bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salivary secretion of paracetamol in man
Authors: Kamali F , Fry J R , Bell G D 
Published: April 2011

Abstract
Plasma and saliva paracetamol levels were measured by HPLC in ten healthy volunteers who took a therapeutic dose after an overnight fast. Salivary levels of the drug were consistently and significantly higher than those in plasma for the first 50 min after oral ingestion, but saliva and plasma levels correlated closely during the elimination phase. There was a highly significant correlation between the AUC 0-α calculated from saliva and plasma paracetamol concentration-time curves. The elevated saliva/plasma ratio for the first 50 min was not due to loss of paracetamol from plasma during sample preparation, binding to plasma protein or adsorption to the buccal mucosa. Administration of probenecid in an attempt to block possible active secretion of paracetamol into saliva did not significantly alter the saliva/plasma concentration ratio for the first 50 min, but did significantly reduce this ratio in the time period 125–360 min. The experimental data conformed to a recently proposed model in which elevated saliva/plasma ratios during the early stages following oral ingestion were related to ongoing absorption into the arterial system.
The packing characteristics of physical and formulated mixtures of Oxytetracycline and lactose powders
Authors: Adeyemi M O , Pilpel N 
Published: April 2011

Abstract
Measurements have been made of the tap densities and angles of internal flow of physically mixed and formulated mixtures of oxytetracycline and lactose powders. The differences between the two types of mixtures are ascribed to differences in the packing and surface morphologies of the particles.
Evaluation of reversible polymorphic phase transitions by thermal analysis
Authors: Shah A C , Britten N J 
Published: April 2011

Abstract
Crystalline states of 1,2-dihydro-6-neopentyl-2-oxonicotinic acid, an investigational antidiabetic drug, were evaluated by thermal analyses. Two polymorphs were detected for the drug, Form I (m.p. 193 °C) and Form II (m.p. 196 °C). Interconversion of the polymorphs upon cyclic solid-melt transitions provided confirmation of the crystal forms. Solidification of the melt was observed to occur either at 162 or 182°C with the formation of Form I or Form II crystals, respectively. Form I underwent partial conversion to Form II upon heating at 10°C min−1 when nucleating crystals of Form II were present in the sample. Differential scanning calorimetry (DSC) thermograms were recorded for different lots of the drug, solventrecrystallized samples, and a series of known mixtures of Form I and II polymorphs. The study illustrates the usefulness of cyclic heat-cool studies to characterize polymorphic crystal forms of drugs.
Determination of the aryltetralin lignan content of podophyllum resins and roots/rhizomes
Authors: Drew Sheila E , Conway Sarah J , Jennings Penny , Helliwell Keith 
Published: April 2011

Abstract
A simple, quantitatively reproducible method for determining the aryltetralin lignan content of the resins and roots/rhizomes of Podophyllum hexandrum and P. peltatum is described. The method confirms that P. hexandrum resins and roots/rhizomes contain approximately four times the quantity of lignans as do those of P. peltatum and also that there is a significant variation in the lignan content of P. hexandrum resins.
Prostaglandin D2-induced catalepsy in rats: role of 5-hydroxytryptamine
Authors: Bhattacharya S K , Rao P J R Mohan 
Published: April 2011

Abstract
Prostaglandin D2 (PGD2), the major PG in the rat brain, induced a dose-related catalepsy in rats on intracerebroventricular (i.c.v.) administration. This cataleptic response was significantly attenuated following the i.c.v. administration of pharmacological agents that decrease rat brain 5-hydroxytryptamine (5-HT) activity. PGE1 synergized but PGF2α antagonized the catalepsy induced by PGD2. PGD2 and PGE1 have previously been shown to augment rat brain 5-HT activity, whereas PGFα inhibited it. It is therefore likely that the observed effects of these PGs on catalepsy involve a central 5-HT mechanism.
β-Adrenergic activities of octopamine and synephrine stereoisomers on guinea-pig atria and trachea
Authors: Jordan Roy , Midgley John M , Thonoor C Mohan , Williams Clyde M 
Published: April 2011

Abstract
The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on β1- and β2- adrenoceptors in guinea-pig atria and trachea have been compared with that of noradrenaline. The rank order of potency of the (-)-forms on β1-adrenoceptors was noradrenaline &gt; m-synephrine. m-octopamine = p-octopamine &gt; p-synephrine. m-Synephrine was 100-fold, m-and p-octopamine about 6000-fold, and p-synephrine about 40 000-fold less active than noradrenaline. The (+)-forms were 1-2 orders of magnitude less active than their (-)-counterparts. The four (-)-compounds were more than four orders of magnitude less active than noradrenaline on β2,-adrenoceptors, and the (+)-forms had no detectable activity in concentrations as high as 10−4 M. If m-and p-octopamine are co-released with noradrenaline in amounts proportional to their concentration, their activities at these structures are too low to be physiologically significant.
Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450
Authors: Duenas-Laita Antonio , Barry Michael G , Mathuna Padraic Mac , Feely John 
Published: April 2011

Abstract
The effect of chronic treatment with amiodarone on hepatic oxidative metabolism using an in-vivo [14aminopyrine breath test and on hepatic cytochrome P450 was examined in Wistar rats. Aminopyrine demethylation was significantly impaired but returned to pretreatment values following amiodarone for 4 weeks. In contrast the levels of cytochrome P450 were significantly depressed during treatment and at 4 weeks following treatment. While an inhibitory effect on oxidative metabolism may explain the reported drug interactions with amiodarone, the discrepancy between its in-vivo effects and cytochrome P450 levels may suggest the development of ‘compensatory’ extra-hepatic site of drug metabolism.
A new nasal decongestant, A-57219: a comparison with oxymetazoline
Authors: DeBernardis John F , Winn Martin , Kerkman Daniel J , Kyncl John J , Buckner Steven , Horrom Bruce 
Published: April 2011

Abstract
2-(4-Amino-3,5-dichlorobenzyl)imidazolin hydrochloride (A-57219), has α1-agonist/α2-antagonist activity and was more effective and long-acting than oxymetazoline on canine nasal mucosa, in-vitro and in-vivo. Upon intranasal administration to dogs, the compound was devoid of systemic effects up to a concentration 1000 times that needed for local decongestant effect (1&#x006d;̇65 μg, atomized from a 1 μg mL-1 solution) suggesting limited mucosal absorption. After nasal administration to rats for 15 days at a concentration 1000 times greater than that required for nasal decongestion, no mucosal tissue toxicity or systemic effects were seen.
Preparation of Biodegradable Poly(±)lactide Microparticles Using a Spray-Drying Technique
Authors: Bodmeier Roland , Chen Huagang 
Published: April 2011

Abstract
Drug containing biodegradable poly(±)lactide microparticles were prepared by using a spray-drying technique. Formulations containing model drugs in either a dissolved (progesterone) or dispersed state (theophylline) were spray-dried. The spray-drying method was less dependent on the solubility characteristics of the drug when compared with traditional microencapsulation techniques such as phase separation or solvent evaporation techniques. Differential scanning calorimetry and scanning electron microscopy were used to characterize the microparticles. The drug release profiles were characterized by a rapid release phase (burst effect) followed by a slow release phase, the extent of each phase being dependent on the drug loading.
The Effect of Acute Dyflos (DFP) Treatment on [3H]Nicotine Binding to Mouse Brain Homogenate
Authors: Scimeca Joseph A , Martin Billy R 
Published: April 2011

Abstract
One possible adaptive mechanism that might arise due to inhibition of cholinesterase in the brain is a down regulation of central cholinergic receptors. Therefore studies were performed to determine the effect of acute dyflos exposure on [3H]nicotine binding. Specific [3H] nicotine binding was demonstrated to be saturable, reversible, stereospecific, and inhibited by a number of nicotinic compounds. Scatchard analysis of specific [3H]nicotine binding produced a curvilinear plot that was resolved into high- and low-affinity sites with Kd values of 6.1 ± 2.5 and 114 ± 13 nM, and Bmax values of 11.8 ± 3.5 and 182 ± 24 fmol (mg protein)−1, respectively. The nicotinic binding sites in brain homogenate from dyflos-treated mice that were killed 20 min or 10 h after exposure did not exhibit significant alterations in binding parameters from control mouse brain homogenate. However, brain homogenate from treated mice that were killed 24 h after exposure resulted in statistically significant differences in the low-affinity KD and Bmax values from controls. Since no alterations were found in the high-affinity binding parameters and dyflos had only a minimal effect on the low-affinity site at 24 h, it was concluded that nicotinic receptor down regulation does not appear to be the mechanism through which the mouse functionally adapts to cholinesterase inhibition caused by acute dyflos treatment.
Selective β2-adrenoceptor antagonists: derivatives of ICI 118,551 and a binary aryloxypropanolamine
Authors: Nathanson James A , Hunnicutt Edward J 
Published: April 2011

Abstract
Recent studies indicate that selective β2-adrenoceptor antagonists may be of use in the treatment of glaucoma. ICI 118,551, its desmethyl-, didesmethyl-, and ethyl- analogues, and a putative highly β2-selective binary aryloxypropanolamine (4d) have been evaluated for their ability to inhibit β-adrenergic-stimulated adenylate cyclase activity in rabbit ciliary process and heart. Potency ratios (Ki heart/Ki ciliary process) were 440 for ICI 118,551; 9.3 for the desmethyl analogue; 8.2 for the didesmethyl analogue; 720 for the ethyl analogue; and 11 for the binary aryloxypropanolamine. The values for the ethyl derivative of ICI 118,551 indicate that it is the most oculoselective β-adrenoceptor antagonist yet reported.
Equilibrium binding of spermine and histamine to salmon sperm DNA and poly(dGdC)
Authors: Winkle Stephen A , Crooks Peter A 
Published: April 2011

Abstract
Studies using the solute-enhanced phase partition technique demonstrate that the endogenous amines histamine and spermine bind to both salmon sperm DNA and poly(dGdC) in a markedly cooperative fashion. Both compounds exhibited DNA sequence-dependence effects in their mode of binding. The linear aliphatic spermine molecule binds more strongly than histamine to both DNA types.
The influence of components on the rectal absorption of cefazolin in rats
Authors: van Hoogdalem Ewoud J , Geerts Joan A M , de Boer Albertus G , Breimer Douwe D 
Published: April 2011

Abstract
A study has been made to identify the component(s) responsible for the absorption-promoting effect of MGK medium chain glyceride preparation commercially available as a mixture of glyceryl-1-monooctanoate, glyceryl-1,3-dioctanoate, glyceryl-1,2-dioctanoate, glyceryl trioctanoate, octanoic acid and glycerol. The action of the individual constituents has been evaluated on the rectal absorption of cefazolin in conscious rats. The results indicate that the action of MGK can be completely explained by the effect of glyceryl-1-monooctanoate, which both enhanced the extent and rate of cefazolin uptake.
Action of a chronic arecoline administration on mouse motility and on acetylcholine concentrations in the CNS
Authors: Molinengo L , Fundaró A M , Cassone M C 
Published: April 2011

Abstract
The modifications of mouse motility and of the levels of acetylcholine (ACh) in two sections of the CNS caused by a chronic administration of 4.5; 9.5; 28.5 and 60 mg kg-−1 day−1 of arecoline for 20 days have been studied. At low doses (4.5 and 9.5 mg kg−1 day−1), arecoline caused no modification of the ACh levels and of the motility. The higher doses (28.5 and 60 mg kg−1 day−1) caused a reduction of the mouse motility and an increase of the ACh levels in the subcortical structures of the CNS of the mouse.
Ocular distribution of aspirin and salicylate following systematic administration of aspirin to rabbits
Authors: Valeri P , Romanelli L , de Paolis L , Martinelli B 
Published: April 2011

Abstract
The distribution of aspirin and salicylate 30 min after the intravenous administration of different doses of aspirin has been investigated in the rabbit eye. HPLC enabled a rapid and sensitive determination of both substances. A considerable dose-dependent penetration into all ocular tissues was observed with both aspirin and salicylate. Aspirin concentrations were higher than in plasma in all ocular tissues with the exception of the lens. These results show that an unhydrolysed drug may have a direct local effect by acetylating lens protein or other ocular constituents.
The Biochemical Actions of Phentolamine and Papaverine on Rat Perfused Skeletal Muscle
Authors: Preedy Victor R , Garlick Peter J 
Published: April 2011

Abstract
The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine-treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use.
Differential displacement of opioids from plasma protein binding sites by di-isopropylfluorophosphate in the mouse
Authors: Green Paul G , Kitchen Ian 
Published: April 2011

Abstract
Di-isopropylfluorophosphate (DFP) displaced the opioid drug, alfentanil, from plasma proteins in-vivo and in-vitro in mice but was without effect on the structurally related compound, fentanyl. This action probably accounts for the enhanced entry of alfentanil into the brain of DFP-treated animals and its enhanced antinociceptive activity.
Stereospecific Absorption and Degradation of Cephalexin
Authors: Tamai Ikumi , Ling He-Yan , Timbul Simanjuntak-Matheus , Nishikido Jyou , Tsuji Akira 
Published: April 2011

Abstract
Stereospecific absorption and degradation of two stereoisomers about the α-amino group at the 7-position of cephalexin (CEX) have been investigated in the rat intestine. The L-isomer (L-CEX) was not found to be present either in serum or urine after oral administration, but the D-isomer (D-CEX) was well absorbed. In contrast to the saturable uptake of D-CEX (Kt = 10.54 ± 1.73 mM, pH = 6.0) by the in-vitro everted intestinal sac, no appreciable uptake of L-CEX was observed. However, L-CEX competitively inhibited the uptake of D-CEX by the in-vitro everted intestine and the inhibitory constant (Ki) of L-CEX was determined to be 0.67 ± 0.09 mM. L-CEX was rapidly degraded in-vitro in the intestinal tissue homogenate, serum and urine, while there was no appreciable degradation of D-CEX. Analysis of the major metabolite of L-CEX by high-performance liquid chromatography identified it as 7-aminodeacetoxycepha-losporanic acid (7-ADCA). Furthermore, 7-ADCA was detected in serum after oral administration of L-CEX, indicating significant absorption of L-CEX as well as D-CEX. The results obtained suggest that both L- and D-CEX can be absorbed through the intestinal brush-border membrane via the same mechanism, most likely through the dipeptide transport system, and that the affinity of L-CEX to the carrier system is higher than that of D-CEX. However, owing to L-CEX having a higher affinity to the hydrolysing enzymes that are present in the intestinal tissue, serum, and urine, intact L-CEX was immediately hydrolysed after absorption and was not detectable in these samples. These results, demonstrating stereospecific transport and metabolism of CEX, provide strong evidence for a mechanism of carrier-mediated uptake in the absorption of CEX.
Toxicity of Solubilized and Colloidal Amphotericin B Formulations to Human Erythrocytes
Authors: Forster D , Washington C , Davis S S 
Published: April 2011

Abstract
The toxicity of a number of solubilized or colloidal amphotericin B formulations to human erythrocytes has been studied in-vitro. All the solubilized formulations studied, using poloxamer F127 or L92, or sodium deoxycholate as solubilizing agents, showed similar toxicity, erythrocyte lysis being greater than 90% for amphotericin B concentrations between 4 to 8 μg mL−1. Emulsion formulations stabilized by poloxamers showed reduced toxicity, while those stabilized by egg lecithin showed less than 5% erythrocyte lysis up to an amphotericin B concentration of 200 μg mL−1. The mechanisms of the differential toxicity is considered to be due to the differences in the equilibrium concentration of free amphotericin B in the aqueous phase.
Tissue Distribution and Excretion of Amodiaquine in the Rat
Authors: Winstanley P A , Edwards G , Curtis C G , Orme M L'E , Powell G M , Breckenridge A M 
Published: April 2011

Abstract
14C-Labelled amodiaquine ([14C]AQ) has been administered to male Wistar rats by oral and intravenous routes (n = 6 for each route of administration). Excretion of total 14C-activity was predominantly in the faeces after both oral and intravenous administration. After oral administration 86 ± 8.3% (mean ± s.d.) of the 14C administered had been excreted (77 ±9% in the faeces, 7 ± 1 % in the urine and 2 ± 2% in cage washings) over 72 h. Of the 14C administered, 4 ± 1% was recovered from the tissues, and this was widely distributed, with the main organs of accumulation being kidney, liver, red bone marrow and spleen. After intravenous administration, 102.6 ± 9.7% of the 14C had been excreted (90.9 ± 9.6% in faeces, 10.9 ± 0.8% in urine and 0.5 ± 0.2% in cage washings) over 72 h. High-performance liquid chromatographic analysis of urine and faeces samples following oral administration of 14C-AQ (8.6 mg kg−1; base) revealed recoveries of 210 ± 70 μg amodiaquine (AQ) and 123 ± 32 μg desethylamodiaquine (AQm) in the faeces, and 2.4 ± 0.5 μg AQ and 18.5 ± 4.1 μg AQm in the urine. Female Wistar rats (n = 6) each received [14C]AQ orally and were killed at the following times: 0.5, 1, 3, 6, 24 and 48 h. Autoradiographs were prepared from each animal and these revealed significant amounts of radioactivity in the tissues at 48 h. This was accumulated maximally by liver and kidney. Radioactivity was detected in bone marrow at 48 h. These data show that after oral administration of [14C]AQ to rats, significant amounts of radiolabel were accumulated in the liver, and haemopoietic tissues, which are the sites of observed toxicity in man. Of the excreted radiolabel, only a small proportion was in the form of AQ or AQm.
Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat
Authors: Young N A , Lewis S J , Harris Q L Gg , Jarrott B , Vajda F J E 
Published: April 2011

Abstract
The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg−1), clonazepam (0.3 mg kg−1) or vehicle (1 mL kg−1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor.
Retention and Distribution of Liposome-entrapped [3H]Methotrexate Injected into Normal or Arthritic Rabbit Joints
Authors: Foong W C , Green K L 
Published: April 2011

Abstract
Normal or arthritic rabbits were injected intra-articularly (i.a.) with free [3H]methotrexate ([3H]MTX) or liposomes containing [3H]MTX with [14C]cholesteryl oleate as a lipid marker. The distribution of 3H and 14C in the injected joint and other tissues was determined. Free [3H]MTX was rapidly cleared from the joint, 79% being excreted in the urine within 24 h of injection. Liposome-entrapment retarded [3H]MTX clearance from the joint (P &lt; 0.001), 45.5% being recovered from the joint 24 h after injection. Uptake of liposomes by the inflamed synovium was lower than expected, 4% liposomal [3H]MTX injected being associated with the synovium after 24 h. Nevertheless, this was 40-fold greater than when free [3H]MTX was injected. Liposome entrapment should improve the efficacy and reduce the side effects of drugs injected directly into the joint cavity.
Facile plasma-catalysed degradation of penicillin alkyl esters but with no liberation of the parent penicillin
Authors: Nielsen Niels Mørk , Bundgaard Hans 
Published: April 2011

Abstract
The methyl ester and some glycolamide esters of benzyl-penicillin and ampicillin were shown to be rapidly degraded by human plasma at 37 °C with no parent penicillin being produced. The plasma-catalysed degradation which was also observed in rat plasma proceeds most likely through hydrolytic cleavage of the β-lactam bonds of the penicillin esters and is suggested to be due to the presence of an ester-specific β-lactamase in plasma. The results show that the failure of simple alkyl esters of penicillins to function as prodrugs is not due to a high enzymatic stability of the esters, as widely believed, but rather to a pronounced susceptibility to undergo hydrolytic cleavage of their β-lactam ring in-vivo. Since double ester prodrugs of penicillins, such as the pivaloyloxymethyl ester of ampicillin, are readily hydrolysed in plasma to yield the parent penicillin although at a rate lower than e.g. that of inactivation of a simple methyl ester, the plasma enzyme apparently attacking the β-lactam bond of penicillin esters appears to have a high degree of specificity for the ester structure.
The effect of ciprofibrate on gastric secretion in the rat
Authors: Eason C T , Pattison A , Howells D D , Bonner F W 
Published: April 2011

Abstract
The potential of ciprofibrate to inhibit gastric secretion has been investigated in the rat. A significant gastric antisecretory effect was observed following a single oral administration of 300 and 500 mg kg−1 and following a single intraduodenal dose of 100, 300 and 500 mg kg−1. The toxicological significance of this finding is discussed in the light of a spate of recent publications linking changes in gastric morphology with hypergastrinaemia produced as a secondary effect of inhibition of acid secretion.