bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of Ocular Penetration of Amikacin Sulphate by Association to Poly(butylcyanoacrylate) Nanoparticles
Authors: Losa C , Calvo P , Castro E , Vila-Jato J L , Alonso M J 
Published: April 2011

Abstract
The main objective of this paper was to investigate the ability of polycyanoacrylate nanoparticles to improve the corneal penetration of hydrophilic drugs. Three different nanoparticle formulations were prepared by changing the nature of the stabilizer agent (Dextran 70000, Synperonic F 68 and sodium lauryl sulphate). The significant influence of the stabilizer type on the particle size, electrophoretic mobility and on the drug loading efficiency was proved. Moreover, the ocular disposition of amikacin was affected by its association to nanoparticles, displaying the most interesting results when Dextran 70000 was employed for preparation of nanoparticles. The increase of the amikacin concentration in cornea and aqueous humour was statistically significant for this nanoparticle formulation with respect to the other formulations and the control solution. The in-vitro release profiles obtained using a dialysis system were similar for all the nanoparticle formulations and for the control solution, indicating that drug molecules are desorbed from the nanoparticles quickly enough to maintain the equilibrium concentration in the dialysis system.
Assay of Pyrogens by Interleukin-6 Release from Monocytic Cell Lines
Authors: Taktak Y S , Selkirk S , Bristow A F , Carpenter A , Ball C , Rafferty B , Poole S 
Published: April 2011

Abstract
A novel in-vitro system has been developed for the detection and quantification of pyrogen in pharmaceutical products. The measured variable was evoked secretion of the pyrogenic cytokine interleukin-6 from MONO MAC 6 monocytic cells incubated with the product. The interleukin-6 was detected using a specific and sensitive ELISA developed for this purpose. The test system detected pyrogenic contamination in 3 batches of therapeutic human serum albumin which had caused adverse reactions in recipients. The contamination was not detected in conventional tests: the rabbit pyrogen test and the limulus amoebocyte lysate test.
Improvement of Absorption Rate of Indomethacin and Reduction of Stomach Irritation by Alginate Dispersions
Authors: Shiraishi Sumihiro , Imai Teruko , Iwaoka Daisuke , Otagiri Masaki 
Published: April 2011

Abstract
The dissolution rates of indomethacin from low molecular weight (mol. wt) alginate dispersions were significantly enhanced in comparison with that of indomethacin alone. The dispersion with lower mol. wt alginate exhibited more rapid dissolution rate than that of dispersion with higher mol. wt alginate. These enhanced dissolution rates of indomethacin by alginate may be due to the improvement of wettability and the decrease of crystallinity and crystal size. The absorption rate from alginate dispersions was enhanced in comparison with that from indomethacin alone, and enhanced only the rate of bioavailability in beagle dogs and volunteers. In addition, indomethacin-induced gastric lesions were reduced by dispersing indomethacin in alginate.
Studies to determine whether there is tolerance or cross-tolerance to the antisecretory effect of morphine and clonidine in the rat intestine
Authors: Margaritis Jamie , Coupar Ian M , Bentley Geoffrey A 
Published: April 2011

Abstract
Intra-arterial infusions (4 μg min−1) of prostaglandin E2 (PGE2) were used to stimulate intestinal fluid secretion in anaesthetized rats. Morphine (0·625–40 mg kg−1) produced a dose-dependent restoration of fluid transport from secretion to the normal rate of absorption. Pretreatment with up to eight doses of morphine (20 mg kg−1) did not induce tolerance, rather it enhanced the antisecretory effect of a subsequent acute dose of morphine. It seems probable that this was caused by the accumulation of morphine in the intestine. Clonidine (4–1000 μg kg−1, like morphine, produced a dose-dependent reversal of stimulated fluid secretion. Pretreatment with clonidine (4 × 0·25 mg kg−1) caused a shift of the clonidine antisecretory dose-response curve to the right, demonstrating tolerance. Pretreatment with clonidine also caused cross-tolerance to the antisecretory effect of morphine. The results suggest that there is a close relationship between opioid- and α2-adrenoceptors in controlling inhibition of intestinal fluid secretion.
Selective In-vitro Inhibition of Hepatic Oxidative Metabolism by Quinolones: 7-Ethoxyresorufin and Caffeine as Model Substrates
Authors: Valero Fernando , De La Torre Rafael , Segura Jordi 
Published: April 2011

Abstract
The in-vitro inhibition of several metabolic pathways has been studied in 3-methylcholanthrene-treated rats. The specificity of the 7-ethoxyresorufin O-de-ethylase reaction has been determined in the presence and absence of ciprofloxacin, enoxacin, norfloxacin, ofloxacin, nalidixic acid, oxolinic acid and pipemidic acid. For the caffeine N3-demethylation reaction, enoxacin and pipemidic acid were used. Enoxacin (IC50=105 μM, Ki = 65 μM) and pipemidic acid (IC50 = 115 μM, Ki=160 μM) significantly inhibited 7-ethoxyresorufin O-de-ethylase reaction and caffeine N3-demethylation (IC50 = 60 μM for enoxacin and IC50 = 185 μM for pipemidic acid) by a competitive mechanism. Other quinolones had lower or no (ofloxacin) inhibitory capacity. The order of inhibitory activity observed is in agreement with results obtained previously from in-vivo studies in man. No activity was detected towards ethylmorphine N-demethylation.
Regional Distribution of Imipramine, Desipramine and Specific [3H]Desipramine Binding Sites in the Rat Brain after Acute and Chronic Treatment with Imipramine
Authors: Daniel Wladyslawa , Danek Leokadia , Janczar Lucyna , Nocon Halina , Melzacka Miroslawa 
Published: April 2011

Abstract
Regional distribution of imipramine, desipramine and specific [3H]desipramine binding sites in the rat brain after acute and chronic treatment of rats with imipramine has been investigated. Both substances were distributed unevenly within rat brain after single and prolonged administration of imipramine. This was partly connected with the regional cerebral blood flow, lipid content in the regions and lipophilicity of the substances investigated. It was also found that the number of specific [3H]desipramine binding sites was different in the various brain areas, and that prolonged administration of imipramine led to a decrease of their number in some of those regions. No correlation was found between the regional cerebral distribution of desipramine and the regional density of specific [3H]desipramine binding sites.
The Effect of Immunization with Protein-sulphanilic Acid Conjugate on Sulphanilic Acid Disposition in the Rat
Authors: Yamamoto Akira , Kawaratani Toshitaka , Aisaka Ayumi , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
Rats were immunized with bovine γ-globulin-sulphanilic acid conjugate and the plasma concentration of sulphanilic acid examined after an intravenous injection of this drug. There was a significant increase in plasma half-life and AUC and a significant decrease in clearance of sulphanilic acid in the immunized rats compared with the control. In the immunized rats, binding of sulphanilic acid to macromolecules in serum, determined by ultrafiltration, decreased with increase of sulphanilic acid concentration. At low concentrations, there was a significant increase in % binding of the drug in the zerum of immunized rats compared with controls. There was also a significant reduction in urinary excretion of total drug in the immunized rats compared with controls. These findings suggest that sulphanilic acid-specific antibodies in the serum of immunized animals bind [14C]sulphanilic acid, giving rise to higher serum levels thereby making it unavailable for normal excretory processes.
Evaluation of in-vitro leishmanicidal activity of hydrazones of thiophene carboxaldehydes against promastigotes of Leishmania infantum and Leishmania tropica
Authors: Savornin B , Madadi N E , Delmas F , Gasquet M , Timon-David P , Vanelle P , Maldonado J 
Published: April 2011

Abstract
The lack of leishmanicidal drugs has prompted the synthesis and testing of new hydrazones of thiophene carboxaldehydes against three Leishmania strains. The compounds were obtained by condensation of appropriate hydrazines with thiophene 2-carboxaldehyde (series 7), thiophene 3-carboxaldehyde (series 2), and 5-nitrothiophene-2-carboxaldehyde (series 3). Leishmanicidal activity was assessed against promastigotes of Leishmania strains, grown in-vitro in nutrient broth medium complemented with fresh rabbit blood. The minimal inhibitory concentrations were evaluated against pentamidine, as a reference drug. Several compounds exhibited significant leishmanicidal activity, the best being ten times more active than pentamidine.
New heteroaryl derivatives of fentanyl
Authors: Llama E F , Del Campo C , Capo M 
Published: April 2011

Abstract
The preparation of analogues of fentanyl with N-phenyl replaced with a heterocyclic aromatic ring, and with N-alkyl/arylalkyl N-acyl substituents is reported. Only those compounds carrying an N-phenylethyl substituent were active in the rat tail-withdrawal test. Fentanyl (1) is the prototype of the 4-anilido-piperidine class of opioid analgesics (Casy & Parfitt 1986). Several recent publications (Casy & Huckstep 1988; Bagley et al 1989) on this series have dealt with heterocyclic and aromatic modifications of the fentanyl molecule. Although the antinociceptive potency of most novel derivatives was greater than that of morphine, they had reduced activity when compared with fentanyl itself. To acquire further information on the structure-reactivity relationships of the series, new heteroaryl derivatives have been prepared and tested for antinociceptive activity.
Diuretic and saliuretic effects of 1,3-dipropyl-8-cyclopentylxanthine, a selective A1-adenosine receptor antagonist
Authors: Collis M G , Shaw G , Keddie J R 
Published: April 2011

Abstract
We have previously shown that 8-phenyltheophylline (8-PT), a non-selective antagonist at adenosine A1-and A2-receptors, has a diuretic effect. In this study, the diuretic and adenosine antagonist effects of the A1-receptor selective compound 1,3-dipropyl-8-cyclopentylxanthine (CPX) have been examined in the conscious rat. CPX (0.1 and 0.3 mg kg−1 i.v.) significantly attenuated bradycardic but not hypotensive responses evoked by adenosine. In contrast, 8-PT (3 mg kg−1 i.v.) significantly antagonized both adenosine-induced bradycardia and hypotension. CPX (0.1 and 0.3 mg kg−1 i.v.) evoked a dose-related diuretic and saliuretic response in the conscious rat. These results indicate that the diuretic effects of adenosine antagonists are associated with blockade of the A1-receptor sub-type.
The Plasma Disposition and Renal Elimination of Digoxinspecific Fab Fragments and Digoxin in the Rabbit
Authors: Timsina M P , Hewick D S 
Published: April 2011

Abstract
Administering digoxin-specific antibody fragments (DSFab, 1·9 mg kg−1, i.v.) to rabbits 1 h after digoxin (15 μg kg−1 or 12·5 μCi kg−1, i.v.) produced a redistribution of digoxin associated with a 5-fold elevation in total plasma concentration and 36–86% reductions in elimination half-life, apparent volume of distribution at steady-state and total body clearance (CLT). Renal clearance (CLR) was also reduced (54%), but urinary digoxin excretion was increased by one-third (35% vs 25%). This apparent anomaly is due to the large rise in total plasma digoxin concentration with a consequent increase in the area under the plasma concentration curve (AUC). The AUC, which is the denominator term in calculating CLR (and CLT), was increased to a greater extent than urinary digoxin excretion (numerator term in calculating CLR) so that an overall reduction in CLR occurred. The initial presence of digoxin appeared to alter the distribution of DSFab, since their plasma concentrations were markedly higher when the antibody was given after the hapten. The digoxin also reduced (from 3 to 1%) the amount of detectable DSFab in the urine.
A Rapid Filtration Assay for the Glycine Binding Site on the NMDA Receptor in Rat Cortical Membranes using [3H]Dichlorokynurenic Acid
Authors: Canton Thierry , Doble Adam , Miquet Jean-Marie , Jimonet Patrick , Blanchard Jean-Charles 
Published: April 2011

Abstract
A filtration binding assay using [3H]dichlorokynurenic acid to label the glycine binding site on the N-methyl-d-aspartic acid receptor has been evaluated on rat cortical membranes. This ligand binds to a single population of binding sites following mass action kinetics with a Kd of 29 Nm and a capacity of 5·73 pmol (mg protein)−1. The pharmacological specificity of the binding site is identical to that previously reported for this binding site using [3H]glycine as a radioligand. Agonists showed lower affinity and antagonists higher affinity when [3H]dichlorokynurenic acid was used compared with [3H]glycine. The higher affinity of [3H]dichlorokynurenic acid compared with [3H]glycine make it the more suitable compound with which to label the glycine site.
Cardiovascular Effects of LAS 30538, a New Vascular Selective Ca2+-Channel Blocker
Authors: Cardelús I , Bou J , Llenas J , Berga P , Gristwood R W 
Published: April 2011

Abstract
A new compound, 1-[2-(2,6-dimethylphenoxy)ethyl]-α,α-bis-(p-fluorphenyl)-4-piperidine methanol (LAS 30538), was found to have potent vasodilator effects. Its vasorelaxant activity was demonstrated in rat perfused hindlimbs contracted with 80 Mm K+, having an IC50 value of 40 Nm. In conscious spontaneously hypertensive rats, LAS 30538 administered orally, caused dose-dependent sustained falls in systolic blood pressure with an ED30 value of 11 mg kg−1. In pithed rats, LAS 30538, strongly inhibited vasoconstriction induced by the α2-adrenoceptor agonist B-HT 933 and the calcium agonist compound Bay K8644 with ED50 values of 4 mg kg−1 p.o. and 1·3 mg kg−1 i.v., respectively. Results from electrophysiological studies carried out using guinea-pig papillary muscles partially depolarized by 22 Mm K+ are consistent with LAS 30538 acting as a Ca2+-channel blocker. When compared with verapamil, in guinea-pig and rabbit isolated heart preparations, LAS 30538 caused less cardiodepression and bradycardia. The results suggest that LAS 30538 may have some advantages over other Ca2+-channel blockers such as verapamil in causing less myocardial depression for a given level of vasodilatation.
Effects of selective histamine receptor antagonists on skin responses to intradermal bradykinin in healthy volunteers
Authors: Li Kam Wa Tin C , Cooke Ernest D , Turner Paul 
Published: April 2011

Abstract
The effects of chlorpheniramine and cimetidine on the cutaneous responses to intradermal injections of bradykinin were investigated in a randomized, double-blind, placebo-controlled, cross-over study. Chlorpheniramine significantly attenuated the increase in cutaneous blood flow and erythema induced by bradykinin but not the weal response. Cimetidine was without influence on these parameters and the effects of the combined therapy of chlorpheniramine and cimetidine were not significantly different from those due to chlorpheniramine alone. These results suggest that the cutaneous vasodilator effect of bradykinin is in part due to histamine release acting on histamine H1-receptors.
Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor, in rats
Authors: De La Lastra C Alarcon , Martin M J , Marhuenda E 
Published: April 2011

Abstract
Oral treatment with silymarin was found to be effective in the prevention of gastric ulceration induced by cold-restraint stress, in rats. Statistically significant ulcer index values with respect to the control group, were observed. In 6 h pyloric-ligated animals silymarin showed a significant reduction in the number and severity of the ulcers; however, it did not alter the gastric secretion volume or acidity although histamine concentration was significantly decreased. In absolute ethanol-induced ulcers, treatment with silymarin 1 or 2 h before the anti-ulcerogenic agent, did not prevent the formation of gastric lesions. Furthermore, the hexosamine content was decreased significantly, but the total protein output was enhanced, showing similar values to those with the standard drug, carbenoxolone. These results suggest that the anti-ulcerogenic effect of silymarin could be related to its inhibitory mechanism of enzymatic peroxidation by the lipoxygenase pathway, avoiding leukotriene synthesis.
Safety Aspects of Non-ionic Surfactant Vesicles: A Toxicity Study Related to the Physicochemical Characteristics of Non-ionic Surfactants
Authors: Hofland H E J , Bouwstra J A , Verhoef J C , Buckton G , Chowdry B Z , Ponec M , Junginger H E 
Published: April 2011

Abstract
Two different toxicity models were used to assess the relationship between the physicochemical properties of non-ionic surfactant vesicles (NSVs), and the safety of these vesicles for topical drug administration. The vesicles used in this study consisted of polyoxyethylene alkyl ethers (CnEOm) in which the number of C atoms (n) varied between 12 and 18 and the number of oxyethylene units (m) between 3 and 7. The physicochemical properties of the vesicles are described in terms of hydrophilic-lipophilic balance (HLB) values, and critical micelle concentrations (CMC), and the rigidity of the bilayers as determined by the gel-liquid transition temperatures and the cholesterol content of the bilayers. The first toxicity model, comprising the measurement of the ciliary beat frequency, is a tool to assess the safety of intranasally applied formulations. Studies using this ciliotoxicity model revealed that by increasing the length of the alkyl chain of the surfactant, a decrease in toxicity was observed. The opposite correlation was found if the length of the polyoxyethylene headgroup was increased. Furthermore, it was observed that gel-state vesicles produce less of an effect on the ciliary beat frequency than liquid state vesicles. The second toxicity model, comprising the determination of cell proliferation of human keratinocytes, is a method to assess skin irritancy. In contrast to the ciliotoxicity model the length of the polyoxyethylene headgroup and of the alkyl chains did not seem to have an effect on the safety of the vesicles. However, the bond by which the headgroup is linked to the alkyl chain, showed a very strong effect on the toxicity of the surfactant: oleyl-EO5 ester vesicles were found to have an effect on the cell proliferation, which was one-sixteenth that of the oleyl-EO5 ether vesicles. The cholesterol content did not appear to have an effect on the proliferation of the keratinocytes. Neither the HLB nor the CMC values appeared to have an effect on the safety of the NSV formulations as observed in both toxicity models.
Roles of PMN Leucocytes, Platelets and Some Mediators in Rat Hind-paw Oedema Induced by Two Phospholipase A2 Enzymes From Trimeresurus mucrosquamatus Venom
Authors: Wang Jih-Pyang , Teng Che-Ming 
Published: April 2011

Abstract
Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimerusurus mucrosquamatus venom induced rat hind-paw oedema. Recovered myeloperoxidase activity increased within 1 h and was greatly elevated in the rat paw 3–6 h after subplantar injection of these venom PLA2 enzymes. Methotrexate pretreatment significantly reduced not only the peripheral leucocyte count but also venom PLA2-induced paw oedema. In rat isolated PMN leucocyte suspension, venom PLA2 induced superoxide radical formation. Paw swelling caused by TMVPLA2 I or TMVPLA2 II was only slightly or not, respectively, reduced in the rats pretreated with anti-platelet plasma, which reduced peripheral blood platelet count by &gt;96%, suggesting platelets are not involved. In isolated platelet preparation, TMVPLA2 I induced platelet activation in a concentration-dependent manner, while TMVPLA2 II had no effect. Pretreatment with diphenhydramine/methysergide greatly suppressed the oedematous responses caused by the two venom PLA2 enzymes; the residual responses were significantly further depressed by aspirin. The oedematous responses caused by the enzymes were also suppressed by FPL 55712, BW 755C, dexamethasone, superoxide dismutase/catalase, isoprenaline and terbutaline. However, BN 52021 and L 652731, both platelet aggregating factor antagonists, were not effective on these responses. Thus, in addition to histamine and 5-hydroxytryptamine release by the mast cells in PLA2-induced paw oedema (Wang & Teng 1990), the results of this study indicate minor, but significant, roles for neutrophils and inflammatory mediators including prostaglandins, leukotrienes and superoxide radicals.
Effects of Platelet Activating Factor on Contractions and Ca Influx Induced by Noradrenaline and Potassium in Rat Rubbed and Intact Aorta. Comparison with Its Hypotensive Effect in Anaesthetized Normotensive Rats
Authors: Orallo Francisco , Verde Ignacio , Loza Ma Isabel , Alzueta Alejandro F , Campos Manuel , Freire-Garabal Manuel 
Published: April 2011

Abstract
In order to clarify the mechanism of hypotensive activity of platelet activating factor (PAF), the effects of this drug on blood pressure in anaesthetized normotensive rats, on KCl- and noradrenaline-induced 45Ca uptake and contractile responses in rat aorta rings with and without endothelium were studied. PAF (3 μg kg−1, i.v.) showed long-lasting hypotensive effects in anaesthetized normotensive rats accompanied by a significant increase in heart rate. PAF (0·1–10 μm) did not relax the contractions induced by noradrenaline (10 μm) or K+ (60 Mm) in rubbed or intact rat aorta. PAF did not affect the basal uptake of 45Ca2+ nor that induced by the two vasoconstrictor agents. In experiments in a calcium free medium, PAF (10 μm) had no effect on the noradrenaline- (10 μm) induced contractions. These results suggest that the hypotensive activity of PAF in normotensive anaesthetized rats is not due to a direct effect on rubbed and intact rat aorta rings (acting within the cell or blocking Ca2+ influx through l-type transmembrane calcium channels).
Use of prostaglandin E1 (lipo-PGEi) to treat Raynaud's phenomenon associated with connective tissue disease: thermographic and subjective assessment
Authors: Katoh Kyoshi , Kawai Takako , Narita Masahiro , Uemura Junta , Tani Kenji , Okubo Takao 
Published: April 2011

Abstract
Four patients with connective tissue disease who had been suffering from severe Raynaud's phenomenon were treated with an intravenous infusion of prostaglandin E1 (PGE1) and its effectiveness was assessed by thermography and a questionnaire approach. PGE1 in a lipid microsphere formulation (lipo-PGE1) produced a significantly greater increase in lesional skin temperature compared with treatment with PGE1 clathrated in α-cyclodextrin 12 months previously in the same group of patients. These results were supported by the subjective assessment obtained from the patients by questionnaire.
Anti-inflammatory activity of oleanolic acid in rats and mice
Authors: Singh G B , Singh Surjeet , Bani S , Gupta B D , Banerjee S K 
Published: April 2011

Abstract
Oleanolic acid displayed anti-inflammatory activity in carrageenan and dextran-induced oedema in rats. It elicited marked anti-arthritic action in adjuvant-induced polyarthritis in rats and mice and in formaldehyde-induced arthritis in rats. Oleanolic acid checked the inflammation-induced increased serum transaminase levels. It reduced exudate volume and inhibited leucocyte infiltration in carrageenan-induced pleurisy in rats. It is devoid of any analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the parturition time in pregnant rats or castor oil-induced diarrhoea in rats. Oral LD50 was found to be greater than 2 g kg−1 in mice and rats.