bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade by 4-Aminopyridine of the Muscarinic-receptor-mediated Responses of Guinea-pig Atria and Trachea
Authors: Urquhart Robert A , Broadley Kenneth J 
Published: April 2011

Abstract
The potassium channel blocker 4-aminopyridine (4-AP) has been shown to antagonize the negative inotropic effects of muscarinic receptor agonists on atrial preparations. This is consistent with muscarinic agonists mediating their negative inotropy through the opening of potassium channels. In the present study, the possibility of a direct antagonism of the muscarinic receptor was examined by comparing the effects of 4-AP upon the responses to carbachol of isolated left atria (negative inotropy) and tracheal spirals (contraction) from reserpine pretreated guinea-pigs. The latter response is K+ channel-independent. The concentration-response curve for carbachol on the paced left atria was displaced 520-fold to the right by 4-AP (10 Mm). 4-AP alone caused dose-related contractions of the tracheal spirals. Carbachol-induced contractions were, however, superimposed upon the raised tone and there were substantial rightwards shifts of the concentration-response curves of 4·7- and 31·4-fold by 1 and 10 Mm of 4-AP, respectively. Thus 4-AP appears to have muscarinic receptor antagonistic blocking properties. The blockade of the atrial responses was, however, substantially greater and could be attributed to an additional blockade of muscarinic receptor-linked potassium channels. The negative inotropic responses of the A1- adenosine receptor agonist l-phenylisopropyladenosine (l-PIA) were also antagonized by 4-AP, but to a lesser extent than for carbachol. After allowing for the muscarinic receptor blocking activity of 4-AP, carbachol was still antagonized more effectively than L-PIA. This could be due to the presence of a K+ channel-independent component in the response to l-PIA which is not susceptible to 4-AP.
Dopamine Receptor Mediated Hypothermic Action of B-HT 920 in Rats
Authors: Verma A , Kulkarni S K 
Published: April 2011

Abstract
The hypothermic action of the thiazoloazepine derivative B-HT 920, an α2-adrenoceptor agonist has been investigated in rats. B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-azepine dihydrochloride) (0·25–10 mg kg−1 i.p.) induced a dose-dependent hypothermia. The peak effect was seen within 60·90 min and lasted up to 120 min. Its action was potentiated by the selective D1-dopamine agonist SKF 38393 and inhibited by the D2-anatagonists haloperidol (1 mg kg−1) and sulpiride (100 mg kg−1). The hypothermic action of B-HT 920 was centrally mediated; i.c.v. administration of 10 μg produced a significant fall in rectal temperature which was sensitive to blockade by haloperidol. B-HT 920 also potentiated the hypothermic action of apomorphine (0·1 and 0·5 mg kg−1) in a haloperidol sensitive manner. Reserpine (5 mg kg−1 i.p.) pretreatment reduced the hypothermic response of B-HT 920 (0·5 mg kg−1) but sensitized the response due to the combination of B-HT 920 (0·5 mg kg−1) and apomorphine (0·1 mg kg−1). Neither the selective α2-adrenoceptor antagonists, yohimbine (1 mg kg−1) or idazoxan (1 mg kg−1), the histamine antagonist mepyramine (10 mg kg−1) nor the 5-HT antagonist cyproheptadine (5 mg kg−1) inhibited B-HT 920-induced hypothermia. Similarly, the selective α1-antagonist prazosin (1 mg kg−1) and the β-antagonist propranolol (10 mg kg−1) failed to modify the hypothermic action of B-HT 920. These observations demonstrated hypothermia induced by B-HT 920 is mediated by postsynaptic D2-receptors and D1- and D2-receptor interplay is essential for the full expression of hypothermia in rats.
Enhancement of 4-biphenylacetic acid bioavailability in rats by its β-cyclodextrin complex after oral administration
Authors: Puglisi G , Santagati N A , Ventura C A , Pignatello R , Panico A M , Spampinato S 
Published: April 2011

Abstract
4-Biphenylacetic acid, a potent non-steroidal antiinflammatory agent forms a solid inclusion complex with β-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2·9 mg kg−1 for the complex and of 6·2 mg kg−1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone.
Effects of calcium channel inhibitors on the hypothermic response to oxotremorine in normo and hypercholinergic rats
Authors: Pucilowski Olgierd , Overstreet David H , Rezvani Amir H , Janowsky David S 
Published: April 2011

Abstract
The Flinders Sensitive Line of rats (FSL) has been selectively bred to have increased sensitivity to cholinergic drugs. Typically, these rats react with twice as great a hypothermic effect to muscarinic agonists such as oxotremorine, as do similarly bred Flinders Resistant Line rats (FRL). We compared the effects of three chemically different calcium channel inhibitors (diltiazem, nicardipine and verapamil) on the hypothermia induced in FRL and FSL rats by oxotremorine (0·2 mg kg−1 s.c). Each drug was injected i.p. in a dose of 20 μmol kg−1 30 min before oxotremorine. Methylatropine (2 mg kg−1 s.c.) was administered 15 min before oxotremorine to block the peripheral effects of the agonist. The hypothermic effect of oxotremorine in FSL rats was antagonized by nicardipine and diltiazem. In contrast, verapamil failed to influence the hypothermic response in FSL rats. Verapamil significantly (P &lt; 0·05) augmented oxotremorine hypothermia in FRL rats. Diltiazem and nicardipine were without effect on oxotremorine-induced hypothermia in FRL rats. There were no significant changes in temperature in separate groups of FRL and FSL rats treated with calcium channel inhibitors alone.
Role of calcium in the analgesic action of tetrahydroisoxazolepyridinol and muscimol
Authors: Aram S Raj , Ramaswamy S , Bapna J S 
Published: April 2011

Abstract
The role of calcium in the analgesic activity of 4,5,6,7-tetrahydroisoxazole-(5,4-c) pyrídin-3-ol (THIP) and muscimol has been investigated using the acetic acid assay procedure. THIP and muscimol produced significant analgesic response. Whilst neither calcium chloride nor nifedipine in the doses employed significantly altered the number of writhings, calcium chloride antagonized the analgesic responses of THIP and muscimol while nifedipine potentiated them. Similar responses were recorded for morphine. These findings suggest that THIP and muscimol, like morphine, might alter the calcium movements across the plasma membrane to elicit the analgesic response.
Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity
Authors: Sakane Toshiyasu , Akizuki Motohiro , Yoshida Masako , Yamashita Shinji , Nadai Tanekazu , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
The aim of the present study has been to confirm the existence of a transport pathway for a drug (cephalexin) to the cerebrospinal fluid (CSF) directly from the nasal cavity, by comparing the drug's concentrations in CSF after intranasal (i.n.), intravenous (i.v.) and intraduodenal (i.d.) administration. Higher levels of the drug were found in CSF following i.n. administration compared with the i.v. and i.d. routes, even though its plasma concentrations were similar. These findings suggest the existence of a direct transport pathway for cephalexin from the nasal cavity to the CSF. The concentration of drug in CSF at 15 min after i.n. administration was higher than that at 30 min. In contrast, its concentrations in CSF at 15 min after i.v. and i.d. administration were not significantly different from those at 30 min. The results confirm the presence of a direct transport pathway to CSF from the nasal cavity. This pathway may represent a new delivery route to CSF and possibly to brain parenchyma.
Formulation Effects on the Mechanical Properties of Metronidazole Tablets
Authors: Itiola O A , Pilpel N 
Published: April 2011

Abstract
The individual and interaction effects of nature of binder (N), concentration of binder (C) and the physical form of the formulation (P) on the tensile strengths (T—a measure of the bond strength of tablets) and the brittle fracture index values (BFI—a measure of the lamination tendency of tablets) of metronidazole tablets have been studied using a 23 factorial experimental design in each case. Changing binder concentration from a ‘low’ to a ‘high’ level increased T and reduced the BFI of the tablets. Methylcellulose 20 exhibited stronger binding effect and greater ability to reduce the lamination tendency of the tablets than polyvinylpyrrolidone of molecular weight 44000. Granular formulations produced tablets with lower T values but also with lower BFI values than tablets produced from powdered formulations. The ranking of these individual effects on tensile strength was P &gt; C &gt; N while the ranking for the BFI was P &gt; N &gt; C. For the interaction effects, the ranking for tensile strength was P—N ≫ N—C &gt; P—C while the ranking for the BFI was N—C ≫ P—C &gt; P—N.
Saturable, Non-Michaelis-Menten Uptake of Liposomes by the Reticuloendothelial System
Authors: Kume Yoshihiro , Maeda Fumiyo , Harashima Hideyoshi , Kiwada Hiroshi 
Published: April 2011

Abstract
Multilamellar vesicles (300–350 nm) were infused into the rat femoral vein at the rate of 4, 40 and 400 nmol phosphatidycholine min−1 for 6 h using [3H]inulin as an aqueous marker. The time courses of blood concentration of vesicles, normalized for infusion rate, were not superimposable, showing the non-linearity of liposome disposition in the blood circulation. These time courses of blood concentration were well fitted by a single Michaelis-Menten equation. On the other hand, the time courses of tissue content could not be so accommodated. Additionally, the observed relationship between the uptake of liposomes by the liver and their clearance from it and other organs differed essentially from a simulation based on Michaelis-Menten type saturable kinetics. Therefore, it is suggested that there is a time-dependent non-Michaelis-Menten type process in the phagocytosis of macrophages in the reticuloendothelial system.
In-vitro Evidence for Carrier-mediated Uptake of Acidic Drugs by Isolated Bovine Brain Capillaries
Authors: Terasaki Tetsuya , Kang Young Sook , Ohnishi Toshimasa , Tsuji Akira 
Published: April 2011

Abstract
[3H]Acetic acid was taken up into the isolated brain capillaries in a temperature and concentration dependent manner. The initial uptake rates were pH dependent over the range 5.0–7.4. An increase of the uptake rate with decrease in medium pH was not seen in the presence of unlabelled acetic acid (10 mM). The uptake of [3H]acetic acid was significantly reduced in the presence of several drugs having a monocarboxylic group. The initial uptake of [14C]salicylic acid was also pH dependent and was inhibited by acetic acid and acidic drugs. A mutually competitive inhibition was observed for the uptake of acetic acid and salicylic acid. The present study demonstrates that acidic drugs having a monocarboxylic group are transported by a common carrier-mediated system into the brain capillaries.
The Use of a Radiolabelled Saccharin Solution to Monitor the Effect of the Preservatives Thiomersal, Benzalkonium Chloride and EDTA on Human Nasal Clearance
Authors: Batts Alison H , Marriott Christopher , Martin Gary P , Bond Steven W , Greaves Jane L , Wilson Clive G 
Published: April 2011

Abstract
The effect of thiomersal, benzalkonium chloride and ethylenediaminetetraacetic acid (EDTA) on the nasal mucociliary clearance of healthy volunteers has been investigated using a modified saccharin test and gamma scintigraphy concomitantly. A significant correlation was found between the two techniques. Using each subject as his/her own control, none of the preservatives significantly altered the rate of clearance or proportion cleared from the nasal cavity after the administration of a single dose. This result is at variance with some in-vitro findings.
Determination of Lipophilicity and Hydrogen-bond Donor Acidity of Bioactive Sulphonyl-containing Compounds by Reversed-phase HPLC and Centrifugal Partition Chromatography and their Application to Structure-activity Relations
Authors: Altomare Cosimo , Tsai Ruey-Shiuan , Tayar Nabil El , Testa Bernard , Carotti Angelo , Cellamare Saverio , De Benedetti Pier G 
Published: April 2011

Abstract
The lipophilic character of two large series of substituted benzenesulphonamides (BzSA) and 4-aminodiphenylsulphones (4-ADS) has been assessed by two chromatographic methods, i.e. reversed-phase HPLC using a relatively novel octadecylpolyvinyl packing and centrifugal counter-current chromatography (CPC). The octadecylpolyvinyl stationary phase proved an interesting alternative to the more common octadecylsilane type stationary phase for obtaining retention parameters correlated to partition coefficients (i.e. log P). The CPC method, being far less time-consuming and markedly more precise than the classical shake-flask method, offers a promising alternative for measuring partition coefficients. The parameter Δlog Poct-hep, i.e. log Poctanol minus log Pheptane, was also determined for both congeneric series and was indicative of a similar H-bonding capacity for the SO2NH2 and 4-NH2-C6H4-SO2 groups. QSAR analyses of carbonic anhydrase inhibition by BzSA and antimycobacterial activity of 4-ADS show the capacity of the new lipophilicity parameters to express the hydrophobic component of the drug-enzyme interactions and to reveal a possible role of H-bond donor capacity in governing the antimycobacterial activity of 4-ADS.
Effect of chronic administration of nicotine or cocaine on steroidogenesis in rat adrenocortical cells
Authors: Krueger Rick J , Lin Chaomei , Fung Yiu K 
Published: April 2011

Abstract
Rats were implanted subcutaneously with osmotic mini-pumps containing either 0.9% NaCl, nicotine (1.5 or 4.5 mg kg−1 day−1), or cocaine (30 mg kg−1 day−1), for 14 days. Neither nicotine nor cocaine treatment significantly altered the maximal rate of steroidogenesis in adrenocortical cell preparations from the animals. However, pretreatment with cocaine increased the sensitivity of the preparation to stimulation by ACTH, the ED50 was 5 pM compared with 10 pM from control animals. Addition of nicotine or cocaine at concentrations up to 100 μM to adrenal cell suspensions from naive rats did not stimulate steroidogenesis or increase the sensitivity of cells to ACTH stimulation. These results suggest that the primary chronic effect of nicotine on steroidogenesis is exerted at the level of the hypothalamus and/or pituitary and not directly on adrenocortical cells. On the contrary, pretreatment with cocaine causes persistent changes in adrenocortical cells.
Influence of lipophilic counter ions on the transport of ionizable hydrophilic drugs
Authors: Neubert Reinhard , Fischer Silke 
Published: April 2011

Abstract
The influence of lipophilic counter ions on the transport of the hydrophilic drugs pholedrine and bretylium across artificial lipid membranes has been studied using a permeation model system. The transport of both drugs was markedly enhanced by hexylsalicylate and by salts of fatty acids with a maximum at decanoate. The transport of pholedrine was additionally increased by bile salts such as desoxycholate.
Differential responses of human and rat cartilage to degrading stimuli in-vitro
Authors: Ismaiel S , Hollander A P , Atkins R M , Elson C J 
Published: April 2011

Abstract
Human cartilage biopsies incubated for 2 days in-vitro with 15% synovial fluid from rheumatoid arthritis patients contained less glycosaminoglycans (GAG) than control biopsies. Recombinant human (rHu-) interleukin-1α (IL-1α) and IL-1β at 10 or 100 ng mL−1 had no effect on human cartilage GAG levels. Similarly, GAG loss from human cartilage biopsies into medium over 5 days was significantly increased by synovial fluid but unaffected by 100 ng mL−1 IL-1α or IL-1β compared with controls. However, when rat femoral head cartilage samples were incubated with 100 ng mL−1 rHu-IL-1α or IL-1β for 5 days there was a significant increase in GAG loss from the cartilage into medium, whilst human synovial fluid significantly decreased the loss of GAG from rat cartilage into medium, compared with controls. The results demonstrate that human and rat cartilage differ from each other in their responses to degrading stimuli and suggest that animal cartilage may have limited application for the screening of drugs intended for the treatment of human arthritides.
Antidiuretic effect of bremazocine and U-50,488 in rats after α2-adrenoceptor blockade
Authors: Bianchi Giancarlo 
Published: April 2011

Abstract
The role of α2-adrenoceptors and κ-opioid receptors in urination was studied in rats. In water-loaded rats (40 mL kg−1 p.o.) the κ-opioid agonist bremazocine (0.05-0.2 mg kg−1 i.p.) induced a dose-related diuretic response in the second hour after administration, but had no effect in the first hour. When rats were pretreated with the α2-adrenoceptor antagonist idazoxan (1 mg kg−1 s.c.), bremazocine induced a dose-related antidiuretic response in the first hour; thereafter the rats showed an increase of urination similar to that with bremazocine alone. The antidiuretic effect of bremazocine was dependent on the dose of idazoxan with maximal response after 1–3 mg kg−1. Similar results were obtained with bremazocine in the presence of yohimbine (1 mg kg−1 s.c). The antidiuretic profile of bremazocine after idazoxan was shared by U-50,488 (2.5–10 mg kg−1 i.p.), although this compound alone at the high dose reduces urine output in the first hour. The antidiuresis induced by bremazocine in the presence of idazoxan in water-loaded rats was completely antagonized by 10 but not 2 mg kg−1 i.p. of the opioid antagonist naloxone. Thus, κ-opioid agonists, in addition to their diuretic effect, also produce an antidiuretic response which may be mediated by α2-adrenoceptors.
Histological Findings in Rabbit Lymph Nodes After Endolymphatic Injection of Liposomes Containing Blue Dye
Authors: Hirnle P 
Published: April 2011

Abstract
Liposomes produced from phosphatidylcholine and cholesterol and containing Patent Blue V have been injected endolymphatically in the rabbit. The lymph nodes stained dark blue and retained this colour until termination of the experiment after 28 days. No toxic effects were observed histologically. The liposomes were deposited within the macrophages in a fine granular pattern. Because endolymphatic injection of such liposomes produces excellent contrast between retroperitoneal lymph nodes and their surrounding fatty tissue, it can improve both the radicality and the selectivity of lymphonodectomy in oncological surgery.
Characterization of Albumin-acacia Complex Coacervation
Authors: Burgess D J , Kwok K K , Megremis P T 
Published: April 2011

Abstract
Complex coacervation between oppositely charged albumin and acacia mixtures has been studied, and the applicability of the various theoretical treatments of complex coacervation (the Voorn-Overbeek, Veis-Aranyi, Nakajima-Sato, and Tainaka theories) to this system has been assessed. Under optimum conditions where maximum coacervate yield occurred, the Voorn-Overbeek theory appeared to apply. However, away from the optimum coacervation conditions, coacervate sol formation was observed, which is in accordance with the Veis-Aranyi and Tainaka theories. Microelectrophoretic measurements were used to determine optimum pH and ionic strength conditions for maximum coacervation, based on the method of Burgess & Carless (1984). The effects of pH and ionic strength on coacervate yield are reported. Around the optimum conditions for maximum coacervation a viscous coacervate phase and a relatively clear equilibrium phase are formed.
Inhibitory Effects of Non-narcotic Antitussive Drugs on Cholinergically and Non-cholinergically Mediated Neurogenic Contractions of Guinea-pig Isolated Bronchial Muscle
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: April 2011

Abstract
We have examined the actions of non-narcotic antitussive drugs on the response evoked by electrical field stimulation or by acetylcholine (ACh) and neurokinin A (NKA) on guinea-pig bronchial strip chain. Electrical field stimulation (1–32 Hz, 0.5 ms, 30 V for 5 s) evoked a biphasic contraction in a frequency-dependent manner, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Dextromethorphan (1–300 μM) and tipepidine (0.1–100 μM) caused a concentration-dependent inhibition in the height of the biphasic contraction, but noscapine (1–300 μM) was less effective. Submaximal contractions of bronchial muscle evoked by exogenous ACh (1–30 μM) were inhibited by tipepidine (10–100 μM), but not by dextromethorphan (10–100 μM) or noscapine (10–100 μM), while those evoked by exogenous NKA (10–300 nM) were augmented by these drugs. The results indicate that in guinea-pig isolated bronchial muscle, dextromethorphan inhibited both neurally-mediated responses but not those to the exogenously applied agent. Tipepidine caused an inhibition similar to the non-cholinergically mediated response of dextromethorphan, it also caused a more profound inhibition of the cholinergically mediated response and selectively antagonized ACh. Noscapine had no effect.
Cyclic Nucleotide Content of the Rat Anococcygeus During Relaxations Induced by Drugs or by Non-adrenergic, Non-cholinergic Field Stimulation
Authors: Mirzazadeh Shokoufeh , Hobbs Adrian J , Tucker John F , Gibson Alan 
Published: April 2011

Abstract
Low concentrations of sodium nitroprusside (0.2 and 1 μM) relaxed carbachol-induced tone of the rat anococcygeus but did not affect the content of either cGMP or cAMP; higher concentrations (10, 100 and 1000 μM) produced greater relaxation (&gt; 60%) and a rise in cGMP but not cAMP. In the presence of the cGMP-phosphodiesterase inhibitor M&B 22948 (10 μM), 1 μM sodium nitroprusside produced greater relaxation and a selective increase in cGMP. Forskolin (0.5–250 μM) caused relaxation and a selective increase in cAMP; the concentration-response relationships of the two effects were similar. Non-adrenergic, non-cholinergic (NANC) field stimulation (10 Hz; 20 s trains) reduced tone by 52% but had no effect on cyclic nucleotide content; in the presence of 10 μM M&B 22948 or 1 μM sodium nitroprusside, NANC stimulation produced a greater degree of relaxation and increased cGMP but not cAMP content. The results show that NANC stimulation acts like sodium nitroprusside, causing a selective increase in cGMP, and this supports the proposal that NANC transmission in the rat anococcygeus involves an endogenous nitrate; the possibility that multiple pools of cGMP exist in the anococcygeus is discussed.