bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of bezafibrate on hyperlipidaemia in experimental nephrotic syndrome in rats
Authors: Williams A J , Baker F E , Walls J 
Published: April 2011

Abstract
The effects of bezafibrate on hyperlipidaemia in experimental nephrotic syndrome in rats has been investigated. The treated group received bezafibrate l0 mg kg−1 p.o. daily. No significant differences in total serum cholesterol occurred, but a significant reduction in serum triglyceride (P &lt; 0.005) and elevation in HDL cholesterol (P &lt; 0.005) occurred. These findings may have implications for therapeutic intervention in severe hyperlipidaemia of the nephrotic syndrome in man.
Further investigation on aldehyde reductase activity in ageing rat tissues
Authors: Danh H Cao , Pasquier-Béchet P , Benedetti M Strolin , Dostert P 
Published: April 2011

Abstract
Aldehyde reductase (AR) activity was measured in whole brain, different brain areas, kidney and duodenum of 23-26 months old rats and then compared to matched animals of 3 months. No significant changes in AR activity were found in whole brain of old rats with D-glucose as substrate. A significant increase in AR activity in old rats was found in striatum (12%), cerebellum (26%), midbrain (6%), brainstem (19%) and hypothalamus (13%) with p-nitrobenzaldehyde, in striatum (14%), midbrain (10%), brainstem (52%), hypothalamus (9%) and hippocampus (20%) with D-glucuronate, in cerebellum (21%) with D-xylose, in striatum (43%), cerebellum (19%) and brainstem (22%) with DL-glyceraldehyde, and in brainstem (15%) with pyridine 3-aldehyde. A significant decrease in AR activity in old rats was found in midbrain (16%), brainstem (19%) and hypothalamus (19%) with D-xylose, and in midbrain (13%) with DL-glyceraldehyde. A significant decrease in AR activity in old rats was found in kidney with p-nitrobenzaldehyde (30%), D-xylose (31%), DL-glyceraldehyde (33%), pyridine 3-aldehyde (27%) and in duodenum with p-nitrobenzaldehyde (21%), but a significant increase was found in duodenum with pyridine 3-aldehyde (29%). Preliminary experiments show an increase (42%) of sorbitol dehydrogenase activity in whole brain of old rats. The present results clearly indicate that the AR activity increase in the brain of old rats is the high-Km form of aldehyde reductase. However, as the activity of the enzyme responsible for the catabolism of sorbitol increases, its accumulation in the brain with age seems to be improbable; this is different from what happens in the eye where enzymatic changes with age appear to favour sorbitol accumulation, which is responsible for cataractogenesis.
Cyclic nucleotides fail to affect mucus glycoconjugate secretion from canine tracheal explants
Authors: Barbieri Edward J , Barsigian Carl 
Published: April 2011

Abstract
Canine tracheal explants, incubated overnight with [3 H]glucosamine, elicited an enhanced secretion of ethanol-precipitated [3 H]labelled glycoconjugate when challenged with methacholine, 10 μM. Neither the β-adrenoceptor agonist isoprenaline, 10 μM, nor the phosphodiesterase inhibitor theophylline, 10 mM, had any significant effect on glycoconjugate secretion. Dibutyryl cyclic AMP, 1 mM, and dibutyryl cyclic GMP, 1 mM, alone or in combination with theophylline, 10 mM, were devoid of activity on unstimulated or methacholine-stimulated tracheal explants. The calcium ionophore A23187, 10 μM, stimulated [3 H]glycoconjugate secretion from each of the tissues tested; however, the cyclic nucleotides failed to modify this response. These data indicate that the cyclic nucleotides play little, if any, role in mucus glycoconjugate secretion by the canine trachea.
Biochemical and ultrastructural study of the effects of proline analogues on collagen synthesis in 3T6 fibroblasts
Authors: Carrington M J , Fornieri C , Bartlet C P , Heale G , Levene C I 
Published: April 2011

Abstract
The effects of two proline analogues, l-3,4-dehydroproline and l-azetidine-2-carboxylic acid, on collagen synthesis by cultured 3T6 fibroblasts have been studied. Prolyl hydroxylase activity was partially inhibited in cells cultured with dehydroproline for 24 h, resulting in the synthesis of collagen in which the proline was underhydroxylated. Azetidine had no effect on prolyl hydroxylase and less effect on the degree of hydroxylation of proline. Fibroblasts grown in the presence of either analogue and fixed in-situ contained greatly distended cisternae of the rough endoplasmic reticulum. Proline analogues otherwise caused few ultrastructural changes in the cells. Treated cells which had been handled more roughly during preparation for electron microscopy contained many large cytoplasmic vacuoles in addition to dilated cisternae. Our results indicate that the major effect of the proline analogues was the inhibition of prolyl hydroxylation. However, electron microscopy of the treated cells revealed hitherto unreported cytoplasmic damage.
A study on the aetiology of reserpine ulceration and the antiulcer action of solcoseryl in rat stomach
Authors: Cho C H , Ogle C W , Dai S 
Published: April 2011

Abstract
The aetiology of reserpine-induced gastric ulcer formation and the antiulcer effects of solcoseryl were studied in rats. Intraperitoneal injection of reserpine produced severe ulceration, as well as mast cell and histamine depletion, in the gastric glandular mucosa. Mepyramine and Cimetidine markedly antagonized the gastric lesions, but did not influence the reduced mast cell count; atropine pretreatment significantly inhibited both parameters. Intramuscular injection of solcoseryl lessened ulcer severity and prevented the decreased mast cell counts and histamine levels in reserpine-treated rats. However, the same dose of solcoseryl injected intraperitoneally was ineffective. Solcoseryl, irrespective of the route of administration, did not influence the gastric secretory activities of reserpine. It is concluded that resperine ulceration is both cholinergic- and histamine-mediated, and that the antiulcer effects of solcoseryl appear to be due to prevention of histamine depletion in the gastric mucosa.
Effect of caffeine on the plasma protein binding and the disposition of ceftriaxone
Authors: Kwon Kwang-Il , Bourne David W A , Ho Paul C 
Published: April 2011

Abstract
The effects of caffeine on the in-vitro protein binding and the pharmacokinetics of ceftriaxone (a highly protein bound cephalosporin) were investigated. Caffeine failed to decrease in-vitro protein binding of ceftriaxone. Rabbit plasma concentrations of ceftriaxone (30 mg kg−1 i. v.) were elevated significantly (P &lt;005 at 0.3, 0.6 and 1 h after injection) when caffeine 5 or 10 mg kg−1 i.v. was co-administered compared with ceftriaxone given alone. Caffeine increased the volume of distribution of the central compartment (V1) for ceftriaxone significantly from 49 ± 38 ml kg−1 (mean ± s.d., n = 6) to 97 ± 33 ml kg−1 (caffeine 5 mg kg−1, P &lt;0.05), and 94 ± 8 ml kg−1 (caffeine 10 mg kg−1, P &lt;0.05) and decreased the volume of distribution of the peripheral compartment (V2) from 145 ± 106 ml kg−1 (mean ± s.d., n = 6) to 31 ± 18 ml kg−1 (caffeine 5 mg kg−1, P &lt;0.05) and 36 ± 31 ml kg−1 (caffeine 10 mg kg−1, P &lt; 0.1). The rate of transfer of ceftriaxone to the peripheral compartment (k12) was also decreased significantly (P &lt;0.05) after caffeine. The elevated plasma concentration of ceftriaxone, increased V1 value and the decreased V2 and k12 values are probably the result of caffeine altering the distribution of ceftriaxone to the central and the peripheral compartments.
Lack of effect of BW755c on glucose-induced insulin secretion in the rat in-vivo
Authors: Byford A J , Furman B L 
Published: April 2011

Abstract
Glucose-induced elevations in plasma immunoreactive insulin (IRI) were examined in anaesthetized rats pretreated with BW755c, sodium meclofenamate or vehicle. Neither drug influenced the glucose-induced hyperinsulinaemia or the glucose disappearance rate. The results do not support a physiological role for arachidonic acid metabolites in the regulation of glucose-induced insulin secretion.
The effect of some excipients on the physical properties of a paracetamol tablet formulation
Authors: Esezobo S 
Published: April 2011

Abstract
The effects of the addition of the excipients sorbitol, sodium lauryl sulphate and Aerosil on the physical properties of a paracetamol tablet formulation have been evaluated. Increase in the concentration of sorbitol and sodium lauryl sulphate caused a decrease in the hardness with a corresponding increase in the friability, disintegration and dissolution rates of the tablets.
The mode of incorporation of the excipient, Aerosil, greatly influenced the physical properties of the paracetamol tablets. When added internally, the tablets' strength decreased while the friability, disintegration and dissolution rates increased. However, when Aerosil was added externally, the strength of the tablets increased while their friability, disintegration and dissolution rates decreased.
Vapour and liquid diffusion of model penetrants through human skin; correlation with thermodynamic activity
Authors: Barry B W , Harrison S M , Dugard P H 
Published: April 2011

Abstract
This work investigates vapour and liquid permeation through human skin of model penetrants benzyl alcohol, benzaldehyde, aniline, anisole and 2−phenylethanol applied in model vehicles butanol, butyl acetate, isophorone, isopropyl myristate, propylene carbonate, toluene, n-heptane and water. Vapour permeation was a linear function of thermodynamic activity as measured by headspace gas chromatography, except when the vehicle was n-heptane. Liquid permeation did not always follow simple thermodynamic predictions, e.g. for the penetrant, benzyl alcohol, when the vehicle damaged the skin (toluene, n-heptane) or when propylene carbonate produced low fluxes and isopropyl myristate, high values. At comparable thermodynamic activities, liquid fluxes were often ten-fold higher than vapour fluxes, and these differences were reflected by the partition coefficients and the amount of penetrant entering the stratum corneum membrane. The conclusion was that liquid fluxes were membrane controlled, whereas an interfacial effect probably contributed to low vapour permeation.
Stimulation of PGE2 synthesis and water and electrolyte secretion by senna anthraquinones is inhibited by indomethacin
Authors: Beubler E , Kollar G 
Published: April 2011

Abstract
The effect of dried senna pod extract, containing 10% sennoside B, on colonic electrolyte and fluid transport was examined in the anaesthetized rat in-situ. Oral administration of senna pod extract dose-dependently (17.5−30 mg kg−1, calculated as sennoside B) reversed net absorption of water, sodium and chloride to net secretion and increased potassium secretion. Senna pod extract stimulated the output of prostaglandin E2 into the colonic lumen. Inhibition of prostaglandin biosynthesis by pretreatment of the rats with indomethacin (10 mg kg−1) significantly inhibited the effects of senna pod extract (17.5–30 mg kg−1) both on net fluid transport and on prostaglandin E2 synthesis. The inhibitory effect of indomethacin on net fluid transport induced by senna pod extract (30 mg kg−1) was dose-dependent. It is concluded that anthraquinones exert their laxative action at least partially via stimulation of colonic fluid and electrolyte secretion, and that this secretion is mediated by stimulation of endogenous prostaglandin E2 formation.
Disposition of radiolabelled suppositories in humans
Authors: Jay Michael , Beihn Robert M , Digenis George A , Deland Frank H , Caldwell Larry , Mlodozeniec Arthur R 
Published: April 2011

Abstract
The disposition of Witepsol H 15 suppositories radiolabelled with [99m Tc] technetium hydroxymethyldiphosphonate was studied after rectal administration in volunteers. The migration of the radiolabel was monitored continuously by external scintigraphy. The resulting scintiphotos were superimposed on lower GI radiographs to determine the extent of spreading of the dosage form in the rectum. The dosage form migrated approximately 5−7 cm into the rectum in nearly all of the studies and was, in general, confined to the lower and middle regions of the rectum. Since the venous supply to the lower rectum leads primarily to the inferior vena cava, the data presented here indicate that the metabolism of drugs sensitive to the ‘first-pass’ effect may be partially avoided by their rectal administration.
Age-related changes in the activities of the amine metabolizing enzymes of rat eye
Authors: Cao Danh H , Strolin Benedetti M , Mousset A , Pasquier-Béchet P 
Published: April 2011

Abstract
Age-related changes in the activities of the amine metabolizing enzymes of rat eye
Eye MAO-A, MAO-B, semicarbazide-sensitive amine oxidase (SSAO) and aldehyde reductase (AR) activities were measured in young and old rats. When enzyme activity is expressed as nmol (mg protein)−1 min−1, a significant decrease (18–23%) of SSAO activity in the eye of old rats was found, whereas there was no significant difference in MAO-A and MAO-B activities. A significant increase of AR activity with D-xylose (67%), DL-glyceraldehyde (64%), D-glucuronate (43%) and D-glucose (21%) was found in the eye of old rats. These results suggest that changes in the activities of the amine metabolizing enzymes of rat eye with age might have consequences for their function in senescence; particularly, the increase of AR activity might be involved in cataract formation.
Uptake of amino β-lactam antibiotics into rat intestinal brush border membrane vesicles
Authors: Iseki Ken , Iemura Akihiro , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
Uptake of amino β-lactam antibiotics into rat intestinal brush border membrane vesicles has been examined for characterization of the transport of the antibiotics through the gut wall of the rat. The uptake of cephradine, cephalexin and ampicillin into membrane vesicles was similar, and there were no significant changes in the uptake in the presence of a NaCl or a KCl gradient. These results suggested that the carrier-mediated transport systems relating to amino acids and glucose were not concerned with the intestinal absorption mechanism of amino β-lactam antibiotics.
Comparative pharmacokinetics of theophylline and ethylenediamine following single and repeated doses of a sustained-release aminophylline preparation to volunteers
Authors: Cotgreave Ian A , Caldwell John 
Published: April 2011

Abstract
Plasma concentrations of theophylline and ethylenediamine have been measured by HPLC after a single dose and also after a further four consecutive doses at 12 h intervals of a tablet containing 225 mg aminophylline in a sustained release matrix (Phyllocontin) had been taken by volunteers. A dissolution study of the product showed the release of theophylline to follow zero-order kinetics, to be independent of bath pH, and to be complete in 6.5 h, while the release of ethylenediamine depended upon the pH of the medium and was more extensive in acid solutions. After one tablet, the plasma theophylline concentrations reached a maximum of 4 μg ml−1 at 5 h and fell slightly at 7 h. Immediately before the fifth dose, the trough plasma value was 4.7 μg mol−1, and this rose to 7.7 μg ml−1 5 h after the dose. The areas under the plasma level-time curves (AUC) were significantly (P &lt; 0.001) increased by the chronic regimen, and although the individual values were highly variable, the increase in AUC from the first to the fifth dose was significantly (P &lt; 0.001) correlated within each subject. Ethylenediamine concentrations after a single dose reached a peak of 0.16 μg ml−1 at 1 h, and returned to baseline values in 5–7 h. After the fifth dose, the plasma levels and kinetics were no different from those obtained with the first dose indicating that ethylenediamine did not accumulate as a result of chronic administration of aminophylline in a form designed to give steady-state levels of theophylline.
Absorption and metabolism of hexamethylmelamine and pentamethylmelamine in rat everted perfused gut segments: correlation with in-vivo data
Authors: Borm Paul J A , Frankhuyzen-Sierevogel Ank C , Weller Erwin B C , Noordhoek Jan 
Published: April 2011

Abstract
The intestinal oxidative metabolism of hexamethylmelamine (HMM) and pentamethylmelamine (PMM) has been studied in microsomes, isolated mucosal cells and intestinal perfused segments. (sub)Cellular systems revealed an almost equal Km (53–65 μM) and Vmax (5.6–7.0 nmol min−1 g−1 intestine) for both compounds. Detailed studies in everted intestinal perfused segments, showed that HMM is metabolized to a far greater extent than PMM (e.g. 11-times, at 80 μM substrate concentration) while PMM transport was 3 times greater than the transport of unchanged HMM. Only when perfused segments were used as an in-vitro tool was a good correlation observed between the in-vivo and in-vitro rate of intestinal metabolism of HMM and PMM. It is concluded that this is due to preservation of structural integrity of the mucosa for both absorptive and metabolic processes.
Vascular smooth muscle cells: a major source of the semicarbazide-sensitive amine oxidase of the rat aorta
Authors: Lyles Geoffrey A , Singh Iqbal 
Published: April 2011

Abstract
Several methods have been used to study the distribution of the semicarbazide-sensitive amine oxidase (SSAO) within the wall of the rat aorta. After separation of the smooth muscle-containing layers of the tunica media from the connective tissue of the tunica adventitia, much higher specific enzyme activity (measured with 1 μM benzylamine) was found in homogenates of the media than of adventitia. Similar results were obtained for MAO-A (with 1 mM 5-HT as substrate). SSAO activity was also considerably higher in homogenates of cells (predominantly smooth muscle) isolated from medial tissue by enzymatic dissociation with collagenase and elastase compared with homogenates of cells (mostly of connective tissue origin) from the adventitia. Histochemical staining resulting from SSAO activity (with benzylamine as substrate) occurred predominantly and intensely over the tunica media in rat aortic sections, although some occasional staining of adventitial sites was also observed. Staining was prevented by the SSAO inhibitors hydroxylamine (1 μM) and semicarbazide (1 mM), but not by the MAO inhibitor, clorgyline (1 mM). These results indicate that SSAO is associated predominantly, although not exclusively, with the smooth muscle cells in the rat aorta. Our findings that β-aminopropionitrile (BAPN) is a reversible, competitive inhibitor (Ki around 2 times 10−4 M) of SSAO, in contrast to the irreversible inhibition of the connective tissue lysyl oxidase by BAPN reported by others, provides further evidence that these enzymes are not identical.
Circadian changes in procainamide and N-acetylprocainamide kinetics in the rat
Authors: Bruguerolle B , Jadot G 
Published: April 2011

Abstract
The aim of this study was to investigate the possible influence of the time of administration on procainamide and N-acetylprocainamide (NAPA) kinetics in the rat. A single 50 mg kg−1 i.p. dose of procainamide was given to Wistar AF SPF adult male rats maintained under controlled environmental conditions (LD: 06.00h-18.00h) at four different fixed times i.e. 10.00, 16.00, 22.00 and 04.00h. Procainamide and NAPA plasma levels were determined by an immunoenzymatic method. Our data showed significant 24 h variation of the following pharmacokinetic parameters: highest elimination half-lives at l0.00h (t 1/2 β = 0.736 ± 0.020h) for procainamide and at 04.00h (t 1/2 β = 3.55 ± 0.08h) for NAPA (P &lt; 0.001); highest apparent volume of distribution at 04.00h for procainamide (Vd = 2.35 ± 0.17 litre) (P &lt; 0.05); highest ratio AUC NAPA/AUC procainamide at 04.00h (1.039 ± 0.056) (P &lt; 0.001). Procainamide clearance and Cmax and AUC for procainamide and NAPA were not significantly dependent on time of day. These data indicate a 24 h variation in the metabolism of procainamide which is converted to NAPA, the N-acetylation being greatest at 04.00h.
Significance of particle size of mebendazole in the treatment of tapeworm infections
Authors: Gemmell M A , Johnstone P D , Oudemans G 
Published: April 2011

Abstract
Taenia hydatigena and Echinococcus granulosus in dogs have been used as a model to evaluate the response of these parasites to increasing doses of mebendazole in different dose forms (powder, micronized powder and tablets of micronized powder). Overall the micronized powder proved to be the most active, the tablets less so and the normal powder least active. Statistical confirmation was obtained that the use of this drug in different dose forms changed the rate of the response, suggesting that in the treatment of human hydatid disease caused by Echinococcus spp and cysticercosis caused by Taenia solium, the dosage form may be a vital factor in the drug's efficacy.
Effects of metoclopramide and domperidone on cholinergically mediated contractions of human isolated stomach muscle
Authors: Sanger G J 
Published: April 2011

Abstract
The experiments examine the actions of metoclopramide and domperidone on the responses evoked by electrical field stimulation or by acetylcholine, in longitudinal muscle strips obtained from human stomach. Electrical field stimulation evoked contractions which were predominantly cholinergically mediated; metoclopramide 0.28-28 μM caused a concentration-dependent increase in the height of these contractions. In the presence of atropine and barium chloride, electrical stimulation evoked relaxations of the stomach muscle, probably by stimulating non-adrenergic, non-cholinergic inhibitory nerves; metoclopramide 28 μM had no effect on these relaxations. Metoclopramide 0.003-2.8 μM had no effect on contractions evoked by exogenous acetylcholine, although higher concentrations of the drug increased the contractions. The results suggest that in human isolated stomach, low concentrations of metoclopramide may increase electrically evoked cholinergic activity by increasing the release of neuronal acetylcholine. Stimulation by metoclopramide of cholinergic activity in the gut may therefore be an important mechanism by which the drug increases gastrointestinal motility during therapy. Cholinergically mediated contractions were not increased by domperidone, and other mechanism(s) of action may therefore be important for this drug.
5-Hydroxytryptamine receptor antagonism by metoclopramide and ICS 205–930 in the guinea-pig leads to enhancement of contractions of stomach muscle strips induced by electrical field stimulation and facilitation of gastric emptying in-vivo
Authors: Buchheitt K H , Costall B , Engel G , Gunning S J , Naylor R J , Richardson B P 
Published: April 2011

Abstract
Contractions induced by electrical field stimulation of isolated circular muscle strips, taken from the guinea-pig stomach, were enhanced by metoclopramide, ICS 205–930 and MDL 72222 at concentrations similar to those shown to antagonize at neuronal 5-hydroxytryptamine receptor sites in a variety of preparations. Metoclopramide, MDL 72222 and ICS 205–930 also facilitated gastric emptying in-vivo. The abilities of metoclopramide, MDL 72222 and ICS 205–930 to enhance stomach muscle contraction processes and to facilitate gastric emptying may be the consequence of 5-hydroxytryptamine receptor antagonism.