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1.
Eur J Nutr ; 63(3): 821-834, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38196008

RESUMEN

PURPOSE: Vitamin D status and its association with age-related decline in physical performance and strength have already been highlighted in various ways, but data on the situation in developing countries are scarce. This study aimed to investigate vitamin D status, its association with muscle mass and function, and other potential determinants such as age, sex, lifestyle factors (physical activity, dietary behavior), self-perceived health status, medication intake, education and financial situation in adults from Kosovo. METHODS: This cross-sectional study included 297 participants (54.5% women), aged ≥ 40 years. Serum 25-hydroxyvitamin D (25(OH)D) concentration, hand grip strength and physical performance tests, body composition, vitamin D dietary intake and knowledge were assessed. The interaction between serum 25(OH)D status, lifestyle factors and muscle traits was investigated. RESULTS: Vitamin D deficiency (< 50 nmol/L) was observed in 47.5% of the total population, of whom 14.7% of them were severely deficient (< 30 nmol/L). No associations were found between 25(OH)D concentration and age. Daily dietary intake of vitamin D was low (1.89 ± 0.67 µg) and 87.6% of individuals did not take vitamin D supplements. However, vitamin D supplementation was the only variable that added statistical significance (p < 0.05) to the prediction of vitamin D status (3.8%). On the other hand, age, medication intake and vitamin D level contributed significantly to the overall regression model, explaining 24.9% of the 30-s chair stand performance as an indicator of lower-body strength endurance. CONCLUSION: Vitamin D deficiency is highly prevalent among community-dwelling adults in Kosovo and low serum 25(OH)D has been associated with low muscle strength. This implies an urgent need for the development of comprehensive prevention strategies, focusing on pharmacological (supplementation) but also on non-pharmacological strategies such as education, food fortification or lifestyle advices.


Asunto(s)
Fuerza de la Mano , Deficiencia de Vitamina D , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , Vida Independiente , Vitamina D , Vitaminas , Suplementos Dietéticos , Rendimiento Físico Funcional , Estilo de Vida
2.
Eur J Nutr ; 62(5): 2129-2138, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36964250

RESUMEN

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.


Asunto(s)
Gastritis Atrófica , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Masculino , Persona de Mediana Edad , Humanos , Femenino , Anciano , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiología , Cloruro de Sodio Dietético/efectos adversos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Estudios Transversales , Factores de Riesgo , Gastritis Atrófica/complicaciones , Atrofia/complicaciones
3.
Int J Mol Sci ; 24(17)2023 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-37686414

RESUMEN

Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21-30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effect was found in the three DNA damage treatments as well as in PC and UCB possibly due to circadian changes on oxidative stress, but no intervention group effect was observed for any of the markers. In conclusion, bolus vs. continuous glucose administration had no significant acute effect on DNA damage and markers of oxidative stress in healthy men.


Asunto(s)
Diabetes Mellitus Tipo 2 , Glucosa , Humanos , Masculino , Peróxido de Hidrógeno , Estrés Oxidativo , Daño del ADN , Bilirrubina , Biomarcadores , Voluntarios
4.
J Physiol ; 600(8): 1889-1911, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35156712

RESUMEN

Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1-13 C]-acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT-qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low-density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome). KEY POINTS: Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations. Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low-density lipoprotein (LDL) receptor expression. Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels. This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).


Asunto(s)
Enfermedad de Gilbert , Hipercolesterolemia , Animales , Bilirrubina/metabolismo , Colesterol/metabolismo , Femenino , Enfermedad de Gilbert/metabolismo , Hiperbilirrubinemia/metabolismo , Hipercolesterolemia/metabolismo , Lipoproteínas LDL/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Gunn , Receptores de LDL/genética , Receptores de LDL/metabolismo , Caracteres Sexuales , Esteroles/metabolismo
5.
Cardiovasc Diabetol ; 21(1): 54, 2022 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-35436955

RESUMEN

BACKGROUND: Mildly elevated bilirubin, a by-product of hemoglobin breakdown, might mitigate cardiometabolic risk factors including adiposity, dyslipidemia, and high blood pressure (BP). We investigated the cross-sectional relationship between (total) bilirubin and baseline cardiometabolic risk factors in 467,519 UK Biobank study participants. METHODS: We used multivariable-adjusted linear regression to estimate associations between bilirubin levels and risk factors of cardiometabolic diseases including body mass index (BMI), waist and hip circumferences (WC, HC), waist-to-hip ratio (WHR), fat mass (FM), and trunk FM, and the blood lipids: apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apoB/apoA-I, lipoprotein (a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL/HDL, TC/HDL, triglycerides (TG). Log-transformed bilirubin was modelled with restricted cubic splines and predicted mean values with 99% confidence intervals (CI) for each risk marker were estimated, separately. Second, we applied principal component analysis (PCA) for dimension reduction to in turn six anthropometric traits (height, weight, BMI, WC, HC, and WHR) and all above lipids. Last, we estimated associations (99%CI) between bilirubin and three components of the metabolic syndrome, i.e. WC, TG, and BP using logistic regression. RESULTS: After multivariable adjustments, higher levels of bilirubin were inversely associated with indicators of general adiposity (BMI and FM) and of body fat distribution (WC, HC, WHR, and trunk FM) in both men and women. For example, women with mildly elevated bilirubin (95th percentile equal to 15.0 µmol/L), compared to women with low bilirubin (5th percentile equal to 4.5 µmol/L), had on average a 2.0 kg/m2 (99% CI 1.9-2.1) lower BMI. Inverse associations were also observed with dyslipidemia among men and women. For example, mildly elevated bilirubin among men (95th percentile equal to 19.4 µmol/L) compared to low levels of bilirubin (5th percentile equal to 5.5 µmol/L) were associated with approx. 0.55 mmol/L (99% CI 0.53-0.56) lower TG levels, with similar inverse associations among women. Multiple-trait analyses using PCA confirmed single-trait analyses. Men and women with mildly elevated bilirubin levels ≥ 17.1 µmol/L, compared to low-normal bilirubin < 10 µmol/L had 13% (99% CI 8%-18%) and 11% (99% CI 4%-17%) lower odds of exceeding systolic BP levels of ≥ 130 mm Hg, respectively. CONCLUSIONS: Higher levels of bilirubin were inversely associated with cardiometabolic risk factors including adiposity, dyslipidemia, and hypertension.


Asunto(s)
Bilirrubina , Factores de Riesgo Cardiometabólico , Dislipidemias , Hipertensión , Obesidad , Apolipoproteína A-I , Apolipoproteínas B , Bilirrubina/sangre , Índice de Masa Corporal , HDL-Colesterol , Estudios Transversales , Bases de Datos Factuales , Dislipidemias/diagnóstico , Dislipidemias/epidemiología , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Lípidos , Masculino , Obesidad/diagnóstico , Obesidad/epidemiología , Triglicéridos , Reino Unido/epidemiología
6.
Eur J Nutr ; 61(1): 169-182, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34240265

RESUMEN

PURPOSE: Cardiovascular diseases and cognitive decline, predominant in ageing populations, share common features of dysregulated one-carbon (1C) and cardiometabolic homeostasis. However, few studies have addressed the impact of multifaceted lifestyle interventions in older adults that combine both nutritional supplementation and resistance training on the co-regulation of 1C metabolites and cardiometabolic markers. METHODS: 95 institutionalised older adults (83 ± 6 years, 88.4% female) were randomised to receive resistance training with or without nutritional supplementation (Fortifit), or cognitive training (control for socialisation) for 6 months. Fasting plasma 1C metabolite concentrations, analysed by liquid chromatography coupled with mass spectrometry, and cardiometabolic parameters were measured at baseline and the 3- and 6-month follow-ups. RESULTS: Regardless of the intervention group, choline was elevated after 3 months, while cysteine and methionine remained elevated after 6 months (mixed model time effects, p < 0.05). Elevated dimethylglycine and lower betaine concentrations were correlated with an unfavourable cardiometabolic profile at baseline (spearman correlations, p < 0.05). However, increasing choline and dimethylglycine concentrations were associated with improvements in lipid metabolism in those receiving supplementation (regression model interaction, p < 0.05). CONCLUSION: Choline metabolites, including choline, betaine and dimethylglycine, were central to the co-regulation of 1C metabolism and cardiometabolic health in older adults. Metabolites that indicate upregulated betaine-dependent homocysteine remethylation were elevated in those with the greatest cardiometabolic risk at baseline, but associated with improvements in lipid parameters following resistance training with nutritional supplementation. The relevance of how 1C metabolite status might be optimised to protect against cardiometabolic dysregulation requires further attention.


Asunto(s)
Carbono , Enfermedades Cardiovasculares , Anciano , Envejecimiento , Betaína , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Colina , Suplementos Dietéticos , Femenino , Homocisteína , Humanos , Masculino
7.
Int J Cancer ; 2021 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-33899229

RESUMEN

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML  = 0.87, 95% CI: 0.76-0.99, HR-CEL  = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML  = 1.28, 95% CI: 1.05-1.56, HR-CEL  = 1.17; 95% CI: 0.96-1.40, HR-MH-G1  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

8.
Horm Behav ; 124: 104784, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32504693

RESUMEN

Dietary intake of polyunsaturated fatty acids (PUFAs) or saturated fatty acids (SFAs) differently modulates neurophysiological and behavioral functions in response to altered hypothalamic-pituitary-adrenal (HPA)-axis activity and an individual's development. In this context, an individual's social environment, including social interactions and social hierarchies, is closely related to hormone concentrations and possibly interacts with dietary fatty acid effects. We investigated if dietary supplementation with walnut oil (high in PUFAs) and coconut fat (high in SFAs), compared to a control group, affects body mass gain, cortisol and testosterone concentrations, plasma fatty acids, and social behavior in male domestic guinea pigs from adolescence to adulthood. For analyses of cortisol and testosterone concentrations, social interactions were included as covariates in order to consider effects of social behavior on hormone concentrations. Our results revealed that SFAs increased escalated conflicts like fights and stimulated cortisol and testosterone concentrations, which limited body mass gain and first-year survival. PUFAs did not remarkably affect social behavior and hormone concentrations, but enabled the strongest body mass gain, which probably resulted from an energetic advantage. Neither sociopositive nor agonistic behaviors explained age-specific differences in hormone concentrations between groups. However, a high number of subdominant individuals and lower testosterone concentrations were related to increased cortisol concentrations in adult PUFA males. Our findings demonstrate the importance of dietary fatty acids regarding behavioral and endocrine developmental processes and adaptations to the social environment by modulating HPA-axis function and body homeostasis.


Asunto(s)
Grasas de la Dieta/farmacología , Ácidos Grasos/farmacología , Maduración Sexual/efectos de los fármacos , Conducta Social , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Ácidos Grasos Insaturados/farmacología , Cobayas , Jerarquia Social , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Saliva/química , Saliva/metabolismo , Maduración Sexual/fisiología , Testosterona/sangre
9.
Platelets ; 31(7): 884-896, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-31747815

RESUMEN

Bilirubin ditaurate (BRT), a conjugated bilirubin analogue, has demonstrated anti-platelet characteristics following acute ex vivo exposure. Scavenging of mitochondrial superoxide and attenuation of granule exocytosis suggested a potential benefit for including BRT for storage. With no reports of cytotoxicity following acute exposure, the impact of 35µM BRT on platelet function was investigated, in clinically suppled units, for up to seven days. Exposure to 35µM BRT significantly reduced mitochondrial membrane potential and increased glucose consumption until exhaustion after 72 hours. Platelet aggregation and activation was significantly impaired by BRT. Mitochondrial superoxide production and phosphatidylserine expression were significantly elevated following glucose exhaustion, with decreased viability observed from day five onwards. Lactate accumulation and loss of bicarbonate, support a metabolic disturbance, leading to a decline of quality following BRT inclusion. Although acute ex vivo BRT exposure reported potentially beneficial effects, translation from acute to chronic exposure failed to combat declining platelet function during storage. BRT exposure resulted in perturbations of platelet quality, with the utility of BRT during storage therefore limited. However, these are the first data of prolonged platelet exposure to analogues of conjugated bilirubin and may improve our understanding of platelet function in the context of conjugated hyperbilirubinemia.


Asunto(s)
Bilirrubina/análogos & derivados , Plaquetas/efectos de los fármacos , Conservación de la Sangre/métodos , Taurina/análogos & derivados , Bilirrubina/farmacología , Bilirrubina/uso terapéutico , Humanos , Taurina/farmacología , Taurina/uso terapéutico
10.
Ann Nutr Metab ; 76(4): 213-222, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32690847

RESUMEN

BACKGROUND: The Nutrition Societies of Germany, Austria, and Switzerland as the joint editors of the "D-A-CH reference values for nutrient intake" have revised the reference values for vitamin B6 in summer 2019. SUMMARY: For women, the average requirement (AR) for vitamin B6 intake was derived on the basis of balance studies using a pyridoxal-5'-phosphate (PLP) plasma concentration of ≥30 nmol/L as a biomarker of an adequate vitamin B6 status. The recommended intake (RI) was derived considering a coefficient of variation of 10%. The RIs of vitamin B6 for men, children, and adolescents were extrapolated from the vitamin B6 requirement for women considering differences in body weight, an allometric exponent, growth factors as appropriate, and a coefficient of variation. For infants aged 0 to under 4 months, an estimated value was set based on the vitamin B6 intake via breast feeding. The reference value for infants aged 4 to under 12 months was extrapolated from the estimated value for infants under 4 months of age and the average vitamin B6 requirement for adults. The reference values for pregnant and lactating women consider the requirements for the foetus and the loss via breast milk. Key Messages: According to the combined analysis of 5 balance studies, the AR for vitamin B6 to ensure a plasma PLP concentration of ≥30 nmol/L is 1.2 mg/day for adult females and the extrapolated AR for adult males is 1.3 mg/day. The corresponding RIs of vitamin B6 are 1.4 mg/day for adult females and 1.6 mg/day for adult males, independent of age. For infants, the estimated value is 0.1 mg/day and 0.3 mg/day, depending on age. The AR of vitamin B6 for children and adolescents ranges between 0.5 and 1.5 mg/day, and the RI is between 0.6 mg/day and 1.6 mg/day. During pregnancy, the AR is 1.3 mg/day in the first trimester and 1.5 mg/day in the second and third trimesters; the RI is 1.5 mg/day in the first trimester and 1.8 mg/day in the second and third trimesters. For lactating women, the AR is 1.3 mg/day and the RI is 1.6 mg/day.


Asunto(s)
Ingesta Diaria Recomendada , Vitamina B 6/normas , Adolescente , Adulto , Austria , Biomarcadores/sangre , Niño , Preescolar , Femenino , Alemania , Humanos , Lactante , Recién Nacido , Lactancia , Masculino , Persona de Mediana Edad , Estado Nutricional , Monoéster Fosfórico Hidrolasas/sangre , Embarazo , Estándares de Referencia , Valores de Referencia , Suiza , Adulto Joven
11.
Crit Rev Clin Lab Sci ; 55(2): 129-139, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29390925

RESUMEN

Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Assessment of bilirubin concentrations is typically conducted as part of routine liver function testing. Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts, however, may indicate the presence of Gilbert's syndrome (GS), a benign condition that is present in ∼5-10% of the population. In this case, mildly elevated unconjugated bilirubin in GS is strongly associated with "reduced" prevalence of chronic diseases, particularly cardiovascular diseases (CVD) and type 2 diabetes mellitus (and associated risk factors), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic by-product of heme catabolism and emphasize the importance of understanding its potential beneficial physiologic and detrimental pathophysiologic effects, in order to appropriately consider bilirubin test results within the clinical laboratory setting. With this information, we hope to improve the understanding of disorders of bilirubin metabolism, emphasize the diagnostic importance of these conditions, and outline the potential impact GS may have on resistance to disease.


Asunto(s)
Enfermedad de Gilbert/diagnóstico , Bilirrubina/sangre , Enfermedad de Gilbert/sangre , Enfermedad de Gilbert/genética , Glucuronosiltransferasa/genética , Humanos , Hiperbilirrubinemia
12.
Am J Physiol Heart Circ Physiol ; 315(3): H429-H447, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-29600900

RESUMEN

Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert's syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.


Asunto(s)
Bilirrubina/metabolismo , Enfermedades Cardiovasculares/etiología , Sistema Cardiovascular/metabolismo , Hiperbilirrubinemia/complicaciones , Animales , Bilirrubina/sangre , Enfermedades Cardiovasculares/fisiopatología , Humanos , Hiperbilirrubinemia/fisiopatología
13.
Br J Nutr ; 120(11): 1240-1251, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30322410

RESUMEN

PUFA modulate hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol concentrations and therefore affect physiological stress responses and the regulation of energy balance in the short- and long-term. Especially dietary intake of n-3 PUFA and a lowered n-6:n-3 ratio are highly encouraged due to beneficial and diminishing effects on basal cortisol secretions. However, the time of such effects to occur and how plasma PUFA patterns affect cortisol concentrations in the short-term was rarely investigated. In order to address this, we supplemented forty male and forty female guinea pigs with diets high in the essential PUFA α-linolenic acid (ALA, 18 : 3n-3) and linoleic acid (LA, 18 : 2n-6) for 20 d. Saliva cortisol concentrations in relation to altering plasma PUFA patterns during this time span were analysed in a repeated measurement design both during basal conditions (individual housing) in 5-d intervals and during stressful social confrontations. We detected very fast plasma PUFA accumulation rates, corresponding to the major dietary PUFA, which resulted in plasma PUFA plateau phases after 10 d. ALA negatively and LA positively affected saliva cortisol concentrations throughout the study. A positive effect of the plasma n-6:n-3 ratio on saliva cortisol concentrations was detected during peak plasma PUFA accumulations and social confrontations, while no effects were detected in relation to plasma PUFA plateau phases. These results suggest that the plasma n-6:n-3 ratio diminishes HPA axis activity during altered physiological conditions only and highlights the importance of altering plasma PUFA patterns for HPA axis functions and the control of energy balance and physiological stress.


Asunto(s)
Ácidos Grasos Insaturados/sangre , Hidrocortisona/metabolismo , Saliva/metabolismo , Alimentación Animal , Animales , Conducta Animal , Dieta , Ácidos Grasos/metabolismo , Femenino , Cobayas , Masculino , Reproducibilidad de los Resultados , Ácido alfa-Linolénico/metabolismo
14.
Reprod Fertil Dev ; 30(8): 1077-1086, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29306361

RESUMEN

Reproductive functions in female mammals can be significantly affected by the actions of dietary polyunsaturated fatty acids (PUFAs) on steroid hormone secretion rates. Nevertheless, the effects of plasma free PUFAs on the oestrous cycle have seldom been considered. Therefore, in the present study, the diet of domestic guinea pigs was supplemented with high concentrations of different PUFAs and the effects of altered plasma PUFA patterns on steroid hormone concentrations, measured non-invasively, and body mass during oestrus and dioestrus were analysed. The oestrous cycle was characterised by increased oestrogen and cortisol concentrations in oestrus, corroborated by lowest bodyweight, whereas progesterone concentrations were highest in dioestrus. Plasma concentrations of the long-chain PUFAs docosahexaenoic acid (DHA; 22:6 ω3) and arachidonic acid (AA; 20:5 ω6) affected steroid hormone concentrations differently in oestrus and dioestrus. DHA positively affected oestrogen and progesterone concentrations and diminished cortisol concentrations only in oestrus. In contrast, AA negatively affected oestrogen and stimulated cortisol concentrations in oestrus and reduced progesterone concentrations in general. These findings imply selective and opposite contributions of DHA and AA to ovarian functions during different stages of the oestrous cycle, indicating a high biological relevance of plasma free PUFAs in female reproductive function.


Asunto(s)
Peso Corporal/efectos de los fármacos , Estradiol/sangre , Ciclo Estral/efectos de los fármacos , Ácidos Grasos Insaturados/farmacología , Progesterona/sangre , Animales , Ciclo Estral/sangre , Femenino , Cobayas , Humanos , Hidrocortisona/sangre
15.
Perception ; 46(10): 1171-1182, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28669245

RESUMEN

It is well known that visually impaired people perform better in orientation by sound than sighted individuals, but it is not clear whether this enhanced awareness also extends to other senses. Therefore, the aim of this study was to observe whether visually impaired subjects develop superior abilities in olfactory perception to compensate for their lack of vision. We investigated the odor perception of visually impaired individuals aged 7 to 89 ( n = 99; 52 women, 47 men) and compared them with subjects of a control group aged 8 to 82 years ( n = 100; 45 women, 55 men) without any visual impairment. The participants were evaluated by Sniffin' Sticks odor identification and discrimination test. Identification ability was assessed for 16 common odors presented in felt-tip pens. In the odor discrimination task, subjects had to determine which of three pens in 16 triplets had a different odor. The median number of correctly identified odorant pens in both groups was the same, 13 of the offered 16. In the discrimination test, there was also no significant difference observed. Gender did not influence results. Age-related changes were observed in both groups with olfactory perception decreasing after the age of 51. We could not confirm that visually impaired people were better in smell identification and discrimination ability than sighted individuals.


Asunto(s)
Discriminación en Psicología/fisiología , Percepción Olfatoria/fisiología , Trastornos de la Visión/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
16.
Immun Ageing ; 13: 22, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27375767

RESUMEN

BACKGROUND: Ageing, inactivity and obesity are associated with chronic low-grade inflammation contributing to a variety of lifestyle-related diseases. Transforming growth factor-ß (TGF-ß) is a multimodal protein with various cellular functions ranging from tissue remodelling to the regulation of inflammation and immune functions. While it is generally accepted that aerobic exercise exerts beneficial effects on several aspects of immune functions, even in older adults, the effect of resistance training remains unclear. The aim of this study was to investigate whether progressive resistance training (6 months) with or without nutritional supplementation (protein and vitamins) would influence circulating C-reactive protein and TGF-ß levels as well as TGF-ß signalling in peripheral mononuclear cells (PBMCs) of institutionalised adults with a median age of 84.5 (65.0-97.4) years. RESULTS: Elastic band resistance training significantly improved performance as shown by the arm-lifting test (p = 0.007), chair stand test (p = 0.001) and 6-min walking test (p = 0.026). These results were paralleled by a reduction in TGF-ß receptor I (TGF-ßRI) mRNA expression in PBMCs (p = 0.006), while circulating inflammatory markers were unaffected. Protein and vitamin supplementation did not provoke any additional effects. Interestingly, muscular endurance of upper and lower body and aerobic performance at baseline were negatively associated with changes in circulating TGF-ß at the early phase of the study. Furthermore, drop-outs of the study were characterised not only by lower physical performance but also higher TGF-ß and TGF-ßRI mRNA expression, and lower miRNA-21 expression. CONCLUSIONS: Progressive resistance training with elastic bands did not influence chronic low-grade inflammation but potentially affected TGF-ß signalling in PBMCs through altered TGF-ßRI mRNA expression. There appears to be an association between physical performance and TGF-ß expression in PBMCs of older adults, in which the exact mechanisms need to be clarified.

17.
Eur J Appl Physiol ; 116(5): 885-97, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26931422

RESUMEN

PURPOSE: Regular resistance exercise training and a balanced diet may counteract the age-related muscular decline on a molecular level. The aim of this study was to investigate the influence of elastic band resistance training and nutritional supplementation on circulating muscle growth and degradation factors, physical performance and muscle quality (MQ) of institutionalized elderly. METHODS: Within the Vienna Active Ageing Study, 91 women aged 83.6 (65.0-92.2) years were randomly assigned to one of the three intervention groups (RT, resistance training; RTS, resistance training plus nutritional supplementation; CT, cognitive training). Circulating levels of myostatin, activin A, follistatin, IGF-1 and GDF-15, as well as MQ and functional parameters were tested at baseline as well as after 3 and 6 months of intervention. RESULTS: MQ of lower extremities significantly increased in the RT group (+14 %) and RTS group (+12 %) after 6 months. Performance improved in the RT and RTS groups for chair stand test (RT: +18 %; RTS: +15 %). Follistatin increased only in the RT group (+18 %) in the latter phase of the intervention, accompanied by a decrease in the activin A-to-follistatin ratio (-7 %). IGF-1, myostatin and GDF-15 levels were not affected by the intervention. CONCLUSION: Our data confirm that strength training improves physical performance and MQ even in very old institutionalized women. This amelioration appears to be mediated by blocking muscle degradation pathways via follistatin rather than inducing muscle growth through the IGF-1 pathway. As plasma levels of biomarkers reflect an overall status of various organ systems, future studies of tissue levels are suggested.


Asunto(s)
Envejecimiento/fisiología , Ejercicio Físico/fisiología , Músculo Esquelético/fisiología , Entrenamiento de Fuerza/métodos , Activinas/sangre , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Envejecimiento/metabolismo , Suplementos Dietéticos , Femenino , Folistatina/sangre , Factor 15 de Diferenciación de Crecimiento/sangre , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Músculo Esquelético/metabolismo , Miostatina/sangre
19.
Clin Sci (Lond) ; 129(1): 1-25, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25881719

RESUMEN

Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.


Asunto(s)
Envejecimiento/sangre , Bilirrubina/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus Tipo 2/sangre , Neoplasias/sangre , Enfermedades Cardiovasculares/mortalidad , Enfermedad Crónica , Diabetes Mellitus Tipo 2/mortalidad , Humanos , Neoplasias/mortalidad , Pronóstico , Tasa de Supervivencia
20.
Mutagenesis ; 30(5): 701-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25958389

RESUMEN

Wood dust was classified by the IARC as a human carcinogen which causes sinonasal tumours. However, the exposure in different industries varies strongly and the risks of workers depend on the specific situation which can be assessed by the use of biomonitoring methods. The aim of this study was to investigate the workers who are exposed to low dust levels (below the permitted concentrations) with cytogenetic and biochemical methods. Micronuclei (MNi) which are indicative for genomic damage, nuclear buds which reflect gene amplification, binucleated cells which are caused by mitotic disturbances and acute cytotoxicity parameters (pyknosis, karyorrhexis, condensed chromatin, karyolysis) were monitored in buccal and nasal cells of workers of a veneer factory (n = 51) who are exposed to volatile wood-derived compounds, in carpenters of a furniture factory which use no synthetic chemicals (n=38) and in a control group (n = 65). Additionally, markers were measured in blood plasma which reflect inflammations (C-reactive protein, CRP) and the redox status, namely malondialdehyde (MDA) and oxidised low density proteins (oxLDL). No induction of micronucleated cells was observed in both epithelia in the two exposure groups while all other nuclear anomalies except pyknosis were increased; also one health-related biochemical marker (MDA) was significantly elevated in the workers. Taken together, the results of our study show that exposure to low levels of wood dust does not cause formation of MNi indicating that the cancer risks of the workers are not increased as a consequence of genetic damage while positive results were obtained in earlier studies with workers who are exposed to high dust levels. However, our findings indicate that wood dust causes cytotoxic effects which may lead to inflammations.


Asunto(s)
Citotoxinas/toxicidad , Polvo , Mucosa Bucal/efectos de los fármacos , Mutágenos/toxicidad , Mucosa Nasal/efectos de los fármacos , Exposición Profesional/efectos adversos , Madera/toxicidad , Adulto , Femenino , Humanos , Inflamación , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos , Persona de Mediana Edad , Mucosa Bucal/citología , Mucosa Nasal/citología , Estrés Oxidativo/efectos de los fármacos
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