RESUMEN
OBJECTIVE: Studies of relationships between tobacco sales and socio-economic/sociodemographic characteristics are well documented. However, when analysing the data that are collected on geographic areas, the spatial effects are seldom considered, which could lead to potential misleading analytical results. This study addresses this concern by applying the spatial analysis method in studying how socio-economic factors and tobacco outlet density are related in New Jersey, USA. STUDY DESIGN: A spatial regression method applied to tobacco outlet and socio-economic data obtained in 2004 in New Jersey, USA. METHOD: This study assessed the association between tobacco outlet density and three demographic correlates - income, race and ethnicity - at the tract level of analysis for one state in the north-eastern USA. Data for 1938 residential census tracts in the state of New Jersey were derived from 2004 licences for 13,984 tobacco-selling retail outlets. Demographic variables were based on 2000 census data. When applying a regression model, the residuals of an ordinary least squared (OLS) estimation were found to exhibit strong spatial autocorrelation, which indicates that the estimates from the OLS model are biased and inferences based on the estimates might be misleading. A spatial lag model was employed to incorporate the potential spatial effects explicitly. RESULTS: Agreeing with the OLS residual autocorrelation test, the spatial lag model yields a significant coefficient of the added spatial effect, and fits the data better than the OLS model. In addition, the residuals of the spatial regression model are no longer autocorrelated, which indicates that the analysis produces more reliable results. More importantly, the spatial regression results indicate that tobacco companies attempt to promote physical availability of tobacco products to geographic areas with disadvantageous socio-economic status. In New Jersey, the percentage of Hispanics seems to be the dominant demographic factor associated with tobacco outlet distribution, followed by median household income and percentage of African Americans. CONCLUSION: This research applied a spatial analytical approach to assess the association between tobacco outlet density and sociodemographic characteristics in New Jersey at the census tract level. The findings support the common wisdom in the public health research domain that tobacco outlets are more densely distributed in socio-economically disadvantaged areas. However, incorporating the spatial effects explicitly in the analysis provides less biased and more reliable results than traditional methods.
Asunto(s)
Comercio , Hispánicos o Latinos , Áreas de Pobreza , Características de la Residencia , Industria del Tabaco/economía , Negro o Afroamericano , Análisis por Conglomerados , Humanos , New JerseyRESUMEN
Empowerment theory represents an expansive view of individual and collective behavior that includes the active participation of individuals and groups in altering and shaping the socioenvironmental context. Critical to health educators are local interventions that yield participation of community members and empowerment for participants. The concept of social cohesion embraces participation but expands this behavioral emphasis to incorporate notions of trust, connectedness, and civic engagement. This study presents two data sets on the relationship of participation to empowerment. The first replicates and extends previous research by examining participation with interactional as well as intrapersonal empowerment. Second is the examination of how the quality of the participatory experience--the cohesive nature of participation--is related to interactional and intrapersonal empowerment. Findings support and extend previous findings, reliably cluster residents by the degree of connectedness in their participatory experiences, and reveal that social cohesion is related to intrapersonal empowerment.
Asunto(s)
Participación de la Comunidad/psicología , Poder Psicológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , New England/epidemiología , Ajuste Social , Apoyo SocialRESUMEN
Lactoferrin (Lf) and serum transferrin (Tf) combine high-affinity iron binding with an ability to release this iron at reduced pH. Lf, however, retains iron to significantly lower pH than Tf, giving the two proteins distinct functional roles. In this paper, we compared the iron-release profiles for human Lf, Tf, and their N-lobe half-molecules Lf(N) and Tf(N) and showed that half of the difference in iron retention at low pH ( approximately 1.3 pH units) results from interlobe interactions in Lf. To probe factors intrinsic to the N-lobes, we further examined the specific role of two basic residues that are proposed to form a pH-sensitive dilysine trigger for iron release in the N-lobe of Tf [Dewan, J. C., Mikami, B., Hirose, M., and Sacchettini, J. C. (1993) Biochemistry 32, 11963-11968] by mutating Arg 210 to Lys in the N-lobe half-molecule Lf(N). The R210K mutant was expressed, purified, and crystallized, and its crystal structure was determined and refined at 2.0-A resolution to a final R factor (R(free)) of 19.8% (25.0%). The structure showed that Lys 210 and Lys 301 in R210K do not form a dilysine interaction like that between Lys 206 and Lys 296 in human Tf. The R210K mutant retained iron to lower pH than Tf(N), consistent with the absence of the dilysine interaction but released iron at approximately 0.7 pH units higher than Lf(N). We conclude that (i) the ability of Lf to retain iron to significantly lower pH than Tf is due equally to interlobe interactions and to the absence in Lfs of an interaction analogous to the dilysine pair in Tfs, even when two lysines are present at the corresponding sequence positions, and (ii) an appropriately positioned basic residue (Arg 210 in human Lf) modulates iron release by inhibiting protonation of the N-lobe iron ligands, specifically His 253.
Asunto(s)
Hierro/metabolismo , Lactoferrina/química , Transferrina/química , Sitios de Unión , Carbonatos/química , Cristalografía por Rayos X , Humanos , Concentración de Iones de Hidrógeno , Lactoferrina/genética , Lisina/química , Modelos Moleculares , Mutación , Fragmentos de Péptidos/química , Unión Proteica , Conformación Proteica , Proteínas Recombinantes/químicaAsunto(s)
Lactoferrina/química , Lactoferrina/metabolismo , Transferrina/química , Transferrina/metabolismo , Animales , Humanos , Lactoferrina/genética , Mutación Puntual , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Relación Estructura-ActividadRESUMEN
We determined the cardiovascular effects of 0.91, 1.34, and 1.74 MAC of desflurane/nitrous oxide anesthesia (60% inspired nitrous oxide contributed 0.5 MAC at each level) in 12 healthy, normocapnic male volunteers. Desflurane/nitrous oxide anesthesia decreased systemic blood pressures, cardiac index, stroke volume index, systemic vascular resistance, and left ventricular stroke work index, and increased pulmonary arterial pressures and central venous pressure in a dose-dependent fashion, while heart rate was 10%-12% and mixed venous oxygen tension was 2-4 mm Hg higher at all MAC levels than at baseline (awake). Desflurane/nitrous oxide anesthesia modestly increased left ventricular end-diastolic cross-sectional area (preload) and decreased velocity of left ventricular circumferential fiber shortening, systolic wall stress (afterload), and area ejection fraction; this combination of changes indicates myocardial depression. At approximately comparable MAC levels, heart rate was lower and systemic blood pressures, central venous pressure, left ventricular stroke work index, and systemic vascular resistance usually were significantly higher during anesthesia with desflurane and nitrous oxide than during desflurane anesthesia alone (same volunteers, data collected in crossover design). After 7 h of anesthesia, regardless of the background gas, somewhat less cardiovascular depression and/or modest stimulation was apparent: cardiac index, area ejection fraction, and velocity of left ventricular circumferential fiber shortening recovered to or toward awake values, whereas heart rate was further increased. Evidence of circulatory insufficiency did not develop in any volunteers during the study. Segmental left ventricular function was normal at baseline, and no segmental wall-motion abnormalities, ST-segment change, or dysrhythmias developed.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anestésicos/farmacología , Hemodinámica/efectos de los fármacos , Isoflurano/análogos & derivados , Óxido Nitroso/farmacología , Administración por Inhalación , Adulto , Desflurano , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Humanos , Isoflurano/farmacología , MasculinoRESUMEN
The low solubility of sevoflurane in blood suggests that this agent should enter and leave the body more rapidly than isoflurane. However, the closeness of sevoflurane and isoflurane tissue/blood partition coefficients suggests that the rates of equilibration with and elimination from tissues should be similar. We tested both predictions, comparing sevoflurane with isoflurane and nitrous oxide in seven volunteers. We measured the rate at which the alveolar (end-tidal) (FA) concentration of nitrous oxide increased toward an inspired (FI) concentration of 65%-70%, then measured the concurrent rise in FA and mixed expired concentrations (FM) of sevoflurane and isoflurane at respective FI values of 1.0% sevoflurane and 0.6% isoflurane for 30 min. Minute ventilation (VE) was measured concurrently with the measurements of anesthetic concentrations. For the potent agents, we also measured VE, FA, and FM for 6-7 days of elimination. FA/FI values at 30 min of administration were as follows: nitrous oxide, 0.986 +/- 0.003 (mean +/- SD); sevoflurane, 0.850 +/- 0.018; and isoflurane, 0.733 +/- 0.027. FA/FA0 (FA0 = the last FA during administration) values after 5 min of elimination were as follows: sevoflurane, 0.157 +/- 0.020; isoflurane, 0.223 +/- 0.024. Recovery (volume of anesthetic recovered during elimination/volume taken up) of sevoflurane (101% +/- 7%) equaled recovery of isoflurane (101% +/- 6%). Time constants for a five-compartment mammillary model for sevoflurane were smaller than those for isoflurane for the lungs but were not different from isoflurane for the other compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anestésicos/farmacocinética , Éteres/farmacocinética , Isoflurano/farmacocinética , Éteres Metílicos , Administración por Inhalación , Adulto , Humanos , Masculino , Óxido Nitroso/farmacocinética , Sevoflurano , Distribución TisularRESUMEN
Leucine- and methionine-enkephalins inhibit the Na+-dependent transport of proline into plasma membrane vesicles derived from synaptosomes. Glycine transport is weakly inhibited by enkephalins whereas there is no inhibition of transport of glutamic acid, aspartic acid, or gamma-aminobutyric acid. The inhibition of proline uptake is observed with des-tyrosyl-enkephalins but not with morphine, dynorphin(1-13), or beta-endorphins. Furthermore, enkephalin-induced inhibition of proline transport is not antagonized by naloxone. [Leu]enkephalinamide and modified [Leu]enkephalins with greater selectivity for the delta-subclass of enkephalin binding sites are less effective than [Leu]enkephalin in the inhibition of proline transport. Specific binding of [3H]Leu-enkephalin to the plasma membrane vesicles is demonstrated, and des-Tyr-[Leu]enkephalin competes with Leu-enkephalin for [Leu]enkephalin binding sites. The similarity in the concentrations of des-Tyr-[Leu]enkephalin required to compete for specific [Leu]enkephalin binding and to inhibit proline transport suggests that a specific subclass of enkephalin binding sites, distinguished by their recognition of both the enkephalins and their des-tyrosyl derivatives, may be associated with the synaptic proline transport system.
Asunto(s)
Encefalina Leucina/farmacología , Encefalina Metionina/farmacología , Encefalinas/farmacología , Prolina/metabolismo , Receptores Opioides/metabolismo , Sinaptosomas/metabolismo , Aminoácidos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Membrana Celular/metabolismo , Encefalinas/metabolismo , Cinética , Naloxona/farmacología , Relación Estructura-ActividadRESUMEN
Insulin stimulates in a dose-dependent manner (concentration range of 0.1 - 10 microM) the synaptosomal uptake of amino acids characterized by high-affinity, Na+-dependent, veratridine-sensitive transport systems. This stimulation is observed in synaptosomes prepared from each of several regions of the adult rat brain. Both the initial rate of amino acid uptake and the overall capacity for amino acid accumulation are increased. Since these transport systems have been associated with the neurotransmitter role of the amino acids, we postulate that insulin can modulate neurotransmission in the rat central nervous system by increasing the efficiency of neuroactive amino acid reuptake.
Asunto(s)
Aminoácidos/metabolismo , Encéfalo/metabolismo , Insulina/farmacología , Neurotransmisores/metabolismo , Sinaptosomas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Cinética , Ratas , Ratas Endogámicas , Sinaptosomas/efectos de los fármacos , Distribución Tisular , Veratridina/farmacologíaRESUMEN
Evidence is presented which suggests that proline, pipecolic acid, and glycine are accumulated by a common transport system in rat brain cortical synaptosomes and synaptosomal plasma membrane vesicles. This system is Na+ dependent and appears to be similar to the iminoglycine transport system present in renal tubules and in renal brush border membranes. The opioid pentapeptides Leu- and Met-enkephalin specifically inhibit the uptake of these three imino/amino acids, presumably by interaction with a nonopioid receptor, since the inhibition is not affected by the opiate antagonist naloxone and occurs with des-tyrosyl enkephalins as well as with the intact pentapeptides.
Asunto(s)
Corteza Cerebral/metabolismo , Encefalina Leucina/farmacología , Encefalina Metionina/farmacología , Iminoácidos/metabolismo , Sinaptosomas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Glicina/metabolismo , Cinética , Narcóticos/farmacología , Ácidos Pipecólicos/metabolismo , Prolina/metabolismo , Ratas , Ratas Endogámicas , Sodio/farmacología , Sinaptosomas/efectos de los fármacosRESUMEN
The high affinity, sodium-dependent uptake of proline by rat brain synaptosomes was inhibited by the opioid pentapeptides, Leu-enkephalin and Met-enkephalin. The synaptosomal uptake of other putative neurotransmitter amino acids including glutamic acid, aspartic acid, gamma-aminobutyric acid, and taurine was not altered in the presence of enkephalins. The uptake of a neuroinactive amino acid, leucine, was also unaffected by enkephalins. The extent of proline uptake was half-maximal at a Leu-enkephalin concentration of 1 microM. Both the initial rate of transport and the overall capacity for proline accumulation were reduced. The effect of the enkephalins was vectorial since carrier-mediated efflux of proline was not altered in the presence of enkephalins. Morphine and the opioid peptides, dynorphin and beta-endorphin, were without effect on proline uptake. The inhibition of proline uptake by enkephalins was not diminished by prior incubation of the synaptosomal preparation with naloxone; however, the inhibition was attenuated by 1-butanol. The des-tyrosyl fragments of the enkephalins were as inhibitory as the intact pentapeptides. A modified enkephalin ([D-Ser2]Leu-enkephalin-Thr) with selective affinity for the delta subclass of enkephalin receptor was effective in inhibiting proline uptake. On the basis of the selectivity of these effects, we propose that there is a specific population of nerve endings in the cerebral cortex that contains both a proline-transport system and binding sites for Leu- and Met-enkephalin and furthermore, that these binding sites may be related to the putative delta receptor.
Asunto(s)
Encefalina Leucina/farmacología , Encefalina Metionina/farmacología , Prolina/metabolismo , Sinaptosomas/metabolismo , Animales , Ácido Aspártico/metabolismo , Transporte Biológico/efectos de los fármacos , Corteza Cerebral/metabolismo , Glutamatos/metabolismo , Ácido Glutámico , Cinética , Neurotransmisores/metabolismo , Ratas , Ratas Endogámicas , Sinaptosomas/efectos de los fármacos , Taurina/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The release of preloaded [14C]neuroactive amino acids (glutamic acid, proline, gamma-aminobutyric acid) from rat brain synaptosomes can occur via a time-dependent, Ca2+-independent process. This Ca2+-independent efflux is increased by compounds that activate Na+ channels (veratridine, scorpion venoms), by the ionophore gramicidin D, and by low concentrations of unsaturated fatty acids (oleic acid and arachidonic acid). Saturated fatty acids have no effect on the efflux process. Neither saturated nor unsaturated fatty acids have an effect on the release of [14C]leucine, an amino acid not known to possess neurotransmitter properties. The increase in the efflux of neuroactive amino acids by oleic and arachidonic acids can also be demonstrated using synaptosomal membrane vesicles. Under conditions in which unsaturated free fatty acids enhance amino acid efflux, no effect on 22Na+ permeability is observed. Since Na+ permeability is not altered by fatty acids, the synaptosomes are not depolarized in their presence and, thus, the Na+ gradient can be assumed to be undisturbed. We conclude that unsaturated fatty acids represent a potentially important class of endogenous modulators of neuroactive amino acid transport in nerve endings and further postulate that their action is the result of an uncoupling of amino acid transport from the synaptosomal Na+ gradient.
Asunto(s)
Aminoácidos/metabolismo , Ácidos Araquidónicos/farmacología , Corteza Cerebral/metabolismo , Neurotransmisores/metabolismo , Ácidos Oléicos/farmacología , Sinaptosomas/metabolismo , Animales , Ácido Araquidónico , Calcio/farmacología , Glutamatos/metabolismo , Ácido Glutámico , Cinética , Ácido Oléico , Prolina/metabolismo , Ratas , Ratas Endogámicas , Sinaptosomas/efectos de los fármacos , Veratridina/farmacología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
From measured effects of amino acids on synaptosomal tyrosine uptake and from published data on human CNS levels of amino acids hypothetical calculations were made to compare CNS tyrosine availability for catecholamine synthesis in the hyperphenylalaninemic and non-hyperphenylalaninemic condition. These calculations indicate an approximately two-fold reduction in the availability of tyrosine in phenylketonuria that is due solely to a reduction in CNS tyrosine alone.
Asunto(s)
Encéfalo/metabolismo , Fenilcetonurias/metabolismo , Sinapsis/metabolismo , Tirosina/metabolismo , Aminoácidos/metabolismo , Animales , Corteza Cerebral/metabolismo , Humanos , Cinética , Ratas , Ratas Endogámicas , Sinaptosomas/metabolismoRESUMEN
High-affinity, Na+-dependent synaptosomal amino acid uptake systems are strongly stimulated by proteins which are known to bind free fatty acids. The rate of uptake as well as the overall level of accumulation is increased by such proteins as bovine serum albumin, hepatic fatty acid binding protein, beta-lactoglobulin, and fetuin. Such a stimulation is not observed with proteins which do not bind fatty acids. The transport activity of synaptosomal preparations can be directly correlated with the free fatty acid content of the preparation. Thus, incubation with albumin reduces the free fatty acid content of synaptosomal preparations, suggesting that the stimulatory effects of the proteins are related to their removal of inhibitory fatty acids formed by hydrolysis of membrane lipids during incubation. Inhibition of amino acid uptake is seen with most cis-unsaturated long chain fatty acids while saturated and trans-unsaturated fatty acids have relatively little or no effect. Under conditions in which the ionophore gramicidin D causes an increase of 22Na flux into synaptosomes, oleic acid (50 microM) has no effect on the influx. These data are consistent with the hypothesis proposed earlier by us [Rhoads, D. E., Peterson, N. A., & Raghupathy, E. (1982) Biochemistry 21, 4782] that Na+-dependent amino acid transport carrier proteins reside in a relatively fluid lipid domain in the synaptosomal membrane and that the effects of cis-unsaturated fatty acids are mediated by interactions with such domains.
Asunto(s)
Aminoácidos/metabolismo , Ácidos Grasos no Esterificados/farmacología , Sodio/farmacología , Sinaptosomas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Corteza Cerebral/metabolismo , Cinética , Masculino , Ratas , Ratas Endogámicas , Albúmina Sérica Bovina/farmacología , Relación Estructura-Actividad , Sinaptosomas/efectos de los fármacosRESUMEN
Synaptosomal membrane vesicles have been employed to study the energetics of proline transport and the inhibition of proline transport by unsaturated free fatty acids. Active uptake of proline into synaptosomal membrane vesicles requires extravesicular Na+ and is primarily driven by a Na+ gradient created by diluting K+-loaded vesicles into Na+-containing buffers. Uptake of proline under these conditions is enhanced up to 2-fold by a valinomycin-induced diffusion potential (interior negative). Proline transport is reduced in the absence of external C1- or internal K+. Strong (40-90%) inhibition of proline uptake occurs upon collapse of the Na+ gradient by ionophores such as gramicidin D or activation of the action potential Na+ channel by veratridine or Tityus serrulatus venom. Less (15-25%) inhibition is obtained with the proton ionophore carbonyl cyanide m-chlorophenylhydrazone, which also prevents the stimulation of proline uptake by the valinomycin-induced diffusion potential. Unsaturated free fatty acids inhibit proline uptake. The inhibition is greatest for arachidonic acid and was somewhat less for oleic acid. The saturated fatty acids palmitic and stearic have little or no inhibitory capacity. Endogenous unsaturated free fatty acids may exert similar inhibitory effects on the reuptake systems for neuroactive amino acids and thus modulate their action in the central nervous system.
Asunto(s)
Corteza Cerebral/metabolismo , Ácidos Grasos no Esterificados/farmacología , Membranas Intracelulares/metabolismo , Prolina/metabolismo , Sinaptosomas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Membranas Intracelulares/efectos de los fármacos , Cinética , Potenciales de la Membrana/efectos de los fármacos , Ratas , Ratas Endogámicas , Sinaptosomas/efectos de los fármacos , Valinomicina/farmacología , Veratridina/farmacologíaRESUMEN
The Na+-dependent synaptosomal uptakes of proline, aspartic acid, glutamic acid, and gamma-aminobutyric acid were strong inhibited by monounsaturated fatty acids. With oleic acid, half-maximal inhibition was observed at about 15 microM. The Na+-independent uptakes of leucine, phenylalanine, histidine, and valine were less sensitive to inhibition by the unsaturated fatty acids. In contrast, the uptakes of all of these amino acids were unaffected by saturated fatty acids. The inhibition of proline uptake (and that of the other Na+-dependent amino acids) by oleic acid was overcome by the addition of serum albumin and the data presented further indicate that the previously reported stimulation of proline uptake by albumin could be related to its fatty acid binding properties.
Asunto(s)
Aminoácidos/metabolismo , Ácidos Grasos no Esterificados/farmacología , Sinaptosomas/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Ratas , Ratas Endogámicas , Albúmina Sérica Bovina/farmacología , Sodio/metabolismo , Sinaptosomas/efectos de los fármacos , Factores de TiempoRESUMEN
Bovine serum albumin (BSA) is shown to stimulate selectively the synaptosomal uptakes of those amino acids that are dependent on external Na+ and that are inhibited by veratridine. Thus, the stimulation can be seen in the case of aspartic acid, glutamic acid, glycine, proline, and gamma-aminobutyric acid, but not with serine and threonine. Further, studies on the interaction of veratridine, valinomycin, and BSA on the uptake of proline suggest that the primary action of the albumin is to increase the influx of proline. Such an action could result as a consequence of stabilization of the Na+ gradient by increased endogenous levels of ATP. Intrasynaptosomal ATP was increased in the presence of BSA but significantly decreased by veratridine.
Asunto(s)
Aminoácidos/metabolismo , Albúmina Sérica Bovina/farmacología , Sodio/metabolismo , Sinaptosomas/metabolismo , Veratridina/farmacología , Veratrina/análogos & derivados , Animales , Ouabaína/farmacología , Ratas , Valinomicina/farmacologíaRESUMEN
Scorpion (Tityus serrulatus) venom strongly inhibited the Na+-dependent uptake of (( 14C ))proline by rat brain synaptosomal preparations. In addition, the efflux of proline was enhanced markedly by scorpion venom. The inhibitory effects of the venom were also demonstrated in synaptosomal vesicle preparations where proline uptake was energized by an artificially imposed Na+ gradient. In both preparations, the effect of scorpion venom was additive with the inhibitory effect of veratridine on Na+-dependent amino acid uptake. The inhibitory effects of both compounds were abolished by tetrodotoxin. The Na+-dependent uptakes of amino acids (e.g. proline, glutamic acid, and gamma-aminobutyric acid) were much more sensitive to inhibition by the toxin than the Na+-independent uptakes (e.g. leucine and phenylalanine). The results of the present study indicate that the scorpion venom may exert its inhibitory effect on Na+-dependent transport by decreasing the transmembrane Na+ gradient. Efflux of accumulated proline, which is presumably controlled by maintenance of this Na+ gradient, was stimulated 3- to 4-fold by the scorpion venom.