bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of inwardly rectifying K+ channels in secretory responses of human ileal mucosa
Authors: Burleigh David E 
Published: May 2003

Abstract
In acute secretory diarrhoea the primary event driving fluid secretion is a transcellular, electrogenic, serosal to mucosal transport of chloride ions. Such transport requires the maintenance of an electrically negative cell membrane voltage, which is achieved through a basolateral outward leakage of potassium ions. The aim of this study was to investigate the nature of K+ channel involvement in facilitating secretory processes in the human ileum. Muscle-stripped mucosal preparations of human ileal mucosa were set up in Ussing chambers for recording short-circuit current and transmucosal conductance. Escherichia coli heat-stable toxin and vasoactive intestinal peptide (VIP) produced concentration-dependent increases in short-circuit current. Responses to the heat- stable toxin were unaffected by basolateral application of 4-aminopyridine (5 mm), glibenclamide (10 μm) or a combination of charybdotoxin (0.3 μ m) plus apamin (0.3 μm). However, basolateral barium (0.2–5 mm) caused a concentration-dependent inhibition. Responses to VIP were similarly affected by barium (0.05–1 mm). These results suggested that electrogenic chloride transport by human ileal mucosa required the presence of basolateral K+ channels. The use of selective K+-channel inhibitors and low concentrations of barium suggested that the channels involved might be of the inwardly rectifying type.
Pharmacological characterization of MP349, a novel 5-HT1A-receptor antagonist with anxiolytic-like activity, in mice and rats
Authors: Wesołowska Anna , Paluchowska Maria H , Gołembiowska Krystyna , Chojnacka-Wójcik Ewa 
Published: May 2003

Abstract
The purpose of this study was to further characterize the pharmacological effects of MP349 (trans-1-(2-methoxyphenyl)-4-(4-succinimidocyclohexyl)piperazine), a new serotonin 5-HT1A postsynaptic receptor antagonist, using several biochemical and behavioural assays. The silent 5-HT1A-receptor antagonist WAY 100635 (N-{2-[4-(2–1-piperazinyl]ethyl)-N-pyridinyl)cyclohexanecarboxamide) was used as a reference compound in in-vivo tests, and diazepam served as standard anxiolytic drug in animal models of anxiety. In this study we showed that MP349 bound with moderate affinity (Ki = 234 nm) for α-adrenoceptors, and with very low affinity (Ki &gt; 2600 nm) for 5-HT2A, dopamine D1, D2 and benzodiazepine receptors. The effects of MP349 on presynaptic 5-HT1A receptors were studied in two models (mice and rats). Like WAY 100635, MP349 antagonized the hypothermia induced by the 5-HT1A-receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DPAT) in mice. Neither MP349 nor WAY 100635 administered alone induced hypothermia. In a rat microdialysis study, MP349 (like WAY 100635) did not affect 5-HT dialysate level in the prefrontal cortex; however, when given before 8-OH-DPAT, it inhibited the decrease in 5-HT release induced by the 5-HT1A agonist. The data demonstrated that MP349 behaved like a functonal antagonist of presynaptic 5-HT1A receptors. The potential anxiolytic activity of MP349 and reference drugs was examined in a conflict drinking test in rats, a plus-maze test in rats and a four-plate test in mice. MP349 and WAY 100635 produced anxiolytic-like effects, though somewhat weaker than those induced by diazepam, and only in the case of diazepam the anxiolytic-like effects were dose-dependent. Moreover, MP349 administered in doses inducing anxiolytic-like effects did not disturb the locomotor activity (open field test) or locomotor coordination (rota-rod test) of rats. These and earlier results indicated that MP349 was an antagonist of 5-HT1A receptors which exhibited anxiolytic-like activity in an animal model of anxiety.
Pharmaceutical strategies to prevent ventilator-associated pneumonia
Authors: McCrory Roisin , Jones David S , Adair Colin G , Gorman Sean P 
Published: May 2003

Abstract
The increasing incidence of hospital-acquired (nosocomial) infection is a disturbing phenomenon resulting in significant patient mortality and putting considerable strain on healthcare budgets and personnel. One particularly serious aspect of nosocomial infection is that of ventilator-associated pneumonia (VAP). This arises in patients who receive mechanical ventilation within the intensive care unit. The quoted incidence of VAP varies widely (5–67%) and the reported mortality of patients with VAP is in the range of 24–71%. This review will examine the many factors that account for these wide ranges reported, including the patient population under investigation, the causative organism, the method of diagnosis, interventions employed and preventative strategies. The use of bioactive and drug-impregnated biomaterials for endotracheal tube construction is discussed as novel approaches to the prevention of VAP.
Design and validation of a dynamic flow model simulating encrustation of biomaterials in the urinary tract
Authors: Gorman Sean P , Garvin Clare P , Quigley Fergus , Jones David S 
Published: May 2003

Abstract
A number of models exist for assessing encrustation on biomaterials employed as devices in the urinary tract. However, static urine models are suitable only for assessment of biomaterials residing in the bladder and the dynamic models available suffer from a number of disadvantages, notably their complexity and limitation to short-term assessment. The dynamic model described herein is a relatively simple design incorporating the ability to assess a large number of biomaterials in replicate fashion and over long periods of time. The biomaterials tested in the dynamic model conform to the urethral catheter and ureteral stent devices that experience urine flow within the urinary tract. The model was initially validated using Percuflex as a test biomaterial. The mass of calcium and magnesium, representing hydroxyapatite and struvite encrustation, respectively, on Percuflex was detected by atomic absorption spectrometry. No significant differences in encrustation levels were detected either between vessels or between biomaterial positions on any mandrel within the vessels, indicating the suitability of the dynamic model for reproducible determination of biomaterial encrustation. The dynamic model was then used to compare the encrustation of biomaterials commonly employed in urinary-tract devices, namely polyurethane, Percuflex and silicone. Calcium and magnesium levels on polyurethane and Percuflex were shown to be statistically similar, whereas silicone exhibited significantly reduced encrustation. When, subsequently, comparisons were made of biomaterial encrustation between the dynamic model and a static model, calcium and magnesium levels arising from the latter model were significantly higher on each of the biomaterials. However, the same rank order of encrustation resistance was observed for the biomaterials in both models, with silicone performing better than polyurethane or Percuflex. The prediction of in-vivo performance based on in-vitro models of encrustation is often difficult, although the model described provides a more accurate method for assessing the potential of novel and existing biomaterials for use in urinary medical devices requiring flow of urine.
In-vitro and in-vivo antibacterial activity evaluation of a polyurethane matrix
Authors: Lee Sun-Hee , Kim Sung-Ryul , Kim Jung Sun , Bae Hae-Rahn , Lee Chi-Ho , Kim Dae-Duk 
Published: May 2003

Abstract
Various in-vitro and in-vivo methods for evaluation of the duration of antibacterial activity were compared using a controlled-release polyurethane matrix developed for the prevention of surface bacterial adhesion and growth. Cefadroxil was incorporated into this polyurethane matrix by a solvent casting method before the matrix was coated with polyurethane in tetrahydrofuran solution. The release of cefadroxil from the matrix into distilled water at 37 °C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activity of the matrix against Escherichia coli and Staphylococcus aureus was evaluated by measuring the diameters of the inhibition zone and the optical density of the broth. The matrices were also implanted subcutaneously in rats and the duration of the antibacterial activity was determined by measuring the inhibition zone. The results showed that duration of antibacterial activity of the polyurethane matrix was successfully determined in-vitro by these methods, and the results differed from the conventional in-vitro release study. It was also possible to determine the duration of action of the matrix in-vivo by implanting the matrix in rats, and then measuring the antibacterial activity of the matrix at predetermined time intervals. While a good correlation was observed between the in-vitro and in-vivo methods used in this study to evaluate the duration of the antibacterial activity of the polymeric matrix, the conventional in-vitro release study did not coincide with these results.
Synthesis and hydrolytic behaviour of 2-mercaptoethyl ibuprofenate–polyethylene glycol conjugate as a novel transdermal prodrug
Authors: Davaran Soodabeh , Rashidi Mohammad R , Hashemi Mahdi 
Published: May 2003

Abstract
Thiolated derivatives of ibuprofen and its polyethylene glycol ester were synthesized via condensation of 2-mercaptoethyl ibuprofenate with carboxy-terminated polyethylene glycol. The release of ibuprofen from this polymeric prodrug has been studied under conditions simulating those encountered in the skin. The polymeric prodrug of ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH 8.5 (15% at pH 7.4) after 48 h at 37 °C. The polymer–drug conjugate was subjected to enzymatic hydrolysis in human plasma. The polymer showed considerable enzymatic hydrolysis (68% after 48 h). The results showed that the polymeric prodrug model of non-steroidal anti-inflammatory drugs (NSAIDs) described here can be used in topical formulations of NSAIDs. It is expected that the novel thiol derivative will have both enhanced transdermal penetration and stability to oxidation which make it a suitable candidate for transdermal formulations.
Protective effect of Artemisia douglasiana Besser extracts in gastric mucosal injury
Authors: Repetto Marisa , Maria Alejandra , Guzmán Jorge , Giordano Oscar , Llesuy Susana 
Published: May 2003

Abstract
The aim of this work was to evaluate markers of oxidative stress in ethanol-induced gastric ulcers and the protective antioxidant activity in-vivo of Artemisia douglasiana Besser extracts in ethanol-treated rats. Ethanol-induced oxidative damage is believed to be associated with generation of reactive oxygen molecules, which leads to oxidative stress. A. douglasiana is used in folk medicine as a cytoprotective agent against peptic ulcer. Different bioassays were performed: in-vivo stomach chemiluminescence, tert-butyl hydroperoxide initiated chemiluminescence (in-vitro chemiluminescence), total antioxidant capacity (TRAP) and catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in stomach homogenates. When ethanol (3 g kg−1) was administered, the in-vivo chemiluminescence increased by 107%, in-vitro chemiluminescence by 108%, SOD by 130% (P&lt;0.001), and catalase and TRAP decreased by 43 and 59% (P&lt;0.05 and 0.001, respectively). A. douglasiana (400 mg kg−1) pretreatment decreased in-vivo chemiluminescence by 41% (P&lt;0.05), in-vitro chemiluminescence by 66% (P&lt;0.001) and SOD by 56% (P&lt;0.001) and increased catalase by 14% and TRAP by 168% (P&lt;0.001, respectively) but GPx activity was not significantly different from the ethanol group. These results illustrate the significant antioxidant activity of A. douglasiana extract in-vivo and in-vitro.
Enhancement of polyethylene glycol (PEG)-modified cationic liposome-mediated gene deliveries: effects on serum stability and transfection efficiency
Authors: Kim Jin-Ki , Choi Sung-Hee , Kim Cheong-Ok , Park Jeong-Sook , Ahn Woong-Shick , Kim Chong-Kook 
Published: May 2003

Abstract
In this study, we modified cationic liposomes either by polyethylene glycol (PEG)-grafting or PEG-adding methods, and compared the physical properties of transfection complexes and transfection efficiency in-vitro and prolonged circulation in-vivo. The PEG-grafted transfection complexes were prepared by mixing plasmid DNA with PEG-grafted cationic liposomes, which were composed of DSPE-PEG 2000 and cationic lipids. The PEG-added transfection complexes were prepared by adding DSPE-PEG 2000 to the mixture of cationic liposomes and plasmid DNA. The particle sizes of the PEG-modified transfection complexes (˜200 nm) changed a little over 4 weeks compared with the conventional transfection complexes. In the presence of serum, the transfection efficiency of the conventional transfection complexes was lowered whereas the transfection efficiency of the PEG-modified transfection complexes was maintained. Moreover, the transfection efficiency of the conventional transfection complexes was significantly reduced when they were stored. However, the transfection efficiency was stable for the PEG-modified transfection complexes, even after two weeks of storage. Of the in-vitro transfection efficiencies, there was no difference between PEG-grafted and PEG-added transfection complexes. When the conventional, PEG-grafted, and PEG-added transfection complexes were administered into mice by the tail vein, the PEG-added transfection complexes showed a prolonged circulation of plasmid DNA compared with other transfection complexes. These results suggest that the PEG-added transfection complexes could be a useful non-viral vector because of their simplicity in preparation, enhanced stability and prolonged circulation compared with the conventional transfection complexes.
Thermal gelation of aqueous curdlan suspension: preparation of curdlan jelly
Authors: Hino Tomoaki , Ishimoto Hayato , Shimabayashi Saburo 
Published: May 2003

Abstract
Curdlan jelly was prepared by heating an aqueous curdlan suspension at 70 °C for 5 min. Theophylline, as a model drug, was entrapped in the jelly network. Curdlan jelly had a hardness comparable with that of commercially available jelly for confectionary. Syneresis was observed for 8 days after the preparation and was not detected during the experimental term from the gel prepared from 10% w/v curdlan suspension. Release of theophylline from the jellies was sustained, and was increasingly delayed with an increase in the curdlan concentration. An aqueous curdlan suspension was studied by means of differential scanning calorimetry (DSC) up to 80 °C and down to 25 °C, and subsequent re-heating to 30 °C. Enthalpy increased with the concentration of curdlan, while the temperature at the onset of the endothermic peak decreased with the concentration of curdlan. The enthalpy due to thermal gelation of 1 mg curdlan was 12.2 mJ. An increase in curdlan concentration decreased the enthalpy and lowered the onset temperature of the endothermic peak during the DSC re-heating scan. The results are due to an increase in the amount of non-freezing water and freezing bound water and a decrease in free water. The number of water molecules entrapped in the curdlan jelly as non-freezing water was 8.1 per glucopyranose residue.
Estimation of absorption parameters from the non-steady-state phase in the rat gut perfusion model
Authors: Corrigan Owen I , Gubbins Rachel H , O'Driscoll Caitriona M 
Published: May 2003

Abstract
The aim of the study was to calculate absorption parameters, including permeability coefficients (Papp), from the non-steady-state portion of the outflow to inflow concentration ratio vs time profiles and compare them with those obtained via the more traditionally used steady-state phase. The rat in-situ intestinal perfusion method was used. The compounds studied, diclofenac and macrogol 4000 (polyethylene glycol (PEG) 4000), were perfused at four different flow rates (0.1–2.0 mL min−1). The estimates of Papp from the non-steady-state data were systematically lower for both compounds. The non-steady-state analysis gave estimates of the intestinal radius, r. The internal diameter of the intestine segment increased as the flow rate increased. When this effect was taken into account similar Papp estimates were obtained by the two approaches. Thus the convention of using a constant value of intestinal radius in the steady-state equation leads to an over estimate of the Papp when high flow rates are employed. The different trends observed, between Papp and perfusate flow rate, for the two compounds, macrogol 4000 and diclofenac, may be linked to increased surface area and exposure to membrane pores of larger size. The longitudinal spreading coefficient, De, increased with flow rate and was approximately 1000 times greater than that estimated for molecular diffusion. The high values obtained were consistent with the non-smooth biological surface and peristaltic movement present in-vivo.
The increased intestinal absorption rate is responsible for the reduced hepatic first-pass extraction of propranolol in rats with cisplatin-induced renal dysfunction
Authors: Okabe Hiromi , Mizukami Akiko , Taguchi Masato , Aiba Tetsuya , Yasuhara Masato , Hashimoto Yukiya 
Published: May 2003

Abstract
The mechanisms responsible for the increased bioavailability of propranolol in renal dysfunction were investigated in rats. Experimental acute renal failure (ARF) was induced by intraperitoneal injection of cisplatin (5 mg kg−1). ARF induced a significant increase in blood propranolol concentration after intra-intestinal administration. The extent of bioavailability (F) of propranolol at an intestinal dose of 15 mg kg−1 was 16.4% and 26.9% in control and ARF rats, respectively, and the F value at a 37.5 mg kg−1 dose was 54.7% and 81.4% in control and ARF rats, respectively. In contrast, the blood propranolol concentration following intraportal infusion was not increased significantly in ARF rats. The hepatic first-pass extraction (Eh) was dose-dependent and saturable: Eh of propranolol in control rats was 58.0% and 18.3% at 8 and 20 mg kg−1, respectively, and Eh in ARF rats was 50.8% and 19.9% at 8 and 20 mg kg−1, respectively. The initial absorption rate of propranolol from the intestine in ARF rats was significantly greater compared with control rats. These results indicated that the increased bioavailability of propranolol in rats with cisplatin-induced renal dysfunction was mainly a result of the increased absorption rate in the intestine followed by the partial saturation of hepatic first-pass metabolism.
Topical Corticosteroid Prescribing Patterns following Changes in Drug Benefit Status
Authors: Campbell Chole A , Cooke Charmaine A , Weerasinghe Swarna DS , Sketris Ingrid S , McLean-Veysey Pam R , Skedgel Chris D 
Published: May 2003

OBJECTIVE: To examine changes in prescribing patterns for topical corticosteroid products dispensed to elderly patients in Nova Scotia, Canada, after all but 2 combination topical corticosteroid products were removed from the Nova Scotia Seniors' Pharmacare Program benefit list. METHODS: Administrative prescription claims from the Nova Scotia Seniors' Pharmacare Program were used to identify the number and costs of topical corticosteroid, antifungal, antibiotic, and combination corticosteroid products dispensed. Time-series analysis was used to compare the periods before (April 1, 1999–March 31, 2000) and after (April 1, 2000–March 31, 2001) the delisting. RESULTS: In 1999–2000, 26 031 of 103 400 eligible elderly patients (25%) and in 2000–2001, 22 837 of 95 550 eligible elderly (24%) received a prescription for a defined topical product. Nova Scotia Seniors' Pharmacare Program expenditures for all topical products decreased from $11.88 to $10.60 (CND) per beneficiary per year (11%) after the policy revision. Topical combination products decreased from 18% of all topical products dispensed to 14%, while the percentage of potent corticosteroid products dispensed increased from 24% to 27% over the study period. Pre- and post-policy time–trend analysis showed statistically significant increasing trends in cost per beneficiary for all topical products and potent corticosteroid products. Combination corticosteroid products showed no change in trends for costs per beneficiary before, and a slight increasing trend after, the policy revision. CONCLUSIONS: Prescribing of topical corticosteroid combination products in Nova Scotia decreased following the formulary revision. There was an increase in potent topical corticosteroid prescribing. Future study involving evaluation of patient outcomes would be useful.
Chromium as Adjunctive Treatment for Type 2 Diabetes
Authors: Ryan Gina J , Wanko Nancy S , Redman Andrea R , Cook Curtiss B 
Published: May 2003

OBJECTIVE: To review the chemistry, pharmacology, efficacy, and safety of trivalent chromium in the treatment of type 2 diabetes and hyperlipidemia. DATA SOURCES: The English literature was searched from 1966 through May 2002 using MEDLINE, International Pharmaceutical Abstracts, and EMBASE. The key words included chromium, glucose, lipids, and diabetes. Pertinent references from review articles and studies were used as additional sources. DATA SYNTHESIS: Trivalent chromium is an essential nutrient and has a key role in lipid and glucose metabolism. Supplementation with chromium does not appear to reduce glucose levels in euglycemia. It may, however, have some efficacy in reducing glucose levels in hyperglycemia. The effects of chromium on lipid levels are variable. Chromium in doses <1000 μg/d appears to be safe for short-term administration. Kidney function and dermatologic changes need to be monitored. CONCLUSIONS: Chromium appears to be a safe supplement and may have a role as adjunctive therapy for treatment of type 2 diabetes. Additional large-scale, long-term, randomized, double-blind studies examining the effect of various doses and forms of chromium are needed.