bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Age on Cardiovascular Effects of Increased Dietary Sodium and Angiotensin-converting Enzyme Inhibiton in Normotensive Wistar Rats
Authors: Teräväinen Terttu-Liisa , Mervaala Eero Ma , Laakso Juha , Paakkari Ilari , Vapaatalo Heikki , Karppanen Heikki 
Published: April 2011

Abstract
Recent studies have shown that increased intake of dietary sodium chloride produces blood pressure-independent increase in cardiac and renal mass even in young normotensive rats. With advancing age the harmful cardiovascular effects of increased dietary sodium are not so well known. In the present study the influence of advancing age on the cardiovascular effects of increased intake of sodium (control diet, 0.3% and high-sodium diet, 2.6% sodium in the chow) were examined in young and aged (3 and 18 months old, respectively, at the beginning of the experiment) male normotensive Wistar rats in a six-week study. Moreover, the potential role of renin-angiotensin system in ageing during normal and a high-sodium intake was studied using a pharmacological tool, angiotensin converting enzyme (ACE) inhibitor ramipril.
Ageing did not significantly modify basal systolic blood pressure measured by the tail cuff method. A high intake of sodium chloride increased blood pressure significantly only in aged rats, while in young rats it increased renal weight. Left ventricular weight was not affected by high-sodium diet in either age group. The ACE inhibition during control diet lowered blood pressure and decreased left ventricular weight in young rats only and these effects were completely blocked by a high-sodium diet. The maximal vascular contraction force of mesenteric arterial rings to noradrenaline was decreased with ageing while endothelium-dependent and -independent relaxation responses were unaltered with ageing. The sensitivity to sodium nitroprusside was impaired by the high-sodium diet in young rats. In both age groups the urinary excretion of calcium was increased during the high-sodium diet.
In conclusion, the increased intake of sodium produced different changes in cardiovascular function in normotensive rats depending on age. With advancing age, the sensitivity to sodium-induced increase in blood pressure was increased. In aged rats a high intake of dietary sodium elevated blood pressure, while in young rats it increased renal mass without increase in blood pressure. In both age groups sodium did not affect left ventricular hypertrophy. Both high-sodium intake and ageing attenuated or even abolished the cardiovascular effects of ACE inhibition.
Possible Involvement of Protein Kinase C in the Modulation of Inotropic and Chronotropic Effects Induced by Ouabain in Rat Right Atrial Muscles
Authors: Satoh Hiroyasu , Narushima Itaru , Nakashima Toshikatsu 
Published: April 2011

Abstract
Modulations of the inotropic and chronotropic effects of ouabain and protein kinase C (PKC) stimulation with phorbol esters in rat right atria were examined. Cumulative administration of ouabain (3–30 μm) caused a positive inotropic effect in a concentration-dependent manner, but did not produce a chronotropic effect. A single administration of ouabain (30 μm) also had similar effects: +744 ± 84% (n = 23, P &lt; 0.01) in the contractile force and −0.7 ± 1.3% (n = 23, P &gt; 0.05) in the sinus rate. Addition of phorbol esters reinforced the ouabain-evoked positive inotropic effect: 26.5 ± 8.9% (n = 6, P &lt; 0.05) with 100 μm 4-β-phorbol-12,13-dibutyrate (PDB), and 6.4 ± 3.3% (n = 6, P &gt; 0.05) with 100 μm 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Simultaneously, the mixture of ouabain and phorbol ester raised the resting tension. Phorbol esters alone caused a positive inotropic effect (by about 21–27%). Non-PKC activating phorbol ester, 4-α-phorbol-12,13-didecanoate (PDD, 100 μm), did not have any effect. Pretreatment with the PKC inhibitor (staurosporine 100 μm) significantly decreased the ouabain-induced positive inotropic effect and caused a negative chronotropic effect, but H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride) (5 μm) had no effect.
These results suggest that PKC stimulation may be involved in the ouabain-evoked responses in the right atria of rat as seen by increased cellular Ca2+ concentration (and Ca2+-sensitivity); thus the positive inotropic effect may not be due only to modulation of Na+/K+ pump activity.
Effects of Nonanal, trans-2-Nonenal and 4-Hydroxy-2,3-trans-nonenal on Cyclooxygenase and 12-Lipoxygenase Metabolism of Arachidonic Acid in Rabbit Platelets
Authors: Sakuma Satoru , Fujimoto Yohko , Tagano Shinya , Tsunomori Masahide , Nishida Hiroko , Fujita Tadashi 
Published: April 2011

Abstract
The effects of nonanal, trans-2-nonenal and 4-hydroxy-2,3-trans-nonenal on the formation of thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets were examined.
Nonanal and trans-2-nonenal at concentrations ranging from 0.25 to 2 μm inhibited TXB2, HHT and 12-HETE formation, reducing the amounts of these three arachidonic acid metabolites by 50% at nonanal and trans-2-nonenal concentrations of approximately 0.25 μm. The inhibition of TXB2, HHT and 12-HETE formation induced by 4-hydroxy-2,3-trans-nonenal (50% inhibition by 4-hydroxy-2,3-trans-nonenal at a concentration of approximately 100 μm) was 400 times weaker than that induced by nonanal and trans-2-nonenal.
These results suggest that nonanal and trans-2-nonenal can be modulators of platelet arachidonic acid metabolism by affecting the activity of cyclooxygenase and 12-lipoxygenase.
Epidural Metabolism of Articaine to its Metabolite Articainic Acid in Five Patients after Epidural Administration of 600 mg Articaine
Authors: Vree Tom B , van Oss Gertjan E C J M , Gielen Mathieu J M , Booij Leo H D J 
Published: April 2011

Abstract
The clinical pharmacokinetics, metabolism and renal excretion of articaine and its metabolite articainic acid have been investigated in man after epidural administration. (±)-Articaine and its metabolite (±)-articainic acid have different pharmacokinetic constants (P = 00079) except for lag-time (tlag; 0.06 min), first phase distribution of elimination (t½α; 0.49 ± 0.21 h), and elimination half life (t½α; 2.19 ± 0.98 h), which are all the same for both compounds. The total body clearance of articaine (103 ± 57 L h−1) is 10 times higher than that of the metabolite articainic acid (10.7 ± 1.80 L h−1, P = 0.0079). With similar half-life (t½β) values (2 h), the volumes of distribution (Vβ) are 10 times higher for the parent drug than for the metabolite ((329 ± 212 L compared with 38.4 ± 7.5 L, respectively; P = 0.0079). The difference between the areas under the curves for total plasma articainic acid and that formed in the plasma gives an indication of the percentage metabolism during epidural transfer (5.38 ± 1.51%). This percentage of metabolism corresponds to a mean epidural transfer time of 5 min. The main compound in the urine is articainic acid (64.2 ± 14.4%), followed by articainic acid glucuronide (13.4 ± 4.97%) and the parent drug (1.45 ± 0.77%). In total, 79.0 ± 18.5% of the dose is recovered in the urine. The renal clearance of articaine is 22.5 ± 13.9 mL min−1, whereas that of articainic acid is 119.6 ± 30.1 mL min−1 (P &lt; 0.0001). The apparent renal clearance of articainic acid glucuronide was 25.4 ± 12.0 mL min−1. This value does not differ from that of the parent drug (P &gt; 0.8). Articainic acid glucuronide is not present in plasma, but has an apparent renal clearance of 25 mL min−1.
These results suggest that articainic acid is glucuronidated by the tubular cells and then excreted.
Pharmacodynamic and Pharmacokinetic Studies in Rats of S-8-(2-Furyl)- and R-8-Phenyl-2-(di-n-Propylamino)Tetralin, Two Novel 5-HT1A Receptor Agonists In-vitro with Different Properties In-vivo
Authors: Yu Hong , Liu Ye , Li Hong B , Martin Arnold R , Hacksell Uli , Lewander Tommy 
Published: April 2011

Abstract
R- and S-8-(2-Furyl)- and R- and S-8-phenyl-2-(di-n-propylamino)tetralins (R- and S-LY-55 and R- and S-LY-49, respectively), novel enantiopure dipropylaminotetralins, have been screened as 5-HT1A receptor ligands.
All had nanomolar affinities for 5-HT1A receptors and fully inhibited forskolin-stimulated adenylyl cyclase in-vitro (i.e. the four compounds appeared to be 5-HT1A agonists). It was also found that the enantiomers of LY-55 behaved as typical 5-HT1A receptor agonists in rats in-vivo by inducing a typical behavioural 5-HT syndrome, hypothermia and a decrease in 5-HT synthesis and turnover, indicating effects both on postsynaptic 5-HT1A receptors and somatodendritic 5-HT1A autoreceptors. In contrast, R- and S-LY-49 did not cause any 5-HT1A receptor-related effects in-vivo except for a partial inhibition of 5-HT synthesis after high doses. The 5-HT1A receptor antagonist WAY-100635 was shown to attenuate the R-LY-49-induced inhibition of 5-HT synthesis, indicating the compound to be a weak agonist at somatodendritic 5-HT1A autoreceptors. R-LY-49 at a high dose and with a long pre-treatment time interval inhibited the hypothermic and behavioural effects, but not the inhibition of 5-HT synthesis induced by the 5-HT1A receptor agonist R-8-hydroxy-(dipropylamino)tetralin (R-8-OH-DPAT). Taken together, these findings seem to indicate, that R-LY-49 is a weak partial agonist at 5-HT1A receptors. A comparative pharmacokinetic study showed that the enantiomers of LY-55 entered the brain rapidly after subcutaneous administration and reached peak brain tissue/plasma concentration ratios within 15–30 min of injection, whereas the brain concentrations of R-LY-49 increased slowly, reaching a relatively low peak brain tissue/plasma concentration ratio 90 min after injection despite their similar lipophilicity.
The differences between the pharmacological activity of the two compounds in-vivo seem to be explained by their different abilities to cross the blood-brain barrier, and a weak agonistic activity of R-LY-49 on 5-HT1A receptors, both pre- and postsynaptically, compared with S-LY-55. Further studies are, however, needed for a deeper understanding of these differences.
Comparative Pharmacokinetics and Interspecies Scaling of Amphotericin B in Several Mammalian Species
Authors: Hutchaleelaha Athiwat , Chow Hsiao-Hui , Mayersohn Michael 
Published: April 2011

Abstract
This study employed several interspecies scaling methods, to evaluate the applicability of extrapolating to man, pharmacokinetic information obtained from animals for amphotericin B, an anti-fungal drug.
Pharmacokinetic parameters from four animal species (mouse, rat, monkey and dog) and man were obtained from the literature or from analysis of data reported in the literature. The allometric relationships (obtained from four animal species) as a function of species body weight (W; kg) for systemic clearance per maximum life span potential (CLS/MLP), steady-state volume of distribution (VSS), apparent volume of distribution (Vβ) and volume of the central compartment (VC) were: 5691W1.096; 2.46W0.839; 3.08W0.948 and 1.07W0.965, respectively. The allometric relationships for half-life (h) and mean residence time (h) did not scale well with body weight. The prediction of pharmacokinetic parameters in man from the allometric equations do not always agree with those reported in the literature which are based upon a limited number of studies with few human subjects. The plasma concentration-time profiles from these animals were adjusted by normalizing the concentration with dose/W0.948, and re-plotted on different pharmacokinetic time scales.
The syndesichrons plot produced an almost superimposable profile of adjusted concentrations as a function of adjusted time among the four species.
Ambroxol Improves the Broncho-spasmolytic Activity of Clenbuterol in the Guinea-Pig
Authors: Pairet Michel , Engelmann Peter , von Nicolai Hubertus , Champeroux Pascal , Richard Serge , Rauber Gerhard , Engelhardt Günther 
Published: April 2011

Abstract
The effects of ambroxol on the spasmolytic action of clenbuterol were investigated on acetylcholine-induced bronchospasm in guinea-pigs.
Ambroxol (50 mg kg−1 day−1) or vehicle was administered orally for 14 days. Approximately 45 min after the final dose on day 14, the animals were anaesthetized and the spasmolytic effects of clenbuterol (3, 6 or 12 μg kg−1 injected intravenously) were determined by use of acetylcholine (40 μg kg−1, i.v.)-induced bronchoconstriction. For both vehicle- and ambroxol-treated animals, a positive linear relationship was observed between the log-dose of clenbuterol and the percent inhibition of bronchospasm. The calculated ED25 of clenbuterol (i.e. the dose producing 25% inhibition of the acetylcholine-induced bronchospasm) was 3.98 μg kg−1 (3.29 to 4.82 μg kg−1, 95% confidence interval) in the presence of ambroxol and 5.81 μg kg−1 (4.98 to 6.79 μg kg−1) in the absence of ambroxol. The linear regressions with or without ambroxol differed from each other (P &lt; 0001) but ran parallel (covariance analysis), enabling us to calculate a relative potency, the value of which was 1.46 (1.16 to 1.84).
These results demonstrate that the spasmolytic activity of clenbuterol is significantly improved in animals pretreated with ambroxol.
Anti-ulcer Activity of Cromakalim (BRL 34915), a Potassium-channel Opener, Against Experimentally Induced Gastric and Duodenal Ulcers in Rats and Guinea-pigs
Authors: Goswami Sailendra , Jain Sunita , Santani Devdas 
Published: April 2011

Abstract
The effect of cromakalim, a potassium-channel opener, was studied on pylorus ligation-induced, aspirin-induced and water-immersion plus restraint stress-induced gastric ulcers in rats and on histamine-induced duodenal ulcer in guinea-pigs.
Pretreatment with cromakalim (50–500 μg kg−1, p.o.) resulted in a significant reduction in the incidence of gastric and duodenal ulceration in each model. The anti-ulcer activity of cromakalim was comparable with that of cimetidine. Cromakalim at 100, 250 and 500 μg kg−1 caused a reduction in the volume of the gastric content in pylorus-ligated rats, and a dose of 250 μg kg−1 resulted in a significant reduction in total acidity (28.81 ± 11.73 mEq L−1, P &lt; 0.02) in the pylorus ligation model. A significant reduction in total acid output was observed at doses of 250 μg kg−1 (84.27 ± 22.33 mEqH+, P &lt; 0.02) and 500 μg kg−1 (120.17 ± 24.49 mEq H+, P &lt; 001) in pylorus-ligated rats. A significant reduction in the ulcer index in pylorus-ligated rats was observed at all cromakalim doses: 50 μg kg−1 (0.23 ± 009, P &lt; 0.05), 100 μg kg−1 (0.15 ± 0009, P &lt; 0.02), 250 μg kg−1 (0.12 ± 0.05, P &lt; 0.01) and 500 μg kg−1 (0.14 ± 0.03, P &lt; 0.02). A significant reduction in the ulcer index of aspirin-treated rats was also observed at all cromakalim dose levels: 50 μg kg−1 (0.39 ± 0.03. P &lt; 0.01), 100 μg kg−1 (0.28 ± 0.06, P &lt; 0.01), 250 μg kg−1 (0.22 ± 0.04, P &lt; 0.001) and 500 μg kg−1 (0.28 ± 0.03, P &lt; 0.01). In the water-immersion plus restraint stress-induced gastric ulcer model, cromakalim significantly reduced gastric ulceration at all the dose levels: 50 μg kg−1 (28.2 ± 2.12, P &lt; 0.001), 100 μg kg−1 (20.24 ± 1.71, P &lt; 0.01), 250 μg kg−1 (19.95 ± 1.46, P &lt; 0.001) and 500 μg kg−1 (21.61 ± 3.00, P &lt; 0.001) but there was no consistent reduction of gastric bleeding. In addition to gastric ulcers, duodenal lesions were also reduced by pretreatment with cromakalim at all dose levels: 50 μg kg−1 (97.87 ± 20.03 mm2, P &lt; 0.02). 100 μg kg−1 (70.72 ± 12.82 mm2, P &lt; 0.02), 250 μg kg−1 (48.32 ± 8.42 mm2, P &lt; 0.01) and 500 μg kg−1 (55.50 ± 12.50 mm2, P &lt; 0.01). Cromakalim at a dose of 100 μg kg−1 also reduced total acidity (99.36 ± 9.12 mEq L−1, P &lt; 0.02) and total acid output (172.22 ± 45.33 mEq of H+, P &lt; 0.05) in this model.
These findings demonstrate the anti-ulcer activity of cromakalim in different experimental models and suggest its potential use in ulcer therapy.
Effects of Selective β-Adrenoceptor Antagonists on Gastric Ulceration in the Rat
Authors: Kaan Sheung Kei , Cho Chi Hin 
Published: April 2011

Abstract
Metoprolol and butoxamine, β-adrenoceptor antagonists which act selectively at the β1 and β2-adrenoceptors, respectively, have been investigated for their actions on the ethanol, indomethacin and cold-restraint stress ulcer models.
Oral administration of butoxamine but not metoprolol significantly attenuated gastric mucosal damage in the three types of ulcer model. Intraperitoneal injection of butoxamine reduced indomethacin ulceration but not that of the other two models. The stimulatory effect of butoxamine on the gastric mucosal potential difference and intramucosal mucus level correlated positively with its anti-ulcer action. Only oral administration of butoxamine significantly increased the mucosal prostaglandin E2 (PGE2) level but not after intraperitoneal injection. Oral administration of butoxamine also significantly increased the mucosal PGE2 level in the three types of ulcer model but this drug was only effective in the indomethacin ulcer model after intraperitoneal injection. Gastric acid and pepsin output were not affected by either drug. Metoprolol significantly reduced systemic blood pressure; this could be attributed to a reduction in gastric mucosal blood flow.
These results imply that β2-adrenoceptors play a significant role in the pathogenesis of gastric ulceration. We suggest that the anti-ulcer effect of butoxamine was in part a result of strengthening of the mucosal barrier but that this was not effected by modification of acid or pepsin secretions in the stomach. Stimulation of PGE2 in the gastric mucosa could contribute in part to the anti-ulcer action of the drug, especially when given by the oral route.
Antagonistic Effects of OPC-14597, a Novel Antipsychotic Drug, on Quinpirole- and (–)-Sulpiride-induced Changes in Evoked Dopamine Release in Rat Striatal Slices
Authors: Yamada Shigeto , Harano Mutsuo , Yokoo Hideyasu , Tanaka Masatoshi 
Published: April 2011

Abstract
The effects of a newly synthesized quinolinone derivative, 7-{4-(4-(2,3-dichlorophenyl)-1-piperazinyl) butoxy}-3,4-dihydro-2-(1H)-quinolinone (OPC-14597), a novel antipsychotic drug, on electrically evoked dopamine release in rat striatal slices were investigated.
OPC-14597 (0.1–10 μm) had no effect on the dopamine release evoked in the striatal slices. The decrease induced by quinpirole, a dopamine receptor agonist, in evoked dopamine release was attenuated by supervision with OPC-14597 (1 and 10 μm) which by itself had no effect on evoked dopamine release. The increase induced by (–)-sulpiride, a dopamine receptor antagonist, in evoked dopamine release was, moreover, also attenuated by 1 and 10 μm OPC-14597.
These findings indicate that OPC-14597 antagonizes both dopamine agonist- and antagonist-induced changes in evoked dopamine release in striatal slices in rats.
Antiperoxidative Activity of Neolignans from Magnolia obovata
Authors: Haraguchi Hiroyuki , Ishikawa Harumi , Shirataki Noritoshi , Fukuda Ayumi 
Published: April 2011

Abstract
Honokiol and magnolol, neolignans in Magnolia obovata, have been evaluated as antioxidants.
Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH and mitochondrial lipid peroxidation induced by Fe(III)-ADP/NADH were inhibited by these compounds. These neolignans protected mitochondrial respiratory chain enzyme activity against NADPH-induced peroxidative stress and protected red cells against oxidative haemolysis. The anti-oxidative activity of honokiol was more potent than that of magnolol.
Neolignans in M. obovata were shown to be effective in protecting biological systems and functions against oxidative stress.
Enhanced Anti-tumour Effects of Acriflavine in Combination with Guanosine in Mice
Authors: Kim Sang Geon , Kim Choon Won , Ahn E-Tay , Lee Kyung-Yung , Hong Eun-Kyung , Yoo Bo-Im , Han Yung-Bok 
Published: April 2011

Abstract
The anti-tumour activity of acriflavine in combination with guanosine has been evaluated in solid or ascitic tumour-implanted animal models. Guanosine is known to potentiate the anti-tumour effects of some chemotherapeutic agents.
Administration of acriflavine (15 mg kg−1 day−1, i.m., 14 days) to ICR mice subcutaneously implanted with Ehrlich carcinoma resulted in ∼30% inhibition in tumour growth. In contrast, minor tumour growth inhibition was observed in animals treated with guanosine at the same daily dose. Treatment of animals with both acriflavine and guanosine (AG60, 1:1, w/w) at 30 mg kg−1 resulted in ∼65% inhibition in tumour growth rate. Whereas treatment with acriflavine or guanosine resulted in 70% or 30% decrease in tumour weight, respectively, treatment of tumour-implanted mice with AG60 (30 mg kg−1) resulted in a 96% decrease in tumour weight, relative to control, 14 days after tumour-cell implantation. Dose-related inhibition in tumour growth rate was also observed in animals treated with AG60, with maximum (65%) inhibition noted at a dose of 30 mg kg−1 (ED50 23 mg kg−1). Suppression of body weight increase and elevated plasma glucose levels by acriflavine or AG60 indicated that glucose utilization might be impaired. The anti-tumour effect of AG60 was also determined in CDF1 mice intraperitoneally implanted with Ehrlich ascitic tumour. Ehrlich ascitic tumour proliferation was completely suppressed by AG60 (30 mg kg−1, i.p.). Microscopic analyses of intraperitoneal touch-prints revealed that AG60 was more effective in suppressing tumour proliferation than acriflavine alone. Fluorescent microscopic examinations demonstrated that acriflavine avidly bound with Yac-1 cell plasma membrane, leading to morphological changes in the cells, such as bleb formations, swelling and ballooning. The time-related changes in tumour cell morphology by acriflavine or AG60 might represent energy depletion, followed by osmotic lysis as a result of cationic influx. Enhanced anti-tumour activity of acriflavine in combination with guanosine might be explained by the blocking of nutrient transport through selective acriflavine binding with plasma membrane and by concomitant guanosine perturbation of cellular ATP production.
This study demonstrates that guanosine enhances the anti-tumour effects of acriflavine against a variety of cancer cells without serious adverse effects, providing a preclinical basis for potential application of this combination against cancer proliferation.
In-vitro Interaction of Artemisinin with Intact Human Erythrocytes, Erythrocyte Ghosts, Haemoglobin and Carbonic Anhydrase
Authors: Bakhshi Hamid B , Gordi Toufigh , Ashton Michael 
Published: April 2011

Abstract
The kinetics of the interaction of the antimalarial compound artemisinin with human erythrocytes, erythrocyte ghosts, haemoglobin and carbonic anhydrase were evaluated in-vitro. Artemisinin plasma concentrations, measured by HPLC (high pressure liquid chromatography), decreased with time during incubations with whole blood and erythrocyte suspensions of varying haematocrit. Artemisinin concentrations declined more rapidly during incubations under oxygen-poor as compared to oxygen-rich conditions. Artemisinin concentrations did not decrease during incubation with erythrocyte ghosts suspended in plasma suggesting that the drug does not bind avidly to red blood cell membranes. There was no decline in concentrations of artemisinin in the presence of carbonic anhydrase. The disappearance of the drug in solutions containing haemoglobin was very rapid and was even more so when the incubation was performed under an argon- instead of oxygen-rich atmosphere. The results suggest that drug blood clearance may be considered for inclusion in a pharmacokinetic model, but does not invalidate in-vivo plasma concentration-time data and their relevance for clinical effects. Furthermore, caution is advised when relating measurements of in-vitro potency to drug levels in patients. Finally, the enhanced artemisinin disappearance when oxygen tension is low may contribute towards the explanation of the selective toxicity of the endoperoxide drugs to Plasmodium falciparum parasite.