bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasorelaxant Effect of Trapidil on Human Basilar Artery
Authors: Okumura Reiko , Hatake Katsuhiko , Wakabayashi Ichiro , Suehiro Akira , Hishida Shigeru , Kakishita Eizo 
Published: April 2011

Abstract
We have investigated the vasorelaxant effect of trapidil on human isolated basilar artery. Trapidil (10−5-10−4 m) dose-dependently caused relaxation in vascular strips with or without endothelium, with no significant difference between the two types of strips. The relaxation responses were not inhibited by atropine, propranolol or methylene blue. Trapidil increased the concentration of 6-keto-PGF1α, a prostacyclin degradation product, released from an artery ring in the incubation medium, but trapidil-induced relaxation was not inhibited by indomethacin. Pretreatment of vascular strips with 10−5 m trapidil increased the relaxation responses to forskolin and dibutyryladenosine cyclic monophosphate but not to sodium nitroprusside or 8-bromoguanosine cyclic monophosphate. Trapidil induced a significant increase in the cAMP concentration but not in the cGMP concentration in artery strips. These results suggest that the relaxation response to trapidil is not caused by prostacyclin release or an increase in cGMP in the smooth muscle, but possibly by an increase in the cAMP levels, probably via an inhibitory effect on cAMP phosphodiesterase.
Failure of Verapamil and Diltiazem to Attenuate the Pressor Response to Hypothalamic Stimulation: A Possible Mechanism
Authors: Eferakeya Adego E , Osunkwo Uche A 
Published: April 2011

Abstract
The effects of verapamil or diltiazem on pressor responses to posterior hypothalamic stimulation, injected noradrenaline or tyramine were studied in urethane-anaesthetized normotensive, deoxycorticosterone acetate (DOCA), renal and spontaneously hypertensive rats at the early and established phases of hypertension. Pressor responses to the pressor stimuli were significantly enhanced in the early and established phases of hypertension when compared with the normotensives. While the magnitude of pressor responses in the established phase of renal or spontaneously hypertensive rats was significantly higher (P &lt; 0·05) than the corresponding value in the early phase, in contrast, the pressor response in the early phase of DOCA hypertension was significantly higher than that of the established phase. Verapamil or diltiazem significantly (P &lt; 0·005) inhibited pressor responses to injected noradrenaline or tyramine in all groups of rats but not that to hypothalamic stimulation, irrespective of the stage of hypertension. When the probable mechanism of the hypothalamic pressor response's resistance to the calcium antagonists was studied in-vitro, ATP significantly (P &lt; 0·005) inhibited the relaxant effect of the calcium antagonists in the rat aortic strips. Our data indicate that verapamil or diltiazem is ineffective in inhibiting the pressor response to posterior hypothalamic stimulation. The probable mechanism of the resistance and the clinical implication of the findings are discussed.
Iontophoretic permeation of sodium cromoglycate through synthetic membrane and excised hairless mouse skin
Authors: Li L C , Vu N T , Allen L V 
Published: April 2011

Abstract
The iontophoretic transport properties of sodium cromoglycate were characterized using a synthetic membrane and excised hairless mouse skin. The permeation rate of sodium cromoglycate through the synthetic membrane was found to be linearly dependent on the density of electrical current applied. Passive diffusion through the excised hairless mouse skin was not demonstrated for sodium cromoglycate; however, under iontophoresis, an appreciable permeation was exhibited by the drug through the animal skin, which was also found to be a function of the electrical current density.
Ageing influences haloperidol-induced changes in the permeability of the blood-brain barrier in the rat
Authors: Saija A , Princi P , Imperatore C , De Pasquale R , Costa G 
Published: April 2011

Abstract
The effect of the dopaminergic antagonist haloperidol on the permeability of the blood-brain barier (BBB) to [14C]α-aminoisobutyric acid was studied in 10–12- and 28–30-week old rats. Following the intraperitoneal injection of haloperidol (1 mg kg−1), an increase in the permeability of the BBB, with respect to younger animals, was observed within the occipital cortex, striatum, hippocampus and hypothalamus in the older rats. No correlation was found between haloperidol-induced changes and age-related differences in the permeability of the BBB. Such age-associated increase in the vulnerability of the BBB when challenged with haloperidol might be related to a deterioration of the dopaminergic control of cerebrovascular permeability.
Similar effects of nifedipine and hydralazine on anaesthesia and hypermotility induced by pentobarbitone in mice
Authors: Sansone Mario , Pavone Flaminia , Battaglia Mario , Daniel Władysława , Vetulani Jerzy 
Published: April 2011

Abstract
Nifedipine, a dihydropyridine calcium channel blocker, and hydralazine, a non-calcium channel antagonist vasodilatator, enhanced pentobarbitone-induced sleeping time and reversed locomotor hyperactivity induced by a subhypnotic dose of the barbiturate in mice. The similarity of the behavioural effects, exerted by nifedipine and hydralazine, suggest that haemodynamic factors may play an important role in the interaction of calcium channel antagonists with barbiturates.
Effect of Theophylline on the Intestinal Clearance of Drugs in Rats
Authors: Bair Chi-Horng , Huang Jin-Ding 
Published: April 2011

Abstract
Intestinal eχsorption of salicylic acid, urea and quinidine was measured during the perfusion of the rat intestinal lumen with Tyrode solution. The intestinal clearance (CLi) of the three compounds was measured by dividing the rate of appearance in the intestinal luminal perfusate by the plasma concentration of the compound. Co-administration of theophylline (0 −2 mg h−1) with the test agents increased the CLi of salicylic acid, did not alter the CLi of urea, but decreased the CLi of quinidine. The effect of theophylline on the CLi of quinidine was enhanced with increasing dose. Theophylline was found to increase microclimate-pH at the intestinal surface, but the magnitude of ΔpH alone could not explain the effect of theophylline on the CLi of quinidine. The data, together with previous observations, suggest that the intestinal eχsorption of drugs was affected by the microclimate pH and by the unstirred water layer. Theophylline affects CLi of salicylic acid and quinidine partly by increasing the microclimate pH of the intestine. Theophylline may also affect quinidine CLi by inhibiting the carrier-mediated pathway.
Effects of Calcium Antagonists on Rat Normal and Skinned Fundus
Authors: Burchés E , Cortijo J , OróN J D , Ortiz J L , Morcillo E J 
Published: April 2011

Abstract
Calcium chloride (CaCl2) (0·1−25 Mm, in K+-depolarized tissue), KCl (10−112 Mm) and acetylcholine (1 × 10−9 m−1 Mm) produced concentration-dependent contractions of rat isolated fundus. Verapamil (0·01−100 μm), cinnarizine (1−100 μm), trifluoperazine (10−500 μm) and dantrolene (50−250 μm) each produced a concentration-related rightward and downward shift of the log concentration-effect curve for CaCl2. The rank order of potencies of these antagonists, measured as the IC50 against Ca2+ (25 Mm)-induced contraction of depolarized fundus, was verapamil (2.5 μm) &gt; cinnarizine (8·7 μm) &gt; trifluoperazine (85·1 μm) &gt; dantrolene (&gt; 250 μm). Cinnarizine (0·5 Mm) and trifluoperazine (0·5 Mm), but neither verapamil nor dantrolene depressed Ca2+ (20 μm)-evoked contraction of rat skinned fundus preparations. In intact preparations of rat fundus, verapamil had greater inhibitory effects on contractions produced by KCl than against those elicited by acetylcholine while trifluoperazine depressed to the same extent the responses to these two spasmogens. Dantrolene was without effect on contractions elicited by KCl or acetylcholine. Cinnarizine inhibited acetylcholine-induced responses but enhanced contractions to KCl. Augmentation of KCl-induced responses by cinnarizine is resistant to verapamil (1 μm). This enhancing effect of cinnarizine was not observed for KCl-induced contraction of guinea-pig fundus or rat gastro-oesophageal sphincter. In the rat fundus, cinnarizine (1−100 μm) produced an additional and concentration-related contraction when added on the plateau contraction to KCl (100 Mm). The enhancing effect and the direct contraction produced by cinnarizine are at least partly dependent on extracellular Ca2+. It is concluded that distinct differences exist between the calcium antagonists examined. The action of verapamil is restricted to the plasmalemma whereas cinnarizine and trifluoperazine also act on the intracellular contractile machinery. Dantrolene is scarcely effective as a calcium antagonist in rat fundus.
Compatibility study between acetylcysteine and some commonly used tablet excipients
Authors: Kerc̆ J , Src̆ic̆ S , Urleb U , Kanalec A , Kofler B , s̆Mid-Korbar J 
Published: April 2011

Abstract
Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), HPLC and TLC were used to investigate the interactions between the mucolytic drug acetylcysteine and a number of commonly used tablet and capsule excipients. Acetylcysteine was found to be compatible with micro-crystalline cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch, saccharose and magnesium stearate. Acetylcysteine thermal stability (onset degradation temperature) was decreased in mixtures with corn starch, magnesium stearate, saccharose and lactose. Interactions of acetylcysteine with lactose, PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC and studied in detail with FT-IR, HPLC and TLC. The results suggest that acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded during storage at conditions of high temperature and humidity.
Polyethylene glycol: its adverse gastric effects in rats
Authors: Cho C H , Hui W M , Liao N X , Liu X G , Lam S K , Ogle C W 
Published: April 2011

Abstract
The effects of polyethylene glycol (PEG) on gastric function and on lesion formation, evoked by topical applications of absolute ethanol to an ex-vivo stomach chamber preparation have been examined. Parenteral injection (i.p. or s.c.) of PEG with different molecular weights (PEG 300, 400 or 4000), dose-dependently reduced the gastric mucosal blood flow and volume of gastric secretion; these effects were greater in rats given PEG by the i.p. route, which also lowered acid output. Topical application of 1·5 mL absolute ethanol produced severe gastric mucosal injury, which was exacerbated by PEG; this lesion-aggravating effect was higher in the i.p.-injected groups. These findings indicate that when PEG is given by injection, it can adversely affect gastric function and increase the damaging action of alcohol. It is suggested that the use of PEG as a vehicle for injection should be re-assessed.
MK−801 antagonizes the lethal action of centrally and peripherally administered cypermethrin in mice and rats
Authors: Chugh Vati , Sankaranarayanan A , Sharma P L 
Published: April 2011

Abstract
The present study investigated the effect of MK−801, an N-methyl-d-aspartate antagonist, on the convulsant lethal action of cypermethrin administered centrally or peripherally. Cypermethrin produced severe convulsions and death in a dose-dependent manner. MK−801 (0·5, 1 and 2 mg kg−1, intraperitoneally) significantly increased the onset time of convulsions and decreased the mortality in the peripherally treated cypermethrin group. MK-801 (1·0 and 2·0 mg kg−1) attenuated the convulsant action of cypermethrin (50 μg, intracerebroventricularly) significantly. Survival rate was also increased significantly. However, MK−801 (0·5 mg kg−1) did not produce any significant protective effect against centrally administered cypermethrin. These results suggest excitatory amino acids to be a target for pyrethroid-induced neurotoxicity.
Epi-fluorescence Microscopy and Image Analysis Used to Measure Diffusion Coefficients in Gel Systems
Authors: Henry B T , Adler J , Hibberd S , Cheema M S , Davis S S , Rogers T G 
Published: April 2011

Abstract
A method using epi-fluorescence microscopy and image analysis has been developed to follow and quantify the diffusion of fluorescent compounds through gels. Two mathematical approaches were employed to calculate diffusion coefficients. The spatial resolution provided by the fluorescence microscope allowed diffusion to be followed over very short distances; accordingly diffusion coefficients were obtained within minutes, even for slowly diffusing systems. The method was successfully applied to the diffusion of macromolecules into agar, carbopol and mucus gel systems.
Effect of Oily Vehicles on Absorption of Mepitiostane by the Lymphatic System in Rats
Authors: Ichihashi Teruhisa , Kinoshita Haruki , Takagishi Yasushi , Yamada Hideo 
Published: April 2011

Abstract
[14C]Mepitiostane in various vehicles was administered to the small intestine of anaesthetized rats with cannulated thoracic ducts, and the effect of lipids on lymphatic absorption was examined. The extent of lymphatic absorption was greatest when administered in triolein and sesame oil, which are triglycerides of long-chain fatty acids. Absorption in the presence of other vehicles was in the order of 10% Tween 80 aqueous solution &gt; monolein &gt; oleic acid ∼ oleic acid/monolein (2:1 mol/mol) &gt; aqueous suspension. Differences between the extents of lymphatic absorption of mepitiostane in the various formulations were not due to variation in the lymph flow but to the increased secretion of chylomicron and very low density lipoproteins. During absorption of mepitiostane from the small intestine, oil affected not only the penetration into epithelium cells and the metabolism in them, but also the partition between blood and lymph.
Effect of Bile on Absorption of Mepitiostane by the Lymphatic System in Rats
Authors: Ichihashi Teruhisa , Kinoshita Haruki , Takagishi Yasushi , Yamada Hideo 
Published: April 2011

Abstract
The effects of bile and site of gastrointestinal absorption on the lymphatic absorption of the highly lipophilic drug, mepitiostane were examined using thoracic duct-cannulated rats. The lymphatic absorption from the small intestine was very small in the absence of bile compared with that when bile was present. The lymphatic absorption was greatest when drug was administered to the upper small intestine with bile, was smaller for the lower regions of the small intestine, and was negligible for the stomach and the large intestine. A correlation was observed between the extent of lymphatic absorption and the secretion of chylomicron and very low density lipoproteins after administration to various regions with or without bile. The portal absorption data of mepitiostane confirmed that site specificity occurs in the partition of drug between blood and lymph.
Effects of Salicylate and Other Enhancers on Rectal Absorption of Erythropoietin in Rats
Authors: Mizuno A , Ueda M , Kawanishi G 
Published: April 2011

Abstract
To develop a new treatment for patients with anaemia in which erythropoietin (EPO) can be given without injection, the effects of promoters of the rectal absorption of EPO were studied. Recombinant human (rHu) EPO (5000 units) in a dosing solution or in a rectal suppository was placed in the rectum of healthy rats and changes in serum EPO levels were monitored by an enzyme-linked immunosorbent assay. Without a promoter, rHuEPO was not absorbed. Sodium glycocholate, sodium caprate, and sodium salicylate in the solution of rHuEPO increased the absorption of rHuEPO. Sodium salicylate or sodium caprate in the suppository with rHuEPO also increased its absorption. The bioavailability of rHuEPO in a suppository containing 5% sodium salicylate compared with that by an intravenous injection was 1·2%. rHuEPO given in rectal suppositories containing sodium salicylate and inserted once a day for 6 consecutive days increased erythropoiesis in peripheral blood.
In-vivo Blood-brain Barrier Transport of a Novel Adrenocorticotropic Hormone Analogue, Ebiratide, Demonstrated by Brain Microdialysis and Capillary Depletion Methods
Authors: Shimura Takesada , Tabata Shigeru , Terasaki Tetsuya , Deguchi Yoshiharu , Tsuji Akira 
Published: April 2011

Abstract
The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-d-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16·9 MBq mL−1) or [14C]sucrose (29·2 MBq mL−1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 μL min−1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167·8 ± 62·2 μL (g brain)−1, which was about seven times higher than that of [14C]sucrose (24·9 ± 4·0 μL g brain)−1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for ≥ 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1·47 × 10−2 ± 0·17 × 10−2 and was about eight times higher than that for [14C]sucrose (1·92 × 10−3 ± 0·36 × 10−3), indicating significant transport of ebiratide to the brain interstitial fluid. Accordingly, it was demonstrated that ebiratide is taken up into the brain in the intact form possibly via an absorptive-mediated transport through the blood-brain barrier.
Failure of tetrodotoxin to inhibit the prostaglandin-induced secretory response of rat small intestine in-vitro
Authors: Hardcastle J , Hardcastle P T 
Published: April 2011

Abstract
Tetrodotoxin (TTX, 10 μm) did not inhibit prostaglandin E2 (PGE2)-stimulated increases in electrical activity in intact or stripped sheets of rat small intestine, although it reduced basal electrical activity in the intact preparation. Basal and PGE2-stimulated cAMP production by enterocytes isolated from the small intestine was unaffected by TTX. Thus its reported ability to inhibit prostaglandin-induced fluid secretion in-vivo does not appear to represent a direct interaction of the neurotoxin with the mechanism of prostaglandin action at the enterocyte.
The effect of temperature and pH on the deacetylation of diamorphine in aqueous solution and in human plasma
Authors: Barrett David A , Dyssegaard Astrid L P , Shaw P Nicholas 
Published: April 2011

Abstract
The effect of temperature on the kinetics of the deacetylation of diamorphine and 6-monoacetylmorphine was studied in human plasma. Diamorphine was rapidly and quantitatively degraded to 6-monoacetylmorphine with initial half-lives of 354, 18 and 3 min at temperatures of 4, 25 and 37°C, respectively. Further deacetylation to morphine was not detected. In aqueous solution, diamorphine was quantitatively degraded to give 6-monoacetylmorphine as the major product and morphine as a minor product, the rate of deacetylation being dependent on temperature and pH. At pH 4·0 and 5·6 diamorphine had a half-life of greater than 14 days at all temperatures but at alkaline pH diamorphine was rapidly deacetylated. The rate of deacetylation of 6-monoacetylmorphine was consistently slower than that of diamorphine under identical conditions of pH and temperature. A method is described for the rapid stabilization and subsequent assay of diamorphine in plasma which will prevent errors in estimation of the drug due to unwanted hydrolysis.
The pharmacokinetics of oral itraconazole in AIDS patients
Authors: Smith D , Van De Velde V , Woestenborghs R , Gazzard B G 
Published: April 2011

Abstract
To test the hypothesis that absorption of orally administered itraconazole may be reduced in patients with the Acquired Immunodeficiency Syndrome (AIDS), 8 patients with AIDS were given two 100 mg capsules of itraconazole for 15 days. Plasma levels were measured by HPLC hourly for the first 8 h following ingestion, then at 24, 48, 72 and 96 h on days 1, 8 and 15. Peak plasma levels occurred after approximately 4 h. Mean peak plasma concentrations were 446 ± 196 and 530 ± 214 ng mL−1 at days 8 and 15. The area under the curve over 24 h (AUC0–24) was 2105 ± 1241, 7679 ± 3838 and 8748 ± 4385 ng mL−1 h for days 1, 8 and 15, respectively. Steady-state was achieved after one week of dosing. There was no evidence of hepatotoxicity and one patient stopped itraconazole due to a rash. It may be concluded that the absorption of oral itraconazole capsules is reduced in AIDS patients, by a factor of approximately 50%, when compared with normal volunteers. AIDS patients may require higher doses of itraconazole than used in non-AIDS patients to achieve comparable plasma levels.
Some Features of Cannabis Plants Grown in the United Kingdom from Seeds of Known Origin
Authors: Pitts J E , Neal J D , Gough T A 
Published: April 2011

Abstract
The cannabinoid content of UK-grown plants (up to the 6th generation) from Moroccan, Sri Lankan and Zambian seedstock was determined by TLC, GLC and HPLC. All plants from the 5th and 6th series resembled their parents, and UK-grown plants were always much greener than those grown overseas. Cannabinoid content remained broadly typical of the source countries. However, tetrahydrocannabinolic acid (THCA) consistently predominated over tetrahydrocannabinol (THC) to a far greater extent than in the original plants; the THCA/THC ratio was 17 in UK-grown plants compared with 2·0 in the plants from the original areas. Two types of plant emerged from the Moroccan seedstock, one tending to increased cannabidiol (CBD), the other tending to zero levels of this component. The first generation Sri Lankan plants revealed one type of plant with an increased CBD/THC ratio (1·7 compared with 0·11) but this returned to the original value in the succeeding generations. Other Sri Lankan plants had low or undetectable levels of CBD. Moroccan and Sri Lankan CBD-rich plants did not contain cannabichromene, although this cannabinoid was found in THC-rich plants. Zambian plants did not appear to show such a pattern. Zambian seedstock plants had total tetrahydrocannabivarin (diol and acid) levels greater than THC but the ratio was progressively reversed in succeeding generations. The study concludes that the ratios of particular cannabinoids is greatly influenced by the environment.
The Effects of Various Peptides on Human Isolated Gut Muscle
Authors: Bennett A , Stamford I F , Sanger G J , Bloom S R 
Published: April 2011

Abstract
The effects of eleven peptides of gastrointestinal origin have been studied on the contraction, relaxation and spontaneous activity of circular and longitudinal muscle strips from different regions of the human gastrointestinal tract. The effects varied with the peptides and sometimes with the region and muscle layer. There was either contraction, no effect, or relaxation and/or inhibition of an acetylcholine-induced contraction. Responses to some peptides are consistent with the possibility that they may contribute directly to the control of motility: galanin, neurotensin and substance P might be involved in contraction, and vasoactive intestinal peptide, peptide histidine isoleucine and peptide histidine methionine might be inhibitory transmitters.