Changes in thyroid function with age: results from the Pizarra population-based longitudinal study.

BACKGROUND: Results of studies examining the influence of age on thyroid function and TSH levels, in the absence of thyroid disease, remain controversial. The aim of this study was to determine the course of thyroid function over 11 years in a population with normal thyroid function. METHODS: This is a population-based prospective study started in 1995-1997 (first phase), and reassessed 6 (second phase) and 11 years later (third phase). RESULTS: The TSH and FT4 in the third phase were significantly increased (p=0.001 and p=0.001, respectively), with the values being higher particularly from the age of 50 years. In those persons with a baseline TSH≥1.2 and <3 µIU/mL, the OR of having a TSH of 3-5 µIU/mL in the third phase was 6.10 (p=0.004). In those with a baseline TSH≥3 and ≤5 µIU/mL, the OR of having a TSH of 3-5 µIU/mL in the third phase was 20.8 (p<0.0001). Similar results were found for FT4. CONCLUSION: In a population free of clinical thyroid disease, TSH and FT4 values rise over the years. This increase occurs in all age groups, but depends mainly on the basal concentrations of TSH and FT4.

Cross-reactivity of insulin analogues with three insulin assays.

BACKGROUND: Immunometric assays have recently shown higher specificity in the detection of human insulin than radioimmunoassays with almost no cross-reaction with proinsulin or C peptide. The introduction of the new insulin analogues on the market, however, has raised the need to define their cross-reactivity in these assays. Several studies have been published in this regard with different results. METHODS: The analogues studied were insulins lispro, aspart, glargine, detemir, and glulisine. Insulin concentrations were measured in Immulite(®) 2000 and Advia Centaur(®) XP (Siemens Healthcare Diagnostics), and Elecsys(®) Modular Analytics E170 (Roche). All samples were processed 15 times in the same analytical run following a random sequence. Those samples which showed statistically and clinically significant changes in insulin concentration were reprocessed using increasing concentrations of analogue, and this was done twice, using two different serum pools, one with a low concentration of insulin and one with a high concentration of insulin. RESULTS: In the Elecsys(®) E170 analyser, glargine showed statistical changes (comparison of mean concentrations with p < 0.05) and clinically significant changes in measured insulin (percentage difference 986.2% > reference change value: 59.8%), and the interference increased with increasing concentrations of analogue; the differences were not significant in the case of the other analogues. In the Advia Centaur(®) and Immulite(®) 2000 only the results for glulisine did not present significance (percentage difference 44.7% < reference change value 103.5%). Increasing concentrations of aspart, glargine, and lispro showed increased interference in Immulite(®) 2000. CONCLUSIONS: In the Elecsys(®) E170 assay, relevant cross-reactivity was only detected with insulin glargine, whereas in the other analysers all analogues except glulisine showed significant interference.

Hypovitaminosis D and incidence of obesity: a prospective study.

The aim of this study was to assess the relationship between obesity and vitamin D status cross-sectionally, the relationship between obesity and the incidence of hypovitaminosis D prospectively and inversely the relationship between vitamin D status and incidence of obesity in a population-based cohort study in Spain. At baseline (1996-1998), 1226 subjects were evaluated and follow-up assessments were performed in 2002-2004 and 2005-2007, participants undergoing an interview and clinical examination with an oral glucose tolerance test. At the second visit, 25-hydroxyvitamin D and intact parathyroid hormone concentrations were also measured. Prevalence of obesity at the three visits was 28.1, 36.2 and 39.5%, respectively. The prevalence of vitamin D deficiency (25-hydroxyvitamin D ≤ 20 ng/ml (≤ 50 nmol/l)) was 34.7%. Neither obesity at baseline (OR=0.98, 95% CI: 0.69-1.40, P=0.93) nor the development of obesity between baseline and the second evaluation (OR=0.80, 95% CI: 0.48-1.33, P=0.39) were significantly associated with vitamin D status. In subjects who were non-obese (BMI <30 kg/m²) at the second evaluation, 25-hydroxyvitamin D values ≤ 17 ng/ml (≤ 42.5 nmol/l) were significantly associated with an increased risk of developing obesity in the next 4 years (OR=2.35, 95% CI: 1.03-5.4, P=0.040 after diverse adjustments). We conclude that vitamin D deficiency is associated with an increased risk of developing obesity.

Reduction of body weight, liver steatosis and expression of stearoyl-CoA desaturase 1 by the isoflavone daidzein in diet-induced obesity.

BACKGROUND AND PURPOSE: The lack of safe and effective treatments for obesity has increased interest in natural products that may serve as alternative therapies. From this perspective, we have analysed the effects of daidzein, one of the main soy isoflavones, on diet-induced obesity in rats. EXPERIMENTAL APPROACH: Rats made obese after exposure to a very (60%) high fat-content diet were treated with daidzein (50 mg·kg(-1)) for 14 days. The dose was selected on the basis of the acute effects of this isoflavone on a feeding test. After 14 days, animals were killed and plasma, white and brown adipose tissue, muscle and liver studied for the levels and expression of metabolites, proteins and genes relevant to lipid metabolism. KEY RESULTS: A single treatment (acute) with daidzein dose-dependently reduced food intake. Chronic treatment (daily for 14 days) reduced weight gain and fat content in liver, accompanied by high leptin and low adiponectin levels in plasma. While skeletal muscle was weakly affected by treatment, both adipose tissue and liver displayed marked changes after treatment with daidzein, affecting transcription factors and lipogenic enzymes, particularly stearoyl coenzyme A desaturase 1, a pivotal enzyme in obesity. Expression of uncoupling protein 1, an important enzyme for thermogenesis, was increased in brown adipose tissue after daidzein treatment. CONCLUSIONS AND IMPLICATIONS: These results support the use of isoflavones in diet-induced obesity, especially when hepatic steatosis is present and open a new field of use for these natural products.

El Laboratorio Clínico en el sistema asistencial / The clinical laboratory in the health care system

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Vitamin D deficiency in Spain: a population-based cohort study.

BACKGROUND: Vitamin D deficiency is common worldwide. No homogenous reference values have yet been established and no studies of values have been conducted in Spain involving a large number of participants. OBJECTIVE: To study the population concentrations of vitamin D in a representative sample of the Spanish population. SUBJECTS/METHODS: The study involved two cohorts from Spain, the Asturias study and the Pizarra study, which are two prospective, population-based studies involving 2260 participants. In 1262 subjects (age: 20-83 years) we studied 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), calcium, phosphorus and creatinine. RESULTS: The median population values of 25-hydroxyvitamin D and iPTH were 22.46 ng/ml and 42.29 pg/ml, respectively. The values of 25-hydroxyvitamin D were significantly higher in summer and correlated with age (ß = -0.05 ± 0.01, P < 0.0001), creatinine (ß = 6.42 ± 1.17, P < 0.0001) and iPTH (-0.07 ± 0.01, P < 0.0001), but not with calcium, phosphorus or sex. The increase in iPTH with age was seen whatever the values of 25-hydroxyvitamin D, and was greater in the older persons. The concentration of iPTH rose continuously with effect from 25-hydroxyvitamin D values below ≈30 ng/ml. Values above ≈35 ng/ml were associated with a significantly lower concentration of iPTH. CONCLUSIONS: One-third (33.9%) of the Spanish population may be at risk for Vitamin D deficiency. The 25-hydroxyvitamin D values above 30 ng/ml can safely discard 'hyper PTH'. The increase in iPTH concentration is greater in older persons for similar values of 25-hydroxyvitamin D.

Central versus peripheral antagonism of cannabinoid CB1 receptor in obesity: effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist, in Zucker rats.

The endogenous cannabinoid system plays an important modulatory role in feeding behaviour and metabolism, acting at both central and peripheral levels. Chronic administration of cannabinoid CB(1) receptor antagonists has been found to be effective in experimental obesity. However, clinically available cannabinoid receptor antagonists are inverse agonists that can target CB(1) receptors located in both central circuits regulating appetite and motivation and in peripheral organs regulating metabolism and energy expenditure. This profile complicates understanding of cannabinoid CB(1) receptor blockade as a therapeutic strategy in obesity and metabolic disorders. This review aims to explore the relevance of both inverse agonism and peripheral cannabinoid receptor blockade on the beneficial actions of chronic cannabinoid receptor blockade, by comparing the actions of the reference antagonist/inverse agonist rimonabant and the newly designed drug LH-21. LH-21 is a triazol derivative and a neutral cannabinoid receptor antagonist; it has a poor penetration rate into the central nervous system. When given acutely it decreases food intake and enhances the anorectic actions of oleoylethanolamide, a feeding suppressant lipid that acts on peripheral sensory terminals in a similar way as rimonabant. Unlike rimonabant, chronic administration of LH-21 (3 mg/kg) reduces feeding but does not improve hypertriglyceridaemia or hypercholesterolaemia; nor does it reduce liver fat deposits in Zucker rats. These results suggest that the inverse agonism and/or the antagonism of central cannabinoid CB(1) receptors are necessary for the metabolic benefits of cannabinoid CB(1) receptor blockade, but not for the appetite reduction.

Selenium concentrations in serum of individuals with liver diseases (cirrhosis or hepatitis): relationship with some nutritional and biochemical markers.

Serum concentrations were measured in individuals (n = 50) with liver diseases (cirrhosis and hepatitis) by hydride generation atomic absorption spectrometry in a cross-sectional study. Mean serum selenium levels determined in patients with cirrhosis (n = 12) or with hepatitis (n = 38) were significantly lower (P<0.01) than those measured in control groups mainly due to a decreased liver function. Mean serum selenium concentrations were significantly lower in cirrhotic individuals when compared with patients with hepatitis (P<0.05). Therefore, the severity of the live injury is a factor conditioning the impairment in the selenium body status observed in individuals with hepatopathies. In hepatic patients serum total cholesterol levels showed a significant correlation with serum selenium concentrations (r=0.912, P<0.05) demonstrating the important role of selenium as an antioxidant agent; similarly, gamma-glutamic-transferase levels were significantly correlated with the serum selenium levels (r=-0.803, P<0.05) indicating that when the intensity of the hepatic injury increases (enhancement in serum GGT levels) concomitantly the serum selenium levels decrease significantly. No significant relationships between serum selenium levels and sex or age of patients were observed.

Multicentric reference values for some quantities measured with the Elecsys 2010 analyser.

Several clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning thyrotropin, non-protein bound thyroxine, triiodothyronine, cobalamines and folates, using an Elecsys 2010 analyser. All the logistic work has been done in co-operation with the supplier of the analyser (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are in fact derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done represents a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.

Serum and urine selenium concentrations in patients with cardiovascular diseases and relationship to other nutritional indexes.

Serum and urine selenium levels were determined in patients with cardiovascular diseases by hydride generation atomic absorption spectrometry. Mean serum Se concentrations measured in patients with acute myocardial infarction (AMI; n = 32) or with ischemic cardiomyopathy (n = 50) were significantly lower than those determined in control groups. In AMI patients, serum triglyceride levels showed a positive significant correlation with the serum Se concentration (r = 0.59, p < 0.05). This result reinforces the important role of Se as an antioxidant agent in this disease. Mean urine Se concentrations of AMI patients (n = 33) were also significantly lower to those determined in the control group (p < 0. 05). This reaction of the organism contributes to regulate the Se homeostasis to keep the body Se status as high as possible.

Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus.

Serum and urine selenium levels were determined in patients with diabetes by hydride generation atomic absorption spectrometry. Mean serum selenium concentrations measured in patients with diabetes mellitus (64.9 +/- 22.8 micrograms/l) were significantly lower than those determined in the control group (74.9 +/- 27.3 micrograms/l) (P < 0.05). Mean serum selenium concentrations were not significantly different between the two groups of diabetic patients considered (P > 0.05). Mean urine selenium concentration in diabetic patients (18.8 +/- 10.7 micrograms/l) were not significantly different from those measured in the control group (20.2 +/- 10.1 micrograms/l) (P < 0.05). No significant differences in serum and urine selenium levels were found if related to sex of patients (P > 0.05). Application of linear regression analysis to serum and urine selenium levels and patients' age showed a non-statistically significant correlation (P > 0.05). Given the marked overlap between the two ranges of the populations, the predictive values of serum selenium in diabetic patients are low.

Serum zinc and copper concentrations and Cu/Zn ratios in patients with hepatopathies or diabetes.

The serum zinc and copper levels, as well as Zn/Cu ratios, were determined in 30 patients (18 with diabetes and 12 with hepatopathies) and compared to healthy-age matched controls by atomic absorption spectrometry. Serum Zn (0.946 +/- 0.302 mg/l) and Cu (0.952 +/- 0.355 mg/l) concentrations were not significantly different in patients with hepatopathies as compared to controls (p > 0.05). Serum Zn concentrations (0.778 +/- 0.164 mg/l) were significantly lower in diabetic patients than those determined in controls (p < 0.01). In contrast, Cu levels (0.987 +/- 0.305 mg/l) were not significantly different (p > 0.05) than in controls. Serum Cu/Zn ratios were not significantly different in patients with diabetes or hepatopathies than those measured in healthy controls (p > 0.05). In patients, no statistically significant differences were observed in the Zn, Cu and Cu/Zn with respect to sex (p > 0.05) or age (p > 0.05).

Urine arsenic concentrations in healthy adults as indicators of environmental contamination: relation with some pathologies.

Arsenic concentrations were determined in 126 urine samples by hydride generation atomic absorption spectrometry. Samples were mineralized with nitric acid in a thermostated mineralization block. This technique was compared with a method that involves mineralization in a microwave digestion bomb. A mean recovery percentage of 100.80 +/- 5.57% was obtained. The relative standard deviation ranged from 1.7 to 10.52%. It was found that subject sex and age did not affect urine As levels (P > 0.05). The mean urine As levels in patients with hepatic injury (4.24 +/- 1.98 micrograms/l), diabetes (3.44 +/- 2.36 micrograms/l) and myocardial infarction (3.64 +/- 1.85 micrograms/l) were not statistically different (P > 0.05) to that found in the control group (healthy subjects) (3.68 +/- 2.27 micrograms/l). This result could be related to the fact that the regulation of As in the human organism is independent of these diseases. Measured As concentrations in the eight basic health zones of the study area were not statistically different (P > 0.01). This fact demonstrates the existence of a similarly low environmental As distribution in coastal and mountainous zones.

Serum selenium levels as indicators of body status in cancer patients and their relationship with other nutritional and biochemical markers.

A cross-sectional study of serum selenium levels in patients (n = 59) with different types of cancer from southeastern Spain was carried out using hydride generation atomic absorption spectrometry. The subjects were divided into four groups according to the cancer location (respiratory, digestive, haematological and gynaecological groups). Serum selenium levels in all patients (54.41 +/- 24.80 mg/l) were significantly lower (P < 0.001) than those determined in control groups [healthy subjects from the same area (n = 130) and institutionalized elderly people (n = 93)]. Mean serum selenium concentrations were not significantly different among the four groups considered (P > 0.05). Linear regression analyses performed on serum selenium levels and biochemical markers (total cholesterol, triglycerides, transaminases, uric acid and urea) did not establish any statistically significant correlation (P > 0.05). No significant relationships between serum selenium concentrations and sex or age of patients was observed (P > 0.05). Given the marked overlap between the two ranges of the populations (the means are within approx. 1/2 S.D.) the predictive values of serum selenium are low. Thus, there is indeed a statistical significance between the means, but selenium cannot be used to determine whether or not a patient has cancer disease.

Zinc and copper concentrations in serum from Spanish women during pregnancy.

A cross-sectional study of serum zinc (Zn) and copper (Cu) levels in 31 healthy pregnant women and 51 healthy, nonpregnant controls living in the Mediterranean area of Granada, Spain, was performed. The subjects were divided into two groups: Group A, consisted of pregnant women in three categories according to the trimester of pregnancy, and Group B consisted of nonpregnant women acting as controls. In pregnant women, serum Zn levels were found from 0.300-1.340 mg/L and serum Cu from 0.936-2.304 mg/L, whereas in the nonpregnant women group, the mean serum levels were 0.947+/-0.265 mg/L for Zn and 1.092+/-0.365 mg/L for Cu. Serum Zn progressively decreased with gestation. Mean Zn levels were 0.829+/-0.253, 0.846+/-0.329, and 0.620+/-0.142 mg/L, corresponding to the first, second, and third trimesters of pregnancy, respectively. Serum Zn concentrations were significantly lower in pregnant women as compared to controls: 0.712+/-0.236 mg/L vs 0.947+/-0.265 mg/L, respectively (p < 0.05). In contrast, Cu levels increased with period of gestation from 1.053+/-0.498 mg/L in the first trimester to 1.616+/-0.304 mg/L in the second and 1.689+/-0.344 mg/L in the third. Serum Cu levels in the second and third trimesters of pregnancy were significantly higher (p < 0.05) than those determined during the first trimester and for nonpregnant controls. Both Zn and Cu during pregnancy did not appear to be dependent on the subject's age (p > 0.05).

Downmodulation of HLA class I expression by dexamethasone in MCF-7 cell line.

Several reports have shown the importance of MHC class I antigens in enabling the host to regulate tumour growth in vivo. Glucocorticoid hormones have strong immunosuppressive effects and are known to be regulators of gene transcription. In this report the expression of Major Histocompatibility Complex (MHC) class I antigens in six breast carcinoma cell lines have been studied before and after treatment with the synthetic glucocorticoid dexamethasone. Hence, HLA class I expression in the MCF-7 cell line was down-regulated in the presence of dexamethasone. This down-modulation of expression appeared to be mediated by transcriptional mechanisms, as revealed by HLA-class I mRNA levels.