A. Cabrera de León

Androgens and androgen receptors in breast cancer.

Aromatase (CYP19) converts adrenal and ovarian androgens into estrogens, which supports the growth of estrogen-dependent breast cancers. Anti-aromatase agents are displacing antiestrogens as the first-line treatment for estrogen receptor positive breast cancers. Androgens can act as estrogen precursors, but besides this capability they can also directly act on breast cancer cells by binding to androgen receptors, which are present in the majority of breast cancer specimens. Epidemiological and clinical evidences suggest that higher levels of circulating androgen increase the risk of developing breast cancer. Androgen receptor gene polymorphisms which render the more transcriptionally active receptors have been related to a lower risk of breast cancer. It is currently accepted that androgens act as antiproliferative agents in the presence of estrogens in some breast cancer cell lines. However, emerging evidence suggests that direct androgenic activity might also stimulate cell growth in a subset of estrogen-resistant breast tumors. Here we discuss the supporting evidence which proposes that androgens themselves are actively involved in breast carcinogenesis and its clinical behaviour.

Impaired fasting glucose, ancestry and waist-to-height ratio: main predictors of incident diagnosed diabetes in the Canary Islands.

Diabet. Med. 29, 399–403 (2012)

Serum Resistin and Polymorphisms of Androgen Receptor CAGn and GGNn and Aromatase TTTAn

There is evidence that androgens are regulators of insulin resistance (IR), and may be involved in the regulation of resistin, a cytokine that has been related with IR. Earlier studies found that androgen receptor length polymorphisms CAGn and GGNn and the aromatase polymorphism TTTAn may influence receptor or enzyme activity and serum concentrations of androgens. This study was designed to determine whether polymorphism length was related to serum resistin concentration and to other variables related with IR. In 1,580 persons chosen randomly from the general population of the Canary Islands (Spain), we measured polymorphism length, waist circumference, waist/hip ratio, BMI, and serum glucose concentration. In smaller subgroups, we also measured C‐peptide (n = 677), resistin (n = 583), and leptin concentration (n = 754) and estimated IR (homeostasis model assessment‐IR (HOMA2‐IR)). In men, polymorphism length correlated with resistin concentration (CAGn, r = 0.13, P = 0.031; TTTAn, r = 0.15, P = 0.005; GGNn, r = −0.15, P = 0.026), and the correlations were confirmed in multivariate regression models. The length of CAGn and TTTAn correlated inversely with C‐peptide (r = −0.13, P = 0.016 and r = −0.21, P < 0.001, respectively) and with estimated IR (r = −0.12, P = 0.032 and r = −0.19, P = 0.001, respectively). In men, length of the CAGn, GGNn, and TTTAn was associated with serum resistin concentration. These results support the hypothesis that androgens may be involved in the regulation of resistin. Resistin may be a link between IR and androgens.

Inverse association between serum resistin and insulin resistance in humans

AIM To determine how serum concentrations of resistin are distributed in humans in relation to insulin resistance, type 2 diabetes, and obesity. METHODS Cross-sectional, descriptive study carried out in a random sample (n=713, 43% men, 18-75 years) of general population of inhabitants of the Canary Islands (Spain). Serum resistin concentration, HOMA2-IR, anthropometric parameters, drug consumption and physical activity were recorded. RESULTS There were no differences in resistin concentration between participants with and without diabetes (3.1+/-0.2 vs. 3.2+/-0.1ng/mL; p=0.566), or between obese and non-obese participants (3.1+/-0.1 vs. 3.2+/-0.1ng/mL; p=0.803). Individuals with abdominal obesity (waist-hip ratio [WHR] >or=1 in men or >or=0.9 in women) had lower concentrations of resistin (3.0+/-0.13 vs. 3.4+/-0.1ng/mL; p<0.001). The correlations between resistin and HOMA2-IR (r=-0.231; p<0.001) and between resistin and WHR (r=-0.202; p<0.001) were inverse. Multivariate analysis corroborated the inverse association of this cytokine with HOMA2-IR, WHR and, in women, also retained in the model the direct association between resistin and physical activity and the inverse association between resistin and antihypertensive agents. CONCLUSIONS In this population resistin is inversely associated with insulin resistance and abdominal obesity.

Tabaquismo en adolescentes. Prevalencia estimada mediante declaración y cotinina sérica

Resumen Fundamento la actual epidemia de tabaquismo es responsable de mas muertes que ninguna otra anterior. La jovenes son el principal objetivo de la publicidad de la industria tabaquera. En este estudio se pretende averiguar la prevalencia de tabaquismo en adolescentes y su entorno, asi como la concordancia entre encuesta y cotinina serica y la prevalencia total de exposicion (activa mas pasiva). Sujetos y Metodos Estudio transversal en 439 alumnos de educacion secundaria. Se les realizo extraccion de sangre y un cuestionario anonimo sobre su consumo de tabaco y el existente en su entorno. Se analizo la concordancia entre ambos metodos. Resultados El 56% de los adolescentes habia fumado en alguna ocasion. La prevalencia declarada de tabaquismo fue del 34% (IC95%= 29,49-38,51), llegando al 40% en las chicas y al 23% en los chicos. La concordancia entre cotinina y declaracion solo fue alta para fumadores activos (Kappa = 0,68 para uno o mas cigarrillos/dia y 0,76 para 10 o mas cigarrillos/ dia). La prevalencia de tabaquismo en el entorno familiar, social y escolar era significativamente mas alta entre los fumadores (80%, 71% y 88%, respectivamente) que entre los no fumadores (65%, 24% y 78%). La combinacion de cuestionario mas cotinina detecto una prevalencia total de exposicion superior al 64%. Conclusiones La altisima prevalencia de exposicion al tabaco y la asociacion entre el consumo de los adolescentes y el de su entorno reclaman programas educativos contra el tabaco que incluyan los ambitos familiar, social y escolar. La concordancia entre declaracion y cotinina es buena solo a partir de frecuencias diarias de consumo.

Cytokine profile in collagen-induced arthritis: differences between syngeneic and allogeneic pregnancy.

Abstract.Objective:To identify the differences in cytokine profile between allogeneic and syngeneic pregnancy in mice with collagen-induced arthritis (CIA).Methods:Mice (strain B10.RIII) were injected with bovine collagen. Females were mated with males of the same strain (syngeneic pregnancy) or with males of strain B10. Q (allogeneic pregnancy). Concentrations of cytokines were measured during pregnancy and after delivery, and the onset and evolution of arthritis was followed in all female animals throughout the study period.Results:In female mice that developed CIA, cytokine concentrations were lower in allogeneic pregnancies than syngeneic pregnancies. When paired cytokine concentrations were compared in each animal during and after pregnancy, MCP-1 was lower during gestation than after delivery in both groups of pregnant mice, IL-6 was lower during gestation than after delivery only in allogeneic pregnancies, and IL-10 was lower during gestation than after delivery in allogeneic pregnancies, whereas in syngeneic pregnancies IL-10 was higher during gestation than after delivery.Conclusions:Allogeneic pregnancy was associated with less arthritis because of lower concentrations of proinflammatory cytokines (IL-6 and others), not because of an increase in the concentration of antiinflammatory cytokines (IL-10).

Anti-ENA profiles related with anti-SS-A/Ro. The detection of Ro52 and Ro60 according to the presence of SS-B/La, and ANA pattern and titer

Anti-Ro52 (Ro52) and anti-Ro60 (Ro60) antibodies are associated with different clinical entities. We investigated their relationship with the presence of anti-SS-B/La (SSB) antibody, the pattern and titer of antinuclear antibody (ANA), and the variations in antibody profiles related with anti-SS-A/Ro (SSA) positivity. Our aim was to develop a strategy to increase the efficiency of anti-extractable nuclear antigen (ENA) determinations. Statistical analyses were based on the Chi-squared test for categorical variables, the Mann-Whitney U test to compare profiles, and the odds ratio (OR) and 95% confidence interval (95% CI) to estimate the risk of variability. We analyzed 800 SSA-positive samples with Ro52 or Ro60 reactivity. The most frequent profiles were Ro52+Ro60+SSB (n=349, 43.6%); Ro52+Ro60 (n=126, 15.8%); Ro52 (n=121, 15.1%) and Ro60 (n=71, 8.9%). In samples positive only for SSA and an ANA titer ≤1:640, the most likely profile was positivity for either Ro52 or Ro60, whereas when the ANA titer was >1:640, positivity for both Ro52 and Ro60 simultaneously was more likely (p<0.001). In samples positive for both SSA and SSB, the most likely profile was Ro52+Ro60+SSB regardless of the ANA titer (p=0.001). When only SSA was positive and the ANA staining pattern was nucleolar, centromeric or cytoplasmic, Ro52 positivity was most likely (p<0.001). When both SSA and SSB were positive, both Ro52 and Ro60 were likely to be positive regardless of the ANA staining pattern. In 28.7% of the patients the profile was variable. Variability was significantly greater in those with the SSA profile (23/67) than with the SSA+SSB profile (15/105; OR=1.9, 95% CI=1.1-3.3; p=0.025), and the difference in variability was greatest between the Ro52+Ro60 profile (8/23) and the Ro52+Ro60+SSB profile (8/68; OR=4.2, 95% CI=1.9-9.5; p<0.001). We conclude that to increase efficiency in the immunology laboratory, positivity for Ro52 and Ro60 individually or simultaneously can be deduced from SSB status and the ANA pattern and titer. In general, for the most frequent anti-ENA findings, priority should be given to retesting autoantibodies not detected in the initial analysis.