Menstrual cycle phases and dosage of synthetic hormonal contraceptives influence diurnal rhythm characteristics of distal skin temperature.

This study aimed to explore how natural menstrual cycle phases and dosage of oral hormonal contraceptives (OC) influence the diurnal rhythm of distal skin temperature (DST) under real-life conditions. Participants were 41 healthy females (23.9 ± 2.48 y), comprising 27 females taking monophasic hormonal oral contraceptives (OC users) and 14 females with menstrual cycles (non-OC users). Wrist DST was continuously recorded and averaged over two consecutive 24-hour days during (pseudo)follicular and (pseudo)luteal menstrual phases. Diurnal rhythm characteristics, i.e. acrophase and amplitude, describing timing and strength of the DST rhythm, respectively, were calculated using cosinor analysis. Results show that non-OC users experienced earlier diurnal DST maximum (acrophase, p = 0.019) and larger amplitude (p = 0.016) during the luteal phase than during the follicular phase. This was observed in most (71.4%) but not all individuals. The OC users showed no differences in acrophase or amplitude between pseudoluteal and pseudofollicular phases. OC users taking a higher dosage of progestin displayed a larger amplitude for DST rhythm during the pseudoluteal phase (p = 0.009), while estrogen dosage had no effect. In conclusion, monophasic OC cause changes in diurnal DST rhythm, similar to those observed in the luteal phase of females with menstrual cycles, suggesting that synthetic progestins act in a similar manner on skin thermoregulation as progesterone does.

The 24-h profile of the DNA repair enzyme 8-oxoguanine glycosylase 1 (OGG1) is associated with age, TNF-α, and waist circumference in healthy adults.

It is unknown how the DNA repair enzyme OGG1 relates to healthy aging in humans, in particular to inflammaging, that is associated with increased levels of TNF-α. This study aimed (1) to investigate how 24-h profiles for OGG1 change during healthy aging and (2) to analyze the relationship of OGG1 with TNF-α, central body fat, cortisol and oxidative DNA/RNA damage. In a cross-sectional study in 20 healthy older and 20 young women, salivary levels of OGG1, TNF-α, cortisol and oxidative DNA/RNA damage were quantified by ELISAs every 4 h for a 24-h period. Trunk circumferences were taken as measures of central body fat. Older women, compared to young women, exhibited significantly lower protein levels of OGG1 throughout the whole 24-h period, a 2.5 times lower 24-h mean level for OGG1 (P < 0.00001) and loss of 24-h variation of OGG1. Both age groups demonstrated significant 24-h variation for TNF-alpha, cortisol and oxidative damage. The 24-h mean level for TNF-α was more than twice as high in older compared to young women (P = 0.011). Regression analysis detected that age, TNF-α and waist circumference were negative significant predictors of OGG1, explaining 56% of variance of OGG1 (P < 0.00001), while levels of cortisol and oxidative damage were no predictors of OGG1. Results indicate a strong decrease of protein levels of OGG1 and a loss of 24-h variation during natural cellular aging. The negative relationship, found between OGG1 and TNF-α and between OGG1 and waist circumference, suggests involvement of proinflammatory processes in DNA repair.

Diurnal relationship between core clock gene BMAL1, antioxidant SOD1 and oxidative RNA/DNA damage in young and older healthy women.

BACKGROUND AND OBJECTIVES: BMAL1 is a core clock gene that positively regulates circadian rhythms. In animals, BMAL1 further acts as transcription factor for the SOD1 gene which encodes the major antioxidant enzyme superoxide dismutase. SOD1 protects against oxidative damage that is a major factor for human aging. Mice lacking mBmal1 exhibit premature aging phenotypes which might be related to a reduced expression of SOD1. The purpose of this study was to explore the circadian relationship between BMAL1, SOD1, oxidative RNA/DNA damage and aging in healthy humans. SUBJECTS AND METHODS: In a cross-sectional study design, buccal mucosa cells and saliva samples were obtained from 21 young (23.7 ± 2.3 yrs) and 21 older women (66.8 ± 5.7 yrs) within 24 h at 4-h intervals (08:00, 12:00, 16:00, 20:00, 24:00 and 04:00 h). Transcript levels of BMAL1 and SOD1 were measured by real-time quantitative PCR. Protein levels of SOD1 were determined by immunoblotting and densitometry. Levels of oxidative RNA/DNA damage and melatonin were quantified by enzyme immunosorbent assays. RESULTS: Transcript levels of BMAL1 and SOD1 mRNAs as well as protein levels of SOD1 and melatonin exhibited significant 24-h variation in each age group (P < 0.010, Friedman tests). The mRNA expression patterns of BMAL1 and SOD1 showed similar 24-h rhythmicity and positive relationships were found. Strongest relationships occurred in young women at 12:00 h (rs = 0.81, P = 0.005) and in older women at 08:00 h (r = 0.84, P < 0.001). Maximum levels of SOD1 mRNA appeared within 24 h in both age groups at 24:00 h. In both age groups, the timing of maximum level for SOD1 protein was delayed relative to the timing of maximum level for SOD1 mRNA. This delay was larger in older women (8 h) compared to young women (4 h). Older women showed higher oxidative RNA/DNA damage at all time-points compared to young women (P < 0.020). The oxidative RNA/DNA damage decreased continuously from 08:00 to 20:00 h (P < 0.001) in both age groups. Although oxidative damage and SOD1 protein levels declined simultaneously, only weak and non-significant relationships were noted. CONCLUSIONS: This study demonstrates that transcript levels of SOD1 and protein level of SOD1 follow a circadian pattern of expression in healthy young and older women. The time-shift found between the 24-h maximum levels of SOD1 mRNA and SOD1 protein could be explained by the time needed for translation of SOD1 protein. The positive relationship found between expression levels of SOD1 mRNA and BMAL1 mRNA is in line with animal studies showing that BMAL1 acts as transcription factor and regulates the circadian synthesis of SOD1 mRNA. Differences between young and older women found in the timing of 24-h maxima as well as differences observed in 24-h relationships between characters might be due to age-related alterations in the circadian system. Absence of relationships between levels of SOD1 and oxidative RNA/DNA damage argue for a more complex interaction between the antioxidant system and the circadian system.

The Influence of Melatonin and Light on VEGF Secretion in Primary RPE Cells.

(1) Background: Retinal pigment epithelial cells (RPE) cells constitutively secrete vascular endothelial growth factor (VEGF) in the retina, protecting the neuronal cells and the choroid. Increased VEGF secretion, however, can result in neovascularization and edema. Many factors regulate VEGF secretion. In this study, we investigated the effect of external stimuli in relation to diurnal rhythm on constitutive VEGF secretion. (2) Methods: Single-eye RPE cell culture was prepared from porcine eyes. RPE cells were cultured in darkness, treated with daylight or room light, and treated with melatonin at different time frames, either respectively or in combination. Supernatants were collected and VEGF content evaluated using ELISA. Expression of the clock protein BMAL1 was evaluated with Western blot. (3) Results: VEGF secretion of the RPE shows a diurnal rhythm. While the rhythm is not influenced by either light or melatonin, the amount of secreted VEGF can be increased by nocturnal melatonin, especially in combination with morning daylight. These findings disclose another layer of VEGF regulation in the retina.

Neonatal variables, altitude of residence and Aymara ancestry in northern Chile.

Studies performed in the Andean plateau, one of the highest inhabited areas in the world, have reported that reduced availability of oxygen is associated to fetal growth retardation and lower birth weight, which are established predictors of morbidity and mortality during the first year of life. To test this hypothesis, perinatal variables of neonates born at the Juan Noé Hospital of Arica, Chile, were analyzed in relation to altitude of residence and Aymara ancestry of their mothers. The study population comprised the offspring of 5,295 mothers born between February 2004 and August 2010. Information included birth weight, height, head circumference, gestational age, altitude of residence and socioeconomic status, and was obtained from medical records. Mother´s ancestry was assessed based on surnames which were linked to percentages of Aymara admixture estimates relying on 40 selected ancestry informative markers. After correcting for the effect of multicollinearity among predictor variables, neonates born to mothers with an increased component of Aymara ancestry showed significantly higher birth weight and height at sea level, a marginally significant (p-value 0.06) decrease of birth weight and a significant decrease of height with altitude in comparison with the offspring of mothers with low Aymara ancestry. Since observed tendencies are suggestive of a possible genetic adaptation to hypoxia of the Chilean Aymara, we discuss briefly preliminary evidence related to fetal oxygen transport, particularly polymorphisms in the promoters of the HBG1 and HBG2 genes that are modulators of HbF synthesis, obtained in this ethnic group.

Human biological research since 2006 at the Christian-Albrechts-University in Kiel--aging, chronobiology, and high altitude adaptation.

This article reviews the research at the Department of Human Biology at the Christian-Albrechts-University in Kiel since 2006. The research focuses on the investigation of recent human populations with respect to aging, chronobiology, and adaptation to high altitude. The research areas are outlined presenting findings, ongoing projects and future directions. Aging research examines biological changes in humans considering that aging is a multidimensional process. Changes in body composition, resting energy metabolism, oxidative stress, and sleep have been examined. The applicability of specific research methods to older people has been tested. Chronobiological research concentrates on investigating circadian rhythms of humans. The emphasis lies on the sleep-wake rhythm, body temperature rhythms, hormonal rhythms (cortisol and melatonin) and the circadian expression of so-called clock genes which are involved in the generation of circadian rhythms. Association studies examine the relationship between defined chronobiological phenotypes and clock gene polymorphisms. Genetic aspects are as well investigated within the third research area on the adaptation of native populations to life at high altitude in the South American Andes. Both candidate gene analysis and epigenetic parameters are investigated. Future research will concentrate on the aging of the circadian system.

Schleswig: medieval leprosy on the boundary between Germany and Denmark.

Leprosy was a well-recognized and dreaded disease in medieval Europe. The disease is reported to have reached Germany with the Roman invasion and it was present in Scandinavia in the first centuries AD. This paper estimates and analyzes the frequency of leprosy among adult people buried in one of five medieval cemeteries in the city of Schleswig. Seven different dichotomous osteological lesions indicative of leprosy were analyzed, and it was possible to score at least one of these conditions on 350 adult skeletons (aged 15 or older). The scores were transformed to a statistic indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. It was found that the frequency of leprosy in the five cemeteries varied between 9 and 44%. Four of the five cemeteries showed frequencies ranging from 35 and 44% and with no statistically significant differences among them. The fifth cemetery showed a significantly lower frequency of leprosy (9%). The distribution of female age at death does not appear to be affected by leprosy status. This means that females experienced a considerably elevated risk of dying once they had contracted leprosy as the disease usually has a mid-adulthood age of onset. In four of the five cemeteries males with leprosy died in higher ages than men without leprosy--in two of the cemeteries the difference was statistically significant. This indicates that leprosy usually added less to the risk of dying among men than among women in medieval Schleswig.

Comparison of three segmental multifrequency bioelectrical impedance techniques in healthy adults.

BACKGROUND: The analysis of segmental or limb bioimpedance has gained importance in human population biology. However, standardized measurement techniques are needed. AIM: This study compared three techniques for segmental analysis (T1, conventional electrode measurement; T2, use of a novel additional switching unit; T3, equipotentials instead of switching unit) which are often used in population biology. SUBJECTS AND METHODS: The techniques were compared in 124 healthy adults (19-83 years) using a tetrapolar bioimpedance analyser (Nutriguard-M) at multiple frequencies (5, 50, 100 kHz) to gain whole-body and segmental resistances, reactances and phase angles. RESULTS: Repeated measures ANOVA yielded a significant technique effect for most variables (26/27), a significant interaction technique ×  sex for half (13/27), and a significant interaction technique ×  age for a quarter (7/27) of variables. CONCLUSIONS: Differences exist between the three techniques which are primarily caused by inconsistent current pathways. A comparison with literature data showed that, in addition, subject's posture during measurement, electrode contact and electrode site may lead to inconsistent resistance and reactance values. This makes comparisons between different populations difficult. Therefore, this study recommends generally using the T2 technique which is standardized, easy to use and, thereby, well suited for field studies in large population groups.

The cortisol awakening response is related with PERIOD1 clock gene expression in older women.

BACKGROUND AND OBJECTIVE: The cortisol awakening response (CAR) is a useful endocrine marker for the hypothalamic-pituitary-adrenal axis activity. Recent studies suggest that the cortisol level influences the expression of the hPER1 clock gene which is involved in the generation of biological rhythms. This study aimed to analyze the relationship between CAR and hPER1 gene expression with respect to human aging. SUBJECTS AND METHODS: Salivary cortisol levels were determined in 20 older women (mean age ± SD, 67.9 ± 5.12 yrs) and 30 young women (24.4 ± 2.13 yrs) at awakening (T0) and at 15 min, 30 min, 45 min, and 60 min after awakening (T15, T30, T45, T60) by enzyme linked immunosorbent assay. CAR was calculated as difference of the cortisol levels at T0 and T30. The expression of the hPER1 gene at 0800 h was determined from oral mucosa cells by relative quantification using h36B4 as house-keeping gene. Additional variables, which may affect the CAR, were assessed by questionnaire. Relationships between CAR and other variables were analyzed by correlation and regression analyses. RESULTS: Older women showed significantly lower mean cortisol levels than young women at all five time points (P < 0.05 to P < 0.01). The cortisol levels at T30, T45, and T60 correlated positively and significantly with hPER1 gene expression in older women (each, P < 0.01), but not in young women. In both older and young women, the CAR correlated positively with the hPER1 gene expression. This relationship was very strong in older women (r = -0.90, P<0.001) and non-significant in young women (r = 0.33, P = 0.390). Regression analysis showed that hPER1 gene expression was the only significant predictor of CAR (r² = 0.798, SEM = 0.07, P < 0.001) in older women. CONCLUSIONS: The present study documents the influence of cortisol secretion on hPER1 gene expression in older women. The morning cortisol increase as indicated by CAR correlated positively and significantly with hPER1 gene expression in older women suggesting that hPER1 expression increases in response to the morning cortisol increase in older women. The higher hPER1 response to cortisol increase in older women could be due to the finding that the hPER1 response to cortisol increase seems to be sensitive only at low cortisol levels, but not at higher cortisol levels. This would explain why the older women with low cortisol levels showed an increase of hPER1 expression with increasing cortisol level, whereas young women with higher cortisol levels did not.

Declarative memory performance is associated with the number of sleep spindles in elderly women.

OBJECTIVE: Recent evidence suggests that the sleep-dependent consolidation of declarative memory relies on the nonrapid eye movement rather than the rapid eye movement phase of sleep. In addition, it is known that aging is accompanied by changes in sleep and memory processes. Hence, the purpose of this study was to investigate the overnight consolidation of declarative memory in healthy elderly women. SETTING: Sleep laboratory of University. PARTICIPANTS: Nineteen healthy elderly women (age range: 61-74 years). MEASUREMENTS: We used laboratory-based measures of sleep. To test declarative memory, the Rey-Osterrieth Complex Figure Test was performed. RESULTS: Declarative memory performance in elderly women was associated with Stage 2 sleep spindle density. Women characterized by high memory performance exhibited significantly higher numbers of sleep spindles and higher spindle density compared with women with generally low memory performance. CONCLUSION: The data strongly support theories suggesting a link between sleep spindle activity and declarative memory consolidation.

Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers.

Melatonin concentration and core body temperature (CBT) follow endogenous circadian biological rhythms. In the evening, melatonin level increases and CBT decreases. These changes are involved in the regulation of the sleep-wake cycle. Therefore, the authors hypothesized that age-related changes in these rhythms affect sleep quality in older people. In a cross-sectional study design, 11 older poor-sleeping women (aged 62-72 yrs) and 9 older good-sleeping women (60-82 yrs) were compared with 10 younger good-sleeping women (23-28 yrs). The older groups were matched by age and body mass index. Sleep quality was assessed by the Pittsburgh Sleep Quality Index questionnaire. As an indicator of CBT, oral temperature was measured at 1-h intervals from 17:00 to 24:00 h. At the same time points, saliva samples were collected for determining melatonin levels by enzyme-linked immunosorbent assay (ELISA). The dim light melatonin onset (DLMO), characterizing the onset of melatonin production, was calculated. Evening changes in melatonin and CBT levels were tested by the Friedman test. Group comparisons were performed with independent samples tests. Predictors of sleep-onset latency (SOL) were assessed by regression analysis. Results show that the mean CBT decreased in the evening from 17:00 to 24:00 h in both young women (from 36.57°C to 36.25°C, p < .001) and older women (from 36.58°C to 35.88°C, p < .001), being lowest in the older poor sleepers (p < .05). During the same time period, mean melatonin levels increased in young women (from 16.2 to 54.1 pg/mL, p < .001) and older women (from 10.0 to 23.5 pg/mL, p < .001), being lowest among the older poor sleepers (from 20:00 to 24:00 h, p < .05 vs. young women). Older poor sleepers also showed a smaller increase in melatonin level from 17:00 to 24:00 h than older good sleepers (mean ± SD: 7.0 ± 9.63 pg/mL vs. 15.6 ± 24.1 pg/mL, p = .013). Accordingly, the DLMO occurred at similar times in young (20:10 h) and older (19:57 h) good-sleeping women, but was delayed ∼50 min in older poor-sleeping women (20:47 h). Older poor sleepers showed a shorter phase angle between DLMO and sleep onset, but a longer phase angle between CBT peak and sleep onset than young good sleepers, whereas older good sleepers had intermediate phase angles (insignificant). Regression analysis showed that the DLMO was a significant predictor of SOL in the older women (R(2) = 0.64, p < .001), but not in the younger women. This indicates that melatonin production started later in those older women who needed more time to fall asleep. In conclusion, changes in melatonin level and CBT were intact in older poor sleepers in that evening melatonin increased and CBT decreased. However, poor sleepers showed a weaker evening increase in melatonin level, and their DLMO was delayed compared with good sleepers, suggesting that it is not primarily the absolute level of endogenous melatonin, but rather the timing of the circadian rhythm in evening melatonin secretion that might be related to disturbances in the sleep-wake cycle in older people.

Accuracy of a portable multisensor body monitor for predicting resting energy expenditure in older people: a comparison with indirect calorimetry.

BACKGROUND: Accurate and comfortable methods are needed to determine resting energy expenditure (REE) in older people who are characterized by a lowered metabolic rate. The portable SenseWear® armband (SWA) body monitor, worn on the right upper arm, can easily be used by this age group in an ambulatory manner. OBJECTIVE: The purpose of this study was to evaluate the reliability and accuracy of the SWA armband in determining REE in healthy, normal-weight older people. METHODS: Participants were 49 older, community-dwelling volunteers aged 60-87 years. Reliability was tested in all subjects. Accuracy was analyzed in 32 subjects by comparing REE estimated by SWA against REE measured by indirect calorimetry as a criterion method. Data were simultaneously and continuously recorded for 20 min in the morning. In the same subjects, REE determined by SWA from night recording was evaluated for accuracy against indirect calorimetry. The agreement between methods was assessed by the Bland-Altman procedure. RESULTS: (1) REE measured by SWA was reliable when comparing 2 consecutive measurements (typical error: 1.9%). (2) REE calculated from morning recording (1,543 ± 181 kcal/24 h) was higher than REE from night recording (1,564 ± 192 kcal/24 h; p = 0.018). (3) Compared with REE by indirect calorimetry (1,377 ± 228 kcal/24 h) for accuracy, the SWA overestimated mean REE in the older people by 12 and 14%, respectively, for morning and night recording (each p < 0.001). CONCLUSIONS: The SWA provides a reliable estimate of REE in healthy older subjects and has the advantage of easy handling. The 20-min recording time, which was recommended by the manufacturer, can be applied. However, the SWA overestimates REE in this group, possibly due to age-related changes in skin conductance and thermoregulation, both being measured by sensors of the SWA armband. This requires improving the SWA by developing better fitting algorithms for predicting REE in older people.

Reliability and accuracy of segmental bioelectrical impedance analysis for assessing muscle and fat mass in older Europeans: a comparison with dual-energy X-ray absorptiometry.

Segmental determination of muscle and fat mass (MM, FM) attains growing importance for judging effects of training and malnutrition in older people. This study evaluated the reliability and accuracy of segmental bioelectrical impedance analysis (sBIA) for use in older people. In 72 (40 men, 32 women) healthy elderly (mean age 69.0 ± 4.8 years), the MM and FM of right and left arm (RA, LA), right and left leg (RL, LL), and trunk were determined by sBIA (BC-418-MA, Tanita) and dual-energy X-ray absorptiometry (DXA) as a reference method. The sBIA provided in both sexes reliable values for limb and truncal MM and FM, except for MM of RL in women. The accuracy of sBIA displayed sex-specific bias. For MM, accurate values were noted for men's trunk and women's limbs (except LA). By contrast, MM was significantly underestimated in men's limbs by 6-18% and overestimated in women's LA (13%) and trunk (14%). Estimates of FM were accurate for men's arms as well as women's legs and trunk. However, FM was significantly overestimated in men's legs (34-37%) and trunk (60%), but underestimated in women's arms (27-35%). The proportional deviations of sBIA estimates from DXA values for limbs and trunk were significantly related to the respective MM or FM. The sBIA tends to underestimate MM in men and to overestimate in women. The reverse occurs for FM. The actual equations of the Tanita device may not completely represent the European older population and should be partly revised.

Genetics of the autoimmune polyglandular syndrome type 3 variant.

BACKGROUND: Autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D) are the most common autoimmune endocrine disorders. They occur frequently together in the same individual. This disease combination is denominated as autoimmune polyglandular syndrome type 3 variant (APS3v). This review aims to describe the genetic and pathological background of the syndrome. The joint susceptibility genes for AITD and T1D as well as the underlying pathogenetic mechanisms contributing to the development of autoimmunity are summarized. SUMMARY: Family and population studies showed that the APS3v syndrome has a strong genetic background. Whole genome and candidate gene approaches identified several gene variations that are present in both AITD and T1D. Most important common disease susceptibility genes are human leucocyte antigen (chromosome 6), cytotoxic T-lymphocyte-associated antigen 4 (chromosome 2), protein tyrosine phosphatase nonreceptor type 22 (chromosome 1), forkhead box P3 (X chromosome), and the interleukin-2 receptor alpha/CD25 gene region (chromosome 10), all of which contributing to the susceptibility to APS3v. With respect to the underlying pathogenetic mechanisms, these genes are altogether involved in the immune regulation, in particular in the immunological synapse and T-cell activation. In addition to these common genes, there are further candidate genes with joint risk for AITD and T1D, in particular the v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 gene (chromosome 12) and C-type lectin domain family 16 member A gene (chromosome 16). The latter one might be involved in pathogen recognition. CONCLUSIONS: AITD and T1D share common susceptibility gene variants that possibly act pleiotropically as risk factors for the development of autoimmunity in APS3v. The functional consequences of the genetic variants as well as their interactions should be explored in greater detail. In particular, the functional consequences of the variants of forkhead box P3 predisposing to APS3v need to be elucidated. Finally, further large-scale genome-wide associations studies of single-nucleotide polymorphism variations capturing many thousand individual genetic profiles are warranted to identify further genes that are linked to the etiology of APS3v.

Prevalence of sarcopenia among older community-dwelling people with normal health and nutritional state.

This study analyzed whether sarcopenia, a risk factor for disability in the aged, also occurs in healthy community-dwelling elders with normal nutritional state. As indicators, body cell mass (BCM) and lean body mass (LBM) were determined in 110 Germans (ages 60-83) using bioimpedance analysis. Nutritional status, muscle function, anthropometry, and physical activity level were investigated. Sarcopenia was already present in well nourished healthy elders. Its prevalence depended on the measure of muscle mass used (BCM percent, 22 percent males, 20 percent females; LBM percent, 4 percent males, 11 percent females). In conclusion, screening for presence of sarcopenia is needed in healthy, well-nourished elderly populations requiring an international standardization.

The proinflammatory cytokine TNF-alpha -308 AA genotype is associated with polyglandular autoimmunity.

Data regarding polymorphisms of immunoregulatory genes in polyglandular autoimmunity (PGA) are lacking. We have analyzed whether the polymorphism of the proinflammatory cytokine gene TNF-alpha; -308 and mutations of the autoimmune regulator (AIRE) gene were associated with PGA in adults. Sixty-seven patients with PGA and 209 healthy controls were genotyped by multiplex minisequencing with capillary electrophoresis on an ABI PRISM-310 genetic analyzer. HLA DRB1 typing was performed using polymerase-chain-reaction-amplified DNA hybridized with sequence-specific-oligonucleotide probes (PCR-SSO). The TNF-alpha; -308*A allele occurred more frequently in patients (0.269) than in controls (0.163, P = 0.008, P(c) = 0.016). Also, TNF-alpha; -308*A carriers were more frequent in patients than controls (47.8% vs. 31.1%, OR = 1.89, 95%CI = 1.19-3.00). The frequency of the AA genotype was increased in PGA (P = 0.014, P(c) = 0.042). PGA patients with autoimmune thyroid disease and the TNF-alpha; -308 AA genotype showed the highest prevalence of thyroid autoantibodies (TPO, P = 0.04; Tg, P = 0.003). HLA-DRB1*03 and TNF-alpha; -308*A alleles were strongly associated in patients with PGA (87.5%, P(c) < 0.00001). The AIRE R257X and 13bpdel mutations were not observed in patients with PGA. The association of TNF-alpha; -308*A with PGA might be directly or indirectly due to the association with HLA-DRB1*03.

Validation of the BIOPAC indirect calorimeter for determining resting energy expenditure in healthy free-living older people.

The BIOPAC indirect calorimeter for measuring resting energy expenditure (REE) is less cumbersome than many other calorimeters. We tested the hypothesis that the BIOPAC calorimeter is as well suited for determining REE in older people as traditional calorimeters. In 50 healthy persons (24 men and 26 women; age range, 61-83 years), REE by BIOPAC was validated against Vmax Spectra indirect calorimeter as a criterion method. Resting energy expenditure by BIOPAC was recorded at 2 different time intervals to find optimal conditions for older persons. Also, REE by 7 published equations was validated. The Bland-Altman procedure was used to test agreement between methods. Multiple regression analysis was applied to develop a new equation for predicting REE from BIOPAC. The BIOPAC calorimeter and most empirical equations significantly overpredicted mean REE in both sexes. Mifflin's equation best-predicted mean REE. Limits of agreement were wide for BIOPAC and narrow for most empirical equations. The Lührmann and Müller equations had smallest limits of agreement in men (+/-950 kJ/24 h) and the Harris-Benedict and Müller equations in women (+/-672 kJ/24 h). A new equation was developed for the BIOPAC device improving both predictions of mean and individual REE (R(2) = 0.671, standard error of the estimate = 136 kJ/24 h). Using this equation, 72.9% of subjects were lying within 10% of measured REE, compared with only 12.5% when using the manufacturer's algorithm. In conclusion, the BIOPAC calorimeter is suitable for measuring REE in healthy older adults when the new prediction equation is applied. This calorimeter is not applicable to frail older persons.

[Genetics of thyroid autoimmunity - update and clinical relevance]. / Genetik der Schilddrüsenautoimmunität - Update und klinische Relevanz.

The autoimmune thyroid diseases with the main phenotypes Graves' disease and Hashimoto's thyroiditis belong to the most frequently occurring autoimmune diseases. Genetic factors play a major role in their etiology, and in the past a couple of susceptibility genes have been identified. These are immunoregulatory genes like the HLA class II genes, the CTLA-4 gene and the PTPN22 gene and thyroid-specific genes for the TSH receptor and thyroglobulin. Even though this knowledge contributed to a better understanding of the pathogenesis of the autoimmune thyroid diseases, up to now the clinical relevance has been discussed insufficiently. Hence, this review provides an update of all relevant susceptibility genes for thyroid autoimmunity and discusses their significance for the clinical work.

Exposure to toxic agents alters organic elemental composition in human fingernails.

BACKGROUND AND OBJECTIVE: The human fingernail plate is highly keratinized. The keratin structure is held together by disulfide bonds. The organic elements sulfur and nitrogen occur almost exclusively in amino acids of the nail plate. This study analyzed whether occupational exposure to harmful chemical agents alters the organic elemental composition in fingernails. SUBJECTS AND METHODS: Participants were 71 occupationally exposed workers (49 hairdressers, 22 painters) and 49 unexposed controls. Aspects of exposure were assessed by questionnaire. Nail clippings of index and little fingers were analyzed for sulfur (S), nitrogen (N), carbon (C), and hydrogen (H) contents, using an automatic elemental analyzer (Vario EL III, Elementar Analysensysteme, Hanau, Germany). C/N, N/S, and C/S ratios were calculated. Reliability of elemental measurements was tested in a subset. RESULTS: Reliability analysis of elemental measurements showed a very good agreement. Both painters and hairdressers displayed in their fingernails significantly lower percentages of sulfur, but higher percentages of carbon than unexposed controls. A trend was observed in that sulfur content was lowest in those hairdressers who reported structural changes in their fingernails. As a consequence, the C/S and N/S ratios were significantly increased in both exposed groups. CONCLUSION: The occupational use of harmful substances leads to decreased sulfur levels in the exposed persons, probably due to diminution of sulfur-rich proteins in the nails, resulting from destruction of disulfide-bonds by alkaline and acid groups. Thus, the C/S ratio seems to be a useful indicator for the amount of damage of nail protein by harmful agents.

The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.

BACKGROUND: The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D. METHODS: In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used. RESULTS: The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034). CONCLUSION: The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.