bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single injection of a biodegradable microsphere formulation of the ACTH-(4–9) analogue ORG 2766 accelerates functional recovery after brain damage
Authors: Wolterink Gerrit , Bouwman Theo R M , Eenink Mart J D , De Nijs Henrik , van Ree Jan M 
Published: April 2011

Abstract
The functional recovery from impaired motor activity induced by 6-hydroxydopamine lesions in rat nucleus accumbens was accelerated by subcutaneous treatment with the ACTH-(4–9) analogue Met/O2/-Glu-His-Phe-D-Lys-Phe (ORG 2766). Treatment was effective after daily injections of ORG 2766 dissolved in saline during the first 6 days following the lesion (ED50: 28.5 ng kg−1 day−1) or after a single injection of the peptide in a biodegradable microsphere formulation administered after the lesion (ED50:8.9 ng kg−1 day−1). This study shows that a single injection of a microsphere preparation can replace multiple injections with ORG 2766 in order to facilitate functional recovery after brain damage.
Diffusion coefficient in native mucus gel of rat small intestine
Authors: Winne Dietrich , Verheyen Walter 
Published: April 2011

Abstract
The diffusion coefficients of [3H] water, urea, benzoic acid, antipyrine, aminopyrine, α-methyl-glucoside, L-phenylalanine and of hydrogen ions were measured at 38 °C in native mucus gel from rat small intestine. The diffusion in the gel was reduced to 37–53% (for hydrogen ions to 7%) compared with buffer solution. In addition, the buffering capacity of the gel retarded the permeation of hydrogen ions before a steady state flux was attained. A model calculation revealed that in the preparation a gel layer of 80 μm thickness represents 23% of the total permeation resistance for substances with high epithelial permeability. The aqueous part of the pre-epithelial diffusion resistance amounts to 77% of the total resistance.
Antinociceptive and anti-inflammatory activity of a novel quipazine derivative (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake
Authors: El-Mahdy Samiha A M , Alhaider A A , Mahgoub Afaf A 
Published: April 2011

Abstract
The anti-inflammatory and antinociceptive activities of a novel quipazine derivative 2(4-(3-chloropropyl)piperazinyl) quinoline (AAL-13), a selective inhibitor of 5-hydroxytryptamine (5-HT) reuptake, has been examined. Anti-inflammatory activity was assessed by measuring the inhibition of a cotton pellet granuloma and of carrageenan-induced paw oedema in rats, and of cantharidin-induced topical inflammation in the mouse ear. Antinociceptive activity was studied by using the modified Randall-Selitto method. Indomethacin was used as a reference. AAL-13 slightly inhibited granuloma formation (13%, P &lt; 0.02) at 100 mg kg−1 day−1 for 7 days, whereas half that dose had no significant effect. There was significant inhibition of carrageenan-induced rat paw oedema (35%, P &lt; 0.05 and 103%, P &lt; 0.001) 3 h after single doses of AAL-13 (50 and 100 mg kg−1 p.o., respectively). Three hours after i.p. injection, the oedema inhibition was 58% (P &lt; 0.05) and 86% (P &lt; 0.001) for doses of 25 and 50 mg kg−1, respectively. In comparison, indomethacin (3, 6 and 12 mg kg−1 p.o.) inhibited oedema by 59% (P &lt; 0.02), 65% (P &lt; 0.01) and 63% (P &lt; 0.02), respectively. Intraperitoneally, only the 12 mg kg−1 dose produced significant inhibition (82%, 3 h after carrageenan injection, P &lt; 0.05). AAL-13 (1.5 mg/ear) had a significant anti-inflammatory effect on the mouse ear (52%, inhibition, P &lt; 0.05), while indomethacin (3 mg/ear) gave 43% inhibition (P &lt; 0.05). AAL-13 raised the pain threshold and analgesic index in both inflamed and non-inflamed rat paw similarly, while indomethacin (2–3 mg kg−1) was more active in the inflamed paw. However, the larger dose of indomethacin (12 mg kg−1) did raise the threshold in non-inflamed limbs. AAL-13 (up to 100 mg kg−1 daily for 7 days) was devoid of any ulcerogenic effect on the stomach, while indomethacin was lethal in doses greater than 3 mg kg−1 daily. We postulated that the anti-inflammatory and antinociceptive activity of AAL-13 might be due to its ability to block 5-HT and noradrenaline reuptake.
Evaluation of Protein Binding Effect on Local Disposition of Oxacillin in Rat Liver by a Two-compartment Dispersion Model
Authors: Yano Yoshitaka , Yamaoka Kiyoshi , Minamide Toshiomi , Nakagawa Terumichi , Tanaka Hisashi 
Published: April 2011

Abstract
The effect of protein binding upon the hepatic uptake of oxacillin was evaluated in the rat isolated perfused liver, based on the two-compartment dispersion model by means of the fast inverse Laplace transform (FILT). The perfusion experiment was carried out using the perfusates without and with bovine serum albumin (BSA, 40 g L−1). Oxacillin was injected as a pulse through the portal vein, and the outflow concentration-time course of oxacillin was fitted to the dispersion model using the non-linear least squares program MULTI(FILT). The partition ratio (k'), which is the measure of the extent of the reversible distribution into the hepatic tissue, was 0.163 ± 0.041 (s.d.) in the presence of BSA, and 0.095 ± 0.018 in the absence of BSA, which suggests interaction of the albumin-bound drug with the hepatic tissue. The elimination rate constant (ke) from the perfusate in the absence of BSA was 8.0 ± 0.55 min−1 and that in the presence of BSA was 3.3 ± 1.4 min−1 while the unbound fraction of the drug in the presence of 40 gL−1 BSA was 0.282. The hepatic elimination rate of oxacillin was not proportional to the unbound concentration of drug suggesting hepatic uptake of the bound fraction.
The effects of oral administration of (—)-menthol on nasal resistance to airflow and nasal sensation of airflow in subjects suffering from nasal congestion associated with the common cold
Authors: Eccles Ronald , Jawad Moutaz S , Morris Sara 
Published: April 2011

Abstract
The effects of oral administration of a lozenge containing 11 mg (—)-menthol on nasal resistance to airflow (NAR) and nasal sensation of airflow in 62 subjects suffering from nasal congestion associated with naturally acquired common cold infection have been studied. NAR was measured by posterior rhinomanometry and nasal sensation of airflow by means of a visual analogue scale (VAS). The effects of the lozenge were compared with a candy placebo lozenge in a double blind randomized trial. NAR showed a significant increase (P &lt; 0.05) in both the menthol and placebo groups over the 2 h experiment with no difference between the groups at any time. The VAS scores showed significant changes of subjective improvement in nasal sensation of airflow (P &lt; 0.001) in the menthol-treated group 10 min after dosing whereas the placebo group showed no change. It is concluded that dosing with 11 mg menthol in subjects with common cold has no effect on NAR as measured by posterior rhinomanometry but causes a marked change in nasal sensation of airflow with a subjective sensation of nasal decongestion.
Polyphloretin phosphate (PPP) antagonists of prostaglandin action also inhibit prostaglandin biosynthesis in-vitro
Authors: Curtis-Prior P B , Oblin A R , Bennett A , Parkinson N A , Orloff A M 
Published: April 2011

Abstract
Several polyphloretin phosphate (PPP) fractions (low mol. wt LC1259; high mol. wt LC1261; crude mixture, LC101) were confirmed in their established property as antagonists of the pharmacological actions of prostaglandins in a preparation of guinea-pig isolated ileum stimulated by prostaglandin (PG)E2. Further samples of the same material were then compared in-vitro with indomethacin in their ability to inhibit prostaglandin biosynthesis from arachidonic acid by a microsomal enzyme preparation. All three PPP fractions potently inhibited prostaglandin generation, with the rank order of potency LC1259 = LC101 = indomethacin &gt; LC1261. The oral LD50 in mice was 25 mg kg−1 for indomethacin and &gt; 1 g kg−1 for LC101. PPP fractions (especially LC101) may therefore have therapeutic potential as anti-inflammatory agents.
AHR-15010—A Novel Anti-arthritic Agent
Authors: Nolan J C , Walsh D A , Lo Y , Gathright C E , Radvany C H , Foxwell M , Whitman L , Graff G , Sancilio L F 
Published: April 2011

Abstract
AHR-15010 (3-(2-methoxyphenoxy)-1,2-propanediol bissulphamate ester) is a compound of novel structure that displays anti-arthritic activity in adjuvant arthritis in rats. When given orally from days 18 through day 50, (excluding weekends) after adjuvant injection, AHR-15010, at doses of 3.16 to 100 mg kg−1, produced significant anti-inflammatory activity and reduced the severity of the hind paw joint lesions as monitored by X-ray analysis. AHR-15010, however, has no acute anti-inflammatory activity in the Evans Blue-carrageenan pleural effusion assay in rats, has no analgesic activity in mice, and has no activity in a classic, delayed-type, hypersensitivity assay in mice or in a cotton pellet granuloma test in rats. These data, in conjunction with biochemical data showing that AHR-15010 has no prostaglandin synthetase inhibiting activity, suggest that AHR-15010 is an anti-arthritic with a unique mechanism of action. AHR-15010 is a carbonic anhydrase inhibitor. Data are presented that suggest that AHR-15010 and acetazolamide, a prototype carbonic anhydrase inhibitor, may present novel approaches to the treatment of arthritis.
Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by a different mechanism
Authors: Volterra G , Borsini F , Lecci A , Meli A 
Published: April 2011

Abstract
The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg−1 i.p., 60 min) or nortriptyline (8 mg kg−1 i.p., 60 min) increased temperature in both reserpine (2.5 mg kg−1 s.c, 18–19 h) and apomorphine (16 mg kg−1 s.c, 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg− i.p 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg−1 s.c, 30 min), the ?1-adrenoceptor blocking drugs prazosin (3 mg kgsp&gt;−1 s.c., 90 min) and phenoxybenzamine (20 mg kg−1 i.p., 65 min), the ?-adrenoceptor blocking drug (±)-propranolol (10 mg kg−1 i.p., 120 min), and the opioid antagonist naloxone (2 mg kg−1 i.p., 15 min). In contrast the selective D2-antagonist (±)-sulpiride (100 mg kg−1 i.p., 90 min), and the ?2-antagonist yohimbine (2 mg kg−1 i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.
Study on the histamine-like activity of guanfacine
Authors: Martinez-Mir M I , Doñate F , Estañ L , Morales-Olivas F J , Rubio E 
Published: April 2011

Abstract
The effects of guanfacine have been studied on guinea-pig isolated atria and diethylstilboestrol-treated rat isolated uterus to determine whether it possesses histamine-like activity. Guanfacine produced a concentration-dependent negative chronotropic effect which was not modified by ranitidine (0.1 μM). In rat isolated uterus contracted by KCl, clonidine (5–5000 μM) produced concentration-dependent relaxation which was blocked by ranitidine (0.1 μM), but guanfacine only produced relaxation at high concentrations (100–1000 μM), and this was not affected by ranitidine (0.1 μM). It is concluded that guanfacine, unlike clonidine, does not produce effects due to activation of H2-receptors in either guinea-pig atria or rat uterus.
A Simple Method for the Preparation of Liposomes for Pharmaceutical Applications: Characterization of the Liposomes
Authors: Perrett Stephen , Golding Michael , Williams W Patrick 
Published: April 2011

Abstract
A new method for the preparation of liposomes is described that avoids the use of pharmaceutically unacceptable solvents and energy-expensive procedures such as sonication. The method is based on the initial formation of a proliposome mixture containing lipid, ethanol and water, which is converted to lipsomes by a simple dilution step. Measurements using 6-carboxyfluorescein as a marker indicate that water-soluble drugs can be trapped with extremely high efficiency (65–80% depending on lipid composition). The structural organization of the proliposome mixture and the final liposomes were characterized using electron microscopy and 31P-NMR.
Distribution of Subcutaneously Administered Inulin between Blood and Peripheral Lymph in the Rabbit
Authors: Lamka J , Krejčová V , Vondráčková Z , Gallová Š , Květina J 
Published: April 2011

Abstract
In experiments on rabbit peripheral lymph, the contribution of the blood and lymphatic system to the whole-body distribution of inulin after subcutaneous administration has been investigated and the effects of hyaluronidase and of thermal stimulus at the administration site examined. Inulin concentrations in lymph exceeded plasma concentrations by more than 100-fold. At the end of the experiment (90 min) the amount of drug in the total lymph collected was about one-seventh the amount found in urine. The blood system, as a result of higher circulation at the administration site distributes inulin from the subcutis more rapidly than does lymph. Hyaluronidase did not influence inulin concentrations in blood and lymph but thermal stimulus significantly decreased both concentration and total distribution. The decrease resulted from a developed oedema and vasoconstriction in the skin and subcutis of the cannulated extremity.
Thixotropic phenomenon in flocculated aqueous dispersions of acrylate methacrylate copolymers
Authors: Okor R S 
Published: April 2011

Abstract
Aqueous gels of two analogous, water-insoluble copolymers A and B have been formed by addition of excess water to concentrated ethanol solutions of the polymers. A and B differed only in their content of cationic groups in a ratio 2:1 (A: B). The gels were converted permanently to fluids (i.e. gel-sol transformation) at high shear rates. Stability of the resulting polymer dispersions depended on the presence and mutual repulsion of the polymer cations. Polymer B dispersions were less stable to the flocculating effect of an electrolyte (sodium chloride). At certain critical concentrations, 0.2 M NaCl (for polymer A), or 0.1 M NaCl (for polymer B) the electrolyte flocculated the otherwise stable dispersions to a gel structure. The electrolyte-flocculated gels were readily redispersed to fluids by shaking but reverted to gels on standing (thixotropic). In contrast the original coacervated gels (without electrolyte) could not be redispersed easily with manual shaking. Lower polymer-polymer interaction in the thixotropic system relates possibly to increases in particle size and irregularity of particle shape during flocculation.
A new method for assessment of drug absorption from muscle: application of a local perfusion system
Authors: Nara Eiji , Hatono Tetsuya , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
Drug absorption from muscle has been examined using the rabbit hind leg, isolated by cannulating the femoral artery and vein, and perfused with or without bovine serum albumin (BSA) using a single-pass technique. A model compound, [14C]sucrose, was injected into the musculus gastrocnemius, and its appearance in the venous outflow was monitored and kinetically analysed by statistical moment theory. The fraction absorbed and mean arrival time in the venous outflow were calculated to be 103% and 50.5 min, respectively, in the BSA-containing system. The results of perfusion experiments without BSA were not significantly different, suggesting possible use of the simpler BSA-free perfusion system to obtain information on the muscular absorption of drugs.
Chronic D1-receptor blockade: effects on D2-receptor agonist-induced yawning in rats
Authors: Hietala Jarmo , Lappalainen Jaakko , Syvälahti Erkka 
Published: April 2011

Abstract
The effects of chronic treatment with the selective D1 dopamine receptor antagonist SCH 23390 (0.25 mg kg−1 s.c. twice daily for 18 days, 4 days withdrawal on yawning induced by the D2-receptor agonist quinpirole has been investigated. Low doses of quinpirole (20 and 50 μg kg−1 s.c.) induced dose-related yawning behaviour in rats. The yawning response to quinpirole was not significantly different in the presence or absence of SCH 23390 pretreatment. However, chronic treatment with SCH 23390 alone significantly suppressed yawning behaviour. The results suggest that chronic D1-receptor blockade with SCH 23390 does not alter the function of the D2-receptor population mediating yawning behaviour. However, after withdrawal it may result in behavioural activation as seen by suppression of yawning behaviour in the present study.
First-derivative spectrophotometric determination of salbutamol in pharmaceutical preparations
Authors: Hackmann E R M , Benetton S A , Santoro M I R M 
Published: April 2011

Abstract
The development of a first-order derivative spectrophotometric assay of salbutamol as a single-component and in combination with beclomethasone dipropionate in pharmaceutical formulations is described. The method eliminates the interference of tablet excipients and allows the determination of both components without their previous separation. The precision of the method for the assay of salbutamol in tablets was 1.0% with an average recovery of 98.8%. In the assay of the two-component preparation, the precision was 1.1%, with average recoveries for salbutamol of 99.3% and for beclomethasone dipropionate of 99.4%.
Intestinal Absorption of Drugs. The Influence of Mixed Micelles on on the Disappearance Kinetics of Drugs from the Small Intestine of the Rat
Authors: Poelma F G J , Breäs R , Tukker J J , Crommelin D J A 
Published: April 2011

Abstract
The solubilization of the hydrophilic drugs paracetamol and theophylline, and the lipophilic drugs dantrolene, griseofulvin and ketoconazole has been determined in mixed micellar aqueous dispersions composed of 10 mM taurocholate + 5 mM oleic acid. The solubilization of dantrolene and paracetamol has also been determined in aqueous (mixed) micellar dispersions of 1 g L−1 lysophosphatidyl-choline (LPC), or taurocholate/LPC. The influence of these (mixed) micelles on the absorption of the model drugs from solution was studied in the rat chronically isolated internal loop. Absorption kinetics of the drugs were evaluated on the basis of the disappearance rate of the drug dissolved in the perfusion medium in this loop. Absorption experiments with taurocholate/oleic acid in the perfusate resulted in a reduction of the disappearance rate for the lipophilic drugs and the hydrophilic drug theophylline. This could partly be ascribed to the decreased fraction of drug free in solution as a result of its micellar solubilization for dantrolene, griseofulvin and ketoconazole, but the decrease in the disappearance rate of theophylline was unexpected. Taurocholate/oleic acid, LPC and taurocholate/LPC micelles had no effect on the disappearance of paracetamol. The disappearance rate of dantrolene in the presence of LPC alone was not altered, in spite of the decreased fraction of the drug free in solution owing to its micellar solubilization. In contrast, taurocholate/LPC micelles caused a reduction in the rate of disappearance of dantrolene, as expected according to the phase-separation model. In-vitro, taurocholate and taurocholate/LPC reduced the molecular cohesion of porcine intestinal mucus, whereas LPC alone did not exhibit an effect on the gel structure of mucus. It is concluded that the transfer of solutes across the pre-epithelial aqueous diffusion layer (including the mucus) and the epithelium is unaltered by (mixed) micelles at concentrations in the physiological range.
Non-synaptic Cholinergic Modulation of Neurogenic Twitches of the Guinea-pig Ileum
Authors: Kadlec O , Hynie S , Mas̆ek K , S̆eferna I , S̆evc̆ík J 
Published: April 2011

Abstract
The effect of cholinergic and anticholinergic compounds on conduction of neuronal excitation has been studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment (10 mm) so that the aboral segment might be also invaded, eventually. Drugs were added to the middle segment to affect neuronal propagation (non-synaptic effects) which was monitored by twitch height of the aboral segment. The application of acetylcholine to the middle segment augmented aboral twitches. The effects of nicotine, pilocarpine and oxotremorine were selectively blocked by (+)-tubocurarine, pirenzepine and atropine, respectively. The effect of acetylcholine was suppressed by pirenzepine and atropine and mimicked by doubling of KC1 concentration. The effect of acetylcholine may be thus explained by the facilitated propagation of nerve action potentials in partially depolarized cholinergic terminals via stimulation of muscarinic receptors. The adenylate cyclase system is not directly involved in the mechanism of muscarinic facilitation of neuronal propagation in the terminals; however, it may participate in the modulation of a final common effector mechanism.
Inhibitory Effect of 2-Hydroxypropyl-β-cyclodextrin on Crystal-growth of Nifedipine During Storage: Superior Dissolution and Oral Bioavailability Compared with Polyvinylpyrrolidone K-30
Authors: Uekama Kaneto , Ikegami Kengo , Wang Zheng , Horiuchi Yasuhide , Hirayama Fumitoshi 
Published: April 2011

Abstract
To prevent the crystal-growth of nifedipine during storage, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) was employed as a hydrophilic drug carrier and compared with polyvinylpyrrolidone K-30 (PVP). Amorphous nifedipine powders were prepared by spray-drying with HP-β-CyD or PVP, and their crystal-growing behaviour at accelerated storage conditions were examined by X-ray diffraction analysis and microscopy. Although PVP initially retarded the crystallization of nifedipine, it failed to control the increase of crystal size after prolonged storage at 60°C., 75% r.h., resulting in a remarkable decrease in dissolution rate in water. In sharp contrast, a relatively fine and uniform size of nifedipine crystals was maintained in the HP-β-CyD system even after accelerated storage conditions. The enhanced dissolution observed for all the HP-β-CyD systems in a dissolution medium containing 0·1% non-ionic surfactant HCO-60 were clearly reflected in the in-vivo absorption of nifedipine following oral administration to dogs. These results suggest that HP-β-CyD is particularly useful in solving problems encountered on storage of amorphous nifedipine in solid dosage forms.
Stomach outline visualization in gastrointestinal transit studies using scintigraphy
Authors: Course N J , Newton J M , Short M D 
Published: April 2011

Abstract
A major disadvantage of gamma scintigraphy in gastrointestinal transit studies is the inability to provide adequate delineation of anatomical details. As an aid to the important requirement of outlining the stomach to ensure accurate quantification of the time at which material empties from this organ, a new technique is described, using short half-life 81mKr gas to provide clearer identification of the stomach outline and position.