bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-nociceptive activity of nitric oxide synthase inhibitors in the mouse: dissociation between the effect of l-NAME and l-NMMA
Authors: Babbedge R C , Hart S L , Moore P K 
Published: April 2011

Abstract
The anti-nociceptive effect of selective inhibitors of nitric oxide synthase has been assessed in a formalin-induced paw-licking model in mice. l-NG-Nitro arginine methyl ester (l-NAME) but not l-NG-monomethyl arginine (l-NMMA) exhibited anti-nociceptive activity in both the early and late phases of paw licking following intraperitoneal administration. The effect on the late phase response was more pronounced. l-NAME (0·1–100 μg) and l-NG-nitro arginine base (l-NOARG; 10 μg) but not d-NAME (10 μg) were also anti-nociceptive following intracerebroventricular administration. l-NAME (10 μg) administered by this route did not influence locomotor activity. l-NMMA was inactive at doses up to 40 μg by this route. At higher doses (75–200 μg) l-NMMA produced a similar and non-dose related reduction in early/late phase paw-licking time. d-NMMA (100 μg) was inactive. The greater anti-nociceptive effect of l-NAME in this model accords with recently published biochemical data indicating that l-NAME is several orders of magnitude more potent than l-NMMA as an inhibitor of brain nitric oxide synthase. These data support the use of l-NAME as a selective tool to investigate the central pharmacological effects of nitric oxide.
The Effect of Carbohydrate Additives in the Freeze-Drying of Alkaline Phosphatase
Authors: Ford Annette W , Dawson Peter J 
Published: April 2011

Abstract
Alkaline phosphatase was used as a model in studies to assess the effects of lyophilization on biological activity and molecular integrity in the presence or absence of added carbohydrate. The stability of the activity of alkaline phosphatase, lyophilized in Tris buffer alone or in the presence of the carbohydrates mannitol, lactose or trehalose was examined. Enzyme activity in formulations with Tris buffer alone or with mannitol was considerably reduced by freeze-drying and further storage at elevated temperatures; freeze-drying with mannitol failed to maintain activity at a temperature of 37°C over 21 days, whilst the loss of activity was more gradual when freeze-dried in buffer alone and stored at higher temperatures. Lactose and trehalose maintained the alkaline phosphatase activity after freeze-drying and, furthermore, preparations containing trehalose retained activity even when the material was subjected to temperatures of up to 45°C for up to 84 days. At 56°C the alkaline phosphatase activity did not show a significant drop until 14 days with the lactose formulation or until 21 days with trehalose. After 84 days at 56°C, 30% of the activity still remained in the formulation containing trehalose. In addition to the changes in the enzyme activity, FPLC chromatographic traces and SDS-PAGE gels demonstrated compositional differences between each formulation after storage.
Effect of Bicarbonate-free Balanced Salt Solutions on Fluid Pump and Endothelial Morphology of Rabbit Corneas In-vitro
Authors: Doughty Michael J , Newlander Kflly , Olejnik Orest 
Published: April 2011

Abstract
Corneas from young adult albino rabbits were exposed, in-vitro, to various bicarbonate-free balanced salt solutions under an applied hydrostatic pressure of 20 cmH2O at 35°C for up to 4·5 h. The solutions were buffered with a HEPES-MOPS mixture, phosphate salts or acetate-citrate salts (pH 7·1–7·4). All of these solutions support a net fluid pump activity attributed to the corneal endothelium although the net fluid pump rates were less than those measurable with a bicarbonate-buffered, CO2-equilibrated Ringer solution. Evaluation of the endothelia by scanning electron microscopy revealed no evidence of any acute toxic effect of the balanced salt solutions. Morphometric analyses of cell size and shape revealed a normal mosaic for endothelia exposed to commercial balanced salt solution for 5 h. The results further indicate that exogenous bicarbonate is not required for the net fluid pump function of the mammalian corneal endothelium.
Host Reaction against Empty Alginate-polylysine Microcapsules. Influence of Preparation Procedure
Authors: Vandenbossche Geert M R , Bracke Marc E , Cuvelier Claude A , Bortier Hilde E , Mareel Marc M , Remon Jean-Paul 
Published: April 2011

Abstract
Microcapsules, prepared with alginate and polylysine, were injected intraperitoneally into mice and the number of peritoneal leucocytes as well as the cells sticking to the capsule wall were counted after 4–28 days. A significant increase in host reaction was observed when the microcapsules contained an outer layer of polylysine as compared with calcium alginate beads without polylysine or microcapsules coated with an outer layer of alginate. The alginate sources influenced the host reaction significantly. After an intraperitoneal residence of 4 days, the microcapsules were mainly surrounded by macrophages. After 28 days, several cell layers surrounded the microcapsules; macrophages, multinucleate giant cells, fibroblasts and mesothelial cells.
Host Reaction against Alginate-polylysine Microcapsules Containing Living Cells
Authors: Vandenbossche Geert M R , Bracke Marc E , Cuvelier Claude A , Bortier Hilde E , Mareel Marc M , Remon Jean-Paul 
Published: April 2011

Abstract
Syngeneic and nude mice were injected intraperitoneally with saline, empty microcapsules, aggregates of tumourogenic MO4 cells, encapsulated non-tumourogenic MO cells and encapsulated MO4 cells. The host reaction 4 days after injection, was evaluated by counting the leucocytes in the peritoneal cavity and the cells sticking to recovered microcapsules. A significantly lower number of peritoneal leucocytes was found in mice injected with empty microcapsules or encapsulated MO cells as compared with encapsulated MO4 cells. Histological evaluation showed a significantly higher number of cells sticking to microcapsules containing cells as compared with empty microcapsules. These observations showed that the cellular host reaction against intraperitoneal implants can be evaluated by counting the leucocytes in the peritoneal lavage and histology of recovered capsules.
Bromhexine plus Oxytetracycline: the Effect of Combined Administration Upon the Rheological Properties of Mucus from the Mini-pig
Authors: Martin Gary P , Loveday Bernard E , Marriott Christopher 
Published: April 2011

Abstract
Three adult mini-pigs were employed to assess the effects of a twice daily dosage (40 mg kg−1) of oxytetracycline hydrochloride (OTC) and a combination of OTC with (0·5 mg kg−1) bromhexine hydrochloride (BHC) on the rheological properties and wet weight of secreted tracheal mucus. Mucus was collected daily from open-ended tracheal pouches established surgically in the mini-pigs. After a five day control period, either OTC or OTC plus BHC was administered twice daily with the normal diet. Each study period was followed by a five day washout period when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. OTC was shown to increase the residual shear viscosity (P &lt; 0·01) and increase the instantaneous compliance (P &lt; 0·01). An increase in the wet weight of the collected mucus occurred in one pig only (P &lt; 0·01). When BHC was co-administered with OTC, all of these changes were abolished. Evidence was obtained to suggest that BHC increased the concentration of OTC within the secreted mucus. BHC appeared to reverse the mucospissic activity of OTC in-vivo.
Effects of LP-805, a Newly Developed Vasodilator, on Myocardial Metabolism in Ischaemic Dog Hearts
Authors: Ichihara K , Morimoto T , Tsujitani M , Abiko Y 
Published: April 2011

Abstract
The effects of LP-805, a newly developed vasodilator, on changes in the myocardial energy and carbohydrate metabolism induced by ischaemia were studied in open-chest anaesthetized dogs. Ischaemia was induced by ligating the left anterior descending coronary artery for 3 min. The myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered 3 min after the onset of ischaemia. Energy change potential was decreased, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were increased by ischaemia. These findings indicated that the myocardial metabolism was converted from an aerobic to an anaerobic type by ischaemia. LP-805 (10, 30, or 100 μg kg−1) was injected intravenously 5 min before the onset of ischaemia. LP-805 prevented the myocardial energy depletion and alterations of myocardial carbohydrate metabolism due to ischaemia, indicating that it appeared to convert the anaerobic metabolism back to aerobic metabolism in the ischaemic myocardium. In conclusion, LP-805 may reduce the ischaemic influence on the myocardium.
A comparison of the incorporation of model steroids into non-ionic micellar and microemulsion systems
Authors: Malcolmson Carole , Lawrence M Jayne 
Published: April 2011

Abstract
The incorporation of testosterone and two of its esters, and progesterone and one of its esters (log Poct varying from 3·3 to 6·9) into 2% w/w soybean oil/Brij 96 microemulsions and Brij 96 surfactant systems has been examined. Possible sites of incorporation have been investigated. The drug carrying improvement of an oil-in-water microemulsion over a micellar system appears to depend on the solubility of the drug in the dispersed oil phase and is significant only for very lipophilic drugs.
Reduced kallikrein excretion by liposome-encapsulated cyclosporin in the rat
Authors: Akbarieh Mostafa , Adam Albert , Legris Fabien , Tawashi Rashad 
Published: April 2011

Abstract
Different phospholipids and methods of preparation were used to produce cyclosporin encapsulated in liposomes. The optimal formulation of cyclosporin-liposome was compared to the oily cyclosporin after intraperitoneal administration of 25 mg kg−1 body weight to rats. Urinary kallikrein excretion was significantly reduced with the liposomal form. The abrupt increase of kallikrein excretion after the tenth day with the control oil preparation suggests that cyclosporin toxicity could be present at the tubular level, and the encapsulation of cyclosporin in liposomes reduces tubular damage.
Influence of intravenous infusion of ethanol on regional blood flow in conscious rats
Authors: Tabrizchi Reza , Pang Catherine C Y 
Published: April 2011

Abstract
The effects of intravenous infusions of ethanol and saline (0·9% NaCl) on mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), cardiac contractility (dP/dtmax) and systemic haemodynamics were studied in conscious, unrestrained rats by the radioactive microsphere technique. Saline (0·03 and 0·06 mL min−1 kg−1 for 12 min each dose) in the time-control group did not affect MAP, HR, TPR, dP/dtmax or vascular conductances in any organs or beds. While the low dose ethanol (2·4 mg min−1 kg−1) did not alter MAP, HR, TPR, systemic haemodynamics or dP/dtmax, the high dose (4·8 mg min−1 kg−1) slightly reduced MAP and TPR but did not affect HR, cardiac output or dP/dtmax. Both doses of ethanol vasodilated the intestine and spleen, but vasoconstricted the skin. The high dose caused additional vasodilatation in the heart and testes and the low dose also constricted the skeletal muscle bed. Our results show that ethanol, at non-hypotensive or slightly hypotensive doses, has marked vasodilator effects in the heart, intestine, spleen and testes.
Structural Requirements for the Direct and Cytochrome P450-dependent Reaction of Cyclic α,β-Unsaturated Carbonyl Compounds with Glutathione: a Study with Coumarin and Related Compounds
Authors: Fry Jeffrey R , Fentem Julia H , Salim Alena , Tang S P Anna , Garle Michael J , Whiting Donald A 
Published: April 2011

Abstract
The interaction of glutathione (GSH) with coumarin, or one of a series of compounds related to coumarin, was assessed in the absence and presence of liver microsomes (direct reaction and indirect reaction, respectively) to determine the structural requirements for direct and mono-oxygenase-mediated reaction of cyclic α,β-unsaturated carbonyls with GSH. Acrolein was used as a positive control for the direct reaction, and produced complete or nearly complete depletion of GSH under all assay conditions. 5,6-Dihydro-2H-pyran-2-one and 2-cyclohexen-1-one also produced substantial depletion of GSH in the direct reaction, which was not increased by the addition of liver microsomes. Coumarin, 2H-pyran-2-one and precocene I (a substituted pyran lacking the 2-one structure) were not substrates for the direct reaction but did cause depletion of GSH when incubated in the presence of rat or human liver microsomes. These depletions were dependent on a functioning mono-oxygenase system as judged by the effects of omission of cofactors, addition of competitive or inactivating inhibitors of cytochrome P450, and induction. Dihydrocoumarin, ∂-valerolactone, cyclohexanone and 4H-pyran-4-one were not substrates for either the direct or indirect reaction. These findings are rationalized on the basis of a direct nucleophilic attack of GSH on the α,β-centre of the α,β-unsaturated carbonyl compounds, which is hindered by benzenoid resonance in coumarin and 2H-pyran-2-one, for which enzyme-mediated reaction with GSH, probably via a 3,4-epoxide, is the favoured mechanism.
In-vitro permeation of some β-blockers across the hairless mouse skin
Authors: Ghosh Tapash K , Chiao Charles S , Gokhale Rajeev D 
Published: April 2011

Abstract
To support the development of a suitable transdermal dosage form for β-blockers, in-vitro, skin permeation studies of nine β-blockers were conducted at 37°C across the excised abdominal skin of hairless mouse mounted on the receptor compartment of a two-chambered Valia-Chien glass diffusion cell. The drugs varied in lipophilicity, whereas pKa values were comparable. Permeability coefficients were calculated from the steady-state flux values. Agreement was found between the permeability coefficient and the drug lipophilicity, expressed as the octanol-bufter distribution coefficient.
Effect of Bay K 8644 on the synthesis and metabolism of dopamine and 5-hydroxytryptamine in various brain areas of the rat
Authors: Colado M I , Ormazabal M J , Alfaro M J , Martin M I 
Published: April 2011

Abstract
The effects of Bay K 8644 (1,2 and 4 mg kg−1, i.p.) on the synthesis and metabolism of dopamine and 5-hydroxytryptamine (5-HT) in rat brain after m-hydroxybenzylhydrazine administration were studied. Bay K 8644 (2 and 4 mg kg−1, i.p.) caused an increase in the synthesis of both dopamine in the striatum and 5-HT in the midbrain and striatum, measured as the accumulation of 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytryptophan, respectively. Moreover, Bay K 8644 at the dose of 4 mg kg−1 increased the turnover of dopamine in the striatum and of 5-HT in midbrain and striatum. These neurochemical changes were antagonized by the calcium channel antagonist nimodipine (10 mg kg−1, i.p.). It is concluded that dihydropyridine receptors may mediate the brain region-specific changes in the dopaminergic and 5-HT-ergic neurotransmission which occur following activation of neuronal calcium channels.
Stereoselective binding of β-blockers to purified rat α1-acid glycoprotein
Authors: Murai-Kushiya Mami , Okada Satoshi , Kimura Toshio , Hasegawa Ryuichi 
Published: April 2011

Abstract
The stereoselectivity of binding of four β-blockers, pindolol, propranolol, oxprenolol and acebutolol, to purified rat α1-acid glycoprotein (AAG) was examined using equilibrium dialysis. Pindolol and propranolol were bound stereoselectively to AAG, whereas binding of oxprenolol was non-stereospecific. Neither of the enantiomers of acebutolol bound to either AAG or any other plasma protein. The affinity of (+)-pindolol was 25 times that of (–)-pindolol, as determined in a single enantiomer experiment. Both enantiomers of propranolol demonstrated two classes of binding sites in AAG, the total binding for the high affinity site for (+)-propranolol being double that of (–)-propranolol, which could explain the higher binding of the (+)-enantiomer in racemate experiments. These results further showed that stereoselective binding to a rat AAG is not a property common to all β-blockers.
Centpropazine affinity to cortical noradrenergic receptors and effect on their responsiveness in the rat
Authors: Dikshit M , Chalecka-Franaszek E , Nalepa I 
Published: April 2011

Abstract
We have studied the in-vitro effect of centpropazine on cerebral cortical noradrenergic receptors measured as the accumulation of second messengers, cyclic AMP and inositol phosphate, stimulated by noradrenaline, and the binding to α1- and β-adrenoceptors. Centpropazine inhibited inositol phosphate, but not the cyclic AMP accumulation in the cerebral cortical slices of the rat. It moderately antagonized the specific binding of [3H]prazosin but did not affect the specific binding of the β-adrenoceptor ligand, [3H]CGP 12177, to cerebral cortical membranes.
A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea
Authors: Washio Kanetoshi , Makaya Osami , Sasaki Hitoshi , Nishida Koyo , Nakamura Junzo , Shibasaki Juichiro 
Published: April 2011

Abstract
We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p-formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg−1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3-(p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit.
Contraction Induced Either by Iso-osmolar or Hyper-osmolar Potassium-rich Solutions Influences Relaxant Responses to Pinacidil and Verapamil in Rat Isolated Aorta
Authors: Nielsen Claus Brøsckner 
Published: April 2011

Abstract
Relaxant responses of pinacidil and verapamil were studied in rat isolated aorta contracted by either iso-osmolar or hyper-osmolar potassium-rich solutions. Relaxant response profiles of pinacidil and verapamil in rat isolated aorta contracted by 124 mm K+ hyper-osmolar Krebs solutions showed marked reductions in inhibiting Emax values and substantial increases in corresponding IC50 values in comparison with results obtained at iso-osmolar conditions. Changes in the slopes of the fitted log concentration-relaxation curves were also observed, whereas pinacidil relaxation curves obtained after initial contraction induced by 30 mm K+ Krebs solutions were only slightly influenced by osmolarity, a definite decrease in Emax occurred for verapamil at hyper-osmolar conditions. Initial tension development was much slower and maximal tension lower when induced by 124 mm K+ in hyper-osmolar compared with iso-osmolar Krebs solutions. After incubation in Ca2+-deprived EGTA-containing Krebs solutions the maximal tension produced by 124 mm K+ iso-osmolar Krebs solution in rat aorta was nearly 95% reduced, whereas it was only reduced by 50% at hyper-osmolar conditions. Hyper-osmolarity as established by direct addition of potassium chloride to Krebs solutions in order to induce contraction in vascular smooth muscle could influence the in-vitro action profile, potency and intrinsic activity of the two vascular relaxant drugs.
Effects of Dopamine on the Gastrointestinal Tract of Chicks
Authors: Lot Theodore Y 
Published: April 2011

Abstract
The effects of dopamine on the gastrointestinal tract of chicks have been investigated. Dopamine caused concentration-related contractions of the upper oesophagus, crop or lower oesophagus but relaxed the duodenum, ileum, large intestine or caecum in a concentration-related fashion. By means of specific antagonists, the presence of muscarinic, histamine (H1), α-adrenergic, 5-HT-ergic and dopaminergic receptors were established in the lower oesophagus and their stimulation caused contraction while β-adrenergic-receptor stimulation caused relaxation. Contraction of the lower oesophagus induced by dopamine was abolished by lysergic acid diethylamide and was antagonized by moderate concentrations of haloperidol or pimozide. Tachyphylaxis developed to repeated administration of a large concentration of dopamine. These findings suggest that contraction of the lower oesophagus of chicks by dopamine is largely mediated by 5-hydroxytryptamine release and that stimulation of dopaminergic receptors contributes to a lesser extent.
The Adverse Effect of Glycation of Human Serum Albumin on its Preservative Activity in the Freeze-Drying and Accelerated Degradation of Alkaline Phosphatase
Authors: Ford Annette W , Allahiary Zahra 
Published: April 2011

Abstract
The effects of a glycated protein additive on the stability of freeze-dried biological standards were studied using alkaline phosphatase as a model. Alkaline phosphatase was formulated with artificially glycated albumin, freeze-dried, sealed into glass ampoules and subjected to accelerated degradation studies at temperatures from —20 to 56°C. Alkaline phosphatase, freeze-dried without an additive in neutral buffer, lost over 95% of its activity, but when freeze-dried with human serum albumin it retained approximately 70% of the initial activity. Both deliberately glycated and native albumin protected approximately 70% of the initial activity on freeze-drying and this protection was maintained during storage of the freeze-dried product at temperatures of 20°C or below for up to 16 weeks. At 37°C or above, alkaline phosphatase activity was lost in a time- and temperature-related manner with changes appearing in the SDS-PAGE gels and FPLC chromatograms but, with the artificially glycated albumin formulations, this loss of activity and the changes in the gels and chromatograms happened earlier and at lower temperatures. Formulations with trehalose at 1% w/v and 15% w/v, but without albumin, preserved some 40% of alkaline phosphatase activity following freeze-drying. Further, approximately half of that activity was maintained after 16 weeks' storage at all temperatures up to 56°C by the 15% trehalose without albumin. This study indicates that, in the formulation of freeze-dried biological standards, if albumin is to be used, the initial degree of glycation should be kept to a minimum and combinations of albumin and reducing sugar should be avoided. Trehalose 15% provides an acceptable alternative where exposure to high temperature is likely to occur.
The effect of silymarin and gamma radiation on nucleic acids in rat organs
Authors: Haková H , Mišúrová E 
Published: April 2011

Abstract
The influence of silymarin on radiation-induced changes in concentrations of RNA and DNA was followed in male Wistar rats. The liver, spleen and bone marrow were examined at 30 h, 7, 14 and 21 days after 6 Gy whole-body gamma irradiation or 30 h and 7 days after 3 Gy whole-body gamma irradiation. Following silymarin treatment, a mild increase in the concentration and total content of RNA and DNA in liver and bone marrow at days 7 and 14 after administration was found; in spleen, total content of DNA significantly increased at 30 h. Silymarin administered 1 h before irradiation, moderated radiation-induced changes in nucleic acids in its target organ, liver, and in spleen and bone marrow. We suggest that beneficial effects of silymarin on radiation injury to the membranes of liver cells resulted primarily from its antioxidative ability and its ability to act as a radical scavenger, thereby preventing membrane permeability changes.