bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of pravastatin and cholestyramine on triglyceride‐rich lipoprotein particles and Lp(a) in patients with type II hypercholesterolemia
Authors: Barbi Giorgio , Corder Clinton N. , Koren Eugen , McConathy Walter , Ye S. Q. , Wilson Paul 
Published: January 2005

AbstractThe effects of treatment, on plasma lipids in patients with Type II hypercholesterolemia, for 8–24 weeks was determined with pravastatin (PR) and cholestyramine (CH) given alone or in combination. The first 8 weeks of treatment included a parallel placebo (P) control, while the subsequent period to 24 weeks compared four groups (40 and 80 mg PR, CH, and PR + CH). There were seven to nine patients per group (average age of 58 years). Cholesterol (C) and low‐density lipoprotein cholesterol (LDL‐C) decreased with PR and CH. There were inconsistent and nonsignificant effects on triglycerides and high‐density lipoprotein cholesterol (HDL‐C). Apolipoproteins A‐I, A‐II, B, and Lp(a) were measured, and only Apo‐B decreased with drug therapy. Lipoprotein particles characterized by their specific apolipoprotein content were also measured. LpB Cholesterol ester‐rich, containing predominantly Apo‐B, decreased with PR and CH relative to their respective baselines, but not relative to P. Similarly, triglyceride‐rich, LpBc, a complex lipoprotein particle containing apolipoproteins A‐I, A‐II, B, C, D, and E decreased relative to baseline, but not with respect to P. This study has further defined the effect of PR and CH on lipids and lipoprotein particles in patients with Type II hypercholesterolemia. These effects might be favorable in relation to reduction of risk factors in atherosclerosis. © 1992 Wiley‐Liss, Inc.
Memory‐enhancing effect of a cerulein analogue following peripheral administration in the rat
Authors: Itoh Shinji , Takashima Akira , Igana Ken'ichi , Maeda Yumino 
Published: January 2005

AbstractOur previous studies demonstrated that cerulein (CER) has a potent preventive action on amnesia induced by electroconvulsive shock, administration of scopolamine, puromycin, anisomycin, NMDA receptor antagonists, and protein kinase C inhibitors. The present study was aimed at finding more effective CER analogues which could enhance memory processes. Five CER analogues were synthesized and the potencies in passive and active avoidance responses and in the Morris water pool test were examined in the rat. Among the preparations, des‐Gln2‐[Leu5, Nle8]‐CER was found to possess particularly potent effects on memory acquisition and/or storage. The effects were apparent in less than 1 μg/kg single subcutaneous (s.c.) injection for at least 120 hr in passive avoidance response and 15 days in active avoidance response. Memory impairments induced by scopolamine and puromycin were well improved in passive avoidance response. In the Morris water maze test, disordered behaviors caused by scopolamine and protein kinase C inhibitor were totally restored to the normal state by s.c. injection of this CER analogue. © 1992 Wiley‐Liss, Inc.
Pharmacological properties of adenosine receptors and adenosine binding proteins
Authors: Schwabe U. , Fein T. , Lorenzen A. 
Published: January 2005

AbstractTwo major subtypes of adenosine receptors occur in different tissues which have been distinguished by pharmacological and biochemical criteria. The A1 adenosine receptor has a high‐affinity for adenosine and mediates inhibition of adenylyl cyclase, whereas the A2 adenosine receptor usually has a lower affinity and mediates stimulation of the enzyme. Furthermore, evidence has been obtained that A1 receptors increase the conductance of receptor‐regulated potassium channels, induce inactivation of calcium channels, and modulate the breakdown of phosphoinositides by phospholipase C. Selective agonists and antagonists have been developed for both receptor subtypes. In addition, both adenosine receptors have extensively been characterized by radioligand binding studies. Suitable radioligands for the A1 receptor are the agonist [3H]2‐chloro‐N6‐cyclopentyladenoisine (CCPA) and the antagonist [3H]8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX)and for the A2a receptor [3H]2‐[p‐(carboxyethyl)phenethylamino]‐ 5′‐N‐carboxamidoadenosine (CGS 21860). Furthermore, photoaffinity ligands were developed from adenosine derivatives, which can be covalently incorporated into the binding unit of both receptor subtypes. With this approach, it has been shown that the A1 receptor has an apparent molecular weight of approximately 36 kDa and the A2a receptor of 45 kDa. A second approach to elucidate the structure of adenosine receptors involves the purification of receptor protein by affinity chromatography. With this procedure, cerebral A1 receptors have been purified to apparent homogeneity. More recently, the structure of receptor subtypes has been elucidated by cloning the receptors from a cDNA library. Furthermore, a novel adenosine binding with [3H] 5′ ‐N‐ethylcarboxamidoadenosine ([3H]NECA). The pharmacological profile of this NECA‐binding protein has been determined in competition experiments with adenosine receptor ligands. It can be distinguished from that of A2a adenosine receptors and other adenosine binding proteins. We propose the name Ax for this unique adenosine binding protein. © 1993 Wiley‐Liss, Inc.
Acadesine: Prototype adenosine regulating agent for treating myocardial ischemia‐reperfusion injury
Authors: Mullane Kevin , Young Mark 
Published: January 2005

AbstractAcadesine is an adenosine regulating agent currently being developed for treatment of ischemia‐reperfusion injury in the setting of cardiac surgery. While the cardioprotective effects of adenosine are well recognized, the intrinsic hemodynamic and cardiac effects of adenosine limit its potential usefulness as a therapeutic agent. In contrast, acadesine has been shown to elevate endogenous levels of adenosine during periods of ischemia without exhibiting systemic hemodynamic action. The site‐specific and event‐specific mechanism of action thus provides cardioprotection without the adverse sequelae commonly observed with adenosine. This review describes the pertinent literature which establishes acadesine's action as an adenosine regulating agent, and discusses past and recent studies which focus on the cardioprotective actions of acadesine. These studies include in vitro and in vivo models of regional and global ischemia, and models of cardiac surgery. Aspects of dose‐response, timing of administration, and pharmacokinetics of acadesine are described which reconcile prior controversy regarding acadesine'e cardioprotective actions. These studies, taken together, demonstrate that acadesine is the prototype of a new class of adenosine regulating agents useful as therapy for cardiac ischemia. © 1993 Wiley‐Liss, Inc.
Beneficial role of adenosine in myocardial ischemic and reperfusion injury
Authors: Hori Masatsugu , Kitakaze Masafumi , Takashima Seiji , Morioka Toshikazu , Sato Hiroshi , Minamino Tetsuo , Inoue Michitoshi , Kamada Takenobu 
Published: January 2005

AbstractAdenosine has been recognized as an important regulator of myocardial function and coronary vascular tone in the ischemic myocardium. 5′‐Nucleotides, which converts 5′‐adenosine monophosphate to adenosine, is responsible for adenosine production in the ischemic myocardium. We have found that α1‐adrenergic receptors activated in ischemic hearts increase both 5′‐nucleotidase activity and adenosine production. The primary role of endogenous adenosine is to increase coronary blood flow through adenosine A2 receptors. This adenosine‐induced coronary vasodilation is amplified by α2‐adenosine stimulation. Stimulation of adenosine A2 receptors also attenuates both free radical generation by activated leukocytes and the aggregation of platelets. In turn, adenosine A1 receptor activation attenuates β‐adrenoceptor‐mediated increases in myocardial contractility, Ca2+ influx into myocytes and norepinephrine release form the presynaptic nerves. Any or all of these effects may attenuate ischemic and reperfusion injury. Indeed, endogenous and exogenous adenosine appears to ameliorate contractile dysfunction and infarct size following ischemia and reperfusion. Therefore, we believe that adenosine plays an important role as a modulator of ischemic and reperfusion injury. © 1993 Wiley‐Liss, Inc.
Amantadine increases striatal dopamine turnover in MPTP‐treated mice
Authors: Rojas Patricia , Altagracia Marina , Kravzov Jaime , Rios Camilo 
Published: January 2005

AbstractAmantadine is used in the symptomatic treatment of Parkinson's disease to improve the akinesia and rigidity associated with this neurodegenerative disorder. Amantadine acts on the synthesis and release of dopamine (DA). In order to further characterize its mechanism of action, the drug was administered to MPTP‐treated mice which were used as a model of the neurochemical deficits associated with Parkinson's disease. The DA turnover in corpus striatum was evaluated. Adult male Swiss albino mice were injected ip with 12.5 mg/kg (82.6 μmol/kg) or 25 mg/kg (165 μmol/kg) of amantadine and 30 min later with MPTP (30 mg/kg, 143 μmol/kg). Both the amantadine and MPTP treatments were repeated for 3 consecutive days. Groups of mice were treated with amantadine or MPTP alone. Seven days after the last injection of drugs, the striatal content of DA and homovanillic acid (HVA) were measured by HPLC‐EC analysis. Additional groups of mice were treated with 3 consecutive daily doses of MPTP (30 mg/kg, 143 μmol/kg) and 7 days after the last administration received a single dose of amantadine at 25 mg/kg (165 μmol/kg). Turnover rate was measured by HVA content determination. The results indicate that amantadine induced a significantly increased striatal DA turnover rate (34%) in MPTP‐treated animals as compared with those animals treated with only MPTP. © 1993 Wiley‐Liss, Inc.
N‐(n‐propyl)‐n‐(3‐fluoro‐4‐pyridinyl)‐1h‐3‐methylindol‐1‐amine hydrochloride (HP 184): In vitro spontaneous release of acetylcholine and norepinephrine
Authors: Smith Craig P. , Brougham Linda R. , Huger Francis P. , Davis Larry , Klein Joseph T. , Effland Richard C. 
Published: January 2005

AbstractIt has been shown that a single injection of N‐(n‐propyl)‐N‐(3‐fluoro‐4‐pyridinyl‐1H‐3‐methylindol‐1‐amine hydrochloride) (HP 184) (0.6‐4.8 mg/kg, or 2‐15 μmoles/kg, sc) reversed passive avoidance deficits in rats with combined cholinergic and noradrenergic lesions. This report describes the effects of HP 184 on NE and ACh release from rat brain slices. In contrast to 4‐aminopyridine (4‐AP), tyramine, or veratridine, HP 184 only enhanced spontaneous release and had no effect on electrical stimulation (ES). Chromatographic analysis showed that the spontaneous release from [3H]choline‐loaded striatal slices correlated with increased release of ACh, not choline efflux. HP 184 also enhanced ACh spontaneous release in the absence of both extracellular calcium and functional vesicles (as defined by ES and vesamicol). In frontal cortical slices, HP 184 caused [3H]NE release in a calcium independent fashion different from that induced by veratridine, and was not affected by uptake blockers. In contrast to the cholinergic profile, the [3H]NE release induced by HP 184 required intact storage vesicles, since release was blocked by reserpine pretreatment. The results show that HP 184 can release both NE and ACh in vitro, and, coupled with the dual lesion results, suggest it may have use in diseases involving cholinergic and noradrenergic deterioration. © 1993 wiley‐Liss, Inc.
Potentiation of 5‐methoxy‐n,n‐dimethyltryptamine‐induced head‐twitches by diazepam: Evidence for involvement of adenosine uptake inhibition
Authors: Moser Paul C. 
Published: January 2005

AbstractPrevious work shows that benzodiazepines potentiate head‐twitches induced by 5‐HT agonists and that this action is not mediated via the GABA receptor complex. In the present study the involvement of adenosinergic mechanisms in this effect has been examined, as in addition to their actions at the GABA receptor, benzodiazepines also inhibit adenosine uptake. The adenosine antagonists caffeine (0.3‐30 mg/kg ip) and 1,3‐dipropyl‐8‐(2‐amino‐4‐chlorophenyl)xanthine (0.03‐1 mg/kg ip) dose‐dependently inhibited the ability of diazepam (4 mg/kg ip) to potentiate head‐twitches induced by 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT; 2.5 mg/kg ip) without affecting head‐twitches induced by 5‐MeODMT alone at a higher dose (10 mg/kg), which induced a similar number of head‐twitches to the combination of 5‐MeODMT and diazepam. The adenosine uptake inhibitors papaverine, mioflazine, and dilazep all potentiated head‐twitches induced by 5‐MeODMT, but this effect was seen at only a single dose of each compound. The benzodiazepine antagonist flumazenil did not inhibit the potentiation of head‐twitches by diazepam but did itself potentiate head‐twitches at 30 mg/kg, consistent with its ability to inhibit adenosine uptake. In contrast, the adenosine uptake inhibitor dipyridamole and the peripheraltype benzodiazepine receptor antagonist Ro 5‐4864, which also inhibits adenosine uptake, failed to potentiate head‐twitches. The adenosine agonists N6‐cyclohexyladenosine, 5'‐(N‐ethylcarboxamido‐adenosine), and (–)‐N6‐(R‐phenylisopropyl)adenosine were similarly without effect. These results confirm previous findings that the potentiation of head‐twitches by benzodiazepines is not mediated via an action at benzodiazepine receptors and suggest that inhibition of adenosine uptake is an important component of the mechanism involved. © 1993 wiley‐Liss, Inc.
Amiridine (NIK‐247) and cerebrocrast in the alleviation of cholinergic lesion‐induced learning deficit in male rats
Authors: Männistö Pekka T. , Kutepova Olga , Leinonen Katri , Lang Aavo , Soosaar Andres , Suomela Annika , Borisenko Sergey A. 
Published: January 2005

AbstractLearning of the male rats was impaired by injecting ethylcholine aziridinium (AF64A) bilaterally into the basal magnocellular nuclei of Meynert. The performance of the rats in a passive avoidance test and in a one‐way active avoidance test was significantly improved by giving a novel acetylcholinesterase inhibitor, amiridine (NIK‐247; 9‐amino‐2,3,5,6,7,8‐hexahydro‐1H‐cyclopenta(b)‐quinoline monohydrate hydrochloride) after each learning session but not when the drug was given before the sessions. Cerebrocrast, an antagonist of L‐type calcium channels, was not effective in either case. Rather it worsened the learning results when given after the sessions of the active avoidance test. The conclusions in the passive avoidance test were hampered by the observed inconsistent effects of cholinotoxin. © 1993 wiley‐Liss, Inc.
Cloning and sequence of the human α7 nicotinic acetylcholine receptor
Authors: Doucette‐Stamm Lynn , Monteggia Lisa M. , Donnelly‐Roberts Diana , Wang Mei Tai , Lee John , Tian Jingxiang , Giordano Tony 
Published: January 2005

AbstractA rat clone for the nicotinic acetylcholine receptor (nAChR) α7, generated by reverse transcriptase‐polymerase chain reaction (rtPCR) from a region which did not exhibit significant homology to other rat nAChRs, was used to probe human cDNA libraries. A number of clones corresponding to the human α7 were isolated and sequenced. The human sequence showed 87% identity at the nucleic acid level to the rat sequence and 96% identity at the amino acid level. Unlike the rat α7 nAChR, the human gene does not appear to be the most divergent member of the nAChR family. The cloning of the human α7 will make it possible to study the functional formation of human neuronal nAChR channels containing the α7 subtype. © 1993 wiley‐Liss, Inc.
Effects of chlorisondamine on nicotinic receptor binding in whole brain and nicotine‐induced changes in locomotor activity in rats
Authors: Decker Michael W. , Majchrzak Mark J. , Cadman Evelyn D. , Arnerić Stephen P. 
Published: January 2005

AbstractChlorisondamine, a nicotinic cholinergic receptor antagonist, can block many of the in vivo effects of nicotine for weeks after a single icv injection. The time course of this effect was examined in a single group of rats by assessing the effects of nicotine on locomotor activity at 1, 3, and 6 weeks after the icv administration of 23 nmol of chlorisondamine. The effects of nicotine on locomotor activity were biphasic as has been previously reported, with decreases in activity early in the session and increases in activity later in the session. These effects of nicotine were blocked in chlorisondamine‐treated rats at 1 or 3 weeks but not 6 weeks after administration of chlorisondamine. Nicotinic receptor binding in the brains of chlorisondamine‐treated rats revealed no change in Bmax but a significant increase in affinity (47–59% decrease in Kd) 1, 3, 6, or 7 weeks after treatment. In contrast to its effects on affinity when administered icv, chlorisondamine did not alter binding affinity when added directly to the incubation buffer in vitro. Thus, although chlorisondamine significantly alters neuronal nicotinic cholinergic receptor binding affinity, this effect of chlorisondamine on binding affinity does not appear to be a direct effect of chlorisondamine on the receptor or to match the time course of chlorisondamine blockade of nicotine‐induced changes in locomotor activity. © 1994 Wiley‐Liss, Inc.
Actions of the general anesthetic propofol (2,6‐diisopropylphenol) on the binding of [3h]nicotine to rat cortical membranes
Authors: Prince Richard J. , Lineberry Jeffrey W. , Lippiello Patrick M. 
Published: January 2005

Abstract[3H]nicotine bound to rat cortical membranes in a biphasic manner consistent with previous models of receptor function. The kinetics of binding were characterized by a rapid component with a rate constant of 0.007 min−1 nM−1 and a slower component with an apparent rate constant of 0.024 min−1. Dissociation was monophasic with a rate constant of 0.046 min−1. Addition of 3 mM propofol caused the abolition of the slow component of association and increased the rate constants for the rapid component to 0.012 min−1 and for dissociation to 0.086 min−1. Under non‐equilibrium conditions propofol caused a dose‐dependent increase in the binding of [3]Hnicotine, which reached 147% of the control value at 3 mM propofol. The equilibrium binding of [3H]nicotine was unaffected by the drug. These results are consistent with propofol causing enhanced desensitization at the cortical nicotinic acetylcholine receptor, suggesting an alternative to receptor agonists which bind to active sites as a method of modulating receptor function. © 1994 Wiley‐Liss, Inc.
Effects of Japanese herbal medicine “Sho‐saiko‐to” on in vitro production of tumor necrosis factor‐alpha on peripheral blood mononuclear cells
Authors: Yamashiki Masayoshi , Nishimura Akira , Nomoto Minoru , Nakano Takeshi , Sato Tetsuro , Suzuki Hiroyuki , Zheng Qiao‐Xi , Klapproth Jan‐Michael , James Stephen P. , Kosaka Yoshitane 
Published: January 2005

Abstract“Xiao‐Chai‐Hu‐Tang” is a herbal medicine that has been used for the treatment of pyretic diseases in China for several thousand years. In Japan, this medicine was modified into “Sho‐saiko‐to,” a prescription drug with standard quality and volume of ingredients. It is widely used as a biological response modifier in the treatment of chronic viral liver diseases. Several researchers have reported improvement of general physical conditions and the drug's usefulness in preventing liver cancer development. In this in vitro study, peripheral blood mononuclear cells (PBMC) were obtained from 12 healthy volunteers, and Sho‐saiko‐to (TJ‐9) was added to the cultures of the PBMC. Dose‐dependent increases in the levels of tumor necrosis factor‐α (TNF‐α) were observed in the cultures. Similar but smaller increases in the TNF‐α levels were also observed when other Japanese herbal medicines, Dai‐saiko‐to (TJ‐8) or Saiko‐keishi‐to (TJ‐10), were added to the cultures. These results demonstrated that the increases of TNF‐α levels are specifically due to Sho‐saiko‐to and other drugs with similar ingredients. TNF‐α is believed to have anti‐tumor effects and also to have an important role as IL‐1 in the defense mechanism of the body. Therefore, the induction of TNF‐α could also be useful in clinical treatment, and this effect could be one of the mechanisms by which Sho‐saiko‐to demonstrates efficacy in the treatment of patients with chronic viral liver diseases. © 1994 Wiley‐Liss, Inc.
Synthesis and biological evaluation of lorglumide‐like hybrid cholecystokinin‐A receptor antagonists
Authors: van der Bent Arie , van den Brink Ingrid , Ijzerman Adriaan P. , van Wijngaarden Ineke , Soudijn Willem 
Published: January 2005

AbstractThe evaluation of gross structural homologies between the competitive cholecystokinin‐A (CCK‐A) receptor antagonists lorglumide and devazepide formerly enabled the development of compact hybrid analogues [Van der Bent et al. (1992): J Med Chem 35:1042–1049]. In the follow‐up study described here, we aimed to closely examine the structural and functional relationship between N‐acyglutamic acids like lorglumide and our hybrid derivatives. For this purpose, the most potent hybrid CCK‐A antagonist (Ki = 0.09 μM) was modified by the addition of the propionic acid moiety that is unique to the N‐acylglutamic acids. Additionally, a number of propionic acid and butyric acid derivatives were prepared in order to explore the SAR profile of the carboxylic acid moiety in this series. The prepared compounds were tested in vitro as antagonists of the binding of [3H]‐(±)‐L‐364,718 to rat pancreas membranes. With CCK‐A affinities above 1 μM, all derivatives of the initial hybrid structure, including the propionic acid derivative that closely resembles lorglumide, proved to be considerably less potent. It would appear that the retained structural differences between lorglumide and the novel hybrid antagonists result in a divergence of their binding modes that precludes a favourable interaction of the added functionality of the latter compounds. Alternatively, the obtained results may question the vital role that has been attributed to the carboxylic acid function of the N‐acylglutamic acids as a counterion to a cationic residue in the binding site. © 1994 Wiley‐Liss, Inc.
Analgesic interactions produced by dipyrone and either morphine or D‐propoxyphene in the pain‐induced functional impairment model in rat
Authors: López‐Muñnoz Francisco J. , Villalón Carlos M. , Terrón José A. , Salazar Luis A. 
Published: January 2005

AbstractThe analgesic synergism of drug mixtures containing dipyrone in combination with either morphine or d‐propoxyphene were examined in the pain‐induced functional impairment model in the rat (PIFIR). Pain was produced by intra‐articular injection of uric acid in the right hind limb, inducing its dysfunction. Animals then received the following treatments: dipyrone (160, 285, 506, 900, 1,600 or 2,846 μmoles·kg−1, sc), morphine (3, 6, 10, 18, 31, or 55 μmoles·kg−1, sc), d‐propoxyphene (84, 150, 266, 473, or 841 μmoles·kg−1) or a combination using the ED33 of each drug, namely, dipyrone/morphine (834/18 μmoles·kg−1) or dipyrone/d‐propoxyphene (834/187 μmoles·kg−1). The recovery of functionality after the above treatments was considered as an expression of analgesia. The analgesic effects produced by the combination dipyrone/morphine were similar to those expected on the basis of addition of analgesic effects of the individual drugs. However, analgesia produced by the combination dipyrone/d‐propoxyphene was significantly higher (P < 0.01) than that induced by each component alone. The percent change was 33% over the addition of individual analgesic effects. The analysis of the time‐course curve of the simultaneous administration of dipyrone/d‐propoxyphene showed a maximum of analgesia of 95% at 1 h after administration and then persisted until the end of the experiment (up to 3 h). The total analgesic effect determined from the area under the time‐course curve showed 332.5 area units; this represented the highest analgesic effect among the drugs tested. These results are relevant in view of the inability of dipyrone, morphine, and d‐propoxyphene to produce that highest analgesic effect.