RESUMO
Bidirectional communication between the immune and neuroendocrine systems is not well understood in the context of traumatic brain injury (TBI). The purpose of this study was to characterize relationships between cerebrospinal fluid (CSF) cortisol and inflammation after TBI, and to determine how these relationships differ by outcome. CSF samples were collected from 91 subjects with severe TBI during days 0-6 post-injury, analyzed for cortisol and inflammatory markers, and compared to healthy controls (n=13 cortisol, n=11 inflammatory markers). Group-based trajectory analysis (TRAJ) delineated subpopulations with similar longitudinal CSF cortisol profiles (high vs. low cortisol). Glasgow Outcome Scale (GOS) scores at 6months served as the primary outcome measure reflecting global outcome. Inflammatory markers that displayed significant bivariate associations with both GOS and cortisol TRAJ (interleukin [IL]-6, IL-10, soluble Fas [sFas], soluble intracellular adhesion molecule [sICAM]-1, and tumor necrosis factor alpha [TNF]-α) were used to generate a cumulative inflammatory load score (ILS). Subsequent analysis revealed that cortisol TRAJ group membership mediated ILS effects on outcome (indirect effect estimate=-0.253, 95% CI (-0.481, -0.025), p=0.03). Correlational analysis between mean cortisol levels and ILS were examined separately within each cortisol TRAJ group and by outcome. Within the low cortisol TRAJ group, subjects with unfavorable 6-month outcome displayed a negative correlation between ILS and mean cortisol (r=-0.562, p=0.045). Conversely, subjects with unfavorable outcome in the high cortisol TRAJ group displayed a positive correlation between ILS and mean cortisol (r=0.391, p=0.006). Our results suggest that unfavorable outcome after TBI may result from dysfunctional neuroendocrine-immune communication wherein an adequate immune response is not mounted or, alternatively, neuroinflammation is prolonged. Importantly, the nature of neuroendocrine-immune dysfunction differs between cortisol TRAJ groups. These results present a novel biomarker-based index from which to discriminate outcome and emphasize the need for evaluating tailored treatments targeting inflammation early after injury.
Assuntos
Lesões Encefálicas/imunologia , Hidrocortisona/imunologia , Inflamação/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/reabilitação , Estudos de Casos e Controles , Estudos de Coortes , Citidina Difosfato Colina/uso terapêutico , Método Duplo-Cego , Proteína Ligante Fas/líquido cefalorraquidiano , Proteína Ligante Fas/imunologia , Feminino , Escala de Resultado de Glasgow , Humanos , Hidrocortisona/líquido cefalorraquidiano , Hipotermia Induzida/métodos , Molécula 1 de Adesão Intercelular/líquido cefalorraquidiano , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-10/líquido cefalorraquidiano , Interleucina-10/imunologia , Interleucina-1beta/líquido cefalorraquidiano , Interleucina-1beta/imunologia , Interleucina-6/líquido cefalorraquidiano , Interleucina-6/imunologia , Masculino , Pessoa de Meia-Idade , Nootrópicos/uso terapêutico , Prognóstico , Estudos Prospectivos , Índices de Gravidade do Trauma , Resultado do Tratamento , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Persistent exposure to environmental stressors causes dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR) levels throughout the brain. Social subordination in socially housed female rhesus results in distinctive stress-related physiological and behavioral phenotypes that are dependent on the ovarian hormone estradiol (E2). In the present study, we utilized ovariectomized adult female rhesus monkeys undergoing hormone replacement with E2 to test the hypothesis that the chronic psychosocial stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic regions implicated in emotional processing including the prefrontal cortex, temporal lobe (amygdala and hippocampus), and hypothalamus. Furthermore, we tested the hypothesis that peripheral administration of a corticotropin-releasing hormone (CRH) receptor antagonist (astressin B) would reverse the alterations in GABAAR binding within these regions in subordinate females. After subjects received astressin B or saline for three consecutive days, GABAAR BPND was determined by positron emission tomography (PET) using (18)F-flumazenil as a radioligand. T1-weighted structural magnetic resonance imaging scans were also acquired for PET scan co-registration, in order to perform a region of interest analysis using the pons as a reference region. Compared to socially dominant females, subordinate females exhibited increased GABAAR BPND in the prefrontal cortex but not in the temporal lobe or the hypothalamus. Administration of astressin B eliminated the status difference in GABAAR BPND in the prefrontal cortex, suggesting that the chronic stressor of social subordination modulates GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal regions.
Assuntos
Dominação-Subordinação , Estradiol/farmacologia , Ovariectomia , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de GABA-A/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Flumazenil/análogos & derivados , Processamento de Imagem Assistida por Computador , Macaca mulatta , Imageamento por Ressonância Magnética , Fragmentos de Peptídeos/farmacologia , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
Contemporary research indicates that brain development occurs during childhood and into early adulthood, particularly in certain regions. A critical question is whether premature or atypical hormone exposures impact brain development (e.g., structure) or function (e.g., neuropsychological functioning). The current study enrolled 40 girls (aged 6-8 years) diagnosed with premature adrenarche (PA) and a comparison group of 36 girls with on-time maturation. It was hypothesized that girls with PA would demonstrate lower IQ and performance on several neuropsychological tasks. The potential for a sexually dimorphic neuropsychological profile in PA was also explored. No significant univariate or multivariate group differences emerged for any neuropsychological instrument. However, effect size confidence intervals contained medium-sized group differences at the subscale level. On-time girls performed better on verbal, working memory, and visuospatial tasks. Girls with PA showed improved attention, but not a sexually dimorphic profile. These results, though preliminary, suggest that premature maturation may influence neuropsychological functioning.
Assuntos
Adrenarca , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Deficiências do Desenvolvimento/fisiopatologia , Testes Neuropsicológicos , Puberdade Precoce/complicações , Nível de Alerta , Criança , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Inteligência , Análise Multivariada , Aprendizagem VerbalRESUMO
BACKGROUND: Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. METHODS: Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. RESULTS: Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. CONCLUSIONS: (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.
Assuntos
Dieta , Hierarquia Social , Isoflavonas/administração & dosagem , Proteínas de Soja/administração & dosagem , Estresse Psicológico/complicações , Animais , Anovulação/etiologia , Densidade Óssea , Doenças Ósseas Metabólicas/psicologia , Dexametasona , Proteínas Alimentares/administração & dosagem , Estradiol/sangue , Feminino , Hidrocortisona/sangue , Macaca fascicularis , Distúrbios Menstruais/etiologia , Pré-Menopausa , Progesterona/sangueRESUMO
In this note a squared output signal is generated from an astable circuit. Its frequency has a linear dependence on the resistance value of a resistive temperature sensor. The main circuit to obtain this direct relationship is the generalized impedance converter configured as a capacitor controlled by a sensor resistance. The proposed measurement method allows a direct analog-to-digital interface of information involved in resistive sensors. The converter finds applications in portable low voltage and low power design of instrumentation electronic systems.
RESUMO
The serotonin (5HT) reuptake transporter (SERT) plays a key role in 5HT homeostasis by recycling 5HT into the presynaptic neurons. Recently, polymorphisms in the length of the promoter region of the gene that encodes SERT have been linked to functional differences in reactivity to psychosocial stress, as the short (s) promoter length allele shows reduced transcriptionally activity in vitro and is associated with reduced 5HT activity and increased vulnerability to affective disorders. Given 5HT's important role in appetite regulation, polymorphisms in the SERT gene could also affect metabolic parameters. In addition, since reduced 5HT activity may also predispose females to reproductive deficits, polymorphisms in the SERT gene may help explain individual differences in ovulatory function. The present study, using a rhesus monkey model, tested the hypothesis that the presence of the s-variant allele would be associated with altered metabolic regulation and impaired ovulatory cycles compared with the l/l genotype. Females homozygous for the long allele in the SERT gene (l/l, n = 19) were compared to those with the s-variant allele (l/s or s/s, n = 20). All females had similar social histories. Body weights (P = 0.026) but not heights (P = 0.618) were significantly lower in s-variant compared to l/l females. In addition, both BMI (P = 0.032) and sagittal abdominal diameters (SAD) (P = 0.031), as indices of adiposity, were significantly lower in s-variant females. Consistent with these differences, fasting and non-fasting levels of leptin were significantly lower in s-variant females (P = 0.002). While there were no genotype differences in non-fasting levels of insulin, s-variant females had significantly lower concentrations of insulin during a fast than did l/l females (P = 0.052). Neither glucose, T 3, T 4, nor ghrelin varied significantly between groups during either the fasted or non-fasted condition (P > 0.05). Analysis of a subset of females indicated that significantly fewer s-variant females (62.5%) exhibited ovulatory cycles than l/l females (100%, P < 0.05). However, there were no differences in serum estradiol or progesterone in l/l females and those s-variant females that did ovulate (P > 0.05). In addition, females with the s-variant genotype also had reduced 5HT activity (P = 0.030), assessed from the acute increase in serum prolactin following the administration of the 5HT reuptake inhibitor, citalopram. Finally, s-variant females were significantly less responsive to glucocorticoid negative feedback (P = 0.030) yet more responsive to corticotropin releasing hormone (CRH, P = 0.016) in terms of plasma cortisol than were l/l females. These data indicate that adult female rhesus monkeys with the s-variant polymorphism in the SERT gene exhibit metabolic and reproductive alterations in conjunction with reduced serotonergic responsivity and increased LHPA activity and suggest the possibility that this genotype may predispose females exposed to psychosocial stressors to further metabolic and reproductive deficits.
Assuntos
Macaca mulatta/genética , Macaca mulatta/metabolismo , Polimorfismo de Nucleotídeo Único , Reprodução/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Animais , Glicemia/análise , Retroalimentação Fisiológica , Feminino , Grelina , Glucocorticoides/metabolismo , Insulina/sangue , Leptina/sangue , Macaca mulatta/sangue , Metabolismo/genética , Ovulação/genética , Ovulação/fisiologia , Hormônios Peptídicos/sangue , Prolactina/sangue , Serotonina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Hormônios Tireóideos/sangueRESUMO
We examined the contribution of 5-HT1A autoreceptors (with [11C]WAY100635 positron emission tomography) to amygdala reactivity (with blood oxygenation level-dependent functional magnetic resonance imaging) in 20 healthy adult volunteers. We found a significant inverse relationship wherein 5-HT1A autoreceptor density predicted a notable 30-44% of the variability in amygdala reactivity. Our data suggest a potential molecular mechanism by which a reduced capacity for negative feedback regulation of 5-HT release is associated with increased amygdala reactivity.
Assuntos
Tonsila do Cerebelo/fisiologia , Homeostase/fisiologia , Receptor 5-HT1A de Serotonina/fisiologia , Adulto , Depressão/metabolismo , Retroalimentação/fisiologia , Humanos , Imageamento por Ressonância Magnética , Oxigênio/sangue , Piperazinas/farmacologia , Tomografia por Emissão de Pósitrons , Piridinas/farmacologia , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/farmacologiaRESUMO
Behaviors that activate the hypothalamic-pituitary-adrenal (HPA) axis or suppress the hypothalamic-pituitary-thyroidal (HPT) axis can disrupt the hypothalamic-pituitary-gonadal (HPG) axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that serve as psychogenic stressors and present metabolic challenges. Complete recovery of gonadal function depends upon restoration of the HPA and HPT axes. Hormone replacement strategies have limited benefit because they do not promote recovery from these allostatic endocrine adjustments in the HPA and HPT axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only an alteration in the hypothalamic-pituitary-ovarian (HPO) axis. Further, use of sex hormones masks deficits that accrue from altered HPA and HPT function. Long-term deleterious consequences of stress-induced anovulation may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the HPA and HPT axes. Failure to reverse the hormonal milieu induced by stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes have the potential to permit resumption of ovarian function along with recovery of the HPT and HPA axes. Full endocrine recovery offers better individual, maternal, and child health.
Assuntos
Anovulação/diagnóstico , Anovulação/tratamento farmacológico , Estresse Psicológico/psicologia , Amenorreia/etiologia , Anovulação/fisiopatologia , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotireoidismo/fisiopatologia , Ovário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/terapiaRESUMO
OBJECTIVE: To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. DESIGN: Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.
Assuntos
Amenorreia/psicologia , Doenças Hipotalâmicas/psicologia , Adaptação Psicológica , Adulto , Afeto , Amenorreia/complicações , Atitude , Índice de Massa Corporal , Estudos Transversais , Depressão/etiologia , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Humanos , Doenças Hipotalâmicas/complicações , OvulaçãoRESUMO
Deterioration in cognitive function-particularly learning, memory, and attention-has been reported by women with breast cancer who receive adjuvant chemotherapy. Deficits in cognitive function reported by women with breast cancer are similar to those experienced by women as a consequence of natural or surgical menopause. The basis of these deteriorations may include reductions in reproductive hormone levels, particularly estrogens and progesterones, that occur as a result of adjuvant chemotherapy. This paper critically examines the literature related to the impact of adjuvant chemotherapy and reproductive hormone changes on cognitive function in women with breast cancer and suggests direction for future research in this area. The paper proposes a framework for investigation of the problem and discusses the challenges associated with the conduct of this research.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Hormônios Esteroides Gonadais/uso terapêutico , Neoplasias da Mama/psicologia , Feminino , Hormônios Esteroides Gonadais/fisiologia , HumanosRESUMO
Two experiments were conducted to understand the influence of estrogen exposure on cardiovascular responses to acute stress measured by impedance cardiography. Study I compared stress responses of 29 postmenopausal women who used postmenopausal hormone replacement therapy (HRT) and 29 who did not use HRT. Women who did not use HRT had higher systolic blood pressure and pulse pressure responses to the tasks relative to HRT users. Study 2 compared stress responses of 38 healthy postmenopausal women not initially on HRT who were randomly assigned to transdermal estradiol or placebo treatment for 6-8 weeks. HRT assignment did not influence substantially women's cardiovascular responses to stress. Characteristics correlated with HRT use, not HRT itself, or differences in type, duration, and dosage may account for the discrepancy in results.
Assuntos
Terapia de Reposição de Estrogênios , Hemodinâmica/fisiologia , Pós-Menopausa/fisiologia , Estresse Fisiológico/fisiopatologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine whether fasting in women would suppress GnRH/LH drive in a high- versus low-gonadal steroid milieu. DESIGN: Case-control study. SETTING: Academic clinical research center. PATIENT(S): Eleven eumenorrheic women and eleven women taking combined oral contraceptives. INTERVENTION(S): Seven of the eleven women in each group underwent an acute 72-hour fast. Blood samples were obtained at 15-minute intervals for 24 hours before the fast and during the last 24 hours of fasting. MAIN OUTCOME MEASURE(S): Twenty-four-hour profiles of LH, cortisol, and melatonin were assessed. Ovarian activity was tracked with estradiol and progesterone levels, and metabolic responses were gauged by measuring thyroid hormone and beta-hydroxy-butyric acid levels. RESULT(S): Fasting increased beta-hydroxy-butyric acid and reduced free thyronine. Fasting in the midfollicular phase had no effect on LH pulsatility or on FSH, estradiol, or subsequent luteal-phase progesterone levels. However, fasting elevated cortisol and resulted in a phase advance in melatonin secretion of 81 minutes in both the midfollicular and luteal phases. CONCLUSION(S): Fasting in women elicited expected metabolic responses and apparently advanced the central circadian clock without compromising reproductive function.
Assuntos
Ritmo Circadiano/fisiologia , Jejum/fisiologia , Hidrocortisona/metabolismo , Hormônio Luteinizante/metabolismo , Melatonina/metabolismo , Ácido 3-Hidroxibutírico/sangue , Adulto , Estudos de Casos e Controles , Análise por Conglomerados , Estradiol/sangue , Estradiol/metabolismo , Jejum/metabolismo , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Fase Folicular/fisiologia , Humanos , Hidrocortisona/sangue , Fase Luteal/fisiologia , Hormônio Luteinizante/sangue , Melatonina/sangue , Ovulação/fisiologia , Progesterona/sangue , Progesterona/metabolismo , Tironinas/sangue , Tironinas/metabolismoRESUMO
Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.
Assuntos
Neurotransmissores/uso terapêutico , Síndrome do Ovário Policístico/prevenção & controle , Feminino , HumanosRESUMO
OBJECTIVE: To consider the systemic benefits of cyclic ovarian function. METHODS: Review and interpretation of extant data and concepts, with a focus on the physiologic impact of gonadal steroid exposures upon key nonreproductive target tissues in women. RESULTS: The role of cyclic ovarian function in reproductive processes such as menstruation, folliculogenesis, and conception is well understood. Less is known about the impact of the characteristic sex steroid fluctuations associated with ovulatory menstrual cycles upon what are typically viewed as nonreproductive tissues, such as the limbic lobe and cerebral cortex. The explosion in knowledge regarding the molecular mechanisms of steroid action has expanded our appreciation of the complex and often subtle nature of this impact. CONCLUSIONS: A clear understanding of the systemic benefits of cyclic ovarian function is required to advise patients adequately about the risks and benefits of exogenous hormone use for the remediation or induction of anovulatory states. The inherent complexity of steroid hormone action coupled with the recognition that there is a long list of reproductive and nonreproductive target tissues obviates simple statements about the risks and benefits of hormonal manipulation and anovulatory states.
Assuntos
Ovário/fisiologia , Ovulação/fisiologia , Adolescente , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Ciclo Menstrual/fisiologia , Pessoa de Meia-Idade , Pós-Menopausa , Reprodução/fisiologiaRESUMO
BACKGROUND: Preclinical studies demonstrate that 17beta-estradiol (E(2)) increases serotonin-2A receptor (5-HT(2A)R) density in rat frontal cortex. METHODS: We investigated the impact of hormone replacement therapy on 5-HT(2A)R binding potential (BP) using positron emission tomography and [(18)F]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E(2), 0.1 mg/d, and following 2 to 6 weeks of E(2) plus micronized progesterone (P) 100 mg per os twice daily. Regional BPs in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were calculated by Logan analysis. RESULTS: There was a main effect of time (p = .017) for 5-HT(2A)R BP, which increased 21.2%+/-2.6% following combined E(2) and P administration relative to baseline. This effect was evident in all cerebral cortex regions examined. CONCLUSIONS: 5-HT(2A)R BP increased in widespread areas of the cerebral cortex following combined E(2) + P administration.
Assuntos
Encéfalo/metabolismo , Estradiol/metabolismo , Progesterona/metabolismo , Receptores de Serotonina/metabolismo , Tomografia Computadorizada de Emissão , Ligação Competitiva , Encéfalo/diagnóstico por imagem , Estradiol/administração & dosagem , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Pessoa de Meia-Idade , Progesterona/administração & dosagemRESUMO
A code for the implementation of treatment plannings in hadrontherapy with an active scan beam is presented. The package can determine the fluence and energy of the beams for several thousand voxels in a few minutes. The performances of the program have been tested with a full simulation.
Assuntos
Íons , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Fenômenos Biofísicos , Biofísica , Carbono , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/estatística & dados numéricosRESUMO
OBJECTIVE: To determine if polycystic-appearing ovaries (PAO) are associated with differences in risk factors for cardiovascular disease among women with polycystic ovary syndrome (PCOS). DESIGN: Case-control sub-study. SETTING: Division of Reproductive Endocrinology, Magee-Womens Hospital. PATIENT(S): Women with PCOS (n = 63) and non-PCOS controls (n = 56). INTERVENTION: Transvaginal ultrasonography and single sample venipuncture. MAIN OUTCOME MEASURE(S): Ultrasound ovarian appearance, fasting insulin, lipoproteins, androgens, LH/FSH ratio, anthropomorphic measurements, and blood pressure. RESULT(S): Women with PCOS had higher androgen and fasting insulin levels, a more adverse lipid profile, greater waist-hip and LH/FSH ratios, and a larger ovarian volume than controls. Thirty-three percent of the cases with PCOS, but only 5% of controls, showed PAO on ultrasound study (P<.01). PCOS cases with and without PAO had comparable levels of fasting insulin, lipids, and blood pressures. PCOS cases with PAO had a higher LH/FSH ratio (P=.028), increased levels of serum androstenedione (P=.029) and testosterone (P=.055), and greater ovarian volume (P=.024) compared to non-PAO patients. CONCLUSION: Women with PCOS have greater cardiovascular risk than controls. Within PCOS cases, however, the ultrasound appearance of polycystic ovaries does not appear to further intensify the cardiovascular disease risk profile of these women.
Assuntos
Doenças Cardiovasculares/complicações , Ovário/patologia , Síndrome do Ovário Policístico/complicações , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Colesterol/sangue , Bases de Dados Factuais , Feminino , Humanos , Lipoproteínas/sangue , Ovário/diagnóstico por imagem , Fatores de Risco , UltrassonografiaRESUMO
OBJECTIVE: To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers. DESIGN: Randomized, controlled open trial. INTERVENTION: Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period. MAIN OUTCOME MEASURES: Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels. STATISTICAL ANALYSES PERFORMED: Group-by-time analysis of variance with repeated-measures, chi 2 test. RESULTS: Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% at baseline vs 13% at 12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men). The milk group gained 0.6 kg more than control group (P < .01); however, weight gain was less than predicted, which suggests some compensation for the added energy from milk. Blood pressure decreased similarly over time in both groups. Total and low-density lipoprotein cholesterol levels, and the ratio of total cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride levels increased within the normal range in the milk group (P = .002). Quality of life scores were high at baseline and remained high throughout. APPLICATIONS/CONCLUSIONS: Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice.