bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Spasmogenic and Relaxant Responses in Aortae from C57/BL/KsJ Diabetic Mice with Those from Their Non-Diabetic Litter Mates
Authors: Piercy V. , Taylor S.G. 
Published: April 2003

We have investigated the responsiveness of thoracic aorta from the C57/BL/KsJ-<i>db/db</i> mouse (a model of type II diabetes) using a small-vessel myograph. The maximum tension developed in response to phenylephrine was greater in diabetic mice compared with non-diabetic (+/?) mice (2.7 ± 0.1 and 1.8 ± 0.1 mN/mm, respectively). Responses to phenylephrine were enhanced in tissues from both phenotypes when pre-incubated with <i>L</i>-NAME (100 µmol/l) and after the addition of oxyhaemoglobin (3 µmol/l), suggesting that endogenous NO release occurs in both. The maximum relaxation to carbachol was less in <i>db/db</i> mice (32 ± 4%) than in +/? mice (49 ± 5%) whilst that to sodium nitroprusside was similar (>90%). However, the concentration-effect curve to both vasorelaxants in <i>db/db</i> mice lay to the right of that in the +/? mice. These results suggest that the responsiveness of the vasculature is altered in the <i>db/db</i> mouse. Since this mouse is a model of type II diabetes this may be a consequence of hyperglycaemia and/or insulin resistance.
Morphometric and Functional Changes of Rat Pituitary Somatotropes and Lactotropes after Central Administration of Somatostatin
Authors: Milošević Verica , Brkić Branislava , Velkovski S.D. , Sekulić Milka , Lovren Mirjana , Starčević Vesna , Severs W.B. 
Published: April 2003

This study examined effects of intracerebroventricularly (i.c.v.) administered somatostatin (SRIH-14 and SRIH-28) on growth and function of pituitary somatotropes (GH cells) and lactotropes (PRL cells). Male rats received three i.c.v. injections (1 µg/5 µl) of SRIH-14 or SRIH-28 every second day. Blood samples were collected for hormone assays and pituitaries were removed for histological and morphometric evaluation 5 days after the last i.c.v. treatment. Compared to control animals, SRIH treatment decreased (p < 0.05) pituitary weight and all morphometric measurements obtained in GH and PRL cells. Concentrations of serum growth hormone (GH) and prolactin (PRL) in both SRIH-treated groups were also lower (p < 0.05) than in control rats. These findings suggest that centrally administered somatostatin is specifically involved in the control of growth and secretory activity of GH and PRL cells. Thus, pharmacological manipulation of SRIH receptors reached from cerebrospinal fluid may alter systemic effects of GH and PRL.
Bopindolol: A Slowly Dissociating Antagonist from the β-Adrenoceptors in Guinea Pig Atria
Authors: Hosohata Yoshiaki , Hattori Kaoru , Shen Yang , Okuyama Masahiro , Kaneko Hiroyuki , Ohnuki Toshio , Suzuki Jun , Nagatomo Takafumi 
Published: April 2003

The dissociating and/or residual inhibitory effects of bopindolol from β-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10<sup>–9</sup> to 10<sup>–8</sup> mol/l) and the active metabolite 18-502 (10<sup>–9</sup> mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10<sup>–7</sup> mol/l) and metabolite 18-502 (10<sup>–8</sup> and 10<sup>–7</sup> mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD<sub>2</sub> values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10<sup>–7</sup> mol/l) and propranolol (10<sup>–7</sup> and 10<sup>–8</sup> mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10<sup>–7</sup> mol/l) and propranolol (10<sup>–6</sup> mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10<sup>–5</sup> mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive β-antagonists rather than easily reversible β-adrenoceptor antagonists.
Subacute Cocaine Treatment Changes Expression of Mouse Liver Cytochrome P450 Isoforms
Authors: Powers James F. , Shuster Louis 
Published: April 2003

Acute administration of single high doses of cocaine (50 or 60 mg/kg) produces liver injury in mice that have been pretreated with inducers of mixed function oxidases. Multiple low doses of cocaine (10–30 mg/kg) will produce hepatotoxicity without prior induction. To establish whether cocaine can induce its own activation, mice were given three daily injections of cocaine. Total cytochrome P450 content of the liver did not change. After 3 days the amount of cytochrome P450 2B10, as measured by pentoxy resorufin-O-dealkylase activity and immunoblotting, increased 3-fold. Cytochrome P450 2A5-catalyzed coumarin 7-hydroxylase activity and immunoreactive protein increased by about 50%. Enzyme activities and Western blotting of isoforms 1A, 2E, and 3A showed no change during this time. Chronic cocaine increased N-hydroxylation of norcocaine. Immunoinhibition studies showed that cytochrome P450 2A5 was the major isoform responsible for norcocaine N-hydroxylation. These results demonstrate that chronic cocaine can induce its own metabolism. Similar increases were also observed in mice not susceptible to liver injury from chronic cocaine.
Effect of Am-80, a Synthetic Derivative of Retinoid, on Experimental Arthritis in Mice
Authors: Nagai Hiroichi , Matsuura Satoko , Bouda Keiko , Takaoka Yuko , Wang Ting , Niwa Satoru , Shudo Koichi 
Published: April 2003

Am-80 is a newly snythesized retinoid with the structure of one aromatic amide among retinobenzoic acids. It exhibits specific biological activities of retinoic acid such as the activation of cellular differentiation and proliferation. We investigated the effect of Am-80 on collagen-induced arthritis (CIA) in mice and the immunopharmacological action on the production of several cytokines in the in vitro and in vivo models. Am-80, at doses of 0.3, 1 and 3 mg/kg, significantly inhibited the severity and development of the arthritis index, progression of foot pad swelling, bone damage and histopathological alterations. Am-80 also inhibited the production of anti-type II collagen (CII) IgG antibody, but did not affect the delayed-type hypersensitivity (DTH) response in arthritic mice. To determine the inhibitory mechanism of Am-80, we studied the effect of Am-80 on the production of cytokines. Am-80 did not affect the production of IFN-γ by Th1 cells (1E10.H2 cells) and IL-4 by Th2 cells (D10.G4.1 cells), respectively. Am-80 selectively inhibited bacterial lipopolysaccharide (LPS)-induced IL-6, but not TNF-α and IL-1β, production in mice. Moreover Am-80 inhibited IL-1β induced IL-6 production and IL-6 mRNA expression in human osteoblast-like cells (MG-63). The inhibition of IL-6 production by Am-80 was due to downregulation of the pretranscription or the transcription of IL-6 in MG 63 cells. These findings suggest that the inhibitory effect of Am-80 on CIA is partially by modulating the production of the proinflammatory cytokine, IL-6.
Effects of Losartan on the Sexual Behavior of Male Rats
Authors: Chan Paul , Liu Ju-Chi , Tong Yat-Ching , Chen Yi-Jen , Wang Chia-Chen , Tomlinson Brian , Cheng Juei-Tang 
Published: April 2003

Many commonly used antihypertensive drugs such as diuretics and beta-blockers can interfere with sexual function in both sexes, causing loss of libido, impairment of erectile function and ejaculation in men, and delay or prevent orgasm in women. Newly developed antihypertensive drugs should ideally not interfere with the patients’ quality of life including sexual function. This study examined the effects of losartan, a nonpeptide, specific antagonist for type I angiotensin II receptors, on the male sexual behavior of rats. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were treated with losartan 30 mg/ kg/day or saline control for 7, 30 and 90 days. Dark-cycle video recording was used to analyze the male sexual activities of the rats. No significant alteration in male sexual performance was observed after 7 and 30 days of treatment with losartan. In contrast, SHRs treated with propranolol 5 mg/kg/day showed increases in intromission latency, ejaculation latency and postejaculatory period indicating decreased libido and erectile and ejaculatory function. Upon completion of 90 days of losartan administration, the mount latency of the SHR was significantly increased, suggesting a decrease in libido although other parameters were unchanged and there was no effect in WKY rats. It is therefore concluded that losartan may have an advantage in preservation of sexual function when used clinically for the treatment of hypertensive disorders.
Misoprostol-Inhibited Rat Gastric Emptying Is Independent of Gastric Inhibitory Polypeptide Release
Authors: Chang Full-Young , Chen Tseng-Shing , Lee Shou-Dong , Doong Ming-Luen , Wang PaulusS. 
Published: April 2003

We studied the effects of orally or intraperitoneally administrated misoprostol on rat gastric emptying and looked what was the role of gastric inhibitory polypeptide (GIP) in this emptying. The rats initially received oral misoprostol at doses of 1, 10, 50, and 100 μg/kg. Another group of rats received misoprostol intraperitonally at doses of 10, 50, 250, and 500 μg/kg. Using an oral radiochromium motility marker, the liquid gastric emptying was measurement 30 min after misoprostol treatment. The plasma GIP levels were measured by a home-made radioimmunoassay kit. Oral treatments at the doses of 1 and 10 μg/kg did not influence emptying, whereas other doses delayed emptying (p < 0.01). Except the 10- μg/kg injection, other doses exhibited a dose-dependent inhibition in emptying (p < 0.01). Neither oral feeding nor intraperitoneal injection changed plasma GIP levels. We conclude that liquid gastric emptying is disturbed after various routes of misoprostol treatment; GIP appears less important in the misoprostol-mediated gastric emptying.
Histamine H<sub>2</sub> Receptor Antagonism by T-593: Studies on cAMP Generation in Hepa Cells Expressing Histamine H<sub>2</sub> Receptor
Authors: Tashiro Takao , Ono Kageyoshi , Watanabe Tsuyoshi , Inoie Masukazu , Arai Hirotoshi , Kimura Satoshi , Kurokawa Kiyoshi 
Published: April 2003

Histamine H<sub>2</sub> receptor antagonism by T-593 was investigated in Hepa cells expressing canine histamine H<sub>2</sub> receptors. T-593 inhibited generation of cAMP in Hepa cells stimulated by 10<sup>–5</sup> mol/l histamine with an IC<sub>50</sub> value of 2.3 × 10<sup>–6</sup> mol/l, <i>(S)</i>-(–)-T-593, one of the enantiomers comprising racemic T-593, inhibited cAMP generation with an IC<sub>50</sub> value of 6.1 × 10<sup>–7</sup> mol/l. On the other hand, the other enantiomer <i>(R)</i>-(+)-T-593 exhibited only a negligible effect. Incubation of the cell with <i>(S)</i>-(–)-T-593 for 60 min depressed the maximal response of the concentration-response curve of histamine with a nonparallel rightward shift. The slope of a Schild plot was 1.27. In contrast, <i>(S)</i>-(–)-T-593 caused a parallel rightward shift of the curve, with a Schild plot slope that did not significantly differ from unity, by treating the cells for 15 min. The H<sub>2</sub> receptor-blocking action of <i>(S)</i>-(–)-T-593 remained almost unaffected after washing out the drug, whereas the effect of ranitidine was reversible after washing. These results suggest that T-593 possesses a time-dependent unsurmountable antagonistic action against histamine H<sub>2</sub> receptor. T-593 may interact with the histamine H<sub>2</sub> receptor molecule in a slowly associable and dissociable manner.
Effects of Green Tea Catechins on Membrane Fluidity
Authors: Tsuchiya Hironori 
Published: April 2003

Catechins originating from green tea have been used in plaque inhibition for caries prevention and treatment for liver damage because of their antibacterial activity against cariogenic bacteria and protective activity on hepatic cells. The effects of catechins on membrane fluidity were studied by a fluorescence polarization method using liposomes prepared with dipalmitoylphosphatidylcholine and dioleoylphosphatidylcholine to assess their pharmacological mechanism at μmol/l levels found in human body fluids after clinical application. All eight catechins tested, ranging from 1 to 1,000 μmol/l, significantly reduced membrane fluidity in both hydrophilic and hydrophobic regions of lipid bilayers. Catechin gallate esters were superior in fluidity reduction to the corresponding nonesters. The fluidity-reducing degree was different between the <i>cis</i> and <i>trans</i> forms, suggesting the stereospecific activity of catechins. A reference antiplaque agent, chlorhexidine, similarly reduced membrane fluidity at the antibacterial concentration. (+)-Catechin (250 μmol/l) and (–)-epigallocatechin gallate (2.5 μmol/l) significantly prevented the membrane fluidization induced by hepatotoxic chloroform. These results indicate that the reduction in membrane fluidity is responsible for the antiplaque and hepatoprotective effects of green tea catechins.
Effects of Mannitol and Dimethylthiourea on <i>Helicobacter pylori</i>-Induced IL-8 Production in Gastric Epithelial Cells
Authors: Kim Hyeyoung , Seo Jeong Yeon , Kim Kyung Hwan 
Published: April 2003

The present study aims at investigating the effects of mannitol and dimethylthiourea, known hydroxyl radical scavengers, on lipid peroxidation as an indicative of oxidative damage, NF-κ B activation and IL-8 production by <i>Helicobacter pylori</i> in gastric epithelial cells. A human gastric epithelial cell line, AGS, treated with or without mannitol and dimethylthiourea, was incubated in the absence or the presence of <i>H. pylori.</i> As a result, <i>H. pylori</i> significantly stimulated the productions of lipid peroxide and IL-8. Treatment with <i>H. pylori</i> resulted in the activation of two species of NF-κ B dimers (a p50/p65 heterodimer and a p50 homodimer). Mannitol and dimethylthiourea significantly inhibited lipid peroxide production, NF-κ B complex formation and IL-8 production by <i>H. pylori.</i> In conclusion, mannitol and dimethylthiourea may attenuate <i>H. pylori</i>-induced gastric inflammation by inhibiting lipid peroxidation and NF-κ B activation and thereby decreasing IL-8 production.
Changes of Superoxide Dismutase in Cultured Rat Aortic Smooth Muscle Cells (A7r5) by an Incubation of Vitamin E
Authors: Huang Wen-Pin , Chan Paul , Chen Yi-Jen , Chen Chi-Ming , Liao Shue-Sen , Chin Wan-Tai , Cheng Juei-Tang 
Published: April 2003

Supplementation of antioxidants such as vitamin E and vitamin C as health promotion food is popular recently. Epidemiological studies supported the beneficial effect of these antioxidants because oxygen free radicals have been linked to the process of diseases and aging. The present study evaluated the effect of α-tocopherol (vitamin E) on the changes of superoxide dismutase (SOD) in cultured rat aortic smooth muscle cells (A7r5) after a short-term (2 days) or long-term (7 days) incubation. Incubation of A7r5 cells with vitamin E at a concentration of 50 μmol/l for 2 days caused an increase of both the activity and mRNA level of SOD. At higher concentrations, such as 100 or 200 μmol/l, vitamin E failed to enhance SOD more effectively. However, after incubation for 7 days, vitamin E caused a decrease in both the activity and mRNA level of SOD in a concentration-dependent manner. Otherwise, the protein amount of SOD remained the same in these samples regardless of the concentration of vitamin E or the duration of incubation. The obtained results suggest that vitamin E can increase the effect of SOD to result in the beneficial influence of this antioxidant only at low concentration under a short-term supplementation because a down-regulation of SOD was observed in cells receiving a long-term incubation.
Renal Vascular Reactivity to P<sub>2</sub>-Purinoceptor Activation in Spontaneously Hypertensive Rats
Authors: Fernández Oscar , Wangensteen Rosemary , Osuna Antonio , Vargas Félix 
Published: April 2003

This study was performed to determine the possible contribution of an imbalance between P<sub>2X</sub> (vasoconstriction) and P<sub>2Y</sub> (vasodilation)-purinergic reactivity to the increased vascular resistance of spontaneously hypertensive rats (SHR). The vasoactive responses to α,β-methylene ATP and 2-methylthio ATP specific agonists, respectively, for P<sub>2X</sub> and P<sub>2Y</sub> purinergic receptors were characterized in isolated perfused kidneys from Wistar Kyoto (WKY) and SHR. To analyze P<sub>2X</sub>- and P<sub>2Y</sub>-purinergic reactivity we used phenylephrine and barium chloride, or acethylcholine (ACh) and sodium nitroprusside (NP) as reference compounds, respectively. The renal vasculature from SHR showed markedly enhanced reactivity to α,β-methylene ATP, phenylephrine and barium chloride. The dose-response curves were characterized by a similar threshold, with a greater maximal response. There were no significant differences in the dose-response curves or in maximal vasodilation to 2-methylthio ATP, ACh or NP when both groups were compared, except at the dose of 10<sup>–6</sup> g/g kidney weight of NP in which the SHR group showed an increased responsiveness. The results indicate that the increased responsiveness of kidneys from SHR to α,β-methylene ATP may be due to nonspecific functional changes in the renal vasculature rather than to a specific alteration in the activity of renal P<sub>2X</sub>-purinoceptors. Our results also indicate that P<sub>2Y</sub>-purinergic reactivity, nitric oxide-induced vasodilation and the cGMP-dependent mechanisms of vasodilation are well preserved in SHR.
Differential Effect of Antiallergic Drugs on IgE-Mediated Cutaneous Reaction in Passively Sensitized Mice
Authors: Satoh Taku , Tahara Eiichi , Yamada Tomohiro , Watanabe Chie , Itoh Takashi , Terasawa Katsutoshi , Nagai Hiroichi , Saiki Ikuo 
Published: April 2003

We investigated the effect of several antiallergic agents on murine IgE-mediated biphasic cutaneous reaction. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (anti-DNP) IgE antibody. Skin reaction was elicited by an epicutaneous challenge of dinitrofluorobenzene (DNFB) and occurred biphasically with immediate-phase response (IPR) and late-phase response (LPR) at 1 and 24 h, respectively. Classical histamine H1 receptor antagonists and some chemical mediator-release inhibitors, such as diphenhydramine and terfenadine, inhibited IPR, but not LPR. In contrast, leukotriene B<sub>4</sub> (LTB<sub>4</sub>) receptor antagonist (ONO-4057) inhibited LPR only. Antagonists for LTC<sub>4</sub>, D<sub>4</sub>, E<sub>4</sub> receptor (ONO-1078) and platelet-activating factor (PAF) receptor (Y-24180) significantly inhibited both IPR and LPR, similarly to prednisolone. We recently found that a third-phase inflammatory reaction with marked infiltration of eosinophils (named very-late-phase response; vLPR), which is supposed to be a more important reaction in allergic diseases, was induced, peaking at day 8 following IPR and LPR in this model. The effect of these drugs on the triphasic skin reaction can be scored based on efficacy against IPR / LPR / vLPR; +/+/+ (prednisolone, a PAF receptor antagonist Y-24180, cyclosporin A and FK-506), +/–/– (diphenhydramine), +/+/– (azelastine and LT receptor antagonist ONO-1078), and –/+/+ (an LTB<sub>4</sub> receptor antagonist ONO-4057). Thus the inhibitory effect on vLPR as well as LPR may relate to the inhibition of eosinophil function mediated by LTB<sub>4</sub> and PAF and/or T cells. These findings may provide the basis for a treatment modality using various antiallergic agents in allergic disease.
Pharmacological Properties of the Gastric H<sup>+</sup>/K<sup>+</sup> ATPase Inhibitor, AU-461
Authors: Cheon Hyae Gyeong , Kim Hyun Jung , Mo Hye Kyoung , Lee Byoung Ho , Choi Joong-Kwon 
Published: April 2003

AU-461 (1-(2-methyl-4-methoxyphenyl)-4-[(2-hydroxyethyl)amino]-6-β,β,β-trifluoroethoxy-2,3-dihydropyrrolo[3,2-c]quinoline) was tested for its ability to act as an anti-ulcer agent. AU-461 inhibited gastric H<sup>+</sup>/K<sup>+</sup> ATPase activities with IC<sub>50</sub> values of 12.15 and 4.20 μmol/l for rabbit and pig enzymes, respectively. The inhibition was reversible, and competitive with respect to the activating cation K<sup>+</sup>. When AU-461 was examined for the in vivo antisecretory activity, we found that AU-461 reduced the histamine-stimulated acid secretion as well as the basal secretion in rat stomach. Duration of the antisecretory effect was about 6 h upon oral administration. AU-461 prevented dose-dependently the ulcer formation produced by either ethanol or NaOH. This protective effect was not altered by indomethacin pretreatment. In addition, the elevated plasma gastrin by the oral administration of AU-461 was returned to control by 12 h. Taken together, these results suggest that AU-461 could be developed as a new therapeutic agent for peptic ulcer disease.
Decreasing Cyclic GMP Exerts Similar Positive Functional Effects on Cardiac Myocytes Regardless of Initial Level
Authors: Yan Lin , Huang Mark W. , Scholz Peter M. , Weiss Harvey R. 
Published: April 2003

We tested the hypothesis that lowering the level of cyclic GMP would have positive functional effects on isolated rabbit ventricular myocytes regardless of the basal cyclic GMP level. Cell shortening data were collected with a video detector; O<sub>2</sub> consumption data were obtained with a Clark electrode; intracellular cyclic GMP levels were obtained by radioimmunoassay. Data were obtained: (1) at baseline; (2) after the addition of 1H-[1,2,4]oxadiazolo[4,3-α]quinoxaline-1-one (ODQ) 10<sup>–6</sup> and 10<sup>–4</sup> mol/l, a selective soluble guanylyl cyclase inhibitor, and (3) after zaprinast 10<sup>–6</sup> mol/l, a cyclic GMP phosphodiesterase inhibitor, followed by ODQ 10<sup>–6</sup> and 10<sup>–4</sup> mol/l. We found that ODQ 10<sup>–4</sup> mol/l significantly decreased the cyclic GMP level from 493 ± 75 to 301 ± 78 (fmol/100,000 myocytes) and increased percent shortening (Pcs, %; 4.9 ± 0.3 vs. 5.8 ± 0.6) and maximum rate of shortening (Rs, μm/s; 58.7 ± 5.7 vs. 73.6 ± 4.9). Zaprinast significantly increased the cyclic GMP level from 419 ± 140 to 599 ± 241 and decreased Pcs (6.2 ± 0.5 vs. 4.4 ± 0.4) and Rs (65.5 ± 5.3 vs. 49.6 ± 4.3). After zaprinast, ODQ 10<sup>–4</sup> mol/l decreased the cyclic GMP level to 439 ± 139 and increased percent shortening and rate of shortening by a similar percentage compared to the non-zaprinast treated myocytes. We conclude that in rabbit ventricular myocytes, a reduction in the level of myocyte cyclic GMP increases myocyte function independent of the initial cyclic GMP level.