bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the modulating effects of temperature, albumin, pH and calcium on the free fractions of phenobarbitone and phenytoin
Authors: Melten J W , Wittebrood A J , Wemer J , Faber D B 
Published: April 2011

Abstract
The effects of temperature, albumin, pH and Ca2+ on the binding of phenobarbitone and phenytoin to human serum albumin in buffer have been investigated using equilibrium dialysis. The free fractions of both anticonvulsants were much increased by raising the temperature. Lower free fractions were observed by increasing the albumin concentration from 5–8 g litre−1 and by raising pH from 6 to 9. No significant effect on the free fractions was observed by changing (at pH 7.4) the Ca2+ concentration from 0 to 5 mM. The observed differences in free fractions at 37 °C., as determined in phosphate, borate and Krebs-Ringer buffer at pH 7.4, indicate that great care is needed in the choice of dialysis fluid for dialysis of clinical samples.
The activity of non-steroidal anti-inflammatory drugs in the rat mesenteric vasculature
Authors: Stanton Bryan J , Coupar Ian M , Burcher Elizabeth 
Published: April 2011

Abstract
Rat isolated, perfused mesenteric blood vessels have been used to determine whether non-steroidal anti-inflammatory drugs (NSAIDs) display selectivity for inhibition of vasoconstrictor responses to noradrenaline compared with those to calcium. The rank order of potency of the NSAIDs for inhibition of responses to noradrenaline was: meclofenamate &gt; flufenamate = diclofenac &gt; indomethacin &gt; fenbufen &gt; phenylbutazone &gt; ibuprofen &gt; ketoprofen &gt; naproxen &gt; paracetamol (included as an inhibitor of cyclo-oxygenase). All NSAIDs show selectivity for noradrenaline (mean selectivity molar ratio = 0.19; s.e.m. 0.15–0.23) but there was a positive correlation (r = 0.98, P &lt; 0.001) between inhibition of responses to noradrenaline and those to calcium. The depressant effect of meclofenamate and of fenbufen, the most potent and most selective in the series, respectively, on responses to noradrenaline, was completely reversed to control values by prostaglandin E2. The results support previous findings that inhibition of cyclo-oxygenase in rat mesenteric blood vessels leads to a loss of response to noradrenaline. Comparison of the present data for inhibition of responses to noradrenaline in the mesentery with published data indicates that the mesentery bears a greater similarity to other in-vitro rather than in-vivo models for screening NSAIDs.
Chronic subcutaneous treatment with acebutolol: haemodynamic effects and metabolism in spontaneously hypertensive rats
Authors: Heimburger M , Davy M , Midol-Monnet M , Beslot F , Cohen Y 
Published: April 2011

Abstract
Chronic administration of acebutolol (15 mg kg−1 s.c. three times a week for five weeks, then 30 mg kg−1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of β2 vascular receptors.
ICI 180080, a novel selective thromboxane receptor antagonist: synthesis and relative activity
Authors: Brown George R , Foubister Alan J 
Published: April 2011

Abstract
The preparation of a novel potent thromboxane receptor antagonist ICI 180080, 5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1, 3-dioxan-cis-5-yl] heptenoic acid, is described together with its methyl ether and methyl ester. Thromboxane antagonist pA2 data against U 46619 is presented for rabbit thoracic aorta in-vitro (ICI 180080, pA2 = 7.5). The relative antagonist pA2 values obtained are discussed in terms of the chemical structure of the molecules. The potent activity of ICI 180080 is attributed to a specific orientation of the phenolic oxygen, due to an intramolecular hydrogen bond.
Comparison of bioavailability in man of tamoxifen after oral and rectal administration
Authors: Tukker J J , Blankenstein M A , Nortier J W R 
Published: April 2011

Abstract
The bioavailability of tamoxifen from 40 mg suppositories was tested in six male volunteers and compared with that of tamoxifen (Nolvadex) tablets. Plasma concentrations of tamoxifen and its major metabolites, 4-hydroxytamoxifen and N-desmethyltamoxifen, were measured by extraction from plasma obtained at different times after administration, separated by HPLC, converted on-line to fluorescent phenanthrene derivatives and quantified with a fluorescence detector. The mean relative bioavailability from the suppositories was 28%; the addition of a surf active agent diminished the bioavailability to 13%. Simulation of repeated administration of 40 mg suppositories suggests a mean steady state plasma concentration for tamoxifen of approximately 70 ng ml−1, i.e. 30% of the steady state value after simulated oral administration. Rectal administration of tamoxifen leads to a lower bioavailability than that by oral administration and therefore cannot be recommended when used in equivalent doses.
The use of [3H]vasopressin for in-vivo studies of controlled delivery from an Accurel/collodion device in the Brattleboro rat
Authors: Kruisbrink J , Boer G J 
Published: April 2011

Abstract
Accurel polypropylene/collodion controlled drug-delivery devices containing 22 μg [3H]-vasopressin (VP) were implanted s.c. in VP-deficient Brattleboro rats. This caused a decrease in their urine production for at least 50 days, at which time the Accurel device was removed. Release of VP was followed by measurements of tritium radioactivity and by radioimmunoassay of VP in the urine. These parameters showed a constant pattern during the whole period. After re-implantation of the Accurel devices in another group of Brattleboro rats, release of VP continued to give the same level of urine production as during the last period of the first implantation. It is concluded that release of VP in-vivo is not influenced by encapsulation of the Accurel polymer by connective tissue, or that adaptation of the kidney adds to the maintenance of the urine production at this low level. In-vivo release rate is calculated to be about 1% of the original load each day. The in-vitro release in a flow cell system appeared to produce the same release rate which indicates that these data have a predictive value for the in-vivo situation.
Disposition of aprophen in rats
Authors: Aarbakke Jarle , Miura George A , Brown Nesbitt D , Gray Richard R , Gordon Richard K , Doctor B P , Chiang Peter K 
Published: April 2011

Abstract
The pharmacokinetics of [14C]aprophen and its distribution were determined after intravenous administration to rats. The drug was distributed rapidly with a t½ (α) of 4 min to highly perfused organs like the brain, kidney and adrenals. An elimination phase was apparent 10 min after injection with a t½ (β) of 23.5 min. The high plasma clearance of the drug was due both to a large volume of distribution and to a high metabolic rate. Aprophen could be hydrolysed to diphenylpropionic acid and diethylaminoethanol in-vivo and in-vitro. Diethylaminoethanol competed with [3H]QNB binding to muscarinic receptors of N4TG1 cells, whereas diphenylpropionic acid did not. The lower plasma concentrations and lower binding activity of diethylaminoethanol compared with aprophen indicate that unchanged aprophen is largely responsible for the in-vivo actions.
Tolerance to the anticonvulsant effect of clonazepam in mice: no concurrent change in plasma concentration
Authors: Haigh J R M , Feely M , Gent J P 
Published: April 2011

Abstract
Clonazepam was administered for 10 or more days on three different dose regimens (0.5, 0.25 and 0.08 mg kg−1 twice daily) to mice given pentetrazol by slow intravenous infusion. Plasma concentrations of clonazepam were assayed by high performance liquid chromatography. Tolerance developed to the anticonvulsant effect of clonazepam at all doses but was incomplete and could be overcome by increasing the dose. With the 0.5 and 0.25 mg kg−1 regimens there was no significant change in the drug plasma concentrations during development of tolerance; on the lowest dose, levels were below the limits of accurate detection. Anticonvulsant tolerance does not seem to be the result of a disturbance in clonazepam metabolism.
The effect of pentobarbitone anaesthesia and hypothermia on the hepatic clearance of indocyanine green and S(−)-acenocoumarol in the rat
Authors: Daemen M J A P , Thijssen H H W , Vervoort-Peters H T M , Smits J F M , Boudier H A J Struyker 
Published: April 2011

Abstract
The effect of pentobarbitone anaesthesia and the effect of hypothermia associated with the anaesthesia on the blood clearance of indocyanine green (ICG) and of S(−)-acenocoumarol (AC) was investigated in male Wistar rats using the constant rate infusion technique. During anaesthesia, body temperature was regulated by heat supply. At normothermia (rectal temperature of 37.5 °C), pentobarbitone anaesthesia decreased ICG clearance from 8.0 ± 1.7 ml min−1 (mean ± s.e.m., n = 3) in the conscious state to 4.3 ± 0.6 ml min−1 and AC clearance from 4.9 ± 0.4 ml min−1 to 3.4 ± 0.3 ml min−1. Hypothermia further reduced the clearances of the compounds to 0.9 ± 0.1 and 2.5 ± 0.2 ml min−1 for ICG and AC, respectively. The effect of hypothermia was reversible. The results show that pharmacokinetic constants obtained in the anaesthetized animal may differ greatly from those in the conscious one. If pharmacokinetic experiments are performed in the anaesthetized animal, body temperature should be controlled and a slight hyperthermia is most favourable. Our pharmacokinetic data on ICG seriously question the use of this drug to estimate liver blood flow in the rat.
The use of ordered mixtures for improving the dissolution rate of low solubility compounds&
Authors: Nyström C , Westerberg M 
Published: April 2011

Abstract
The dissolution rate of micronized griseofulvin has been investigated, both for the agglomerated raw material and the material formulated as an ordered mixture, by means of the USP XX paddle method. During the experiments, which were performed at sink condition and constant temperature, the effects of adding a surfactant and of agitation were tested. The ordered mixture with sodium chloride gave a fast dissolution rate, practically independent of the test parameters. Micronized griseofulvin alone gave dissolution profiles that were improved by adding polysorbate 80 and by increased agitation, but the dissolution rates obtained were much lower than those for the ordered mixture. It was concluded that the rate limiting step in the dissolution of griseofulvin as the raw material is the penetration of the dissolution medium into the agglomerates. With an ordered mixture, these agglomerates were deaggregated during the mixing process, producing a system in which the entire external surface area of the primary particles was exposed to the dissolution medium. This conclusion was supported by calculation of the contact surface areas taking part in the dissolution process for the systems tested. The procedure developed in this study could be applied to preformulation work where a cohesive, low solubility drug of hydrophobic nature is to be formulated.
Role of efficacy in the assessment of the actions of α-adrenoceptor agonists in rat aorta with endothelium
Authors: Malta E , Schini V , Miller R C 
Published: April 2011

Abstract
Concentration-effect curves to phenylephrine are shifted to the right in the presence of endothelium in rat aorta while responses to clonidine are practically abolished. Analysis of the concentration-effect curves showed that the effect of endothelium could possibly be explained by a reduction in relative intrinsic efficacy of the two agonists by between 3.5- and 6-fold. Published observations on the modulatory effects of agonist-induced contractions by endothelium in the rat aorta tend to support this explanation. It is further concluded that this reduction in efficacy could be related to the basal release of an endothelium-derived substance and that changes in tissue contractility in the presence of endothelium cannot necessarily be taken as evidence for a stimulated liberation of endothelium-derived products by agonists.
Presynaptic actions of piribedil on the cardiovascular system of the pithed rat
Authors: Moron A , Cuffi L , Vila E , Badia A 
Published: April 2011

Abstract
The influence of piribedil on cardiovascular sympathetic responses has been studied in the pithed rat. Piribedil (0.3–1 mg kg−1) inhibited the increases of diastolic blood pressure induced by spinal cord electrical stimulation at the level Th5-L4. This effect was reversed by sulpiride (0.3 mg kg−1) but not by yohimbine (0.3 mg kg−1). The cardiovascular responses induced by noradrenaline were unaffected by piribedil (0.3–1 mg kg−1). However piribedil (0.3–1 mg kg−1) did not modify the heart rate increase induced by spinal cord electrical stimulation at the C7-Th1 level. These results suggest that piribedil inhibits the vascular sympathetic transmission in the pithed rat via stimulation of presynaptic dopamine receptors.
Potentiation of dermorphin-induced antinociception by peptidase inhibitors
Authors: Sakurada Shinobu , Watanabe Hiromi , Sakurada Tsukasa , Andoh Ryuichiro , Kisara Kensuke , Sasaki Yusuke , Suzuki Kenji 
Published: April 2011

Abstract
We have investigated the effect of amastatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, on the antinociceptive activity induced by intracerebroventricular administration of dermorphin, a heptapeptide. In addition, the potency of dermorphin was compared with that of one of its metabolites, N-terminal tetrapeptide (Tyr-D-Ala-Phe-Gly), by using the tail pressure test. The antinociceptive activity induced by dermorphin was not potentiated by simultaneous administration of amastatin or captopril. However, there was potentiation when dermorphin was combined with both peptidase inhibitors. Moreover, the N-terminal tetrapeptide was 84 times less potent than its parent heptapeptide when administered intracerebroventricularly. The results suggest that the cleavage of Tyr1-D-Ala2 and Gly4-Tyr5 bonds by brain endopeptidase modulates dermorphin-induced antinociceptive activity.
Liver function in patients on long-term paracetamol (co-proxamol) analgesia
Authors: Hutchinson D R , Schilds A F , Parke D V 
Published: April 2011

Abstract
Eleven patients on long term co-proxamol therapy for pain, in general practice, showed no abnormalities of liver or renal function, as assessed by serum prealbumin concentrations and blood enzyme and electrolyte activities. This indicates that although the preparation is hepatotoxic when taken acutely in overdose, in chronic therapeutic dosage it appears to be free from this hazard.
Tissue atenolol levels following chronic β-adrenoceptor blockade using oral atenolol in dogs
Authors: Davies M K , McAinsh J 
Published: April 2011

Abstract
Tissue atenolol concentrations are high following chronic continuous β-adrenoceptor blockade in dogs. Furthermore, significant concentrations of this poorly lipid soluble drug are found within the central nervous system after chronic dosing. It is suggested that all β-adrenoceptor blocking agents may enter the central nervous system in significant and sufficient quantities to account for a central antihypertensive action of this group of compounds. Sequestration of β-adrenoceptor agents in the CNS or other tissues may account for other clinically observed effects including adaptive effects.
A comparison of the effects of fentanyl and alfentanil on the sleeping times of the intravenous induction agents
Authors: Dingwall A E , Pleuvry B J 
Published: April 2011

Abstract
The effect of increasing doses of fentanyl and alfentanil administered before four intravenous induction agents (thiopentone, methohexitone, Althesin and etomidate) on the sleeping time were studied in mice. A biphasic pattern of sleeping time was noted with the more rapidly metabolized and eliminated compounds. Possible explanations are discussed.
In-vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine-induced inflammation
Authors: Chindavijak B , Belpaire F M , Bogaert M G 
Published: April 2011

Abstract
In rats with inflammation induced by turpentine injection, changes in drug disposition occur in-vivo and in the perfused isolated liver. Therefore the biotransformation of a low extraction drug, antipyrine, and of two high extraction drugs, lignocaine and propranolol, has been evaluated in the 9000g supernatant fraction of the liver of turpentine-treated rats. Aminopyrine N-demethylase activity and cytochrome P450 content were also measured. Turpentine treatment significantly reduced the in-vitro breakdown of the three drugs; aminopyrine N-demethylase activity and cytochrome P450 content were also decreased. Similar results were found in the proadifen-treated rats, except that in those, the cytochrome P450 content was slightly increased. The changes in drug disposition seen after turpentine-induced inflammation, could therefore be due in part to a change in hepatic enzymatic activity.
Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat
Authors: Ishizawa Takayuki , Hayashi Masahiro , Awazu Shoji 
Published: April 2011

Abstract
A means of enhancing absorption of the antibiotic, fosfomycin, has been investigated using promoters in rat jejunum and colon. Polyoxyethylene lauryl ether (BL-9EX), saponin, the sodium salts of fatty acids and mixed micelles were effective at 1% in increasing fosfomycin absorption. Of the sodium salts of saturated medium-chain fatty acids examined, the strength of this effect was in the order caprate &gt; laurate &gt; caprylate. Mixed micelles, consisting of fusogenic lipids and sodium taurocholate, enhanced fosfomycin absorption independently of the degree of unsaturation of the lipids; their effectiveness far exceeded that of sodium taurocholate alone. The action of these promoters was more evident in the colon than in the jejunum, except for the sodium salts of bile acids and disodium ethylenediaminetetraacetate (EDTA-2Na). The effects of glycocholate and taurocholate were essentially the same at both absorption sites, but that of EDTA-2Na was much greater in the jejunum than the colon. Improved fosfomycin absorption was observed at more than 0&#x006d;̇5% sodium caprate concentrations in both the jejunum and colon. BL-9EX was effective at 0&#x006d;̇1% in the jejunum or at 0&#x006d;̇05% in the colon. The effectiveness at these low concentrations demonstrates the practicality of promoters for improving fosfomycin absorption with only minor membrane damage, especially in the colon.
Nasal administration of desmopressin by spray and drops
Authors: Harris A S , Hedner P , Vilhardt H 
Published: April 2011

Abstract
A solution of desmopressin was administered intranasally as a spray using a metered dose pump, or as drops using a single dose pipette or rhinyle catheter. Volunteers, and patients with diabetes insipidus, were given an intranasal dose of 20 μg desmopressin by each method. The antidiuretic activity was measured by determination of urine osmolality and diuresis. Each delivery system was equally effective in producing a rapid onset of activity, a highly reproducible magnitude of effect and duration of the antidiuretic effect which lasted for more than 8 h. The pipette and spray pump offer a choice of single dose administration without preservative, or for chronic use, well-controlled, reproducible dosing, respectively.
The effect of hydroxocobalamin on the nitroprusside-induced relaxation of rat aortic preparations
Authors: Hewick D S , Butler A R , Davidson A 
Published: April 2011

Abstract
Hydroxocobalamin (HOCb) when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio had no significant effect on the relaxation of noradrenaline-pre-contracted rat aortic rings. However, the addition of HOCb did prolong the time taken for the relaxant response to occur. The time taken for a 0&#x006d;̇34 μM SNP dose to exert 50% of its relaxant effect was increased by about 120 and 35% with 10:1 and 1:1 HOCb/SNP molar ratio mixtures, respectively. A 0&#x006d;̇5:1 HOCb/SNP molar ratio mixture caused no prolongation. In incubations with [14C]SNP, it was found that mixing with equimolar, or greater, amounts of HOCb, reduced aortic tissue uptake of radioactivity. The results support the hypothesis that both SNP alone and SNP/HOCb complexes breakdown extracellularly to release the same amount of active species, but that in the case of the complexes the active agent is released at a slower rate.
Cross-tolerance development to the prolongation of pentobarbitone-induced sleep by Δ8-tetrahydrocannabinol and 11-hydroxy-Δ8-tetrahydrocannabinol in mice
Authors: Watanabe K , Narimatsu S , Yamamoto I , Yoshimura H 
Published: April 2011

Abstract
Repeated administration (5 mg kg−1 day−1 i.v.) of Δ8-tetrahydrocannabinol and its active metabolite, 11-hydroxy-Δ8-tetrahydrocannabinol caused tolerance to develop to their prolonging effect on pentobarbitone-induced sleep in mice. Reciprocal cross-tolerance also developed after seven daily doses of these cannabinoids. The magnitude of the tolerance developed by the metabolite was greater than that by Δ8-tetrahydrocannabinol. The results suggest that 11-hydroxy-Δ8-tetrahydrocannabinol plays an important role both in the sleep-prolonging effect of Δ8-tetrahydrocannabinol and its tolerance development.
Extraordinary postmortem stability of kappa opioid receptors in guinea-pig brain
Authors: Ori Carlo , Su Tsung-Ping , Weissman Arthur D , London Edythe D 
Published: April 2011

Abstract
Postmortem delay can be an important variable in biochemical studies on autopsy tissue. We subjected guineapig brains to gradual cooling, simulating temperature conditions of human postmortem brains, in order to assess the sensitivity of kappa receptors to postmortem degradation. Kappa receptor specific binding was defined as the (-)-[3H]ethylketocyclazocine bound in the presence of 100 nM D-ala2-D-leu5-enkephalin and 30 nM morphine. Postmortem delays of up to 16 h did not alter the affinity or density of kappa binding sites. The remarkable stability of kappa receptors may greatly facilitate the study of this opioid receptor subtype in human brain.
The characterization of the mechanical properties of microcrystalline cellulose: a fracture mechanics approach
Authors: Mashadi Ali B , Newton J M 
Published: April 2011

Abstract
The mechanical properties of compressed beam specimens of microcrystalline cellulose (Avicel pH 101) have been assessed in terms of the tensile strength (σt), Young's modulus (E) and the following fracture mechanics parameters: the critical stress intensity factor (KIC), the critical strain energy release rate (GIC) and the fracture toughness (R). Increase in the compaction pressure used to form the beams resulted in compacts with higher values of tensile strength, Young's modulus, KIC, GIC and R, indicating that the compacts became less brittle as their porosity decreased. Extrapolation of the values of σt, E, KIC, GIC and R to provide values at zero porosity indicated that the material had values of 30 Nm m−2, 0&#x006d;̇0103 GPa, 1&#x006d;̇21 MN m−3/2, 1&#x006d;̇98 times 102 Nm−1 and 2&#x006d;̇19 times 103 Nm−1, respectively. These provide a range of values whereby a fuller characterization of the mechanical properties of pharmaceutical materials can be made.