bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal absorption of sodium cefoxitin in rats: effect of formulation
Authors: Nishihata Toshiaki , Yoshitomi Hironori , Higuchi Takeru 
Published: April 2011

Abstract
The absorption of cefoxitin from rat intestine, rectum and small intestine was greater when the powdered form was administered than when an aqueous solution was given. Cefoxitin absorption from the small intestine was significantly increased after its administration in suppository form prepared with a triglyceride base, although rectal absorption from the suppository did not differ from that of the drug in powdered form. The increase in absorption by the small intestine from the suppository form may be due to fatty acids produced from triglyceride by lipase.
[3H]Taurine binding on a cardiac sarcoplasmic fraction from rats, rabbits and pigs
Authors: Quennedey M C , Velly J , Schwartz J 
Published: April 2011

Abstract
A subcellular fraction was isolated from heart ventricles by differential centrifugation. Enzyme markers and electron microscopy showed that this fraction was rich in sarcoplasmic reticulum. It bound [3H]taurine specifically. Taurine might contribute to the regulation of Ca2+ transfer in the sarcoplasmic reticulum.
An approach to reduce the number of skin samples in testing the transdermal permeation of drugs
Authors: Langguth P , Spahn H , Mutschler E , Hübner K 
Published: April 2011

Abstract
Although glyceryl trinitrate (GT) is a drug that easily permeates through skin, the variations in its transepidermal fluxes were high. The arithmetic mean of the GT flux (n = 31 skin samples from different individuals) was 16.5 μg cm−2 h−1 with a standard deviation of 42%. The extreme values were 4.1 and 36.9 μg cm−2 h−1, i.e. they differed by a factor of 9. Wide variations were also found for ephedrine, frusemide, caffeine, ethacrynic and benzoic acids and especially trospium chloride. All these fluxes were determined in an in-vitro permeation model at 32 °C using human epidermis. With the aim of standardizing epidermal preparations on their permeability, the extent to which the in-vitro GT fluxes through a human epidermal preparation correlate with those of other compounds was evaluated. The resulting standardization procedure consisted of two interactive parts: (i) the correlation of the flux of a test-substance with that of GT using epidermal samples from three donors and estimating the minimum, mean and maximum flux of the test compound and (ii) quantitation of the transepidermal permeation of the test compound with those standardized epidermal preparations by calculating the GT standard coefficient defined by the slope of the line derived from the relation between GT flux units and the corresponding flux from the test compound.
Pharmacological actions of ICI 180080, a novel thromboxane receptor antagonist
Authors: Jessup C L , Jessup R , Wayne M 
Published: April 2011

Abstract
ICI 180080 (5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid) potently inhibited contractions of rat and rabbit aortae and guinea-pig trachea elicited by 11,9-epoxymethano PGH2 (U-46619). This antagonism was selective because contractions of aortae to noradrenaline and 5-hydroxytryptamine and trachea to histamine were not antagonized by ICI 180080. Schild analysis of data obtained from experiments on rabbit aortae indicated that this thromboxane receptor antagonism was competitive (pA2 = 7.50, slope = 1.07). Addition of ICI 180080 to human platelet-rich plasma caused dose-related inhibition of U-46619-induced platelet aggregation. This modification of platelet aggregation was not associated with inhibition of thromboxane synthetase, cyclo-oxygenase or lipoxygenase. ICI 180080 did not modify the primary phase of ADP-induced aggregation of human platelets neither did it affect the platelet inhibitory activity of prostacyclin. When dosed orally to anaesthetized guinea-pigs, ICI 180080 (5–50 mg kg−1) caused dose-related inhibition of U-46619-evoked bronchoconstriction. We conclude that ICI 180080 is a potent, selective, competitive, orally active thromboxane antagonist.
Adrenal catecholamine concentration after chronic treatment with bromocriptine and haloperidol
Authors: Baksi Samarendra N , Hughes Maysie J , Strahlendorf Howard K 
Published: April 2011

Abstract
Adrenal catecholamine concentration was measured by HPLC with electrochemical detection in male rats after ten days of bromocriptine and haloperidol (0.05,0.5 and 5.0 mg kg−1) and vehicle (1.0 ml kg−1) treatments subcutaneously. There were four rats in each group. The results indicate that bromocriptine treatment significantly increased dopamine (DA), noradrenaline (NA) and adrenaline (A) content in a dose-dependent manner. The NA/DA ratio was unchanged, but the A/NA ratio was significantly increased after treatments with two higher doses of the drug. Haloperidol treatment, on the other hand, had no significant effect on dopamine and a biphasic effect on adrenaline content. Noradrenaline concentration increased only after the lowest dose of the drug. There was no significant change in NA/DA or A/NA ratios in any group. The dopamine metabolite, dihydroxyphenylacetic acid (DOPAC), was not detected in any adrenal gland.
Effect of fluoxetine pretreatment on the neurochemical changes induced by amfonelic acid combined with spiperone in rats
Authors: Fuller Ray W , Snoddy Harold D 
Published: April 2011

Abstract
Combined treatment with amfonelic acid plus spiperone caused large increases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and a decrease in dopamine in rat striatum. 5-Hydroxytryptamine (5-HT) was decreased in striatum (but not in hypothalamus), and 5-hydroxyindoleacetic acid (5-HIAA) was increased in the striatum. Pretreatment with fluoxetine, an inhibitor of uptake into 5-HT neurons, antagonized the decrease in 5-HT and the increase in 5-HIAA and in the ratio 5-HIAA/5-HT but did not antagonize the changes in dopamine or its metabolites. The amfonelic acid-spiperone combination apparently causes increased release of dopamine in striatum, and the released dopamine is accumulated by 5-HT nerve terminals via the membrane uptake carrier. Inhibition of that carrier by fluoxetine prevents the release of 5-HT caused by the dopamine influx.
Evaluation of official instrumental methods for the determination of particulate matter contamination in large volume parenteral solutions
Authors: Montanari L , Pavanetto F , Conti B , Ponci R , Grassi M 
Published: April 2011

Abstract
The distribution pattern of particle contamination in nine different types of LV parenteral solutions and the possibility of correlating the counts made with two official instruments (Coulter Counter and HIAC) were studied. Two hundred containers of LV parenteral solutions (corresponding to 40 batches) produced in Italy, were sampled. Each bottle was submitted to HIAC and Coulter Counter countings, for particle sizes ranging between 2 and 25 μm. For about 50% of the products, the two straight lines that represent the distribution of particle contamination obtained with the two methods did not cross-over within the studied size range, the Coulter Counter counts always proving higher than the HIAC ones. In the other cases, the cross-over point of the two lines occurred at varying size levels. Statistical analysis of the results pointed to a relationship between the contamination values obtained with the two counting methods for sizes ranging between 2 and 5 μm, but there was no correlation for sizes equal to, or higher than, 10 μm. From the maximum contamination levels established by the BP and the FU IX for the HIAC method, the corresponding values were calculated for the Coulter Counter method. Similarly the values were calculated the HIAC method based on the maximum values set for the Coulter Counter.
Non-isotopic spectrophotometric determination of the unbound fraction of drugs in serum
Authors: Lim C-F , Wynne K N , Barned J M , Topliss D J , Stockigt J R 
Published: April 2011

Abstract
A spectrophotometric method to measure the free fraction of highly-bound drugs in serum has been established for a range of non-steroidal anti-inflammatory drugs (NSAIDs) and for frusemide. Spectrophotometry is used to measure fractional transit of drug from a large volume of dialysate to a small volume of serum during dialysis to equilibrium. The method, which depends on the principle that drug transit from dialysate to serum is proportional to serum binding, requires neither isotopic drug preparations nor specific drug assays, is independent of extraction efficiency from the dialysate and requires no measurements from the serum compartment. Estimates of percent unbound fraction (%UF) for aspirin (6.0 ± 0.9%), phenylbutazone (0.9 ± 0.2%), and frusemide (1.8 ± 0.2%) were comparable with those obtained with 14C drug preparations. Values for %UF were determined for eleven additional NSAIDs. The method was valid for a four-fold change in serum: dialysate ratio. Kinetics of frusemide binding to serum were comparable using [14C]frusemide and the test method. This technique may have general application in establishing the %UF for substances that are extensively bound to serum proteins and for identifying sera that show abnormal binding.
Effects of various cephem antibiotics on ethanol metabolism and their structure-activity relations
Authors: Kamei Chiaki , Sugimoto Yukio , Muroi Nobuaki , Tasaka Kenji 
Published: April 2011

Abstract
The effects of various cephem antibiotics and related compounds on ethanol metabolism were studied in association with their chemical structures. In rats, cefoperazone, cefbuperazone, cefamandole, latamoxef, cefmetazole, cefotetan, cefmenoxime and cefminox which have the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group at position 3 of the cephem ring caused a significant increase in the blood acetaldehyde concentration. In the last three compounds, disulfiram-like activity was less potent than that evaluated in the preceding compounds. Cefazolin and ceftezole having a 1H-tetrazol group at position 7 also showed a disulfiram-like activity. A single administration of 1H-tetrazol also increased the blood acetaldehyde concentration. Both blood ethanol and acetaldehyde values were increased significantly on administration of these drugs. In beagle dogs, cefoperazone induced a less remarkable but much more sustained increase in the blood acetaldehyde. These results indicate that the 1H-tetrazol group, as well as the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group, is responsible for inducing a disulfiram-like action and that there is a difference in the potency of the disulfiram-like activity among the drugs having a [(1-methyl-1H-tetrazol-5-yl)thio] methyl group at position 3 of the cephem ring in relation to those in which the side chain is substituted at position 7.
The affinity of some selective muscarinic receptor antagonists for the muscarinic receptor mediating endothelial-dependent relaxation of the rabbit and rat thoracic aorta
Authors: Choo L K , Malta E , Mitchelson F 
Published: April 2011

Abstract
The pKB values determined for pirenzepine, 4-DAMP, secoverine and gallamine against acetylcholine-mediated relaxant effects in rabbit aorta indicate that this muscarinic receptor closely resembles that which mediates contraction of non-vascular smooth muscle. The results of the present study argue against the presence of a novel type of muscarinic receptor mediating endothelium-dependent relaxation.
Inhibition of dimaprit- and pentagastrin-induced gastric acid secretion in cats by the new histamine H2 antagonist, CM 57755
Authors: Lavezzo A , Manzoni L , Bianchetti A , Manara L 
Published: April 2011

Abstract
The antisecretory effects of CM 57755, a new histamine-H2 receptor antagonist, have been compared with those of cimetidine on gastric acid secretion induced by intravenous infusions of dimaprit or pentagastrin into conscious cats with chronically implanted gastric fistulae. Intravenous infusion of CM 57755 induced a parallel shift to the right of the dimaprit dose-response curve. The potency of CM 57755 was comparable with that of cimetidine as shown by similar doses causing a 5-fold displacement to the right of the dimaprit dose-response curve (4.9 μmol kg−1 h−1 for CM 57755 and 4.7 μmol kg−1 h−1 for cimetidine). Unlike that with dimaprit, the acid secretion stimulated by increasing doses of pentagastrin was inhibited by CM 57755 with depression of the maximal effect, indicating noncompetitive antagonism. In a second series of experiments the time course of the anti-secretory action of intragastrically administered CM 57755 was studied from the gastric acid secretion induced by constant infusion of dimaprit. At equieffective doses, CM 57755 caused more sustained inhibition than cimetidine.
Acceleration of large intestine transit time in rats by sennosides and related compounds
Authors: Leng-Peschlow Elke 
Published: April 2011

Abstract
Sennosides A + B and their natural metabolites, sennidins A + B, rheinanthrone and rhein, as well as the synthetic laxative danthron, were investigated for their influence on small and large intestine transit time in rats. Carmine red, as a marker, was administered through a gastric tube for small intestine transit or intracaecally by a chronically implanted catheter for colon transit. High doses of sennosides (250–500 mg kg−1) given orally from 20 min or up to 6h before marker administration had no effect on small intestine transit time. The metabolites and danthron (10–100 mg kg−1 p.o.) also did not accelerate upper gastrointestinal passage. Intracaecal administration at the same time as carmine red, however, reduced the time for the appearance of the first coloured faeces from more than 8 h in the controls to 46 ± 9 min after sennosides, 34 ± 11 min after sennidins, 53 ± 83 min after rhein and 16 ± 4 min after rheinanthrone (50 mg kg−1 of each). Danthron was ineffective. Thus, sennosides and their natural metabolites specifically influence large intestinal motility. Acceleration of colonic transport seems to be a major component of the laxative action whereas for danthron motility changes are not responsible for its laxative action. Indomethacin partly inhibited the acceleration of large intestine transit induced by sennosides. An involvement of endogenous prostaglandins may therefore be possible, although a local bolus administration of PGF2α or PGE2 into the caecal lumen neither influenced transit time nor induced diarrhoea.
Coulter Counter measurements of solubility and dissolution rate of sparingly soluble compounds using micellar solutions
Authors: Nyström C , Bisrat M 
Published: April 2011

Abstract
A Coulter Counter, Model TAII, was used to determine both solubility and surface specific dissolution rate of two sparingly soluble materials suspended in micellar solutions. The equilibrium solubility increased linearly with surfactant concentration, thereby making it possible by extrapolation to characterize materials with an aqueous solubility down to 1 ppm or less. At high concentrations (&gt;0.1% w/v) the effect of surfactant concentration on the surface specific dissolution rate was less than that predicted from the increased bulk solubility.
Phosphorolysis of 5′-deoxy-5-fluorouridine in human plasma, serum and blood platelets
Authors: Meynial D , Malet-Martino M C , Lopez A , Martino R 
Published: April 2011

Abstract
During the course of the study of 5′-deoxy-5-fluorouridine (5′dFUrd) plasma protein binding using 19F NMR spectroscopy, phosphorolytic cleavage of 5′dFUrd into 5-fluorouracil (5FU) was observed. This transformation was due to the enzymatic content of residual blood cells present in plasma, since the percentage conversion of 5′dFUrd into 5FU was lower as the number of residual blood cells fell, and an ‘acellular’ plasma or a serum effected a negligible phosphorolyis of 5′dFUrd. As platelets were the contaminants of the plasma samples studied, and a concentrate of human platelets demonstrated a high phosphorolytic activity towards 5′dFUrd, it was concluded that these blood cells were responsible for the 5′dFUrd cleavage. Thymidine phosphorylase, being the only pyrimidine nucleoside phosphorylase in human platelets, is suggested by the present results to catalyse 5′dFUrd phosphorolysis and is therefore not as specific for 2′-deoxyribonucleosides as has been reported.
The binding of amsacrine to human plasma proteins
Authors: Paxton J W , Jurlina J L , Foote S E 
Published: April 2011

Abstract
Determination of amsacrine plasma protein binding by both equilibrium dialysis and ultracentrifugation gave similar results and indicated that amsacrine is highly bound (approximately 97%) in human plasma. This binding is independent of amsacrine concentration over the range 1–100 μmol litre−1, but is very sensitive to plasma pH and, to a lesser extent, to temperature. Approximately 20% of the drug appeared to be covalently bound to plasma proteins. Amsacrine was bound by all plasma proteins investigated including albumin, α1-acid glycoprotein and various γ-globulins. The binding to albumin appeared to occur by two processes, a saturable process at a single site with a KD of 13.9 μmol litre−1 and a non-saturable process. Despite differences in individual protein concentrations, no significant difference was observed in the unbound amsacrine fraction in plasma from patients receiving this drug for treatment of acute myelogenous leukaemia and plasma from healthy individuals.
Prophylactic and therapeutic efficacy of the soman-simulator, pinacolyl dimethylphosphinate
Authors: Van Helden H P M , Van Der Wiel H J , Wolthuis O L 
Published: April 2011

Abstract
Atropinized rats, intoxicated with 6 or 8 × LD50 soman and subsequently treated with the oxime HI-6 died several hours after intoxication. Oral or intravenous administration of the soman-simulator, pinacolyl dimethylphosphinate (PDP), given at progressively increasing time intervals before soman, appeared to be very active in preventing death and secondary failure of neuromuscular transmission that followed HI-6-induced recovery. Therapeutically, PDP was only effective when given immediately after soman intoxication and oxime treatment. In animals that received no treatment otherwise, intravenous administration of PDP 10 min before intoxication with 1 × LD50 soman did not enhance lethality.
Pharmacological studies with SK&F 94120, a novel positive inotropic agent with vasodilator activity
Authors: Gristwood R W , Eden R J , Owen D A A , Taylor E M 
Published: April 2011

Abstract
The pharmacological properties of SK&F 94120 on the cardiovascular system have been studied in laboratory animal species. The compound was shown to have positive inotropic activity on hearts from guinea-pig, cat, dog and marmoset in-vitro and in cat and dog in-vivo. These responses in-vivo occurred in association with minimal changes in heart rate. Positive inotropic activity was not caused by SK&F 94120 in rat or hamster hearts in-vitro, thereby indicating a species dependence in myocardial response. SK&F 94120 was shown to have vasodilator activity in cats in-vivo. Detailed studies carried out on anaesthetized cats indicated that the compound caused a balanced dilatation of both resistance and capacitance blood vessels. Haemodynamic studies in anaesthetized cats indicated that, as a consequence of the positive inotropic and vasodilator actions, SK&F 94120 causes significant increases in cardiac output and stroke volume. Studies in conscious dogs showed the compound to be active as a positive inotrope after oral administration. The above properties suggest that this compound possesses useful haemodynamic properties for the treatment of congestive heart failure.
The effect of auranofin on the colonic transport of Na+ and fluid in the rat
Authors: Hardcastle J , Hardcastle P T , Kelleher D K , Fondacaro J D 
Published: April 2011

Abstract
Auranofin in the mucosal fluid caused a dose-dependent inhibition of fluid and Na+ absorption by everted sacs of rat colon. Serosal auranofin was without effect. (Na+ + K+)ATPase activity of homogenates of mucosal scrapes of rat colon was inhibited by auranofin in a dose-related manner, while Mg2+-ATPase activity was little affected. These actions of the drug on colonic transport mechanisms could contribute to the diarrhoea associated with auranofin therapy.
Sodium deprivation increases the antinociceptive activity of morphine
Authors: Poggioli Rosanna , Vergoni Anna Valeria , Bertolini A 
Published: April 2011

Abstract
In rats maintained for 50 days on a low-sodium diet and with a compensatory hyperactivity of the renin-angiotensin system, the antinociceptive activity of morphine was significantly longer-lasting than in controls. It is suggested that the renin-angiotensin system modulates opioid system responsivity.
A comparison of the effects of hyperosmotic salicylate solutions in closed and perfused rectal in-situ loops of rats
Authors: Derrick Gillian M , Thomas Norman W , Wilson Clive G 
Published: April 2011

Abstract
The effects of presentation of hyperosmotic solutions of sodium salicylate to the closed and perfused rectal loop preparations commonly used in assessing drug absorption nave been compared. Epithelial cell loss was quantified in control and treated loops. Tissue damage was significantly greater (P &lt; 0.01) in treated perfused loops. Fluid efflux, which was associated with a small but significant change in the haematocrit value, was noted in both systems.
A study of powder adhesion to metal surfaces during compression of effervescent pharmaceutical tablets
Authors: Sendall F E J , Staniforth J N 
Published: April 2011

Abstract
Effervescent tablets were produced using four different formulations containing citric and/or tartaric acid and sodium bicarbonate with povidone and macrogol 6000. The same formulations were prepared with the addition of 1% sucrose ester powder. The adhesion of each formulation to the metal faces of tableting machine punch tips was determined using electron microscopy, surface roughness measurements and quantification of punch weight variations during tablet production. The basic formulations were inherently adhesive and produced tablets with a weak, porous structure which were qualitatively and quantitatively rougher than conventional, non-effervescent compressed tablets. Both formulations containing tartaric acid produced tablets with a lower surface roughness and with less tendency to stick to tablet punch faces than the two formulations containing citric acid alone. The addition of a water-soluble sucrose ester had a beneficial effect especially on the formulations with inherently high adhesive tendencies.
Self-association of local anaesthetic drugs in aqueous solution
Authors: Attwood D , Fletcher P 
Published: April 2011

Abstract
The aggregation characteristics of a series of local anaesthetic drugs in water and electrolyte solution have been examined using total intensity light scattering, photon correlation spectroscopy and vapour pressure osmometry. The association of cinchocaine hydrochloride was micellar. An appreciable increase in the effective diffusion coefficient as solutions of cinchocaine were diluted close to the critical micelle concentration was observed and has been discussed. The association of amethocaine hydrochloride could be described using a co-operative stepwise association model. No association could be detected in water or 0.1 mol dm−3 electrolyte for butacaine hemisulphate and the hydrochlorides of procaine, proparacaine, mepivacaine, lignocaine, bupivacaine and prilocaine at drug concentrations of less than 0.2 mol dm−3.