bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypotensive responses to the putative adenosine A3 receptor agonist N6‐2‐(4‐aminophenyl)‐ethyladenosine in the rat
Authors: Carruthers Alan M. , Fozard John R. 
Published: January 2005

AbstractThe hypotensive response to the putative adenosine A3 receptor agonist, N6‐2‐(4‐aminophenyl)ethyladenosine (APNEA), has been further investigated. In pithed rats with blood pressures maintained at normal values with angiotensin II, the hypotensive response to APNEA was resistant to blockade by 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX) at a dose of 0.5 mg kg (1.7 μmol kg) iv, which abolished the bradycardia to APNEA and that to the prototype A1 receptor agonist, N6‐cyclopentyladenosine (CPA). The xanthine‐resistant hypotensive responses to APNEA were broadly similar in pithed animals whose blood pressures were maintained by phenylephrine, clonidine, or the inhibitor of nitric oxide (NO) synthase, NG‐nitro‐L‐arginine methyl ester (L‐NAME). The blocker of ATP‐dependent potassium (KATP) channels, glibenclamide, did not affect the hypotensive response to APNEA in animals infused with angiotensin II. Thus, the xanthine‐resistant hypotensive response to APNEA is not an effect dependent on a particular agonist‐receptor interaction. Neither the release of NO, newly synthesized from L‐arginine, nor activation of glibenclamide‐sensitive KATP channels can explain the putative A3 receptor‐mediated hypotensive response to APNEA. © 1993 wiley‐Liss, Inc.
Acadesine attenuates ischemic cardiac dysfunction in the isolated blood‐perfused rabbit heart
Authors: Young Mark A. , Mazur Curt , Mullane Kevin 
Published: January 2005

AbstractAcadesine (AICA‐riboside) is a nucleoside analog with cardioprotective properties. Most previous studies demonstrating cardioprotection with acadesine have been conducted in buffer‐perfused hearts, and no study has investigated the dose‐response relationship to acadesine in a blood‐perfused model. The objective of this study was to investigate the dose‐related cardioprotective effects of acadesine in donor‐perfused, isolated rabbit hearts subjected to 12 × 3 min episodes of global ischemia with intervening periods of reperfusion of 5 min duration. Five groups of hearts were studied: saline control and four treatment groups of acadesine, 0.1, 0.2, 0.5, 2.0 gm/kg/min (0.4, 0.8, 2.0, 8.0 μmol/kg/min) constant intravenous infusion to the support animal. Left ventricular (LV) pressure and coronary blood flow (CBF) in the isolated hearts were measured. In control hearts, baseline LV developed pressure averaged 129 ± 7 mmHg and declined to 43 ± 3% of baseline after 12 periods of ischemia and reperfusion. Acadesine significantly improved recovery of function at the lower doses tested, i.e., hearts treated with 0.1, 0.2, and 0.5 mg/kg/min (0.4, 0.8, 2.0 μmol/kg/min) recovered 61 ± 5%, 67 ± 7%, and 65 ± 7% of LV pressure, respectively (P < 0.05 vs. saline). This protective effect was not observed with the highest dose of acadesine, 2.0 mg/kg/min (8.0 μmol/kg/min) (52 ± 6%). The greatest recovery of function corresponded to plasma acadesine concentrations of 27 ± 6.0 μM, but the beneficial effect was lost when plasma concentrations reached 205 ± 28 μM. These results suggest that repetitive episodes of ischemia and reperfusion induced stunning in isolated blood‐perfused rabbit hearts, and that the severity of this dysfunction is attenuated by treatment with acadesine. © 1994 Wiley‐Liss, Inc.
Safety pharmacology of the respiratory system: Techniques and study design
Authors: Murphy Dennis J. 
Published: January 2005

AbstractThe known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo‐ or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow‐volume and pressure‐volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post‐dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs.
CL 284,846, a novel sedative‐hypnotic: Evaluation of its metabolites for pharmacological activity in vitro and in vivo
Authors: Vanover Kimberly E. , Mangano Richard M. , Barrett James E. 
Published: January 2005

AbstractCL 284,846, N‐[3‐3‐cyanopyrazolo[1,5‐a]pyrimidin‐7‐yl(phenyl)]‐N‐ethylacetamide, is a novel non‐benzodiazepine sedative‐hypnotic with benzodiazepine‐like sedative effects, but with less apparent liability for accompanying undesired side effects. Three metabolites of the parent sedative‐hypnotic have been isolated and identified, a desethyl metabolite, CL 284,859, a desethyl‐5‐keto metabolite, CL 345,644, and a 5‐keto metabolite, CL 345,905. In experiments to determine the ability of these compounds to displace [3H]‐flunitrazepam from rat cortical benzodiazepine receptors, the IC50 values were 205 nM for CL 284,846 compared to 4.5 nM for diazepam as a positive control, and 11 μM for CL 284,859. The other two metabolite, CL 345,644 and CL 345,905, failed to displace [3H]‐flunitrazepam. In a second experiment designed to evaluate in vivo receptor‐mediated activity, CL 284,846 (3.0 mg/kg; 9.836 μmol/kg) was established as a discriminative stimulus (DS) in rats. While CL 284,846 (0.03ndash;3.0 mg/kg; 0.098–9.836 μmol/kg) showed a doserelated increase in drug‐appropriate responding and one dose of triazolam (0.3 mg/kg; 0.875 μmol/kg) substituted as a positive control, all three metabolites (3.0–100.0 mg/kg; 10.3–341.3 μmol/kg for CL 284,859; 6.0–201.2 μmol/kg for CL 345,644; 9.3–311.5 μmol/kg for CL 345,905) failed to substitute for the DS effects of CL 284,846. These results suggest that CL 284,859, CL 345,644, and CL 345,905, the metabolites of the sedative‐hypnotic CL 284,846, have no significant neuropharmacological effects at central benzodiazepine receptors and, thus, do not contribute to the activity of the parent compound. © 1994 Wiley‐Liss, Inc.
DIVERSOMERTM technology: Solid phase synthesis, automation, and integration for the generation of chemical diversity
Authors: Dewitt Sheila Hobbs , Schroeder Mel C. , Stankovic Charles J. , Strode John E. , Czarnik Anthony W. 
Published: January 2005

AbstractThe drug discovery process depends upon the synthesis and testing of thousands of compounds to bring a new drug through discovery, clinical testing, development, and FDA approval. Recent advances in high throughput screening have created the need for the accelerated synthesis of small organic molecules. By combining solid phase chemistry, organic synthesis, and automation with a unique apparatus capable of performing techniques common to organic synthesis, “libraries” of organic compounds (DIVERSOMERSTM) are efficiently generated. This was demonstrated by the multiple simultaneous synthesis of 40 hydantoins and 40 benzodiazepines, related to Dilantin® and Valium®, respectively. © 1994 Wiley‐Less, Inc.
D2 and 5‐HT2 modulation of psychostimulant‐induced facilitation of brain stimulation reward
Authors: Tsibulsky Vladimir , Dashevsky Boris , Frank Robert A. 
Published: January 2005

AbstractPrevious research in our laboratory demonstrated that mixed D2/5‐HT2 antagonists (i.e., MDL 28, 133A, and risperidone) attenuate both amphetamine and cocaine‐induced facilitation of brain stimulation reward. The relative contributions of dopaminergic and serotonergic antagonism to these effects was assessed in the present study. Factorial combinations of the D2 antagonist eticlopride and the 5‐HT2 antagonist MDL 100,907 were evaluated for their ability to reverse both cocaine and amphetamine‐induced facilitation of brain stimulation reward. Eticlopride significantly reduced the effects of both amphetamine and cocaine, while MDL 100,907 had no effect on self‐stimulation thresholds when administered alone, or in combination with eticlopride. Thus, no evidence for serotonergic regulation of the euphoric effects of psychostimulants was obtained. © 1995 Wiley‐Liss, Inc.
Profile of analgesic interaction between aspirin and d‐propoxyphene obtained by means of the surface of synergistic interaction
Authors: López‐Muñoz Francisco J. 
Published: January 2005

AbstractThe analgesic effects of aspirin [acetyl salicylic acid (ASA)] and d‐propoxyphene (PROP) administered either separately or in 24 different combinations were determined in the pain‐induced functional impairment in the rat (PIFIR) model. This allowed the detection of the profile of analgesic interaction of the combinations. Furthermore, we set out to determine the optimal degree of potentiation obtained with a specific combination of the above drugs by means of the surface of synergistic interaction of the combinations. This parameter was calculated from the total analgesic effect produced by the combination after having subtracted the analgesic effect produced by each drug alone. The ED50 for ASA and PROP were 210.4 ± 1.2 and 66.3 ± 1.2 mg/kg, respectively. Over the dose ranges used, the analgesic activities of either ASA or PROP tended to be smaller than those of their respective combinations. Furthermore, 10 combinations showed various degrees of potentiation (P < 0.01), while the others (14) exhibited additive analgesic effects. The combination of ASA (562.3 mg/kg, po) and PROP (31.6 mg/kg, sc) produced the maximum analgesic effect. However, 5 combinations of ASA with PROP (56.2–56.2, 100–56.2, 177.8–56.2,316.2–56.2, and 177.8–31.6 mg/kg) produced the highest potentiation effects. The surface of synergistic interaction clearly showed which combination of these analgesic drugs produced the highest degree of potentiation in the rat. This study shows that a specific ratio of combination of analgesic drugs can produce optimum potentiation of their analgesic effects. © 1995 Wiley‐Liss, Inc.
Clinical and regulatory perspectives on general/safety pharmacology tests: Results of a pharmaceutical industry survey
Authors: Murphy Dennis J. , Gossett Kent A. , Kerns William D. 
Published: January 2005

AbstractGeneral/safety pharmacology is an emerging discipline within the pharmaceutical industry in which unanticipated effects of new drug candidates on major organ function (i.e., secondary pharmacological effects) are critically assessed in a variety of animal models. A survey was conducted to obtain customer input on the role and strategies of this emerging discipline. Four surveys were distributed to each of 30 U.S. pharmaceutical companies. Two surveys went to individuals within the regulatory department, and two went to individuals within the clinical department of each company. All responses were returned anonymously to the survey authors. Sixty‐six responses from at least 19 different companies were obtained. The responses from the clinical and regulatory departments were essentially the same and led to the following conclusions: (1) Major organ functions are monitored routinely in clinical trials to assess potential adverse drug effects; (2) major organ function studies are considered an essential part of non‐clinical drug safety testing; (3) respiratory, gastrointestinal, autonomic, and endocrine evaluations are considered an important part of major organ function studies, whereas cardiovascular, renal and central nervous evaluations are considered essential; (4) non‐clinical testing of these major organ functions should be conducted early in drug development, preferably before initiation of clinical trials; and (5) organ function investigations involving mechanisms of secondary pharmacological effects or drug interaction are considered an important part of general/safety pharmacology testing. © 1995 Wiley‐Liss, Inc.
Effect of cutaneous stimulation on the development of misdirected wiping reflexes in skin‐grafted Discoglossus pictus
Authors: Baker Robert E. , Veltman Wim A. M. , Corner Michael A. 
Published: January 2005

AbstractThe frog, Discoglossus pictus, has been studied with respect to wiping reflex behavior developing after skin rotations performed at larval stages. Misdirected wiping reflexes were obtained only from belly skin‐grafts placed on the animals's back; back skin‐grafts on the belly failed to elicit any misdirected limb movements in this species. We found that misdirected reflexes occurred more readily in 3‐week and older animals if not subjected to any previous test experience, than in younger naive frogs. Frogs that had been exposed to daily cutaneous stimulation between 2 to 4 weeks after metamorphosis showed a delayed development of misdirected responses.
System organization of alimentary behavior in the newborn and the developing cat
Authors: Anokhin Peter K. , Shuleikina Kira V. 
Published: January 2005

AbstractThis review deals with the structural, behavioral, and EEG correlates of searching for food and food intake. Data were collected on freely behaving kittens of 1 to 60 days of age with chronically implanted electrodes. The 1st manifestations of hunger involve activation of limbicreticular structures and electroencephalographic (EEG) activity consisting of fast oscillations of 30–40–60 cps, correlated with general behavioral arousal as manifested by motor restlessness and vocal reactions. The more specific behavior form of hunger‐feeding motivation‐involves structures that include the motor and parietal cortex, amygdala, and medial hypothalamus; the EEG activity consists of high‐amplitude, slow waves of 3–6 or 6–8 cps; and the behavioral correlate is purposeful search for the mother's teat or food. Satiation is associated with activity of the synchronizing structures in the forebrain and lower brain stem, as well as in the relay nuclei that transmit the sensory flow from oral afferents; EEG activity consists of regular rhythms of 10–14 and 2–4 cps; and the behavioral correlate is the act of feeding.
The relationship between sucking and grasping in the human newborn: A precursor of hand‐mouth coordination?
Authors: Brown Josephine V. , Fredrickson W. Timm 
Published: January 2005

AbstractThe relationship between grasping and sucking, a possible precursor of hand‐mouth coordination, was examined in human newborns of varying gestational ages. Grasping was elicited by rapidly titling the infant backwards while he rested on a padded board and held a grasp bar. Infants were titled 4 times under each of 3 conditions: grasping, sucking, and grasping‐while‐sucking. The dependent variables were strength and duration of grasp and frequency and amplitude of sucks during the 15 sec following the tilt. The results indicated that grasping did not affect sucking but that sucking increased the strength and the duration of the grasp. Furthermore, either response system was more highly correlated with indices of maturity of the central nervous system when elicited in the presence rather than the absence of the other. We conclude that in human newborns sucking may be dominant over grasping but that both are part of an integrated system which may form the basis for the development of hand‐mouth coordination.
An observational study of caretaking behavior of male and female mice housed together
Authors: Priestnall Robin , Young Susan 
Published: January 2005

AbstractA time‐sampling procedure was employed to examine the caretaking behavior of male mice housed with lactating females and their litters, and to investigate the effects of the male's presence on the behavior of the female. The incidences of 14 categories of behavior were recorded over 20 hr distributed throughout the period of lactation. The development of litters was monitored by regular weighing. The results show, contrary to earlier findings, that males display just as much caretaking behavior as females. Differences in other forms of behavior can be related to the increased nutritional needs of the nursing mothers. The presence of the male seems to have very little influence on the behavior of the female and no effect at all upon the physical development of the litter.
Individual differences during the development of the domestic chick's attraction toward intermittent light
Authors: Simner Marvin L. 
Published: January 2005

AbstractStable and persisting individual differences occur in the domestic chick's attraction toward normally preferred rates of intermittent white light in the vicinity of 4 flashes per second during the period around hatching when this preference develops. These differences are not linked to fluctuations in the test environment, high levels of indiscriminate responding toward flicker in those most attracted, the presence of an alternate rate preference in those least attracted, or to differences among chicks in arousal level or locomotor ability.
Specificity of litter odors in the control of home orientation among kittens
Authors: Freeman Natalie C. G. , Rosenblatt Jay S. 
Published: January 2005

AbstractThe specificity of maternal‐home cage odors governing home orientation was tested in 8‐ to 11‐day‐old kittens. Kittens were first tested for home orientation from the adjacent corner in their own home cages and cages of other mothers with litters of the same age. The majority of kittens oriented successfully in their own cages but not in strange mothers' cages. They then lived for 48 hr in the strange mothers' cages. At the end of this time they showed no improvement in orientation in their own home cages. Moreover, after an additional 24 hr in their own home cages they showed no improvement in their own home cage. Home orientation involves 2 odor components: 1 general to different mothers and 1 specific to each mother.
The onset of rhythmic activities in normal and high‐risk infants
Authors: Field Tiffany , Ting George , Shuman H. H. 
Published: January 2005

AbstractThe onset of rhythmic activities was compared for 2 groups of high‐risk infants (a preterm Respiratory Distress Syndrome and a postterm postmature group) and a normal term group over their 1st year of life. The postterm postmature group experienced earlier onsets of rhythmic activities. The preterm RDS group showed delays in the onset of rhythmic activities, but when a correction was made for the prematurity, did not differ from the other groups. These differences suggest that the onset dates for rhythmic activities are not affected by the perinatal complications of RDS or postmaturity, but are related to gestational age differences. A comparison of the 3 groups on Bayley 1st‐year motor skills revealed group differences even after an adjustment for gestational age differences, suggesting that the development of motor skills, unlike the development of rhythmic activities, may have been affected by these perinatal complications.
Effects of the duration of dark rearing on visually guided behavior in the kitten
Authors: Crabtree John W. , Riesen Austin H. 
Published: January 2005

AbstractForty‐eight kittens were dark reared or light reared from birth for 1 to 8 months and formed 6 age groups. Following rearing the kittens were examined daily in several tasks of visually guided behavior. Compared to younger dark‐reared groups of kittens, older deprived groups showed longer acquisition times for visual placing to a surface, visual tracking, visually guided reaching to a serrated edge and moving object, and visually guided locomotion on elevated platforms. After dark rearing durations of 3 months or longer, deprived groups displayed overall deficiencies in obstacle avoidance during their 1st postdeprivation month. The older dark‐reared groups gave some indication of a direct relationship between duration of dark rearing and both delay in acquisition times for the visually guided behaviors and deficiency in obstacle avoidance. One interpretation of the results is that during dark rearing the kitten may acquire nonvisual behaviors which could interfere with and prolong its development of visually guided behavior subsequent to deprivation.
Postnatal undernutrition in rats: Attempts to develop alternative methods to food deprive pups without maternal behavioral alteration
Authors: Codo W. , Carlini E. A. 
Published: January 2005

AbstractTwo methods were investigated as attempts to undernourish rat pups without the disturbances in maternal behavior that accompany the procedures used to date for this purpose. In the 1st method, a litter of 12 pups was raised by both a lactating mother and a “sensitized” female. The sensitized female was provided under the assumption that she could correct for the deficit in maternal care when 1 mother raises a large litter. The results showed that the pups raised by the 2 females were constantly removed by the females from each other's nests; the females engaged in constant fighting and showed altered maternal behavior. As a consequence the pups lost more weight than control underfed young. The 2nd method consisted of removing 6‐8 nipples from virgin females which were mated 10 days later. After delivery these females raised litters of 6 pups. Their maternal behavior was equal to that of unoperated controls, and at weaning the pups had 20–50% less body weight. This method could be useful to study undernutrition effects on behavior, without confounding experimental variables.
Lateral differences and head‐turning responses to somesthetic stimulation in premature human infants
Authors: Lewkowicz David , Gardner Judith , Turkewitz Gerald 
Published: January 2005

AbstractHead‐turning responses to somesthetic stimulation of the perioral region were studied at weekly intervals in 25 prematurely born infants. No regular changes associated with age were evident. The premature infants were more likely to turn towards than away from a stimulus; however, they were less so than are full‐term infants. The infants were as likely to turn towards the stimulus when it was on the left as when it was on the right; however, they were more likely to turn away from a stimulus on the left than on the right. Comparisons with full‐term infants indicated reduced lateral differences in responding. Such a reduction is in sharp contrast with the previous finding of marked postural asymmetry in a comparable sample of prematurely born infants. These data indicate a possible sequence in the development of head‐turning responses to somesthetic stimulation and the assumption and maintenance of an asymmetrical head posture which consists of (1) a right‐turning postural bias, (2) contralateral responding to somesthetic stimulation, (3) lateral differentiation of contralateral responding, (4) ispilateral responding, and (5) lateral differentiation of ipsilateral responding.