bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular reactivity in experimental acute renal failure
Authors: Yates M S , Askey Elizabeth A , Wilmot Susan E , Bowmer C J
Published: April 2011

Vascular reactivity in-vivo and in-vitro was examined in rats with acute renal failure produced by bilateral nephrectomy or intramuscular glycerol injection. Bilaterally nephrectomized rats displayed enhanced pressor responses to noradrenaline and angiotensin. However, the contractile responses to noradrenaline, angiotensin and potassium chloride of aortic rings and portal vein segments from nephrectomized rats were not significantly different from the responses obtained in vessels from sham-operated controls. Rats with glycerol-induced ARF which were pretreated with indomethacin had significantly lower pressor responses to noradrenaline and angiotensin than similarly treated control animals. Aortic rings from glycerol-injected rats produced significantly smaller contractions to noradrenaline than preparations from controls. This difference was not abolished by incubation of vessels with indomethacin. The findings suggest that the absence of kidneys or the presence of damaged renal tissue and not uraemia itself have pronounced but opposite effects on vascular reactivity. The depression of vascular reactivity in glycerol-induced ARF does not appear to be a result of increased production of prostaglandins.
Tensile anisotropy of some pigmented tablet film coating systems
Authors: Okhamafe Augustine O , York Peter
Published: April 2011

The tensile properties of representative tablet film coating systems, containing hydroxypropyl methylcellulose alone and in combination with either polyvinyl alcohol, polyethylene glycol 400 and polyethylene glycol 1000 and pigmented with either talc or titanium dioxide, have been investigated. Tensile anisotropy was observed between film samples cut parallel to, and perpendicular to, the direction of rotation of the casting substrate and factors accounting for this phenomenon are presented.
Penetration of the human nail plate: the effects of vehicle pH on the permeation of miconazole
Authors: Walters Kenneth A , Flynn Gordon L , Marvel John R
Published: April 2011

In order to assess the relative permeability of the nail plate to ionized and unionized drugs the permeation of miconazole at varying pH has been followed as a function of time. The pH was adjusted from 3.1 to 8.2 to obtain between 5 and 100% dissociation of the drug. No significant difference in the rate of permeation was demonstrated. The data suggests that the ionic form of miconazole dissolves as easily in the nail plate as the free base and, therefore, topical bioavailability can be enhanced by decreasing the formulation pH thereby increasing drug solubility.
Some actions of sodium nitroprusside and glyceryl trinitrate on guinea-pig isolated trachealis muscle
Authors: Kishen R , Pleuvry B J
Published: April 2011

The smooth muscle relaxant actions of sodium nitroprusside and glyceryl trinitrate have been compared to those of aminophylline and isoprenaline on isolated guinea pig trachealis muscle. Ethacrynic acid (0.25 times 10−4 M), an alkylator of sulphydryl groups, interacted differently with the four agents. In the presence of ethacrynic acid the concentration response curve of the muscle preparation to sodium nitroprusside and glyceryl trinitrate was shifted to the higher concentration ranges and the maximum response was severely reduced. The concentration response curve for isoprenaline was shifted to the higher concentration ranges with no change in the maximum response and the response to aminophvlline was unchanged. These results argue against common intermediate sites of action involving sulphydryl groups of the four agents in guinea-pig trachealis.
Prolongation of thiopentone-induced sleep by trazodone and its metabolite, m-chlorophenylpiperazine
Authors: Adamus Anna , Sansone Mario , Melzacka Miroslawa , Vetulani Jerzy
Published: April 2011

Trazodone and its metabolite, m-chlorophenylpiperazine (CPP) prolonged significantly thiopentone-induced sleep in mice. Neither trazodone, nor CPP changed the cerebral concentrations of thiopentone. As cyproheptadine by itself did not affect thiopentone sleep and did not antagonize the effect of CPP, the effect of trazodone and CPP seems to be independent of their respective 5-HT-antagonistic and 5-HT-agonistic properties.
Evidence for the dissociation of morphine analgesia, tolerance and dependence
Authors: Kaneto Hiroshi , Yamazaki Akira , Kihara Tsuyoshi
Published: April 2011

A single large dose of morphine produced profound analgesia accompanied by the development of tolerance and physical dependence. The tolerance developed acutely within 24 h and was further intensified, reaching a peak on the 5th day, then gradually disappeared. Partial or complete masking of morphine analgesia by naloxone inhibited the development of the acute, but could not prevent the development of the delayed, tolerance. These results suggest there are two kinds of tolerance and that the analgesic effect is separate from tolerance. Similarly, treatment with morphine produced physical dependence which was precipitated by naloxone, Unlike tolerance, dependence did not develop when morphine analgesia was completely masked by naloxone. The findings provide for the dissociation or morphine analgesia, tolerance and dependence.
Lymphatic transport of sodium cefoxitin in the presence of sodium 5-methoxysalicylate after injection into rat rectal connective tissue, femoral muscle and femoral vein
Authors: Nishihata Toshiaki , Kim Suni , Kamada Akira , Frederick Gregory , Dillsaver Margaret , Higuchi Takeru
Published: April 2011

Lymphatic uptake of sodium cefoxitin after injection into rectal connective tissue was greater than after injection into the femoral muscle of rats. Coadministration with sodium 5-methoxysalicylate enhanced lymphatic drug uptake at both sites. This enhancement may be an indirect result of 5-methoxysalicylate's suppression of vascular permeation of the cefoxitin. An adjuvant-induced increase in lymphatic fluid flow may also be partially involved in the enhancement of cefoxitin lymphatic transport.
Characterization of enhanced intestinal permeability; electrophysiological study on the effects of diclofenac and ethylenediaminetetraacetic acid
Authors: Yamashita Shinji , Saitoh Hidetaka , Nakanishi Kunio , Masada Mikio , Nadai Tanekazu , Kimura Toshikoro
Published: April 2011

The mechanism of the enhancing effects of diclofenac sodium and disodium ethylenediaminetetraacetate (EDTA) on intestinal permeability to sulphanilic acid were investigated in the rat isolated jejunum by an electrophysiological technique. The results suggested that diclofenac sodium increased the mucosal-to-serosal flux rate of sulphanilic acid by enhancing both transcellular and paracellular permeabilities while the effect of EDTA was located only in the paracellular pathway.
Analysis of particulate contamination in ampoules using a light blockage particle analyser
Authors: Alexander D M , Veltman A M
Published: April 2011

A method of opening ampoules without introducing particles has been developed and the level of particulate contamination in a number of ampoule solutions using a light blockage particle analyser (HIAC) has been determined. Low levels of contamination were found and a method of setting limits of particulate contamination in ampoules is suggested.
In-vitro and in-vivo protection of acetylcholinesterase by eseroline against inactivation by diisopropyl fluorophosphate and carbamates
Authors: Galli A , Aiello P Malmberg , Renzi G , Bartolini A
Published: April 2011

The protective action of eseroline—(3aS, 8aR)-l,2,3,3a,8,8a-hexahydro-l,3a,8-rimethyl-pyrrolo[2,3-b]indol-5-ol—salicylate against (DFP) diisopropyl fluorophosphate and carbamate poisoning of cholinesterases (ChEs) has been examined in-vitro with human erythrocytes and purified preparations of electric eel acetylcholinesterase (AChE) and of horse serum butyrylcholinesterase (BuChE), and in-vivo using mice. Eseroline afforded 50% protection (ED 50) of erythrocyte AChE against inactivation by 1 μM DFP, physostigmine or neostigmine, at concentrations of 4.3, 22 and 23.5 μM, respectively, while for eel AChE protection against 10 and 30 μM DFP, 0.3 and 1 μM physostigmine and 1 μ m neostigmine the eseroline ED 50 values were 0.3, 0.4. 0.7, 1.9 and 5.6 μM, respectively. On the other hand, up to 0.3 mM eseroline did not appreciably affect the inhibitory action of the same drugs on horse serum BuChE. Eseroline concentrations in the range 0.1-1 mM were able to reactivate 20-42% of erythrocyte AChE previously inhibited by 100 μM physostigmine, but failed to reactivate the DFP (10 μM)-pretreated enzyme to any extent. Finally, eseroline salicylate injected into mice (10 mg kg−1 s.c.) protected an average of 82 and 26% of the animals against lethal doses of DFP (7mg kg−1 s.c.) and physostigmine sulphate (1 mg kg−1 i.p.) respectively, which were administered 15 min later. These results indicate that the protective activity of eseroline correlates well with its own anti-ChE profile, and that the effectiveness of the protection depends largely on the rate of AChE inhibition by the agents used to inactivate the enzyme.
The effects of neostigmine on the response of the rat anococcygeus muscle to field stimulation are not a consequence of Cholinesterase inhibition
Authors: Smith J A , Spriggs T L B
Published: April 2011

Neostigmine (5 times 10−7 to 5 times 10−6 M) and physostigmine (10−5 M) each augment the responses of the rat anococcygeus muscle to field stimulation whereas iso-OMPA (5 times 10−6 to 5 times 10−4 M) or BW 62c47 (5 times 10−7 to 5 times 10−5 M) do not. At a concentration of 10−5 M, neostigmine, BW 62c47 and iso-OMPA respectively produced a 48, 50 and 68% inhibition of cholinesterase activity in homogenates of anococcygeus muscle. The ED50 for cholinesterase inhibition by neostigmine (1.4 times 10−5 M) is approximately 15 fold greater than the ED50 for the augmentation of the response to field stimulation (9.5 times 10−7 M). It is concluded that the action of neostigmine in augmenting the response of the rat anococcygeus muscle to field stimulation is not a consequence of cholinesterase inhibition even though stimulation of muscarinic receptors is implicated.
Particulate contamination in ampoules
Authors: Alexander D M , Veltman A M
Published: April 2011

The particulate contamination in 19 formulations of solutions in ampoules supplied by eight South African manufacturers, thirty-three batches in all, was analysed using a HIAC PC 320 light blockage particle analyser linked to a CMB 60 sensor. Results showed that the level of contamination was generally low and that, where comparisons could be made, manufacturers both of the ampoules and the solutions maintained similarly high standards. Problems in this field appeared to be related to the formulation or the quality of the raw material.
The effect of some benzimidazoles on the disposition of antipyrine and tolbutamide from the rat isolated perfused liver
Authors: Ward S A , Mihaly G W , Tjia J F , Back D J
Published: April 2011

The anthelmintic benzimidazoles, mebendazole, albendazole and flubendazole have been screened for any propensity to alter the disposition of antipyrine and tolbutamide in the rat isolated perfused liver preparation. The benzimidazoles were added as a 2.5 mg bolus dose into the perfusate reservoir 5 min before the administration of either antipyrine or tolbutamide. Neither mebendazole or albendazole produced any significant effect on the pharmacokinetics of either of the substrate drugs. In contrast, flubendazole significantly decreased the clearance of antipyrine (by 40%) indicating inhibition of mixed function oxidase activity. However, flubendazole did not alter the disposition of tolbutamide. The results suggest that not all benzimidazoles inhibit hepatic drug metabolizing enzymes and that different forms of cytochrome P-450 are involved in the metabolism of antipyrine and tolbutamide.
Effect of implanted ethylene-vinyl alcohol copolymer matrices containing 5-fluorouracil on Ehrlich ascites carcinoma
Authors: Miyazaki Shozo , Takeuchi Shigemi , Sugiyama Mieko , Takada Masahiko , Hosokawa Masuo , Koga Yutaka , Kobayashi Hiroshi
Published: April 2011

The antitumour activity of ethylene-vinyl alcohol (EVAl) copolymer matrices containing 5-fluorouracil (5-FU) was evaluated against Ehrlich ascites carcinoma in mice. A prolongation of the life-span of tumour-bearing mice following intraperitoneal implantation of therapeutic matrices was noted. These results indicated that EVAl matrices containing 5-FU may be effective in cancer chemotherapy. Matrices composed of EVAl copolymer could be useful vehicles for implanted, inserted, or surface-applied delivery systems for anticancer agents.
Phthalic acid esters inhibit arachidonate metabolism by rat peritoneal leucocytes
Authors: Tavares I A , Vine N D
Published: April 2011

Phthalic acid esters concentration-dependently inhibited the formation of both cyclo-oxygenase and lipoxygenase arachidonate products by rat peritoneal leucocytes. Phthalates are extracted by human transfusion blood stored in pvc bags, and might similarly affect the blood cells when administered to patients.
In-vivo metabolism in the rat and mouse of antrafenine to 1- m-trifluoromethylphenylpiperazine
Authors: Caccia S , Conti I , Notarnicola A
Published: April 2011

The analgesic antrafenine forms 1- m-trifluoromethylphenylpiperazine (mCF3PP) during its biotransformation in the rat and mouse. At least 14 and 3% of an antrafenine dose (25 mg kg−1 p.o.) reaches the systemic circulation as mCF3PP in the mouse and rat respectively. The metabolite easily enters the brain, reaching concentrations several times those in body fluids. This, together with the fact that mCF3PP is known to produce several pharmacological effects compatible with a stimulatory action on 5-hydroxytryptamine postsynaptic receptors, suggests that this metabolite may contribute to the parent drug's pharmacological effects.
Photon correlation spectroscopy of surface active cationic drugs
Authors: Atherton A D , Barry B W
Published: April 2011

Photon correlation spectroscopy (PCS) has been used to examine the aggregation in aqueous NaCl solution of a series of antidepressant and antihistamine drugs (hydrochlorides of imipramine, clomipramine, amitriptyline, butriptyline, protriptyline, doxepin, dothiepin, iprindole, diphenhydramine, bromodiphenhydramine, orphenadrine) propranolol hydrochloride and propantheline bromide. Critical micelle concentrations were measured by surface tension and PCS. Micellar sizes were investigated as functions of drug structure and drug and NaCl concentration. Generally, antidepressants formed the largest micelles. We propose that the antidepressants aggregate in a similar fashion to the phenothiazines by stacking with size increasing by addition of single monomers to stacks and by addition of more stacks to the aggregate.
19F NMR spectroscopy study of the metabolites of flucloxacillin in rat urine
Authors: Everett J R , Jennings K , Woodnutt G
Published: April 2011

19F NMR spectroscopy was used to monitor the metabolites of flucloxacillin in the urine of a rat dosed with its sodium salt. 19F NMR signals were detected and quantified from flucloxacillin and three metabolites. The 19F NMR method involves minimal sample preparation and is free from interference by endogenous urine components. High-field spin-echo 1H NMR spectroscopy and HPLC were used to confirm the results.
The sustained release of pyrimethamine base or pyrimethamine pamoate from a biodegradable injectable depot preparation in mice
Authors: Coleman M D , Mihaly G W , Ward S A , Edwards G , Howells R E , Breckenridge A M
Published: April 2011

The pharmacokinetics and mass fate in mice, of pyrimethamine (425 mg kg−1 s.o.) administered subcutaneously either as the base (BASE) or the pamoate salt (PAM) in an injectable oil mixture (benzyl benzoate-peanut oil 50:50 v/v) have been evaluated. Maximum measured plasma pyrimethamine levels after BASE were attained within 24 h, and were twice as high as after PAM. 25% of animals dosed with BASE died; among the survivors plasma drug levels fell rapidly below the minimum inhibitory concentration (MIC) for Plasmodium berghei (100–200 ng ml−1) by 5 weeks. In contrast, no mice dosed with PAM died and plasma levels were sustained above the MIC for 13 weeks, drug still being detectable in plasma after four months. Overall, there was no significant difference between areas under the curve from zero time to the time of the final sampling of pyrimethamine following PAM or BASE. The rapid initial elimination of 14C-radioactivity (2ṁ64 ± 0ṁ47% dose day−1 over 4 weeks) seen after dosage with [14C]BASE reflected the plasma disposition of pyrimethamine in the mice dosed with BASE. 90% of the excreted 14C was eliminated by one month by which time less than 1% (0ṁ03 ± 0ṁ02%) of the [14C]BASE was recovered from the injection site. Both BASE and [14C]BASE studies suggest that exhaustion of this preparation occurred by 7 weeks. Excretion of 14C-radioactivity after [14C]PAM was gradual and sustained with a low mean daily rate, that was maintained throughout the study i.e. 1ṁ21 ± 0ṁ17% day−1 (4 weeks), 0ṁ88 ± 0ṁ28% day−1 (8 weeks), 0ṁ5 ± 0ṁ31% day−1 (12 weeks), 0ṁ42 ± 0ṁ27% day−1 (16 weeks). At the end of the study, 7ṁ11 ± 1ṁ90% of the [14C]PAM remained in the dose site. No visible tissue reactions were observed to either preparation. Overall recovery of radioactivity was 85ṁ00 ± 11ṁ31% for both [14C]PAM and [14C]BASE. These studies indicate that the PAM preparation is worthy of further long term evaluation.
Magnesium ions and oxytocin sensitivity of the male mouse anococcygeus
Authors: Gibson A
Published: April 2011

The sensitivity of the mouse anococcygeus to contraction by oxytocin was shown to be Mg2+-dependent. Decreasing [Mg2+]0 from the optimal concentration of 1 to 0 mM caused a 20-fold parallel rightward displacement of the oxytocin dose-response curve. Contractions to oxytocin-related peptides (Arg-vasotocin, Arg-vasopressin and Lys-vasopressin) were also Mg2+-dependent, but those to other drugs (carbachol, methoxamine and thyrotrophin releasing hormone) were not. The onset of the potentiating effect of Mg2+ was rapid, full potentiation occurring within 70 s. 1-Deaminopenicillamine 8-ornithine-vasotocin produced competitive antagonism of responses to oxytocin, but was more potent in the absence (pA2 = 8ṁ01) than in the presence of Mg2+ (1 mM; pA2 = 7ṁ52). Thus, physiological concentrations of [Mg2+]0 enhanced oxytocin agonist potency but decreased oxytocin antagonist potency; possible mechanisms are discussed.
An investigation of the structural changes occurring in a cetostearyl alcohol/cetrimide/water gel after prolonged low temperature (4°C) storage
Authors: Patel H K , Rowe R C , McMahon J , Stewart R F
Published: April 2011

Structural changes in a ternary gel prepared using the mixed emulsifier system of cetrimide and cetostearyl alcohol after prolonged low temperature (4°C) storage have been studied using freeze-etch transmission electron microscopy and other techniques. The system changed from an opaque smooth gel of high viscosity, low conductivity and low free water, to a pearlescent milky lotion of low viscosity, high conductivity and high free water. Subsequent equilibration of the thinned system to room temperature (25°C) over 48 h produced an opaque granular gel of similar consistency, but slightly higher conductivity and higher free water than the initial sample. Microscopical examination by both differential interference contrast and freeze-etch electron microscopy showed the system changed from one consisting of a liquid crystalline network localized around cetostearyl alcohol particles, to a system consisting of large waxy plates coexisting with some residual liquid crystalline network. A supportive mechanism for the thinning of the ternary gel at prolonged low temperature storage has been inferred by comparing data with that produced by other workers studying the fusion of phospholipid membranes considered to be morphologically similar to the liquid crystalline network observed in this ternary gel.
Further assessment of glunicate hypolipidaemic activity in the rat
Authors: Renzetti Anna Rita , Criscuoli Marco , Subissi Alessandro
Published: April 2011

The hypolipidaemic activity of glunicate administered orally to rats has been further evaluated. In the fasted normolipidaemic rat, glunicate, in single doses of 10ṁ300 mg kg−1 (as nicotinic acid equivalents), exerted a dose-dependent reduction of plasma triglycerides and cholesterol. At the lower doses, the HDL: total cholesterol ratio was enhanced, but at higher doses it was depressed. Similar results were obtained in the fasted obese Zucker rat, but the acute effects of glunicate seemed less marked in this strain. When the same doses of glunicate were given for 7–8 consecutive days no alteration of the plasma lipid pattern was observed, the reason being that the hypocholesterolaemic action of single doses of glunicate is reduced or abolished in fed animals; this was not due to pharmacokinetic factors depending on feeding. The same lack of hypocholesterolaemic action in fed animals occurred with nicotinic acid.
Age-related changes in sorbitol dehydrogenase activity of rat brain, liver, kidney and eye
Authors: Cao Danh H , Benedetti M Strolin , Dostert P
Published: April 2011

Sorbitol dehydrogenase (SDH) activity was measured in whole brain, different brain areas, liver, kidney and eye of old rats (23–26 months) and compared with matched animals (3 months). A significant increase in SDH activity was found in whole brain (34%) of old rats, as well as in all brain areas studied: brainstem (59%), hypothalamus (38%), cerebral cortex (35%), striatum (30%), midbrain (27%), hippocampus (27%) and cerebellum (19%). The increase in SDH activity in brain of old rats is due to Vmax. These results do not favour an accumulation of sorbitol in brain of old rats. A significant decrease (36%) in SDH activity was found in kidney and no significant change in liver and eye of old rats when compared with young rats. Our previous and present results suggest that an accumulation of sorbitol might occur in some tissues of old rats, particularly in the eye, and cause cataract formation.
Interaction between clonidine and histamine on the guinea-pig isolated trachea
Authors: Floch A , Advenier C
Published: April 2011

In experiments on guinea-pig isolated tracheal spirals, clonidine, in concentrations of 10−6 to 3 times 10−4 M. had a contracting effect which was strongly inhibited by prazosin but not significantly modified by yohimbine. Moreover, clonidine (3 times 10−5 to 3 times 10−4 M) potentiated histamine-induced contractions; this latter effect was inhibited specifically by α1-adrenoceptor antagonists (e.g. prazosin, AR-C 239) but unmodified by yohimbine, nicardipine or agents acting on the arachidonic acid cascade. It would therefore appear that clonidine in high concentrations contracts the guinea-pig trachea by stimulating α1-adrenoceptors and that, contrary to what has been reported with other animal species, notably the dog, the guinea-pig trachea is devoid of α2-adrenoceptors that mediate contractions.
Prostaglandin D2-induced potentiation of hexobarbitone hypnosis in rats: role of 5-hydroxytryptamine
Authors: Bhattacharya S K , Parmar S S
Published: April 2011

Prostaglandin D2 (PGD2) produced a dose-related increase in the duration and incidence of induction of sleep induced by hexobarbitone, in rats. Pretreatment with pharmacological agents known to reduce selectively brain 5-hydroxytryptaminergic activity, significantly inhibited PGD2-induced potentiation of hexobarbitone, indicating that this potentiation is mediated by 5-hydroxytryptamine.
Amphetamine-induced circling behaviour in MPTP-lesioned mice
Authors: Fung Yiu K , Troxel Charles E
Published: April 2011

This study was designed to examine the effect of intra-striatal administration of MPTP on (+)-amphetamine-induced circling behaviour in mice. The results demonstrate that (+)-amphetamine elicits circling behaviour in MPTP-lesioned animals. MPTP produced a 70% depletion of striatal dopamine concentration.
Inhibition of rabbit cardiac adenylate cyclase by theophylline
Authors: Hopwood Alexandra M , Harding Sian E , Harris Peter
Published: April 2011

Theophylline inhibits basal adenylate cyclase activity as well as cyclase stimulated by sodium chloride, sodium fluoride, GTP or 5′-guanylimidodiphosphate. This inhibition is dose-dependent and shows non-competitive inhibition, with respect to MgATP. The presence of adenosine deaminase does not alter the effect of theophylline. The inhibition produced by theophylline is not additive with that due to 2′-deoxyadenosine 3′-monophosphate (a P-site agonist). It is suggested that theophylline may act at the P-site to reduce adenylate cyclase activity.
Ascorbic acid antagonizes the behavioural effects of LSD in cats
Authors: Trulson Michael E , Crisp Terriann , Henderson Leslie J
Published: April 2011

Pretreatment with ascorbic acid (500 mg kg−1 i.p.) antagonized the behavioural effects of lysergic acid diethylamide (LSD) and apomorphine, but not 5-methoxy-N,N-dimethyltryptamine, in cats. The data support the hypothesis that these behavioural effects in cats are due to drug action at both 5-HT and dopamine receptors, and that the action of LSD at dopamine receptors is modulated by ascorbic acid.
A hypothesis for the mode of action of anti-rheumatic drugs in a model of cartilage destruction
Authors: Willoughby D A , Al-Duaij A , de Brito F , Sedgwick A D , Moore A R , Williams J D
Published: April 2011

We have been using as a model rats and mice with air pouches which develop lining cells closely resembling synovium (Edwards et al 1982; Sedgwick et al 1983). These pouches when sufficiently mature, i.e. 6 days, will respond to a variety of stimuli both immune and non-immune with long lasting exudates containing many migrated leucocytes (Sedgwick et al 1983, 1984a).

We examined the breakdown of cartilage in both inflamed and non-inflamed pouches and have found that inflammation protected the rate of loss of proteoglycan from cartilage (Sedgwick et al 1984b. 1985; Willoughby et al 1985). Invariably the cartilage in the inflamed air pouch would float free in exudate while cartilage, in the non-inflamed pouch would adhere to the pouch wall in close proximity to the macrophages and fibroblasts of the lining cells. Unpublished findings from this department (de Brito) have shown that the presence of granulation tissue in close proximity to cartilage will speed proteoglycan loss.
Interaction of cyclosporin A with human lipoproteins
Authors: Sgoutas Demetrios , Macmahon Wendy , Love Ann , Jerkunica Ivanka
Published: April 2011

The ultracentrifugal fractionation of human serum after previous incubation with cyclosporin A showed that, in healthy fasting individuals, 8% of cyclosporin A was found in the very low density lipoproteins (VLDL), 31% in the low density lipoproteins (LDL), 46% in the high density lipoproteins (HDL) and 15% in the non-lipoprotein protein fraction. In non-fasted, healthy and in non-fasted, lipaemic individuals, 7 and 6% of cyclosporin A was found in chylomicrons, 9 and 13% in VLDL, 28 and 30% in LDL, 39 and 37% in HDL, and 12 and 13% in the non-lipoprotein protein fraction, respectively. In patients receiving cyclosporin A the distribution varied from 12 to 19% in VLDL, 21 to 28% in LDL, 33 to 43% in HDL, and 13 to 20% in non-lipoprotein proteins. The interaction between cyclosporin A and isolated normal human lipoproteins was also studied by ultrafiltration. All lipoproteins exhibited a non-saturable, low affinity, high capacity uptake for cyclosporin A. Analysis of the uptake by phospholipid vesicles showed a similar uptake, suggesting that cyclosporin A dissolves in the lipophilic portion of the lipoprotein molecule rather than being associated with specific binding sites.
The effects of new local anti-inflammatory steroids on leucocyte migration and prostanoid liberation in rats
Authors: Bird John , Lay John C , Lee Henry J
Published: April 2011

The local anti-inflammatory potency of steroid-21-oate esters derived from prednisolone was determined by cotton pellet granuloma bioassay. The doses which inhibited granuloma formation by 50% (ID50) were: prednisolone, 0.5 mg/pellet; methyl 20α-dihydroprednisolonate, 5.8 mg/pellet; methyl 20 β-dihydroprednisolonate, 1.2 mg/pellet; methyl 17,20α-acetonidodihydroprednisolonate, 6.0 mg/pellet. When administered at these equipotent local anti-inflammatory doses, only prednisolone depressed plasma corticosterone and promoted thymus involution. Prednisolone reduced neutrophil migration into saline-soaked polyester sponges and depressed the levels of 6-keto PGF1α, PGE2 and elastase in the sponge-induced inflammatory exudate. Methyl 20α- and 20β-dihydroprednisolonate had no effect on cell migration, but depressed the levels of 6-keto PGF1α and elastase. The liberation of 6-keto PGF1α, PGE2 and elastase and neutrophil migration were inhibited by methyl 17,20α- and β-acetonidodihydroprednisolonate, but the effect of the β-epimer on cell migration was transient. These data suggest that steroid acid esters which have local and topical anti-inflammatory properties exert their effect in a similar fashion to glucocorticoids with a ketol side-chain (e.g. prednisolone) with respect to liberation of prostaglandins and lysosomal enzymes. However, their effect on neutrophil migration was variable, depending on their structural features. Furthermore, the systemic effects of these new derivatives were drastically reduced indicating that they may be of potential benefit in prolonged treatment.
Mechanism of the inhibitory effect of thiopentone on stimulus-secretion coupling in chromaffin cells
Authors: Matsumoto Tomikichi , Sumikawa Koji , Kashimoto Takeshi
Published: April 2011

This study was undertaken to clarify the mechanism of action of thiopentone on stimulus-secretion coupling in cholinergic postsynaptic cells using cultured bovine adrenal chromaffin cells. Thiopentone (20–100 μm) inhibited carbachol-induced Ca2+ uptake into, and catecholamine release from, the cells in a concentration-dependent manner. The inhibition of catecholamine release was almost parallel to the inhibition of Ca2+ uptake. The inhibitory effect of thiopentone was not overcome by an increase in the concentration of carbachol, whereas that of alcuronium was. Contrary to the inhibition by diltiazem, which was reversed by increasing the Ca2+ concentration, the inhibition by thiopentone was not overcome by a high Ca2+ concentration. Compared with the inhibition of carbachol-induced catecholamine release, a higher concentration of thiopentone was required to inhibit high K+ (56 mM KCl)-induced catecholamine release (200 μm thiopentone exhibited 32% inhibition). The results suggest that thiopentone blocks the stimulus-secretion coupling in the chromaffin cells as a result of inhibiting Ca2+ uptake through nicotinic receptor-linked channels. The linkage between receptor stimulation and Ca2+ channel activation seems to be the process most susceptible to inhibition by the barbiturate.
Racemic and optically active trans 2,6-dimethyl analogues of the reversed ester of pethidine
Authors: ranch S K B , Casy A F , Cittern P , Madani A E
Published: April 2011

The preparation and stereochemical characterization of (±)-1, trans 2,6-trimethyl-4-phenyl-4-propionoxypiperidine hydrochloride and its (+)- and (−)-antipodes are described. The absolute configurations of the antipodes were established by X-ray analysis of the corresponding (−)-4-piperidinol hydrobromide. In antinociceptive tests on mice and rats, the (+)-2S,6S ester proved the more potent antipode by factors of at least 10 (rats) and 20 (mice), a result consistent with earlier proposals made about the probable uptake conformation of pethidine reversed esters at opioid receptors.
Antitumour effect of fibrinogen microspheres containing doxorubicin on Ehrlich ascites carcinoma
Authors: Miyazaki Shozo , Hashiguchi Norio , Yokouchi Chizuko , Takada Masahiko , Hou Wei-Min
Published: April 2011

The antitumour activity of fibrinogen microspheres containing doxorubicin has been evaluated against Ehrlich ascites carcinoma in mice in terms of changes in body weight and survival. Tumour cell injections were made on day 0 and microsphere injections on day 1, both intraperitoneally. The suppressive effect of the drug-containing microspheres on increase in body weight was higher than that of the free drug, and tumour-bearing mice given the microspheres lived longer than those given the free drug.
Laxatives and the production of autacoids by rat colon
Authors: Capasso F , Mascolo N , Autore G , Romano V
Published: April 2011

The effects of some laxatives were examined on the formation of histamine, 5-hydroxytryptamine (5-HT) and prostaglandin-like material (PG-LM) by rat intestine in-vitro. Castor oil, senna, sulphosuccinate and bisacodyl, but not mannitol or lactulose, in doses that cause laxation, increased the formation of histamine, 5-HT and PG-LM. Indomethacin or hydrocortisone reduced the increase of PG-LM formation. The data support the idea that the laxative effects of these intestinal secretagogues are due to increased intestinal production of PG-LM, histamine and 5-HT.
Spectrofluorimetric analysis and buccal absorption of mediroxamine
Authors: Randhawa M A , Blackett A N , Turner P
Published: April 2011

Medifoxamine is a new investigational antidepressant drug. Its buccal absorption at pH 5–9, which can be considered as an in-vivo model of passive drug transfer through a lipid membrane, was studied in six normal, healthy volunteers to predict its pharmacokinetic profile in man. Maximum absorption of medifoxamine occurred at pH 8, which is close to its pKa (8.5).
Mechanism of dissolution of cholesterol-calcium bilirubinate compressed discs in monooctanoin
Authors: Mulligan S C , Corrigan O I
Published: April 2011

The dissolution of cholesterol monohydrate and calcium bilirubinate (neutral salt) mixtures in monooctanoin was investigated using the static disc method. The intrinsic dissolution rate of calcium bilirubinate was orders of magnitude (∼ 1000 fold) lower than that of cholesterol. Cholesterol release decreased as its weight fraction in the solid decreased. In model systems containing below 50% cholesterol dissolution became negligible. The release profiles deviated from the classical model for dissolution from two component mixtures. The observed dissolution profiles of both components were greater than predicted by theory. Anomalous positive curvatures in dissolution profiles suggested that calcium bilirubinate initially reduced the surface area available for cholesterol dissolution. A model, taking into account the change in surface area, was used to fit the cholsterol dissolution data. The results were consistent with the reported relationship between human gallbladder stone cholesterol content and average stone weight loss.
Factors influencing the tissue distribution of coenzyme Q10 intravenously administered in an emulsion to rats: emulsifying agents and lipoprotein lipase activity
Authors: Kimura Akio , Yamaguchi Hiroyuki , Watanabe Keiichi , Hayashi Masahiro , Awazu Shoji
Published: April 2011

The tissue distribution of coenzyme Q10 (CoQ10) administered intravenously in an emulsion prepared with egg yolk phosphatidylcholine (PC), egg yolk sphingomyelin (SPM) or a combination of PC and a polyoxyethylene derivative of hydrogenated castor oil (HCO-60) (PC + HCO-60) was investigated. The disappearance from the plasma of CoQ10 administered in three different emulsions of lipid particle size less than 0.5 μm varied with the particular emulsifer. Its disappearance occurred most rapidly from the PC emulsion; with the addition of HCO-60, its disappearance was much slower. In the reticuloendothelial system, the concentration of CoQ10 was higher in the spleen, for both the SPM and PC + HCO-60 emulsions than for the PC emulsion. HCO-60 reduced the CoQ10 distribution in the liver from the PC emulsion. Differences in disappearance rates from the plasma are thus considered to be due to the extent of CoQ10 distribution in the liver. CoQ10 concentration in the heart, a target organ, was greatest with the PC emulsion. Its distribution was related to lipoprotein lipase (LPL) activity in this organ. The effects caused by HCO-60, however, could not be explained by LPL activity alone. CoQ10 distribution in the adrenal gland and kidney can be explained partly by LPL activity but in the presence of HCO-60, the distribution mechanism apparently involves other factors.
Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol
Authors: Joseph Xavier , Balazs Tibor
Published: April 2011

The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500–600 g) is a more sensitive model than the rabbit for studies of this nature.
Optimizing the pentetrazol infusion test for seizure threshold measurement
Authors: Nutt D J , Taylor S C , Little H J
Published: April 2011

Seizure thresholds in mice were determined using the pentetrazol infusion method. Concentration of infusate and rate of infusion were varied to assess the optimal parameters for seizure threshold detection. Seizure threshold elevations were produced by flurazepam and threshold decreases by FG 7142. An infusion rate of 1.1 ml min−1 was best for detecting both increases and decreases in threshold. However a concentration of 2.5 mg ml−1 gave optimal measurement of elevations in threshold whereas decreased thresholds were best detected with a concentration of 10 mg ml−1.
Ultrasonically mediated solute permeation through polymer barriers
Authors: Julian Thomas N , Zentner Gaylen M
Published: April 2011

The effects of ultrasound on the permeation of benzoic acid through polydimethylsiloxane, and hydrocortisone through cellulose was investigated. Ultrasonic irradiation resulted in a 23% increase in the permeability coefficient of hydrocortisone in a cellulose film. A 14% increase in permeability coefficient was observed for benzoic acid in a polydimethylsiloxane film. The effects of ultrasound on stagnant aqueous diffusion layers, membrane-solution interfacial temperature, membrane integrity, and diffusant stability were investigated. These factors were not responsible for the observed increases in permeability.
Determination of cotinine in biological fluids of non-smokers by packed column gas-liquid chromatography
Authors: Feyerabend C , Bryant A E , Jarvist M J , Russell M A H
Published: April 2011

A method is described for the analysis of cotinine in plasma, saliva and urine using packed-column gas-liquid chromatography, which is sufficiently sensitive and reproducible for quantitative study of the low levels resulting from exposure of non-smokers to other people's smoke. The lower limit of detection of cotinine in these fluids was 100 pg ml−1. The coefficient of variation over the range 0.25 to 2.0 ng ml−1 averaged 7.7%. In a sample of 85 non-smokers the concentrations of cotinine in plasma correlated 0.82 with those in urine and saliva, while the correlation between the saliva and urine concentrations was 0.91. Saliva cotinine concentrations were quantitatively related to passive exposure to parental smoking in a population study of 569 non-smoking schoolchildren.
Acute effect of nicotine on the striatal dopaminergic system in the rat
Authors: Fung Yiu K , Lau Yuen S
Published: April 2011

The acute effects of nicotine (1.5 mg kg−1 day−1) on the striatal dopaminergic system have been examined in the rat. Twenty-four hours after nicotine treatment, spontaneous locomotor activity in response to apomorphine or (+)-amphetamine and the binding of [3H]spiperone to striatal particulates were determined. Pretreatment of nicotine did not alter the characteristics of [3H]spiperone binding to striatal dopamine receptors. The nicotine treatment did not affect the apomorphine-induced locomotor activity, however, the (+)-ampnetamine-stimulated locomotor activity was attenuated. These results suggest that nicotine acutely alters the presynaptic dopaminergic activity without significantly affecting the postsynaptic dopaminergic function.
Studies on metronidazole tablet formulations
Authors: Itiola O A , Pilpel N
Published: April 2011

Incorporating polyvinylpyrrolidone, gelatin and methylcellulose binding agents in a metronidazole formulation alters the tensile strength, disintegration and dissolution times of the tablets by reducing their wettability as measured by the adhesion tension of water. Correlations have been established between the disintegration times, D and the dissolution times t50, t90 and t1 (derived from the equation of Noyes & Whitney). A correlation has also been established between the adhesion tension of water on the tablets and the disintegration and dissolution times. These correlations depend on the nature and concentration of binder used.
Investigation of the binding of various tricyclic neuroleptics and antidepressants to α1-acid glycoprotein
Authors: Schley J , MÜLler-Oerlinghausen B
Published: April 2011

Recent studies have shown that the interaction of various tricyclic neuroleptics and antidepressants with isolated α1-acid glycoprotein occurs at one common binding site and with relatively high association constants. The aim of the present study was to find differences in the binding of some phenothiazines, thioxanthenes, and several other drugs reported to bind α1-AGP. The findings suggest that the affinity of the phenothiazines and thioxanthenes depends primarily on the existence of the tricyclic skeleton and is generally increased by the basic side chain. Substituents at position 3 of the phenothiazine nucleus influence the affinity in a variable way. The losses of radioactivity by non-specific absorptions to the dialysing chambers were considered for the calculation of the association constants. No correlation between association constants and the antipsychotic potency of neuroleptic drugs could be detected.
Effects of several ergosines on adenylate cyclase activity in synaptosomal membranes of the bovine caudate nucleus
Authors: Šoškić V , Petrović Jelena
Published: April 2011

The effects of several ergosines and different dopamine agonists and antagonists on the activity of dopamine-sensitive adenylate cyclase in synaptosomal membranes of the bovine caudate nucleus were comparatively studied. Among ergot alkaloid derivatives used, ergosinine was the most active in stimulating adenylate cyclase activity. Ergosine, bromoergosine, dihydroergosine, dihydroergocryptine and lisuride also stimulated this enzyme. Dihydroergosinine, bromodihydroergosine and bromoergocryptine did not affect adenylate cyclase activity. Saccharino derivatives of both ergosine and ergosinine were inactive. When used in higher concentrations, ergosine, ergosinine, dihydroergocryptine and lisuride inhibited dopamine-stimulated adenylate cyclase whereas other ergot alkaloid derivatives examined did not. If the extent of dopamine-sensitive adenylate cyclase stimulation is considered as a measure of dopaminergic activity, examination of the structure/dopaminergic activity relationship showed that modifications of ergot alkaloid molecules such as isomerization in position 8, hydrogenation of Δ9(10)-double bond, or introduction of bromine into position 2 of the molecule, lead to a significant decrease of stimulatory effects of adenylate cyclase. Introduction of a saccharino group into position 2 of the molecule caused a total loss of stimulatory activity of both ergosine and ergosinine, probably because of the size of the saccharino residue.
Use of lipid microspheres as a drug carrier for antitumour drugs
Authors: Mizushima Y , Shoji Y , Kato T , Fukushima M , Kurozumi S
Published: April 2011

9-Oxo-15-hydroxy-Δ7,10,13-prostatrienoic acid methyl ester (Δ7PGA1), an antitumour drug was incorporated into lipid microspheres of 0.2 μm diameter (lipo-Δ7-PGA1). In in-vivo experiments, lipo-Δ7-PGA1 had a significantly greater antitumour activity than free Δ7-PGA1 against P388 leukaemia. Lipo-Δ7-PGA1, slightly, but significantly, prolonged the survival time of mice inoculated with L1210 leukaemia, whereas free Δ7-PGA1 did not. Against MM46 ascites tumour, the survival time after treatment with 10 mg kg−1 of lipo-Δ7-PGA1 was significantly greater than that after the same dose of free Δ7PGA1. The results suggest that lipid microspheres can be used as drug delivery carriers for lipid soluble antitumour agents.
Re-evaluation of the L-dopa loading effect on dopamine metabolism in rat striatum
Authors: El Gemayel G , Trouvin J H , Prioux-Guyonneau M , Jacquot C , Cohen Y
Published: April 2011

Investigation by HPLC with electrochemical detection of dopamine (DA) metabolism in rat striatum after L-dopa + benserazide treatment allowed quantification of the time course evolution of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Furthermore, four peaks which did not appear in controls, were detected in treated striatum. One was identified as 3-methoxytyrosine, the level of which was still high 9 h after treatment. 3-Methoxytyrosine, has been detected previously in plasma of parkinsonian patients treated with L-dopa, and the disturbance in DA metabolism could explain some of the side-effects induced by that treatment.
Effect of some vasodilators on cat femoral arteries
Authors: Marin J , Salaices M , De Gregorio A
Published: April 2011

Adenosine, cyclic-AMP (cAMP), papaverine and 1-methyl-3-isobutylxanthine (MIX) evoked dose-dependent vasodilatation in cat femoral arteries precontracted with 75 mM K+. The vasodilator response induced at maximal concentration used was: papaverine > MIX > adenosine = cAMP. With regard to the potency of relaxant effects (IC10) the order was MIX = cAMP = papaverine > adenosine. The dilatation elicited by papaverine, adenosine and cAMP was increased by MIX. Preincubation with adenosine enhanced the relaxation induced by MIX and reduced that produced by cAMP. These results indicate that the effects of adenosine and cAMP seem not to be mediated by specific surface receptors but by a cAMP-dependent mechanism. The interference between adenosine and cAMP could be due to competition for a similar site and/or mechanism.