bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiinflammatory activity of topical auranofin in arachidonic acid‐ and phorbol ester‐induced inflammation in mice
Authors: Griswold Don E. , Chabot‐Fletcher Marie , Webb Edward F. , Martin Lenox , Hillegass Leonard 
Published: January 2005

AbstractThe antiarthritic, organogold compound auranofin was evaluated for its antiinflammatory activity in murine models of cutaneous inflammation. Initial studies involved the use of arachidonic acid‐induced inflammation, an evanescent response characterized by edema and neutrophil infiltration mediated, at least in part, by leukotrienes. The edema and myeloperoxidase (MPO) activity induced by application of arachidonic acid was assayed from the inflamed ears. After application of auranofin (1 mg or 1.47 m̈mol/ear in solution), inhibition of the MPO response was observed but little inhibition of the edematous response occurred. The application of 50 m̈l of 2% auranofin ointment (∼ 1.47 m̈mol/ear) administered after arachidonic acid resulted in the inhibition of both the edematous (54%) and the MPO (50%) components of the inflammatory response to arachidonic acid. It was found that auranofin in vitro weakly inhibited MPO activity, suggesting that inhibition of MPO‐derived oxidants might contribute to the antiinflammatory activity. In order to characterize further this antiinflammatory activity, the effect of auranofin on the response to the cutaneous application of phorbol ester (PMA) was studied. This psoriaform lesion involves intense infiltration of neurotrophils, microabcess formation and epidermal cell proliferation. The ear thickness and the MPO response were measured at 4 h after PMA application. In this model, auranofin in solution displayed marked, dose‐related antiinflammatory activity. The ED50s were calculated to be 0.12 (0.18 m̈mol) and 0.14 mg (0.21 m̈mol)/ear, respectively. An investigation of the antiinflammatory activity of the ointment was limited to the edematous response because of interference with the MPO analysis; however, potent antiinflammatory activity of the auranofin ointment proved to be dose‐related with an ED50 of 0.3% (0.22 m̈mol) at 2 h and 0.6% (0.44 m̈mol) at 4 h after PMA. In addition, if the response was allowed to proceed for 2 h before the application of ointment, further progression of the inflammation was essentially abolished. Despite strong inhibition of the inflammatory response, no significant alteration of PMA‐induced increased DNA content was demonstrable. Overall, the completeness of inhibition and potency observed with auranofin suggest that it may be of utility in the treatment of inflammatory diseases of the skin. ©1995 Wiley‐Liss, Inc.
Inhibition of pyruvate dehydrogenase kinase by halogenated acetophenones
Authors: Espinal Joseph , Leesnitzer Tony , Hassman Angela , Beggs Mark , Cobb Jeff 
Published: January 2005

AbstractThe activity of pyruvate dehydrogenase (PDH), and hence of glucose oxidation, is regulated by reversible phosphorylation. We have searched for novel PDH‐Kinase inhibitors using a high‐throughput microtiter plate assay. A series of halogenated acetophenones with potent activity against PDH‐Kinase (IC50 1–3 μM) and inactive towards other protein kinases was identified. The lead compound displayed non‐linear kinetics and was shown to be an uncompetitive inhibitor with respect to ATP. These novel inhibitors of PDH‐Kinase may be potential new drug leads for the treatment of diabetes or ischaemic conditions. © 1995 Wiley‐Liss, Inc.
Good laboratory practices and other regulatory issues: A European view
Authors: Sullivan Andrew T. 
Published: January 2005

AbstractSafety pharmacology studies provide information on the effects of new chemical entities on physiological function in experimental animals and complement classical toxicology studies which assess effects on bodily structure. Data from these studies help to predict possible adverse effects of a compound that might be seen during administration to man, and should therefore be classified as safety studies. It is a regulatory requirement in most areas of the world that safety studies be carried out in compliance with the principles of Good Laboratory Practice. The way in which United Kingdom pharmaceutical companies approach safety pharmacology has been surveyed, and a comparison has been made with practices in the United States. © 1995 Wiley‐Liss, Inc.
Structure – activity relationships of nicotinic acetylcholine receptor agonists as potential treatments for dementia
Authors: Holladay Mark W. , Lebold Suzanne A. , Lin Nan‐Horng 
Published: January 2005

AbstractThe ability of nicotine to enhance cognition in animals and humans and to exert neuroprotective and anxiolytic‐like effects, as well as the negative correlation between smoking and Alzheimer's (and Parkinson's) disease, suggest a possible role for nicotinic agents in the treatment of some of the deficits that result from these conditions. Numerous compounds are known which activate neuronal nicotinic acetylcholine receptors (nAChRs) and which might serve as lead compounds toward the development of such agents. The diversity of nAChRs suggests the possibility of developing selective compounds which would have more favorable side‐effect profiles than the existing agents. An overview of the nicotinic system and model systems used to study nicotinic receptors is presented, followed by a discussion of structure–activity relationships of known lead compounds in assays that are thought to reflect therapeutic potential or possible side effects. © 1995 Wiley‐Liss, Inc.
History of combinatorial chemistry
Authors: Furka Árpád 
Published: January 2005

AbstractThe paper describes and compares the utility of the three chemical methods used for the synthesis of combinatorial libraries: (1) the mixed reactant method, (2) the portioningmixing method, and (3) light‐directed synthesis. It also deals with historical aspects of these methods and with the most important screening methods associated with them. © 1995 Wiley‐Liss, Inc.
Antinociceptive effects of the alkaloid epibatidine: Further studies on involvement of nicotinic receptors
Authors: Badio Barbara , Shi Dan , Martin H. Martin , Daly John W. 
Published: January 2005

AbstractEpibatidine is a potent analgetic agent with high affinity for nicotinic receptors. The antinociceptive effects of epibatidine are blocked by both competitive and noncompetitive nicotinic antagonists. The L‐type calcium channel activator Bay K 8644 potentiates the antinociceptive effects of epibatidine, while nifedipine antagonizes the antinociceptive effects. Acute treatment with chlorisondamine leads to long‐term blockade of the antinociceptive effects of epibatidine. The antinociceptive effects of epibatidine are reduced in mice rendered tolerant to the behavioral effects of nicotine by chronic nicotine or caffeine treatment. Epibatidine has very high affinity for the major central nicotinic receptor to which [3H]nicotine binds. However, unlike nicotine and cytisine, epibatidine is very potent at ganglionic‐type nicotinic receptors. Epibatidine in cultured cells causes desensitization of both ganglionic and neuromuscular nicotinic receptors. Thus, like nicotine, chronic treatment with epibatidine might be expected to lead to tolerance. These studies establish epibatidine as a tool for the study of nicotinic pathways involved in pain perception. © 1995 Wiley‐Liss, Inc.
Procedure for the evaluation of the bioavailability of topical formulations in vivo as the rate and extent to which the active drug product is transferred from the vehicle to the skin
Authors: Vergés Josep , Castañeda‐Hernández Gilberto , Moragas José M. 
Published: January 2005

AbstractA procedure was developed for the in vivo evaluation of the bioavailability of topical formulations containing a limited amount of the active drug product estimated as the rate and extent to which the drug is released from the vehicle to the skin. It is assumed that drug transfer follows Fick's law of diffusion. The formulation tested was a cream containing 40 μmol/ml (20 mg/ml) of sertaconazole, a novel imidazole antifungal agent, applied to healthy volunteers. Eight 9 cm2 squares were marked in the volar forearm surface and 0.1 ml of the cream was applied to each square by gentle rubbing with a plastic thimble. The actually applied dose was estimated considering the drug amount that adhered to the thimble. Then one area at a time was cleansed at 0, 1, 2, 4, 6, 8, 12, and 24 h and the amount of sertaconazole transferred to the skin was estimated by determination of the amount of drug removed by cleansing. Drug release from the vehicle to the skin increased with time, but then reached a plateau. The maximal amount of drug transferred to the skin was 85.5 ± 3.3% (mean ± S.D.) of the actually applied dose, and this value was considered an expression of the extent of drug release. The rate of release was estimated as the half‐life of the transfer process, which was 1.83 ± 0.76 h. This procedure is suitable for the evaluation of topical formulations containing a limited amount of the active drug product. © 1995 Wiley‐Liss, Inc.
Cyclic AMP and adenyl cyclase in the developing rat brain
Authors: Schmidt M. J. , Palmer E. C. , Dettbarn W.‐D. , Robison G. A. 
Published: January 2005

AbstractThe level of endogenous cyclic AMP in the rat brain in vivo began to increase markedly between the third and sixth days after birth, as did the ability of norepinephrine to stimulate the formation of cyclic AMP in brain tissue in vitro. Adenyl cyclase activity in broken cell preparations, when measure in the absence of sodium fluoride, increased with age up to a point, but began to decline between the fifth and ninth days postpartum. Activity continued to increase when measured in the presence of fluoride, suggesting that the apparent stimulatory effect of this ion may in fact be the reversal of an inhibitory influence which is absent or almost absent at birth. Cyclase activity at all ages was restricted to particulate matter, whereas apparent phosphodiesterase activity was present in particulate as well as soluble fractions. The catabolic system for cyclic AMP developed in a similar manner in both fractions. Theophylline produced the same degree of inhibition of this system at all ages.
Ontogenesis of sleep in human prematures after 32 weeks of conceptional age
Authors: Dreyfus‐Brisac C. 
Published: January 2005

AbstractThe ontogenesis of sleep was studied in prematures from 32 to 41 weeks of gestational age The characteristics of the EEG, the patterns and rate of respiration, the cardiac rate, body motility comprised of localized and diffuse movements, localized and diffuse jerks, clonic movements and electromyo‐graphic activity of the chin, as well as periods of total quietness were observed and correlated with the progressive organization of behavior in these infants. The data obtained at each gestational age, i.e., at 32–34 weeks, 35–37 weeks, and 38–41 weeks, were compared to those obtained in full‐term newborns. The relationships between the different events and the features of the EEG and of the respiratory patterns were ascertained and compared to similar data obtained in the full‐term newborn. This comparison shows that the premature at 40 weeks of gestational age has not attained a level of organization as high as that of the full‐term newborn. An hypothesis suggesting a possible mechanism of this discrepancy is presented.
Protein malnutrition induced during gestation: Its effect on pup development and maternal behavior
Authors: Massaro Thomas F. , Levitsky David A. , Barnes Richard H. 
Published: January 2005

AbstractRepeated time‐lapse photographic observations were used to examine the ontogeny of behavioral development in prenatally malnourished rat pups following birth. Pups born to dams receiving a low protein diet (7% casein by weight) were fostered at birth to well‐nourished dams and behavioral observations were made at 4‐day intervals. Dams nursing gestationally malnourished pups were observed to spend more time in the nesting area with their pups towards the end of lactation. Moreover, the behavioral development (locomotion, feeding, and rearing and climbing activity) of gestationally malnourished offspring was depressed when compared to their controls. The results indicate that prenatal undernutrition alters the behavioral development of the offspring and maternal behavior of the dam in a manner which reduces the exposure of the pup to the immediate environment.
Effects of feeding on state and cardiac regulation in the infant
Authors: Harper R. M. , Hoppenbrouwers T. , Bannett D. , Hodgman J. , Sterman M. B. , McGinty D. J. 
Published: January 2005

AbstractThe effects of feeding on polygraphic state patterns and associated cardiac rates were examined in 8 normal infants using data collected during 12‐hr continuous monitoring sessions at 1 week and at 1, 2, 3, 4, and 6 months of age. The distribution of states and corresponding heart rate values were tabulated for each minute during 2‐hr periods preceding and following wakenings with and without feedings. Rapid eye movement (REM) sleep was significantly more prevalent immediately following a waking accompanied by feeding than waking alone. Moreover, a distinct relationship was demonstrated between feeding periods and the ongoing sleep cycle. In younger infants (1 week to 1 month), heart rates in quiet sleep (QS) and REM were higher after feeding than before, suggesting a general arousal influence. This was not the case with nonfeeding wakenings. In older infants (2–3 months), heart rates were higher after nonfeedings periods than before, but similar before and after feeding periods.
The development of sexual behavior in the rat: Role of preadult nutrition and environmental conditions
Authors: Hansen Stefan , Larsson Knut , Carlsson Sven G. , Sourander Patrick 
Published: January 2005

AbstractRats were subjected to pre‐ and postnatal undernutrition by restricting the food intake of their mothers (U); another group of rats was normally fed (N). Each nutrition group was divided into 3 subgroups by varying the degree of environmental stimulation: animals in the Max group were stimulated by handling and enriched rearing conditions; the Min group rats were subjected to social isolation; rats in the control condition (C) were raised under ordinary laboratory conditions. The onset of sexual activity was not affected in the U‐C male rats, but was delayed in both U‐Min and N‐Min rats. Although no difference existed in the age of puberty between the N‐Max and N‐C animals, the U‐Max rats displayed an advancement of puberty by 7 days in comparison to the U‐C rats. Undernutrition did not affect female sexual maturation; however the Max condition delayed this process in both nutrition groups.
Exploration, distraction, and habituation in rats reared in isolation
Authors: File Sandra E. 
Published: January 2005

AbstractRats reared in isolation have been reported to show increased motor activity; the purpose of the present experiment was to establish whether they also show enhanced exploratory and orienting responses. Rats were reared in isolation or in social groups from Day 20 to Day 45. Subgroups of each rearing condition were either left undisturbed, received daily handling, or received daily handling and were given objects in their cages. From Day 45 all the rats were rehoused in groups of 6, and testing began at Day 73. In a 1st test exploration was measured by the number of contacts with objects placed in the home cage; in a 2nd test exploration was measured by responses to a holeboard; and in a 3rd test orienting was measured by the distraction produced by the presentation of a tone. When tested in novel situations, in contrast to their enhanced motor activity, isolates showed reduced exploration and orienting. This may have been due to a discrepancy between their adaptation level (established during rearing) and their current level of sensory input. In all the tests the isolates showed normal habituation, both within sessions and between sessions. An inability to habituate is not, as has been claimed, a general characteristic of isolates.
Effects of amount of contact between mother and child on the mother's nursing behavior
Authors: Carlsson Sven G. , Fagerberg Helena , Horneman Göran , Hwang Carl‐Philip , Larsson Knut , Rödholm Margaretha , Schaller Joseph , Danielsson Bernt , Gundewall Christer 
Published: January 2005

AbstractShort‐term effects of different amounts of body contact between mother and newborn on human nursing behavior were studied. Extended contact immediately after parturition was related to an increase in affective components of maternal nursing behavior observed on postpartum Days 2 and 4.
Neonatal ultrasounds elicited by odor cues
Authors: Conely Lynn , Bell Robert W. 
Published: January 2005

AbstractUltrasounds were monitored from neonatal rats following placement on 1 of 5 types of bedding material. Odors associated with the home cage or an adult male inhibited neonatal ultrasonic signaling. Odors associated with a novel lactating female elicited initially high rates of signaling, the rate lowering across the age range of pups tested. Odors associated with a novel virgin female or with an absence of animal odors elicited increasing rates of signaling across the age range tested.
Differential effects of handling on exploration in male and female rats
Authors: Weinberg Joanne , Krahn Emily A. , Levine Seymour 
Published: January 2005

AbstractIn this study, sex differences in the exploratory behavior of handled and nonhandled animals were measured under conditions of both high and low stimulus variation. The apparatus used was a hole‐board, which provided an exploratory response independent of ambulation. Significant effects of handling were found: nonhandled animals decreased head‐dipping over days whereas handled animals maintained a high rate. Sex differences were also observed: patterns of head‐dipping for males and females differed over days depending on whether objects were present (high stimulus variation) or absent (low stimulus variation) under the hole‐board; females also head‐dipped for longer durations than males when objects were present; further, males and females showed completely opposite patterns of exploration depending on handling treatment and on level of stimulus variation. We conclude that handling differentially affects males and females, particularly as level of stimulus variability changes.
Maternal behavior of wild and domestic Rattus norvegicus recorded continuously in dual‐chambered cages
Authors: Hughes Carroll W. , Harlan Rebecca S. , Michael Plaut S. 
Published: January 2005

AbstractContinuous measurements of maternal behavior–the amount of time the mother was in contact with the litter and quality of nest–indicated no differences between these 2 stocks of rats. A decrease in both measures was found for both stocks over the 22 days of postnatal observation. The data indicated that the mother was with the litter more during the light portion of the 24‐hr light‐dark cycle and that wild rat mothers were in contact with their litters more than domestic mothers in the period around light offset.
The effects of litter size during gestation and lactation on rat development prior to weaning
Authors: Wehmer Francine , Jen Kai‐Lin Catherine 
Published: January 2005

AbstractPhysiological and behavioral development of rats was affected by prenatal nutrition and postnatal litter size. Prenatal nutrition was manipulated by combining differences in maternal nutrition with variation of prenatal litter size produced by pre‐mating isolation of 1 uterine horn. The pups were reared in postnatal litters of either 4 or 12. During the 1st postnatal week, development and free behavior were affected only by the prenatal treatments. During the 2nd postnatal week, both prenatal and postnatal effects were observed. Development and behavior during the 3rd postnatal week reflected only postnatal litter size. Brain weight at weaning was influenced by both the prenatal and postnatal treatments.
Response of the infant rat to light prior to eyelid opening: Mediation by the superior colliculus
Authors: Routtenberg Aryeh , Strop Marguerite , Jerdan Janice 
Published: January 2005

AbstractAlthough the influence of light on the infant rat before Day 14, when its eyelids open, are presumed to be minimal, we have shown that as early as postnatal Day 6, male and female albino rats demonstrate negative phototaxis. Bilateral enucleation eliminates negative phototaxis. whereas unilateral enucleation does not. Rearing in the dark does not prevent the expression of the behavior. Knife cuts on postnatal Day 5, which undercut the dorsal midbrain involving the superior colliculus, prevent the expression of this response to light. Unilateral dorsal midbrain knife cuts and posterior cortex lesions have no effect. These results call attention to an early period in the postnatal development of the rat when it is capable of exhibiting negative phototaxis. The superior colliculus in the dorsal midbrain appears to be crucial for demonstrating this behavior.
Alleviation of forgetting in preweanling rats
Authors: Spear Norman E. , Smith Gregory J. 
Published: January 2005

AbstractThree experiments tested the learning and retention of neonatal rats (7, 9, and 12 days of age) with a nondirectional active avoidance task, using a vibrotactile conditioned stimulus. The hypothesis was that the substantial deficit of these animals in 24‐hr retention is due, at least in part, to a deficiency in memory retrieval. In Experiment I, a reactivation treatment was found to alleviate the forgetting over the 24‐hr period for 12‐day olds although having somewhat lesser effect for animals 9 days of age. The reactivation treatment seemed ineffective for rats 7 days of age. Experiments II and III confirmed the reliability of the reactivation effects with 9‐ and 12‐day olds, while adding further control conditions and providing new information concerning the ontogenesis of latent inhibition.
Neurological development of kittens
Authors: Villablanca Jaime R. , Olmstead Charles E. 
Published: January 2005

AbstractThe neurological development of the kitten was studied from birth to 120 days of age. Three motor features present at birth disappeared within the 1st 45 days of life. The labyrinthine head and body righting reactions were present at birth; the latter matured only by 25 days of age when the air righting reaction (mature by 35 days) started to appear. Limb placing reactions developed progressively with proprioceptive components being present at birth whereas tactile components evolved slowly from early contact lifting to forepaws contact placing (60 days) and narrow plank walking (75 days). Standing and walking were well developed by 45 days. Eye opening occurred at 9.5 days and several eyeblink reactions (including blink to light) were present at birth. Adequate binocular coordination was seen by 47 days. Vision progressed parallel to the clearing of the ocular media which were fairly transparent by 32 days. Visually guided paw placing and the visuopalpebral blink reflex matured later (by 37 and 59 days, respectively). The external auditory canal and pinna were fully developed by 12 and 31 days, respectively; spontaneous and tactile pinna movements were present at birth; orienting to animal and nonanimal sounds was well developed by 6.5 and 18 days, respectively; spatial sound localization was developed by 16 days and differential responding to animal sounds matured by 24.5 days. Somatic responses and olfaction were present at birth but matured further thereafter. Playful interactions between kittens started by 10–15 days and well developed play behavior was seen by 36–40 days. In brief, all neurological functions mature progressively during the 1st 3 postnatal months.