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OBJECTIVES: Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions. STUDY DESIGN: Matched cohort study. METHODS: National register data were obtained from individuals born between 1934 and 1958. Migraine cases (aged 25-58 years) were identified by migraine diagnoses and redeemed migraine medication. Migraine cases were matched with non-cases (N = 340,850) and date of diagnosis or medication redemption was defined as index year. Dementia was identified by dementia diagnoses and redeemed dementia medication. RESULTS: We observed a 1.46 (95% CI: 1.26-1.69) times higher dementia rate in individuals with a migraine diagnosis and a 0.86 (95% CI: 0.76-0.97) times lower rate when using migraine medication. We found the highest dementia rate among individuals with MA, who also used migraine medication (HR = 2.23; 95% CI: 1.19-4.17), and the lowest rate among individuals with MO, who also used medication (HR = 1.25; 95% CI: 0.75-2.10). The number of migraine medication prescriptions was not associated with dementia. CONCLUSIONS: Being registered with a migraine diagnosis was associated with a higher dementia rate, while use of prescribed migraine medication was not. The differences in the dementia rate among migraine cases identified via diagnoses versus medications warrants further investigation.
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Demência , Humanos , Estudos de Coortes , Demência/epidemiologiaRESUMO
Laser light scattered from a target is the most-direct measurement for diagnosing laser absorption in a direct-drive implosion. The 3ω gated optical imager beamlets diagnostic images unabsorbed light from all 60 OMEGA beams as distinct "beamlet" spots for each beam. The implosion can be diagnosed using the position and intensity of these beamlets. The position of each beamlet in the image is determined by refraction and can be used to fit the coronal plasma density profile of the implosion. The inferred plasma density profiles are comparable to the profiles predicted by the 1D hydrodynamics code LILAC but suggest that the predictions underestimate the density farther out in the corona. The intensity of light in each spot depends on the cumulative effects of absorption and cross-beam energy transfer along the beamlet's path through the corona. The measured variation in intensity and polarization between similar spots indicates that absorption during OMEGA implosions is less uniform than previously known.
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Slow and fast light, or large changes in the group velocity of light, have been observed in a range of optical media, but the fine optical control necessary to induce an observable effect has not been achieved in a plasma. Here, we describe how the ion-acoustic response in a fully ionized plasma can produce large and measurable changes in the group velocity of light. We show the first experimental demonstration of slow and fast light in a plasma, measuring group velocities between 0.12c and -0.34c.
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Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
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Biomarcadores , Autoavaliação Diagnóstica , Nível de Saúde , Autorrelato , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We measure cross-beam energy transfer (CBET) saturation by ion heating in a gas-jet plasma characterized using Thomson scattering. A wavelength-tunable ultraviolet (UV) probe laser beam interacts with four intense UV pump beams to drive large-amplitude ion-acoustic waves. For the highest-intensity interactions, the power transfer to the probe laser drops, demonstrating ion-acoustic wave saturation. Over this time, the ion temperature is measured to increase by a factor of 7 during the 500-ps interaction. Particle-in-cell simulations show ion trapping and a subsequent ion heating consistent with measurements. Linear kinetic CBET models are found to agree well with the observed energy transfer when the measured plasma conditions are used.
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The picosecond evolution of non-Maxwellian electron distribution functions was measured in a laser-produced plasma using collective electron plasma wave Thomson scattering. During the laser heating, the distribution was measured to be approximately super-Gaussian due to inverse bremsstrahlung heating. After the heating laser turned off, collisional ionization caused further modification to the distribution function while increasing electron density and decreasing temperature. Electron distribution functions were determined using Vlasov-Fokker-Planck simulations including atomic kinetics.
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STUDY QUESTION: Is exposure to gestational stress in the critical time window for the normal differentiation and growth of male reproductive tissue associated with male reproductive function in offspring in later life? SUMMARY ANSWER: Exposure to stressful life events (SLEs) in early, but not late gestation, are associated with reduced adult male reproductive function, consistent with the hypothesis that events during early prenatal life programme adult male reproductive function. WHAT IS ALREADY KNOWN: Animal studies suggest that gestational stress may impact on the reproductive function of male offspring, but human evidence is sparse. STUDY DESIGN, SIZE, DURATION: Using a prospective longitudinal cohort, we examined the association between number and type of maternal stressors during pregnancy in both early and late gestation and reproductive function in 643 male Generation 2 (offspring) at age 20 years. Mothers and their male Generation 2 (offspring) from The Raine Study participated. Mothers prospectively reported SLEs during pregnancy recorded at gestational weeks 18 and 34 using a standardized 10-point questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 643 male Generation 2 (offspring) underwent testicular ultrasound examination and semen analysis and provided serum for reproductive hormone analysis. Multivariate linear regression analysis was used to examine associations. MAIN RESULTS AND ROLE OF CHANCE: Of 643 recruited males, 407 (63%) were exposed to at least one SLE in early gestation. Fewer SLEs were reported in late gestation (n = 343, 53%). Maternal SLE exposure in early gestation was negatively associated with total sperm count (ß = -0.31, 95% CI -0.58; -0.03), number of progressive motile sperm (ß = -0.15, 95% CI -0.31; 0.00) and morning serum testosterone concentration (ß = -0.04, 95% CI -0.09; -0.00). No similar effects of maternal SLE exposure in late pregnancy were detected. The large sample size and an objective detailed direct assessment of adult male reproductive function with strict external quality control for sperm quality, as well as detailed prospectively collected information on prenatal SLEs in two distinct time windows of pregnancy reported by the women in early and late gestation along with other risk factors, imply minimal possibility of recall, information bias and selection bias. When assessing our results, we adjusted for a priori chosen confounders, but residual confounding or confounding by factors unbeknown to us cannot be ruled out. LIMITATIONS, REASONS FOR CAUTION: It is not possible to measure how SLEs impacted differently on the mother's experience or perception of stress. Resilience (coping) gradients may alter cortisol levels and thus modify the associations we observed and the mothers' own perception of stress severity may have provided a more precise estimate of her exposure. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that exposure to SLEs in early, but not late gestation, are associated with reduced adult male reproductive function. Improved support for women with exposure to SLEs during pregnancy, particularly during the first trimester, may improve the reproductive health of their male offspring in later life. Intervention studies of improved pregnancy support could provide more insight into this association and more information is needed about the potential specific epigenetic mechanisms underlying this association. STUDY FUNDING/COMPETING INTEREST(S): The male fertility sub-study was funded by NHMRC Grant 634 457. The core management of the Raine Study is funded by University of Western Australia, Curtin University, Telethon Kids Institute, Women and Infants Research Foundation, Edith Cowan University, Murdoch University, The University of Notre Dame Australia and Raine Medical Research foundation. Dr Bräuner's salary was supported by Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis foundation in Denmark. All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Infertilidade Masculina/etiologia , Efeitos Tardios da Exposição Pré-Natal , Contagem de Espermatozoides , Estresse Psicológico , Testosterona/sangue , Feminino , Idade Gestacional , Humanos , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos , Análise do Sêmen , Motilidade dos Espermatozoides , Testículo/diagnóstico por imagem , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVES: Previously, we developed and validated an easy test to measure muscle fatigability during sustained maximal handgrip contraction in older persons using a Martin Vigorimeter device. This study aimed at validating the equation to estimate grip work (GW) during sustained maximal handgrip contraction, by monitoring continuously the grip strength (GS) decay using a Jamar Dynamometer-like (JD) device. DESIGN: Cross sectional, explorative study. SETTING: Data collection took place at The National Research Centre for the Working Environment in Copenhagen, Denmark. PARTICIPANTS: 962 subjects, belonging to a subgroup of the Copenhagen Aging and Midlife Biobank, were enrolled. METHODS: GS was recorded continuously during sustained maximal contraction until it dropped to 50% of its maximum and fatigue resistance (FR, time to fatigue) was noted. GW, area under the force-time curve, was compared to its estimate which was calculated as GWestimated=GSmax*0.75*FR. RESULTS: Excellent correlation was found between GWestimated and GWmeasured (R²=0.98 p<0.001). The equation slightly overestimated GW by 6.04 kg*s (95% CI[-0.08, 12.15]) with a coefficient of variation method error of 6%. CONCLUSION: GW estimation is a valid parameter reflecting muscle work output during a sustained maximal grip effort in healthy middle-aged community-dwelling persons when using a JD. GW estimation is a promising outcome parameter in comprehensive geriatric assessment and its validation for commonly used instruments in geriatric practice will increase its clinical implementation.
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Avaliação Geriátrica/métodos , Força da Mão/fisiologia , Dinamômetro de Força Muscular , Músculo Esquelético/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Algoritmos , Estudos Transversais , Dinamarca , Feminino , Nível de Saúde , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Projetos de PesquisaRESUMO
A supersonic gas-jet target platform has been activated on the OMEGA Laser System. An analytic model for gas dynamics in a supersonic nozzle was used to predict gas-plume parameters and to design nozzles for use in laser-plasma experiments. The gas-jet system was analyzed with a Mach-Zehnder interferometer to study neutral density and with Thomson scattering to study plasma parameters on the OMEGA Laser System. These initial measurements demonstrate the capabilities of the OMEGA gas jet as a platform for future laser-plasma interaction science.
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Background: Fishing in distant waters for months may induce physiological stress. Aims: To assess the physiological stress reactions in fishermen working for 2-3 months continuously in 6-h shifts on trawlers in the Barents Sea. Methods: The crew of five trawlers fishing in the Barents Sea from January to April 2004 were invited to participate. In the week before and 5-7 days after the trip, the following measures were collected: salivary cortisol four times a day, 24-h urinary cortisol, blood pressure, heart rate, serum cholesterol, serum high-density lipoprotein (HDL-cholesterol), HbA1c (glycosylated haemoglobin) and weight. In addition, 24-h urinary cortisol, blood pressure and heart rate were measured three times. A questionnaire on health, social conditions and work environment was obtained after the trip. Results: In total, 136 men agreed to participate. Full data were obtained for 96 fishermen (70%). A significant decrease in salivary and urinary cortisol was found during the trip. Adjustment for age, body mass index, smoking, shift work schedule and time of day for sample collection did not change this finding. Systolic and diastolic blood pressure declined significantly and remained significantly lower after the trip compared to before the trip. Serum cholesterol/HDL ratio declined significantly, whereas triglycerides, HbA1c and weight were unchanged. Conclusions: Working up to 3 months on 6-h shifts, 84 h a week, with moderate physical activity, even in artificial light and cold weather on a ship, did not result in increased physiological stress.
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Fenômenos Fisiológicos/fisiologia , Navios , Isolamento Social , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Biomarcadores/urina , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Colesterol/análise , Colesterol/sangue , HDL-Colesterol/análise , HDL-Colesterol/sangue , Hemoglobinas Glicadas/análise , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/análise , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade , Navios/métodosRESUMO
OBJECTIVES: Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels. METHODS: This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear. RESULTS: Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors. CONCLUSION: No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.
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Lipídeos/sangue , Indústria Manufatureira , Ruído Ocupacional/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Estudos Transversais , Dinamarca , Monitoramento Ambiental/métodos , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Exposição Ocupacional/análise , Fatores de Risco , Triglicerídeos/sangueRESUMO
OBJECTIVE: To explore physical health problems and their causes in patients with severe mental illness, as well as possibilities for prevention and treatment from the patients' and staff's perspectives. METHOD: We conducted six focus groups with patients and staff separately, from three out-patient clinics treating patients with schizophrenia or substance-use disorder comorbid to another psychiatric disorder. Focus groups were audio-recorded, transcribed verbatim and analysed using a template approach. RESULTS: Paramount physical health problems are weight issues, cardiovascular diseases and poor physical shape. Main causes are lifestyle, the mental disorder and organisational issues. Patients and staff expressed similar opinions regarding physical health problems and their causes. Possibilities for prevention and treatment includes a case manager and binding communities with like-minded, as well as management support and implementation of physical health into daily psychiatric practice. Although patients and staff suggested different possibilities for prevention and treatment, they support one strategy: less fragmentation of the treatment system and cooperation between psychiatric and somatic healthcare. CONCLUSION: To prevent and treat physical health problems in patients with severe mental illness, support in daily structure and lifestyle changes is needed. Management support is needed to change daily practice and implement routines regarding physical health.
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Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Nível de Saúde , Estilo de Vida , Transtornos Mentais , Adulto , Dinamarca , Feminino , Grupos Focais , Promoção da Saúde , Humanos , MasculinoRESUMO
AIM: To examine associations of DNA damage, cardiovascular risk factors and physical performance with vitality, in middle-aged men. We also sought to elucidate underlying factors of physical performance by comparing physical performance parameters to DNA damage parameters and cardiovascular risk factors. METHODS: We studied 2487 participants from the Metropolit cohort of 11 532 men born in 1953 in the Copenhagen Metropolitan area. The vitality level was estimated using the SF-36 vitality scale. Cardiovascular risk factors were determined by body mass index (BMI), and haematological biochemistry tests obtained from non-fasting participants. DNA damage parameters were measured in peripheral blood mononuclear cells (PBMCs) from as many participants as possible from a representative subset of 207 participants. RESULTS: Vitality was inversely associated with spontaneous DNA breaks (measured by comet assay) (P = 0.046) and BMI (P = 0.002), and positively associated with all of the physical performance parameters (all P < 0.001). Also, we found several associations between physical performance parameters and cardiovascular risk factors. In addition, the load of short telomeres was inversely associated with maximum jump force (P = 0.018), with lowered significance after exclusion of either arthritis sufferers (P = 0.035) or smokers (P = 0.031). CONCLUSION: Here, we show that self-reported vitality is associated with DNA breaks, BMI and objective (measured) physical performance in a cohort of middle-aged men. Several other associations in this study verify clinical observations in medical practice. In addition, the load of short telomeres may be linked to peak performance in certain musculoskeletal activities.
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Doenças Cardiovasculares/metabolismo , Dano ao DNA/genética , Exercício Físico/fisiologia , Índice de Massa Corporal , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , AutoimagemRESUMO
PURPOSE: To analyse whether psychological demands and decision latitude measured on individual and work-unit level were related to prescription of antihypertensive medication. METHODS: A total of 3,421 women and 897 men within 388 small work units completed a questionnaire concerning psychological working conditions according to the job strain model. Mean levels of psychological demands and decision latitude were computed for each work unit to obtain exposure measures that were less influenced by reporting bias. Dispensed antihypertensive medication prescriptions were identified in The Danish National Prescription Registry. Odds ratios (OR) comparing the highest and lowest third of the population at individual and work-unit level, respectively, were estimated by multilevel logistic regression adjusted for confounders. Psychological demands and decision latitude were tested for interaction. Supplementary analyses of 21 months follow-up were conducted. RESULTS: Among women, increasing psychological demands at individual (adjusted OR 1.54; 95 % CI 1.02-2.33) and work-unit level (adjusted OR 1.41; 95 % CI 1.04-1.90) was significantly associated with purchase of antihypertensive medication. No significant association was found for decision latitude. Follow-up results supported an association with psychological demands but they were not significant. All results for men showed no association. Psychological demands and decision latitude did not interact. CONCLUSION: High psychological work demands were associated with the purchase of prescribed antihypertensive medication among women. This effect was present on both the work-unit and the individual level. Among men there were no associations. The lack of interaction between psychological demands and decision latitude did not support the job strain model.
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Anti-Hipertensivos/uso terapêutico , Doenças Profissionais/epidemiologia , Doenças Profissionais/psicologia , Estresse Psicológico/psicologia , Local de Trabalho/psicologia , Adulto , Tomada de Decisões , Dinamarca/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Distribuição por Sexo , Fumar/epidemiologia , Inquéritos e Questionários , TrabalhoRESUMO
Water in lakes and reservoirs accumulate phosphorous (P) from both internal and external loads. The external P load (EPL) coming from the watershed is considered to be the main cause of eutrophication of water bodies, and control strategies therefore focus on its reduction. However, algae blooms and anoxic conditions often continue even after EPL have been controlled, being the internal P load (IPL) originating from the sediment the main sources of P. To assess the efficiency of the adsorbent Phoslock (a modified bentonite) in controlling P concentrations in water and immobilize releasable P in sediments, mesocosm trials were carried out in a eutrophied reservoir and a model was described and applied that determines the amount of adsorbent and the application frequency necessary to control P concentrations in a eutrophied reservoir. The mesocosm trials confirm that Phoslock reduced P concentrations to or below the limits that define water in mesotrophic state, in approximately 2 weeks. The modeling results suggest that periodic reapplications of the adsorbent are required, unless EPL is reduced by 36 %, which allows the P concentrations in the water column to be constant. Such reduction in EPL would allow future applications of the adsorbent to be required only for control of IPL. The developed model allows planning remediation actions by determining quantities and frequencies for application of adsorbents for P control in eutrophied lakes and reservoirs.
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Recuperação e Remediação Ambiental/métodos , Eutrofização , Lagos/química , Fósforo/análise , Poluentes Químicos da Água/análise , Bentonita/química , Sedimentos Geológicos/química , Modelos Químicos , Fósforo/química , Poluentes Químicos da Água/químicaRESUMO
The purpose of this study was to determine whether recovery from burnout is associated with improved cognitive functioning, and whether such improvement is associated with changes in hypothalamic-pituitary-adrenal axis activity and return to work. Forty-five former burnout patients were followed up after 1.5 years with a neuropsychological examination, diurnal salivary cortisol measurements, dexamethasone suppression test (DST), and self-ratings of cognitive problems. At follow-up, improved cognitive performance was observed on several tests of short-term memory and attention. Self-rated cognitive problems decreased considerably, but this decrease was unrelated to the improvement on neuropsychological tests. Diurnal salivary cortisol concentrations at awakening, 30 min after awakening, and in the evening, did not change from baseline to follow-up, nor did the cortisol awakening response. However, slightly, but significantly, stronger suppression of cortisol in response to the DST was observed at follow-up. Improvements in subjective or objective cognitive functioning and changes in diurnal cortisol concentration were unrelated to the extent of work resumption. However, a decreased DST response at follow-up was partially related to improved cognitive performance and work resumption. The clinical implications are that burnout seems to be associated with slight and significantly reversible cognitive impairment, and that self-rated cognitive change during recovery poorly reflects objective cognitive change.
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Esgotamento Profissional/fisiopatologia , Esgotamento Profissional/psicologia , Cognição/fisiologia , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Retorno ao Trabalho , Saliva/química , Adulto , Ritmo Circadiano/fisiologia , Transtornos Cognitivos/psicologia , Dexametasona , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estresse Psicológico/complicaçõesRESUMO
Panic disorder (PD) is an anxiety disorder characterized by recurrent panic attacks with a lifetime prevalence of 4.7%. Genetic factors are known to contribute to the development of the disorder. Several lines of evidence point towards a major role of the norepinephrine system in the pathogenesis of PD. The SLC6A2 gene is located on chromosome 16q12.2 and encodes the norepinephrine transporter (NET), responsible for the reuptake of norepinephrine into presynaptic nerve terminals. The aim of the present study was to analyze genetic variants located within the NET gene for association with PD. The case-control sample consisted of 449 patients with PD and 279 ethnically matched controls. All cases fulfilled the ICD-10 diagnostic criteria for PD. Genotyping was performed using the Sequenom platform (Sequenom, Inc, San Diego, USA). To test for allelic and haplotypic association, the PLINK software was used, and COMBASSOC was applied to test for gene-wise association. After quality control 29 single nucleotide polymorphisms (SNPs) spanning the gene-region were successfully analyzed. Seven SNPs located within the 5' end of the gene were significantly associated with PD. Furthermore, the NET gene showed overall evidence for association with the disease (P = 0.000035). In conclusion, the present study indicates that NET could be a susceptibility gene for PD.
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Predisposição Genética para Doença/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Norepinefrina/metabolismo , Transtorno de Pânico/genética , Transtorno de Pânico/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/fisiopatologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
AIMS/HYPOTHESIS: The hormone glucagon-like peptide 1 (GLP-1) is released in response to a meal from the intestinal L-cells, where it is processed from proglucagon by the proconvertase (PC)1/3. In contrast, in the adult islets proglucagon is processed to glucagon by the PC2 enzyme. The aim of the study was to evaluate if, during the development of diabetes, alpha cells produce GLP-1 that, in turn, might trigger beta cell growth. METHODS: Beta cell mass, GLP-1 and insulin levels were measured in the gerbil Psammomys obesus (P. obesus), a rodent model of nutritionally induced diabetes. Furthermore, the presence of biologically active forms of GLP-1 and PC1/3 in alpha cells was demonstrated by immunofluorescence, and the release of GLP-1 from isolated P. obesus, mouse and human islets was investigated. RESULTS: During the development of diabetes in P. obesus, a significant increase in GLP-1 was detected in the portal vein (9.8 ± 1.5 vs 4.3 ± 0.7 pmol/l, p < 0.05), and in pancreas extracts (11.4 ± 2.2 vs 5.1 ± 1.3 pmol/g tissue, p < 0.05). Freshly isolated islets from hyperglycaemic animals released more GLP-1 following 24 h culture than islets from control animals (28.2 ± 4.4 pmol/l vs 5.8 ± 2.4, p < 0.01). GLP-1 release was increased from healthy P. obesus islets following culture in high glucose for 6 days (91 ± 9.1 pmol/l vs 28.8 ± 6.6, p < 0.01). High levels of GLP-1 were also found to be released from human islets. PC1/3 colocalised weakly with alpha cells. CONCLUSIONS/INTERPRETATION: GLP-1 release from alpha cells is upregulated in P. obesus during the development of diabetes. A similar response is seen in islets exposed to high glucose, which supports the hypothesis that GLP-1 released from alpha cells promotes an increase in beta cell mass and function during metabolic challenge such as diabetes.
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Diabetes Mellitus/metabolismo , Gerbillinae/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células Secretoras de Glucagon/metabolismo , Hiperglicemia/metabolismo , Obesidade/metabolismo , Regulação para Cima/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus/etiologia , Diabetes Mellitus/patologia , Dieta/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Glucagon/patologia , Glucose/farmacologia , Humanos , Hiperglicemia/patologia , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologiaRESUMO
This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.