500 μg kg−1 day−1 i.p.), testosterone (500 μg kg−1 day−1 i.p.), or vehicle (polyethylene glycol 200 i.p.). On the seventh day of these interventions, S-warfarin (6.3 mg kg−1 i.p.) was given; prothrombin complex activity (PCA) was then measured over the next 72 h. In addition, a group of sham-operated rats were given S-warfarin, alone. The control prothrombin times were lower in castrated rats (17&#x006d;̇9 ± 0&#x006d;̇4 s) than in sham-operated rats (19sham-operatedl ± 0&#x006d;̇6 s). Warfarin, over the first 24 h of its administration, caused a significant (P &lt; 0&#x006d;̇01) fall in PCA in each group of rats, the fall PCA in castrated rats pretreated with vehicle being significantly (P &lt; 0&#x006d;̇05) less than that seen in the sham-operated rats. The fall was the same in castrated rats given vehicle or those given 17β-oestradiol. In contrast, warfarin caused a greater fall in PCA in the presence of testosterone than in the other groups of castrated rats.
The twin impinger: a simple device for assessing the delivery of drugs from metered dose pressurized aerosol inhalers
Authors: Hallworth G W , Westmoreland D G 
Published: April 2011

Abstract
The development is described of the twin impinger, a two-stage separation device for assessing the drug delivery from metered dose inhalers and other oral inhalation delivery devices. The discharged aerosol is fractionated by firing through a simulated oropharynx and then through an impinger stage of defined aerodynamic particle size cut-off characteristics. The fine (pulmonary) fraction which penetrates is collected by a lower impinger. It is demonstrated that this device is able to assess individually the fine particle delivery of both components of two-drug aerosols. Formulations showing undue agglomeration or serious crystal growth of drug are readily detected. The twin impinger is shown to be a valuable device for routine quality assessment of aerosols during product development, stability testing and for quality assurance and comparison of commercial products.
Influence of cardiopulmonary resuscitation on plasma concentrations of nimodipine in the dog
Authors: Huyghens L P , Rosseel M T , Calle P A , Buylaert W A 
Published: April 2011

Abstract
The influence of cardiopulmonary resuscitation on the plasma concentrations of nimodipine in the anaesthetized dog has been examined. Nimodipine was given as a bolus injection followed by a maintenance infusion. When, during the maintenance infusion, the dogs were subjected to cardiac arrest followed by external cardiac massage combined with artificial ventilation (basic life support), a fast and almost threefold increase in the steady-state plasma concentrations of nimodipine was observed. When the maintenance infusion of nimodipine was stopped immediately before cardiac arrest and basic life support, the nimodipine concentrations decreased. These results indicate that during basic life support, there is a decreased transfer of infused nimodipine from plasma to the tissues. This is also supported by the fact that for antipyrine, a drug with a smaller volume of distribution than nimodipine, the increase in plasma concentrations when infused during cardiac arrest and basic life support, was much smaller. When nimodipine was started after restoration of the spontaneous circulation (advanced life support) in dogs that had been subjected to cardiac arrest and basic life support, the plasma concentrations were not significantly higher than in control dogs. It can be concluded that the fate of nimodipine is markedly altered during basic life support but not in the period following restoration of spontaneous circulation.
Effect of inflammation and proadifen on the disposition of antipyrine, lignocaine and propranolol in rat isolated perfused liver
Authors: Chindavijak B , Belpaire F M , Bogaert M G 
Published: April 2011

Abstract
The effect of inflammation, induced in rats by injection of turpentine oil, on drug disposition has been evaluated in rat isolated perfused livers. The drugs studied were a low extraction drug, antipyrine, and two high extraction drugs, lignocaine and propranolol. Turpentine significantly increased the half-life of antipyrine and of propranolol, but not that of lignocaine. Proadifen (SKF 525A) significantly increased the half-life of all three drugs. Turpentine decreased the clearance of antipyrine significantly by about 50% and that of propranolol non-significantly by about 20%, but did not affect the clearance of lignocaine. Proadifen significantly decreased the clearance of all three drugs, but this was most pronounced for antipyrine. In both turpentine- and proadifen-treated rats a significant increase in volume of distribution of propranolol was observed. The results show that, as with proadifen, turpentine-induced inflammation affects the hepatic clearance of antipyrine in the rat isolated perfused liver. With both high extraction drugs, the effect of inflammation on their clearance was low or absent, in contrast to the effect of proadifen. This suggests that a possible effect of inflammation on intrinsic clearance is not large enough to influence the hepatic clearance of the high extraction drugs.
Adenosine reduces agonist-induced production of inositol phosphates in rat aorta
Authors: Long C J , Stone T W 
Published: April 2011

Abstract
In rat aortic strips rendered permeable with digitonin, inositol trisphosphate induced an efflux of 45Ca from the tissue. This release was not affected by adenosine. In tissues not treated with digitonin the contents of inositol trisphosphate (IP3) and its metabolite inositol 1-phosphate (IP1***) were significantly enhanced by noradrenaline in the lithium-treated rat aorta. Adenosine was without effect on levels of IP1 or IP3 in tissues which had not been pretreated with noradrenaline, however, the noradrenaline-enhanced tissue content of IP1 was reduced by adenosine in a dose-dependent manner. The reduction in IP1 content by adenosine was enhanced by the uptake blocker dipyridamole (10 μM) and was blocked by the adenosine receptor antagonist 8-phenyltheophylline (10 μM). Adenosine may therefore lower production of inositol phosphates and thus reduce the stimulated release of calcium from intracellular stores. It is proposed that a reduction in phosphatidylinositol turnover may play a role in adenosine-mediated relaxation of blood vessels.
The effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on guinea-pig uterine microflora
Authors: Malhi J S , Gard P R , Hanlon G W , Marriott C 
Published: April 2011

Abstract
This study used guinea-pigs as a mammalian model to investigate the effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on the integrity of the cervical mucus plug. It was shown that under normal circumstances the uterus is sterile, but following drug administration microorganisms began to appear in the uterus with no significant effect on the vaginal microbial population. It therefore appears that these two mucolytic agents may reduce cervical mucus viscoelasticity. After the animals had been mated, microorganisms were isolated from the uterus even in the absence of drug treatment.
Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice
Authors: Parmar N S , Tariq M , Ageel A M 
Published: April 2011

Abstract
The effect of proglumide ((±)-4-benzamido-N,N-dipropylglutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg−1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists.
Nitrates do not affect prostacyclin formation by rat arteries: this is unrelated to increased vascular prostacyclin formation with age
Authors: Bennett A , Melhuish P B , Stamford I F 
Published: April 2011

Abstract
The question of whether vasodilator nitrates act by releasing prostacyclin is controversial. Since the ability of blood vessels to form prostacyclin changes with age, we have investigated whether this may explain the discrepancies in the literature. It does not, since isosorbide dinitrate or glyceryl trinitrate incubated with rat aorta or vena cava from male Wistar rats had little or no effect on the release of prostacyclin, measured as 6-keto-PGF1α. We confirm that the aorta produces substantially more prostacyclin than the vena cava. The arterial production of prostacyclin was greater in rats weighing 350-400 g than in those weighing 116-152 g, but the production by the veins was similar in both groups.
Spectrophotometric study of the photodecomposition kinetics of nifedipine
Authors: Majeed Ibraheem A , Murray Wallace J , Newton David W , Othman Sadeq , Al-turk Walid A 
Published: April 2011

Abstract
Nifedipine is a photosensitive compound. Irradiation for 4 h under a fluorescent lamp placed 30 cm from a solution of nifedipine in 95% ethanol leads to complete photo-oxidation as determined spectrophotometrically. The disappearance of the reduced form and appearance of the oxidized form is best described by zero-order kinetics at concentrations higher than 4 times 10−4 M. At lower concentrations pseudo-first order kinetics are followed. Monochromatic irradiation of nifedipine at wavelengths 400 to 700 nm in 25 nm increments showed no change in the absorbance at 280 nm, and, except for a hyperchromic effect at 237 nm, no other spectral changes were observed. Its photo-oxidation was dependent on the intensity of light and increased exponentially as solutions were irradiated progressively closer to a fluorescent light source. The pH studies showed that aqueous solutions of nifedipine photo-oxidized fastest at pH 2.
Guanethidine N-oxidation in human liver microsomes
Authors: McManus M E , Davies D S , Boobis A R , Grantham P H , Wirth P J 
Published: April 2011

Abstract
The capacity of human liver microsomes to N-oxidize guanethidine from 25 subjects has been assessed. Guanethidine N-oxidation was optimal at pH 8&#x006d;̇5 and proceeded at only 16% of the maximal rate at pH 7&#x006d;̇4. The mean rates of guanethidine N-oxidation at pH 8&#x006d;̇5 and 7&#x006d;̇4 were 2&#x006d;̇46 ± 0&#x006d;̇89 (mean ± s.d., n = 25) and 0&#x006d;̇38 ± 0&#x006d;̇22 (mean ± s.d., n = 22), respectively. Interindividual differences in the rate of guanethidine N-oxidation at pH 8&#x006d;̇5 and 7&#x006d;̇4 were 17- and 11-fold, respectively. The cytochrome P450 inhibitors, proadifen and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), at both pH 8&#x006d;̇5 and 7&#x006d;̇4 caused less than 20% reduction in the rate of guanethidine N-oxidation by human liver microsomes. These data indicate that guanethidine N-oxidation can be used as a measure of flavin-containing monooxygenase activity in human liver.
Tomoxetine and the stereoselectivity of drug action
Authors: Oberlender Robert , Nichols David E , Ramachandran P V , Srebnik Morris 
Published: April 2011

Abstract
The phenoxypropylamine derivative tomoxetine has been shown to inhibit noradrenaline (NA) uptake into synaptosomes from rat hypothalamus (Wong et al 1982). Differences in the potencies of the resolved optical isomers, (-)-tomoxetine (I) and (+)-tomoxetine were also noted, the (-)-isomer being more potent than the racemate or the (+)-isomer in-vitro and in-vivo.
Antinociceptive effects of (±)-, (+)- and (-)-nefopam in mice
Authors: Fasmer O B , Berge O-G , Jørgensen H A , Hole K 
Published: April 2011

Abstract
The antinociceptive activity of (±)-, (+)- and (-)-nefopam in mice has been examined using the hot-plate, formalin and tail-flick tests. Nefopam was administered by the intraperitoneal, intracerebroventricular (i.c.v.) and intrathecal (i.th.) routes. Intraperitoneal injection of (±)-nefopam (10–20 mg kg−1) had powerful analgesic effects in the hot-plate and formalin tests. In the tail-flick test it produced a weak, but significant elevation of the response latencies. In spinalized animals, however, the effect was abolished, indicating that nefopam prolonged the tail-flick latencies by activation of descending pain-modulating pathways. (±)-Nefopam (5–20 μg) elicited analgesia in the hot-plate test after i.c.v. or i.th. injection. These findings suggest that nefopam has both a spinal and a supraspinal site of action. (+)-Nefopam was significantly more potent than (-)-nefopam after both systemic and central administration.
Effects of nicorandil and verapamil, antianginal agents, on plasma digoxin concentrations in rats and dogs
Authors: Hinohara Y , Yamazaki T , Kuromaru O , Homma N , Sakai K 
Published: April 2011

Abstract
The effects of equihypotensive doses of nicorandil and verapamil on plasma digoxin concentrations have been assessed in rats and dogs. In a single digoxin dose study, digoxin (1 mg kg−1) alone, or in combination with nicorandil (5 mg kg−1) or verapamil (25 mg kg−1) was given orally to rats. When given chronically to rats, a single dose of digoxin (1 mg kg−1) orally for 7 consecutive days was followed, on day 8, by digoxin alone, or together with nicorandil (5 mg kg−1) or verapamil (25 mg kg−1). In dogs, a loading dose of digoxin (50 μg kg−1) was given orally on day 1, then 25 μg kg−1 was administered for the following 6 days. On day 8, digoxin (50 μg kg−1) was given with nicorandil (5 mg kg−1) or verapamil (20 mg kg−1). In rats, the AUC0–24 and Cmax of plasma digoxin were enhanced significantly by coadministration of verapamil, but not by nicorandil. In dogs, verapamil significantly increased the Cmax of plasma digoxin, but not the AUC. Nicorandil had no effect on either parameter.
Studies on the mechanisms of action of activated charcoal on theophylline pharmacokinetics
Authors: Mckinnon R S , Desmond P V , An P J Harm , Kamm M , Ghabrial H , Martin C J , Mashford M L 
Published: April 2011

Abstract
Oral administration of repeated doses of activated charcoal to volunteers and dogs significantly increased the systemic clearance of intravenously administered theophylline and decreased its elimination half-life. This effect is most likely to be due to theophylline entering the gut and being adsorbed onto the charcoal. The mechanism by which intravenously administered theophylline enters the gut has been examined. Its biliary excretion after intravenous administration to patients with T-tube biliary drainage accounted for 0ṁ28% of the dose and a similarly small biliary excretion was found in dogs. In the latter total biliary diversion had no effect on the clearance or half-life of theophylline after intravenous administration. In two dogs the theophylline content of jejunal aspirate was comparable with that of simultaneously withdrawn venous plasma samples. These results suggest that the presence of charcoal in the gut represents a sink adsorbing theophylline entering the lumen by diffusion across the intestinal wall, and by this mechanism it increases clearance of the drug even after intravenous administration.
Measurement ex-vivo of the inhibition of fatty acid biosynthesis by bezafibrate administration in different rat tissues
Authors: Ayala Antonio , Machado Alberto 
Published: April 2011

Abstract
The action of bezafibrate on fatty acid biosynthesis pathways has been examined in rat tissues. The drug abolished the induction of fatty acid synthesis that occurs on refeeding the animals with a high carbohydrate diet and by insulin administration in liver and adipose tissue. The rates of fatty acid biosynthesis in these tissues were estimated from the incorporation of 3H into lipids from 3H2O.
Gastric mucosal cytoprotection in the rat by cysteine
Authors: Salim Aws S 
Published: April 2011

Abstract
The free radical scavengers methyl-methionine sulphonium bromide and cysteine (5%) protected the rat gastric mucosa against ischaemic injury produced by reserpine (5 mg kg−1 i.p.). Pretreatment with 1 mL of 5% cysteine by gavage completely protected against injury rats with no ligation and 70% of rats with pyloric ligation after they had been given aspirin (200 mg kg−1 by gavage), a dose that produced gastric mucosal injury in 40% of rats with no ligation and 70% of rats with pyloric ligation after 4 h. Ethanol (1 mL of 40% solution by gavage) after 1 h produced gastric mucosal injury in all animals and pretreatment with 1 mL of 5% cysteine by gavage completely protected 80% of non-ligated and 70% of pyloric-ligated rats against this injury. This protection was not associated with any significant effect on H+ output. The data suggest that cysteine maintains gastric mucin by a mechanism independent of acid secretion.
Structural and conformational analogy between cholecystokinin and ergopeptines
Authors: Hughes Richard A , Andrews Peter R 
Published: April 2011

Abstract
The central nervous system (CNS) peptide cholecystokinin (CCK) and the ergopeptine alkaloids exhibit common pharmacology in the brain, particularly via catecholaminergic systems. We report here structural similarities between CCK and the ergot alkaloids, and the subsequent conformational analysis of the peptide undertaken to establish whether or not a three-dimensional relationship exists between the compounds. Two low-energy conformations of CCK that mimic the ergopeptine ergotamine are identified, one arising from an X-ray crystal structure and the other from a Dreiding model-based, computer-assisted search. The pharmacological, structural and conformational observations strongly support the hypothesis that CCK and the ergopeptines share common sites of action in the CNS.
Problems of haemoglobin freeze-drying: evidence that water removal is the key to iron oxidation
Authors: Labrude Pierre , Chaillot Bernard , Vigneron Claude 
Published: April 2011

Abstract
Formation of methaemoglobin during freeze-drying of oxyhaemoglobin raises the question of the cause and mechanism of the oxidation. Haemoglobin with or without lyoprotector (250 mM glucose or amino acid salt) has been subjected to freeze drying changes in either or both of two constraints—vacuum and rise in temperature. A rise in temperature from -40 to +10°C had no substantial denaturing effect on haemoglobin whether protected or not. Maintenance of a vacuum over frozen haemoglobin for 18 h often produced subtotal desiccation. Unprotected haemoglobin was partially oxidized (39% MetHb) whereas protected haemoglobin was not (&lt;4% MetHb). Haemoglobin was also dried by rapid dehydration of thin films in a stream of air at room temperature (20 °C). The methaemoglobin content was then 43% whereas the amino acid salt or glucose limited it at 4 and 7%, respectively. Haemoglobin is oxidized, therefore, only because of the removal of water. Protectors, not specific in structure and action, probably work by holding or reinforcing the critical number of hydration layers around haemoglobin.
Comparative studies with the enantiomers of the glycol metabolite of propranolol and their effects on the cardiac β-adrenoceptor
Authors: Ogg G D , Neilson D G , Stevenson I H , Lyles G A 
Published: April 2011

Abstract
The two enantiomers ((R)- and (S)-) of propranolol glycol, a metabolite of propranolol, have been synthesized, and their effects upon the β-adrenoceptor studied by two methods. The ability of these compounds to antagonize the inotropic actions of isoprenaline was examined on spontaneously beating rat atrial preparations. Also, the effects of these enantiomers upon the binding of [3H]dihydroalprenolol to β-receptors in rat cardiac ventricular membranes was studied. Experiments with the atria indicated that the (S)-glycol was a reversible competitive antagonist of isoprenaline with a potency approximately one thousand times lower than that of (±)-propranolol. In contrast, the (R)-glycol appeared to act as an irreversible antagonist, producing complex dose-response curves. The effects of these compounds to cause displacement of alprenolol binding were consistent with the organ bath data. The interaction of the (S)-glycol with the β-receptor binding site was reversible (Ki of 27&#x006d;̇6 ± 4&#x006d;̇2 μM) but less potent than that of (±)-propranolol (Ki of 0&#x006d;̇99 ± 0&#x006d;̇07 nM). On the other hand, pretreatment of ventricular membranes with the (R)-glycol, followed by extensive washing techniques, resulted in alprenolol binding which did not regain control values, providing further evidence for an irreversible effect upon the β-receptor. The possible significance of these pharmacological actions of the two enantiomers is discussed in terms of the in-vivo metabolic pathways for propranolol.
Dose-related inhibition of the drug-metabolizing enzymes of rat liver by the pyrrolizidine alkaloid, monocrotaline
Authors: Dalvi R R 
Published: April 2011

Abstract
Adult, male Sprague-Dawley rats were given 0, 10, 20, 40 or 80 mg kg−1 of monocrotaline intraperitoneally and the following toxicity parameters determined 24 h post treatment. Compared with the control none of the doses caused significant change in either the relative liver weight or the hepatic microsomal protein concentration. Microsomal cytochrome P450 content and activities of benzphetamine N-demethylase and aniline hydroxylase did not differ from the control at 10 or 20 mg kg−1 dosage. But, there was a significant loss of cytochrome P450 at 40 and 80 mg kg-1 dosages and decrease in the activity of the two enzymes only at the highest dose. Similarly, the highest dose caused a marked elevation of serum sorbitol dehydrogenase and glutamic pyruvic transaminase activity suggestive of severe liver damage.