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BACKGROUND: The relation between low-grade inflammation and metabolic dysfunction in obesity is not fully explored. OBJECTIVE: To evaluate immune parameters in the obese state and after a lifestyle intervention program. METHODS: Patients with obesity (n = 87) from an academic obesity clinic were compared with controls with regard to macrophage and T-cell activation (reflected by serum levels of soluble CD163 (sCD163) and soluble IL-2 receptor (sIL-2R), respectively), and an array of cytokines, chemokines, and growth factors. In addition, these parameters and regulatory T-cells (Treg), were studied in 27 patients who followed a 75-week lifestyle intervention (dietary advice, exercise, and psychoeducation). RESULTS: Mean sIL-2R and sCD163 levels were higher in patients than controls (sIL-2R:2884 ± 936 pg/ml vs. 2207 ± 813 pg/ml, p = 0.001; sCD163:1279 ± 580 pg/ml vs. 661 ± 271 pg/ml, p < 0.0001 respectively). Patients with metabolic syndrome (MetS) had higher sCD163 than those without (1467 ± 656 pg/ml vs. 1103 ± 438 pg/ml). Patients had higher IL-1ß, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IL-17A, MCP-1/CCL2, MIP-1α/CCL3, MIP-1ß/CCL4, G-CSF, GM-CSF, FGF, IFN-γ, and TNF-α than controls, whereas VEGF-A, PDGF-BB, and eotaxin were lower. Upon intervention, sIL-2R decreased while peripheral Treg frequencies increased within the reference range (p = 0.042 and p = 0.005 respectively). The sIL-2R decrease correlated to a decrease in waist circumference (rho = 0.388, p = 0.045) and in trend to a decrease in MetS components (rho = 0.345, p = 0.078). The Treg increase was unrelated to weight loss or metabolic improvement. Mean sCD163 did not change significantly upon intervention, nor did the cytokines, chemokines, and growth factors (except IP-10/CXCL10). CONCLUSION: In obesity, T-cell homeostasis improves after a lifestyle intervention. Immunologic alterations can occur independently of metabolic improvement.
Assuntos
Promoção da Saúde/métodos , Estilo de Vida , Ativação de Macrófagos/fisiologia , Obesidade , Adulto , Estudos Transversais , Citocinas/metabolismo , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/terapia , Linfócitos T/fisiologiaRESUMO
BACKGROUND: Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile. AIM: To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children. METHODS: We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed. RESULTS: Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters. CONCLUSION: Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.
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Distribuição da Gordura Corporal , Glucocorticoides/metabolismo , Síndrome Metabólica/metabolismo , Obesidade Infantil/metabolismo , Idade de Início , Biomarcadores/metabolismo , Criança , Cortisona/metabolismo , Estudos Transversais , Feminino , Genótipo , Cabelo/metabolismo , Humanos , Hidrocortisona/metabolismo , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/prevenção & controle , Países Baixos/epidemiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/prevenção & controle , Fatores de RiscoRESUMO
Obesity is one of the greatest public health challenges of the 21st century. Obesity is currently responsible for â¼0.7-2.8% of a country's health costs worldwide. Treatment is often not effective because weight regulation is complex. Appetite and energy control are regulated in the brain. Melanocortin-4 receptor (MC4R) has a central role in this regulation. MC4R defects lead to a severe clinical phenotype with lack of satiety and early-onset severe obesity. Preclinical research has been carried out to understand the mechanism of MC4R regulation and possible effectors. The objective of this study is to systematically review the literature for emerging pharmacological obesity treatment options. A systematic literature search was performed in PubMed and Embase for articles published until June 2012. The search resulted in 664 papers matching the search terms, of which 15 papers remained after elimination, based on the specific inclusion and exclusion criteria. In these 15 papers, different MC4R agonists were studied in vivo in animal and human studies. Almost all studies are in the preclinical phase. There are currently no effective clinical treatments for MC4R-deficient obese patients, although MC4R agonists are being developed and are entering phase I and II trials.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Regulação do Apetite/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Obesidade/tratamento farmacológico , Receptor Tipo 4 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/metabolismo , Acetamidas/uso terapêutico , Animais , Regulação do Apetite/genética , Índice de Massa Corporal , Ingestão de Energia/genética , Metabolismo Energético/genética , Frequência do Gene , Genótipo , Humanos , Obesidade/genética , Peptídeos Cíclicos/uso terapêutico , Fenótipo , Pirrolidinas/uso terapêutico , Receptor Tipo 4 de Melanocortina/deficiência , Receptor Tipo 4 de Melanocortina/genética , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Compostos de Espiro/uso terapêutico , alfa-MSH/análogos & derivados , alfa-MSH/uso terapêuticoRESUMO
BACKGROUND: Glucocorticoid replacement therapy in patients with adrenal insufficiency needs to be tailored to the individual patient based on body composition and clinical signs and symptoms as no objective method for assessment of treatment adequacy is available. Current treatment regimens are often not satisfactory, which is shown by the adverse metabolic profile and doubled mortality rates in treated adrenal insufficiency patients. Measurement of cortisol concentrations in hair reflect the long-term systemic cortisol exposure and may be of use in refinement of hydrocortisone treatment. OBJECTIVE: We aimed to study whether long-term cortisol (hydrocortisone) levels, as measured in scalp hair, are similar in children with adrenal insufficiency and healthy children. MATERIAL AND METHODS: We set up a case control study, measuring anthropometric characteristics and hair cortisol concentrations (HCC) in 54 hydrocortisone substituted children with adrenal insufficiency (AI patients) in the age of 4-18 years and 54 healthy children matched for gender and age. RESULTS: Mean HCC were significantly higher in AI patients compared with healthy controls (mean 13·3 vs 8·2 pg/mg, P = 0·02). AI patients also had a higher BMI (P < 0·001) and waist circumference (WC) (P = 0·02). HCC was significantly associated with BMI (P = 0·002) and WC (P = 0·002). HCC explained 13% of the difference in BMI and 29% of the difference in WC between AI patients and controls. CONCLUSION: Hydrocortisone-treated AI patients have increased HCC and adverse anthropometric characteristics compared with healthy controls. HCC measurement may be of value in identifying overtreatment and thereby improve hydrocortisone replacement therapy.
Assuntos
Insuficiência Adrenal/tratamento farmacológico , Glucocorticoides/uso terapêutico , Cabelo/química , Terapia de Reposição Hormonal/métodos , Hidrocortisona/uso terapêutico , Doença de Addison/complicações , Adolescente , Hiperplasia Suprarrenal Congênita/complicações , Insuficiência Adrenal/etiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Monitoramento de Medicamentos , Feminino , Glucocorticoides/análise , Humanos , Hidrocortisona/análise , Hipopituitarismo/complicações , Masculino , Sobrepeso , Circunferência da CinturaRESUMO
The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (p<0.0001). Seven ACC patients (47%) had hair cortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (ß=0.03, p=0.93), hair cortisol levels were associated with BMI (ß=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (ß=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients.
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Carcinoma Adrenocortical/tratamento farmacológico , Cabelo/metabolismo , Hidrocortisona/metabolismo , Mitotano/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Previous research has shown a relationship between the stress hormone cortisol and bipolar disorder. The level of cortisol exposure is usually examined by means of measurements that provide a snapshot of cortisol exposure or by means of dynamic testing. Recently, a new technique has been introduced which can measure, retrospectively, the cortisol level in scalp hair over longer periods of time. AIM: To provide insight into various methods used in psychiatry for measuring the hypothalamus-pituitary-adrenal (HPA)-axis activity and also to highlight recent research into measurements of cortisol in scalp hair of patients with bipolar disorder. METHOD: We give a brief overview of the literature relating to HPA-axis testing in psychiatric patients. As a result of our recent studies with 100 patients suffering from bipolar disorder, we are now able to determine the levels of cortisol in scalp hair. RESULTS: Tests that measure hpa activity can be divided into three categories: point measurements, stimulation tests and inhibition tests. In our recent study of bipolar patients we found that a raised level of cortisol in scalp hair was related to a later onset of bipolar disorder (in patients over 30) or to multiple psychiatric diagnoses. Lower levels of cortisol level in scalp hair of bipolar patients were observed in bipolar patients with comorbid panic disorder. CONCLUSION: The use of hair analysis to measure mean cortisol levels over long periods seems to give added value to the hpa-axis tests currently used for measuring cortisol exposure. The technique may make it easier to differentiate between various subtypes of bipolar disorder.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/epidemiologia , Cabelo/metabolismo , Hidrocortisona/sangue , Transtornos Mentais/epidemiologia , Biomarcadores/metabolismo , Comorbidade , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Transtornos Mentais/sangue , Sistema Hipófise-Suprarrenal/metabolismoAssuntos
Cabelo/química , Hidrocortisona/metabolismo , Protoporfiria Eritropoética/metabolismo , Adulto , Índice de Massa Corporal , Feminino , Humanos , Masculino , Protoporfiria Eritropoética/psicologia , Qualidade de Vida , Autorrelato , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismoRESUMO
Institutional dementia care is increasingly directed towards small-scale and homelike care environments, in The Netherlands as well as abroad. In these facilities, a small number of residents, usually six to eight, live together, and normal daily household activities and social participation are emphasized. In a quasi-experimental study, we studied the effects of small-scale, homelike care environments on residents (n = 259), family caregivers (n = 206) and nursing staff (n = 305). We compared two types of institutional nursing care during a 1 year period (baseline assessment and follow-up measurements at 6 and 12 months): (28) small-scale, homelike care environments and (21) psychogeriatric wards in traditional nursing homes. A matching procedure was applied to increase comparability of residents at baseline regarding functional status and cognition. This study was unable to demonstrate convincing overall effects of small-scale, homelike care facilities. On our primary outcome measures, such as quality of life and behaviour of residents and job satisfaction and motivation of nursing staff, no differences were found with traditional nursing homes. We conclude that small-scale, homelike care environments are not necessarily a better care environment than regular nursing homes and other types of living arrangements should be considered carefully. This provides opportunities for residents and their family caregivers to make a choice which care facility suits their wishes and beliefs best.
Assuntos
Cuidadores/psicologia , Demência/enfermagem , Recursos Humanos de Enfermagem/psicologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Meio Social , Idoso , Idoso de 80 Anos ou mais , Demência/psicologia , Feminino , Seguimentos , Lares para Grupos/normas , Instituição de Longa Permanência para Idosos/normas , Humanos , Relações Interpessoais , Assistência de Longa Duração/psicologia , Assistência de Longa Duração/normas , Masculino , Países Baixos , Casas de Saúde/normas , Satisfação do Paciente , Qualidade de VidaRESUMO
The use of physical restraints still is highly prevalent in institutional long term care settings for older people. We know that the use of restrictive measures, such as belt restraints, do have many negative consequences for residents, and even can be harmful to their health. However, this knowledge does not result in a reduction of physical restraints. This paper describes the search for an intervention (EXBELT) aiming to safely reduce and prevent the use of belt restraints in nursing homes. EXBELT consists of a promotion of institutional policy change that discourages use of belt restraints, nursing home staff education, availability of alternative interventions, and consultation by a nurse specialist. Effect evaluations show that EXBELT is effective on the short and long term. According to a process evaluation, EXBELT was largely performed according to protocol and very well received by nursing home staff and resident's relatives. However, concurrently it is stated that the reduction of physical restraints in Dutch nursing home care runs slowly. The conclusion is that continuing focus is needed to reduce physical restraints in nursing homes and to prevent its use in home care.
Assuntos
Instituição de Longa Permanência para Idosos/normas , Casas de Saúde/normas , Avaliação de Processos em Cuidados de Saúde , Restrição Física/estatística & dados numéricos , Acidentes por Quedas/prevenção & controle , Controle Comportamental/métodos , Demência/complicações , Instituição de Longa Permanência para Idosos/organização & administração , Humanos , Países Baixos , Casas de Saúde/organização & administração , Recursos Humanos de Enfermagem/educação , Inovação Organizacional , Política Organizacional , Qualidade de Vida/psicologiaRESUMO
Background: While cardiovascular diseases is highly prevalent and an important cause of mortality in autistic adults, knowledge on their increased cardiovascular risk is limited. Hence, this study aimed to investigate psychological, behavioral, and physical factors associated with metabolic syndrome (MetS) in adults with autistic traits. Methods: In total, 17,705 adults from the Lifelines Cohort were included and categorized using Autism Spectrum Quotient-10 sum-scores. The quartiles with highest (HQ-traits-group females: n = 2,635; males: n = 1803) and lowest levels of autistic traits (LQ-traits-group, n = idem) were analyzed. Using multivariable logistic regression, the associations between MetS and (self-reported and interviewed) psychological, behavioral, and physically measured factors in these stratified groups were investigated. Results: Among females, MetS was more common in the HQ-traits-group than in the LQ-traits-group (10.0% versus 7.5%, p < 0.01), while this was not the case among males (HQ-traits-group 13.8% versus LQ-traits-group 13.1%, p = 0.52). In both the female and male HQ-traits-group, the presence of MetS was associated with poorer self-reported health, less daily physical activity, and altered leukocyte counts. Conclusion: These findings underline the relevance of adequate cardiovascular prevention in adults with higher levels of autistic traits. Future research could gain more insight into the relationship between cardiovascular risk and autistic traits in females, and into tailored cardiovascular prevention.
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In this review, we provide an overview of recent literature on glucocorticoid (GC) sensitivity in mood disorders. Assessing GC sensitivity is often performed by measuring the cortisol awakening rise (CAR), by challenging the hypothalamic-pituitary-adrenal (HPA) axis using a dexamethasone suppression test (DST) or a dexamethasone/cortisol-releasing hormone test (DEX/CRH); more recently by measuring cortisol as a retrospective calendar in scalp hair. The main findings in mood disorders are higher mean cortisol levels in hair samples and a higher CAR, showing a hyperactivity of the HPA axis. This is in line with the mild resistance for GCs previously observed in challenge tests during mood episodes. GC sensitivity is partly determined by polymorphisms in the genes encoding receptors and other proteins involved in the regulation of the HPA axis. We shortly discuss the glucocorticoid receptor, as well as the mineralocorticoid receptor, the cortisol-releasing hormone receptor-1, and the glucocorticoid receptor co-chaperone FKBP5. Data clearly indicate genetic changes, along with epigenetic changes which influence the set-point and regulation of the HPA axis. Early trauma, as well as influences in utero, appears to be important. Future research is necessary to further clarify the biological background and consequences of an individual's cortisol exposure in relation to mood.
Assuntos
Glucocorticoides/metabolismo , Transtornos do Humor/metabolismo , Hormônio Liberador da Corticotropina , Dexametasona , Epigenômica , Humanos , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Transtornos do Humor/genética , Transtornos do Humor/patologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Polimorfismo Genético/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Glucocorticoides/genética , Proteínas de Ligação a Tacrolimo/genéticaRESUMO
Staphylococcus aureus (S. aureus) colonizes the anterior nares in part of the population and the persistent carrier state is associated with increased infection risk. Knowledge concerning the determinants of S. aureus nasal carriage is limited. Previously, we found that glucocorticoid receptor polymorphisms influence carrier risk, suggesting involvement of glucocorticoids. Our aim was to study long-term cortisol levels in non-carriers, intermittent, and persistent carriers of S. aureus. We hypothesized that cortisol levels are higher in carriers, since cortisol-induced immune suppression would enhance S. aureus colonization. We determined nasal carrier state and long-term hair cortisol levels in 72 healthy subjects. Nasal swabs were collected twice with an interval of 2 weeks. Cortisol levels were determined in hair segments of 3 cm, which corresponds to a period of roughly 3 months. Of all 72 participants, 38 were non-carriers, 10 were intermittent carriers, and 24 were persistent carriers of S. aureus. Cortisol levels did not differ between these carrier groups (p=0.638). Long-term cortisol levels are not associated with S. aureus nasal carriage.
Assuntos
Cabelo/química , Hidrocortisona/análise , Mucosa Nasal/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Portador Sadio/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/microbiologia , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/patogenicidade , Fatores de TempoRESUMO
BACKGROUND: Frailty can lead towards serious adverse consequences, such as disability. With regard to prevention valid screening instruments are needed to identify frail older people. The aim was to evaluate and compare the psychometric properties of three screening instruments: the Groningen Frailty Indicator (GFI), the Tilburg Frailty Indicator (TFI) and the Sherbrooke Postal Questionnaire (SPQ). For validation purposes the Groningen Activity Restriction Scale (GARS) was added. METHODS: A questionnaire was sent to 687 older people (> or = 70 years). (1) Agreement between instruments, (2) internal consistency, (3) cumulative scalability according to Mokken scale analysis and (4) construct validity were evaluated. RESULTS: The response rate was 77%. Prevalence estimates of frailty ranged from 40% to 59%. The highest agreement was found between the GFI and TFI (Cohen's kappa = 0.74). Cronbach's alpha for the GFI, TFI and SPQ was 0.73, 0.79 and 0.26, respectively. The scalability of the three instruments was inadequate (Loevinger's H: 0.28, 0.30 and 0.09 for GFI, TFI and SPQ, respectively). Frailty scores correlated significantly with each other and with the GARS scores. CONCLUSION: Especially the GFI and TFI seem to be useful to identify frail older people. Further research regarding their predictive validity is still needed.
Assuntos
Idoso Fragilizado , Avaliação Geriátrica/métodos , Psicometria/instrumentação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Programas de Rastreamento , Psicometria/normas , Inquéritos e QuestionáriosRESUMO
Delirium is the most common mental disorder at older age in hospitals after acute admission. The pathogenesis of delirium is largely unknown. Hyperactivity of the hypothalamic-pituitary-adrenal axis, leading to increased cortisol levels, has been suggested to play a role in the development of delirium. The effects of cortisol, the most important glucocorticoid (GC) in humans, are mainly mediated by the GC receptor (GR). Several polymorphisms in the GR gene that alter the GC sensitivity are known. The aim of this study was to study the role of these GR polymorphisms in delirium in elderly patients. Patients aged 65 years and older admitted to the medical department or scheduled for hip surgery were included. Delirium was diagnosed using the Confusion Assessment Method. Five single nucleotide polymorphisms in the GC receptor gene were genotyped and haplotypes were constructed. Delirium was associated with impaired cognitive (P < 0.001) and functional function (P < 0.001), as well as with older age (P < 0.001). Homozygous carriers of haplotype 4, characterized by the presence of the BclI and TthIIII minor alleles, had a 92% decreased risk of developing delirium (P = 0.02), independent of age, cognitive, and functional state. Homozygous carriage of the BclI-TthIIII haplotype of the GR gene is related to a reduced risk of developing delirium. This suggests that altered GC signaling may be involved in the pathogenesis and development of delirium in the elderly.
Assuntos
Delírio/genética , Predisposição Genética para Doença , Haplótipos/genética , Receptores de Glucocorticoides/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Cognição/fisiologia , Delírio/fisiopatologia , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Razão de Chances , Fatores de RiscoRESUMO
Intermittent fasting (IF) is a broad concept and covers several fasting regimes. Studies of 'early time restricted feeding' and 'alternate day fasting' with energy restriction show a greater effect on weight and cardiometabolic health in overweight people in the short term, compared to a continuous caloric restriction (CCR). 'Late time restricted feeding' seems to have no or unfavorable effects. Long-term studies (up to 2 years) suggest that IF regimens are not superior to continuous caloric restriction. The few studies available show a similar compliance and metabolic adaptation between IF and CCR. There is insufficient knowledge about long-term safety in various groups of people, the influence of dietary quality and the practical feasibility of IF regimes. As a result, no recommendations can yet be made on the use of IF in the treatment of overweight and related diseases.
Assuntos
Restrição Calórica , Dieta Redutora/métodos , Prática Clínica Baseada em Evidências , Obesidade/dietoterapia , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Ingestão de Energia , Jejum , Humanos , Sobrepeso/dietoterapia , Redução de PesoRESUMO
Obesity is a complex endocrine disease, mainly caused by environmental, behavioral and biological factors. Maintaining weight loss is extremely difficult due to the neuro-endocrine dysregulations that stimulate the body to return to the previous, increased, weight. Identifying underlying weight-gaining factors is needed, including medication-related, psychological and endocrine factors, as well as monogenic obesity. The cornerstone of treatment is optimization of lifestyle and all other contributing factors. Achieving at least 5% weight loss already has important health benefits. If combined lifestyle intervention (CLI) alone is not successful, pharmacotherapy or bariatric surgery can be added for patients with increased weight-related health risks. Recently, novel pharmacotherapy became available, among which, liraglutide 3 mg and the combination therapy naltrexone/bupropion, which leads to an additional 5-6% mean weight loss compared to CLI alone. For rare forms of obesity there are specific drugs that target defects in the regulation of hunger and satiety. Promising new pharmacotherapy for obesity is under development.
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Fármacos Antiobesidade/uso terapêutico , Obesidade/terapia , Cirurgia Bariátrica , Bupropiona/uso terapêutico , Terapia Combinada , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Fome/efeitos dos fármacos , Estilo de Vida , Liraglutida/uso terapêutico , Naltrexona/uso terapêutico , Saciação/efeitos dos fármacos , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
Cortisol has a modulatory influence on cognitive functions in humans. Both impairing and enhancing effects of cortisol administration have been shown for hippocampus-dependent declarative memory, and impairing effects have been shown for prefrontal-cortex-dependent working memory function. Given the high density of glucocorticoid (GC) receptors in the prefrontal cortex, we investigated whether common polymorphisms of the GC receptor (GR) gene (ER22/23EK, N363S, BclI, 9 beta A3669G) modulate the influence of cortisol administration on working memory. Working memory performance was investigated in 169 subjects on 10 mg hydrocortisone (cortisol) and placebo using an item recognition task. No impairing effect of hydrocortisone treatment became evident. However, a sex x genotype interaction on general working memory performance was revealed (p = 0.02). While female heterozygous carriers of the 9 beta G allele displayed faster reaction times than the other genotype groups, 9 beta G heterozygous men were relatively slower. Heritability estimates for memory are roughly 50%, indicating that common genetic polymorphisms have an important impact on cognitive performance. Our results suggest that variants of the GR gene might explain some of the variance attributable to genetic factors. Furthermore, it can be speculated that they modulate the individual vulnerability for memory impairments related to stress-related psychiatric disorders.
Assuntos
Memória de Curto Prazo/fisiologia , Polimorfismo de Nucleotídeo Único , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Adulto , Fármacos do Sistema Nervoso Central/farmacologia , Método Duplo-Cego , Genótipo , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Testes Neuropsicológicos , Tempo de Reação , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Saliva/metabolismo , Caracteres Sexuais , Adulto JovemRESUMO
Pituitary apoplexy is an infrequent but life-threatening complication of pituitary adenomas. When apoplexy occurs in a hormonally active adenoma, this may induce spontaneous remission of the clinical syndrome. In these cases, clinical suspicion of Cushing's disease or acromegaly may arise at presentation, but due to spontaneous remission of active hormone production, it is not possible to biochemically confirm this diagnosis in retrospect. Resolution of clinical symptoms during follow up retrospectively suggests the diagnosis. However, we describe a patient with Cushing's disease presenting with pituitary apoplexy, who was biochemically in remission at presentation. The diagnosis could be confirmed in retrospect using hair cortisol analysis, thereby enabling clinicians to adequately anticipate remission of Cushing's disease.
Assuntos
Síndrome de Cushing , Hidrocortisona , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Síndrome de Cushing/diagnóstico , Cabelo/química , Humanos , Hidrocortisona/análise , Remissão Espontânea , Estudos RetrospectivosRESUMO
BACKGROUND: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis activity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis functioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. METHODS: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major depressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the presence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. RESULTS: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. STRENGTHS AND LIMITATIONS: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. CONCLUSIONS: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. CLINICALTRIALS.GOV: Identifier: NCT02562846.
Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Transtorno Depressivo Maior/terapia , Cabelo , Humanos , Hidrocortisona , Sistema Hipófise-SuprarrenalRESUMO
OBJECTIVES: To assess the need to wear compression stockings for 4 weeks after inversion stripping of the great saphenous vein (GSV) from the groin to the level of the knee. DESIGN: Randomised controlled trial. PATIENTS: A total of 104 consecutive patients with primary complete incompetence of the GSV treated by inversion stripping of the GSV. METHODS: Postoperatively treated limbs underwent elastic bandaging for 3 days. Volunteers were randomised to wear a compression stocking for additional 4 weeks (intervention group) or no compression stocking (control group). The primary outcome was limb oedema as assessed by photoelectric leg volume measurement. Secondary outcome measures were pain scores, postoperative complications and return to full work. RESULTS: The control leg volume was 3657ml (standard deviation, SD 687) preoperatively and 3640ml (SD 540) 4 weeks postoperatively (non significant, N.S.). The stocking leg volume was 3629ml (SD 540) preoperatively, falling to 3534ml (SD 543) (P<0.01) 4 weeks postoperatively. The difference in leg volume between both the groups was not statistically significant. Patients in the control group resumed work earlier (control 11 days, stocking 15 days, P=0.02, Mann-Whitney test). No difference was observed in the number and type of complication and in pain scores during the 4-week follow-up period. CONCLUSIONS: Wearing an elastic compression stocking has no additional benefit following elastic bandaging for 3 days in postoperative care after stripping of the great saphenous vein as assessed by control of limb oedema, pain, complications and return to work.