Showing papers by "Research Triangle Park published in 1981"
TL;DR: The mechanisms of biodegradation of poly (DL-lactide), poly (epsilon-caprolactone), and copolymers of epsilon-caproate sequences with DL-dilactide, delta-valerolactone, and DL-epsil on-decalactone in rabbit were shown to be qualitatively similar.
823 citations
TL;DR: The degradation of poly(ϵ-caprolactone) in rabbits, rats, and water was studied by measurement of changes in intrinsic viscosity, molecular weight, crystallinity, Young's modulus, and weight.
Abstract: The degradation of poly(ϵ-caprolactone) in rabbits, rats, and water was studied by measurement of changes in intrinsic viscosity, molecular weight, crystallinity, Young's modulus, and weight. Degradation proceeds by nonenzymatic random hydrolytic cleavage of ester linkages. The process is autocatalytic, and the kinetic relationship Mn/Mno = exp(–kt) is observed until the Mn has decreased to approximately 5000. Significant weight loss is not observed until this point but, once initiated, the rate of weight loss depends markedly on the particle size. Chain scission is associated with an increase in crystallinity, which partly determines the rate of degradation.
663 citations
TL;DR: To obtain estimates of the frequency of nosocomial infections nationwide, those occurring at the four major sites--urinary tract, surgical wound, lower respiratory tract and bloodstream--were diagnosed in a stratified random sample of 169,526 adult, general medical and surgical patients selected from 338 hospitals representative of the "mainstream" of U.S. hospitals.
475 citations
TL;DR: Cells containing enkephalin‐like immunoreacactivity were found within the somata of three types of hippocampal neurons: granule cells of the dentate gyrus, occasional pyramidal shaped cells of field CA1 stratum pyramidale, and varied scattered interneurons.
Abstract: The distribution of enkephalin-like immunoreactivity in the hippocampal formation of the rat was analyzed. Two specific projection systems are described. The first emerges from the hilus of the dentate gyrus and appears to terminate with notably large boutons on the proximal apical and, to a lesser extent, basal dendrites of hippocampal regio inferior pyramidal cells. This projection corresponds in source, position, and character to the hippocampal mossy fiber system. The second axonal population enters the temporal hippocampal formation from the medial wall of the subicular complex and follows the hippocampal fissure to occupy stratum lacunosum-moleculare of the hippocampus proper and the distal third of the dentate gyrus molecular layer; this pattern corresponds to the distribution of afferent input from the lateral entorhinal cortex and/or perirhinal area. Lesions of the hilus or retrohippocampal area caused a selective depletion of immunoreactivity in the mossy fiber fields and molecular layers of the dentate gyrus, respectively. Enkephalin-like immunoreactivity was found within the somata of three types of hippocampal neurons: 1) granule cells of the dentate gyrus, 2) occasional pyramidal shaped cells of field CA1 stratum pyramidale, and 3) varied scattered interneurons. Of this last group, two types of interneurons were consistently seen. The first occupy the border between stratum radiatum and stratum lacunosum-moleculare and extend processes at right angles to the long axis of the pyramidal cell dentrites, whereas the second lie within stratum radiatum of field CA1 and extend processes in alignment with the long axis of the pyramidal cell dendrites. Cells containing enkephalin-like immunoreactivity were also observed in the subiculum and retrohippocampal region, most notably including layers II and III of the lateral entorhinal cortex-perirhinal area--the probable source of extrinsic immunoreactive input to the hippocampal formation. Intraventricular colchicine treatment intensified the immunoreactive staining of some hippocampal neurons but did not reveal any cell types not seen to be labeled in untreated rats.
356 citations
TL;DR: The discovery of this specific morphine receptor ligand substantiates the hypothesis of multiple opiate receptors and may prove useful for further investigation of the functions of opiate receptor subtypes.
Abstract: The synthetic peptide NH2-Tyr-Pro-Phe-Pro-CONH2 (morphiceptin), which is the amide of a fragment of the milk protein beta-casein, has morphinelike activities and is highly specific for morphine (mu) receptors but not for enkephalin (delta) receptors It is as active as morphine in the guinea pig ileum but much less active in the mouse and rat vas deferens The discovery of this specific morphine receptor ligand substantiates the hypothesis of multiple opiate receptors The ligand, which may be of physiological significance since a very similar, or identical, activity can be detected in enzymatic digests of beta-casein, may prove useful for further investigation of the functions of opiate receptor subtypes
313 citations
TL;DR: The present data indicate that when the release of arachidonic acid is completely inhibited by cyclic AMP or quinacrine,osphatidic acid is redirected entirely to phosphatidylinositol and there is no production of archidonate.
Abstract: An increase in the metabolism of phosphatidylinositol occurs in a wide variety of tissues by the action of specific ligands1–3. In platelets, the interaction of thrombin with its receptor initiates the degradation of phosphatidylinositol by the action of a specific phospholipase C (refs 4–8). In normal conditions of stimulation, the resultant 1,2-diacylglycerol is rapidly and completely phosphorylated to phosphatidic acid4–11. The formation of phosphatidic acid precedes the release of arachidonic acid from the phospholipids of stimulated platelets5. This early appearence of phosphatidate might result in the initial production of arachidonic acid and lysophosphatidic acid by the action of a phospholipase A2 specific for phosphatidate12. Phosphatidate/lysophosphatidate could induce calciumgating13–15 and subsequently stimulate phospholipases of the A2-type8, that degrade phosphatidylcholine, phosphatidyl-ethanolamine and a further fraction of phosphatidylinositol6. Alternatively, the lysophosphatidate produced may serve as a substrate for the transfer of arachidonate directly from other phospholipids16,17 to form new phosphatidate which in turn can release more arachidonate. Overall, such a sequence would be equivalent to phospholipase A2 activation of other phospholipids. Our present data indicate that when the release of arachidonic acid is completely inhibited by cyclic AMP or quinacrine, phosphatidic acid is redirected entirely to phosphatidylinositol and there is no production of arachidonate. In these conditions, the availability of calcium might be profoundly restricted. The correlation in platelets of a phosphatidylinositol by a specific phospholipase A2 might suggest that these phenomena are applicable to activations in other cell systems.
216 citations
TL;DR: After binding to cell surface receptors, insulin, along with its receptor, is internalized by an endocytic process, which in contrast to multiplication-stimulating activity is affinity cross-linked to a protein with an entirely different subunit structure.
Abstract: INSULIN receptor has been purified by affinity chromatography and studied by affinity labeling techniques. It is composed of two types of subunits, α (molecular weight ∼135,000) and β (molecular weight α90,000), which form a disulfide-linked heterotetramer (αβ)2. Both α- and β-subunits are glycoproteins. Both are exposed on the outer surface of the membrane, a is the subunit that is predominantly affinity labeled by insulin and is probably the insulin-binding subunit; however, β may also comprise a portion of the insulin-binding site. Receptors for insulin-like growth factors have also been affinity labeled. A photoaffinity labeling derivative of basic somatomedin affinity labels a protein with a subunit structure very similar to the insulin receptor. In contrast, multiplication-stimulating activity is affinity cross-linked to a protein with an entirely different subunit structure. After binding to cell surface receptors, insulin, along with its receptor, is internalized by an endocytic process, which in ...
186 citations
TL;DR: Methods for predicting creatinine clearance should not be used in patients with liver disease and only two of the methods were consistently accurate in all ranges of renal function.
Abstract: Several formulas for predicting creatinine clearance (Ccr) are used for adjusting drug dosages but limited data are available on their accuracy in patients with significant renal impairment or concurrent disease. We measured 144 Ccr in 103 patients and compared results using four predictive methods. Of nine common diseases in these patients, liver disease was associated with a large (p less than 0.02) prediction error (overprediction). After data from eight patients with liver disease were removed, there was good overall correlation between predicted and measured Ccr (r2 = 0.91 for each method) but only two of the methods (I and IV) were consistently accurate in all ranges of renal function. Methods for predicting Ccr should not be used in patients with liver disease.
164 citations
TL;DR: The results emphasize the importance of the specificity of cellular kinases and the HSV DNA polymerase to the mechanism of antiviral activity and the phosphorylation catalyzed by host cell dThd kinase correlated with the toxicity of some pyrimidine nucleoside analogs.
146 citations
TL;DR: It seems likely that λ and σ mutants result from 2 different mutational mechanisms that may be distinguished on the basis of mutant colony morphology, possibly related to the type of chromosomal damage sustained.
Abstract: The L5178Y/TK+/− → TK−/− mouse lymphona mutagen assay, which allows selection of forward mutations at the autosomal thymidine kinase (TK) locus, uses a TK+/− heterozygous cell line, TK+/− 3.7.2C. Quantitation of colonies of mutant TK−/− cells in the assay forms the basis for calculations of mutagenic potential of test compounds. We have evaluated the banded karyotypes of the parent TK+/− heterozygous cell line, as well as homozygous TK−/− mutants, in order to relate the genetic and morphological properties of mutant colonies. The parent cell line displays karyotype homogeneity, all cells containing normal mouse chromosomes, readily identifiable chromosome rearrangements, and cell line specific marker chromosomes. Mutant TK−/− colonies of the TK+/− 3.7.2C cell line form a bimodal frequency distribution of colony sizes for most mutagenic or carcinogenic test substances. Large-colony (λ) TK−/− mutants with normal growth kinetics appear karyotypically identical within and among clones and with the TK+/− parental cell line. In contrast, most slow-growing small-colony (σ) TK−/− mutants have readily recognizable chromosome rearrangements involving chromosome 11, which contains the thymidine kinase gene locus. It is possible that the heritable differences in growth kinetics and resultant colony morphology in λ and σ mutants are related to the type of chromosomal damage sustained. Large-colony mutants receive minimal damage, possibly in the form of point mutations at the TK locus, while small-colony mutants receive damage to other genetic functions coordinately with loss of TK activity, implying gross insult to chromosomal material. It seems likely that λ and σ mutants result from 2 different mutational mechanisms that may be distinguished on the basis of mutant colony morphology.
143 citations
TL;DR: The GENE-TOX Group on Specific Gene Mutations in Chinese Hamster Ovary (CHO) Cells has evaluated the use of mutational systems in these cells for identification of mutagenic chemicals, finding the CHO/HGPRT assay has a sound genetic and biochemical basis for quantifying specific locus mutation reproducibly.
Abstract: The GENE-TOX Group on Specific Gene Mutations in Chinese Hamster Ovary (CHO) Cells has evaluated the use of mutational systems in these cells for identification of mutagenic chemicals from 261 references in the file of the Environmental Mutagen Information Center, Oak Ridge National Laboratory by February, 1979; 68 references were found to be relevant to the stated task. After establishing that the end-point of mutational measurement occurs at a specific locus and the determinations are quantifiable and reproducible, data from 21 references were found to fulfill such requirements. Among them, 14 were concerned with chemically-induced mutations to resistance to a purine analogue, 6-thioguanine, which selects for variants deficient in the enzyme hypoxanthine—guanine phosphoribosyl transferase (HGPRT). This mutational system is referred to as the CHO/HGPRT assay. Studies with other genetic markers offer promise for the development of quantitative specific genemutational assays, but these studies have not advanced thoroughly enough to assess their value. Several lines of genetic, physiological and biochemical evidence support the premise that the CHO/HGPRT system fulfills the criteria for measurement of specific gene mutations using CHO-K1-BH4 subclone and other appropriate CHO subclones. Based largely on published information, this Work Group has suggested a protocol for testing of chemical agents with consideration of the following: cells, media, culture conditions and their quality control, treatment with test compounds with and without an exogenous metabolic activation system, estimation of cytoxicity (cloning efficiency), optimum expression and selection of the mutant phenotype, calculation of mutation frequency, positive and negative controls, vehicles or solvents, spontaneous mutation frequency, dosage selection and number of doses, and collection of raw data. For interpretation of the mutagenesis data, this Work Group recommends various ways of presenting data, numerous criteria for acceptability of data, the need to use appropriate statistical procedures for data evaluation, and a potential applicability of results to hazard evaluation. Evaluation of test performances with 18 chemicals revealed that the correlation between mutagenicity in CHO/HGPRT assay and animal mutagenicity and carcinogenicity is high. Since the number of chemicals tested was small and 17 of the 18 compounds were direct-acting agents, the utility of the system for identification of various classes of potential mutagens and carcinogens cannot be adequately assessed until more chemical classes, especially promutagens, are tested. However, the assay has a sound genetic and biochemical basis for quantifying specific locus mutation reproducibly. The fact that CHO cells are also useful for determination of chemically-induced chromosome aberration and sister-chromatid exchange adds an additional strength to the assay. Future research should address the possible improvement of procedures for phenotypic expression and application for testing gaseous and volatile liquids, as well as such problems as appropriate metabolic activation system(s) and effective statistical procedures common to perhaps all short-term cellular assays. Recent rapid development of mutagen test systems like the CHO/HGPRT assay calls for a need to update and evaluate the data base generated.
TL;DR: A mechanism for benzene toxicity in which the formation of potentially cytotoxic metabolites, semiquin one, and quinone oxidation products and superoxide radicals, result from autoxidation of at least two polyphenol metabolites of benzene, hydroquinone, and 1,2,4-benzenetriol is supported.
TL;DR: Primary cultures of bovine adrenal medullary chromaffin cells have been maintained in the absence of serum for up to 3 weeks, suggesting ‘conditioning’ of the culture medium.
TL;DR: It is concluded that depletion ofretinal dopamine impairs the timing of retinal responses to light and haloperidol reversed some of the effects of AMT.
TL;DR: The disposition of salicylic acid, phenacetin, caffeine, and codeine, and two metabolites, acetaminophen and morphine, was studied in breast milk and plasma of two lactating mothers after single oral doses of a compound analgesic.
Abstract: The disposition of salicylic acid, phenacetin, caffeine, and codeine, and two metabolites, acetaminophen and morphine, was studied in breast milk and plasma of two lactating mothers after single oral doses of a compound analgesic. Salicylic acid penetrated poorly into milk, with peak levels of only 1.12 to 1.60 micrograms/ml, whereas peak plasma levels were 33 to 43.4 micrograms/ml. The drug was also eliminated more slowly from milk than plasma. In contrast, caffeine and phenacetin kinetics in breast milk and plasma were similar, but milk levels were somewhat lower than plasma levels in both subjects. Metabolically produced acetaminophen levels in both fluids were much higher than those of the parent drug, phenacetin, in one subject, but early plasma and milk phenacetin levels exceeded those of acetaminophen in the other subject, thereafter dropping sharply to assume the pattern of the first subject. Elimination of the metabolite, acetaminophen, from milk was slower than from plasma (subject 1, half-life (t1/2) of drug in milk, 4.7 hr; t1/2 in plasma, 2.9 hr). In both subjects codeine concentrations in milk were 1.5 to 2.4 times as high as in plasma at the same times after drug. Metabolically produced morphine levels in milk from both mothers were low but exceeded those in plasma after 1 hr. Calculations based on average milk concentrations over the 12 hr after drug in subject 1 revealed milk excretion of 0.7% or less of the ingested dose of each drug. Similar calculations based on predicted steady-state milk drug concentrations in subject 2 indicated maximum milk excretion of 2.7% of the dose. In each case caffeine was excreted in the milk in the greatest amount.
TL;DR: Mice were able to minimize inhalation of HCHO more than rats, because of greater sensitivity and lack of tolerance, and this species difference may contribute to differences in respiratory tract toxicity from inhaled HCHO.
TL;DR: Evidence is provided for induction and regulation of guanosine triphosphate cyclohydrolase in adrenal cortex and medulla of rats treated with insulin or reserpine.
Abstract: Guanosine triphosphate cyclohydrolase, the enzyme that is apparently rate-limiting in biopterin biosynthesis, is increased in adrenal cortex and medulla of rats treated with insulin or reserpine. Denervation and hypophysectomy block the increase in medullary and cortical enzyme activity, respectively, whereas cycloheximide presents the increase in both tissues. These results provide evidence for induction and regulation of guanosine triphosphate cyclohydrolase.
TL;DR: The pharmacokinetics of bupropion hydrochloride were found to be linear across the 50–200 mg dose range in both sexes, and when the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found.
Abstract: The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.
TL;DR: Weeks et al. as discussed by the authors reported on a 1975 study of ethnicity-of-interviewer effects among four ethnic minorities (Cubans, Chicanos, Native Americans, and Chinese) and suggested that the findings for blacks and whites are generalizable to other ethnic groups as well.
Abstract: Considerable research has been reported on race-of-interviewer effects in white/black dichotomies. Little is known, however, about interviewer effects on respondents representing other ethnic groups. This article reports on a 1975 study of ethnicityof-interviewer effects among four ethnic minorities (Cubans, Chicanos, Native Americans, and Chinese) and suggests that the findings for blacks and whites are generalizable to other ethnic groups as well. Michael F. Weeks is a Senior Survey Specialist and R. Paul Moore is Director of the Survey Operations Center at the Research Triangle Institute, P. 0. Box 12194, Research Triangle Park, North Carolina 27709. The work upon which this publication is based was performed pursuant to Contract 300-75-0253 with the U. S. Offlce of Education, Department of Health, Education, and Welfare. However, the opinions expressed herein do not necessarily reflect the position or policy of the U. S. Offlce of Education, and no official endorsement by the U. S. Office of Education should be inferred. Public Opinion Quarterly Vol. 45:245-249 ? 1981 by The Trustees of Columbia University Published by Elsevier North-Holland, Inc. 0033-362X/81/0045-245/$2.50 This content downloaded from 157.55.39.161 on Mon, 23 May 2016 05:41:58 UTC All use subject to http://about.jstor.org/terms
TL;DR: 5-hydroperoxyeicosatetraenoic acid (5-HPETE), at sub-micromolar concentrations, causes both a dose-dependent enhancement of histamine release and a reversal of the inhibition ofhistamine release caused by hormones and other agonists which act via adenylate cyclase.
Abstract: Arachidonic acid released from cellular phospholipids is metabolized by two major enzyme systems1. The cyclo-oxygenase pathways are responsible for the production of prostaglandins, thromboxanes and prostacyclin while the lipoxygenase pathways form a series of monoperoxy- and monohydroxyeicosatetraenoic acids. The 5-lipoxygenase pathway eventually leads to the production of both leukotriene B, one of the most potent chemotactic molecules known, and SRS-A (slow-reacting substance of anaphylaxis—leukotrienes C and D). Our earlier studies of the lipoxygenase enzyme(s) suggested that a product (s) of lipoxygenase (s) is both necessary for histamine release from human basophils and blunts endogenous control mechanisms2–4. To test this hypothesis, we have studied the effect of exogenously added products of lipoxygenase pathways on antigen-induced histamine release from human basophilic leukocytes in vitro. The present report demonstrates that 5-hydroperoxyeicosatetraenoic acid (5-HPETE), at sub-micromolar concentrations, causes both a dose-dependent enhancement of histamine release and a reversal of the inhibition of histamine release caused by hormones and other agonists which act via adenylate cyclase. The reduced product of 5-HPETE, 5-hydroxyeicosatetraenoic acid (5-HETE) has both activities, but is approximately 3 to 10 times less potent.
TL;DR: In this article, four historical data bases were examined for estimation of the regional trend in haziness over the past 80 years: surface visibility observations currently operated by the National Weather Service; historical visibility at Blue Hill MA; the NOAA-WMO turbidity network measuring the extinction of solar radiation with a sun photometer since the 1960's; and a set of direct solar radiation monitoring stations operated since 1910.
TL;DR: A review of current ideas about possible mechanisms for formation of combustion aerosols is presented in this article, where available data regarding fly ash size distribution and elemental concentrations in various size fractions were analyzed.
Abstract: The composition and size distribution of particles emitted by coal combustion sources depend upon various mechanisms leading to their formation. A review of current ideas about possible mechanisms for formation of combustion aerosols is presented. Available data regarding fly ash size distribution and elemental concentrations in various size fractions were analyzed. These data were qualitatively compared with theoretical model predictions to indicate the relative contributions of various mechanisms in the formation of aerosols.
TL;DR: In this paper, pregnant outbred albino (CD-1) mice were given 3,3′,4, 4,4′,5,5′hexachlorobiphenyl (HCB) by gavage in cottonseed oil on Days 6-15 of gestation at dosages of 0.1, 1, 2, 4 6, 8, and 16 mg/kg/day.
TL;DR: It is suggested that plasma THC concentration is a poor predictor of simultaneously occurring physiological and psychological pharmacologic effects.
Abstract: The relationship between each of two pharmacologic effects (tachycardia and psychological “high”) of delta-9-tetrahydrocannabinol (THC) and plasma THC concentration was investigated in three male and three female experienced marihuana smokers. Each subject smoked one 1% THC cigarette on two occasions separated by 2 h. Heart rate and subjective psychological self-rating were determined frequently throughout the 4 h study period. Data were analyzed by calculating the area under the parameter versus time curves, constructing hysteresis plots, and calculating the decay rate constants from pharmacologic effect versus time plots. In both males and females, dose inhaled and psychological response were apparently equivalent for the first and second cigarettes. While all subjects exhibited marked tachycardia in response to the first cigarette, heart rate in both male and female subjects was not increased as markedly during the second cigarette. Interestingly, female subjects had less tachycardiac response than males during the second cigarette. Hysteresis plots revealed that both heart rate and subjective psychological effects were elicited in an effect compartment which was “deep” relative to the reference plasma compartment. The time courses of tachycardiac and psychological responses lagged behind the plasma THC concentration-time profile. Zero-order decay rate constants for subjective psychological rating did not change substantially from the first to second cigarette. This study suggests that plasma THC concentration is a poor predictor of simultaneously occurring physiological and psychological pharmacologic effects.
TL;DR: Culture forms of Trypanosoma cruzi are incapable of synthesizing purines de novo from formate, glycine, or serine and require an exogenous purine for growth.
Journal Article•
TL;DR: Differential effects of cations and nucleotide further emphasize the differences that exist between morphine and enkephalin receptors and indicate the complex interactions of cation and nucleotides with opiate-binding sites.
Abstract: The effects of cations and GTP on morphine (µ) and enkephalin (δ) receptors were examined by using binding assays of [3H]naloxone to rat brain membrane preparations and [3H]diprenorphine or [3H]naloxone to neuroblastoma cell membranes. The potencies and Hill coefficients (n) of many opiate agonists and opioid peptides in competing with the binding of the labeled antagonist are reduced by Na+ (100 mM) and GTP (0.1 mM). These effects are qualitatively similar for both subtypes of opiate receptors. However, quantitatively, the effects of GTP are much more profound for morphine receptors than for enkephalin receptors and the effects of Na+ are dependent upon the type of labeled antagonist used rather than upon receptor type. Na+ does not alter the affinity of opiate antagonists. GTP reduces the affinity of naloxone to morphine-binding sites by a factor of 2.5. Mg2+ (5 mM) increases the potency of opiate agonists and enkephalins for both receptor sites. The combination of Na+, GTP, and Mg2+ further reduces the affinity of enkephalins and opiate agonists for enkephalin-binding sites and the affinity of Met- and Leu-enkephalin for morphine-binding sites. However, the combination of Na+, GTP, and Mg2+ partially restores the affinity of [D-Ala2, Leu5]- and [D-Ala2, D-Leu5]enkephalin and morphine for the morphine-binding sites. These differential effects of cations and nucleotide further emphasize the differences that exist between morphine and enkephalin receptors and indicate the complex interactions of cations and nucleotides with opiate-binding sites.
TL;DR: The uptake and concentration of radioactivity associated with hydroquinone and catechol by bone marrow and lymphoid organs can occur independently of the metabolism of benzene in these tissues and is reduced under conditions in which the animal is less susceptible to benzene toxicity.
TL;DR: In this paper, a sampling study was conducted to quantify the relationship of NO, NO2 and O3 concentrations with distance downwind of the San Diego freeway in Los Angeles, and a spatial model was fitted to the empirical NO and NO2 data, which incorporated the effects of dilution, reaction and background level on measured downwind concentration.
TL;DR: The neurochemical properties of bupropion on uptake of biogenic amines and on MAO activity serve to distinguish it from other antidepressant drugs of the tricyclic and MAO inhibitor classes.
Abstract: Bupropion is a novel antidepressant agent. In the present study, an attempt was made to gain some insight into the mechanism of the drug's antidepressant activity. In vitro studies revealed that bupropion was a weak, competitive inhibitor of norepinephrine (NE) uptake into rat hypothalamic synaptosomes and of dopamine (DM) uptake into rat striatal synaptosomes, having IC50 values of 6.5 ± 0.6 × 10−6 M and 3.4 ± 0.4 × 10−6 M, respectively. At 1 × 10−5 M, the drug produced a 20 ± 3% inhibition of serotonin (5-HT) uptake into rat hypothalamic synaptosomes. The drug was also a weak inhibitor of the ATP-Mg+2 stimulated uptake of NE and DM into synaptic vesicles of whole rat brain, having IC50 values of 3.3 × 10−5 M and 6.0 × 10−5 M, respectively. Bupropion had no dose-dependent effect on the spontaneous release of NE, DM, and 5-HT from these synaptosomal preparations in concentrations as high as 1 × 10−4 M. Brain monoamine oxidase (MAO) activity in vitro was not affected by concentrations of the drug ranging from 10−7 M to 10−5 M. Bupropion was also without effect on brain MAO, 1 hr after i.p. doses in rats as high as 100 mg/kg. The ED50 value for bupropion necessary to inhibit the uptake of 3H-catecholamines by 50% into synaptosomes incubated in the serum from rats treated with the drug was 40 mg/kg i.p., while its ED50 value for antidepressant activity, as judged by the ability of bupropion to reverse the immobile posture of “helpless” rats, was 8 mg/kg i.p. These neurochemical properties of bupropion on uptake of biogenic amines and on MAO activity serve to distinguish it from other antidepressant drugs of the tricyclic and MAO inhibitor classes.