bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skin Wound Healing: Some Biochemical Parameters in Guinea-pig
Authors: Buffoni F , Banchelli G , Cambi S , Ignesti G , Pirisino R , Raimondi L , Vannelli G 
Published: April 2011

Abstract
Hairs were removed from the dorsal skin of guinea-pigs and 5–6 wounds (7 × 7 mm) were surgically induced by totally removing the epidermal and part of the dermal surface. They were then allowed to heal. The newly formed wound tissues were dissected at different times during the process and analysed by biochemical and histological methods. Hydroxyproline, proteins, DNA and semicarbazide-sensitive amine oxidase (SSAO) were measured, as were [14C]leucine and [3H]thymidine incorporation in some samples. The peroxidase-like activity of plasma albumin and the histology of wounds stained with haematoxylin-eosin were also studied. It was shown that SSAO enzymes, which are present in normal guinea-pig skin and have a high affinity for benzylamine are localized in fibroblasts. During skin healing in the newly formed tissue there was an increase in protein content which reached a maximum after 4–6 days; DNA content also increased. The rate of incorporation of [3H]thymidine and [14C]leucine paralleled DNA and protein content, respectively. The content of hydroxyproline had greatly decreased with respect to that in normal skin after 2–10 days. SSAO activity increased much less than DNA after 4 days whereas after 10–11 days it increased more than DNA, thus indicating that at this time it was probably produced by fibroblasts. No significant increase in the peroxidase-like activity of albumin was observed 4, 8 or 11 days after surgery. Treatment of the animals with methylprednisolone acetate (20 mg kg−1, i.m.) two days before surgery decreased the rate of skin healing but did not alter the level of albumin peroxidase activity of the plasma. Histology showed that in the animals treated with this drug the re-epithelialization was slower and after 11 days the wound appeared similar in appearance to the 8-day control wounds. In the methylprednisolone-treated animals a positive correlation was observed between the DNA content of regenerating tissue and the hydroxyproline content, whereas a negative correlation was observed in the control wounds. This correlation was in full agreement with the histological observation which showed an increased amount of cytogen collagen in the wounds of the treated animals. The simultaneous study of the biochemical parameters (DNA, proteins, SSAO, hydroxyproline) appears to be a good method for differentiating the pharmacological effects on the different cells which are responsible for wound healing.
γ-Pyrone Compounds as Potential Anti-cancer Drugs
Authors: Liou Shorong-Shii , Shieh Wen-Liang , Cheng Tien-Hsiang , Won Shen-Jeu , Lin Chun-Nan 
Published: April 2011

Abstract
The γ-pyrones, artomunoxanthotrione epoxide, cyclocommunol, cyclomulberrin, and cyclocommunin exhibited potent inhibition of human PLC/PRF/5 and KB cells in-vitro. Dihydroisocycloartomunin showed significant and potent inhibition of human PLC/PRF/5 and KB cells in-vitro, respectively. Cyclomorusin, dihydrocycloartomunin and artomunoxanthone showed significant inhibition of KB cells in-vitro. Based on the above finding and the reported antileukaemic activity of xanthone psorospermin, a series of natural γ-pyrones was prepared and the inhibition of human PLC/PRF/5 and KB cells in-vitro was measured. Structure-activity analysis indicated the epoxide group substituted at 3-hydroxyl and 2,6-; 3,6-; and 3,5-dihydroxyl xanthone enhanced the anti-tumour activity. The epoxide group substituted at the 6-hydroxyl group of 1,6-dihydroxyxanthone did not show anti-tumour activity.
DAU 6215, a novel 5-HT3-receptor antagonist, selectively antagonizes scopolamine-induced deficit in a passive-avoidance task, but not scopolamine-induced hypermotility in rats
Authors: Brambilla Alessandro , Ghiorzi Aldo , Pitsikas Nikolaos , Borsini Franco 
Published: April 2011

Abstract
This study examined the effects of DAU 6215, a selective 5-HT3-receptor antagonist, on either impairment of a passive-avoidance task or hypermotility, both caused by scopolamine in rats. In the first experiment, scopolamine (0·75 mg kg−1, i.p.) disrupted acquisition of a one-trial ‘step through’ passive-avoidance response. Pretreatment with DAU 6215 (1, 10, 30 and 100 μg kg−1, i.p.) antagonized this deficit induced by scopolamine, with a bell-shaped dose-response curve. Scopolamine (0·75 mg kg−1, i.p.) produced a significant increase in locomotor activity which was unaffected by pretreatment with DAU 6215 (10 and 30 μg kg−1, i.p.). The present results further support the suggestion that 5-HT3-receptor antagonists may prevent the memory disturbance caused by a reduction in central cholinergic function in the rat. The inefficacy shown by DAU 6215 on hyperactivity induced by scopolamine appears to rule out the possibility of a pharmacokinetic interference between DAU 6215 and scopolamine.
Solubility, Stability and Ionization Behaviour of Famotidine
Authors: Islam Mohammad S , Narurkar Milind M 
Published: April 2011

Abstract
The pKa of famotidine was determined at 23±0·2°C to be 6·76, 6·98 and 6·89 by a spectrophotometric, solubility, and partitioning method, respectively. The pH-solubility profile of famotidine indicated an intrinsic solubility of 2·7 Mm at 23°C. Degradation of famotidine followed pseudo-first-order kinetics over a pH range of 1–11 at 37±0·2°C and at an ionic strength (μ) of 0·5. The pH-rate profile was accounted for by the specific acid and base catalysed reactions as well as water-catalysed decomposition of both protonated and free famotidine. A pKa of 6·60, determined by potentiometry at 37±0·5°C (μ = 0·5), was used in the kinetic calculations. Maximum stability occurred at pH 6·3. Undissociated acetic acid, dihydrogen phosphate ion and glycine anion were found to contribute to the general acid and base catalyses. pH-dependency of the apparent octanol-water partition coefficient of famotidine indicated a partition coefficient of 0·23 for free famotidine at 23±0·2°C.
Effect of Mode of Incorporation of Disintegrants on the Characteristics of Fluid-bed Wet-granulated Tablets
Authors: Khattab Ibrahim , Menon Anil , Sakr Adel 
Published: April 2011

Abstract
A full factorial experimental design was employed to investigate the effects of mode of disintegrant incorporation and concentration in wet-granulated paracetamol tablets manufactured by topspray fluid-bed. Disintegrants (croscarmellose sodium, sodium starch glycolate, or crospovidone) were incorporated either intragranularly, extragranularly, or distributed equally between the two phases. The results were analysed by a general quadratic equation and response surfaces generated. On examining the results for dissolution studies the combined mode resulted in significantly faster dissolution rates than did the extragranular mode which, in turn, was superior to the intragranular mode of inclusion. These results were reflected in the disintegration studies where the combined mode exhibited the shortest disintegration times for all the disintegrants. Tablet crushing strength was not affected by the mode of incorporation of concentration of the disintegrants. Main as well as interaction effects between the types, mode of incorporation and percent disintegrant employed were significant (P &lt; 0·05) for disintegration time and percent release at 15 min. Croscarmellose sodium exhibited the shortest while crospovidone displayed significantly (P &lt; 0·05) longer disintegration times. Formulations containing crospovidone did not meet official compendial (USP XXII) requirements of 80% in 30 min. In general, croscarmellose sodium and sodium starch glycolate were found to be less sensitive to the mode of incorporation than crospovidone.
Effect of Fat Substitutes, Sucrose Polyester and Tricarballylate Triester, on Digitoxin Absorption in the Rat
Authors: Benmoussa Kamel , Sabouraud Alain , Scherrmann Jean-Michel , Brossard Denis , Bourre Jean-Marie 
Published: April 2011

Abstract
The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and tricarballylate triester (TCTE)) on [3H]digitoxin intestinal absorption was studied in the rat using a small intestine in-situ perfusion technique. The effect of SPE and TCTE was compared with that of sunflower oil, oleic acid, and saline. After 120 min perfusion, 5% SPE emulsion significantly reduced (P &lt; 0·001) digitoxin absorption compared with all other treated groups. Five per cent TCTE emulsion had a less marked effect than SPE (P = 0·0002) and did not differ from sunflower oil. No difference was found between saline and 5% oleate emulsion, which did not reduce digitoxin absorption compared with other treated groups (P &lt; 0·02). When taurocholic acid and lipase were added, results for the saline-, TCTE-, and SPE-treated groups were similar to those above, but the sunflower oil-treated group showed significantly enhanced (P &lt; 0·01) digitoxin absorption. Thin-layer chromatography of the lipid phases showed hydrolysis of sunflower oil in the presence of taurocholic acid and lipase, but not of TCTE or SPE. The inhibitory effect of the nonabsorbable fat substitutes on digitoxin absorption could be related to drug sequestration by the persistent oil phase constituted by the undigested and then unabsorbed fat substitutes. That part of digitoxin dissolved in the undigested oil phase is consequently unavailable for intestinal absorption.
Modulatory Role of Magnesium on the Contractile Response of Rat Aorta to Several Agonists in Normal and Calcium-free Medium
Authors: Noguera M Antonia , D’Ocon M Pilar 
Published: April 2011

Abstract
Acute withdrawal of external Mg2+ increased basal tone of rat isolated aorta incubated in the presence of Ca2+. Above normal levels of Mg2+ (1–4 Mm) inhibited basal tone while much higher levels of the divalent cation (64–256 Mm) evoked contractile responses regardless of the presence of Ca2+. Contractile responses to noradrenaline (1μm) and KCl (80 Mm) were inhibited by addition of cumulative concentrations of Mg2+. Acetylcholine-induced contractions in the presence of physiological concentrations of Mg2+ (1 Mm) decreased gradually to the basal tone, but a sustained contraction was observed in the absence of this ion. In Ca2+-free medium, acetylcholine-induced phasic responses indicate the existence of an acetylcholine-sensitive Ca2+ store. KCl induced contraction only in Krebs solution, although a small residual contraction could be observed in Ca2+-free medium in some experiments. Mg2+-depletion in the extracellular medium increased contractile responses induced by acetylcholine and KCl in Ca2+-free medium. These results suggest that extracellular Mg2+ modulates basal tone, Ca2+ channels and responsiveness to various agents in the absence of Ca2+.
Protective effects of cyclodextrin sulphates against gentamicin-induced nephrotoxicity in the rat
Authors: Uekama Kaneto , Shiotani Kazufumi , Irie Tetsumi , Ishimaru Yasuji , Pitha Josef 
Published: April 2011

Abstract
The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied. Daily subcutaneous injection of gentamicin (100 mg kg−1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex. When cyclodextrin sulphates were given intraperitoneally at 300 mg kg−1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective. Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity. These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment.
The effect of surfactant on drug-plastic sorption phenomenon in solution
Authors: Li L C , Zhang H , Pecosky D A 
Published: April 2011

Abstract
The sorption of calcitriol into PVC from an injectable formulation containing Tween 20, a nonionic surfactant, was studied. The amount of drug sorbed by the plastic decreased as the concentration of the surfactant increased. The apparent partition parameter of the drug between PVC strips and the solution was experimentally determined at three different concentrations of the surfactant. A physical model was developed to describe mathematically the partition equilibrium of the drug between the plastic solid phase, the micellar phase of the surfactant, and the aqueous phase of the solution. This model also allowed the calculation of the drug/plastic and drug/micelle partition parameters using the experimentally determined apparent partition parameters.
Gastrointestinal loss of galanthamine hydrobromide in rats in-situ
Authors: Yamboliev I , Mutafova-Yambolieva V , Mihailova D 
Published: April 2011

Abstract
The disappearance kinetics of the acetylcholinesterase inhibitor galanthamine hydrobromide from the gastrointestinal tract of male Wistar rats, 200–250 g, in-situ has been examined. After 30 min the galanthamine loss was 16% in the stomach (pH 2), 54–85% in the duodenum and the successive small intestinal segments (pH 6·8), 43% in the colon and 76% in the rectum. Compared with the other segments, the disappearance rate was higher in the terminal ileum (0·38 × 10−2 mg cm−1 min) and in the rectum (1–27 × 10−2 mg cm−1 min). In the proximal jejunum, terminal ileum and rectum the disappearance rate was linearly dependent on the galanthamine dose (range 0·5–4 mg, 2–16 mg kg−1). The results suggest that when administered orally, rapid galanthamine absorption could be expected all over the gastrointestinal tract due mainly to the passive diffusion mechanism.
The Decomposition of Phenylmercuric Nitrate in Sulphacetamide Drops During Heat Sterilization
Authors: Parkin J E 
Published: April 2011

Abstract
Analytical methods have been developed which enable phenylmercuric nitrate, mercuric ion and diphenylmercury to be measured in sulphacetamide drops. Application of these methods demonstrate that during heat sterilization of both 10 and 30% sulphacetamide drops containing phenylmercuric nitrate, together with disodium edetate and sodium metabisulphite, there is a 20–30% overall loss of phenylmercuric nitrate. This loss occurs mainly due to the phenylmercuric ion establishing an equilibrium with equimolar amounts of mercuric ion and diphenylmercury.
Do antidiarrhoeal opiates accumulate in the rat intestinal lumen?
Authors: De Luca Anthony , Murray Gerard , Coupar Ian M 
Published: April 2011

Abstract
The opiate antidiarrhoeal drugs loperamide (0·6 mg kg−1, i.p.) or difenoxin (0·77 mg kg−1, s.c), were administered in an anaesthetic mixture (pentobarbitone 60 mg kg−1) to rats. A length of jejunum (approx. 30 cm) was cannulated, washed and then perfused with iso-osmotic saline for 20 min. The perfusion commenced 50 min after drug administration and continued for 20 min. The perfusates were collected for analysis of fluid transport rates and antidiarrhoeal drug content. These doses of the antidiarrhoeals caused marked inhibition of intestinal fluid secretion induced by intra-arterial infusion of vasoactive intestinal peptide. However, neither of the antidiarrhoeal drugs were detected in the intestinal perfusates (&lt; 0·5 ng by HPLC). The results indicate that loperamide and difenoxin have a different pharmacokinetic profile compared with that previously found for morphine under the same conditions.
The effect of three H2-receptor antagonists on the disposition of midazolam in the rat in-situ perfused liver model
Authors: Hughes C M , Swanton J G , Collier P S 
Published: April 2011

Abstract
The rat in-situ perfused liver model was used to investigate the effect of three H2-receptor antagonists on the pharmacokinetic disposition of the short-acting benzodiazepine, midazolam. Perfusion experiments, using standard techniques, were carried out on four groups (one control and three H2-receptor antagonist-treated groups) of male Sprague-Dawley rats (300–350 g). All animals received midazolam 1 mg; the three treated groups received Cimetidine (8 mg), ranitidine (3 mg) or famotidine (0.4 mg). Perfusate and bile samples were collected and assayed for midazolam using gas chromatography. The perfusate data indicated that midazolam disposition was impaired at 10, 50 and 60 min of the experimental period following the addition of cimetidine, whereas ranitidine and famotidine produced an effect at 10 min only; midazolam levels in bile were not affected by the presence of an H2-receptor antagonist. It was concluded that the limited inhibitory effect of cimetidine may be attributed to its lack of specificity for CYP3A, the isoenzyme responsible for the metabolism of midazolam.
The Vagus Nerve and its Non-cholinergic Mechanism in the Modulation of Ethanol-induced Gastric Mucosal Damage in Rats
Authors: Ko J K S , Cho C H , Ogle C W 
Published: April 2011

Abstract
The role of the cholinergic pathway in the vagus nerve in modulating gastric lesion formation by ethanol was examined, using an ex-vivo stomach chamber preparation. Subdiaphragmatic vagotomy significantly increased the lesion areas but lowered acid secretion and gastric mucosal blood flow (GMBF). Atropine had no effect, whereas pirenzepine antagonized ethanol-induced mucosal damage. All three procedures showed similar potencies in depressing acid secretion, but only pirenzepine reversed the fall in the GMBF produced by ethanol. These differential effects of vagotomy, atropine and pirenzepine on gastric function suggest that the cholinergic component in the vagus nerve may not be important in the formation of ethanol-induced gastric damage. The persistent protective action as well as the restoration of ethanolinduced GMBF drop by pirenzepine in vagotomized animals further support this hypothesis. The worsening effect of vagotomy is probably modulated by a non-cholinergic mechanism, the abolition of which makes the gastric mucosa more susceptible to damage by ethanol. The acid-independent protective action of pirenzepine and its influence on the GMBF, which were not exhibited by atropine, are indeed unique and perhaps may be attributed to this non-cholinergic pathway.
Plasma Protein Binding of the Experimental Antitumour Agent Acridine-4-carboxamide in Man, Dog, Rat and Rabbit
Authors: Evans Sean M H , Robertson Iain G C , Paxton James W 
Published: April 2011

Abstract
The plasma binding of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) was investigated in-vitro by equilibrium dialysis for 3 h at 37°C against isotonic phosphate buffer (pH 7·35) using [3H]AC. There were significant species differences with the smallest % free fraction (mean ± s.d.) occurring in human plasma (3·4 ± 0·2), followed by dog (8·1 ±0·4), mouse (14·8 ± 0·8), rat (16·3 ± 0·9) and rabbit (20·2 ± 0·7). In plasma from healthy individuals (n = 5), the % free fraction ranged from 2·7 to 3·8. In physiological solutions of human proteins, the greatest binding was observed for α-acid glycoprotein (AAG) (0·75 g L−1) with a mean free fraction of 24·1 ± 2·2%, followed by albumin (40 g L−1) with 31·6 ± 0·7 and 39·8 ± 2·5% for fatty-acid-free and globulin-free, respectively. There was also some binding to globulins (5 g L−1) with a mean % free fraction of 70·3 ± 1·6 and 84·8 ± 2·2 for Conn’s fraction I and IV, respectively. Binding data from the displacement of [3H]AC by increasing concentrations of AC in human AAG (0·75 g L−1) or albumin solution (40 g L−1) indicated that AAG had 10-fold greater binding affinity for AC (Ka, 7·8 × 104 m−1) compared with albumin (Ka, 6·8 × 103 m−1). In human plasma enriched with AAG there was a significant negative linear correlation (r = 0·932; P &lt; 0·001) between % AC free fraction and increasing AAG concentration over the range 0·6–4·5 g L−1. Small but significant (P &lt; 0·05) increases in AC free fraction occurred in the presence of various metabolites (50 and 100 μm) but, of those tested, only N-monomethyl-acridine carboxamide increased the free fraction to the same extent as parent AC.
Development and Characterization of a Liposome Preparation by a pH-Gradient Method
Authors: Vemuri Sriram , Rhodes C T 
Published: April 2011

Abstract
A pH gradient across liposome bilayers was established in order to load a model drug (orciprenaline sulphate) into liposome vesicles. This method of liposome loading resulted in yields as high as 80–85% encapsulation. An eight-step process was designed to scale-up the process and was evaluated. In this process a diafiltration technique was successfully used to remove the excess orciprenaline sulphate present in the external medium. Finally, drug-loaded liposomes were lyophilized using lactose as an internal and external liposomal cryoprotectant. Five-month stability data for the liposomes is reported. An HPLC technique was used to determine the drug concentration and a laser light-scattering technique was employed to determine the liposome vesicle size and polydispersity factor. Liposomes prepared by the pH-gradient method showed high encapsulation efficiency. Upon storage at 2–8°C the vesicle size increased and encapsulation efficiency decreased with time. These phenomena are attributed to gradual fusion of liposomes and loss of drug to the extra-liposomal media.
Evaluation of a Liposome System for the Delivery of Desferrioxamine to Lungs in Rats
Authors: Tabak A , Hoffer E , Taitelman U 
Published: April 2011

Abstract
Liposomes with various lipid composition and sizes, prepared by two different techniques were evaluated for their potential to deliver desferrioxamine to lungs as a treatment against oxidative lung damage. Multilamellar vesicles (MLV) and reverse evaporation vesicles were prepared out of a lipid mixture containing dipalmitoyl phosphatidylcholine, stearyl amine, cholesterol and vitamin E. The administration of desferrioxamine-encapsulated liposomes to rats by the intravenous route at a dose of 100 mg kg−1, significantly prolonged the presence of desferrioxamine in all the tested organs when compared with the administration of free desferrioxamine. The injection of reverse evaporation vesicles extruded through a 2 μm polycarbonate membrane exhibited a longer residence time of the desferrioxamine and of liposomal vitamin E in lungs compared with the other types of liposomes tested. The examination of liposome components in the bronchoalveolar lavage fluid (BALF) and the alveolar macrophages recovered from BALF revealed that about 7 × 10−3% of the administered desferrioxamine dose was recovered by this technique at 3 and 17 h after liposome administration. This high residual concentration in the alveolar space confirms the hypothesis that liposomes can be delivered to the lung tissue when encapsulated in alveolar macrophages.