bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depression of synaptic transmission and evoked NMDA Ca2+ influx in hippocampal neurons by adenosine and its blockade by LTP or ischemia
Authors: Schubert Peter , Keller Franz , Rudolphi Karl 
Published: January 2005

AbstractNeuronal Ca2+ influx in response to repetitive synaptic activation was determined in rat hippocampal slices by measuring the evoked decreases of the extracellular Ca2+ concentration with ion‐sensitive electrodes in the synaptic layer (ΔCaSpad) and in the CA1 pyramidal cell layer (ΔCaSpyr). The generation of NMDA receptor‐mediated Ca2+ fluxes (NMDA Ca2+ fluxes) was uncovered by measuring the proportion of ΔCa blocked by the NMDA receptor antagonist 2‐amino‐5‐phosphonovalerate (APV); 1 μmol adenosine increased the critical input frequency required to generate synaptic MNDA Ca2+ influx. This effect is apparently exerted by limiting the postsynaptic membrane depolarization and is no longer seen, if the NMDA Ca2+ channels have lost their Mg‐dependent voltage sensitivity. It has been recently reported by Ben‐Ari and co‐workers [(1992) Trends Neurosci 15:333–339] that such a loss of voltage sensitivity, leading to an “upregulation” and persistent generation of NMDA Ca2+ currents, Can be elicited by an activation of the protein kinase C (PKC) and may be responsible for the initiation of synaptic long‐term potentiation (LTP) and for ischemia‐induced nerve cell damage. Consistent with this hypothesis, we found that the depressive effect of 1 μmol adenosine on the generation of NMDA Ca2+ influx or synaptic transmission can be no longer elicited in hippocampal slices after LTP and after preceding transient brain ischemia in vivo. These findings suggest that the mosaic of different adenosine actions includes some which are related to PKC activation. Accordingly, we observed a synaptic modulation by adenosine which was characterized by a reduced Mg‐sensitivity and blocked by phorbol ester treatment. © 1993 Wiley‐Liss, Inc.
An inhibitory postsynaptic potential in spinal nociceptive neurones is mediated by adenosine through activation of ATP‐sensitive K+ channels
Authors: Salter Michael W. , De Koninck Yves , Henry James L. 
Published: January 2005

AbstractInhibitory processes within the dorsal horn participate in regulating the transmission of nociceptive information. Spinal nociceptive neurones are inhibited by cutaneously applied vibration and we have characterized this inhibition physiologically and pharmacologically [Salter et al., 1993]. This inhibition is evoked by activation of Pacinian corpuscle afferents and is mediated in the spinal cord by adenosine acting through P1‐purinergic receptors. The adenosine‐mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP) produced by activating a K+ conductance. Adenosine is known to activate K+ currents in a number of different types of cell [Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987; Gerber et al. 1989] and it has been reported that in cardiac muscle cells the + channels [Kirsch et al., 1990]. Therefore, we investigated the possibility that these channels might mediate the IPSP we have observed in nociceptive dorsal horn neurones upon vibratory stimulation applied to the skin. We found that the inhibition of nociceptive neurones by this stimulation is abolished by glibenclamide, a blocker of ATP‐sensitive K+ Channels [Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b]. In addition, the IPSP evoked by vibratory stimulation was blocked by direct intracellular injection of AYP. These results suggest that the adenosine‐mediated IPSP in nociceptive spinal neurones results from activating ATP‐sensitive K+ channels in these neurones. As this inhibition of nociceptive dorsal horn neurones may be the physiological basis for the analgesia produced by vibratory stimulation in humans [Bini et al., 1984; Lundeberg, 1984; Lundeberg et al., 1984; Ottoson et al., 1981], We suggest that activation of ATP‐sensitive K+ channels ion nociceptive neurones may mediate this analgesia. A diversity of drugs exists which act on ATP‐sensitive K+ channels and we further suggest that such drugs might be therapeutically useful in enhancing the analgesia produced by vibration or in producing analgesia on their own. © 1993 Wiley‐Liss, Inc.
Opportunistic infections: Treatment and developmental therapeutics of cryptosporidiosis and isosporiasis
Authors: St. Georgiev Vassil 
Published: January 2005

AbstractCryptosporidium sp. and Isospora sp. are coccidian protozoans taxonomically related to Toxoplasma gondii and Plasmodium sp. Although associated with many animal species, these pathogens are also the causative agents of cryptosporidiosis and isosporiasis, 2 invasive opportunistic infections in humans. In immunocompetent hosts, the infections are usually self‐limited, flu‐like gastrointestinal disorders which resolve spontaneously. In immunocompromised patients, however, cryptosporidiosis is a severe, debilitating, and prolonged illness, with high morbidity and no known therapy effective against it. Spiramycin has been proven largely ineffective. In recent years, however, the use of immunotherapy is being actively pursued as one potentially useful approach for the treatment of cryptosoporidiosis. Azithromycin, a new macrolide antibiotic, has also shown promise in preclinical studies. In the case of isosporiasis, the combination of trimethoprim and sulphamethoxazole has been found to be effective, although AIDS patients have shown a high rate of relapse and, therefore, the need for suppressive maintenance therapy. © Wiley‐Liss, Inc.
In vitro evaluation of the antiviral activity of SP‐303, an euphorbiaceae shrub extract, against a panel of respiratory viruses
Authors: Wyde Philip R. , Meyerson Laurence R. , Gilbert Brain E. 
Published: January 2005

AbstractThe antiviral dn cytotoxic activity of SP‐303, a naturally occurring polyphenolic polymer (average M.W. = 2,100 daltons) isolated from a Euphorbiaceae shrub, was evaluated in tissue culture. The compound exhibited selective antiviral activity (ratio IC50/EC50 ≥10) against parainfluenza virus type 1, respiratory syncytial virus, influenza A viruses, and influenza B viruses; marginal selective antiviral activity (IC50/EC50 ratio >2 to <10) against parinfluenza virus type 3; and no selective antiviral activity (IC50/EC50 ratio ≤1) against measles virus or adenovirus type 5. Hemagglutination and other studies suggested that SP‐303 may at least partially inactivate virus by direct interaction with virus or host cell lipid membranes. © Wiley‐Liss, Inc.
Transdermal penetration of physostigmine: Effects of oleic acid enhancer
Authors: Meshulam Yacov , Kadar Tamar , Wengier Ada , Dachir Shlomit , Levy Aharon 
Published: January 2005

AbstractThe efficiency of the transdermal penetration of physostigmine through the guinea‐pig skin, in a vehicle containing propionic acid, was studied in the course of developing a transdermal physostigmine pad for the potential treatment of Alzheimer's disease patients. In an attempt to improve drug penetration, the addition of various concentrations of oleic acid(0.5–5%) was tested. The study included histological examination of skin biopsies from application site. The addition of 0.5% oleic acid to the vehicle enhanced the permeation of physostigmine and shortened the time needed to reach steady state levels of blood cholinesterase inhibition, without any damage to the skin. Stable values of physostigmine concentration and of cholinesterase inhibition were measured both in blood and in brain up to 72 h. A high correlation was found between physostigmine concentration in the plasma and cholinesterase inhibition in whole blood samples (r = 0.99 for the values measured up to 48 h). A lower correlation was found between physostigmine concentration and cholinesterase inhibition in the brain (r = 0.57). In a vehicle containing up to 1% oleic acid, physostigmine was stable for at least one month. Oleic acid concentrations higher than 1%, while increasing the flux of the drug through the skin, resulted in considerable skin damage. © Wiley‐Liss, Inc.
Determinants of angiotensin II‐induced hypertrophy versus hyperplasia in vascular smooth muscle
Authors: Owens Gary K. 
Published: January 2005

AbstractThere is clear evidence implicating a role for angiotensin II in control of hypertrophic growth of vascular smooth muscle cells in vivo. However, the specific mechanisms whereby angiotensin II influences smooth muscle cell growth have not been defined. The focus of this mini‐review is to consider how angiotensin II contributes to control of hypertrophic vs. hyperplastic growth of vascular smooth muscle in vivo, and in particular how the differentiated state of the smooth muscle cell may influence growth responsiveness to angiotensin II. © 1993 Wiley‐Liss, Inc.
Endothelin‐1 modulates vascular smooth muscle structure and vasomotion: Implications in cardiovascular pathology
Authors: Ohlstein Eliot H. , Douglas Stephen A. 
Published: January 2005

AbstractEndothelin‐1 modulates vascular smooth muscle tone by exerting potent vasoconstrictor actions through the ETA receptor subtype located on the membranes of vascular smooth muscle cells. This receptor subtype also mediates the growth‐promoting actions of this peptide in vascular smooth muscle cells. The ETA receptor is distinct, however, from the endothelin receptor subtype located on the endothelium; the anatomically and functionally distinct ETB receptor mediates the release of the endothelium‐derived factor nitric oxide, a labile substance which not only produces potent vasodilation but also possesses anti‐mitogenic activity. This report describes the interaction between these two vasoactive factors in the control of cardiovascular function. Under normal conditions the endothelium serves to modulate the contractile and proliferative actions of endothelin‐1. However, many cardiovascular disorders (e.g., hypertension, atherosclerosis, vascular restenosis, subarachnoid hemorrhage, etc.) are associated with both abnormal endothelial cell function, resulting in an inability to synthesize and/or release nitric oxide, and elevated circulating levels of endothelin‐1. Since the resultant loss/inhibition of nitric oxide will augment both the contractile and proliferative actions of endothelin‐1, this has the potential to promote vasoconstriction and smooth muscle hyperplasia/hypertrophy at the site of any such lesion. Since evidence is accumulating that both endothelin‐1 and nitric oxide play pivotal roles in the control of both vascular smooth muscle tone and growth, any imbalance between these two counter‐regulatory systems is likely to have profound pathological consequences within the cardiovascular system. © 1993 Wiley‐Liss, Inc.
The dilemma of biotechnology
Authors: Sapienza Alice M. 
Published: January 2005

AbstractThe 1988 decision by the U.S. Health Care Financing Administration (HCFA) not to accord special reimbursement treatment to Genentech's tissue plasminogen activator (Activase™) was a signal event in the growing dilemma of biotechnology. In the U.S. (and to a degree in Japan and major Western European nations as well), therapeutic biotechnology investment appears to be on a collision course with health care cost containment efforts. During this time of renewed political interest in pharmaceutical pricing, there is urgent need for dialogue among the affected parties. Otherwise, repercussions of a collision could damage both private and public sector biotechnology innovation. The purpose of this article is to outline the nature of, and clarify the reasons for, the dilemma of biotechnology. ©1993 Wiley‐Liss, Inc.
Effect of a novel monamine oxidase‐a inhibitor, bw 1370U87, on urinary 3‐methoxy‐4‐hydroxyphenylglycol in normal volunteers
Authors: Hedeen Kevin M. , White Helen L. , Cooper Barrett R. , Conner Gary W. , Norton Ronald M. 
Published: January 2005

AbstractUrinary 3‐methoxy‐4‐hydroxyphenlglycol (MHPG) levels were measured in 14 normal volunteers during a Phase I study of the novel, reversible monoamine oxidase‐A (MAO‐A) inhibitor BW 1370U87 targeted for the treatment of depression. baseline MHPG excretion (day 0) showed a significant diurnal increase (n = 14, P < 0.05) between 1200 and 2000 h. Oral administration of BW 1370U87 produced significant (35‐45% maximal, P < 0.05) decreases from these basal levels during the same 1200‐2000 h time interval Twenty‐four hours after the dose (dose was given at 0800 h), urinary MHPG levels returned to baseline, consistent with a reversible mechanism of inhibition by BW 1370U87. Decreases in urinary MHPG did not appear to be dose‐dependent between 200‐800 mg BW 1370U87 per day, suggesting that maximal MAO‐A inhibition was achieved at the 200 mg dose. These effects on MHPG excretion may be helpful in predicting the efficacy of BW 1371370U87 in the treatment of depression. © 1993 wiley‐Liss, Inc.
Effect of mannitol treatment on soman‐induced brain and heart lesions in the rat
Authors: Filbert Margaret G. , Dochterman Leland W. , Smith Catherine D. , Forster Jeffry S. , Phann Sorabe , Cann Frank J. 
Published: January 2005

AbstractThe effect of intravenous mannitol on soman‐induced neuropathology and cardio‐myopathy was studied in rats. Soman, an organophosphorus agent, irreversibly inhibits total body acetylcholinesterase and induces a cholinototoxic syndrome in rats which results in the development of sezures, brain damage, and degenerative cardiomyopathy. The severity of the cardiomyopathy parallels the severity of the neuropathology. When mannitol at a dose of 1.5 g/kg was administered at the onset of sezures and followed by a second dose 5 h later, there was a significant increase in 24 h survival. Moreover, the severity of brain lesions was reduced in the piriform cortex, thalamus, amygdala, and the caudate putamen. The same treatment schedule also provided almost complete protection against the concomitant development of degenerative cardiomyopathy. The finding that the mannitol treatments reduced both the severity of the neuropathology and the degenerative cardiomyopathy reinforces the concept of a possible central neurogenic mechanism for the development of the cardiomyopathy. These results suggest that mannitol may be useful to reduce the severity of sezure‐related neuropathology and to provide additional protection to other vital organs which may be secondarily susceptible to neurogenically mediatd pathologic change, such as the heart in rats which develop cardiomyopathy following soman‐induced seizures. © 1993 wiley‐Liss, Inc.
Transient agonist‐like action of the thromboxane A2 receptor antagonist S‐1452 (d‐s‐145 Ca) and its reduction by gradual injection or oral administration
Authors: Asanuma Fujio , Jyoyama Hirokuni , Kurosawa Atsushi 
Published: January 2005

AbstractThe thromboxane A2 receptor antagonist S‐1452, d‐S‐145 Ca, calcium 5(Z)‐1R,2S,3S,4S‐7‐[3‐phenylsulfonylaminobicyclo[2.2.1]hept‐2‐yl]‐5‐heptenoate dihydrate, is a partial agonist and transiently alters platelet shape and smooth muscle contraction in vitro [Hanasaki et al., Biochem Pharmacol 38:2007‐20017, 1989; Otani et al.: Folia Pharmacol Jpn 94:319‐328, 1989: Kakushi et al.: Folia Pharmacol Jpn 98:113‐120, 1991]. A water soluble preparation of the compound d‐S‐145 Na caused transient apnea in mice by a bolus injection through the tail vein. This agonistic effect was seen in the dose range similar to that observed for TXA2 antagonism, which was evaluated as a preventive activity of U46619‐induced sudden death [ED50: 55 μg/kg, iv, for the apnea appearance and 15 μg/kg, iv, for prevention of the U46619‐induced sudden death]. The agonistic and antagonistic effects of d‐S‐145 Na were more marked than those of the l‐enantiomer, 1‐S‐145 Na. d‐S‐145 Na was also agonistic in guinea pigs. Bolus injection through the jugular vein at doses above 10 μg/kg of d‐S‐145 Na caused a transient increase in airway resistance. However, the response disappeared completely or was markedly reduced by gradual injection of the compound at the same dose. The gradual injection of d‐S‐145 Na did not cause a marked alteration in the TXA2 antagonistic activity, which was evaluated as a prevention of U46619‐induced increase in airway resistance. The separation of the agonistic and antagonistic effects of S‐1452 was much more remarkable in dosing S‐1452 through an oral route. In conclusion, the intrinsic agonistic action of S‐1452 can be reduced significantly by gradual injection or oral administration of the compound, without severe reduction of the antagonistic activity against TXA2. © 1993 wiley‐Liss, Inc.
Surviving as a niche player in the pharmaceutical industry: Reflections from the field
Authors: Jorgensen Stig , Jensen Ivan , Edwards Martin 
Published: January 2005

AbstractThe pharmaceutical industry can be divided into a top tier of about 30 major league companies and a second tier (minor league) comprising several thousand. This paper focused on the second tier and the particular challenge of minor league companies—especially niche players—to balance operating requirements and strategic ambitions within limited and limiting resources. In the authors' experience, survival as a niche player requires not only that the company stays on the technology frontier but also that risk willingness and innovative behavior be characteristic of managers' mindset. To this end, the authors share 13 “ground rules” to perform appropriately as a niche player. © 1993 wiley‐Liss, Inc.
Serotonin mechanisms in alcohol drinking behavior
Authors: McBride William J. , Murphy James M. , Yoshimoto Kanji , Lumeng Lawrence , Li Ting‐Kai 
Published: January 2005

AbstractRat lines selectively bred for disparate alcohol‐drinking behaviors exhibit innate differences in the contents of serotonin (5‐HT) in several CNS limbic regions, e.g., nucleus accumbens (ACB), frontal cortex, hypothalamus, and olfactory tubercles. In these regions, the selectively bred alcohol‐preferring (P) line has levels approximately 20% (P > 0.05) lower than values obtained for the alcohol‐nonpreferring (NP) line. In addition, in some limbic regions, the densities of (1) 5‐HT1A receptors are higher by approximately 30% and (2) 5‐HT1B and 5‐HT2 receptors are lower (by 25‐40%) in the P than in the NP line. systemic administration of agents that increase synaptic levels of 5‐HT, such as fluoxetine (a 5‐HT uptake inhibitor), d‐fenfluramine (a 5‐HT releaser) and D, L‐5‐hydroxytryptophan (an immediate precursor of 5‐HT), significantly decreased alcohol consumption of the P line of rats. Systemic (1.0 and 2.0 g/kg ip) administration or local perfusion (100 mM) of ethanol significantly increased the extracellular levels of 5‐HT in the ACB of unselected Wistar rats. An interaction of the dorsal raphe nucleus (DRN) 5‐HT system with the ventral tegmental area (VTA) dopamine (DA) pathway projecting to the ACB was indicated by the findings that DA release in the ACB increased and decreased following stimulation and inhibition, respectively, of DRN 5‐HT neurons. Moreover, an involvement of 5‐HT in mediating alcohol‐stimulated DA release in the ACB is indicated by the observation that local application of a 5‐HT3 antagonist can attenuate this stimulated release. Overall, the data suggest that an innate 5‐HT deficiency in certain limbic structures of the P rat may be a major neurobiological factor underlying their high alcohol drinking characteristics. © 1993 wiley‐Liss, Inc.
Tretinoin: A review of in vivo pharmacological studies
Authors: Cohen Marvin 
Published: January 2005

AbstractTretinoin (all‐trans‐retinoic acid), a metabolite of retinol, has shown efficacy in the treatment of acute promyelocytic leukemia. Preclinical studies in rodents indicated that tretinoin inhibited or prevented chemically‐induced skin papillomas or carcinomas. However, tretinoin had no effect on several types of transplantable tumors. Studies of tretinoin's pharmacodynamic profile indicated a lack of central nervous system or cardiovascular activity. Effects of tretinoin on the immune system were dependent on the animal model employed, both enhancement and suppression being reported. Tretinoin appeared to increase serum triglycerides and lower serum as well as liver cholesterol levels. Additional preclinical studies are needed to establish minimal effective doses and quantitation of the time course of changes induced by this retinoid. © 1993 wiley‐Liss, Inc.
In vivo agonist properties of 7‐hydroxy‐N,N‐di‐n‐propyl‐2‐aminotetralin, a dopamine D3‐selective receptor ligand
Authors: McElroy John , Zeller Kim , Amy Kelly , Ward Kathryn , Cawley James , Mazzola Amie , Keim William , Rohrbach Kenneth 
Published: January 2005

AbstractThe selective dopamine D3 receptor ligand 7‐hydroxy‐N,N‐di‐n‐propyl‐2‐aminotetralin (7‐OH‐DPAT) produced stereotypical sniffing and climbing, increased locomotor activity, and caused 6‐hydroxydopamine‐lesioned animals to rotate in a contralateral direction, behavioral effects highly predictive of dopamine agonist activity. In contrast, 7‐OH‐DPAT was inactive in the conditioned avoidance response, catalepsy, and anti‐apomorphine test, animal models highly predictive of dopamine antagonist activity. These results indicate that 7‐OH‐DPAT is an agonist at dopamine receptors in vivo. © 1993 wiley‐Liss, Inc.
Antagonism of diazepam's anticonflict effects in rats by nicotine, but not by arecoline
Authors: Porter Joseph H. , Heath Gregory F. , Rosecrans John A. 
Published: January 2005

AbstractThe purpose of the present study was to determine the possible role of cholinergic mechanisms in the anticonflict effects of the anxiolytic diazepam. Male Sprague‐Dawley rats were tested with a modified Geller‐Seifter procedure using a multiple reinforcement schedule in which unpunished responding in one component was reinforced according to a fixed‐interval 60‐sec schedule, and punished responding in the other component resulted in both food and a brief electric shock presentation according to a fixed‐ratio 1 schedule. In Experiment 1 (−)‐nicotine antagonized the increase in punished responding that was produced by diazepam. In Experiment 2 diazepam produced selective increases in punished responding that again was antagonized by (−)‐nicotine, a nicotinic cholinergic agonist, whereas arecoline, a muscarinic cholinergic agonist, did not antagonize diazepam's increase in punished responding. Neither drug produced any significant changes in unpunished responding. In Experiment 3 it was shown that the centrally acting nicotinic antagonist, mecamylamine, was able to block nicotine's antagonism of diazepam. These results suggest that there is an interaction between central nicotinic cholinergic mechanisms and diazepam's anticonflict effects in this animal model for anxiolytics, and support clinical observations that smoking can reduce some effects of benzodiazepines. © 1994 Wiley‐Liss, Inc.