bluuebunny/crossref_metadata_2025_split huggingface dataset:
New developments in the diagnosis of the dementias
Authors: Blass John P. , Barclay Laurie L. 
Published: January 2005

AbstractThe most common errors in the diagnosis of dementia are underdiagnosis and overdiagnosis. Underdiagnosis is best avoided by careful use of psychometric screening tests to detect cognitive impairment in patients unaware of their own defect. Overdiagnosis can be avoided by not applying the label of “dementia” until the diagnosis is unequivocal. Complete evaluation is necessary to rule out treatable causes of dementia, and should include medical, neurological, and psychiatric history and examination, simple psychometric tests, laboratory battery, computerized transaxial tomographic brain scan, and electroencephalogram. Ultimately, the diagnosis of dementia may change at follow‐up examination, and the unequivocal diagnosis of a specific form of dementia still requires autopsy and neuropathological examination of the brain. The most common causes of cognitive impairment in the elderly include Alzheimer's disease, multi‐infarct dementia, depression, and other specific illnesses such as tumors, Jakob‐Creutzfeldt disease, and normal pressure hydrocephalus. Even systemic disease can present as dementia. The evaluation outlined above may help distinguish among these causes. New diagnostic techniques may eventually be helpful as well.
Methodological issues in drug assessment research
Authors: Buckalew L. W. 
Published: January 2005

AbstractIncreased sensitivity to methodological issues in drug assessment research is needed in light of challenges to research design, conduct, and outcomes. Major issues presented include (a) the nature and adequacy of placebo controls, (b) problems in maintaining the integrity of “blind” conditions, and (c) the potential design‐compromising effects of informed consent. The necessity of true matching placebos, particularly concerning physical/perceptual characteristics and the ability to produce transitory changes in subjects, was stressed. Though the double‐blind condition has conceptual integrity, the operation of drug and placebo side effects and associated guess bias may confound research results. Use of a triple‐blind condition and addition of a drug‐disguised group is suggested. Last, the issue of informed consent and its implications for the integrity of drug research is a problem deserving more attention.
Selective inhibition of the cyclooxygenase pathway of the arachidonic acid cascade by the nonsteroidal antiinflammatory drug isoxicam
Authors: Pugsley Thomas A. , Spencer Carolyn , Boctor Amal M. , Gluckman Melvyn I. 
Published: January 2005

AbstractThe effects of the nonsteroidal antiinflammatory drug isoxicam on prostaglandin formation by HSDM1C1 mouse fibrosarcoma cells grown in culture and 5‐HETE(5(S)‐5‐hydroxy‐6‐trans, 8,11,14‐cis eicosatetraenoic acid) formation by human leukocytes were determined. Isoxicam inhibited the formation of the cyclooxygenase product prostaglandin E2 with an IC50 of 2.0 μM. In comparison, the reference standards piroxicam and indomethacin had IC50 values of 0.55 μM and 0.14 μM, respectively. Nordihydroguaiaretic acid (NDGA) was inactive up to 10 μM. Isoxicam, piroxicam, and indomethacin were relatively devoid of any significant inhibitory property on 5‐lipoxygenase activity exhibiting IC50 values > 500 μM. In comparison, the compounds BW755C and NDGA, known lipoxygenase inhibitors, had IC50 values of 11 μM and 0.6 μM, respectively. The present findings indicated that isoxicam exhibited a selective inhibition of the cyclooxygenase pathway of the arachidonic acid cascade and that this effect may at least in part be responsible for its antiinflammatory activity observed in animals and humans.
Fluradoline (HP 494), a centrally acting analgesic with antidepressant properties: Antidepressant pharmacology
Authors: Spaulding T. , Fielding S. , Cornfeldt M. , Wilker J. , Ellis D. B. , Novick W. J. , Ong H. H. 
Published: January 2005

AbstractFluradoline (HP 494), a tricyclic dibenz (b, f) oxepine derivative with an analgesic profile, was tested for antidepressant activity. After oral administration, fluradoline was twice as potent as imipramine and similar in potency to desmethylimipramine in blocking tetrabenazine‐induced ptosis. Like standard antidepressants, fluradoline selectively increased response rates for electrical stimulation of the median forebrain bundle using internal capsule‐lesioned rats. Response rates in nonlesioned rats were unaffected. There was partial protection against yohimbine toxicity and no potentiation of 5‐hydroxytryptophan‐induced seizures in mice. When administered to squirrel monkeys, the EEG profile from cortically‐placed electrodes resembled that found for imipramine. Using in vivo and in vitro techniques, it was shown that fluradoline was not a monoamine oxidase inhibitor; however, the compound did block the reuptake of norepinephrine, serotonin and dopamine in brain homogenates. These results suggest that in addition to the analgesic profile, there is a concomitant antidepressant profile which may enhance the spectrum of activity of fluradoline.
The cardioselectivity of β‐adrenergic blocking agents revealed by interaction with salbutamol and isoproterenol in the KCN test in rats
Authors: Awouters F. , Niemegeers C. J. E. , Janssen P. A. J. 
Published: January 2005

AbstractThe interaction of seven β‐adrenergic blocking agents with salbutamol and isoproterenol was studied in the potassium cyanide test in rats. Salbutamol was used at a dose that provided protection from KCN lethality and isoproterenol at an overdose that failed to protect, presumably because of latent cardiotoxicity. Salbutamol‐induced protection was abolished at the following doses (s.c., mg/kg): timolol (0.0085), bunolol (0.010), propranolol (0.038), pindolol (0.15), metoprolol (3.93), atenolol (5.69), and practolol (> 10.0). Survival was restored dose‐dependently in isoproterenol‐overdosed rats only by atenolol (0.44), practolol (0.51) and metoprolol (1.06). The cardioselectivity ratio (i.e., salbutamol antagonism/isoproterenol antagonism) for these three compounds was as follows: practolol (> 19.6), atenolol (12.9), and metoprolol (3.82). The described interaction tests appear to provide experimental data that are useful for the evaluation of cardioselective β‐adrenergic blockade.
A comparison of the cardiovascular and the behavioral changes following naloxone as measures of the degree of physical dependence on morphine in rats
Authors: Marshall Dennis C. , Buccafusco Jerry J. 
Published: January 2005

AbstractBehavioral and cardiovascular changes evoked by naloxone (0.5 mg/kg) were evaluated in unrestrained rats made physically dependent by a constant infusion of morphine at increasing doses over 7 days. The relationship between the duration of morphine administration and the naloxone‐induced cardiovascular changes was investigated to determine the reliability and sensitivity of blood‐pressure measurements in assessing the degree of physical dependence produced in these animals. No significant behavioral or cardiovascular changes from preaddiction levels were observed during morphine infusion. Arterial pressure increased significantly in a dose‐ and time‐dependent manner in response to naloxone injected on days 1, 3, 5, or 7 of the morphine infusion schedule. Heart rate changes which accompanied the increase in blood pressure, however, were similar in magnitude over the course of increasing physical dependence. The frequency of counted behavioral signs precipitated by naloxone over the same infusion schedule indicated a significant, progressive increase only for escape attempts, whereas withdrawal body shakes and writhing peaked early in the schedule and actually declined to very low frequencies by day 7. A high dose of morphine (50 mg/kg) was injected following naloxone‐precipitated withdrawal in an attempts to reverse the abstinence symptoms. The only symptoms significantly inhibited by morphine were the increase in arterial pressure and the occurrence of diarrhea. These results indicate that the absolute increase in arterial blood pressure produced by naloxone in opiate‐dependent animals may serve as a simple, objective, and sensitive measurement, along with traditional behavioral signs, in the assessment of narcotic dependence liability.
A direct vasoaction of inosine in small intramural coronary arteries
Authors: Randall John R. , Mass Howard J. , Jones Carl E. 
Published: January 2005

AbstractThe direct vasoaction of inosine was examined and compared to that of adenosine in small coronary arterial rings (0.3–0.6 mm o.d.) from the dog heart. Rings were contracted with KCI, and relaxation responses to increasing nucleoside concentrations were recorded. Both inosine (16 rings) and adenosine (12 rings) elicited relaxation responses that were linearly related to the logarithm of nucleoside concentration. In eight rings for which both inosine and adenosine responses were obtained, the geometric mean ED50 for adenosine was 0.54 μM, compared to 242 μM for inosine (p < 0.001). The Rmax for the two nucleosides were not significantly different (p > 0.05). In four rings studied, aminophylline abolished the response to adenosine. In five rings studied, aminophylline abolished the response to adenosine. In five rings studied, aminophylline abolished the inosine response in only two rings; in the remaining three rings, the inosine response was attenuated but not abolished. These results indicate that inosine exerts a direct vasodilatory action on small coronary arteries and that this vasoaction is in part aminophylline‐sensitive.
Ultraviolet light‐induced photorelaxation of agonist‐contracted rabbit aorta: Further characterization and the estimation of drug‐receptor rate constants
Authors: Raffa Robert B. , Robinson Mary Jane , Tallarida Ronald J. 
Published: January 2005

AbstractIsolated strips of rabbit thoracic aorta, contracted to a steady‐state isometric tension by measured doses of α‐adrenoceptor agonists, exhibit a transient loss in tension when exposed to a flash of ultraviolet light. This response consists of an initial decrease in tension followed by a spontaneous restoration to equilibrium tension. The time course of the return to equilibrium from maximum relaxation is a biphasic exponential, resolvable into a fast phase and a slow phase. Previous work has shown that the fast phase of recovery is drug‐independent, but that the slow phase of recovery is drug‐dependent; i.e., the rate of return to equilibrium tension is unique for each agonist used to produce the initial contraction. When a system in equilibrium is perturbed in a manner such as this, the return to equilibrium is characterized by a time constant that is a function of the drug concentration. A plot of this time constant against drug consentration yields a straight line of slope and y‐intercept equal to the forward and reverse rate constants, respectively, of the chemical reaction. In this study, equilibrium perturbation by UV light was used to determine the forward and reverse rate constants (k1 and k2) of the drug‐receptor interaction and the dissociation constants (KA = k2/k1) of each of three α‐adrenoceptor agonists, norepinephrine, phenylephrine, and methoxamine. The values of KA reported here for all three agents and for different degrees of passive stretch (0.25‐g and 10‐g preload for norepinephrine, 10‐g preload for phenylephrine and methoxamine) are not significantly different from the corresponding values reported using the method of partial irreversible blockade of receptors. These findings are compatible with the hypothesis that the radiation disrupts the drug‐receptor equilibrium. Regardless of mechanism, however, the photorelaxation phenomenon may provide an additional tool for classifying vasoactive compounds.
Effects of prenalterol, a partial beta adrenoceptor agonist, on the left ventricular function in anesthetized cardiac denervated beagle dogs
Authors: Ek Lars , Bjökman Jan‐Arne , Jandhyala Bhagavan S. 
Published: January 2005

AbstractCardiovascular effects of prenalterol, a partial beta adrenoceptor agonist, were investigated in pentobartial anesthetized dogs. In these preparations, in which the heart was acutely denervated, intravenous administration of prenalterol significantly enhanced contractility (left ventricular max dP/dt) as well as heart rate, and reduced left atrial pressure. Hence the data confirmed that this agent is an effective inotropic as well as a chronotropic agent. Ventricular function curves were determined in these studies to establish the efficacy of the myocardium in handling volume loads at various filling pressures. In order to relate the increased output directly to increases in inotropy, heart rate was kept constant by electrical pacing. Prenalterol significantly shifted these curves upward and to the left, indicating enhanced contractility. In a separate series, it was demonstrated that the inotropic effect of prenalterol persists for longer durations as indicated by the significant shift that occurred in left ventricular function curves 70 min after administration of a single dose of the drug. The data collectively suggest that prenalterol, an orally effective inotropic agent, possesses prolonged duration of action; hence, this drug may be more preferable than dopamine or dobutamine in the treatment of heart failure since the effects of these two agents are transient and are subjected to tolerance during continuous intravenous infusions.
Analgesic effect of acetaminophen‐codeine combination in mice
Authors: Hertz Françoise , Ranson Michèle , Deghenghi Romano 
Published: January 2005

AbstractThe analgesic activity of acetaminophen and codeine phosphate was evaluated in mice (writhing test and hot‐plate test) after oral administration. When the two drugs were administered in combination, a potentiation was obtained; the analgesic effect is 1.8–6.6 times greater than when each drug is given alone. A central component for acetaminophen analgesia was confirmed.
New perspectives for the clinical evaluation of atherosclerosis
Authors: Bond M. Gene , Morley Deborah 
Published: January 2005

AbstractTitle: New perspectives for the clinical evaluation of atherosclerosis. Atherosclerosis is a progressive and degenerative disease of the artery wall that begins relatively early in life but does not become recognized until it is severe enough to result in the development of clinical signs and symptoms. Too often, however, these clinical events are closely associated with morbidity and mortality. Much progress has been made in elucidating those risk factors associated with development of clinical endpoints; however, risk when used in this context is defined as increased chance and, except in unusual circumstances, cannot predict specific individuals who will develop signs and symptoms nor when these events will occur. Several methods have been developed during the last 25 years that have the potential for detecting atherosclerotic plaques in their preclinical stages. High‐resolution, B‐mode ultrasound imaging, particularly, has high sensitivity and specificity in detecting carotid artery plaques and in accurately measuring size characteristics of individual lesions. Reliability studies have demonstrated the possibility of detecting changes in asymptomatic carotid artery atherosclerosis with 95%percnt; confidence, if these changes are greater than ± 0.4 mm. Application of this noninvasive method to identify subjects with asymptomatic lesions, and to monitor plaque changes over time, will aid greatly in determining the efficacy of various therapies and potentially will decrease the mortality and morbidity associated with stroke.
Current approaches to inhibition of proliferation in atherosclerosis
Authors: Handley Dean A. 
Published: January 2005

AbstractAthersclerosis is characterized by progressive arterial stenosis of the major vessels of the systemic circulation. In man, atherosclerotic lesions are composed principally of smooth muscle cells, connective matrix derived from these cells, and variable amounts of lipid. Emphasized is the role of the platelet mitogen, platelet‐derived growth factor (PDGF), as a potent stimulus for the proliferation of smooth muscle cells in the development of atherosclerotic lesions. Animal models of proliferative atherosclerosis are reviewed, as are published references of approaches to inhibit smooth muscle cell hyperplasia in these models by drug administration. The results are discussed in terms of the potential therapeutic application of antiproliferative drugs designed to inhibit the mitogenic role of PDGF as a contributory factor in atherogenesis.
Pharmacological effects of HR 375: A new potential antipsychotic agent
Authors: Hock Franz J. , Kruse Hansjörg , Gerhards Hermann J. , Konz Elmar 
Published: January 2005

AbstractHR 375, a 3‐(4‐(3‐(4‐fluorobenzoyl)‐propyl‐piperazino‐l‐yl‐isoquinolino‐ hydrochloride is a new compound with marked effects in tests of predictive value for neuroleptic activity. Its pharmacological profile is different from classical neuroleptics. HR 375 has inhibitory activity in apomorphine‐induced climbing, amphetamine aggregation toxicity, Sidman avoidance, and amphetamine‐induced hypermotility. On the other hand, only weak activity is seen in antagonizing amphetamine‐induced stereotypy, apomorphine‐turning, and apomorphine emesis. It does not include catalepsy in rats and cynomolgus monkeys even in high doses. Also, its sedative or muscle relaxant properties are weak and short‐lasting. The psychopharmacological profile of HR 375 indicates a split between its effects on the mesolimbic and nigrostriatal system.
The effects of indomethacin upon physiological indices of gastric mucosal integrity
Authors: Pendleton Robert G. , Stavorski John M. 
Published: January 2005

AbstractIndomethacin was studied for its effects on three indices of gastric mucosal integrity in anesthetized cats. Following intragastric administration of the compound under conditions of constant stomach acidity and electrolyte concentrations, the transgastric potential difference declined in a gradual, linear fashion during the 210 min of the experimental period. These changes, which were dose related over the range of 1.25‐5 mg/kg of indomethacin, were accompanied by increased concentrations of luminal pepsin and blood. The results suggest that the transgastric potential difference is a sensitive indicator of gastric mucosal integrity under the conditions of this study.
Response of isolated renal artery rings to adenosine and inosine
Authors: Sinclair Richard J. , Randall John R. , Wise Gary E. , Jones Carl E. 
Published: January 2005

AbstractThe responses to adenosine and its analog, inosine, were compared in isolated rings of canine small renal arteries (0.5–1.3 mm o.d.). The rings were not contracted prior to nucleoside administration in order to detect any contraction response due to the nucleoside itself. Relaxation responses were elicited by progressively increasing the nucleoside concentration in the bathing medium. The maximal response (Rmax) was expressed as a percentage of the decrease in isometric tension. The ED50 for adenosine and inosine was 0.18 ± .002 μM and 202 ± 44 μM, respectively (P < 0.05) The Rmax for inosine was significantly less (P < 0.05) than that for adenosine, with a mean ratio of adenosine Rmax inosine Rmax of 1.47 ± 0.2. The results of these experiments indicated that adenosine and inosine directly relax isolated small renal arterial rings, although the classic in situ renal response to adenosine is increased resistance. Also, the relaxing action of adenosine, but not inosine, is significantly attenuated by 10 μM aminophylline. Further, renal arterial rings exhibit a greater sensitivity to adenosine than that previously reported for canine coronary artery rings, while the response to inosine is virtually identical.
Animal models to investigate drug effects on coronary physiology
Authors: Jones Carl E. , Gwirtz Patricia A. 
Published: January 2005

AbstractCoronary blood flow is regulated by local intrinsic mechanisms according to the oxygen need of the myocardium, but the coronary circulation is also modulated by nervous, humoral, and extravascular influences. Therefore, any method used to study drug effects on the coronary circulation must take into account not only the direct effects of the drug but also any secondary drug effects that might indirectly influence the coronary vasculature. The simplest methods involve the use of isolated vessels. With these methods, the environment of the vessel can be precisely controlled, although usually only vessels larger than true resistance vessels can be studied. Isolated heart models have also been successfully employed, and in these models, effects of the drug on the myocardium must be considered. More complex models include in vivo anesthetized animal techniques with intracoronary drug administratiorl. With these models, drug effects on the coronary circulation as well as on other cardiac variables can be examined. The use of conscious, instrumented animals perhaps provides the most physiologic preparation and is very useful, particularly if intracoronary administration of drugs is employed.
The neuropharmacological profile of tefludazine, a potential antipsychotic drug with dopamine and serotonin receptor antagonistic effects
Authors: Svendsen O. , Arnt J. , Boeck V. , Bøgesø K. P. , Christensen A. V. , Hyttel J. , Larsen J.‐J. 
Published: January 2005

AbstractThe neuropharmacology of tefludazine, a new neuroleptic with phenylindan structure, has been investigated in comparison with cis(Z)‐flupentixol, fluphenazine, haloperidol, methiothepin, thioridazine, and clozapine. Tefludazine showed potent dopamine (DA) antagonistic activity in a broad range of test models in vitro and in vivo in mice, rats, and dogs (receptor binding, antagonism of DA agonist‐induced behavior, inhibition of conditioned avoidance, catalepsy, etc.). High oral activity and long duration of action was found. Interestingly, the cataleptogenic potency at the time of peak effect was seven times weaker than the antistereotypic activity, in contrast with that observed with cis(Z)‐flupentixol, fluphenazine, and haloperidol. In addition to DA antagonism, tefludazine was equipotent at 5‐HT receptors (in vitro receptor binding, 5‐HT antagonism in isolated peripheral tissue, cardiovascular 5‐HT antagonism, antagonism of I‐5‐HTP‐ and 5‐MeODMT‐induced behaviors). No antimuscarinic and low α‐adrenoceptor blocking effect was found in pithed rats and in denervated cat nictitating membrane preparation. The DA/5‐HT activity profile of tefludazine resembled that of methiothepin, which, however, had potent α‐adrenoceptor blocking effect. It is concluded that tefludazine has a neuropharmacological profile that should combine antipsychotic potential with lower risk of extrapyramidal symptoms.