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Biomedical subjects

David L Stevens

Publications and source records attributed to David L Stevens.

7 recordsLinked to original sources
PubMed2006

Time course of the enhancement and restoration of the analgesic efficacy of codeine and morphine by delta9-tetrahydrocannabinol.

Delta9-tetrahydrocannabinol (delta9-THC) synergizes with morphine and codeine by releasing endogenous opioids. These studies determined 1) the duration of enhancement of morphine and codeine by delta9-THC, 2) the effect of (delta9-THC on the time course of fully efficacious doses of the opioids, 3) restoration of efficacy of morphine and codeine by delta9-THC, and 4) duration of restoration. Sub-active combination doses of delta9-THC/morphine or delta9-THC/codeine are equivalent in duration of action and efficacy to high-dose opioids alone. Delta9-THC (20 mg/kg p.o.) significantly restores the antinociceptive effects of both high-dose morphine and codeine (100 and 200 mg/kg p.o., respectively) at later time points at which morphine or codeine was no longer active (360- and 120-min post-administration, respectively). Thus, the cannabinoid/opioid combination might be useful in therapeutics to enhance opioid activity, as well as to restore the efficacy of opioids.

Analgesics, Non-Narcotic↗
PubMed2004

Measuring the competence of residents as teachers.

Medical residents, frontline clinical educators, must be competent teachers. Typically, resident teaching competence is not assessed through any other means than gleaning learner's comments. We developed, evaluated, and integrated into our annual objective structured clinical examination a resident teaching skills assessment using "standardized" students. Faculty observers rated residents using a customized 19-item rating instrument developed to assess teaching competencies that were identified and defined as part of our project. This was feasible, acceptable, and valuable to all 65 residents, 8 students, and 16 faculty who participated. Teaching scenarios have potential as reliable, valid, and practical measures of resident teaching skills.

Educational Measurement↗
PubMed2004

Relative sensitivities of repair-deficient mammalian cells for clonogenic survival after alpha-particle irradiation.

The clonogenic survival of cells of the radiation-sensitive hamster cell lines irs1, irs2, irs3 and xrs5, representing different DNA repair pathways, was compared to that of their parent lines after alpha-particle irradiation. Measurements of nuclear area were made to calculate the probability of surviving a single alpha-particle traversal, the average number of lethal lesions per track and per unit dose, along with the "intrinsic radiosensitivity" of these cells, allowing for the potential of multiple lethal lesions per traversal. For all cell lines studied, alpha particles were found to be more biologically effective per unit absorbed dose than X rays at inducing cell inactivation. The repair-deficient cells showed an enhanced sensitivity to alpha particles compared to their parent line, but the degree of enhancement was less than for X rays. The reduction in additional sensitivity for alpha-particle irradiation was shown not to be due predominantly to differences in cell geometry limiting the probability of a cell nucleus being traversed. The results suggest that both the nonhomologous end-joining pathway and to a lesser extent the homologous recombination repair pathway play a role in successful repair of alpha-particle-induced damage, although a large proportion of damage is not repaired by either pathway.

Alpha Particles↗
PubMed2003

The role of several kinases in mice tolerant to delta 9-tetrahydrocannabinol.

It has been suggested that the cannabinoid receptor type 1 (CB1), a G protein-coupled receptor, is internalized after agonist binding and activation of the second messenger pathways. It is proposed that phosphorylation enhances the down-regulation of the CB1 receptor, thus contributing to tolerance. Alterations in phosphorylation of proteins in the signal transduction cascade after CB1receptor activation could also alter tolerance to cannabinoids. We addressed our hypothesis by evaluating the role of several kinases in antinociceptive tolerance to Delta(9)-tetrahydrocannabinol (THC). We evaluated cAMP-dependent protein kinase (PKA) using KT5720, a PKA inhibitor; protein kinase C (PKC) using bisindolylmaleimide I, HCl (bis), a PKC inhibitor; cGMP-dependent protein kinase (PKG) using KT5823, a PKG inhibitor; beta-adrenergic receptor kinase (beta-ARK) using low molecular weight heparin (LMWH), a beta-ARK inhibitor; and phosphatidylinositol-3 kinase (PI3-K) using 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), a PI3-K inhibitor and PP1, a Src family tyrosine kinase inhibitor. The cAMP analog used was dibutyryl-cAMP and the cGMP analog used was dibutyryl-cGMP. Our data indicate that selective kinases may be involved in cannabinoid tolerance. Mice and rats were rendered tolerant to Delta(9)-THC. The PKG inhibitor KT5823, the beta-ARK inhibitor LMWH, the PI3-K inhibitor LY294002, and inhibition of PKC by bis had no effect on tolerance. At a higher dose, bis attenuated the antinociceptive effect of delta(9)-THC in nontolerant mice. PP1, the Src family tyrosine kinase inhibitor, and KT5720, the PKA inhibitor, reversed THC-induced tolerance. In addition, inhibition of PKA reversed a decrease in dynorphin release shown to accompany THC tolerance in rats. These data support a role for PKA and Src tyrosine kinase in phosphorylation events in delta(9)-THC-tolerant mice.

Animals↗
PubMed2002

Physical and chemical considerations of damage induced in protein crystals by synchrotron radiation: a radiation chemical perspective.

Radiation-induced degradation of protein or DNA samples by synchrotron radiation is an inherent problem in X-ray crystallography, especially at the 'brighter' light sources. This short review gives a radiation chemical perspective on some of the physical and chemical processes that need to be considered in understanding potential pathways leading to the gradual degradation of the samples. Under the conditions used for X-ray crystallography at a temperature of <100 K in the presence of cryoprotectant agents, the majority of radiation damage of the protein samples arises from direct ionization of the amino acid residues and their associated water molecules. Some of the chemical processes that may occur at these protein centres, such as bond scission, are discussed. Several approaches are discussed that may reduce radiation damage, using agents known from radiation chemistry to minimize radical-induced degradation of the sample.

Crystallization↗
PubMed2002

M-FISH analysis shows that complex chromosome aberrations induced by alpha -particle tracks are cumulative products of localized rearrangements.

Complex chromosome aberrations are characteristically induced after exposure to low doses of densely ionizing radiation, but little is understood about their formation. To address this issue, we irradiated human peripheral blood lymphocytes in vitro with 0.5 Gy densely ionizing alpha-particles (mean of 1 alpha-particle/cell) and analyzed the chromosome aberrations produced by using 24-color multiplex fluorescence in situ hybridization (M-FISH). Our data suggest that complex formation is a consequence of direct nuclear alpha-particle traversal and show that the likely product of illegitimate repair of damage from a single alpha-particle is a single complex exchange. From an assessment of the "cycle structure" of each complex exchange we predict alpha-particle-induced damage to be repaired at specific localized sites, and complexes to be formed as cumulative products of this repair.

Alpha Particles↗