bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation of Dipeptoid Mimetics for the Tetrapeptide Cholecystokinin, CCK(30–33)
Authors: Walford S P , Campbell M M , Horwell D C 
Published: April 2011

Abstract
The diastereoselective synthesis of 2,3-methanophenylalanine methyl esters (5) has been achieved in 58% yield. The preparation of the dehydropeptides (1, R = Me; 2, R = H) and the cyclopropylpeptides (3, R = Me; 4, R = H) possessing good binding affinities for the CCK-A and CCK-B receptors is described. Conformational studies of the dipeptide esters 1 and 3 indicated the presence of a β-turn within the peptide backbone, although there was no preference in type. The Phe and Trp moieties, however, did prefer to be situated on the same side of the peptide turn which is favourable for receptor binding.
Studies with Inhibitors of the Glycolytic Enzyme Phosphoglycerate Kinase for Potential Treatment of Cardiovascular and Respiratory Disorders
Authors: McHarg J , Littlechild J A 
Published: April 2011

Abstract
Inhibition of the glycolytic enzyme phosphoglycerate kinase (PGK) in erythrocyte cells could provide a method of treatment for cardiovascular and respiratory disorders. The product of the reaction catalysed by PGK, 1,3-diphosphoglycerate, is converted by another enzyme in erythrocytes to 2,3-diphosphoglycerate, which is an allosteric effector of haemoglobin. For this reason, a series of fluoro-phosphonate inhibitors have been tested for their potency in detailed inhibition kinetic experiments with yeast PGK.
The results were analysed by Lineweaver-Burk and Dixon plots and Ki values obtained. Two fluorophosphonates were found to be inhibitory and both have an electron rich mid-chain functionality, which is thought to provide electrons for hydrogen bonding to residues in the triose binding site of the enzyme.
It is postulated that either the fluorine or mid-chain moieties of the analogues are binding to Asp23 and Asn25 residues in the so called ‘basic patch’ area of the triose site. These residues are shown to bind to the D-hydroxyl moiety on the C2 of the true substrate, 3-phosphoglycerate, in the high-resolution crystal structure of pig muscle PGK co-crystallized with 3-phosphoglycerate.
Molecular Modelling of β Turns in a Cyclic Melanotropin
Authors: Chan Ngai Chung , Branch Sarah K , Moss Stephen H , Pouton Colin W 
Published: April 2011

Abstract
α-Melanocyte stimulating hormone (α-MSH) is a tridecapeptide which interacts with a family of G protein-coupled receptors, the melanocortin receptors, to cause its biological effects.
We have modelled the low energy conformations of the α-MSH derivatives as part of a project to probe the receptor binding conformation of melanocortins, and also to design ligands for targeting cytotoxic drugs to MC1 receptors expressed by melanoma cells. H***ere we report a molecular dynamics study of β turns in a cyclic lactam analogue [Nle4, ***Asp5, D-Phe7, Lye***10]α-MSH.
The data show that it is possible for a β turn to exist in the ring portion of this molecule which contains the melanocortin conserved sequence -His-Phe-Arg-Trp-, even though the lowest energy conformers lack a β turn.
The MS-MS Determination of the Fragmentation Pathways of Some Substituted 1,2,3-Benzotriazin-4-ones with Possible Applications in Metabolic Studies
Authors: Woodland E D , Lawson G , Ostah N 
Published: April 2011

Abstract
1,2,3-Benzotriazin-4-one derivatives are extensively used as herbicides, insecticides and nematicides. Incorporation of these compounds into the human food chain is a cause for concern, since their toxicity to man is well documented.
This work describes the development of a data-base of classical 1,2,3-benzotriazin-4-one fragmentation patterns and consequent sequential neutral mass losses which allows the prediction of the presence of a triazinone derived compound.
Positive and negative ion tandem mass spectrometry techniques were employed since they allow rapid and sensitive structural characterization of drugs and their metabolites in biological fluids through the unambiguous monitoring of daughter ions from pre-selected primary ions.
Effects of Different Absorption Enhancers on the Permeation of Ebiratide, an ACTH Analogue, across Intestinal Membranes
Authors: Yamamoto Akira , Okagawa Taishi , Kotani Atsushi , Uchiyama Tomomi , Shimura Takesada , Tabata Shigeru , Kondo Shuji , Muranishi Shozo 
Published: April 2011

Abstract
The permeation of ebiratide (H-Met(O2)-Glu-His-Phe-d-Lys-Phe-NH(CH2)8NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modified Ussing chamber.
Regional differences were observed in the permeation of ebiratide across intestinal membranes; the order of membrane permeability was jejunum &gt; ileum &gt; duodenum &gt; colon. Overall, the permeation of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to ebiratide. Sodium glycocholate and sodium caprate had no significant enhancing effect on the permeability of the jejunal membrane, but significantly enhanced the permeation of ebiratide through the colonic membrane. On the other hand, N-dodecyl-β-d-maltopyramoside (LM) significantly enhanced the permeation of ebiratide through both jejunal and colonic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membrane damage by the absorption enhancers was evaluated by measuring the amount of protein released from the intestinal membrane. It was found that all the absorption enhancers slightly increased the amount of protein released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediaminetetraacetic acid (EDTA), used as a positive control.
These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and protein drugs, including ebiratide.
Twenty-four-hour Variations in the Effect of Nitrodilators in Rat Aorta: Lack of Influence of the Endothelium
Authors: Hodoglugil Ugur , Uluoglu Canan , Güney H Zafer , Görgün C Zafer , Ercan Z Sevim , Abacioglu Nurettin , Zengil Hakan 
Published: April 2011

Abstract
Time-dependent variations of the vasodilator effects of sodium nitroprusside and glyceryl trinitrate on isolated smooth muscle have been studied on rings of rat thoracic aorta, both endothelium-intact and endothelium-denuded.
For most of the concentrations of sodium nitroprusside used the induced relaxations were significantly dependent on the time the tissues were obtained. However, significant temporal differences were obtained for glyceryl trinitrate-induced relaxations at lower concentrations only for both endothelium-intact and endothelium-denuded preparations. EC50 values of sodium nitroprusside and glyceryl trinitrate (i.e. the concentrations inducing half the maximum response) were also significantly different and they had quite similar rhythmic features both in endothelium-intact and in endothelium-denuded preparations.
These results clearly show that the in-vitro sensitivity of rat thoracic aorta to nitrodilator agents varies over a 24-h period and thus depends on when the animals were killed; the presence of endothelium does not change the rhythm of nitrodilator activity. These variations might be a result of circadian rhythm in the guanylate cyclase-cGMP system which mediates responses to nitrodilator agents.
Effect of Ganglionic Blocking Compounds on In-vivo Fluid Secretion in the Rat Small Intestine
Authors: Delbro Dick S , Lange Stefan 
Published: April 2011

Abstract
It is well-known that enteric, secreto-motor nerves mediate cholera toxin-induced fluid secretion in the rat small intestine. This notion is, in part, derived from experiments on anaesthetized animals in which the response to cholera toxin was antagonized by the ganglionic nicotinic receptor antagonist, hexamethonium. In the current study, such anti-secretory action of ganglionic blocking compounds was analysed in an experiment designed to minimize any possible negative effect of general anaesthesia on intestinal secretion.
Rats were anaesthetized with ether for 5–10 min, during which time a jejunal loop (10–12 cm) was constructed. The loop was challenged with one of the secretagogues, cholera toxin, prostaglandin E1 (PGE1) or okadaic acid. Saline (control) or either of the ganglionic blockers, hexamethonium and chlorisondamine, was administered intravenously. The rats were killed 5 h (cholera toxin) or 1–5 h (PGE1 and okadaic acid) after challenge, and the amount of fluid accumulated in the loops was determined. Cholera toxin-induced secretion was unchanged by hexamethonium but reduced by approximately 80% by chlorisondamine. The difference in effect between the two blockers might relate to the duration of ganglionic blockade. Chlorisondamine blocked secretion induced by either PGE1 or okadaic acid by approximately 60%.
It is suggested that the anti-secretory effect of ganglionic blocking compounds might be a result of blockade of secreto-motor nerves but other mechanisms, for example interference with haemodynamic factors, cannot be ruled out.
The Development of Nao Li Shen and its Clinical Application
Authors: Lu Shou-Long , Liu Xin , Wang Jian-Long , Ying Qi , Hu SHUI-GEN , Hu Ping-Ping , Zhu Guo-Ping , Zhen Hua-Wu , Bai Ying-Tang , Wang Quan 
Published: April 2011

Abstract
The traditional Chinese medicine Nao Li Shen (containing ginseng, gastrodia tuber, chuanxiong rhizome and red sage root) is used in craniocerebral injury, cervical spondylosis and cerebrovascular diseases.
The preparation, as an orally administered liquid, was tested in Mongolian gerbils and shown to increase tolerance to ischaemia and anoxia. Clinical use of the preparation resulted in improvement in 96% of 202 patients, as judged by right cerebral blood flow, TCD and CT examination.
We conclude that Nao Li Shen has a positive curative effect upon craniocerebral injury and sequelae of cerebrovascular diseases.
Effects of Administration of Phentonium Bromide on Opioid Withdrawal Syndrome in Rats
Authors: Pinelli A , Trivulzio S , Tomasoni L 
Published: April 2011

Abstract
This study has tested whether phentonium bromide, a quaternary ammonium anti-muscarinic agent, could reverse the signs of precipitated opioid withdrawal.
Rats were treated with either saline or morphine for 4 days, after which half the rats received naloxone and half saline. Each animal also received one of four doses of phentonium bromide (0, 1, 3 and 9 mg kg−1, i.p.). Administration of phentonium bromide in rats receiving naloxone after chronic morphine treatment reduced the intensity of withdrawal signs such as increased defecation or micturition, salivation and wet-dog shakes, and elevated the nociceptive threshold values.
The effects of administration of phentonium bromide might result from its anti-muscarinic activity interfering peripherally with the mechanisms involved in the regulation of the withdrawal symptoms. The use of this drug is thus suggested as a possible means of controlling some of the signs observed during the acute phase of opioid withdrawal in heroin addicts.
Post-ischaemic Alteration of Excitatory Amino Acid Transport Sites in the Gerbil Hippocampus
Authors: Araki Tsutomu , Kato Hiroyuki , Kogure Kyuya , Itoyama Yasuto 
Published: April 2011

Abstract
Sodium-dependent [3H]d-aspartate binding as a marker of excitatory amino acid transport sites in the gerbil hippocampus was evaluated by quantitative receptor autoradiography 1 h to 7 days after transient cerebral ischaemia for 10 min.
Sodium-dependent [3H]d-aspartate binding in the hippocampal CA1 and CA3 sectors significantly increased in the early post-ischaemic stage. After 7 days, a conspicuous elevation of sodium-dependent [3H]d-aspartate-binding was observed in the hippocampal CA1 sector and dentate gyrus. However, no significant change in the binding was found in the hippocampal CA3 sector. A histological study revealed that transient ischaemia caused severe neuronal damage in the hippocampal CA1 sector and mild damage in the hippocampal CA3 sector. However, no ischaemic neuronal damage was observed in the dentate gyrus. An immunohistochemical study also showed that numerous reactive astrocytes were evident in the hippocampus, particularly in the hippocampal CA1 sector, 7 days after ischaemia.
These results demonstrate that transient cerebral ischaemia can cause marked elevation in excitatory amino-acid transport sites in the hippocampus. Furthermore, our results suggest that the post-ischaemic increase in excitatory amino acid transport sites might reflect expression of reactive astrocytes. These findings are of interest in relation to the mechanisms of ischaemic hippocampal damage.
The Expanded Hansen Approach to Solubility Parameters. Paracetamol and Citric Acid in Individual Solvents
Authors: Barra Jerome , Lescure François , Doelker Eric , Bustamante Pilar 
Published: April 2011

Abstract
In this study two solubility-parameter models have been compared using as dependent variables the logarithm of the mole fraction solubility, lnX2e, and ln(α)/U (originally used in the extended Hansen method), where α is the activity coefficient and U is a function of the molar volume of the solute and the volume fraction of the solvent.
The results show for the first time the proton-donor and -acceptor hydrogen-bonding capacities of paracetamol, as measured by the acidic and basic partial-solubility parameters. The influence of solvents on the differential scanning calorimetry (DSC) pattern of the solid phases was also studied in relation to the solubility models tested. Citric acid was chosen as a test substance because of its high acidity and its proton donor capacity to form hydrogen bonds with basic solvents. The partial acidic and basic solubility parameters obtained from multiple regression were consistent with this property, validating the model chosen.
The results show that the more direct lnX2e variable was more suitable for fitting both models, and the four-parameter model seemed better for describing the interactions between solvent and solute.
Effect of Oral Adsorbent AST-120 on Cyclosporin Absorption in Rats
Authors: Takemoto M , Tsuchida M , Konishi M , Suga A , Jojima K , Naito K 
Published: April 2011

Abstract
The oral adsorbent AST-120 is used to inhibit the progression of renal failure by adsorbing uraemic toxins in the gastrointestinal tract. When AST-120 is administered to patients receiving immunosuppressive medicines, it is important to study the effect of AST-120 on the amount of these and other drugs absorbed. We have, therefore, studied the in-vitro adsorption of cyclosporin by AST-120 and investigated the effect of oral administration of AST-120 on the absorption of cyclosporin in rats.
The in-vitro adsorption ratios of AST-120 for cyclosporin were more than 80%. When pure cyclosporin powder was administered with AST-120, blood cyclosporin concentrations were significantly higher than when cyclosporin was administered alone. When cyclosporin dissolved in medium-chain triglyceride was administered to rats by intramuscular injection there was no significant difference in the blood cyclosporin concentration of rats given combined AST-120 and cyclosporin and those given cyclosporin alone. There was no significant difference between the serum concentration of total bile acids, in rats receiving combined oral AST-120 and cyclosporin dissolved in olive oil, and those receiving orally solely a solution of cyclosporin dissolved in olive oil.
These results suggest that oral administration of AST-120 accelerates the absorption of orally administered cyclosporin from the gastrointestinal tract and does not affect the metabolism of cyclosporin. When a solution of cyclosporin in olive oil is administered orally, however, oral administration of AST-120 has no influence on cyclosporin absorption and does not affect the enterohepatic circulation of bile acids.
A Residence-Time Distribution Analysis of the Hydrodynamics within the Intestine in Man during a Regional Single-pass Perfusion with Loc-I-Gut: In-vivo Permeability Estimation
Authors: Lennernäs Hans , Lee I-Der , Fagerholm Urban , Amidon Gordon L 
Published: April 2011

Abstract
The goal of this study was to determine the most appropriate hydrodynamic model for the Loc-I-Gut in-vivo perfusion system. The general mixing-tank-in-series model, which can approximate single mixing tank and laminar and plug-flow hydrodynamics, was fitted to the observed experimental residence-time distribution curves for the non-absorbable marker [14C]PEG 4000. The residence-time distribution analysis shows that the hydrodynamics of the perfusion solution within the jejunal segment in man is well approximated by a model containing on average between 1–2 mixing tanks in series. The solution is well mixed when using perfusion rates of 20, 30 and 60 mL min−. The average mean residence time estimates from the fitted residence-time distribution were 12 ± 7.6, 15 ± 4.2 and 7.7 ± 4.6 min, respectively, at these three perfusion rates. The mean volumes of the segment (Vs) were 25 ± 15, 45 ± 12 and 46 ± 27 mL, respectively. There were no statistical differences between 20, 30 and 60 mL min− in respect of the number of mixing tanks (n) and mean residence times.
This residence-time distribution analysis indicates that the luminal fluid in the Loc-I-Gut perfusion system is well-mixed, and that permeability calculations based on the well-mixed assumption most closely approximate the actual local (average) membrane permeability within the perfused segment.
Regional Intestinal Permeability in Rats of Compounds with Different Physicochemical Properties and Transport Mechanisms
Authors: Fagerholm Urban , Lindahl Anders , Lennernäs Hans 
Published: April 2011

Abstract
Because the absorption of orally administered drugs depends on intestinal permeability, we have investigated how absorptive capacity varies from the proximal to distal intestine in rats. The effective permeabilities of compounds with a range of physicochemical properties and different absorption mechanisms were estimated by use of a previously validated in-situ, single-pass perfusion model.
The low colonic permeabilities of d-glucose and l-dopa indicate the absence or low capacity of the glucose-and amino-acid-transporters in this region. With the exception of the small and moderately lipophilic nonsteroidal anti-inflammatory drug, naproxen, for which permeability was maintained throughout the intestine, the passive intestinal permeabilities for hydrophilic and lipophilic drugs were approximately twice as high in the jejunum and ileum as in the colon. These observations are in accord with those made in recent studies. However, the reasons for the high colonic permeability of non-steroidal anti-inflammatory drugs, and results obtained in previous animal experiments demonstrating that the colon is the region of the intestine with the highest absorptive capacity were not fully clarified.
These data show that the permeability to hydrophilic and lipophilic drugs decreases along the intestine, whereas it is maintained throughout the intestine for the small and moderately lipophilic naproxen. Further investigations are required to clarify the interplay between membrane composition, fluidity and permeability under various conditions in different absorption models.
Effect of Chitosan on Renal Function in Patients with Chronic Renal Failure
Authors: Jing Shi-Bing , Li Leishi , Ji Daxi , Takiguchi Yasuyuki , Yamaguchi Tatsuaki 
Published: April 2011

Abstract
The effects of chitosan have been investigated on eighty patients with renal failure undergoing long-term stable haemodialysis treatment.
The patients were tested after a control treatment period of 1 week. Half were fed 30 chitosan tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan effectively reduced total serum cholesterol levels (from 10.14 ± 4.40 to 5.82 ± 2.19 mm) and increased serum haemoglobin levels (from 58.2 ± 121 to 68 ± 9.0 g L−). Significant reductions in urea and creatinine levels in serum were observed after 4 weeks of chitosan ingestion. The feeling of physical strength, the appetite and the sleep of patients in the treatment group had improved significantly after 12 weeks of ingestion, compared with those of patients in the control group. During the treatment period, no clinically problematic symptoms were observed.
These data suggest that chitosan might be effective treatment for renal failure patients, although the mechanism of the effect should be investigated further.
In-vivo Assessment of Extrahepatic Metabolism of Paeoniflorin in Rats: Relevance to Intestinal Floral Metabolism
Authors: Takeda Shuichi , Isono Tomoko , Wakui Yoko , Mizuhara Yasuharu , Amagaya Sakae , Maruno Masao , Hattori Masao 
Published: April 2011

Abstract
The extraction ratios of paeoniflorin in gut wall (EG), liver (EH) and lung (EL) were assessed by comparing AUCs after various routes of its administration to estimate the first-pass effects and the metabolism by intestinal flora.
Pulmonary extraction ratio of paeoniflorin was assessed by comparing AUCs calculated from venous and arterial plasma concentrations after its intravenous administration (0.5 mg kg−1). The mean pulmonary extraction ratio was estimated to be 006. The hepatic extraction ratio (EH was assessed by comparing AUCs after intraportal and intravenous administrations (0.5 and 5 mg kg−1). The plasma concentration profiles of paeoniflorin after intraportal administration were very close to those after intravenous administration, suggesting a negligible hepatic extraction ratio of paeoniflorin. The AUC value after intraperitoneal administration (0.5 mg kg−1) was greater than that after intraportal or intravenous administration. This finding suggests that paeoniflorin is not metabolized in the gut wall. The transference of paeoniflorin from the serosal side to the mucosal side was evaluated by the in-vitro everted sac method. The low intestinal permeability (194% at 60 min) was demonstrated by the comparison with phenobarbital (63.1% at 60 min).
We conclude that paeoniflorin is not metabolized by gut wall, liver and lung, its poor absorption from the intestine results in extremely low bioavailability and the unabsorbed fraction of paeoniflorin is degraded by the intestinal flora.
Effects of Oren-gedoku-to and Unsei-in, Chinese Traditional Medicines, on Interleukin-8 and Superoxide Dismutase in Rats
Authors: Wang L M , Yamamoto T , Wang X X , Yang L , Koike Y , Shiba K , Mineshita S 
Published: April 2011

Abstract
This study was conducted to elucidate the mechanisms of action of two Chinese traditional drugs, Oren-gedoku-to and Unsei-in, which have been used for many years in the treatment of inflammatory disorders.
In rats with acetic acid-induced inflammation, both drugs reduced interleukin-8 concentrations in the serum. Neither drug significantly affected superoxide dismutase activity in the serum, although Unsei-in increased superoxide dismutase activity in liver after 1 month of administration. Oren-gedoku-to showed no significant effect on liver superoxide dismutase activity.
It was considered that these medicines exert their anti-inflammatory effects mainly on the early stages of inflammation, wherein increased capillary permeability and migration of leucocytes occur.