bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Disposition of (R)-α-Methylhistamine, a Histamine H3-Receptor Agonist, in Rats
Authors: Yamasaki Seiji , Sakurai Eiichi , Hikichi Noboru , Sakai Naruhiko , Maeyama Kazutaka , Watanabe Takehiko 
Published: April 2011

Abstract
Using a modified HPLC method with a fluorescence spectrophotometer and a weak cation exchanger, it was possible to separate (R)-α-methylhistamine (α-methylhistamine) from histamine in plasma and various tissues. The assay was used to study the disposition and pharmacokinetic analysis of α-methylhistamine after a bolus intravenous administration to rats. After rapid intravenous administration (12·6 mg kg−1), the plasma concentration declined biexponentially with a half-life of 1·3 min in the elimination phase. The area under the plasma concentration-time curve and total body clearance were 130 μg min mL−1 and 97 mL min−1 kg−1, respectively. After administration, α-methylhistamine was immediately transferred to various tissues. The concentration was high in the kidney, lung, and liver (kidney &gt; lung &gt; liver), but low in the brain. The tissue-to-plasma concentration ratios in peripheral tissues were greater than 1, suggesting that the transfer of α-methylhistamine to peripheral tissues was due to a specialized transport mechanism or possibly to tissue binding. However, the finding that the tissue/plasma ratio in the brain was lower than unity suggests that the transport system in this tissue depends on a concentration gradient, and that α-methylhistamine crosses the blood-brain barrier in rats with difficulty.
In-vitro potencies of histamine H2-receptor antagonists on tetraethylammonium uptake in rat renal brush-border membrane vesicles
Authors: Somogyi A A , Simmons N , Gross A S 
Published: April 2011

Abstract
The histamine H2 antagonists cimetidine, ranitidine and famotidine are organic bases that are cleared from the body by active renal tubular secretion involving the organic cation transporter in the proximal tubule. To determine the potential for competition for the transporter between these drugs and other drugs, their inhibitory potencies were assessed in-vitro, using rat renal brush-border membrane vesicles and tetraethylammonium as the substrate. The concentration-dependent effect of cimetidine, ranitidine and famotidine on the 15-s proton-stimulated uptake of tetraethylammonium into the membrane vesicles was studied using five different rat kidneys. The order of inhibition potencies was: cimetidine (mean IC50= 1·07 μm) &gt; famotidine (2·43 μm) &gt; ranitidine (55·4 μm). The results indicate the potential for drug interactions in the kidney, especially for cimetidine and famotidine.
Reversal of chlorpromazine-induced avoidance depression by the N-methyl-d-aspartate antagonist, dizocilpine, in mice
Authors: Mele Andrea , Battaglia Mario , Sansone Mario 
Published: April 2011

Abstract
The non-competitive N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine) was tested, alone or in combination with chlorpromazine, in mice previously trained in the shuttle-box. The lowest doses of dizocilpine (0·02 and 0·04 mg kg−1) attenuated the disrupting action of the neuroleptic (1·5 mg kg−1) on avoidance-performance, while avoidance depression induced by 1·5 and 2 mg kg−1 chlorpromazine was completely or almost completely reversed by 0·08 mg kg−1 NMDA antagonist. The highest dose (0·16 mg kg−1) of dizocilpine did not ameliorate avoidance-performance of mice receiving 2 mg kg−1 chlorpromazine, perhaps because of ataxic effects produced by the drug combination, at these doses. The results support suggestions for a potential use of NMDA antagonists in the treatment of extrapyramidal side-effects of neuroleptics.
Evidence for a dopaminergic involvement in the renal action of centrally administered JA116a, a novel compound with possible dopaminergic activity, in rats
Authors: Orfila G Luz , Angel Jorge , Torres Marysabel , Barbella Yarisma , Israel Anita 
Published: April 2011

Abstract
Intracerebroventricular (i.c.v.) administration of JA116a, induces an increase in urinary volume and sodium excretion in conscious male hydrated rats. The involvement of brain dopaminergic neurons in the JA116a renal action was investigated. Diuretic and natriuretic action of JA116a was blocked by haloperidol pretreatment. The renal effect was prevented by selective dopaminergic neuron, denervation by i.c.v. administration of 6-hydroxydopamine in combination with desmethylimipramine. Our results suggest that JA116a acts centrally, at least in part, via an interaction with endogenous dopamine neurons.
Diuretic effect of NG-nitro-l-arginine methyl ester in the rat
Authors: Li Q , Bowmer C J , Yates M S 
Published: April 2011

Abstract
Intravenous infusion of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester, l-NAME (10 μg kg−1 min−1), to anaesthetized rats produced a diuresis and natriuresis. By contrast, infusion of the same dose of NG-nitro-d-arginine methyl ester had no effect on either urine output or sodium excretion. The effects of l-NAME were first evident 120 min after the start of infusion and by 170 min a fivefold increase in urine volume and sodium excretion was recorded. l-NAME also produced a transient fall in inulin clearance and a persistent decline in renal blood flow. These renal effects of l-NAME were associated with a gradual elevation of mean arterial blood pressure, although this only attained statistical significance, in comparison with saline-infused animals, 170 min after the start of infusion. The findings indicate the diuresis and natriuresis evoked by l-NAME in the rat is a result of a direct tubular action together with a pressure diuresis.
The effect of theophylline on parkinsonian symptoms
Authors: Mally Judit , Stone T W 
Published: April 2011

Abstract
Adenosine is known to inhibit the release of dopamine from central synaptic terminals. The present open trial was therefore conducted to determine whether the adenosine receptor-antagonist theophylline would be of value in Parkinson’s disease. Fifteen parkinsonian patients were treated for up to 12 weeks with a slow release oral theophylline preparation (150 mg day−1), yielding serum theophylline levels of 4·44 mg L−1 after one week. The patients exhibited significant improvements in mean objective disability scores and 11 reported moderate or marked subjective improvement. It is suggested that theophylline might be a useful adjunct to the routine therapy of parkinsonian patients.
The determination of ofloxacin in human skin tissue by high-performance liquid chromatography and correlation between skin tissue concentration and serum level of ofloxacin
Authors: Ohkubo Tadashi , Kudo Masakiyo , Sugawara Kazunobu , Sawada Yukimasa 
Published: April 2011

Abstract
A simple high-performance liquid chromatographic (HPLC) assay was developed for the measurement of ofloxacin in skin tissue, and the correlation between serum levels and skin tissue levels of ofloxacin was determined. The homogenized skin samples were directly introduced into an HPLC system after filtering through a Molcut II membrane filter to remove proteins. The filtrate was concentrated on a pre-column using a phenyl-stationary phase and was then introduced to an analytical column using an ODS-stationary phase by column-switching techniques. Ofloxacin and lomefloxacin as an internal standard were detected by UV absorbance at 300 nm. Determination was possible for ofloxacin over the concentration range 250–3000 ng (g skin tissue)−1; the limit of detection was 100 ng g−1. The absolute recovery of ofloxacin added to skin tissue homogenate was over 72% with a coefficient of variation of less than 4·1%. This method is applied to determination of skin tissue level of ofloxacin in patients after treatment with ofloxacin. The correlation between serum levels and skin tissue levels of ofloxacin was determined for 30 patients after oral administration of ofloxacin. Good correlation was obtained and the coefficient of correlation was 0·84.
Moment analysis of hepatic local disposition of allopurinol and oxipurinol: metabolism kinetics from allopurinol to oxipurinol in the rat isolated perfused liver
Authors: Yasui Hiroyuki , Yamaoka Kiyoshi , Nishimura Masuhiro , Naito Shinsaku , Nakagawa Terumichi 
Published: April 2011

Abstract
Drug metabolism in the liver was examined by the rat isolated perfused liver using the single-pass bolus-input technique. The test compounds, allopurinol and its metabolite oxipurinol, were independently introduced into the liver from the portal vein, and the concentration profiles in the venous outflow were monitored and kinetically analysed by moment theory. The recovery ratios of allopurinol and oxipurinol after the individual administration of each drug were estimated to be 0·17 (±0·08 s.d.) and 1·03 (± 0·02 s.d.), respectively. The outflow recovery ratio of oxipurinol as the metabolite after allopurinol administration was estimated to be 0·80 (±0·07 s.d.). These results indicate that the combined outflow recovery of the precursor and the metabolite after allopurinol administration is almost 100% in the rat liver.
Kinetic analysis of propranolol-induced impairment of its own metabolism in rats
Authors: Kagimoto Noriko , Masubuchi Yasuhiro , Fujita Shoichi , Narimatsu Shizuo , Suzuki Tokuji 
Published: April 2011

Abstract
The effect of repetitive oral administration of propranolol (100 mg kg−1 day−1, 5 days) on the kinetics of liver microsomal propranolol metabolism was investigated in the rat. Vmax values of the high-affinity phase for biphasic kinetics of propranolol 4- and 5- hydroxylase activities were decreased by propranolol pretreatment, while those of the low-affinity phase were unchanged. The Vmax value of monophasic 7-hydroxylase activity was also decreased. On the other hand, the Vmax value of N-desisopropylase activity in the propranolol-treated rats was increased more than 2-fold compared with non-treated (control) rats, resulting in a change from monophasic in control rats to biphasic kinetics in propranolol-treated rats. These findings indicate that repetitive administration of propranolol selectively impairs a CYP2D isozyme that is involved in the high-affinity phases for propranolol ring-hydroxylations.
Study of the mutual effects of sulphadiazine and ciprofloxacin on their uptakes by Pseudomonas aeruginosa
Authors: Richards R Michael E , Reid Raymond G , Hamilton Vivienne E S , Xing Dorothy K L 
Published: April 2011

Abstract
A high-performance liquid chromatography (HPLC) assay was developed for ciprofloxacin and sulphadiazine in Isosensitest broth. Combining the HPLC assay with cell dry-weight determinations indicated that both compounds were able to enhance the uptake of the other by log phase Pseudomonas aeruginosa cultured in the presence of the compounds. It is hypothesized that the increased bacterial uptakes are the reason for the enhanced antibacterial activity previously reported for combinations of ciprofloxacin and sulphadiazine.
8-Hydroxypenillic acid: NMR characteristics and facile formation from 6-aminopenicillanic acid
Authors: Casy A F , Lipczynski A 
Published: April 2011

Abstract
High field NMR (1H and 13C) spectral characteristics in D2O of 8-hydroxypenillic acid and 6-aminopenicillanic acid (6-APA)-sodium bicarbonate mixtures are reported. The ready conversion of 6-APA to 8-hydroxypenillic acid is demonstrated.
Investigation of Synergism with Combinations of Dibromopropamidine Isethionate or Propamidine Isethionate and Polymyxin B
Authors: Richards R Michael E , Xing Dorothy K L 
Published: April 2011

Abstract
Combinations of polymyxin B and dibromopropamidine isethionate exhibited synergistic inhibitory and bactericidal activity against Pseudomonas aeruginosa, Enterobacter cloacae, Proteus mirabilis, Escherichia coli and Staphylococcus aureus. Similar results were obtained with polymyxin B plus propamidine combinations except that propamidine was not as active as dibromopropamidine and the combination of polymyxin B plus propamidine against S. aureus only had additive activity. The antibacterial agents were tested in solutions and in a cream formulation. The findings indicate a potential for the use of selected combinations of these antibacterial agents in the treatment of wound and superficial eye infections.
pH-Dependent and Carrier-mediated Transport of Salicylic Acid Across Caco-2 Cells
Authors: Takanaga Hitomi , Tamai Ikumi , Tsuji Akira 
Published: April 2011

Abstract
The transport of monocarboxylic acid drugs such as salicylic acid was examined in the human colon adenocarcinoma cell line, Caco-2 cells that possess intestinal epithelia-like properties. [14C]Salicylic acid transport was pH-dependent and appeared to follow the pH-partition hypothesis. However, 10 Mm unlabelled salicylic acid significantly reduced the permeability coefficient of [14C]salicylic acid. Kinetic analysis of the concentration dependence of the permeation rate of salicylic acid across Caco-2 cells showed both saturable (K1 = 5·28 ± 0·72 Mm Jmax = 36·6 ± 3·54 nmol min−1 (mg protein)−1) and non-saturable (kd = 0·37 ± 0·08 μL min−1 (mg protein)−1) processes. The permeation rate of [14C]salicylic acid was competitively inhibited by both acetic acid and benzoic acid, which were demonstrated in our previous studies to be transported in the carrier-mediated-transport mechanism which is responsible for monocarboxylic acids. Furthermore, certain monocarboxylic acids significantly inhibited [14C]salicylic acid transport, whereas salicylamide and dicarboxylic acids such as succinic acid did not. From these results, it was concluded that the transcellular transport of [14C]salicylic acid across Caco-2 cells is by the pH-dependent and carrier-mediated transport mechanism specific for monocarboxylic acids.
The Disposition of the Tolcapone 3-O-Methylated Metabolite is Affected by the Route of Administration in Rats
Authors: Funaki Tomoo , Onodera Hideko , Ushiyama Naomi , Tsukamoto Yuko , Tagami Chieko , Fukazawa Hideo , Kuruma Isami 
Published: April 2011

Abstract
Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-l-methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB-COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of &gt; 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). The fraction of the intravenous dose of tolcapone metabolized to the 3-O-methylated metabolite at 10 mg kg−1 was 2·6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5·4% for 20 mg kg−1 and 2·7% for 40 mg kg−1.
Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase
Authors: Yamamoto Ken , Shah Ashok C , Nishihata Toshiaki 
Published: April 2011

Abstract
We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0·25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle.
Menthol and Related Cooling Compounds
Authors: Eccles R 
Published: April 2011

Summary
Menthol and related cooling compounds such as ‘coolant agent 10’, are widely used in products ranging from common cold medications to toothpastes, confectionery, cosmetics and pesticides. The review brings together a range of information on production and chemistry of menthol, and its metabolism, mechanism of action, structure-activity relationships, pharmacology and toxicology. In particular, the coolant action and carminative actions of menthol are discussed in terms of actions on calcium conductance in sensory nerves and smooth muscle. The actions of menthol on the nose, respiratory reflexes, oral cavity, skin and gastrointestinal tract are reviewed.
The Distribution of an Intranasal Insulin Formulation in Healthy Volunteers: Effect of Different Administration Techniques
Authors: Newman S P , Steed K P , Hardy J G , Wilding I R , Hooper G , Sparrow R A 
Published: April 2011

Abstract
The initial deposition pattern in the nasal passages and subsequent clearance of an insulin formulation labelled with 99mTc-human serum albumin have been determined in 12 healthy male volunteers. Four different administration modes from a novel aqueous spray device were compared, involving delivered volumes of 80–160 μL, and with either gentle or vigorous inhalation while firing the device. The entire dose was deposited in the nasal cavity, and no significant radioactivity was deposited in the lungs. A mean 25–33% of the radiolabel remained in the nose after 4h. A significantly smaller area of the nasal mucosa was covered by the smallest (80 μL) bolus, but subsequent clearance rates did not vary significantly with mode of administration. Blood glucose levels fell after administration of the insulin formulation, but no serious episodes of hypoglycaemia occurred.
Subcellular Distribution of Proteolytic Activities Degrading Bioactive Peptides and Analogues in the Rat Small Intestinal and Colonic Enterocytes
Authors: Bai Jane P F 
Published: April 2011

Abstract
The objective of this study was to compare, in rat small intestinal and colonic enterocytes, subcellular distributions of activities degrading the large peptides, neurotensin, acetylneurotensin (8–13), GRF(1–29)NH2 (human growth hormone releasing factor fragment), (desNH2Tyr1,D-Ala2,Ala15)-GRF(1–29)NH2, insulin, and insulin B-chain. Proteolytic activities degrading individual peptides in the 10000-g pellet, rich in intracellular organelles, 27000-g pellet, rich in brush-border membrane, 100000-g pellet, and 100000-g supernatant, rich in cytosol, were determined and compared for both the small intestine and colon. In colonic fractions, the cytosol had highest activity (g protein)−1 degrading three out of four peptides tested, while in small intestinal fractions, the 27000-g pellet had the highest activity (g protein)−1, degrading four out of five peptides tested. In both small intestine and colon, the cytosol had a higher percentage of total proteolytic activity degrading each of the above polypeptides and the highest insulin-degrading activity (g protein)−1. The results suggest that at pH 7·5, proteolytic activities (g protein)−1 in the fraction of subcellular organelles are much lower than those in cytosol and that cytosolic proteolytic activities degrading polypeptides and analogues are significant.
The Stimulative Effect of Diffusion Potential on Enoxacin Uptake across Rat Intestinal Brush-border Membranes
Authors: Hirano Takeshi , Iseki Ken , Miyazaki Shozo , Takada Masahiko , Kobayashi Michiya , Sugawara Mitsuru , Miyazaki Katsumi 
Published: April 2011

Abstract
Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H+-gradient. Momentary dissipation of the H+-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K+-diffusion potential induced by valinomycin. Furthermore, not only the outward H+-gradient but also an inward Cl−-gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl−-gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H+-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.
The Inhibitory Effects of Cephalosporin and Dipeptide on Ceftibuten Uptake by Human and Rat Intestinal Brush-border Membrane Vesicles
Authors: Sugawara Mitsuru , Toda Takaki , Kobayashi Michiya , Iseki Ken , Miyazaki Katsumi , Shiroto Hiroshi , Uchino Jun-Ichi , Kondo Yukifumi 
Published: April 2011

Abstract
The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H+-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent Km and Vmax values of 0·35 min and 2·052 nmol (mg protein)−1 min−1 for human BBMV, and 0·50 mm and 3·056 nmol (mg protein)−1 min−1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver–Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.
Use of Cultured Human Neuroblastoma Cells in Rapid Discovery of the Voltage-gated Potassium-channel Blockers
Authors: Toral Joyce , Hu William , Yi Lynda , Barrett James E , Sokol Patricia T , Ziai M Reza 
Published: April 2011

Abstract
Depolarization of human neuroblastoma cells by high concentrations of extracellular potassium ions, leads to the activation of the voltage-gated potassium channels. The activity of such potassium channels can be effectively and rapidly monitored by tracking the efflux of 86Rb from pre-loaded target cells in response to the depolarizing stimulus. The inclusion of compounds with unknown activity in the assay medium, can result in the identification of novel blockers of the voltage-gated potassium channels. Since this functional assay is performed in 96-well microtitre plates, it represents a rapid and high-volume primary screening method for the detection and identification of the voltage-gated potassium-channel blockers, which may have therapeutic utility in several indications including memory degeneration and cardiac arrhythmias.