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Biomedical subjects

C B Smith

Publications and source records attributed to C B Smith.

At least 109 records · Page 6Linked to original sources
PubMed1989

Intravenous yohimbine. Selective enhancer of norepinephrine and cortisol secretion and systolic blood pressure in humans.

Yohimbine hydrochloride was administered intravenously to nine normal volunteers to assess alpha 2-adrenergic receptor function. Plasma catecholamines, cortisol, and psychophysiological parameters (blood pressure, pulse, somatic symptoms checklist, and visual analogue scales assessing mood) were used as dependent variables. Plasma norepinephrine and plasma cortisol increased significantly after yohimbine administration, while epinephrine remained unchanged. Systolic blood pressure and somatic symptoms were also significantly increased by yohimbine. These findings suggest that low-dose intravenous yohimbine is an effective probe for alpha 2-adrenergic receptors and the hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed1989

Very long-acting narcotic antagonists: the 14 beta-p-substituted cinnamoylaminomorphinones and their partial mu agonist codeinone relatives.

The biological activity of 14 beta-(p-halo and p-methylcinnamoylamino)-7,8-dihydro-N-cyclopropylmethylnorcodei nones and their corresponding morphinones was investigated. In vitro, the codeinones displayed predominantly mu agonist activity in the 3H-etorphine binding assay and mouse vas deferens preparation. In vivo, in the mouse, the compounds showed weak to inactive antinociception in the tail-flick and hot-plate tets; however, they were potent agonists in the phenylquinone test and moderately weak antagonists in the tail-flick vs morphine test. They also substituted for morphine in withdrawn morphine-dependent rhesus monkeys. When given to non-withdrawn morphine-dependent monkeys, the codeinones precipitated a delayed but long-lasting withdrawal syndrome. They all generalized to codeine in the drug-discrimination test in rhesus monkeys and, in the dose range tested, two compounds were self-administered. This activity is consistent with that of a partial mu agonist. On the other hand, all the morphinones had very long-acting and highly potent mu antagonist properties. The data can be reconciled by assuming that the codeinones are partially metabolized to their respective morphinones. These compounds may be especially useful in the treatment of opioid dependence.

Analgesics↗
PubMed1989

Cortical areas involved in horizontal OKN in cats: metabolic activity.

Cerebral cortex improves optokinetic responses to high target velocities, but the specific cortical areas involved are unknown. Using the 14C-deoxyglucose technique, we compared local rates of cerebral glucose utilization in cats viewing a moving optokinetic nystagmus (OKN) drum (experimental group) with those in cats viewing a stationary OKN drum (control group). In the experimental group, glucose utilization was increased in areas 17 and 18 and in 4 areas in suprasylvian cortex (21a, 21b, PMLS, and VLS). There were no changes in glucose utilization in areas 7, 19, 20a, 20b, ALLS, AMLS, DLS, PLLS, the posterior suprasylvian area, and the splenial visual area. The increases in glucose utilization in areas 17 and 18 were most significant in the granular layers (inner III and IV). In areas 21a, 21b, PMLS, and VLS, the increases in glucose utilization extended from layers II through V. There was also a regional distribution of the increase in glucose utilization within each of these areas in the experimental animals. The increase in glucose utilization did not include the rostral portion of PMLS or the borders between areas PMLS and 21a, and VLS and 21b. In addition, there was a smaller increase in glucose utilization at the borders between areas 17 and 18 than in other portions of these 2 areas. The results indicate that areas 17, 18, 21a, 21b, PMLS, and VLS may be involved in the cortical modulation of horizontal OKN. The laminar distribution of label within the cortical areas corresponds with the distribution of projections from the dorsal lateral geniculate nucleus to areas 17 and 18, and from areas 17 and 18 to PMLS. The regional distribution of the metabolic activity within areas 17, 18, and PMLS coincides with that portion of cortex expected to be excited by either the spatial frequency of the stimulus or the retinalslip velocity (drum velocity minus slow phase eye velocity) occurring during the eye movements.

Animals↗
PubMed1988

Cyclic, disulfide- and dithioether-containing opioid tetrapeptides: development of a ligand with high delta opioid receptor selectivity and affinity.

Tetrapeptides of primary sequence Tyr-X-Phe-YNH2, where X is D-Cys or D-Pen (penicillamine) and where Y is D-Pen or L-Pen, were prepared and were cyclized via the side chain sulfurs of residues 2 and 4 to disulfide or dithioether-containing analogs. These peptides are related to previously reported penicillamine-containing pentapeptide enkephalin analogs but lack the central glycine residue of the latter and were designed to assess the effect of decreased ring size on opioid activity. Binding affinities of the tetrapeptides were determined to both mu and delta opioid receptors. Binding affinity and selectivity in the tetrapeptide series were observed to be highly dependent on primary sequence. For example, L-Pen4 analogs displayed low affinity and were nonselective, while the corresponding D-Pen4 diastereomers were of variable affinity and higher selectivity. Among the latter compounds were examples of potent analogs in which selectivity shifted from delta selective to mu selective as the ring size was increased. The relatively high binding affinity and delta receptor selectivity observed with one of the carboxamide terminal disulfide analogs led to the synthesis of the corresponding carboxylic acid terminal, Tyr-D-Cys-Phe-D-PenOH. This analog displayed delta receptor binding selectivity similar to that of the standard delta ligand, [D-Pen2,D-Pen5]enkephalin (DPDPE), and was found to have a 3.5-fold higher binding affinity than DPDPE. All the tetrapeptides were further evaluated in the isolated mouse vas deferens (mvd) assay and all displayed opioid agonist activity. In general, tetrapeptide potencies in the mouse vas deferens correlated well with binding affinities but were somewhat lower. Receptor selectivity in the mvd, assessed by examining the effect of opioid antagonists on the tetrapeptide concentration-effect curves, was similar to that determined in the binding studies.

Animals↗
PubMed1988

Measurement of local cerebral protein synthesis in vivo: influence of recycling of amino acids derived from protein degradation.

A quantitative autoradiographic method for the determination of local rates of protein synthesis in brain in vivo is being developed. The method employs L-[1-14C]leucine as the radiolabeled tracer. A comprehensive model has been designed that takes into account intracellular and extracellular spaces, intracellular compartmentation of leucine, and the possibility of recycling of unlabeled leucine derived from steady-state degradation of protein into the precursor pool for protein synthesis. We have evaluated the degree of recycling by measuring the ratio of the steady-state precursor pool distribution space for labeled leucine to that of unlabeled leucine. The values obtained were 0.58 in whole brain and 0.47 in liver. These results indicate that there is significant recycling of unlabeled amino acids derived from steady-state protein degradation in both tissues. Any method for the determination of rates of cerebral protein synthesis in vivo with labeled tracers that depends on estimation of precursor pool specific activity in tissue from measurements in plasma must take this recycling into account.

Amino Acids↗
PubMed1987

Changes in cortical beta-adrenergic receptor density and neuronal sensitivity to norepinephrine accompany morphine dependence and withdrawal.

Radioligand binding experiments were carried out in conjunction with electrophysiological recordings in vivo in the parietal cortex in rats to assess changes in postsynaptic beta-adrenergic receptor function that result after chronic administration of morphine and during morphine withdrawal. Chronic treatment of rats with morphine for 14 days resulted in a 38% increase in the density of beta-adrenergic receptors in the parietal cortex, as measured by the binding of the specific antagonist [3H]dihydroalprenolol (DHA). In comparison, following withdrawal in the chronic morphine-treated animals, the number of specific [3H]DHA binding sites in this same cortical region was decreased 25%, when compared to saline-treated controls. These alterations in cortical beta-adrenergic receptor density were not accompanied by a significant change in the dissociation constant (Kd) for [3H]DHA or in the inhibitory constants (Ki) for the specific agonists norepinephrine and isoproterenol. Microiontophoretic testing revealed that the changes in beta-adrenergic receptor density found in parietal cortex after chronic morphine treatment and during morphine withdrawal were accompanied by a selective increase and decrease, respectively, in the sensitivity of cerebrocortical neurons in the same region to beta-adrenergic stimulation. These results suggest that changes in central adrenergic function might be related to the formation and/or expression of dependence on morphine.

Animals↗
PubMed1987

Effects of weekly and daily pretreatment with gold sodium thiomalate on adjuvant induced arthritis.

The effect of gold sodium thiomalate on adjuvant induced arthritis in DA rats was investigated. Ten mg/kg gold given in either weekly or daily injections before the administration of adjuvant was able to decrease the severity of arthritis in these animals. One mg/kg gold given as daily injections had no effect on adjuvant induced arthritis. One mg/kg gold given as weekly injections before adjuvant administration reduced the severity of arthritis to a level which was intermediate between that seen in the placebo control and the 10 mg/kg gold groups. The proliferative responses of spleen cells to mitogens in these animals were not altered by in vivo gold therapy.

Animals↗
PubMed1987

Dysfunctional uterine bleeding.

The causes and treatment of abnormal uterine bleeding vary with the patient's age and health. The evaluation can be organized according to physiologic age groups: menarche through adolescence; the childbearing period, and the perimenopausal and postmenopausal years. Dysfunctional bleeding is a diagnosis by exclusion and is related to the basic physiology of normal menstruation. Endometrial sampling, hysteroscopy, and dilatation and curettage are useful in evaluating the post-teenage patient.

Adolescent↗
PubMed1986

Anxiolytic action of CGS 9896 on mouse exploratory behavior.

A new non-benzodiazepine compound proposed as a non-sedating anxiolytic was tested in the mouse exploratory model of anxiety. CGS 9896 significantly increased the number of light dark transitions at doses beginning at 7.5 mg/kg i.p. Analysis of general locomotor activity at these doses revealed no change in spontaneous motor activity in a photocell equipped activity monitor. Pretreatment with the benzodiazepine receptor antagonist, Ro15-1788, 10 mg/kg i.p., blocked the increase in light dark transitions produced by CGS 9896. These data support the interpretation that CGS 9896 acts as an anxiolytic through the benzodiazepine receptor, and appears to have no sedating properties within the anxiolytic dose range.

Animals↗
PubMed1986

Rat cytomegalovirus infection enhances type II collagen arthritis in rats.

The effect of rat cytomegalovirus (RCMV) infection on type II collagen-induced arthritis was studied in DA rats. Rats were infected with RCMV 5 days before, simultaneously with, or 5 days after immunization with calf type II collagen. Control rats were either given type II collagen alone or were injected with normal rat salivary gland (NRSG) simultaneously with collagen immunization. Severity of arthritis in each limb was graded on a scale of 1-4 (maximum score 16). In 5 experiments, peak arthritis scores in the RCMV groups were twice those of the control groups which received NRSG or collagen only (8-9 versus 4-6). Radiographs of involved joints showed greater destruction of cartilage and articular bone in the RCMV rats than in the NRSG control group. Repeated attempts to culture RCMV from joint tissues were unsuccessful. Our results indicate that RCMV infection enhances the arthritic process in this experimental model of an autoimmune arthritis.

Animals↗
PubMed1986

Mouse cytomegalovirus is infectious for rats and alters lymphocyte subsets and spleen cell proliferation.

The Smith strain of mouse cytomegalovirus (MCMV) was infectious for infant and mature DA strain laboratory rats as judged by development of neutralizing antibodies and specific spleen cell proliferation on stimulation with MCMV antigen. An i.p. inoculum of 10(6) PFU of MCMV was fatal for more than two-thirds of infant mice (1-7 days of age), and disseminated viral infection was documented by isolation of virus from body organs. In contrast, weanling and adult rats did not become ill as a result of infection with a larger inoculum of 10(7) PFU. However, these older MCMV infected rats did show transient reversals of T helper/suppressor cell ratios and alterations of immune cell function as detected by in vitro spleen cell proliferation assays. Seven days after MCMV infection, there was a generalized increase in 3H-thymidine incorporation by spleen cells in both resting (unstimulated) cultures and cultures exposed to mitogens (Con A, PHA, LPS) and to MCMV antigen. At 14 days, the spleen cell proliferation in the unstimulated cultures returned to normal but was depressed compared to controls in response to Con A. These observations show that laboratory rats are susceptible to MCMV infection and that asymptomatic infection may occur and cause transient alterations in lymphocyte subsets and in their reactivity to mitogens.

Animals↗