104 research outputs found
Pharmacological profile of a potent, efficacious fentanyl derivative in rhesus monkeys
The recent synthesis of fentanyl derivatives, some of which appear to have novel profiles of pharmacological effects, has provided compelling evidence that ÎŒ opioid efficacy might be altered systematically by modifications in the parent compound fentanyl. In the present study a new 4-(heteroanilido)-piperidine, compound 28, was studied for its effects in rhesus monkeys. In self-administration studies compound 28 maintained rates of lever pressing similar to those maintained by alfentanil; the reinforcing effects of compound 28 were attenuated by the opioid antagonist quadazocine. In drug discrimination studies compound 28 did not substitute for the Îș agonist ethylketocyclazocine and did substitute for the ÎŒ agonist alfentanil. In morphine-treated subjects discriminating between saline and naltrexone, compound 28 did not substitute for naltrexone; however, in morphine-abstinent subjects compound 28 reversed naltrexone lever responding. Moreover, this discriminative stimulus effect in morphine-abstinent subjects was antagonized by naltrexone and by quadazocine in a manner consistent with ÎŒ receptor mediation. Compound 28 also was an effective analgesic in a warm-water, tail-withdrawal procedure and it decreased markedly respiratory function. The analgesic effects as well as the respiratory depressant effects of compound 28 were antagonized by quadazocine. Together, these results show compound 28 to be a potent, efficacious ÎŒ agonist of similar potency to alfentanil. Large differences in apparent efficacy at ÎŒ receptors between compound 28 and another compound in this series (mirfentanil), clearly demonstrate that, within this chemical family, small chemical changes can confer significant differences in pharmacologic effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46340/1/213_2005_Article_BF02245876.pd
Impact of Space Weather on Climate and Habitability of Terrestrial Type Exoplanets
The current progress in the detection of terrestrial type exoplanets has
opened a new avenue in the characterization of exoplanetary atmospheres and in
the search for biosignatures of life with the upcoming ground-based and space
missions. To specify the conditions favorable for the origin, development and
sustainment of life as we know it in other worlds, we need to understand the
nature of astrospheric, atmospheric and surface environments of exoplanets in
habitable zones around G-K-M dwarfs including our young Sun. Global environment
is formed by propagated disturbances from the planet-hosting stars in the form
of stellar flares, coronal mass ejections, energetic particles, and winds
collectively known as astrospheric space weather. Its characterization will
help in understanding how an exoplanetary ecosystem interacts with its host
star, as well as in the specification of the physical, chemical and biochemical
conditions that can create favorable and/or detrimental conditions for
planetary climate and habitability along with evolution of planetary internal
dynamics over geological timescales. A key linkage of (astro) physical,
chemical, and geological processes can only be understood in the framework of
interdisciplinary studies with the incorporation of progress in heliophysics,
astrophysics, planetary and Earth sciences. The assessment of the impacts of
host stars on the climate and habitability of terrestrial (exo)planets will
significantly expand the current definition of the habitable zone to the
biogenic zone and provide new observational strategies for searching for
signatures of life. The major goal of this paper is to describe and discuss the
current status and recent progress in this interdisciplinary field and to
provide a new roadmap for the future development of the emerging field of
exoplanetary science and astrobiology.Comment: 206 pages, 24 figures, 1 table; Review paper. International Journal
of Astrobiology (2019
Competitive and uncompetitive N -methyl- d -aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine
The purpose of the present studies was to examine representative uncompetitive and competitive NMDA antagonists, as well as the glycine/NMDA antagonist, HA 966, in pigeons trained to discriminate either PCP or CGS 19755 from saline. Separate groups of pigeons were trained to discriminate either the uncompetitive, phencyclidine (PCP; 0.32 and 1.0 mg/kg, IM), or the competitive, CGS 19755 ( cis -4-phosphonomethyl-2-piperidine-carboxylic acid; 1.8 mg/kg, IM), NMDA antagonists from saline. Uncompetitive and competitive NMDA antagonists were examined in generalization studies, as were the racemate and the (+) and (â) stereoisomers of HA 966 (3-amino-1-hydroxypyrrolid-2-one). Dizocilpine (MK 801) was fully generalized to PCP but not to CGS 19755. All competitive NMDA antagonists tested were fully generalized to CGS 19755, but not to PCP. The competitive antagonists, however, produced >50% PCP-appropriate responding. The (+) isomer of HA 966 was fully generalized by three of four pigeons discriminating PCP (1.0 mg/kg) or CGS 19755, whereas the racemate and the (â) isomer produced 10% drug-appropriate responding in either discrimination group. The competitive antagonists tended to produce peak drug-appropriate responding at times greater than 60 min after administration, whereas uncompetitive antagonists produced peak drug-appropriate responding at earlier times. HA 966 also had a relatively slow onset of action as compared to PCP. These results suggest that antagonists acting at different modulatory sites of the NMDA receptor complex produce similar, but not identical, discriminative stimuli.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46346/1/213_2005_Article_BF02245248.pd
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Energy input and dissipation in a temperate lake during the spring transition
ADCP and temperature chain measurements have been used to estimate the rate of energy input by wind stress to the water surface in the south basin of Windermere. The energy input from the atmosphere was found to increase markedly as the lake stratified in spring. The efficiency of energy transfer (Eff), defined as the ratio of the rate of working in near-surface waters (RW) to that above the lake surface (P10), increased from âŒ0.0013 in vertically homogenous conditions to âŒ0.0064 in the first 40 days of the stratified regime. A maximum value of EffâŒ0.01 was observed when, with increasing stratification, the first mode internal seiche period decreased to match the diurnal wind period of 24 h. The increase in energy input, following the onset of stratification was reflected in enhancement of the mean depth-varying kinetic energy without a corresponding increase in wind forcing. Parallel estimates of energy dissipation in the bottom boundary layer, based on determination of the structure function show that it accounts for âŒ15% of RW in stratified conditions. The evolution of stratification in the lake conforms to a heating stirring model which indicates that mixing accounts for âŒ21% of RW. Taken together, these estimates of key energetic parameters point the way to the development of full energy budgets for lakes and shallow seas
Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys
The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at ÎŒ, Îș and â-receptors, in rhesus monkeys ( n =3â4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032â0.1 mg/kg) dose-dependently antagonized fentanyl (0.001â0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001â0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non ÎŒ-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1â0.32 mg/kg) did not antagonize the rate-suppressing effects of the â-agonist BW373U86 (0.0.01-1.0 mg/kg) or the Îș-agonist U69,593 (0.001â0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for ÎŒ-over Îș- and ÎŽ-receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46352/1/213_2005_Article_BF02246641.pd
A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation.
OBJECTIVE: The purpose of this study was to evaluate the possible structural changes of the macula in patients with unilateral amblyopia using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 consecutive patients (16 male; mean age 32.4+/-17.6 years; range 6-67 years) with unilateral amblyopia were involved in this study. OCT examinations were performed with a time-domain OCT device, and a custom-built OCT image analysis software (OCTRIMA) was used for OCT image segmentation. The axial length (AL) was measured by a LenStar LS 900 device. Macular layer thickness, AL and manifest spherical equivalent refraction (MRSE) of the amblyopic eye were compared to that of the fellow eye. We studied if the type of amblyopia (strabismus without anisometropia, anisometropia without strabismus, strabismus with anisometropia) had any influence on macular layer thickness values. RESULTS: There was significant difference between the amblyopic and fellow eyes in MRSE and AL in all subgroups. Comparing the amblyopic and fellow eyes, we found a statistically significant difference only in the thickness of the outer nuclear layer in the central region using linear mixed model analysis keeping AL and age under control (p = 0.032). There was no significant difference in interocular difference in the thickness of any macular layers between the subgroups with one-way between-groups ANCOVA while statistically controlling for interocular difference in AL and age. CONCLUSIONS: According to our results there are subtle changes in amblyopic eyes affecting the outer nuclear layer of the fovea suggesting the possible involvement of the photoreceptors. However, further studies are warranted to support this hypothesis
Meeting the home-care needs of disabled older persons living in the community: does integrated services delivery make a difference?
<p>Abstract</p> <p>Background</p> <p>The PRISMA Model is an innovative coordination-type integrated-service-delivery (ISD) network designed to manage and better match resources to the complex and evolving needs of elders. The goal of this study was to examine the impact of this ISD network on unmet needs among disabled older persons living in the community.</p> <p>Methods</p> <p>Using data from the PRISMA study, we compared unmet needs of elders living in the community in areas with or without an ISD network. Disabilities and unmet needs were assessed with the Functional Autonomy Measurement System (SMAF). We used growth-curve analysis to examine changes in unmet needs over time and the variables associated with initial status and change. Sociodemographic characteristics, level of disability, self-perceived health status, cognitive functioning, level of empowerment, and the hours of care received were investigated as covariates. Lastly, we report the prevalence of needs and unmet needs for 29 activities in both areas at the end of the study.</p> <p>Results</p> <p>On average, participants were 83 years old; 62% were women. They had a moderate level of disability and mild cognitive problems. On average, they received 2.07 hours/day (SD = 1.08) of disability-related care, mostly provided by family. The findings from growth-curve analysis suggest that elders living in the area where ISD was implemented and those with higher levels of disability experience better fulfillment of their needs over time. Besides the area, being a woman, living alone, having a higher level of disability, more cognitive impairments, and a lower level of empowerment were linked to initial unmet needs (r<sup>2 </sup>= 0.25; p < 0.001). At the end of the study, 35% (95% CI: 31% to 40%) of elders with needs living in the ISD area had at least one unmet need, compared to 67% (95% CI: 62% to 71%) in the other area. In general, unmet needs were highest for bathing, grooming, urinary incontinence, walking outside, seeing, hearing, preparing meals, and taking medications.</p> <p>Conclusions</p> <p>In spite of more than 30 years of home-care services in the province of Quebec, disabled older adults living in the community still have unmet needs. ISD networks such as the PRISMA Model, however, appear to offer an effective response to the long-term-care needs of the elderly.</p
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