bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of the effects of three guanylyl cyclase inhibitors on the L‐type Ca2+ and muscarinic K+ currents in frog cardiac myocytes
Authors: Abi‐Gerges Najah , Hove‐Madsen Leif , Fischmeister Rodolphe , Méry Pierre‐François 
Published: August 2006

To investigate the participation of guanylyl cyclase in the muscarinic regulation of the cardiac L‐type calcium current (ICa), we examined the effects of three guanylyl cyclase inhibitors, 1H‐[1,2,4]oxidiazolo[4,3‐a]quinoxaline‐1‐one (ODQ), 6‐anilino‐5,8‐quinolinedione (LY 83583), and methylene blue (MBlue), on the β‐adrenoceptor; muscarinic receptor and nitric oxide (NO) regulation of ICa and on the muscarinic activated potassium current IK,ACh, in frog atrial and ventricular myocytes.
ODQ (10 μM) and LY 83583 (30 μM) antagonized the inhibitory effect of an NO‐donor (S‐nitroso‐N‐acetylpenicillamine, SNAP, 1 μM) on the isoprenaline (Iso)‐stimulated ICa which was consistent with their inhibitory action on guanylyl cyclase. However, MBlue (30 μM) had no effect under similar conditions.
In the absence of SNAP, LY 83583 (30 μM) potentiated the stimulations of ICa by either Iso (20 nM), forskolin (0.2 μM) or intracellular cyclic AMP (5–10 μM). ODQ (10 μM) had no effect under these conditions, while MBlue (30 μM) inhibited the Iso‐stimulated ICa.
LY 83583 and MBlue, but not ODQ, reduced the inhibitory effect of up to 10 μM acetylcholine (ACh) on ICa.
MBlue, but not LY 83583 and ODQ, antagonized the activation of IK,ACh by ACh in the presence of intracellular GTP, and this inhibition was weakened when IK,ACh was activated by intracellular GTPγS.
The potentiating effect of LY 83583 on Iso‐stimulated ICa was absent in the presence of either DL‐dithiothreitol (DTT, 100 μM) or a combination of superoxide dismutase (150 u ml−1) and catalase (100 u ml−1).
All together, our data demonstrate that, among the three compounds tested, only ODQ acts in a manner which is consistent with its inhibitory action on the NO‐sensitive guanylyl cyclase. The two other compounds produced severe side effects which may involve superoxide anion generation in the case of LY 83583 and alteration of β‐adrenoceptor and muscarinic receptor‐coupling mechanisms in the case of MBlue.
Effect of SB‐205384 on the decay of GABA‐activated chloride currents in granule cells cultured from rat cerebellum
Authors: Meadows H J , Harries M H , Thompson M , Benham C D 
Published: August 2006

4‐Amino‐7‐hydroxy‐2‐methyl‐5,6,7,8,‐tetrahydrobenzo[b]thieno[2,3‐b]pyridine‐3‐carboxylic acid, but‐2‐ynyl ester (SB‐205384) and other γ‐aminobutyric acidA (GABAA) receptor modulators were tested for their effects on GABA‐activated chloride currents in rat cerebellar granule cells by use of the whole‐cell patch clamp technique.
The major effect of SB‐205384 on GABAA‐activated current was an increase in the half‐life of decay of the response once the agonist had been removed. This is in contrast to many GABAA receptor modulators that have previously been shown to potentiate GABA‐activated currents.
This profile could be explained if SB‐205384 stabilizes the channel in open and desensitized states so that channel closing is dramatically slowed. Such a modulatory profile may produce a novel behavioural profile in vivo.
Pharmacological characterization of the receptors involved in the β‐adrenoceptor‐mediated stimulation of the L‐type Ca2+ current in frog ventricular myocytes
Authors: Arvydas Skeberdis V , Jurevičius Jonas , Fischmeister Rodolphe 
Published: August 2006

The whole‐cell patch‐clamp was used for studying the effects of various β1‐ and β2‐adrenoceptor agonists and antagonists on the L‐type Ca current (ICa) in frog ventricular myocytes.
Dose‐response curves for the effects of isoprenaline (non selective β‐agonist), salbutamol (β2‐agonist), dobutamine (β1‐agonist) on ICa were obtained in the absence and presence of various concentrations of ICI 118551 (β2‐antagonist), metoprolol (β1‐antagonist) and xamoterol (partial β1‐agonist) to derive EC50 (i.e. the concentration of β‐agonist at which the response was 50% of the maximum) and Emax (the maximal response) values by use of a Michaelis equation. Schild regression analysis was performed to examine whether the antagonists were competitive and to determine the equilibrium dissociation constant (KB) for the antagonist‐receptor complex.
Isoprenaline increased ICa with an EC50 of 20.0 nM and an Emax of 597%. ICI 118551 and metoprolol competitively antagonized the effect of isoprenaline with a KB of 3.80 nM and 207 nM, respectively.
Salbutamol increased ICa with an EC50 of 290 nM and an Emax of 512%. ICI 118551 and metoprolol competitively antagonized the effect of salbutamol with a KB of 1.77 nM and 456 nM, respectively.
Dobutamine increased ICa with an EC50 of 2.40 μM and an Emax of 265%. ICI 118551 and metoprolol competitively antagonized the effect of dobutamine with a KB of 2.84 nM and 609 nM, respectively.
Xamoterol had no stimulating effect on ICa. However, xamoterol competitively antagonized the stimulating effects of isoprenaline, salbutamol and dobutamine on ICa with a KB of 58–64 nM.
We conclude that a single population of receptors is involved in the β‐adrenoceptor‐mediated regulation of ICa in frog ventricular myocytes. The pharmacological pattern of the response of ICa to the different β‐adrenoceptor agonists and antagonists tested suggests that these receptors are of the β2‐subtype.
Increased function of inhibitory neuronal M2 muscarinic receptors in diabetic rat lungs
Authors: Belmonte Kristen E , Jacoby David B , Fryer Allison D 
Published: August 2006

The function of inhibitory neuronal M2 muscarinic receptors in diabetic rat lungs was investigated.
Neuronal M2 muscarinic receptors inhibit acetylcholine release from parasympathetic nerves. Thus, stimulation of neuronal M2 muscarinic receptors with muscarinic agonists, such as pilocarpine, inhibits acetylcholine release and vagally induced bronchoconstriction. In contrast, blockade of neuronal M2 muscarinic receptors with selective M2 muscarinic antagonists, such as AF‐DX 116, potentiates acetylcholine release and vagally induced bronchoconstriction.
Rats were made diabetic by streptozotocin (65 mg kg−1, i.v.). After 7–14 days the rats were anaesthetized with urethane (1.5 g kg−1, i.p.), tracheostomized, vagotomized, ventilated and paralysed with suxamethonium (30 mg kg−1, i.v.). Some 7 day diabetic rats were treated with low doses of long acting (NPH) insulin (2 units day−1, s.c.) for 7 days before experimentation. This dose of insulin was not sufficient to restore normoglycaemia in diabetic rats. Thus, insulin‐treated diabetic rats remained hyperglycaemic.
Distal electrical stimulation (5–70 Hz, 6 s, 40 V, 0.4 ms) of the vagi caused bronchoconstriction, measured as an increase in inflation pressure and bradycardia. In diabetic rats, vagally induced bronchoconstriction was significantly depressed vs controls. In contrast, bronchoconstriction caused by i.v. acetylcholine was similar in diabetic and control animals.
The function of neuronal M2 muscarinic receptors was tested with the muscarinic agonist pilocarpine (0.001–100.0 μg kg−1, i.v.) and the antagonist AF‐DX 116 (0.01–3.0 mg kg−1, i.v.). Pilocarpine inhibited vagally‐induced bronchoconstriction (30 Hz, 20–40 V, 0.4 ms at 6 s) and AF‐DX 116 potentiated vagally‐induced bronchoconstriction (20 Hz, 20–40 V, 0.4 ms at 6 s) to a significantly greater degree in diabetic rats compared to controls.
Both frequency‐dependent vagally‐induced bronchoconstriction and M2 muscarinic receptor function could be restored to nearly control values in diabetic rats treated with low doses of insulin.
Displacement of [3H]QNB (1 nM) with the agonist carbachol (10.0 nM–10.0 mM) from diabetic cardiac M2 muscarinic receptors revealed a half log increase in agonist binding affinity at both the high and low affinity binding sites vs controls. In contrast, M2 receptors from insulin‐treated diabetic rat hearts showed no significant difference in binding affinity vs controls.
These data show that neuronal M2 muscarinic receptors in the lungs have increased function in diabetic rats, suggesting that insulin modulates M2 muscarinic receptor function.
Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco‐2) cells
Authors: Cavet M. E. , West M , Simmons N. L. 
Published: August 2006

Human intestinal epithelial Caco‐2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin.
Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para‐amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N‐′methylnicotinamide (10 mM) were without effect.
Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′‐diisothiocyanostilbene‐2‐2′‐disulphonic acid (DIDS, 400 μM).
Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P‐glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti‐P‐glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco‐2 epithelia, and was not itself secreted by the P‐glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK.
Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media.
The substrate specificity of the ciprofloxacin secretory transport in Caco‐2 epithelia is distinct from both the renal organic anion and cation transport. A role for P‐glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco‐2 epithelia.

British Journal of Pharmacology (1997) 121, 1567–1578; doi:10.1038/sj.bjp.0701302
Induction of neutrophil chemotactic factor production by staurosporine in rat peritoneal neutrophils
Authors: Edamatsu Takeo , Xiao Yi‐Qun , Tanabe Jun‐ichi , Mue Suetsugu , Ohuchi Kazuo 
Published: August 2006

Incubation of rat peritoneal neutrophils in medium containing various concentrations of staurosporine (6.4–64 nM) increased the neutrophil chemotactic activity in the conditioned medium in a time‐ and concentration‐dependent manner.
Separation of the neutrophil chemotactic activity in the conditioned medium by isoelectric focusing revealed that staurosporine (64 nM) stimulated the production of basic (pH>8) neutrophil chemotactic factors, while TPA (12‐O‐tetradecanoylphorbol 13‐acetate, 49 nM) stimulated the production of both basic (pH>8) and acidic (pH 5) neutrophil chemotactic factors.
Determination by immunoassay of cytokine‐induced neutrophil chemoattractant (CINC)‐1, ‐2α, ‐2β and ‐3 in the conditioned medium at 4 h revealed that staurosporine (64 nM) and TPA (49 nM) strongly stimulated the production of CINC‐3 (staurosporine, 133.0±3.8; TPA, 26.7±1.0; control, 0.32±0.01 ng ml−1, means±s.e.mean from four samples) compared to CINC‐1 (staurosporine, 55.0±1.2; TPA, 12.2±0.3; control, 0.56±0.01 ng ml−1), and CINC‐2α (staurosporine, 1.09±0.03; TPA, 0.90±0.02; control, <0.10 ng ml−1). CINC‐2β was below the detectable amount (<0.078 ng ml−1).
The level of CINC‐3 mRNA in the peritoneal neutrophils was determined by reverse transcription‐polymerase chain reaction. Staurosporine (64 nM) and TPA (49 nM) enhanced the level of CINC‐3 mRNA time‐dependently, but had no effect on GAPDH mRNA levels.
Production of staurosporine‐induced neutrophil chemotactic factor was inhibited by the protein kinase C inhibitors, H‐7 (IC50, 12.3 μM), calphostin C (IC50, 0.77 μM) and Ro 31‐8425 (24.3% inhibition at 10 μM), and by the tyrosine kinase inhibitor, genistein (IC50, 68.5 μM). Production of TPA‐induced neutrophil chemotactic factor was also inhibited by both inhibitors.
Both the staurosporine‐ and the TPA‐induced increase in CINC‐3 mRNA levels were suppressed by H‐7 and genistein.

British Journal of Pharmacology (1997) 121, 1651–1658; doi:10.1038/sj.bjp.0701322
Characterization of the binding of [3H]‐SB‐204269, a radiolabelled form of the new anticonvulsant SB‐204269, to a novel binding site in rat brain membranes
Authors: Herdon Hugh J. , Jerman Jeffrey C. , Stean Tania O. , Middlemiss Derek N. , Chan Wai N. , Vong Antonio K. , Evans John M. , Thompson Mervyn , Upton Neil 
Published: August 2006

SB‐204269 (trans‐(+)‐6‐acetyl‐4S‐(4‐fluorobenzoylamino)‐3,4‐dihydro‐2,2‐dimethyl‐2H‐benzol[b]pyran‐3R‐ol, hemihydrate) shows potent anticonvulsant activity in a range of animal seizure models, with a lack of neurological or cardiovascular side‐effects. The profile of the compound suggests that it may have a novel mechanism of action. This study describes the characteristics of a binding site for [3H]‐SB‐204269 in rat forebrain membranes.
Specific [3H]‐SB‐204269 binding was saturable and analysis indicated binding to a homogenoeous population of non‐interacting binding sites with a dissociation constant (KD) of 32±1 nM and a maximum binding capacity (Bmax) of 253±18 fmol mg−1 protein. Kinetic studies indicated monophasic association and dissociation. Binding was similar in HEPES or Tris‐HCl buffers and was unaffected by Na+, K+, Ca2+ or Mg2+ ions. Specific binding was widely distributed in brain, but was minimal in a range of peripheral tissues.
Specific [3H]‐SB‐204269 binding was highly stereoselective, with a 1000 fold difference between the affinities of SB‐204269 and its enantiomer SB‐204268 for the binding site. The affinities of analogues of SB‐204269 for binding can be related to their activities in the mouse maximal electroshock seizure threshold (MEST) test of anticonvulsant action.
None of the standard anticonvulsant drugs, phenobarbitone, phenytoin, sodium valproate, carbamazepine, diazepam and ethosuximide, or the newer anticonvulsants, lamotrigine, vigabatrin, gabapentin and levetiracetam, showed any affinity for the [3H]‐SB‐204269 binding site. A wide range of drugs active at amino acid receptors, Na+ or K+ channels or various other receptors did not demonstrate any affinity for the binding site.
These studies indicate that SB‐204269 possesses a specific CNS binding site which may mediate its anticonvulsant activity. This binding site does not appear to be directly related to the sites of action of other known anticonvulsant agents, but may have an important role in regulating neuronal excitability.

British Journal of Pharmacology (1997) 121, 1687–1691; doi:10.1038/sj.bjp.0701331
First Year of Mandatory Reporting of Healthcare-Associated Infections, Pennsylvania An Infection Control—Chart Abstractor Collaboration
Authors: Julian Kathleen G. , Brumbach Arlene M. , Chicora Michelle K. , Houlihan Carol , Riddle Anna M. , Umberger Teanna , Whitener Cynthia J. 
Published: August 2006

Background.In 2004, the Commonwealth of Pennsylvania mandated hospitals to report healthcare-associated infections (HAIs). The increased workload led our Infection Control staff to collaborate with Atlas, a group of chart abstractors.Objective.The objective of this study was to assess our first year of experience with mandatory reporting of HAIs—specifically, to assess Atlas' contribution to surveillance.Design.Cases were selected if they had 1 or more of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes designated by Pennsylvania as a possible HAI. After training by the Infection Control staff, Atlas applied National Nosocomial Infection Surveillance (NNIS) system case definitions for catheter-associated urinary tract infections (UTIs) and surgical site infections (SSIs), and they applied NNIS chest imaging criteria to eliminate cases that were not ventilator-associated pneumonia (VAP). To assess Atlas' performance, Infection Control staff conducted a parallel review.Results.For discharges from the hospital during the fourth quarter of 2004, a total of 410 UTIs, 59 SSIs, and 56 VAPs were identified on the basis of state-designated ICD-9-CM codes; review by Atlas/Infection Control determined that 15%, 15%, and 16% of cases met case definitions, respectively. Of cases reviewed by both Infection Control and Atlas, 87% of the assessments made by Atlas were correct for UTI, and 96% were correct for SSI. For VAP, Infection Control concluded that 39% of cases could be ruled out on the basis of chest imaging criteria; Atlas correctly dismissed these 12 cases but incorrectly dismissed an additional 6 (error, 19%). Surveillance was not timely: 1-2 months elapsed between the time of HAI onset and the earliest case review.Conclusions.With ongoing training by Infection Control, Atlas successfully demonstrated a role in retrospective HAI surveillance. However, despite a major effort to comply with mandates, time lags and other design limitations rendered the data of low utility for Infection Control. States that are planning HAI-reporting programs should standardize an efficient surveillance methodology that yields data capable of guiding interventions to prevent HAI.
Blood Pressure Cuff as a Potential Vector of Pathogenic Microorganisms A Prospective Study in a Teaching Hospital
Authors: Gialluly C. de , Morange V. , Gialluly E. de , Loulergue J. , van der Mee N. , Quentin R. 
Published: August 2006

Objective.To investigate the potential role of blood pressure (BP) cuffs in the spread of bacterial infections in hospitals.Design.A comprehensive, prospective study quantitatively and qualitatively evaluating the bacterial contamination on BP cuffs of 203 sphygmomanometers in use in 18 hospital units from January through March 2003.Setting.A university hospital with surgical, medical, and pediatric units.Results.A level of contamination reaching 100 or more colony-forming units per 25 cm2was observed on 92 (45%) of inner sides and 46 (23%) of outer sides of 203 cuffs. The highest rates of contamination occurred on the inner side of BP cuffs kept in intensive care units (ICUs) (20 [83%] of 24) or on nurses' trolleys (27 [77%] of 35). None of the 18 BP cuffs presumed to be clean (ie, those that had not been used since the last decontamination procedure) had a high level of contamination. Potentially pathogenic microorganisms were isolated from 27 (13%) of the 203 BP cuffs: 20 of these microorganisms wereStaphylococcus aureus, including 9 methicillin-resistant strains. The highest rates of contamination with potentially pathogenic microorganisms were observed on cuffs used in ICUs and those kept on nurses' trolleys. For 4 patients with a personal sphygmomanometer, a genetic link was found between the strains isolated from the BP cuffs and the strains isolated from the patients.Conclusions.The results of this survey highlight the importance of recognizing BP cuffs as potential vectors of pathogenic bacteria among patients and as a source of reinfection when dedicated to a single patient, emphasizing the urgent need for validated procedures for their use and maintenance.
Habitat suitability for tsessebe Damaliscus lunatus lunatus
Authors: Dörgeloh Werner G. 
Published: August 2006

AbstractThe distribution and numbers of tsessebe (Damaliscus lunatus lunatus) have declined considerably in South Africa, partly due to deteriorating habitat conditions. Identifying important habitat variables will assist in managing the species. The objective of this study was to identify habitat variables important for tsessebe and to develop a predictive model of habitat selection for this species in a savanna biome. The study was conducted in the Nylsvley Nature Reserve over a 2‐year period. A total of eighteen habitat variables were measured in ten plant communities at 200 sites. Logistic regression analyses were used to identify predictor variables and to construct a habitat model. Tsessebe were found <2 km from the nearest source of water, in flat areas with slopes of <3° and with <10% rockiness. Their distribution was not influenced by the woody component. Sites where tsessebe were present had significantly lower grass heights and tuft heights, with a higher grass density compared with areas not utilized by tsessebe. Nitrogen and sodium levels were also higher at present sites. Habitat type and grass height were the most significant predictors of tsessebe presence. The selected model had an overall percentage prediction of 85.0%. The model was subdivided into five vegetation‐specific models and each model was tested with independent data.
Correlation between chemical structure and biological activities of Porphyromonas gingivalis synthetic lipopeptide derivatives
Authors: Makimura Y , Asai Y , Taiji Y , Sugiyama A , Tamai R , Ogawa T 
Published: August 2006

Summary
We recently separated a PG1828-encoded triacylated lipoprotein (Pg-LP), composed of two palmitoyl and one pentadecanoyl groups at the N-terminal of glycerocysteine from Porphyromonas gingivalis, a periodontopathic bacteria, and found that Pg-LP exhibited definite biological activities through Toll-like receptor (TLR) 2. In the present study, we synthesized 12 different Pg-LP N-terminal peptide moieties (PGTP) using four combinations of glyceryl (R and S) and cysteinyl (l and d) stereoisomers, and three different acyl group regioisomers, N-pentadecanoyl derivative (PGTP1), S-glycero 2-pentadecanoyl derivative (PGTP2) and S-glycero 3-pentadecanoyl derivative (PGTP3). All the PGTP compounds (RL, SL, SD, RD) tested showed TLR2-dependent cell activation. The activating capacities of the PGTP-R compounds were more potent than those of the PGTP-S compounds, whereas there were no differences between the PGTP-L and -D compounds. Furthermore, the production of interleukin (IL)-6 following stimulation with the PGTP1-RL, PGTP2-RL and PGTP3-RL compounds was impaired in peritoneal macrophages from TLR2 knock-out (KO), but not those from TLR1 KO or TLR6 KO mice. These results suggest that P. gingivalis triacylated lipopeptides are capable of activating host cells in a TLR2-dependent and TLR1-/TLR6-independent manner, and the fatty acid residue at the glycerol position in the PGTP molecule plays an important role in recognition by TLR2.