bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-performance Thin-layer Chromatography for the Determination of Nimesulide in Human Plasma, and its Use in Pharmacokinetic Studies
Authors: Pandya K K , Satia M C , Modi I A , Modi R I , Chakravarthy B K , Gandhi T P 
Published: April 2011

Abstract
A rapid and sensitive high-performance thin-layer chromatographic assay has been developed for the measurement of nimesulide in human plasma. Its use for pharmacokinetic studies has been evaluated.
The method includes a single-stage extraction procedure without the use of an internal standard. Analysis was performed on plasma containing known amounts of the drug, on drug-free plasma, and on plasma containing an unknown quantity of the drug. Known amounts of extract and nimesulide (100 and 200 ng, as external standard) were spotted on precoated silica-gel 60F254 plates by means of a Camag Linomat IV autosampler. Quantification was achieved using a Camag TLC scanner 3. The recovery of the method was 97.10 ± 2.22%. The method was applied for the determination of plasma levels and pharmacokinetic parameters of nimesulide after oral administration of two formulations (100 mg) in healthy volunteers.
The method is a sensitive, economical, rapid and specific assay for nimesulide in human plasma, and is suitable for pharmacokinetic studies after therapeutic doses.
Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes
Authors: Hara Akiyoshi , Hayase Nobumasa , Hashizume Hiroko , Abiko Yasushi 
Published: April 2011

Abstract
The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-l-carnitine (PAL-CAR) or palmitoyl 1-α-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes.
At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 μm, respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 μm) but not at the highest concentration used (1 mm). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 μm to 1 mm. Similarly, dilazep (1 to 100 μm) and K-7259 (1 μm to 1 mm) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 μm, did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis).
These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.
A Comparative Study of Aminophylline- and Acepifylline-induced Seizures and Death in the Chemoconvulsion Model in Rats
Authors: Chakrabarti Amitava , Saini Harsimrat Kaur , Garg Santosh Kumar 
Published: April 2011

Abstract
The convulsive, pro-convulsive and lethal effects of two theophylline-containing bronchodilating agents, aminophylline and acepifylline, have been evaluated in rats.
Aminophylline (theophylline ethylenediamine) caused seizures and death in a dose-dependent manner; an intraperitoneal dose of 250 mg kg− caused seizures and death in all rats. Intraperitoneal doses of acepifylline (theophylline ethanoate of piperazine) up to 1000 mg kg−, however, did not cause seizure or death. Further, pre-treatment of the rats by intraperitoneal administration of a subconvulsive dose (100 mg kg−) of aminophylline caused a significant decrease in CD50 and LD50 values for pentylenetetrazole and a significant increase in the number of positive responders (i.e. rats with a pentylenetetrazole-induced seizure score of 3 or more on a seizure scale ranging from 0 to 6) and death rate compared with those obtained for rats pre-treated with an equivalent intraperitoneal dose (140 mg kg−) of acepifylline (‘equivalent dose’ referred to here denotes the theophylline content of the two preparations).
The study has established the neurosafety profile of acepifylline and documents a safer alternative to aminophylline for use in asthmatics suffering from concomitant epilepsy or other seizure-prone neurological defects.
Effects of Flavonoids Isolated from Scutellariae Radix on the Production of Tissue-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 Induced by Thrombin and Thrombin Receptor Agonist Peptide in Cultured Human Umbilical Vein Endothelial Cells
Authors: Kimura Yoshiyuki , Yokoi Kumi , Matsushita Nobutoshi , Okuda Hiromichi 
Published: April 2011

Abstract
The effects of different flavonoids isolated from the roots of Scutellaria baicalensis Georgi on the production of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) induced by thrombin and thrombin receptor agonist peptide, Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, have been examined in cultured human umbilical vein endothelial cells (HUVECs).
Thrombin and thrombin receptor agonist peptide induced production of both t-PA and PAI-1 and the elevation of intracellular free calcium concentration ([Ca2+]i). Baicalein isolated from Scutellariae Radix dose-dependently inhibited PAI-1 production induced by thrombin and thrombin receptor agonist peptide; its concentrations for 50% inhibition (IC50) were 6.8 and 3.5 μm, respectively. Other flavonoids had no effect. In contrast, flavonoids isolated from Scutellariae Radix had no effect on production of t-PA induced by thrombin and thrombin receptor agonist peptide. Baicalein inhibited the elevation of [Ca2+]; induced by thrombin and thrombin receptor agonist peptide and, at a concentration of 1000 μm, slightly increased t-PA production.
These findings suggest that the mechanism by which baicalein inhibits PAI-1 production induced by thrombin and thrombin receptor agonist peptide might be by reduction of [Ca2+]i elevation. The results suggest that baicalein in Scutellariae Radix might be active as a drug in the treatment of arteriosclerosis and thrombosis.
Effect of Formulation on the Rheology of Theophylline Compound Suspensions in Gelucires
Authors: Ratsimbazafy V , Bourret E , Brossard C 
Published: April 2011

Abstract
The theophylline derivatives, etofylline, diprophylline and proxyphylline, which exhibit increasing aqueous solubitity, were used to prepare suspensions in seven saturated polyglycolysed glycerides (Gelucires) characterized by their rising hydrophilic-lipophilic balance (HLB). Drug concentration was set at 25% w/w and the production temperature was set at the Gelucire melting point plus 30°C in order to obtain suitable suspensions. Various formulation factors were studied.
Ostwald flow indices revealed that the suspensions had a thixotropic shear-thinning behaviour and a relative viscosity which increased as drug aqueous solubility rose and Gelucire HLB decreased. These rheological properties could be explained by the chemical composition of Gelucires and drugs used.
A microstructure was proposed for the liquid suspension such that colloidal particles and aggregates formed in these suspensions directly influenced the observed rheological properties. Observation of solidified suspensions by scanning electron microscopy confirmed this hypothesis. Moreover, a correlation between the relative viscosity of drug suspensions on the one hand and drug concentration, drug solubility and Gelucire HLB on the other allowed for the calculation of the required concentration of each theophylline derivative in each Gelucire to obtain a given viscosity.
Effects of Trecadrine, a β3-Adrenergic Agonist, on Intestinal Absorption of d-Galactose and Disaccharidase Activities in Three Physiopathological Models
Authors: Diez-Sampedro Ana , Milagro Fermin I , Berraondo Beatriz , Zulet Maria A , Martinez J Alfredo , Barber Ana 
Published: April 2011

Abstract
Impairments in intestinal absorptive and digestive processes have been described in several pathophysiological situations, such as in drug-induced diabetes, obesity and hypercholesterolaemia. Furthermore, there is evidence for the occurrence of β3-adrenoceptors in multiple regions of the gastrointestinal tract, but there are no data concerning their possible involvement on jejunal and ileal digestive and absorptive functions. In this work, we have measured the modifications of selective intestinal absorption and disaccharidase activities in alloxan-induced diabetic and in diet-induced obese and hypercholesterolaemic Wistar rats. The action of a β3-adrenergic agonist (Trecadrine) with hypoglycaemic and lipolytic properties on those gastrointestinal functions has been studied.
Increases in the galactose uptake by intestinal rings and in both sucrase and maltase activities were found in diabetic rats. The results obtained after Trecadrine administration to diabetic rats led to an improvement of the altered values. On the other hand, our data show a decrease in sugar absorption and in disaccharidase activities in both obese and hypercholesterolaemic groups, probably related to the low carbohydrate and high fat content of these diets. An amelioration in sucrase activity was observed after treatment with Trecadrine. Finally, Trecadrine administration to control animals significantly inhibited galactose intestinal absorption, which was independently confirmed by additional in-vitro studies.
Overall, these results could be attributed not only to an improvement in the pathophysiological condition (diabetes, obesity and hypercholesterolaemia), but also to a direct effect of the β3-adrenergic agonist on the intestinal absorption processes.
Effect of Plaunotol on Gastric Injury Induced by Ischaemia-Reperfusion in Rats
Authors: Wada Kouichirou , Kamisaki Yoshinori , Nakamoto Kentaro , Kishimoto Yosuke , Ashida Kumiyo , Itoh Tadao 
Published: April 2011

Abstract
Plaunatol, an anti-ulcer drug, increases prostaglandin content in gastric tissue but its effect on radical-mediated gastric damage or activity against reactive oxygen species is unknown. We examined the effects of oral administration of plaunotol (Kelnac) on the acute gastric mucosal lesion and its progression to ulcer lesion induced by ischaemia-reperfusion in rats.
Plaunotol (30 and 100 mg kg−, 15 min before ischaemia) significantly reduced the total erosion area observed immediately after ischaemia-reperfusion. When plaunotol (30 and 100 mg kg−, once a day) was administrated orally 60 min after reperfusion, it prevented the progression from erosion to ulcer. At 72 h after ischaemia-reperfusion, the total area of ulcers lesions was significantly reduced compared with that without plaunotol administration. Furthermore, treatment with plaunotol (100 mg kg−) significantly increased prostaglandin E2 content in gastric tissues of both acute gastric mucosal lesion and gastric ulcer lesion. In in-vitro experiments, plaunotol (1–3 mg mL−) reduced the superoxide radicals generated by leucocytes, but not by xanthine oxidase.
These results indicate that plaunotol has protective effects on both the onset of acute gastric mucosal injury and its progression to ulcer lesion induced by ischaemia-reperfusion.
Both effects of plaunotol on increase in prostaglandin content in gastric tissues and inhibition of superoxide radical from leucocytes may play important roles on the protection against gastric mucosal injury.
Stability Behaviour of Molsidomine-containing Pellet Formulations
Authors: Laicher A , Jünger H , Klemm F H 
Published: April 2011

Abstract
Molsidomine in mixtures with different inactive ingredients has been subjected to a stability test.
The fingerprint chromatogram obtained by HPLC with diode-array detection of mixtures of molsidomine with povidone 25 revealed decomposition products; the detection wavelength of 210 nm resulted in easy detection of the degradation products. Molsidomine-containing pellets were manufactured according to a compact procedure and by applying the active ingredient to placebo pellets. Compared with the nonpareil pellet formulations, compact pellets have a considerably higher water content and undergo decomposition of the active ingredient after storage for 50 months under different conditions.
It is assumed that the decomposition of molsidomine is accelerated by the peroxide found in povidone.
ZD9583, an Orally Effective Thromboxane A2 Synthase Inhibitor and Receptor Antagonist with a Sustained Duration of Action in Rat and Dog
Authors: Brownlie R P , Brownrigg N J , Butcher H M , Garcia R , Jessup R , Lee V J , Tunstall S , Wayne M G 
Published: April 2011

Abstract
The thromboxane A2 (TXA2) synthase inhibitory activity and the TXA2 receptor (TP-receptor) blocking action of ZD9583 ((4Z)-6-[(2S,4S,5R)-2-(1-[2-cyano-4-methylphenoxy]-1-methylethyl)-4-(3-pyridyl)-1,3-dioxan-5-yl]hex-4-enoic acid) has been evaluated in-vitro by use of whole blood and platelets from man, and ex-vivo by use of platelets and whole blood from rats and dogs.
ZD9583 caused concentration–dependent inhibition of human platelet microsomal TXA2 production with an IC50 of 0.017 ± 0.003 μm; this inhibition was associated with an increase in prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) formation. ZD9583 also inhibited collagen-stimulated TXA2 synthesis in whole blood from man, rat and dog giving IC50 values of 0.027 ± 0.005, 0002 ± 0.006 and 0.013 ± 0.01 μm, respectively. The drug did not modify platelet cyclooxygenase activity as inhibition of thromboxane B2 (TXB2) formation was associated with a concomitant increased synthesis of prostaglandin D2 (PGD2), PGE2 and PGF2α. ZD9583 had little effect on cultured human umbilical vein endothelial cell prostacyclin synthase giving an IC50 of 24.2 ± 4.9 μm. In-vitro ZD9583 caused concentration-dependent inhibition of U46619-induced aggregation responses of platelets from man, rat and dog, yielding apparent log A2 values of 8.7 ± 0.12, 8.8 ± 0.2 and 9.3 ± 0.2, respectively. The drug was selective; at concentrations up to 100 μm it did not affect 5-hydroxytryptamine or the primary phases of adenosine diphosphate and adrenaline-induced aggregation. ZD9583 (100 μm) did not, furthermore, modify the platelet inhibitory effects of PGD2, prostaglandin E1 (PGE1) and prostacyclin. Oral administration of ZD9583 (3–10 mg kg−1) to both rats and dogs caused dose-dependant inhibition of collagen-stimulated TXA2 production ex-vivo which persisted for up to 12 h. The drug also caused profound TXA2 receptor blockade in both species for in excess of 12-h after an oral dose of 3 mg kg−1. ZD9583 (3 mg kg−1, p.o.), when administered to dogs over a five-day period at 12 h intervals, did not cause either tachyphylaxis or an accumulation of effect.
We conclude that ZD9583 is a potent, selective, orally active thromboxane synthase inhibitor and TXA2 receptor antagonist.
Stereoselective N-Demethylation of Chlorpheniramine by Rat-liver Microsomes and the Involvement of Cytochrome P450 Isozymes
Authors: Nomura Akio , Sakurai Eiichi , Hikichi Noboru 
Published: April 2011

Abstract
Previous studies have suggested that degradation of the two stereoisomers of chlorpheniramine in the liver might be catalysed by different types of cytochrome P450. Stereoselective N-demethylation of chlorpheniramine and the involvement of cytochrome P450 (CYP) isozymes have, therefore, been investigated in the liver microsomes of eight-week-old male rats.
Incubation of racemic chlorpheniramine with liver microsomes from the male rat resulted in the formation of both enantiomers of monodesmethylchlorpheniramine (DMChp). Further metabolism of DMChp to didesmethylchlorpheniramine (DDMChp) did not, however, occur. The S/R enantiomeric ratio for intrinsic clearance (Vmax/Km) was approximately 2.0, suggesting that the N-demethylation was stereoselective for S-(+)-chlorpheniramine. On the other hand, although the Vmax/Km value for the formation of S-(+)- and R-(–)-DMChp increased with phenobarbitone-inducible rat-liver microsomes, there was no difference between the rates of N-demethylation of the enantiomers. In contrast, 3-methylcholanthrene reduced the intrinsic clearance of S-(+)-chlorpheniramine by N-demethylation and increased its value for R-(–)-chlorpheniramine, showing no stereoselectivity for the N-demethylation of chlorpheniramine. The difference between the intrinsic clearance of the two enantiomers by N-demethylation was because of differences in affinity for the catalysing enzyme. This is indicative of stereoselective involvement of the main enzyme concerned in the N-demethylation of the enantiomers, considered to be CYP 2C11. Anti-CYP 2C11 also partially inhibited the N-demethylation of racemic chlorpheniramine in rat-liver microsomes exposed to phenobarbitone and 3-methylcholanthrene. That CYP 2B1 was involved in the N-demethylation of both enantiomers was also supported by results from an experiment using phenobarbitone-inducible rat-liver microsomes. CYP1A1 did not, however, catalyse the N-demethylation of either enantiomer.
These results indicate that N-demethylation of the S-(+)-enantiomer of chlorpheniramine occurs preferentially in the microsomes, demonstrating the stereoselective contribution of CYP2C11. Immunoinhibition studies suggest, moreover, that the N-demethylation of both chlorpheniramine enantiomers is catalysed by CYP2B1, but not by CYP1A1.
Optimization of the Chiral Inversion of 2-Phenylpropionic Acid by Verticillium lecanii
Authors: Thomason Michael J , Rhys-Williams William , Lloyd Andrew W , Hanlon Geoffrey W 
Published: April 2011

Abstract
Previous studies have demonstrated that Verticillium lecanii might be used as a microbial model of the inversion of 2-arylpropionic acids in man. This paper describes the optimization of the inversion process in respect of culture medium, pH, cell density and substrate concentration.
The study demonstrates that optimum inversion occurs in Sørensen's phosphate buffer at pH 5.5. The extent and rate of inversion were also shown to be dependent on substrate concentration and cell density.
This study will form the basis of the development of a microbial model of the metabolism of 2-arylpropionic acids which might be suitable for the in-vitro screening of new compounds in this class.
Pharmacokinetics of Heterologous and Homologous Immunoglobulin G, F(ab‘)2 and Fab after Intravenous Administration in the Rat
Authors: Bazin-Redureau Martine I , Renard Catherine B , Scherrmann Jean-Michel G 
Published: April 2011

Abstract
Because few pharmacokinetic studies of antibodies and their fragments have compared the influence of species origin and antibody size, the plasma pharmacokinetics of a single intravenous dose (0.7 mg kg−1) of 125I-labelled mouse, rat and human immunoglobulin G (IgG), and mouse F(ab')2 and Fab were investigated in the rat.
IgG reached equilibrium after six distribution half-lives, i.e. only 36–50 h post-dosing, and the distribution volume was about four times the rat plasma volume. IgG elimination half-lives ranged from 5.33 to 8.10 days. Fragmentation of IgG into smaller fragments, F(ab')2 and Fab, resulted in pharmacokinetics that were molecular-weight-dependent with volume of distribution and systemic clearance values inversely related to antibody size.
We conclude that antibody variability in terms of species origin and size influences antibody pharmacokinetics and should be carefully studied before selection of the best antibody for a clinical application.
The Effect of the Calcium Antagonist Nimodipine on the Detoxification of Soman in Anaesthetized Rabbits
Authors: Karlsson Britt M , Waara Lena M , Fredriksson Sten-Åke , Koskinen Lars-Owe D 
Published: April 2011

Abstract
The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 μg kg−1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C + P - and C - P - in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry.
During the sampling, 15–300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL−1; in animals pre-treated with nimodipine (10 mg kg−1) it decreased from 15 to 0.033 ng mL−1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals.
Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.
A Sensitive Assay for Studying Dopaminergic Activity in Cultures of Rat Pituitary Cells
Authors: Giacomelli Sabrina , Braghiroli Laura , Ponzianelli Anna , Koppenaal Dirk W , De Feo Giuseppe 
Published: April 2011

Abstract
The dopaminergic and antidopaminergic activity of drags is frequently assayed in pituitary cell cultures. Here we describe a modified version of the assay based on the use of pituitary cells from prepubertal female rats.
Under our experimental conditions (50000 cells well−1, 2-day culture and 2-h drug-exposure) the assay yielded high selectivity and sensitivity for drug dopaminergic activity. D2 agonistic activity of bromocriptine could be observed at a concentration as low as 10−15 m, the antagonistic activity of haloperidol at 10−16 m. The assay also proved reproducible and simple enough for routine screening of dopaminergic activity.
The assay enabled dopaminergic agonist and antagonist activity to be revealed at very low drug concentrations. The high sensitivity of the assay could be of advantage in studying dopaminergic activity in samples containing active substances present at low concentrations or for disclosing the activity of substances with low dopaminergic potency.
Influence of Certain Calcium-channel Blockers on Some Aspects of Lorazepam-dependence in Mice
Authors: Saad Samir F , Khayyal M T , Attia Amina S , Saad Ehab S F 
Published: April 2011

Abstract
The effect of acute and chronic treatments of the calcium-channel blockers, isradipine, diltiazem and flunarizine in protecting against lorazepam dependence has been demonstrated in mice.
Dependence was induced by twice-daily administration of lorazepam (1 mg kg−1) for 10 days, doubling the dose during the next 10 days. Withdrawal symptoms
and changes in the noradrenaline, dopamine and 5-hydroxytryptamine content of different regions of the brain were observed after either 24-h withdrawal or flumazenil administration. Isradipine inhibited lorazepam withdrawal symptoms, the effect being accompanied in the 24-h withdrawal group by significant decreases in the noradrenaline and dopamine content of the thalamus and hypothalamus and in the noradrenaline content of the mid-brain. In the flumazenil-treated group isradipine produced significant decreases in mid-brain noradrenaline and dopamine levels and in the dopamine content of the thalamus and hypothalamus. Diltiazem did not, on the other hand, afford significant protection against lorazepam withdrawal symptoms and did not induce any significant change in the neurotransmitters studied. Flunarizine significantly inhibited lorazepam withdrawal symptoms, an effect accompanied by significant reduction in noradrenaline and dopamine levels in the thalamus and hypothalamus. Dopamine was also significantly reduced in the cerebral cortex. Similar effects were produced in the flumazenil-treated group, and the noradrenaline content was reduced in the medulla, pons and cerebellum.
It was concluded that isradipine and flunarizine might be of value in ameliorating lorazepam withdrawal symptoms.