bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Intestinal Secretory Response to 5-Hydroxytryptamine in the Rat Jejunum and Ileum In-vitro
Authors: Hardcastle J , Hardcastle P T 
Published: April 2011

Abstract
A secretory response to 5-hydroxytryptamine (5-HT) is observed throughout the intestinal tract; this investigation has compared the nature of this response in the jejunum and ileum of the rat in-vitro.
Different basal electrical activity was observed for jejunal and ileal sheets of rat small intestine. In both intact and stripped preparations the basal short-circuit current (SCC) was greater and the tissue resistance lower in the jejunum than in the ileum. 5-HT caused concentration-dependent increases in SCC in intact and stripped preparations of both regions. EC50 values were similar in the jejunum and ileum, stripped sheets from both regions showing greater sensitivity. In the ileum the maximum increase in SCC induced by 5-HT was similar in intact and stripped sheets, but in the jejunum the response was greater in intact preparations. The jejunal response to 5-HT was reduced in the absence of bicarbonate but unaffected by lack of chloride, whereas the ileal response was inhibited by removal of chloride but unaltered in bicarbonate-free conditions. In intact sheets the tetrodotoxin-sensitive neural component was greater in the jejunum. In stripped sheets a neural component could still be detected in the ileum, but not in the jejunum.
There are, therefore, fundamental differences in the way in which the jejunum and ileum respond to 5-HT stimulation—the jejunal response is primarily a result of stimulation of bicarbonate secretion whereas chloride secretion predominates in the ileum. The myenteric plexus appears to play a more prominent role in the jejunum; in the ileum other neural elements also contribute to the response.
Cirsimarin and Cirsimaritin, Flavonoids of Microtea debilis (Phytolaccaceae) with Adenosine Antagonistic Properties in Rats: Leads for New Therapeutics in Acute Renal Failure
Authors: Hasrat J A , De Bruyne T , De Backer J-P , Vauquelin G , Vlietinck A J 
Published: April 2011

Abstract
In traditional medicine Microtea debilis is used against proteinuria. In ligand-binding studies extracts of Microtea debilis have been shown to inhibit the binding of [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) to adenosine-A1 receptors in rat forebrain membranes. Subsequently, cirsimarin, a flavonoid, was isolated as the active component and was shown to function as adenosine antagonist at the adenosine-A1 receptor in-vitro. In this study we have investigated the adenosine-A2 receptor activity of cirsimarin the in-vivo inhibition of the effects of adenosine by cirsimarin in rats, the absorption of cirsimarin and the inhibition of the binding of [3H]DPCPX to the adenosine-A1 receptor by urine samples obtained after oral administration of crude extract of Microtea debilis, cirsimarin or cirsimaritin to rats.
Cirsimarin inhibited the binding of [3H]5′-N-ethylcarboxamidoadenosine ([3H]NECA) to adenosine-A2 receptors in rat striatum with an inhibition constant, Ki, of 6.5 ± 0.3 μm. The decrease of heart rate and blood pressure induced by adenosine was significantly inhibited by cirsimarin. After oral administration of 8 and 80 mg kg−1 cirsimarin, the compound could not be detected in either plasma or urine, but the presence of cirsimaritin was established. By use of β-glucuronidase, glucuronides of cirsimaritin were also detected in the urine. The concentrations of cirsimaritin in the plasma were 0.126 ± 0.04, 0.138 ± 0.015, and 0.120 ± 0.022 μm, respectively, 2, 5 and 12 h after administration of 8 mg kg−1 cirsimarin. The concentrations of cirsimaritin in the urine at the same times after administration of the same dose were 205 ± 1.86, 5.05 ± 2.6 and 2.06 ± 0.09 μm, respectively. The inhibition of the binding of [3H]DPCPX to the adenosine-A1 receptor by urine samples collected 2, 5 and 12 h after oral administration of 8 mg kg−1 cirsimarin or a crude extract of Microtea debilis containing approximately 8 mg kg−1 cirsimarin and 2.8 mg kg−1 cirsimaritin, or 6.8 mg kg−1 cirsimaritin, was not significantly different from that of urine samples collected from untreated rats, in contrast with urine samples collected 1 and 2 days after oral administration of 80 mg kg−1 cirsimarin. Approximately 3% of the cirsimarin was excreted in the urine as cirsimaritin.
The results indicate that in the kidney and urinary tract the concentrations of cirsimaritin produced after ingestion of more than 8 mg kg−1 cirsimarin can be high enough to inhibit the interaction of adenosine with its receptors; this might explain the effectiveness of Microtea debilis preparations against proteinuria in traditional medicine.
Evaluation of the Long-term Effects of Oleum Origani on the Toxicity Induced by Administration of Streptozotocin in Rats
Authors: Lermioglu Ferzan , Bagci Seyfi , Onderoglu Selda , Ortac Ragip , Tugrul Levent 
Published: April 2011

Abstract
Oleum origani, the essential oil of Origanum onites L., is a traditional plant material used in Turkey for the treatment of several diseases, including diabetes mellitus. This study has evaluated the effect of oleum origani on streptozotocin-induced tissue injury and haematological changes. The effect of oleum origani on glycaemia was also studied.
Long-term administration of oleum origani resulted in significant improvement of tissue injury induced by streptozotocin treatment. No effect on blood glucose levels was detected. In addition, any visible toxicity or disturbance of haematological parameters and tissue structure attributable to the long-term use of oleum origani were not established in normal rats.
The data indicate that long-term use of oleum origani might be effective in preventing or at least in retarding the development of some complications of diabetes mellitus. Further investigation is required to determine the underlying mechanism(s) of the protective effect against tissue injury induced by streptozotocin-treatment of rats.
Oestradiol Release from Self-setting Apatitic Bone Cement Responsive to Plasma-calcium Level in Ovariectomized Rats, and its Physicochemical Mechanism
Authors: Otsuka Makoto , Yoneoka Kazuki , Matsuda Yoshihisa , Fox Jeffrey L , Higuchi William I , Sugiyama Yuichi 
Published: April 2011

Abstract
The effect of plasma calcium levels on the release of oestradiol from a self-setting apatite bone cement containing 0.5% oestradiol was investigated in ovariectomized rats.
The profiles of in-vitro release from the cements in simulated body fluid containing 0, 5 or 10 mg calcium per 100 mL indicated that the rate of release of oestradiol decreased with increasing calcium concentration in the dissolution media. After subcutaneous implantation of oestradiol-loaded cement in healthy and vitamin D-deficient rats, oestradiol release in diseased rats with low plasma calcium levels was significantly higher than that in healthy rats.
These results suggest that in-vitro release of oestradiol from apatite bone cement was dependent on the calcium concentration in the buffer and that the in-vivo release of oestradiol from apatite bone cement was dependent on plasma calcium levels.
Effects of Endotoxin on Neurally-mediated Gastric Acid Secretion in the Rat
Authors: Ramirez Carmen , Calatayud Sara , Beltrán Belen , Martínez-Cuesta Angeles , Barrachina Dolores 
Published: April 2011

Abstract
The effects of a peripheral administration of E. coli endotoxin on neurally-mediated gastric acid secretion and the role of endogenous opioids or PAF receptors in endotoxin effects have been evaluated in the continuously perfused stomach of the anaesthetized rat.
Gastric acid secretion stimulated by distension (20 cm H2O) was reduced dose-dependently by single intravenous bolus injection of endotoxin (0.1–10 μg kg−1). Doses of 5 μg kg−1 induced a peak reduction of distension-stimulated acid output and significantly reduced the secretory response induced by an intravenous bolus of 2-deoxy-d-glucose (150 mg kg−1). This dose of endotoxin did not significantly modify mean systemic arterial blood pressure throughout the experimental period. Pretreatment with the opioid receptor antagonist naloxone (1 mg kg−1, i.v.) or the platelet-activating factor (PAF) receptor antagonist WEB 2086 (2 mg kg−1, i.v.) did not reverse the inhibitory effects of endotoxin (5 μg kg−1, i.v.) on acid secretion stimulated by both distension and 2-deoxy-d-glucose.
These findings suggest that endotoxin-induced acute inhibition of neurally-mediated acid responses, stimulated by gastric distension or administration of 2-deoxy-d-glucose, do not involve the activation of endogenous opioids or PAF receptors.
Evaluation of Liver Function by Co-administration Methodology Using 13C-Labelled Benzoic Acid and Hippuric Acid Coupled with Nuclear Magnetic Resonance Spectroscopy
Authors: Akira Kazuki , Negishi Eiji , Yamamoto Chiaki , Baba Shigeo 
Published: April 2011

Abstract
The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect.
[7-13C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4–0.6 mmol kg−1 were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-13C]hippuric acid formed from [7-13C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-13C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-13C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-13C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8–5.8 μmol min−1 kg−1) and the renal elimination rate constants of hippuric acid (Kre) (0.010–0.021 min−1) in the liver-injured rats were lower than those (Vmax 6.7–11.8 μmol min−1 kg−1; Kre 0.026–0.045 min−1) in the normal rats.
These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.
Predictions of Carbamazepine Concentrations Using a Bayesian Program (PKS System, Abbott): A Retrospective Evaluation in an Outpatient Population
Authors: Gaulier J M , Boulieu R , Fischer C , Mauguiere F 
Published: April 2011

Abstract
This work evaluates the performance of a Bayesian program (PKS System, Abbott) for predicting carbamazepine concentrations in an outpatient population. The retrospective study involved 20 epileptic patients (12 adults and 8 children) receiving carbamazepine monotherapy orally. The program was used to predict measured serum levels after feedback of 0, 1 or 2 steady-state concentrations.
A significant negative prediction bias was observed when no feedback concentration was used for estimation. However, the prediction bias (mean prediction error; m.e.) decreased as soon as one feedback concentration was used for estimation. Precision (mean absolute prediction error; m.a.e.) was significantly improved with one feedback concentration and was even better with two concentrations. Likewise, r.m.s.e. (root mean squared error; composite of bias and precision) regularly decreased when the number of feedback concentrations used was increased. Eleven percent of the estimates were unacceptable clinically (prediction error &gt;2 mg L−) when 1 feedback concentration was used; less than 3% were unacceptable when two concentrations were used.
Thus the performance of the Bayesian dosing program is acceptable when two feedback concentrations are known, and seems able to help the clinician adjust carbamazepine dosage in an outpatient population.
Lecithinization of IL-6 Enhances Its Thrombopoietic Activity in Mice
Authors: Igarashi R , Tsutsumi Y , Fujii H , Tsunoda S , Ochiai A , Takenaga M , Morizawa Y , Mayumi T , Mizushima Y 
Published: April 2011

Abstract
This study was conducted to assess the merit of lecithinization of recombinant human interleukin-6 (IL-6) as a drug delivery system.
IL-6 was lecithinized by covalently binding it with a phosphatidylcholine (lecithin, PC) derivative. The in-vivo thrombopoietic potency of lecithinized IL-6 (PC-IL-6) was greater than that of native IL-6 when administered subcutaneously, although the in-vitro bioactivity of PC-IL-6 was markedly reduced by lecithinization. When PC-IL-6 and native IL-6 were given in doses that produced the same level of thrombopoietic activity, the former stimulated less production of IgG1, a marker of the adverse effects of IL-6, than did the latter. Furthermore, PC-IL-6 persisted in the blood longer than native IL-6.
Based on the above, PC-IL-6 appears to be useful as a drug delivery system and may also be useful in the treatment of drug-induced thrombocytopenia.
Synthesis and Biological Evaluation of New 3-Aralkylamino-2-aryl-2H-1,2,4-pyridothiadiazine 1,1-dioxides as Potential CCK-Receptor Ligands
Authors: de Tullio Pascal , Pirotte Bernard , Neven Philippe , Masereel Bernard , Dewalque Daniel , Diouf Ousmane , Podona Tchao , Caignard Daniel , Renard Pierre , Delarge Jacques 
Published: April 2011

Abstract
A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A and CCK-B receptor ligands.
The compounds were effective as cholecystokinin-ligands in the micromolar range of concentration, c.f. the cholecystokinin receptor antagonists asperlicin, lorglumide or benzotript, and were thus less potent than the best quinazolinones previously reported.
Although the compounds were unsuitable for drug use, the work contributed to our understanding of the chemistry of unusual 2,3-disubstituted pyridothiadiazinedioxides.
Investigation of Physicochemical Changes to l-Asparaginase During Freeze-thaw Cycling
Authors: Jameel Feroz , Bogner Robin , Mauri Frank , Kalonia Devendra 
Published: April 2011

Abstract
l-Asparaginase derived from Erwinia chrysanthemi which is being investigated as an alternative to E. coli for the treatment of lymphoblastic leukaemia has been found in our laboratory to lose activity upon exposure to consecutive freeze-thaw cycles. An investigation was undertaken using several techniques to characterize fully the physicochemical changes l-Asparaginase is undergoing during freeze–thaw cycling leading to the loss of its activity.
A total protein assay suggested that the loss of some enzyme activity was a result of protein precipitation. Circular dichroism (CD) studies showed a decrease of α-helical structure with a concomitant increase in β sheet and random coil content, suggesting alterations in the secondary structure leading to unfolding, the first step of denaturation processes. The elution profiles obtained from size-exclusion chromatography (SEC) studies indicated the formation of several species during the process of freezing and thawing. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) studies showed bands corresponding to 1–3 kDa and 32 kDa, suggesting that some of the species are fragments and shortened monomers resulting from cleavage of monomers. The molecular weight distribution obtained using SEC-linked light scattering indicated a substantial fraction of polydispersed fragments ranging from 900 Da to 3 kDa and a small fraction of aggregates corresponding to 300 kDa.
A scheme was proposed to explain the cascade of events leading to the loss of soluble protein and accompanying loss of enzyme activity. Tetramers of the enzyme dissociate into monomers some of which are cleaved into small fragments. The shortened monomers then aggregate and precipitate.
A Structure-Relationship Study of the Uptake of Aliphatic Polyamine Compounds by Rat Intestinal Brush-border Membrane Vesicles
Authors: Kobayashi Michiya , Suruga Sachie , Takeuchi Hirotaka , Sugawara Mitsuru , Iseki Ken , Miyazaki Katsumi 
Published: April 2011

Abstract
The effects of lipophilicity, ion-diffusion potential and membrane surface potential on the uptake of various aliphatic polyamine compounds by rat intestinal brush-border membrane vesicles (BBMV) have been investigated.
A valinomycin-induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds, and good correlation was observed between lipophilicity and the amount of diffusion-potential-dependent transport of the diamines. In contrast, because of their much lower lipophilicity, tri- and tetraamine compounds were not affected by the diffusion potential. Tetracaine, which can make the membrane surface potential more positive, inhibited the transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV.
These data suggest that the transport mechanism of diamines is similar to that of monoamine compounds in respect to its dependence on ion-diffusion potential and on the membrane surface potential. The extent of the effect of ion-diffusion potential on the rate of transport of the diamines was closely related to the lipophilicity of the diamine. In contrast, only the surface potential contributed to the transport mechanism of lower lipophilic tri- and tetraamine compounds.
Inhibitory Effects of N-acetylcysteine on Superoxide Anion Generation in Human Polymorphonuclear Leukocytes
Authors: Villagrasa Victoria , Cortijo Julio , Martí-Cabrera Miguel , Ortiz José L , Berto Luisa , Esteras Antonio , Bruseghini Leo , Morcillo Esteban J 
Published: April 2011

Abstract
It has been suggested that reactive oxygen species released by activated polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury. Therapeutic action aimed at increasing antioxidant defence mechanisms is still a clinical challenge. This study examines the activity of N-acetylcysteine, a known antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate acetate or the lipid peroxidation promoter t-butyl hydroperoxide.
FMLP (3–300 nm) and phorbol myristate acetate (160 pm–160 nm) induced concentration-related superoxide anion generation. Pre-treatment with N-acetylcysteine (33–333 μm) resulted in concentration-related inhibition of superoxide production induced by FMLP (30 nm) or phorbol myristate acetate (16 nm); –log IC50 values were 3.97 ± 0.07 and 3–91 ± 0.10, respectively. Changes in intracellular calcium ion concentration ([Ca2+]i) induced by FMLP (30 nm) were studied in fura-2-loaded human PMN. FMLP produced a transient calcium response, i.e. a peak followed by decay to a residual value above baseline. N-Acetylcysteine (333 μm) did not affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment with FMLP. Activation by phorbol myristate acetate caused a reduction in glutathione levels from 5.94 ± 0.86 (control) to 1.84 ± 0.51 nmol/3 × 106 cells (P &lt; 0.05 compared with control). Pre-treatment with N-acetylcysteine (333 μm) fully reversed the reduction in glutathione levels induced by phorbol myristate acetate (4.83 ± 0.68 nmol/3 × 106 cells; P &gt; 0.05 compared with control). Exposure to t-butyl hydroperoxide (0.5 mm, 30 min) markedly increased malondialdehyde levels (from 0.03 ± 0.02 to 0.73 ± 0.07 nmol/106 cells), and index of lipid peroxidation. Malondialdehyde levels were significantly reduced in PMN treated with N-acetylcysteine (333 μm; 0.55 ± 0.04 nmol/106 cells; P &lt; 0.05 compared with untreated cells exposed to t-butyl hydroperoxide).
In conclusion, N-acetylcysteine reduces superoxide generation in response to FMLP and phorbol myristate acetate and partially protects against lipid peroxidation in PMN from man. The protection afforded by N-acetylcysteine is not related to alteration of the intracellular calcium signal but might be effected by replenishment of the intracellular glutathione levels.
2′,5′-Dihydroxychalcone as a Potent Chemical Mediator and Cyclooxygenase Inhibitor
Authors: Lin Chun-Nan , Lee Tai-Hua , Hsu Mei-Feng , Wang Jih-Pyang , Ko Feng-Nien , Teng Che-Ming 
Published: April 2011

Abstract
Eleven chalcone derivatives have been tested for their inhibitory effects on platelet aggregation in rabbit platelet suspension and the activation of mast cells and neutrophils.
Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the compounds and some also had a potent inhibitory effect on collagen-induced platelet aggregation and cyclooxygenase. Some hydroxychalcone derivatives showed strong inhibitory effects on the release of β-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti-inflammatory effect of 2′,5′-dihydroxychalcone was greater than that of trifluoperazine. 2′,5′-Dihydroxy and 2′,3,4,4′-tetrahydroxyl chalcones, even at low concentration (50 μm), tested in platelet-rich plasma from man almost completely inhibited secondary aggregation induced by adrenaline.
These results suggest that the anti-platelet effects of the chalcones are mainly a result of inhibition of thromboxane formation.
A Sulphonoglycolipid from the Fern Polypodium decumanum and its Effect on the Platelet Activating-factor Receptor in Human Neutrophils
Authors: Vasänge Mervi , ROLFSEN Wenche , Bohlin Lars 
Published: April 2011

Abstract
The South American fern Polypodium decumanum, traditional name calaguala, has documented clinical use in oral treatment of skin disorders, including psoriasis. The inflammatory mediator platelet-activating factor (PAF), has been implicated in the pathogenesis of psoriasis.
A constituent of a calaguala extract has been shown to have inhibitory activity in a PAF-induced exocytosis model in human neutrophils. The compound was identified as the sulphoquinovosyl diacylglycerol 1,2-di-O-palmitoyl-3-O-(6-sulpho-α-d-quinovopyranosyl)-glycerol by spectroscopic means. When subsequently studied in an in-vitro model for [3H]PAF binding in neutrophils from man the compound caused dose-dependent displacement of [3H]PAF from its receptor with an IC50 value of 2 μm. It is suggested that the compound acts through PAF receptor antagonism in intact human neutrophils.