bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antioxidant Activity of Guaiazulene and Protection Against Paracetamol Hepatotoxicity in Rats
Authors: Kourounakis Angeliki P , Rekka Eleni A , Kourounakis Panos N 
Published: April 2011

Abstract
The effect of guaiazulene, a lipophilic azulene derivative widely found in nature, on radical-mediated processes is examined. The ability of guaiazulene to inhibit rat hepatic microsomal membrane lipid peroxidation and to scavenge hydroxyl radicals, as well as to interact with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), was estimated.
It was found that guaiazulene can inhibit lipid peroxidation very significantly, having an IC50 value of 9.8 μm. It can also scavenge hydroxyl radicals and interact with DPPH. The protection afforded by guaiazulene to rats with paracetamol-induced liver injury was also investigated. Paracetamol hepatotoxicity is caused by the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which causes oxidative stress and glutathione (GSH) depletion. Hepatic cytosolic protein, GSH, glutathione transferase and glutathione reductase levels are determined as indices of hepatic injury with or without the administration of guaiazulene. It was found that all parameters affected by paracetamol are restored to normal by guaiazulene treatment, while the administration of guaiazulene alone has no effect on the performed tests compared with the control values.
It was concluded that the significant protection against paracetamol-induced GSH depletion and hepatic damage afforded by guaiazulene is probably connected with its antioxidant activity. A molecular mechanism of action of guaiazulene is suggested.
Fluorimetric Studies of the Formation of Riboflavin-β-Cyclodextrin Inclusion Complex: Determination of the Stability Constant by use of a Non-linear Least-squares Model
Authors: Loukas Yannis L , Vraka Vassiliki , Gregoriadis Gregory 
Published: April 2011

Abstract
The non-linear least-squares model for calculation of the stability constant (Kst) of a drug-cyclodextrin complex has been used in fluorimetry studies.
Complexation of riboflavin with β-cyclodextrin (β-CyD) was monitored fluorimetrically by measuring changes in the fluorescence intensity of the vitamin in the presence of various amounts of β-CyD. Formation of an inclusion complex was confirmed in the solid state by differential scanning calorimetry (DSC) and in aqueous solution by proton nuclear magnetic resonance spectroscopy (1H NMR).
The experimental Kst value (2112 M−1) derived from the fluorimetry studies appeared to fit well to a 1:1 drug-to-cyclodextrin molar ratio according to the non-linear mathematical model. The model is particularly suitable for fluorescent compounds of which fluorescence intensity is influenced by the presence of cyclodextrins.
Ocular Membrane Permeability of Hydrophilic Drugs for Ocular Peptide Delivery
Authors: Sasaki Hitoshi , Ichikawa Masataka , Yamamura Kenzo , Nishida Koyo , Nakamura Junzo 
Published: April 2011

Abstract
The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl β-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH).
The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.
In-situ Ocular Absorption of Ophthalmic β-Blockers through Ocular Membranes in Albino Rabbits
Authors: Sasaki Hitoshi , Ichikawa Masataka , Kawakami Shigeru , Yamamura Kenzo , Mukai Takahiro , Nishida Koyo , Nakamura Junzo 
Published: April 2011

Abstract
Ocular membranes have been characterized by in-situ absorption of the ophthalmic β-blockers carteolol (hydrophilic) and timolol and befunolol (lipophilic) using a cylindrical cell.
After introduction of drug solution into the cell on the cornea, sclera (bulbar conjunctival and scleral layer) or palpebral conjunctiva, the disappearance of the drug from the cell was determined as in-situ absorption. The ophthalmic drugs disappeared from the conjunctival and scleral membranes although disappearance from the cornea was hardly observed. The conjunctival membrane showed the highest permeability.
Lipophilic drugs were more permeable than hydrophilic. In-situ apparent permeability coefficients of the ophthalmic drugs through the conjunctiva and sclera correlated with the lipophilicity of drugs. A high drug concentration in the aqueous humor was observed after corneal application. There is a relationship between concentrations of drugs in the aqueous humor and previously reported in-vitro apparent permeability coefficients of the drugs in the cornea.
This in-situ method using a cylindrical cell is a useful method of investigating the ocular absorption of ophthalmic drugs.
Degradation of Insulin and Calcitonin and Their Protection by Various Protease Inhibitors in Rat Caecal Contents: Implications in Peptide Delivery to the Colon
Authors: Tozaki Hideyuki , Emi Yasuharu , Horisaka Eri , Fujita Takuya , Yamamoto Akira , Muranishi Shozo 
Published: April 2011

Abstract
The objective of this study was to examine the metabolism of insulin and calcitonin, and their protection by various protease inhibitors, in the large intestine.
Fresh caecal contents were prepared from non-fasted rats and the degradation of insulin and calcitonin was studied in a suspension of rat caecal contents, as a model of the content of the large intestine. Both insulin and calcitonin were metabolized in suspensions of rat caecal contents, but the degradation of calcitonin was much faster than that of insulin. The degradation of insulin was fastest at pH 6.8. Protease inhibitors such as camostat and aprotinin inhibited the degradation of insulin and calcitonin in rat caecal contents, which was consistent with the high chymotrypsin activity of these contents.
These findings suggest that care should be taken when administering peptide drugs to the large intestine for colon-specific drug delivery because they can be degraded in rat caecal contents. Protease inhibitors might be useful for increasing the stability of these peptides in the large intestine, thereby improving their large-intestinal absorption to the systemic circulation.
Low-dose Pulse Methotrexate Inhibits Articular Destruction of Adjuvant Arthritis in Rats
Authors: Kawai Shinichi , Nagai Kasumi , Nishida Shinichi , Sakyo Katsufumi , Murai Etsuko , Mizushima Yutaka 
Published: April 2011

Abstract
The purpose of this study was to determine whether low-dose methotrexate pulse therapy, which had recently become important in the treatment of rheumatoid arthritis, was effective for controlling the progression of articular destruction in rats with adjuvant arthritis.
Intraperitoneal methotrexate at a dose of 0.05 or 0.1 mg kg−1 twice weekly inhibited inflammation in rats with adjuvant arthritis, as shown by reduction of the hind-paw volume. Methotrexate also inhibited articular destruction, as shown by X-ray findings.
Although the mechanisms by which low-dose pulse methotrexate acts on rat adjuvant arthritis are still unclear, our results imply that it might effectively slow the progression of articular destruction in rheumatoid arthritis in man. In addition, assessment of articular destruction in this animal model might be useful when evaluating new treatments for rheumatoid arthritis.
In-vitro Permeability of the Human Nail and of a Keratin Membrane from Bovine Hooves: Penetration of Chloramphenicol from Lipophilic Vehicles and a Nail Lacquer
Authors: Mertin Dirk , Lippold Bernhard C 
Published: April 2011

Abstract
Lipophilic vehicles and especially nail lacquers are more appropriate for topical application on the nail than aqueous systems because of their better adhesion. This work has, therefore, studied the penetration through the human nail plate of the model compound chloramphenicol from the lipophilic vehicles medium chain triglycerides and n-octanol and from a lacquer based on quaternary poly(methyl methacrylates) (Eudragit RL). The results were compared with data obtained with a keratin membrane from bovine hooves.
If the swelling of the nail plate or the hoof membrane is not altered by use of lipophilic vehicles, the maximum flux of the drug is independent of its solubility in the vehicle and is the same as that from a saturated aqueous solution. These vehicles are not able to enter the hydrophilic keratin membrane because of their non-polar character and so cannot change the solubility of the penetrating substance in the barrier. If the concentration of the drug in the nail lacquer is sufficiently high, the maximum flux through both barriers equals that from aqueous vehicles or even exceeds it because of the formation of a supersaturated system. Penetration through the nail plate follows first order kinetics after a lag-time of 400 h. The course of penetration through the hoof membrane is initially membrane-controlled and later becomes a matrix-controlled process because of the membrane's greater permeability. Chloramphenicol is dissolved in the lacquer up to a concentration of 31%. The relative release rates from these solution matrices are independent of the drug concentration but they decrease on changing to a suspension matrix.
These results show that drug flux is independent of the character of the vehicle and that penetration of the drug is initially membrane-controlled and changes to being matrix-controlled as the drug content of the lacquer decreases.
The Role of Mammalian Intestinal Bacteria in the Reductive Metabolism of Zonisamide
Authors: Kitamura Shigeyuki , Sugihara Kazumi , Kuwasako Mie , Tatsumi Kiyoshi 
Published: April 2011

Abstract
Zonisamide (1,2-benzisoxazole-3-methanesulphonamide), a new anticonvulsant, is mainly metabolized to 2-sulphamoylacetylphenol by reduction of the benzisoxazole ring. Recent studies have shown that mammalian liver enzymes are responsible for the reduction of zonisamide. Because intestinal bacteria can also mediate the reduction of xenobiotics, this study was designed to evaluate the role of intestinal bacteria in in-vivo reductive metabolism of zonisamide.
Treatment of rats with antibiotics significantly reduced the urinary and faecal excretion of 2-sulphamoylacetylphenol after oral administration of zonisamide. Re-contamination of the antibiotic-treated rats with microflora restored the excretion of the metabolite. The caecal contents of the control rats had significant zonisamide reductase activity, whereas little or no zonisamide reductase activity was observed with the caecal contents of the antibiotic-treated rats. Eight pure strains of intestinal bacteria were tested for zonisamide reductase activity and the highest was observed in Clostridium sporogenes.
We concluded that intestinal bacteria play a major role in the reductive metabolism of zonisamide to 2-sulphamoylacetylphenol in-vivo.
In-vitro Binding of Propiverine Hydrochloride and Some of its Metabolites to Serum Albumin in Man
Authors: Meisel P , Langner Steffi , Siegmund W 
Published: April 2011

Abstract
The distribution and pharmacological action of propiverine, a bladder spasmolytic agent, are affected by the extent of plasma-protein binding. Because attempts to assess the albumin-binding of propiverine have produced conflicting results, the binding parameters of the drug and some of its metabolites to serum albumin in man have been re-evaluated.
In man propiverine is bound to serum albumin at a single site with high affinity (KA1 = 1.45 × 104 L mol−1) and at least two sites with low affinity (KA2 = 2.5 × 102 L mol−1). The metabolites of propiverine, namely M2 (dealkylated propiverine), M5 (the N-oxide of propiverine) and M6 (the N-oxide of M2), are less firmly bound to serum albumin; this is considered to be non-specific binding. Binding experiments with human serum revealed that there are additional binding proteins. At therapeutic plasma levels the extent of binding was calculated to be 90, 15, 60, and 20% for propiverine and the metabolites M2, M5, and M6, respectively.
The strong binding of propiverine to serum proteins controls its availability to the liver. Because the metabolites are not tightly bound to serum proteins, after metabolism of propiverine its metabolites are easily eliminated.
Neuromuscular and Microvascular Changes Associated with Chronic Administration of an Extract of Teucrium stocksianum in Mice
Authors: Tanira M O M , Ali B H , Bashir A K , El-Sabban F F , Homsi M Al 
Published: April 2011

Abstract
This work examines the effect on the weights of vital body organs, on blood biochemical variables, on neuromuscular coordination and on cerebral microcirculation of aqueous extracts of Teucrium stocksianum, given to mice in drinking water at concentrations of 2 and 4% for 56 days.
The treatment caused progressive impairment of neuromuscular coordination, as evidenced by the time spent on the rota-rod. After photochemical challenge, the time for first observable platelet aggregation in arterioles was shorter than for the control group by 22 and 45% in the 2 and 4% T. stocksianum-treated groups, respectively. Platelet aggregation on the venular side was not affected by the treatment nor were microvascular diameters. Treatment with the plant extract produced no statistically significant effect on the plasma biochemical variables that are considered indices of liver and kidney function. Histologically, brains obtained from mice treated with T. stocksianum showed loss of cerebellar Purkinje cells.
Although it is likely that the accelerated platelet aggregation might have contributed to an ischaemic effect which could, at least in part, have caused the cytotoxicological changes, this does not exclude the possibility of a direct cytotoxicological effect of the plant extract. Further pharmacological and toxicological investigations on Teucrium species seem warranted.
Age-related Changes in [3H]Nimodipine and [3H]Rolipram Binding in the Rat Brain
Authors: Araki T , Kato H , Shuto K , Itoyama Y 
Published: April 2011

Abstract
Ageing is associated with changes in neurotransmission which might be correlated with abnormal calcium metabolism. Because there is evidence that nimodipine can enhance the learning abilities of ageing animals and rolipram can enhance the excitability of neurons, providing a functional basis for cognition-enhancing activity, age-related alterations in the binding of voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic adenosine monophosphate-selective phosphodiesterase (cyclic-AMP PDE) were studied in 3-week- and 6-, 12-, 18- and 24-month-old Fisher 344 rats by use of receptor autoradiography.
[3H]Nimodipine and [3H]rolipram were used to label the voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE, respectively. [3H]Nimodipine binding showed no obvious change in all brain areas of 12- and 18-month-old rats, as compared with 6-month-old animals. In 24-month-old rats, however, [3H]nimodipine binding increased significantly in the striatum and hippocampal CA3 sector. In contrast, [3H]rolipram binding showed no significant change in most brain areas during ageing, except for a transient change only in the hippocampal CA1 sector of 12-month-old animals. [3H]Nimodipine and [3H]rolipram binding showed a significant increase in some brain areas of 3-week-old rats compared with 6-month-old animals.
The results indicate that in rats voltage-dependent L-type calcium channels are more susceptible to ageing processes than calcium/calmodulin-independent cyclic-AMP PDE. Our data also demonstrate that voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE might play roles in developmental processes. These findings might help further elucidation of the relationship between age-related neurological deficits and behavioural pharmacology including cognitive function.
Estimation of the Chemosensitizing Activity of Modulators of Multi-drug Resistance via Combined Simultaneous Analysis of Sigmoidal Dose-Response Curves
Authors: Ecker Gerhard , Chiba Peter , Schaper Klaus-Jürgen 
Published: April 2011

Abstract
The potency of modulators which re-establish sensitivity of resistant tumour cells to cytotoxic drugs is not usually described by ED50 values, even though such values are needed for comparison of modulator activity.
Various methods are reported for the determination of ED50 values of propafenone-type modulators of multi-drug resistance in cytotoxicity assays. Best results were obtained by using a combined simultaneous analysis of dose-response curve families. This approach enables calculation of statistically highly significant ED50 values without any data reduction directly from the original data points obtained in daunomycin cytotoxicity assays.
The method also enables extrapolation of the ED50 values of compounds with low activity or poor solubility, or both.
The Effects of a Triterpene Fraction Isolated from Crataegus monogyna Jacq. on Different Acute Inflammation Models in Rats and Mice. Leucocyte Migration and Phospholipase A2 Inhibition
Authors: Ahumada Carmen , Sáenz Teresa , García Dolores , De La Puerta Rocio , Fernandez Angeles , Martinez Eugenia 
Published: April 2011

Abstract
The plant Crataegus monogyna has action against cardiac insufficiency, angina and arrhythmia. The antiinflammatory properties of the cycloartenol fraction from this plant have been investigated.
Chromatographic fractionation of the hexane extract of Crataegus monogyna Jacq. (Rosaceae) furnished a triterpene fraction containing cycloartenol as the main component (80.87%). The anti-inflammatory activity of the fraction was tested against hind-paw oedema induced by carrageenan in rats. At the highest oral dose (40 mg kg−1) inhibition was 61.5 and 52.5% at 3 and 5 h respectively. In the mouse carrageenan peritonitis test, the triterpene fraction given orally inhibited peritoneal leucocyte infiltration (41.9, 64.7 and 89.4% at 10, 20 and 40 mg kg−1, respectively). The fraction also showed weak inhibition of phospholipase A2 (PLA2) in-vitro.
These results suggest that the fraction containing cycloartenol as the main component exerts an important anti-inflammatory action in-vivo by reducing the oedema.
Characterization of the Influence of some Cyclodextrins on the Stratum Corneum from the Hairless Mouse
Authors: Bentley M Vitória L B , Vianna Renata F , Wilson Susan , Collett John H 
Published: April 2011

Abstract
Differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) have been used to determine the influence of β-cyclodextrin (β-CyD), hydroxypropyl-β-CyD (HP-β-CyD) and γ-CyD on the structural properties of the stratum corneum from the hairless mouse.
Some modest changes in the stratum corneum lipid transition temperature were induced by HP-β-CyD and blue shifts were observed in the FTIR spectra of the C–H asymmetric and symmetric stretching of the lipids from the stratum corneum. Results from TEM studies indicated that HP-β-CyD caused removal and possible disorganization of the lipid matrix that envelopes the corneocytes of the stratum corneum, whereas no effect was seen after treatment of the samples with β-CyD and γ-CyD.
These results suggest that HP-β-CyD can increase the permeability of the stratum corneum possibly as a result of extraction of lipids, and might thus enhance drug permeation through the skin.
Neuromuscular Blockade: Offset Anomalies. Are they Simply Potency-related Receptor Bonding Effects?
Authors: Midgley John M , Stenlake John B 
Published: April 2011

Abstract
Rapid making and breaking of bonds between quaternary ammonium compounds and cholinergic receptors is typical of ion-pair bonding, which is weak, and ion-pair reactions, which are extremely fast. These properties explain the observed rapid association and dissociation of turbocurarine at receptors.
The time course receptor offset is determined by two factors, buffered diffusion due to repetitive bonding, and a potency-related offset-retarding effect. The strength of the latter is a function of chemical structure, which determines the microscopic molecular rate of drug-receptor association and dissociation. Together, buffered diffusion and the potency-related offset-retarding effect provide a complete rational physico-chemical explanation for the marked, yet variable, differences between onset and offset times of non-depolarizing neuromuscular blocking agents.
The influence of a potency-related offset-retarding effect together with differing structural requirements for neuromuscular blocking potency and plasma carboxyesterase hydrolysis, suggests that a high potency ultrashort duration block is unlikely to be achieved in a non-depolarizing compound metabolized by plasma esterases alone.
Role of the Endothelium in the Relaxation Induced by Propofol and Thiopental in Isolated Arteries from Man
Authors: Moreno Lucrecia , Martínez-Cuesta M Angeles , Muedra Vicente , Beltrán Belén , Esplugues Juan 
Published: April 2011

Abstract
Induction of anaesthesia with intravenous propofol and thiopental is often accompanied by hypotension. This study evaluates whether propofol and thiopental induce relaxation of isolated arteries from man and whether this effect is modulated by the endothelium.
Mesenteric artery rings (with and without endothelium) from 12 patients were placed in organ baths and precontracted with phenylephrine before addition of propofol (10−3 M) or thiopental (10−3 M). Relaxation induced by propofol and thiopental was evaluated for rings with intact endothelium in the presence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 10−4 M) or the cyclooxygenase inhibitor indomethacin (10−5 M). The vasodilator effect of propofol was similar for intact and denuded endothelium rings whereas the relaxation induced by thiopental was significantly attenuated in denuded-rings. In intact endothelium rings, l-NAME and indomethacin caused marked inhibition of the relaxation induced by thiopental, but not that induced by propofol.
These results suggest that propofol induces endothelium-independent relaxation of isolated mesenteric arteries in man, whereas thiopental causes endothelium-dependent relaxation mediated by nitric oxide and prostaglandins.