bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible Cytoprotective Mechanism in Rats of D-002, an Anti-ulcerogenic Product Isolated from Beeswax
Authors: Carbajal Daisy , Molina Vivian , Valdés Suria , Arruzazabala Lourdes , Rodeiro Idania , Más Rosa , Magraner Juan 
Published: April 2011

Abstract
D−002 is an anti-ulcerogenic product, isolated from beeswax, which consists of a well-defined mixture of higher primary aliphatic alcohols. It is highly effective against ethanol-induced ulcers. This study was designed to determine if D-002 shows cytoprotective properties on gastric mucosa in ethanol-induced ulcers. The involvement of endogenous prostaglandins in the protective effect of D−002 was also investigated.
When a subulcerogenic dose of indomethacin (10 mg kg−1) was injected simultaneously with oral administration of ethanol, oral pre-treatment with D-002 (5−100 mg kg−1) partially inhibited the gastric protection. D-002 (5 and 25 mg kg−1) administered to normal rats significantly increased the soluble mucus content and also prevented its reduction in rats with ethanol-induced ulcers. In addition, D-002 administered at 5 and 25 mg kg−1 prevented the increase of vascular permeability induced by ethanol (60%) and reduced the concentration of thromboxane B2 (TXB2) in gastric mucosa of rats with ethanol-induced ulcers.
These results support the hypothesis that the anti-ulcerogenic properties of D-002 could be related to a cytoprotective mechanism.
Studies on the Magnitude and the Mechanism of Cough Potentiation by Angiotensin-Converting Enzyme Inhibitors in Guinea-pigs: Involvement of Bradykinin in the Potentiation
Authors: Takahama Kazuo , Araki Tatsuya , Fuchikami Jun-Ichi , Kohjimoto Yoshiro , Miyata Takeshi 
Published: April 2011

Abstract
One adverse effect of the angiotensin-converting enzyme (ACE) inhibitors used for treatment of hypertension and congestive heart failure is the production of dry coughs. Imidapril is a new type of ACE inhibitor with a very low incidence of coughs. The magnitude and the mechanism of cough potentiation of imidapril and other ACE inhibitors has been studied in guinea-pigs.
In normal guinea-pigs single and repeated dosing of imidapril at 0.1 to 100 mg kg−1 had no effect on capsaicin- or citric acid-induced coughs. Single and repeated dosing of enalapril and captopril at 10 to 30 mg kg−1, respectively, significantly increased the number of capsaicin-induced coughs. Repeated dosing of 1 mg kg−1 enalapril also significantly augmented the capsaicin cough. In bronchitic guinea-pigs imidapril also had no effect on the coughs induced by the two stimulants. Enalapril and captopril significantly increased the number of coughs induced not only by capsaicin but also by citric acid. Lower doses of enalapril were enough to augment the capsaicin-induced coughs, whereas medium to large doses failed to augment the cough irrespective of the protocol of administration. Bradykinin-induced discharges of the vagal afferents from the lower airway were significantly increased by enalaprilat but not by imidaprilat. Capsaicin-induced discharges of the afferents were, on the other hand, significantly depressed by enalaprilat, but not by imidaprilat. Interestingly, enalaprilat depression of the discharges was significantly reversed by Hoe-140, a bradykinin B2 receptor blocker. In guinea-pigs pretreated with a low dose of enalapril, arterial infusion of bradykinin significantly potentiated the coughs induced by capsaicin.
The results indicated that imidapril was less potent than enalapril and captopril in potentiating cough responses induced by capsaicin and citric acid in guinea-pigs, and further suggest that bradykinin might be a key substance in the mechanism of the potentiation of coughs associated with ACE inhibitors.
Comparative Study of a Mutant Tissue-type Plasminogen Activator, YM866, with a Tissue-type Plasminogen Activator in a Canine Model of Femoral Arterial Thrombosis
Authors: Kawasaki T , Kaku S , Sakai Y , Takenaka T 
Published: April 2011

Abstract
Because tissue-type plasminogen activator (tPA), used to treat myocardial infarction, has several disadvantages thought to be connected with its low half-life, mutants of tPA have been prepared with longer half-lives. We have compared the thrombolytic effect of such a mutant, YM866, with that of tPA in copper-coil-induced femoral arterial thrombosis in dogs.
One hour after thrombus formation, YM866 was administered by intravenous bolus injection, while tPA was given by the same method or by 60-min infusion under adequate heparinization. Both agents exhibited dose-dependent thrombolysis without systemic fibrinogenolysis. The recanalization rate and recanalization time of YM866 by bolus at 0.2 mg kg−1 were, however, equivalent to those of tPA by infusion at 0.4 mg kg−1 (total dose), whereas the recanalization rate of tPA by bolus was low (0.4 mg kg−1). No significant difference in reocclusion rate, reocclusion time, or patency status after successful thrombolysis was seen.
These results suggest that YM866 administered at a lower dose by intravenous bolus injection exerted a thrombolytic effect equivalent to that of tPA by infusion, and that heparin could not prevent reocclusion after successful thrombolysis even under adequate anticoagulation.
Effect of Amino Acids on the Stability Properties of Nitrofurantoin Suspensions. Flocculation and Redispersion Compared with Interaction Energy Curves
Authors: Gallardo V , Ruiz M A , Vera P , Gonzalez-Caballero F , Delgado A V 
Published: April 2011

Abstract
The influence of the addition of amino acids, lysine, alanine and glutamic acid on the properties of nitrofurantoin suspensions was investigated. Flocculation and redispersability was investigated, taking into account the electrical properties of the nitrofurantoin/solution interface.
We conclude that lysine and glutamic acid, but not alanine, would be suitable amino acids for control of the stability of nitrofurantoin suspensions.
Anti-inflammatory Activity of Polyphosphazene-based Naproxen Slow-release Systems
Authors: Conforti Anita , Bertani Simone , Lussignoli Sabrina , Grigolini Luigi , Terzi Marta , Lora Silvano , Caliceti Paolo , Marsilio Franco , Veronese Francesco M 
Published: April 2011

Abstract
A biocompatible and biodegradable polyphosphazene bearing phenylalanine ethyl ester, imidazole and chlorine (10.7:1:2.5 molar ratio) as substituents of the phosphorus atoms of the polymer backbone was studied for the preparation of polymeric naproxen slow-release systems.
Discs 2.5 cm in diameter and 0.5 mm (thin) or 0.65 mm (thick), loaded, respectively, with 20 and 13.5% naproxen, showed different drug release kinetics, the thin matrices releasing naproxen at a faster rate and for a shorter time. In-vivo studies in rats demonstrated the pharmacological efficacy of these two different delivery systems in the inhibition of acute or chronic inflammatory diseases. Subcutaneous implantation of the thin matrices in rats was found to reduce carrageenan oedema induced both 1 h and 7 days after implantation. Rats implanted with thick matrices showed a reduction in chronic inflammation caused by adjuvant arthritis. Approximately 78% inhibition of arthritic oedema was found 28 days after subcutaneous administration of the matrices whereas 28.7% inhibition was found after daily oral administration of naproxen. Blood levels of naproxen in arthritic rats after matrix implantation showed the presence of drug up to day 28.
These positive results have encouraged us to study a controlled-release system suitable for use in man.
High-performance Thin-layer Chromatography for the Determination of Cetirizine in Human Plasma and Its Use in Pharmacokinetic Studies
Authors: Pandya K K , Bangaru R A , Gandhi T P , Modi I A , Modi R I , Chakravarthy B K 
Published: April 2011

Abstract
A rapid and sensitive high-performance thin-layer chromatography (HPTLC) assay has been developed for the measurement of cetirizine in human plasma and its utility for pharmacokinetic study has been evaluated.
In the proposed HPTLC method, protein-bound cetirizine was freed by proteolysis of plasma proteins by incubating the plasma with 0.35% pepsin and then extracting with 2 mL pH 5.0 phosphate buffer, followed by 4 mL chilled chloroform. The chloroform layer was separated and concentrated. An aliquot of the extract was then spotted on precoated silica-gel 60 F254 plates using a Camag Linomat IV autosampler. Quantification was with the help of a dual-wavelength TLC scanner. The proposed method had a recovery of 98% and the lowest amount of cetirizine that could be detected was 50 ng.
The method was applied for the determination of the plasma levels and pharmacokinetic parameters of cetirizine after oral administration of two marketed preparations in healthy volunteers and the pharmacokinetic parameters determined by the proposed method were in agreement with previously reported values.
Saturable Function of P-Glycoprotein as a Drug-efflux Pump in Multidrug-resistant Tumour Cells
Authors: Miyamoto Ken-Ichi , Koga-Takeda Keiko , Koga Kenjiro , Ohshima Taeyuki , Nomura Masaaki 
Published: April 2011

Abstract
P-glycoprotein acts as an active drug-efflux pump in multidrug-resistant tumour cells. We studied the capacity of P-glycoprotein to extrude drugs from the cells.
For nanomolar concentrations of vinblastine P388/ADR cells, which overexpress P-glycoprotein in the plasma membrane, accumulated vinblastine, at 37°C for 30 min, to a much lower extent than the sensitive cells (P388/S), while in the micromolar range the cellular concentration was similar for both types of cells. When cells were incubated with a low (10 nM) or high concentration (1 μM) of vinblastine while energy deprived, the vinblastine concentration increased only in the resistant cells incubated with the low concentration of vinblastine, and this increased level was lowered to the level under the normal conditions by addition of glucose. In contrast, the cellular concentrations in other cases were increased to the normal level by glucose. After cells were loaded with the low concentration of vinblastine, the cellular vinblastine was extruded more rapidly from the resistant cells than from the sensitive cells. The courses of vinblastine efflux from the cells loaded with the high concentration of vinblastine were similar in both types of cells. NA-382, a reported P-glycoprotein inhibitor, effectively increased the intracellular vinblastine and inhibited the drug efflux only from multidrug-resistant cells, P388/ADR and AH66 cells, which were incubated with the low concentration of vinblastine. Cellular uptake of NA-382 was also less in P388/ADR cells than in P388/S cells in culture with 10 nM but not 1 μM of the agent, and this low level was reversed to the level in the sensitive cells by 10 μM vinblastine.
These results indicate that P-glycoprotein as a drug-efflux pump works effectively under low extracellular concentrations of substrates, but does not under the high concentrations.
Renal Excretion and Accumulation Kinetics of 2-Methylbenzoylglycine in the Isolated Perfused Rat Kidney
Authors: Masereeuw Rosalinde , Moons Miek M , Russel Frans G M 
Published: April 2011

Abstract
The effect of protein binding on kidney function has been studied by investigating the renal accumulation and secretion of the hippurate analogue 2-methylbenzoylglycine in the isolated perfused rat kidney in the absence and presence of bovine serum albumin (BSA).
Experiments were performed with either 2.5% pluronic or a combination of 2.2% pluronic and 2% BSA as oncotic agents; a wide concentration range (1–190 μg mL−1) of 2-methylbenzoylglycine was studied. Tubular secretion appeared to be a function of the amount of unbound drug in the perfusate and was best described by a model consisting of a high and low affinity Michaelis-Menten term. Parameters obtained after the analysis of renal excretion data were maximum transport velocity for the high affinity site (TM,H) = 3.0 ± 2.8 μg min−1, Michaelis-Menten constant for tubular transport for the high affinity site (KT,H) = 0.5 ± 0.8 μg mL−1, maximum transport velocity for the low affinity site (TM,L) = 250 ± 36 μg min−1, and Michaelis-Menten constant for tubular transport for the low affinity site (KT,L) = 62 ± 17 μg mL−1. The compound accumulated extensively in kidney tissue, ratios up to 175 times the perfusate concentration were reached. Accumulation data were best analysed by a two-site model similar to the model used to describe renal excretion. Calculated parameters were theoretical maximum capacity of the high affinity site (RM,H) = 26 ± 23 μg g−1, affinity constant for renal accumulation at the high affinity site (KA,H) = 0.2 ± 0.4 μg mL−1, theoretical maximum capacity of the low affinity site (RM,L)= 1640 ± 1100 μg g−1 and affinity constant for renal accumulation at the low affinity site (KA,L) = 60 ± 58 μg mL−1.
The very high accumulation in kidney tissue could be explained by active tubular uptake, mediated by the secretory mechanisms involved, and dependent on the amount of free drug in the perfusate. This study shows that anionic drugs, subject to active secretion, may reach high concentrations in tubular cells even at low plasma concentrations.
In-vitro and Ex-vivo Inhibition of Blood Platelet Aggregation by Naftazone
Authors: Durand P , Bloy C , Peltier-Pujol F , Blache D 
Published: April 2011

Abstract
Because of the considerable interest in the role of platelets and antiplatelet therapy in cardiovascular disease, including the aggregation of platelets to each other during arterial thrombosis and atherogenesis, we have studied the effect of naftazone (Etioven), an original vasculotropic drug on platelet aggregation.
Rat and human platelets were prepared and incubated in-vitro with different concentrations of naftazone. We found that naftazone inhibited both platelet secretion and aggregation in platelet-rich plasma (PRP) and washed platelets after stimulation with thrombin or ADP. Rats were also treated intraperitoneally for five days with various naftazone doses (0.125-10 mg kg−1) and ex-vivo platelet aggregation compared, at various times after the last injection, with that of control animals. Inhibition by naftazone was dose-dependent in both PRP and isolated platelets. The inhibition was transient, a maximum value (∼ 50%) being obtained about 3–6 h after the last injection, with a return to near-control values after 24 h. Naftazone also facilitated platelet deaggregation after in-vitro stimulation with thrombin or ADP. In another series of experiments, rats were treated intraperitoneally for five days with 10 mg kg−1 of aspirin, ticlopidine, dipyridamole or naftazone. Platelets were prepared and tested for aggregation 90 min after the last injection. Thrombin-induced aggregation in PRP and washed platelets was significantly reduced after in-vivo treatment with ticlopidine and naftazone. Except for dipyridamole, all the drugs inhibited ex-vivo ADP-induced aggregation in PRP. In isolated platelet preparation, only naftazone induced a significant inhibition of ADP-or thrombin-stimulated aggregation.
We conclude that naftazone inhibits platelet aggregation in-vitro and ex-vivo.
Effects of Potassium-channel Opener HOE 234 in Guinea-pig Airways
Authors: Redemann B , Vaali K , Li L , Paakkari I , Vapaatalo H 
Published: April 2011

Abstract
The mechanism of the bronchospasmolytic effect of HOE 234 ((3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6-phenylsulphonylchromane hemihydrate), a novel opener of ATP-sensitive potassium channels, has been studied by in-vitro testing in ring preparations of trachea and different parts of the principle bronchus of guinea-pigs, using methacholine, histamine and KCl as preconstrictors. The contribution of prostanoids was estimated in the presence and absence of indomethacin. Regional differences in the bronchodilatory effect of HOE 234 were compared with that of salbutamol.
HOE 234 had a concentration-dependent relaxing effect on the smooth muscle preparations. In the absence of indomethacin no regional differences were seen for the effect of HOE 234 against the metacholine or KCl preconstriction, whereas with histamine a particularly strong relaxation was detectable in trachea. In the presence of indomethacin, distal bronchus after methacholine and trachea after KCl preconstriction were relaxed significantly more strongly than the other parts. The relaxation of the histamine-constricted trachea rings was not increased in comparison with that without indomethacin pretreatment. Thus the bronchospasmolytic effect of HOE 234 varied depending on the pretreatment, method of preconstriction and part of the airways examined. It was strongest in trachea rings with histamine preconstriction but its potency was clearly less than that of salbutamol. The latter had regionally different effects, being stronger in trachea than in the bronchi for all methods of preconstriction.
The results suggest that the formation of bronchoconstricting prostanoids can attenuate parts of the relaxing effect of HOE 234. The possible advantages of HOE 234 as an anti-asthma drug might be related to an effect on bronchial hyper-reactivity and mucus secretion, because as a direct bronchodilator it is inferior to salbutamol.
Poly(alkyl cyanoacrylate) Nanocapsules as a Delivery System in the Rat for Octreotide, a Long-acting Somatostatin Analogue
Authors: Damgé Christiane , Vonderscher Jacky , Marbach Peter , Pinget Michel 
Published: April 2011

Abstract
Poly(alkyl cyanoacrylate) nanocapsules have been used as biodegradable polymeric drug carriers for subcutaneous and peroral delivery of octreotide, a long-acting somatostatin analogue; their ability to reduce insulin secretion or prolactin secretion in response to oestrogens has been studied in adult male rats.
The nanocapsules, prepared by interfacial emulsion polymerization of isobutyl cyanoacrylate, were 260 nm in diameter and incorporated 60% of octreotide. Administered subcutaneously, the octreotide-loaded (20 μg kg−) nanocapsules suppressed the insulinaemia peak induced by intravenous glucose overload and depressed insulin secretion over 48 h, preventing the secretory rebound; however, glycaemia was unaffected. In parallel, the plasma octreotide concentration increased 2.7 times. Administered perorally to oestrogen-treated rats, octreotide-loaded nanocapsules (200 and 1000 μg kg−) significantly improved the reduction of prolactin secretion (by 72 and 88%, respectively, compared with 32 and 54% with free octreotide) and slightly increased plasma octreotide level.
Thus nanocapsules could be of interest as a biodegradable drug carrier for the administration of octreotide.
Inhibition of Potassium (KATP) Channels Reduces the Short-circuit Current Response of Rat Colonic Mucosa to Acetylcholine
Authors: Darko S K A , Palmerley N D , Burleigh D E 
Published: April 2011

Abstract
Intestinal secretion depends upon electrogenic chloride transport into the gut lumen, which requires maintenance of an electrically negative cell-membrane voltage. We have investigated whether secretory responses of rat colonic mucosa to acetylcholine were sensitive to inhibition of potassium channels and whether selective inhibition could indicate the nature of the channel involved.
Rat colonic mucosa was set up in Ussing chambers, short-circuit current responses obtained to acetylcholine, and the sensitivity of such responses to inhibition of potassium channels was investigated. Non-selective potassium-channel blockade by barium induced concentration-dependent inhibition of responses to acetylcholine. Similar inhibitory effects were obtained using 4-aminopyridine and glibenclamide. 5-Hydroxydecanoate and phentolamine also inhibited the increase in short-circuit current. However, a combination of charybdotoxin plus apamin was without effect.
We conclude that a basolateral outward movement of potassium ions is required for the secretory action of acetylcholine on rat colonic mucosa. The potassium channel involved seems to be ATP-dependent and calcium-insensitive.
Effect of Policosanol on Circulating Endothelial Cells in Experimental Models in Sprague-Dawley Rats and in Rabbits
Authors: Noa MIRIAM , Más Rosa , Mesa Rosario 
Published: April 2011

Abstract
The effect of policosanol on circulating endothelial cells has been studied in different experimental models with endothelium damage.
Oral administration of 25 mg kg− policosanol to Sprague-Dawley rats resulted in significant protection of the endothelial lining against the desquamating effect of citrate. Oral administration of 5 mg kg− policosanol to spontaneously hypertensive rats (SHR) resulted in a significant reduction of circulating endothelial cells compared with controls. Moreover, comparison between groups revealed a lower frequency of aortic lesions in policosanol-treated animals than in controls. On the other hand, administration of 5 mg kg− policosanol to rabbits with intimal hyperplasia induced by cuff placement in the carotid artery resulted in levels of circulating endothelial cells significantly lower than in controls.
These results demonstrate the protective effect of policosanol in different experimental models and suggest its potential for endothelial protection.
A Xanthanolide with Potent Antibacterial Activity against Methicillin-resistant Staphylococcus aureus
Authors: Sato Youichi , Oketani Hideki , Yamada Tomoko , Singyouchi Ken-Ichi , Ohtsubo Tetsuya , Kihara Masaru , Shibata Hirofumi , Higuti Tomihiko 
Published: April 2011

Abstract
This study was conducted to find constituents of an annual herb, Xanthium sibiricum Patr er Widd, with effective antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).
By monitoring antibacterial activity against MRSA strains, it was shown that a sesquiterpene lactone, identified as [3aR-(3aα,7β,8aβ)]-3,3a,4,7,8,8a-hexahydro-7-methyl-3-methylene-6-(3-oxo-1-butenyl)-2H-cyclohepta[b]furan-2-one, or xanthatin, isolated from leaves of the herb, had outstandingly potent activity against S. aureus species, including MRSA; its activity against MRSA and MSSA strains was similar. Other bacteria, e.g. Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa and Salmonella typhi, were also susceptible at the concentrations tested but the compound had no inhibitory effect on some other bacteria, including Escherichia coli.
The results show that xanthatin has outstandingly potent activity against strains of S. aureus but that the activity of the compound is highly species-specific.
Inhibition of the Hepatic Uptake of Paracetamol Sulphate by Anionic Compounds
Authors: Sakuma-Sawada Noriko , Iida Satofumi , Mizuma Takashi , Hayashi Masahiro , Awazu Shoji 
Published: April 2011

Abstract
The effect of anionic compounds on the hepatic uptake of paracetamol sulphate, a conjugative metabolite of paracetamol, has been studied.
Hepatic uptake of paracetamol sulphate by isolated hepatocytes was inhibited by bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, but not by probenecid or cholic acid. Bromosulphophthalein and dibromosulphophthalein also inhibited the uptake of paracetamol sulphate in the rat isolated perfused liver. Saturable uptake of paracetamol sulphate was also observed in the absence of inorganic sulphate. The uptake of paracetamol sulphate was reduced by 1 and 10 mm inorganic sulphate. Bromosulphophthalein and p-nitrophenyl sulphate inhibited the uptake of paracetamol sulphate in the absence of inorganic sulphate.
These results indicate that paracetamol sulphate shares a transporter with bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, all of which contain the sulphate or sulphonate group. Therefore, the sulphate or sulphonate moiety might be crucial for interaction with the transporter, and mutual inhibition of hepatic uptake among these compounds is likely.