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Black Americans with multiple sclerosis (MS) experience higher levels of disease-related disability compared to White Americans (Marrie et al., 2006). Comorbidities such as depression and anxiety, which are underdiagnosed and undertreated in this population, negatively impact quality of life and treatment outcomes for people living with multiple sclerosis (plwMS) (D'Alisa et al., 2006; Marrie et al., 2009; Stepleman et al., 2014). Acts of discrimination toward Black Americans is associated with stress, which is a contributing factor for depression (Carter, 2017; Nadimpalli, 2015; Williams and Mohammed, 2009). This study compared the severity of multiple sclerosis symptoms amongst Black Americans and White Americans, and whether worsened MS symptoms in Black Americans are associated with increased experiences of discrimination. Data was analyzed from 143 plwMS in the Stress Indicators in Minorities with Multiple Sclerosis (SiMMS) study. Using the Mann-Whitney U test, significant differences were found on the NIH Emotional Distress - Anxiety measure (U = 1466.500, p = 0.045) and NIH Sleep Disturbance measure (U = 1467.000, p = 0.044) between the Black participant and the White participant groups. Discrimination was significantly correlated with both NIH Emotional Distress - Anxiety (r = 0.677, p < .001) and NIH Sleep Disturbance (r = 0.446, p = .007) in Black MS individuals. Additionally, several physiological condition and psychological outcome measures were correlated with the NIH Emotional Distress - Anxiety and NIH Sleep Disturbance measures. This study contributes to literature highlighting the negative impacts of discrimination and race related stress on the physical and mental health of Black Americans.
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We report a novel approach to the design and development of microcantilever sensors in which photochemical hydrosilylation is used to modify the microcantilever surface. This process enables individual microcantilevers in multicantilever array chips to be modified separately by focusing the activating UV light sequentially on each particular cantilever. Photochemical hydrosilylation of 11-undecenyltriethylammonium bromide with hydrogen-terminated silicon microcantilever surfaces was carried out to yield a robust quaternary ammonium terminated organic monolayer suitable for chromate detection. The surface functionalities retain their affinity toward Cr(VI), and the organic monolayer is dense enough to generate significant surface stress upon subsequent adsorption of chromate ions from aqueous solutions.
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The potential-induced surface stress of a solid electrode was investigated in an electrochemical cell. Gold-coated atomic force microscopy microcantilevers were used as working electrodes to measure the current-potential response (by cyclic voltammetry) and simultaneous bending characteristics in solutions of NaNO3 and K3Fe(CN)6/NaNO3. The observed changes of differential surface stress at a microcantilever electrode were attributed to electrochemical-potential-induced changes in surface charge density, ion adsorption/desorption, and electron transfer across the electrode surface. The potential dependent change in stress shows promise for the study of microscopic properties at the solid-electrolyte interface.
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OBJECTIVE: The treatment of chronic fissure may be medical or surgical. Indications for assessment, which is the better treatment and under what circumstances, are vital for the appropriate management. The aim of the study was to assess the management of this condition by an expert group of surgeons. METHODS: Consultant members of the Association of Coloproctology of Great Britain and Ireland (n=452) were approached and requested to answer a preset multiple-choice questionnaire. The questionnaire was designed to assess their management strategy and their approach to investigation and treatment under different clinical situations. RESULTS: The overall response was 78% (n = 356). Medical treatment was the first line treatment in 95% of the responders. Lateral anal sphincterotomy without pre-operative endoanal ultrasound and/or anorectal physiology was performed by 57%. Anal dilatation was performed selectively by 36% but only 35% of these would perform a pre-operative endoanal ultrasound or anorectal physiology. CONCLUSION: In the selected group of clinicians lateral anal sphincterotomy remains the procedure of choice in both sexes. Pre-operative assessment using endoanal ultrasound and anorectal physiology is used selectively especially in postpartum women. Anal dilatation remains a subjective procedure and though used selectively, is performed without pre-operative endoanal ultrasound and/or anorectal physiology in majority of cases.
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Fisura Anal/terapia , Pautas de la Práctica en Medicina , Adulto , Actitud del Personal de Salud , Enfermedad Crónica , Dilatación , Femenino , Fisura Anal/cirugía , Humanos , Masculino , Insuficiencia del TratamientoRESUMEN
To gain insight into the role of melatonin and dopamine in retinal development, gene expression of two melatonin receptors, MT1 and MT2, as well as five dopamine receptors, D1, D2, D3, D4 and D5, in the rat eye was analyzed by reverse transcription-polymerase chain reaction across various developmental stages. MT1 transcript levels reached maximum levels at embryonic day (E) 16 and then decreased gradually until reaching adult levels by postnatal day (P) 14. MT2 transcript levels similarly peaked at E16, but then decreased dramatically until birth to its lowest levels, which were maintained throughout the postnatal period. Thus, gene expression of both the MT1 and MT2 receptors showed a striking inverse correlation with maturation of the eye. In contrast to melatonin receptors, gene expression of all dopamine receptor subtypes, except for D3, showed only an increase as development proceeds with highest levels in adulthood. The D3 message was not detected throughout the developmental period examined. Gene expression of D1-like receptors, D1 and D5, showed a substantial increase to adult levels during the fetal period at E16 and E20, respectively. Transcript levels of D2-like receptors, D2 and D4, on the other hand, were not detected before birth but increased significantly to adult levels by P7 and P14, respectively. The present findings suggest the presence of unique developmental mechanisms by which transcription of various G protein-coupled receptors are regulated in the eye.
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Ojo/embriología , Regulación del Desarrollo de la Expresión Génica , Receptores de Superficie Celular/genética , Receptores Citoplasmáticos y Nucleares/genética , Receptores Dopaminérgicos/genética , Envejecimiento/genética , Envejecimiento/metabolismo , Animales , Animales Recién Nacidos , Densitometría/instrumentación , Densitometría/métodos , Embrión de Mamíferos , Ojo/crecimiento & desarrollo , Ojo/metabolismo , Femenino , Masculino , Sondas de Oligonucleótidos/metabolismo , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Receptores de Superficie Celular/clasificación , Receptores Citoplasmáticos y Nucleares/clasificación , Receptores Dopaminérgicos/clasificación , Receptores Dopaminérgicos/metabolismo , Receptores de Melatonina , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosRESUMEN
The pineal hormone melatonin plays an important role in the neuroendocrine control of reproductive physiology, but its effects on hypothalamic GnRH neurons are not yet known. We have found that GT1-7 GnRH-secreting neurons express membrane-bound G protein-coupled melatonin receptors, mt1 (Mel-1a) and MT2 (Mel-1b) as well as the orphan nuclear receptors ROR alpha and RZR beta. Melatonin (1 nM) significantly downregulates GnRH mRNA levels in a 24-h cyclical manner, an effect that is specifically inhibited by the melatonin receptor antagonist luzindole (10 microM). Repression of GnRH gene expression by melatonin appears to occur at the transcriptional level and can be mapped to the GnRH neuron-specific enhancer located within the 5' regulatory region of the GnRH gene. Using transient transfection of GT1-7 cells, downregulation of GnRH gene expression by melatonin was further localized to five specific regions within the GnRH enhancer including -1827/-1819, -1780/-1772, -1746/-1738, -1736/-1728, and -1697/-1689. Interestingly, the region located at -1736/-1728 includes sequences that correspond to two direct repeats of hexameric consensus binding sites for members of the ROR/RZR orphan nuclear receptor family. To begin to dissect the mechanisms involved in the 24-h cyclical regulation of GnRH transcription, we have found that melatonin (10 nM) induces rapid internalization of membrane-bound mt1 receptors through a beta-arrestin 1-mediated mechanism. These results provide the first evidence that melatonin may mediate its neuroendocrine control on reproductive physiology through direct actions on the GnRH neurons of the hypothalamus, both at the level of GnRH gene expression and through the regulation of G protein-coupled melatonin receptors.
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Ritmo Circadiano , Expresión Génica/fisiología , Hormona Liberadora de Gonadotropina/genética , Hormona Liberadora de Gonadotropina/metabolismo , Melatonina/fisiología , Neuronas/metabolismo , Animales , Secuencia de Bases/genética , Línea Celular , Elementos de Facilitación Genéticos/genética , Elementos de Facilitación Genéticos/fisiología , Melatonina/farmacología , Ratones , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Melatonina , Transcripción Genética/fisiología , Triptaminas/farmacologíaRESUMEN
Selective ion exchange is one of the preferred treatment technologies for removing low levels of perchlorate (ClO4-) from contaminated water because of its high efficiency and minimal impact on water quality through the addition or removal of chemicals and nutrients. However, the exceptionally high affinity of ClO4- for type I anion-exchange resins makes regeneration with conventional NaCl brine extremely difficult and costly for practical applications. The present study entails the development of a novel regeneration methodology applicable to highly selective anion-exchange resins. Tetrachloroferrate (FeCl4-) anions, formed in a solution of ferric chloride and hydrochloric acid (e.g., 1 M FeCl3 and 4 M HCl), were found to effectively displace Cl04- anions that were sorbed on the resin. A mass-balance analysis indicated that a nearly 100% recovery of ion-exchange sites was achieved by washing with as little as approximately 5 bed volumes of the regenerant solution in a column flow-through experiment There was no significant deterioration of the resin's performance with respect to ClO4- removal after repeated loading and regeneration cycles. Thus, the new methodology may offer a cost-effective means to regenerate ClO4- -loaded resins with improved regeneration efficiency, recovery, and waste minimization in comparison with conventional brine regeneration techniques.
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Resinas de Intercambio Aniónico/química , Percloratos/química , Compuestos de Sodio/química , Contaminación del Agua/prevención & control , Fenómenos Químicos , Química Física , Compuestos de Cloro/química , Compuestos Férricos/química , Contaminantes Químicos del AguaRESUMEN
The chondroitin sulphate (CS) linkage regions have been isolated from human articular cartilage aggrecan (from 10- to 72-year-olds) by chondroitin ABC endolyase digestion and size-exclusion chromatography. Linkage region hexasaccharides have been characterized and their abundance estimated by high-pH anion-exchange chromatography. The basic structure for the CS linkage region oligosaccharides identified from human aggrecan is as follows: DeltaUA(beta1-3)GalNAc[0S/4S/6S](beta1-4)GlcA(beta1-3)Gal[0S/6S](beta1-3)Gal(beta1-4)Xyl, where DeltaUA represents 4,5-unsaturated hexuronic acid, 4S and 6S represent an O-ester sulphate group on C-4 and C-6 respectively, and 0S represents zero sulphation. There are significant age-related changes in the abundance of the various N-acetylgalactosamine (GalNAc) sulphation forms identified, occurring up to approx. 20 years old. During the period from 10 to 20 years old the level of GalNAc 6-sulphation at the linkage region increases from approx. 43% to approx. 75%, while there is a corresponding reduction in unsulphated (approx. 30% to approx. 20%) and 4-sulphated (approx. 25% to approx. 6%) GalNAc residues. There is also an increase in the incidence of linkage region galactose 6-sulphation (approx. 2% to approx. 10%) which was only observed in linkage regions with GalNAc 6-sulphation. Beyond 20 years old there are few changes in the relative abundance of these GalNAc sulphation variants; however, there is a slight increase in the abundance of 6-sulphation between approx. 20 years old and approx. 40 years old and a slight decrease in its abundance beyond approx. 40 years old. Our data show that in the majority of chains from tissues of all ages the GalNAc residue closest to the linkage region is 6-sulphated, but the level of GalNAc 6-sulphation within the linkage region is lower than the average level observed within the repeat region.
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Envejecimiento , Cartílago Articular/fisiología , Sulfatos de Condroitina/química , Proteínas de la Matriz Extracelular , Proteoglicanos/química , Adolescente , Adulto , Anciano , Agrecanos , Secuencia de Carbohidratos , Niño , Cromatografía por Intercambio Iónico , Humanos , Lectinas Tipo C , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
Microcantilevers modified with a self-assembled monolayer respond sensitively to specific ion concentrations. Here, we report the detection of trace amounts of CrO4(2-) using microcantilevers modified with a self-assembled monolayer of triethyl-12-mercaptododecylammonium bromide. The self-assembled monolayer was prepared on a silicon microcantilever coated with a thin layer of gold on one side. The microcantilever undergoes bending due to sorption of CrO4(2-) ions on the monolayer-modified side. It was found that a concentration of 10(-9) M CrO4(2-) can be detected using this technology in a flow cell. Other anions, such as Cl-, Br-, CO3(2-) (or HCO3-), and SO4(2-), have minimal effect on the deflection of this cantilever. The mechanics of the bending and the chemistry of cantilever modification are discussed.
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BACKGROUND: Noradrenergic dysfunction has been consistently implicated in depression. Much of the evidence, though, has been indirect, such as an attenuated growth hormone response to the alpha2-adrenoceptor agonist clonidine. To more directly examine central functioning of the noradrenergic system in depression, we have used [15O] H2O positron emission tomography (PET) to measure cerebral blood flow (rCBF) in combination with clonidine as a neuromodulatory probe. METHODS: Subjects were six depressed and six healthy women, medication free and matched for age and phase of menstrual cycle. Two PET scans were acquired at baseline and two scans at 20 and 35 min following an intravenous clonidine infusion of 1.4 microg/kg while subjects performed a sustained attention task. RESULTS: The growth hormone response did not show a significant difference between groups. However, PET results revealed a difference in the right superior prefrontal cortex that was resolved as an interaction from decreased rCBF in healthy control subjects but increased rCBF in the depressed group, which was not accounted for by differences in task performance. CONCLUSIONS: This differential effect of clonidine in the right prefrontal cortex provides in vivo evidence of noradrenergic dysfunction in depression, which we postulate arises from functionally impaired presynaptic alpha2-adrenoceptors as well as regionally "supersensitive" postsynaptic cortical alpha2-adrenoceptors.
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Agonistas alfa-Adrenérgicos/farmacología , Atención/efectos de los fármacos , Clonidina/farmacología , Corteza Prefrontal , Tomografía Computarizada de Emisión , Adulto , Circulación Cerebrovascular/fisiología , Femenino , Hormona de Crecimiento Humana/farmacología , Humanos , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Receptores Adrenérgicos alfa/efectos de los fármacosRESUMEN
Chondroitin sulfates were fragmented using the enzymes chondroitin sulfate ABC endolyase and chondroitin ACII lyase; both disaccharide and tetrasaccharide fragments were isolated after reduction to the corresponding 2-deoxy-2-N-acetylamino-D-galactitol (GalNAc-ol) form. These have the structures: Delta UA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)L-IdoA(alpha 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc4S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol, Delta UA(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc4S-ol and Delta UA2S(beta 1--3)GalNAc6S(beta 1--4)GlcA(beta 1--3)GalNAc6S-ol, where Delta UA represents a 4,5-unsaturated hexuronic acid (4-deoxy-alpha-Lthreo-hex-4-enepyranosyluronic acid) and 6S/4S/2S represent O-ester sulfate groups at C6/C4/C2 sites. Complete (1)H-NMR and (13)C-NMR data are derived for these species, which may help to alleviate some of the significant difficulties resulting from signal complexity that are currently hindering the characterization and assignment of major and minor structural components within chondroitin sulfate and dermatan sulfate polymers.
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Sulfatos de Condroitina/química , Dermatán Sulfato/química , Oligosacáridos/análisis , Oligosacáridos/química , Animales , Carbono , Cartílago , Bovinos , Condroitina ABC Liasa/metabolismo , Condroitín Liasas/metabolismo , Sulfatos de Condroitina/metabolismo , Dermatán Sulfato/metabolismo , Disacáridos/análisis , Disacáridos/química , Disacáridos/metabolismo , Hidrógeno , Espectroscopía de Resonancia Magnética , Oligosacáridos/metabolismo , ProtonesRESUMEN
OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.
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Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo/tratamiento farmacológico , Paroxetina/uso terapéutico , Receptores de Serotonina/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tomografía Computarizada de Emisión , Adolescente , Adulto , Factores de Edad , Corteza Cerebral/metabolismo , Trastorno Depresivo/diagnóstico por imagen , Regulación hacia Abajo/efectos de los fármacos , Femenino , Radioisótopos de Flúor , Humanos , Masculino , Paroxetina/farmacología , Pirimidinonas , Receptor de Serotonina 5-HT2A , Receptores de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Tomografía Computarizada de Emisión/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Although the root causes of maternal mortality (MM) in nonindustrialized nations differ from those in the United States, some approaches to improving MM may be universal. Access to care is an issue in the United States aswell as internationally. There are many steps providers can take to improve access, from reducing language an cultural barriers, to taking adequate histories, to addressing such chronic conditions as obesity, diabetes, an hypertension before conception. When providers obtain adequate information before or during pregnancy, they can assess patient risk, plan educational and medical interventions, and introduce preventive measures that can reduce MM-in both the United States and the developing world.
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Accesibilidad a los Servicios de Salud , Mortalidad Materna , Obstetricia/normas , Países Desarrollados , Países en Desarrollo , Femenino , Salud Global , Humanos , Atención Preconceptiva/normas , Embarazo , Atención Prenatal/normas , Estados Unidos , Salud de la MujerRESUMEN
Melatonin, a pineal secretory product, has been shown to exert a direct anti-proliferative action on the androgen-sensitive LNCaP prostate cancer cell line through hitherto undefined mechanisms. In this communication, expression of mt1 melatonin receptor protein in human prostate cancer tissues and LNCaP cells was demonstrated by immunohisto(cyto)chemistry and western blotting, hence supporting the use of LNCaP cell line as a model for the study of melatonin signaling in prostate cancer cell growth. Using 3H-thymidine incorporation assay, LNCaP cell proliferation was inhibited by 2-iodomelatonin, a high-affinity melatonin receptor agonist. Furthermore, melatonin inhibited 3H-thymidine incorporation into LNCaP cells and attenuated 5alpha-dihydrotestosterone (DHT) or 17beta-estradiol (E2)-induced stimulation of LNCaP cell proliferation at physiological and pharmacological concentrations. Similar concentration-dependent inhibition of sex steroid-induced stimulation of thymidine incorporation into LNCaP cells by 2-iodomelatonin was also observed. Interestingly, attenuation of sex steroid-stimulated calcium influx into LNCaP cells by pharmacological concentrations of melatonin was recorded, whereas 2-iodomelatonin had no effect on cytosolic calcium changes induced by sex steroids. In addition, proliferative and cytosolic calcium changes were associated with inhibition of total prostate-specific antigen (PSA) production by LNCaP cells at high physiological and pharmacological concentrations of melatonin. Our data suggest that activated mt1 receptor and attenuated sex steroid-induced calcium influx are two important mechanisms mediating the direct anti-proliferative action of melatonin on androgen-responsive human prostate cancer cells.
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Adenocarcinoma/metabolismo , Calcio/metabolismo , División Celular/efectos de los fármacos , Melatonina/análogos & derivados , Melatonina/farmacología , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias de la Próstata/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Western Blotting , Dihidrotestosterona/farmacología , Relación Dosis-Respuesta a Droga , Estradiol/farmacología , Humanos , Técnicas para Inmunoenzimas , Masculino , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , ARN Mensajero/metabolismo , Receptores de Superficie Celular/genética , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Melatonina , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismoRESUMEN
It is unclear whether the functional changes found in panic disorder reflect disturbed physiology of particular neurotransmitters. One method of investigating altered neurotransmission is to assess regional brain activations in response to agonist challenges. D-Fenfluramine is a medication that induces neuronal release of serotonin. Using ¿15OH(2)O and positron emission tomography (PET), measurements of regional cerebral blood flow (rCBF) were done at t=-20, -5, +20 and +35 relative to the IV D-fenfluramine injection (t=0) in nine panic-disordered and 18 healthy subjects. Subjects were otherwise healthy, right-handed, non-smoking and not taking psychotropic medication. ¿15OH(2)O PET scans were assessed with Statistical Parametric Mapping using individual global cerebral blood flow as a covariate. Comparisons of the (baseline) first two scans between healthy and panic-disordered subjects showed a decreased rCBF in the left posterior parietal-superior temporal cortex in the patient group. Fenfluramine-induced increases as defined by the last two scans minus the first two scans were compared between groups and a significantly greater increase in the same left posterior parietal-superior temporal region was found in panic-disordered subjects. Consistent with this finding, differences between the last two scans (post-fenfluramine) of the healthy and panic-disordered subjects showed an increased rCBF in the left superior temporal cortex in panic-disordered subjects. Functional pathology in the left parietal-superior temporal cortex in panic disorder may be related to abnormal modulation by serotonin.
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Circulación Cerebrovascular/efectos de los fármacos , Fenfluramina , Trastorno de Pánico/metabolismo , Lóbulo Parietal/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina , Lóbulo Temporal/efectos de los fármacos , Adolescente , Adulto , Estudios de Casos y Controles , Dominancia Cerebral/efectos de los fármacos , Femenino , Humanos , Trastorno de Pánico/diagnóstico por imagen , Lóbulo Parietal/irrigación sanguínea , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/metabolismo , Serotonina/metabolismo , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
Distribution of the mt1 melatonin receptor in the guinea pig retina was immunocytochemically investigated using peptide-specific anti-mt1 receptor antibody. Western blots of the guinea pig retina showed a single band at approximately 37 kilodalton (kD) immunoreactive to the anti-mt1 antibody. The most intense immunoreactivity for the mt1 receptor was detected in the cell bodies of ganglion cells. Their dendrites and axons were also immunolabeled. Subpopulations of amacrine cells, the inner plexiform layer, and the outer plexiform layer also exhibited moderate to weak immunolabeling. The mt1-positive amacrine cells were located either at the vitreal border of the inner nuclear layer or displaced in the ganglion cell layer. Double immunolabeling using antibodies to the mt1 receptor and tyrosine hydroxylase revealed that the majority of dopaminergic amacrine cells showed mt1 immunoreactivity. Almost all the ICA type dopaminergic cells were mt1 positive while the 2CA type cells less frequently exhibited mt1 immunoreaction. By double immunolabeling for the mt1 receptor and GABA, more than 50% of the mt1-immunoreactive amacrine cells were shown to be GABAergic neurons. Approximately one-third of the GABAergic amacrine cells were immunolabeled for the mt1 receptor. The present results demonstrate expression of the mt1 receptor in diverse neuronal cell types in the guinea pig retina and provide the first evidence for the direct effect of melatonin on dopaminergic and GABAergic amacrine cells via the mt1 receptor.
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Dopamina/metabolismo , Melatonina/metabolismo , Neuronas Aferentes/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Retina/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Axones/metabolismo , Western Blotting , Dendritas/metabolismo , Electroforesis en Gel de Poliacrilamida , Técnica del Anticuerpo Fluorescente Indirecta , Cobayas , Masculino , Receptores de Melatonina , Células Ganglionares de la Retina/metabolismoRESUMEN
OBJECTIVE: To examine antidepressant augmentation with and hypnotic effects of slow-release melatonin (SR-melatonin) in patients with treatment-resistant depression. DESIGN: Open-label trial. SETTING: Tertiary care outpatient depression clinic. PATIENTS: Nine outpatients who had failed to respond to 2 or more 8-week trials of antidepressant medication. INTERVENTIONS: Patients received SR-melatonin 5 mg per day for the first 2 weeks and 10 mg per day for the final 2 weeks, in addition to their antidepressant medication. OUTCOME MEASURES: Structured Clinical Interview for DSM-IV, Axis 1 Disorders, Hamilton Rating Scale for Depression (HRSD), Beck Depression Inventory, Response Style Questionnaire, sleep and fatigue measures. RESULTS: One patient was excluded after 1 week because of the development of a mixed affective state. In the remaining 8 patients there was a 20% mean decrease in HRSD scores after 4 weeks of treatment, with no individual achieving an improvement of 50% or more. There was a 36% decrease on the 3-item HRSD related to insomnia, with 4 of 8 patients showing at least a 50% improvement on this measure. The greatest decrease in insomnia occurred during the last 2 weeks of the study, following the increase in dosage to 10 mg per day of SR-melatonin. Patients also reported significantly lower levels of fatigue post-treatment. CONCLUSIONS: SR-melatonin may be a useful adjunct for sleep, but does not substantially augment existing antidepressant therapies in some patients with treatment-resistant depression.
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Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Melatonina/administración & dosificación , Adulto , Anciano , Antidepresivos/efectos adversos , Preparaciones de Acción Retardada , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Masculino , Melatonina/efectos adversos , Persona de Mediana Edad , Inventario de PersonalidadRESUMEN
A detection theoretic analysis was employed to examine sensitivity and response bias in two modalities. In Experiment 1, 6 tasters made same-different judgments about the concentration of either sucrose or quinine in pairs of tonic water samples. The beverages were colored, but color was not predictive of the concentration of the sweet or bitter ingredient. When same-different ratings were collapsed to approximate the outcome of a categorical decision, tasters with poorer sensitivity appear to have adopted more extreme response criteria than did tasters with greater sensitivity, irrespective of taste quality, color, or whether pairs of solutions comprised the same or different colors. In Experiment 2, 3 individuals discriminated pairs of 1000-Hz sinusoids differing in amplitude. Six amplitude differences were tested. Rating-scale versions of two paradigms: The single-interval yes-no task and the two-interval same-different task were used to measure sensitivity and bias. There was a preponderance of "same" responses in the same-different task. Estimates of bias obtained from collapsed ratings in both tasks were unaffected by sensitivity, but a consideration of the range over which sets of criteria were spread suggested a general tendency toward more conservative response biases as sensitivity declined.
Asunto(s)
Aprendizaje Discriminativo , Discriminación de la Altura Tonal , Umbral Gustativo , Gusto , Adulto , Atención , Femenino , Humanos , Individualidad , Masculino , Psicoacústica , PsicofísicaRESUMEN
The use of high-field two-dimensional 1H-correlation data is described for the detailed comparison of intact keratan sulfate polymer chains derived from human articular cartilage sources as a function of age. For fetal material the nonreducing chain termini are shown to be sparsely capped by sialyl groups which, if present, are exclusively (alpha2-3)-linked to an unsulfated galactose residue. The asialo capping segment has the structure: Gal-GlcNAc6S-Gal-GlcNAc6S-. Examination of keratan sulfate from 10-year-old cartilage shows that capping by sialyl groups is complete, with (alpha2-3)-linkages predominant; for both this and the 38-year-old cartilage the three capping structures: NeuAc(alpha2-3)-Gal-GlcNAc6S-Gal-GlcNAc6S-, NeuAc(alpha2-3)-Gal-GlcNAc6S-Gal6S-GlcNAc6S-, and NeuAc(alpha2-3)-Gal6S-GlcNAc6S-Gal6S-GlcNAc6S- are clearly recognizable. The level of (alpha2-6)-linked chain capping sialyl groups is significant for 38-year-old cartilage keratan sulfate. Structural information concerning the linkage region to protein and the distribution of galactose environments is readily obtained from the spectra. Signal complexities severely limit the usefulness of two-dimensional correlation spectroscopy at 600 MHz for the examination of N-acetylglucosamine residues within the poly(N-acetyllactosamine) repeat sequence and signals representing fucose placements remain undifferentiated. This nondestructive approach complements current degradative methods for the structural examination of keratan sulfates.