bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of diltiazem on morphine-induced respiratory decline
Authors: Szikszay Margit , Snyder Frederick R , London Edythe D 
Published: April 2011

Abstract
The individual and combined effects of subcutaneous morphine and diltiazem, a calcium channel inhibitor, on arterial blood gases and pH were assessed in conscious Fischer-344 rats. Morphine (4mg kg−1) produced hypercapnia, hypoxia and slight acidosis, as compared with control values. Diltiazem (10 mg kg−1) alone did not affect these parameters; however, it significantly delayed the onset of the aforementioned effects of morphine.
Effect of moderate haemodilution with Fluosol-DA or normal saline on ampicillin kinetics in the rat
Authors: Shrewsbury Robert P 
Published: April 2011

Abstract
The effects of haemodilution with either Fluosol-DA or normal saline on renal excretion and glomerular filtration have been studied in the rat. Ampicillin clearance and renal creatinine clearance were used as in-vivo measures of renal excretion and glomerular filtration, respectively. Rats were moderately exchanged with either fluid and evaluated after 0.5, 24, 48, or 72 h. After exchange, ampicillin clearance was higher, but not significantly different, and the apparent volume of distribution was increased significantly in some groups. These changes are consistent with the effects expected when plasma protein binding is reduced by haemodilution. The percent of ampicillin recovered in urine and the renal creatinine clearance were not statistically different in any group. Thus, moderate haemodilution with either fluid did not change renal function compared with unexchanged animals.
Pharmacological evaluation of an injectable prolonged release emulsion of physostigmine in rabbits
Authors: Benita Simon , Friedman Doron , Weinstock Marta 
Published: April 2011

Abstract
Physostigmine was incorporated in an injectable emulsion in an attempt to prolong its pharmacological activity. Emulsions which remained stable over 6 month storage were prepared using optimal experimental conditions. The in-vitro kinetic examination revealed that the rate-determining step in the release process of physostigmine from the emulsion was its partitioning from the oily phase to the external aqueous phase. The in-vivo results indicated that the physostigmine emulsion was able to inhibit the cholinesterase activity for at least 4 h, while the conventional injection inhibited the cholinesterase activity for only 1 to 2 h. The preliminary pharmacokinetic analysis showed that the physostigmine emulsion apparently increased the bioavailability compared with the conventional injectable solution. This could be attributed either to the protection of the sensitive drug from the enzymatic degradation or to improved absorption. The presence of poloxamer micelles in the aqueous phase was shown to enhance the bioavailability of physostigmine without having any effect on its pharmacological activity or duration.
Characterization of mitomycin C-induced gastrointestinal damage: changes in the gastric absorption of drugs in rats
Authors: Mizuno Masayuki , Kawabata Shigeki , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
The effect of mitomycin C (MMC) pre-administration intravenously on the absorption of drugs from rat stomach has been examined by means of the in-situ loop technique. 48 h after the MMC-treatment, the absorption of salicylic acid, aspirin and sulphanilic acid was not influenced but that of sulphanilamide was significantly increased compared with the control. At 96 h, a differential effect of MMC on the absorption of each drug was seen: the absorption of weakly acidic drugs was significantly decreased while that of bases and strong sulphonic acid increased. The decreased absorption of salicylic acid and aspirin correlated with the reduced gastric mucosal blood flow. At 96 h there were severe haemorrhagic lesions in the gastric mucosae. The increase in absorption of poorly absorbed drugs could be ascribed to the increased permeability of the blood-gastric epithelium barrier as was evidenced by leakage of Evans Blue.
[3H]Noradrenaline-releasing action of vinpocetine in the isolated main pulmonary artery of the rabbit
Authors: Pauló Tünde , Tóth Péter T , Nguyen Tinh Thi , Forgács Lilla , TÖRÖK TamáS L , Magyar Kálmán 
Published: April 2011

Abstract
Vinpocetine (10−6 − 3 × 10−5 M) increased both the resting and the nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 × 10−5 M; corticosterone, 5 × 10−5 M), and inhibited the nerve stimulation-evoked postsynaptic response. The resting transmitter releasing action of vinpocetine increased in the absence of cocaine. Exogenously applied (−)noradrenaline [(−)NA] (10−6 M) or clonidine (10−6 M) inhibited the vinpocetine (3 × 10−5 M)-potentiated [3H]NA release and contracted the circular muscle. The clonidine-induced contraction was abolished by 10−7 M prazosin. The inhibitory action of (−)-NA on vinpocetine-potentiated [3H]NA release was partly antagonized by 3 × 10−7 M yohimbine, a preferential α2-adrenoceptor blocker. In Ca-free Krebs solution containing 1 mM EGTA the neurotransmitter releasing action of vinpocetine was abolished, however, its stimulating action on the resting [3H]NA outflow was not changed. In Na-pump-inhibited arteries (K-free solution), where both the resting and the nerve stimulation-evoked release of neurotransmitter had already been increased, vinpocetine further enhanced the nerve stimulation-evoked release of [3H]NA. It is concluded that vinpocetine may have α2- and α1-adrenoceptor blocking action, as well as a tyramine-like effect. The presynaptic neurotransmitter releasing action of vinpocetine is presumably the consequence of its inhibitory action on the Ca-pump which is suggested by the finding that in K-free solution vinpocetine was able to enhance further the release of neurotransmitter.
Effect of acute renal failure on the disposition and elimination of [3H]N-acetyl procainamide ethobromide in the rat
Authors: Silberstein D J , Bowmer C J , Yates M S , Dean H G 
Published: April 2011

Abstract
The effect of glycerol-induced acute renal failure (ARF) on the disposition and elimination of the organic cation [3H]N-acetyl procainamide ethobromide (APAEB) was investigated in the rat. In rats with ARF the plasma clearance, rate constant for the terminal portion of the plasma concentration-time curve and apparent volume of distribution were all decreased (P &lt; 0.01). Furthermore, the renal clearance of APAEB and the percentage dose excreted in urine were reduced by 85 and 74%, respectively. Decreased renal excretion probably accounted for the altered kinetics of APAEB in ARF because ligation of the renal pedicles of control rats produced changes in the kinetics of APAEB that were similar to those seen in animals with ARF. No change in either the hepatic content of APAEB or its biliary excretion were detected in rats with ARF. Similarly, the hepatic handling of ouabain and taurocholic acid was previously found to be unaltered in ARF; but by contrast, the hepatic uptake and initial biliary excretion of bromosulphophthalein and indocyanine green were decreased (Bowmer & Yates 1984, Br. J. Pharmacol. 83: 773–782). Together these studies indicate that there is a selective impairment of hepato-biliary transport in ARF.
Dopaminergic metabolism in various rat brain areas after L-dopa loading
Authors: Gemayel G El , Trouvin J H , Prioux-Guyonneau M , Jacquot C , Cohen Y 
Published: April 2011

Abstract
The time course of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 3-methoxytyrosine (3-O-Medopa) concentrations in rat brain after treatment with L-dopa + benserazide has been investigated in the striatum, hypothalamus, hippocampus and cerebellum. These areas were selected for their different dopaminergic activities. After L-dopa loading, DA, DOPAC and HVA were increased in all the structures, but the largest increases were in those tissues with the less dopaminergic activity, while 3-MT increased in the hypothalmus, hippocampus and cerebellum but was lowered in striatum. 3-O-Medopa, which is the direct product of the O-methylation of L-dopa, did not show any specific distribution. The data provide evidence that the striatum, by feed-back mechanisms and specific enzymatic activity, is able to ensure a better regulation of dopaminergic activity than the other structures, thereby overcoming excess L-dopa.
The Nature of the Oil Phase and the Release of Solutes from Multiple (w/o/w) Emulsions
Authors: Omotosho James A , Whateley Tony L , Law Tak K , Florence Alexander T 
Published: April 2011

Abstract
The effect of the nature of the oil phase of w/o/w emulsions stabilized by interfacial complexation between span 80 (sorbitan mono-oleate) and albumin has been studied. The long-term stability of the systems has been assessed by photomicrography and by measuring the quantity of an internal marker (NaCl) remaining entrapped with time. The number of multiple oil drops and the diameters of the internal aqueous droplets were determined over 6 weeks, and the amounts of NaCl entrapped over the same period were followed. There were no significant changes in w/o/w emulsions prepared with a range of hydrocarbons (octane, dodecane, hexadecane, toluene and cyclohexane), indicating stable multiple emulsions. The release of NaCl and 5-fluorouracil (5-FU) separately entrapped in the internal aqueous phase of w/o/w emulsions was measured. Diffusion of the un-ionized species of 5-FU across the oil phase or through localized thin oil lamellae is the primary transport mechanism. In the presence of surface active agents, water is solubilized in inverse micelles which would possess the ability to solubilize other water-soluble components, such as NaCl and 5-FU. The mixed inverse micellar units of Span 80 and polysorbate (Tween) 80 therefore act as solute carriers across the liquid hydrocarbon membrane separating the two aqueous phases of the emulsions. The main factor in determining the differences in rates of release from the hydrocarbon emulsions appears to be the droplet size of the internal aqueous phase.
A platelet-aggregating and hypotensive phospholipid isolated from bovine brain
Authors: Yoshida Jun-Ichi , Tokumura Akira , Fukuzawa Kenzi , Terao Motonori , Takauchi Kenkichi , Tsukatani Hiroaki 
Published: April 2011

Abstract
A phospholipid that differs from known active lipids and causes potent platelet aggregation and weak hypotension has been isolated from bovine brain. Its platelet aggregating effect on heparinized platelet-rich plasma from rabbits, was at a threshold concentration of about 0.2 nmol ml−1 as phosphorus. The effect was inhibited by CV-3988. The phospholipid was converted by diazomethane treatment to another active lipid that caused short-term hypotension, but not platelet aggregation, rather it inhibited the aggregation of rabbit heparinized platelets induced by platelet-activating factor.
Investigation of the antimuscarinic and other actions of proadifen in-vitro
Authors: Choo L K , Malta E , Mitchelson F 
Published: April 2011

Abstract
The possibility that proadifen (SKF 525A) antagonizes endothelium-dependent relaxations to acetylcholine (ACh) in isolated blood vessel preparations via a muscarinic receptor blocking action has been investigated. In phenylephrine-contracted rat isolated aortic ring preparations (with endothelium), proadifen (10–100 μm) shifts ACh relaxant curves to the right without affecting the maximal response, yet endothelium-dependent relaxations to ATP are unaffected. At lower concentrations, proadifen (1–10 μm) (i) antagonizes negative inotropic responses to ACh and ATP in guinea-pig left atria, (ii) antagonizes contractile responses to ACh and elevated [K+] in guinea-pig ileal preparations, (iii) displaces (−)-[3H]quinuclidinyl benzilate from muscarinic binding sites in membrane homogenates of guinea-pig ileal longitudinal muscle and (iv) reduces contractile responses to elevated K+] in rat aortic ring preparations. It is concluded that proadifen may possess (i) complex interactions with muscarinic receptors and (ii) Ca2+ entry blocking properties in concentrations 10–100 times lower than those reported to inhibit cytochrome P450-catalysed reactions.
[3H]SCH 23390 identifies D-1 binding sites in rat striatum and other brain areas
Authors: Kilpatrick Gavin J , Jenner Peter , Marsden C David 
Published: April 2011

Abstract
The specific in-vitro binding of [3H]SCH 23390 has been characterized and its use in the identification of D-1 sites in various brain regions examined. At a single ligand concentration (0.4 nM) the specific binding of [3H]SCH 23390 to striatal membranes was routinely 98% of total binding as defined using 10−5 M cis-flupenthixol. Specific binding at 37 °C reached equilibrium at 15 min and was reversible with a t½ for dissociation of 14 min. Specific binding of [3H]SCH 23390 over a range of concentrations (0.01–3.5 nm) was saturable (Bmax 73 pmol g tissue−1) of high affinity (Kd 0.36 nM) and to a single population of binding sites. Specifically bound [3H]SCH 23390 (0.4 m) was stereo selectively displaced by the isomers of butaclamol and flupenthixol but not by the D-2 selective antagonist, sulpiride. 5-HT, noradrenaline and cinanserin caused little or no displacement. Specific binding of [3H]SCH 22390 (0.4 nM; as defined using 10−5 M cis-flupenthixol) showed marked regional variation. Specific binding was highest in the striatum; high levels were also observed in the mesolimbic area and substantia nigra. Lower specific binding was found in the frontal cortex and superior colliculus with the lowest levels in cerebellar preparations. The inclusion of 3 × 10−7 M cinanserin did not alter the extent of specific binding observed in any brain region. The properties of [3H]SCH 23390 suggest it to be an excellent ligand for identification of D-1 sites in a variety of brain regions.
N-Formylpenicillamine and penicillamine as degradation products of penicillins in solution
Authors: Bird A E , Jennings K R , Marshall A C 
Published: April 2011

Abstract
The degradation of several penicillins in unbuffered aqueous solution produces N-formylpenicillamine, in some cases in high yield. Very little or no penicillamine is formed under these conditions. N-Formylpenicillamine was produced from benzylpenicillin at pH values between 2.5 and 7, with a maximum yield of 30% at pH 5, whereas penicillamine was produced only at pH 5 or below in a yield of less than 1%. Benzylpenicillenic acid at pH 5 gave a 20% yield of N-formylpenicillamine and no penicillamine whereas benzylpenicilloic, penilloic and penillic acids gave no N-formylpenicillamine and a small amount of penicillamine.
The effect of sodium deoxycholate given by gavage with heparin on the histology of the intestinal mucosa of the rat
Authors: Guarini S , Adriana Fano Rita , Rompianesi Elena , Maria Martinelli Anna , Ferrari W 
Published: April 2011

Abstract
To gain direct insight into the mechanism of sodium deoxycholate (DOC)-induced enhancement of gastroenteral heparin absorption in rats, we performed light and electron microscopic examination of the mucosa of the small intestine of animals treated orally with DOC, heparin or DOC plus heparin. The sole morphological change observed after DOC and DOC plus heparin administration was a marked reduction in the length and distribution of glycocalyx filaments on the microvilli of epithelial cells. The morphological picture had reverted to normal after 24 h, when the promotion of enteral heparin absorption by DOC is greatly reduced. Thus, we suggest that DOC may promote the enteral absorption of heparin in rats by affecting some as yet unidentified barrier mechanism requiring glycocalyx integrity.
Early inflammatory response to carrageenan in the pleural cavity and paw of rats with altered body temperature
Authors: Thomas George , Socorro Sousa P 
Published: April 2011

Abstract
Polymorphonuclear leucocyte (PMNL) migration and oedema induced by carrageenan in the pleural cavity and paw, respectively, of rats made hyper- or hypothermic by physical and chemical means have been investigated. In rats placed in a warm environment to produce a rise in body temperature, carrageenan caused a moderate but significant increase in PMNL migration compared with the control animals. Opposite effects were obtained with hypothermic animals kept in a cold environment. While hyperthermia produced by amphetamine did not alter the PMNL migration, chlorpromazine-induced hypothermia caused a fall in the number of these cells present in the pleural cavity following carrageenan. Both hyper- and hypothermias, whether induced by physical or chemical means, inhibited the carrageenan paw oedema. The observed changes in the PMNL numbers in the pleural cavity did not reflect their numbers in the peripheral circulation. Results indicate that while a rise or a fall in body temperature may have opposite effects on PMNL migration, in carrageenan inflammation both conditions inhibit oedema formation.
The influence of degradable starch microspheres on liver uptake of 5-fluorouracil after hepatic artery injection in the rat
Authors: Teder H , Aronsen K F , Björkman S , Lindell B , Ljungberg J 
Published: April 2011

Abstract
The effect of degradable starch microspheres (DSM) on the distribution of 5-fluorouracil (5-FU) after hepatic artery injection was studied in normal rats. Carbon-14-labelled 5-FU was injected separately or together with DSM into the hepatic artery. Radioactivity was measured in liver tissue, bile, peripheral blood, and urine. When microspheres were added, the liver uptake of 5-FU was increased; its peak concentration in peripheral blood decreased, as did the early urinary excretion of radioactivity. The addition of degradable starch microspheres to hepatic artery injections of cytostatic drugs might be of value in increasing the drug concentration in tumour tissue and reducing systemic toxicity.
Particulate contamination of Australian ampoules
Authors: Gillies I R , Thiel W J , Oppenheim R C 
Published: April 2011

Abstract
Theoretical predictions and computer simulations indicate that it may be impossible to achieve values of the coefficient of variation usually found in large volume parenterals (LVP) when the intrinsic particulate contamination in small volume parenterals (SVP) is investigated. Snap-opened ampoules from Australian manufacturers containing 5, 10or 20 ml Water for Injections or Sodium Chloride Injection had a high level of particulate contamination, although within the USP XXI SVP limits. Heat-opened ampoules had much lower levels of contamination which were generally below the official LVP limits. Counts ml−1 were typically &lt;10 and &lt;1 for 5 and 20 μm particles, respectively. Coefficients of variation of the 5μm data from an ampoule in any batch examined, typically ranged over 30–70%. Statistical analysis of the 5μm data indicates significant differences between batches. Occasional ampoules had higher 5μm counts than others in the same batch. At no time were the particulate contamination levels considered to be clinically important.
An iterative curve stripping technique for pharmacokinetic parameter estimation
Authors: Dunne Adrian 
Published: April 2011

Abstract
Non-linear least-squares regression is commonly used for pharmacokinetic parameter estimation. Initial parameter estimates are required as a prelude to non-linear least-squares and the quality of the final parameter estimates may depend on these initial values. Polyexponential curve stripping is frequently used for the provision of initial estimates. It is demonstrated that under certain conditions conventional curve stripping yields biased estimates. A new iterative curve stripping technique is developed and is shown to be free of such bias. The two methods are compared using both simulated and real pharmacokinetic data.
The effect of varying carbachol concentration on the slope of Schild plots of selective β-adrenoceptor antagonists in the carbachol-contracted guinea-pig trachea
Authors: Keith R A , Donahue J Y , Salama A I 
Published: April 2011

Abstract
The effect of varying the level of smooth muscle tone induced by carbachol on the Schild analysis of atenolol (β1-selective) and ICI 118,551 (β2-selective) with salbutamol as agonist, on the guinea-pig tracheal preparation has been examined. When 10−6 M carbachol was used to induce near-maximal smooth muscle tone, Schild plot slopes for atenolol and ICI 118,551 were less than 1. Slopes of Schild plots for both drugs were equivalent to 1 when 10−7 M carbachol was used to produce approximately half-maximal smooth muscle tone. Depletion of neuronal noradrenaline by prior treatment with reserpine had no effect on the Schild analysis. Salbutamol produced maximal relaxation and was more potent when tone was induced with 10−7 M carbachol, but was less effective at 10−6 M carbachol. Pretreatment with reserpine increased the potency of salbutamol at each concentration of carbachol. The results suggest that either the level of smooth muscle tone or an unknown effect associated with a high level of smooth muscle tone induced by carbachol may contribute to low slope values of Schild plots of selective β-adrenoceptor antagonists in the carbachol-contracted guinea-pig trachea. The carbachol-contracted guinea-pig trachea can be used to determine theoretically valid pA2 values for selective β-adrenoceptor antagonists as long as substantially less than a maximal level of smooth muscle tone is induced by carbachol.
Enhancement of anti-inflammatory effects of biphenylylacetic acid by its incorporation into lipid microspheres
Authors: Shoji Y , Mizushima Y , Yanagawa A , Shiba T , Takei H , Fujii M , Amino M 
Published: April 2011

Abstract
Using lipid microspheres (LM), average diameter 0.2 μm, and containing methyl and ethyl esters of biphenylylacetic acid (BPAA) in the carrageenan paw oedema tests in rats, it was found that their anti-inflammatory activities were enhanced 3 to 8 times over that of free BPAA. By electron microscopy, LM were seen to be taken up into the endothelial cells of the blood vessels and macrophages at the inflamed sites. In a study using dogs, after an intravenous injection of BPAA-methyl ester incorporated into LM (lipo-BPAA-Me), lipo-BPAA-Me rapidly disappeared from the blood and the BPAA serum level was gradually elevated. These results, together with previous findings, suggest that part of lipo-BPAA-Me was immediately transferred to the inflamed site and taken up by prostaglandin (PG)-producing cells as macrophages. It is considered that the antiinflammatory effects of BPAA are enhanced by incorporating it into LM.
The effect of the molecular weight of polyethylene glycol on the bioavailability of paracetamol-polyethylene glycol solid dispersions
Authors: Vila-Jato José L , Blanco José , Alonso M José 
Published: April 2011

Abstract
A controlled study of the bioavailability of paracetamol in solid dispersion with PEG 6000, 10000 and 20000 has been made. The total amount of paracetamol excreted in urine increased with molecular weight of the PEG, but the rate of absorption of the drug was unaffected.