bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection by Almagate of Ethanol-induced Gastric Mucosal Damage in Rats
Authors: Esplugues J V , Barrachina M D , Martínez-Cuesta M A , Calatayud S , Moreno L , Fernandez A , Puig J , Esplugues J 
Published: April 2011

Abstract
The study was designed to analyse the protective effects of almagate on a model of gastric injury, ethanol-induced mucosal damage, in which acid plays little, if any, role.
Pretreatment with almagate dose-dependently reduced the level of gastric damage induced by oral administration of 1mL 100% ethanol. Administration of 12 μmol kg−1 almagate 30 min before ethanol significantly reduced the area of mucosal damage by 65 ± 10%, and the maximum level of inhibition (74 ± 11%) was obtained with 150 μmol kg−1 almagate. Administration of higher doses of almagate (200–250 μmol kg−1) did not result in any further increase in the level of protection against ethanol-induced gastric damage. Administration of 1 mL 100% ethanol induces substantial damage to the gastric mucosa, with nearly 40% of the length of the section evaluated exhibiting deep necrotic and haemorrhagic damage. Pretreatment with almagate caused a significant diminution in all parameters of histological damage, whereas damage to the epithelial cell layer was only significantly reduced by pretreatment with the highest doses evaluated (25, 50 and 150 μmol kg−1).
Administration of aluminium hydroxide did not modify ethanol-induced mucosal damage, even at doses containing concentrations of aluminium higher than those present in gastroprotective doses of almagate. Pretreatment with sucralfate, another aluminium containing compound, at doses of 250 μmiol kg−1 protected the mucosa, although lower doses did not.
The present study has shown that almagate prevents ethanol-induced gastric mucosal damage. This protective effect seems independent of any antacid activity, related to its content in magnesium, and mediated by an increase in gastroprotective prostaglandins in the mucosa of the stomach.
Some Anti-allergic and Anti-inflammatory Actions of 2-N -Carboxamidinonormianserin (FCC5)
Authors: Leitch Ian M , Temple Diana M , Wei He , Boura Alan L A 
Published: April 2011

Abstract
The aims of these studies were to examine the effects of FCC5 (2-carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2,-a) azepine HCI), an analogue of mianserin, on immediate type hypersensitivity reactions in-vitro.
The actions of FCC5 were examined on the Schultz-Dale reaction of guinea-pig ileum and on histamine and leukotriene release from human- and guinea-pig-sensitized lung fragments. FCC5 (applied topically) was assessed for anti-inflammatory activity in-vivo against phorbol-12-myristate-13-acetate (PMA)-induced oedema in the mouse ear. FCC5 (IC50 = 017 μM) was a potent inhibitor of the Schultz-Dale reaction in-vitro, as assessed by a concentration-dependent attenuation of egg albumin-induced contractions of sensitized guinea-pig isolated ileum. Using human and guinea-pig isolated sensitized lung fragments, FCC5 (1–100 μM) attenuated antigen-induced release of sulphidopeptidoleukotrienes and histamine. FCC5 (50 μg topically) resembled mianserin and indomethacin in attenuating PMA-induced mouse ear inflammation.
These properties together with previously published evidence of long lasting antihistamine properties in-vivo, suggest that FCC5 has therapeutic potential as an anti-allergic agent, especially in pathological conditions where an inflammatory component is present.
A Pharmacokinetic-pharmacodynamic Linking Model for the α2-Adrenergic Antagonism of Idazoxan on Clonidine-induced Mydriasis in the Rat
Authors: Valles Joaquim , Obach Rossend , Menargues Angel , Pruñonosa Joan , Jane Francesc 
Published: April 2011

Abstract
The relationship between concentration and inhibitory effect of the α2-adrenoceptor antagonist idazoxan on clonidine-induced mydriasis has been studied in the rat using pharmacokinetic-pharmacodynamic simultaneous modelling.
Fifteen minutes after the anaesthesia of rats with sodium pentobarbitone (55 mg kg-1, i.p.), and 5 min after the administration of clonidine (0·3 mg kg−1, i.v.) to rats pretreated with idazoxan (3 mg kg−1, i.v., and 3 and 10 mg kg−1, orally) at different time intervals, pupil diameters were assessed. The pharmacokinetics of idazoxan were adequately described by a monoexponential equation. Using a pharmacokinetic-pharmacodynamic linking model, the concentration-effect relationships of idazoxan were derived, and were quantified by the inhibitory simple Emax model. At the effect compartment, the estimated apparent IC50 was 153·6 ng mL−1. Values of clearance, volume of distribution and elimination half-life were 71·2 mL kg−1 min−1, 3134 mL kg−1 and 30-5 min, respectively.
These results could contribute to better characterization of the pharmacodynamic and toxicological profiles of idazoxan in experimental models in which a different pharmacokinetic behaviour of the drug is presumed.
An Evaluation of the Mechanisms of Drug Release from Glyceride Bases
Authors: Sutananta Wanchai , Craig Duncan Q M , Newton J Michael 
Published: April 2011

Abstract
A series of dispersions containing theophylline in Gelucires 43/01, 54/02, 50/02, 50/13 and 55/18 was prepared and the physical structures studied using differential scanning calorimetry. The dissolution, erosion and swelling profiles of the drug dispersions were assessed.
Gelucire 43/01 and 54/02 systems were found to release the drug by a simple diffusion mechanism, with no evidence for erosion or swelling being noted. Gelucire 55/18, however, showed a more complex mechanism involving both diffusion and erosion. On increasing the drug load within the matrices, the predominance of the erosion mechanism increased. Drug release from Gelucire 50/13 matrices took place principally by erosion, although the process was dominated by swelling and subsequent disintegration of the matrix, rather than simple dissolution of the base as was found for Gelucire 55/18. Gelucire 50/02 matrices also exhibited swelling, although drug release occurred predominantly via diffusion.
The study, therefore, demonstrates that Gelucires may release incorporated drugs by a number of mechanisms depending on the chemical composition of the base.
Blood Polyamines in the Rat
Authors: De Vera N , Camón L , Martínez E 
Published: April 2011

Abstract
The physiological concentrations of polyamines in plasma, serum and red blood cells were determined in male Wistar rats, using HPLC with fluorometric detection.
The analysis of the metabolic ratio between polyamines and the frontal cortex/plasma relationship for putrescine, spermidine and spermine, suggest the existence of common mechanisms in the regulation of spermidine in blood and brain.
Fluorescent Substances and High Molecular Weight Protein Aggregates Formed in Rat Heart Mitochondria upon Doxorubicin-induced Lipid Peroxidation
Authors: Fukuda Fumiyasu , Kitada Mitsuo , Horie Toshiharu , Awazu Shoji 
Published: April 2011

Abstract
A rat heart mitochondrial suspension was incubated with doxorubicin, FeCl3 and NADH.
Fluorescent substances and high molecular weight protein aggregates were observed in the mitochondrial membranes upon the formation of thiobarbituric acid-reactive substances.
Since both fluorescent substances and high molecular weight protein aggregates are retained in mitochondrial membranes, they can be of use in the clarification of the site of doxorubicin-induced lipid peroxidation.
Aniracetam, a Pyrrolidinone-type Cognition Enhancer, Attenuates the Hydroxyl Free Radical Formation in the Brain of Mice with Brain Ischaemia
Authors: Himori Norio , Suzuki Tatsuya , Ueno Ken-Ichi 
Published: April 2011

Abstract
We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (· OH) during ischaemia-reperfusion of mouse brain.
The fact that brain ischaemia for 40 min followed by reperfusion increased ·OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxy-benzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring ·OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg−1 showed a smaller increase in the formation of DHBA than those given the vehicle only.
Aniracetam at 100 mg kg−1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg−1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation.
This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.
Scavenging of Free-radicals and Inhibition of Lipid Peroxidation by 3-Phenylsydnone
Authors: Narla Raja Sekhar , Rao M N A 
Published: April 2011

Abstract
The antioxidant properties of 3-phenylsydnone were studied in various models in-vitro.
3-Phenylsydnone scavenged the stable free radical, 1,1-diphenyl-2-picrylhydrazyl, and inhibited the degradation of deoxyribose mediated by hydroxyl radicals, although, to a lesser extent than trolox, a water soluble analogue of vitamin E. Many antioxidants possess pro-oxidant properties due to their ability to reduce ferric ions; however, 3-phenylsydnone was free from pro-oxidant properties, and also inhibited the lipid peroxidation induced by iron, in rat brain homogenates.
Dose Regimen Adjustment for Milrinone in Congestive Heart Failure Patients with Moderate and Severe Renal Failure
Authors: Woolfrey S G , Hegbrant J , Thysell H , Fox P A , Lendrem D W , Lockwood G F , Lasher K , Rogers J , Greenslade D 
Published: April 2011

Abstract
This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment.
All the patients were administered an intravenous loading dose of drug at 50 μg kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0·45 or 0·35 μg kg−1 min−1 for the moderate (chromium-EDTA clearance of 31–75 mL min−1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10–30 mL min−1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (± s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100–300 ng mL−1) for both groups, with values of 239 ± 71 ng mL−1 and 269 ± 32 ng mL−1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL−1, that were not associated with any serious adverse events. As predicted for this highly renally cleared drug, there were differences (P &lt; 0·001) in the total plasma clearance (CLP), renal clearance (CLr), and plasma terminal half-life (t1/2) of drug, with values in the severe group being 44% lower, 75% lower, and about 134% longer respectively, when compared with the moderate group. High (correlation coefficient &gt; 0·8) and significant correlations (P &lt; 0·001) were observed between CLP and CLr and the degree of renal impairment (chromium-EDTA clearance). The apparent volume of distribution was approximately 40% higher (P &lt; 0·01) in the severe group compared with that for the moderate group (moderates were 0·443 ± 0·155 L kg−1). This volume difference suggests a decrease in the plasma protein-binding of milrinone because of the renal disease. The fraction of drug excreted in the urine was 0·705 ± 0·100 for the moderate group and 0·320 ± 0·089 for the severe group (P &lt; 0·001).
These results may suggest an increase in non-renal clearance of the compound, representing a partial compensation mechanism for the reduced renal function. In conclusion, this study has confirmed that the current dose reductions recommended for the use of intravenous milrinone in CHF patients with impaired renal function will yield plasma concentrations of the drug within the therapeutic range.
The Influence of 17-β-Oestradiol and the Natural Oestrous Cycle on α-Adrenoceptor-mediated Responses of the Cardiovascular System in the Rat
Authors: Austin Clare , Chess-Williams Russell 
Published: April 2011

Abstract
The effect of 17β-oestradiol pretreatment and the natural oestrous cycle on responses of rat cardiac and vascular α-adrenoceptors was investigated.
It was found that treatment with the oestrogen had no effect on cardiac adrenoceptor sensitivity, while pretreatment with the hormone caused a significant increase in vascular α2-, but not vascular α1-adrenoceptor responsiveness. Pressor responses of pithed rats to selective oer or α2-adrenoceptor agonists did not alter, however, during the natural oestrous cycle.
These findings suggest that changes in oestrogen levels are capable of altering α-adrenoceptor-mediated vascular responses but that the relatively small changes in oestrogen which may occur throughout the natural oestrous cycle do not appear to alter the responses of these vascular α-adrenoceptors.
Mechanisms Involved in Electrically-induced Responses of Rat Seminal Vesicles
Authors: Sadraei Hassan , Large Bryan J , Hughes Ian E 
Published: April 2011

Abstract
Contractile responses of rat isolated seminal vesicle were elicited by electrical field stimulation (EFS, 10 Hz, 1 ms, 40 V for 5 s), noradrenaline (1 times 10−5 m) and carbachol (1 times 10−5 m).
Guanethidine (2 times 10−5−5 times 10−4 m) progressively reduced the contraction induced by EFS and carbachol to 24 ± 2 and 10 ± 2%, respectively, at the highest concentration (n = 6), while potentiating noradrenaline contraction to a maximum of 154 ± 14% at 2 times 10−5 m (n = 6). Prazosin (1 times 10−6 m) and atropine (2·5 times 10−7 m) completely abolished the response to the corresponding agonist and each reduced the response to EFS to 64 ± 8 and 61 ± 3%, respectively (n = 6). In the presence of both atropine and prazosin a small contraction to EFS remained (14 ± 4%, n = 6), which is unlikely to be due to ATP, since exogenous ATP did not induce a contractile response and had an inhibitory effect on EFS-induced responses. Clonidine (1·25 times 10−5 m) completely blocked responses to noradrenaline and reduced the response to EFS to 68 ± 7% (n = 6). However, when both the adrenergic and cholinergic components of EFS were blocked by prazosin and atropine, clonidine potentiated the remaining response to EFS (323 ± 82%, n = 4). Yohimbine (1 times 10−5 m) blocked the response to noradrenaline and reduced the response to EFS to 37 ± 5% (n = 6) while the carbachol response was unaffected. Both cholinergic and noradrenergic components contribute to the response to EFS but there appears to be little involvement of presynaptic α2-adrenoceptors in regulating neurotransmitter release.
The actions of clonidine and yohimbine are compatible with the suggestion that their effects are due to postsynaptic α1-adrenoceptor blockade.
The Involvement of Dipeptidyl Peptidase IV in Brush-border Degradation of GRF(1–29)NH2 by Intestinal Mucosal Cells
Authors: Bai Jane P F , Chang Li-Ling 
Published: April 2011

Abstract
GRF(1–29)NH2 is degraded mainly by dipeptidyl peptidase IV (DPP IV) in plasma, resulting in inactivated GRF(3–29)NH2. To understand whether improving stability of GRF(1–29)NH2 in the plasma will result in enhanced stability in intestinal mucosal cells, stability of GRF(1–29)NH2 and [desNH2Tyr1,d-Ala2,Ala15]-GRF(1–29)NH2 in rat intestine brush-border membrane and homogenate was examined.
[desNH2Tyr1,d-Ala2,Ala15]-GRF(1–29)NH2, resistant to plasma DPP IV, was much more stable than GRF(1–29)NH2 in enterocytes. Gradient HPLC analysis, mass balance analysis and studies of inhibitor effects revealed that GRF(3–29)NH2 was the major metabolite of GRF(1–29)NH2 due to the action of DPP IV during incubation with brush-border membranes.
It is concluded that the design of peptide analogues to resist plasma enzymes dramatically increases stability in intestinal epithelium.
Effects of Phorbol 12,13-Diacetate and Its Influence on Spasmogenic Responses in Normal and Sensitized Guinea-pig Trachea
Authors: De Diego A , Cortijo J , Villagrasa V , Perpiñá M , Esplugues J , Morcillo E J 
Published: April 2011

Abstract
We have studied the effects of phorbol 12,13-diacetate (PDA) and its influence on a variety of spasmogenic responses in trachea isolated in from normal and sensitized guinea-pigs.
Tracheal preparations were denuded of epithelium, treated with indomethacin (2·8 μm), and cooled to 20°C. In these experimental conditions, tracheal strips contracted to PDA (0·1 nm-1 μm). Contractions to PDA (1 μm) were greater in sensitized tissues. In normal trachea, contractions to PDA (0·1 μm) were depressed by H-7, 1-(5-isoquinolinyl-sulphonyl)-2-methylpiperazine, (50 μm), amiloride (10 μm), verapamil (10 μm) and Ca2+-free exposure. Similar effects were obtained in sensitized trachea except that PDA-induced contraction was resistant to verapamil and Ca2+-free exposure.
Cooling (20°C) of normal trachea substantially depressed the response to CaCl2 (in K+-depolarized tissues), KC1, histamine and 5-hydroxytryptamine without affecting the spasm induced by acetylcholine. This inhibitory effect of cooling was not observed in sensitized trachea. PDA (0·1 μm) did not affect spasmogenic responses at 37°C but counteracted the inhibitory effect of cooling in normal trachea. PDA had no effect on sensitized tissues. PDA (0·1-1μm) did not alter Ca2+-induced contraction of skinned normal and sensitized trachea.
These results support the hypothesis that intracellularly stored Ca2+ plays an important role in the activation of sensitized tracheal muscle.
Rat Tissue Concentrations of Chlorimipramine, Chlorpromazine and their N-Demethylated Metabolites after a Single Oral Dose of the Parent Compounds
Authors: Sgaragli Gian Pietro , Valoti Massimo , Palmi Mitri , Frosini Maria , Giovannini Maria Grazia , Bianchi Loria , Corte Laura Della 
Published: April 2011

Abstract
A single oral dose of 90 mg kg−1 chlorimipramine or chlorpromazine, corresponding to 54.5 or 55.9 μmol, respectively, was given to male Sprague-Dawley rats and concentrations of parent drugs and their N-desmethyl metabolites measured by gas chromatography in plasma and major organs (brain, liver, lung, kidney, heart, spleen and peritoneal fat).
In the case of chlorimipramine, N-desmethyl metabolite levels were consistently higher than those of the parent drug for the entire observation period of 24 h in all tissues except fat, while lower N-desmethyl metabolite/parent compound ratios were observed for chlorpromazine. N-Desmethyl metabolite kinetics of chlorimipramine appeared to be elimination-rate limited, while those of chlorpromazine were formation-rate limited. In all analysed organs, the maximum detectable drug + metabolite concentrations accounted for only 2·3 and 4·6% of the initial dose of chlorimipramine and chlorpromazine. Chlorpromazine treatment gave rise to an area under the total amount-time curve (AUC0–24) for parent drug + metabolites, 3·9-fold that for chlorimipramine. Closer scrutiny discloses a conversion ratio of parent compound to N-desmethyl metabolite of 1·1 for chlorpromazine and of 2·2 for chlorimipramine, indicating the greater efficiency of chlorimipramine metabolism in all compartments. The expected high conversion index found in the liver (2·3) reaches its maximum of 5·4 in the lung. Fractional data analysis of chlorimipramine and chlorpromazine distribution patterns revealed greater organ transfer for the N-desmethyl metabolites than for the more stably-located parent compounds. The N-desmethyl metabolites of chlorimipramine apparently moved from liver to lung, kidney and spleen, whereas N-desmethylchlor-promazine moved preferentially to the brain and lung tissue.
This single dose study of chlorimipramine and chlorpromazine kinetics, highlights the two distinct dispositional processes at work in the rat in all likelihood, attributable to different absorption patterns, to a slower metabolism and, thus, to the longer persistence of chlorpromazine.
Relaxant Effect of Tetrazepam on Rat Uterine Smooth Muscle: Role of Calcium Movement
Authors: Perez-Guerrero C , Herrera M D , Marhuenda E 
Published: April 2011

Abstract
Tetrazepam is a benzodiazepine derivative clinically used as a muscle relaxant. The aim of the present work was to examine its effect on uterine smooth muscle of the rat in estrus.
Tetrazepam required micromolar concentractions to relax contractile responses induced by KCl and acetylcholine in Ca2+ solution, but not oxytocin-induced contraction. In Ca2+-free solution, tetrazepam inhibited Ca2+-induced contractions in depolarized uterus and vanadate-induced contractions.
We suggest that tetrazepam relaxes contractile responses induced by activation of voltage-sensitive calcium channels and receptor-operated calcium channels with little selectivity or that it antagonizes the effect of calcium at subsequent steps, possibly intracellular stores sensitive to vanadate but not sensitive to oxytocin. The inhibition of contraction of rat uterus is not related to high-affinity peripheral benzodiazepine binding sites.
The Presence of Insulin-degrading Enzyme in Human Ileal and Colonic Mucosal Cells
Authors: Bai Jane P F , Hong Hae-Jin , Enberger David A Roth , Wong W Douglas , Buls John G 
Published: April 2011

Abstract
The aim of this research is to characterize the presence of insulin-degrading enzyme in human colon and ileal mucosal cells. Biochemical studies, including the activity-pH profiles, the effects of enzyme inhibitors, immunoprecipitation and western blots, were conducted.
The majority of insulin-degrading activity in colon mucosal cells was localized in the cytosol. In both colon and ileum, cytosolic insulin-degrading activities had a pH optimum at pH 7.5, and were extensively inhibited by each of N-ethylmaleimide, p-chloromercuribenzoate, and 1,10-phenanthroline, but were very weakly affected by each of leupeptin, chymostatin, diisopropyl phosphofluoridate and soybean trypsin inhibitor. In the colon and ileum, more than 93% and 96%, respectively, of cytosolic insulin-degrading activities were removed by the mouse monoclonal antibody to human RBC insulin-degrading enzyme, as compared with less than 20% by the normal mouse IgG for both tissues. Further, a western blot analysis revealed that a cytosolic protein of 110 kD, in both human colon and ileum, reacted with the monoclonal antibody to insulin-degrading enzyme.
It is concluded that insulin-degrading enzyme is present in the cytosol of human colon and ileal mucosal cells.