Bibiana Fabre

Lipoproteins, sex hormones and inflammatory markers in association with prostate cancer

Objective. To evaluate lipoprotein profile and sex hormones in patients with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their possible associations with some inflammatory markers linked to PCa. Methods. A total of 150 men (50–65 years), matched by age and body mass index (BMI), included in this study and divided into three groups according to total prostate specific antigen (PSA), digital rectal examination and prostate biopsy: 50 PCa, 50 BPH and 50 controls. Total cholesterol (Chol), HDL-chol, LDL-chol, triglycerides (TG), total testosterone (T), free T (FT), bioavailable T (BioT), estradiol and SHBG were measured. The free androgen index (FAI) and TG/HDL-chol were calculated. In 25 PCa and 25 controls, C-reactive protein (hs-CRP), adiponectin and insulin were determined. Results. Patients with PCa showed higher TG/HDL-chol and diminished HDL-chol than Controls and BPH. PSA correlated inversely with HDL-chol and directly with TG/HDL-chol. FAI, FT, BioT and estradiol levels were higher, and SHBG and adiponectin were lower in PCa than in Controls. No differences were found in androgens between BPH and PCa. Conclusion. Our most novel findings are that the patients with PCa presented lower total Chol and HDL-chol and higher TG/HDL-chol than BPH and Controls. Patients with PCa showed higher androgens and lower adiponectin than Controls.

Hair cortisol: A new tool for evaluating stress in programs of stress management.

AIMS Longitudinal and experimental studies have shown that chronic stress contributes to the onset and progression of different diseases. Although it is not possible to eliminate stress completely, people can learn to manage it by participating in different kinds of stress management interventions. This study examined the effectiveness of stress management interventions on neuroendocrine responses in stressed students and health professionals, by measuring hair cortisol in comparison to salivary cortisol. MAIN METHODS Salivary and hair cortisol measurements were performed in 37 subjects (31women, 6 men; mean age 34.0±10.6) who attended to a Coping Stress and Quality of Care Program at the University of Buenos Aires. Cortisol was measured at the beginning and at the end of the program. The State-Trait Anxiety Inventory STAI was used to evaluate state and trait anxiety. KEY FINDINGS In subjects who completed the program, no differences were observed in salivary cortisol levels between the first and the last session. However, in these subjects, hair cortisol obtained in the last session was significantly lower than hair cortisol in the first session. SIGNIFICANCE Hair cortisol appears to be a better biomarker than salivary cortisol for evaluation of the effectiveness of a stress reduction program and it seems to be a better indicator of stress system dysregulation as well.

Association between testosterone levels and the metabolic syndrome in adult men

Abstract Objective: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years. Methods: Six hundred and sixty men (45–70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated. Results: The presence of MS was inversely associated with testosterone (χ2, p < 0.001), independently of age (OR 0.802, CI 95%: 0.724–0.887, p < 0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p < 0.0001) and negatively with body mass index (BMI)(r: −0.29, p < 0.0001), WC (r: −0.26, p < 0.0001), TG (r: −0.20, p < 0.0001), TG/HDL-chol (r: −0.20, p < 0.0001), glucose (r: −0.11, p = 0.005) and MS score (r: −0.23, p < 0.0001). Conclusions: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.

Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease.

Abstract Objectives: To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa. Subjects and methods: Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups. Results: Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3–28.0) versus 4.8 (1.1–12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20–90) versus 29.0 (20–118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups. Conclusions: It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

Relationship between cortisol, life events and metabolic syndrome in men

Psychological factors and stressful life events (LE) are considered to play a role in the onset of the metabolic syndrome (MS). We tested the association between LE and cortisol, a marker of chronic stress, with the risk of developing MS and their interaction. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 149 healthy men (mean ± SD age, 58.6 ± 7.7 years) were included in this study. Participants were assessed by the Holmes and Rahe questionnaire about their experience of LE during the previous 1–5 years. MS was diagnosed according to National Cholesterol Education Program-Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Serum cortisol was measured at 08:00–09:00 h. Participants with MS (IDF criteria) reported significantly more past LE (p = 0.009) and greater summed weight of LE (p = 0.049) than those without MS. Furthermore, LE interacted with cortisol in relation to MS: in men with increased serum cortisol levels ( ≥ 13.7 μg/dl), number of LE significantly predicted MS-status (relative risk (RR) = 1.16, p = 0.03), whereas in men with low cortisol, LE were unrelated to MS (p = 0.52). We conclude that LE were significantly more prevalent in men with the MS than without the MS, according to IDF criteria, independent of the effects of age and body mass index, especially in men with increased serum cortisol levels.

Measurement of fasting salivary insulin and its relationship with serum insulin in children.

Background Saliva is a useful sample as a source of hormones for the diagnosis of different diseases, particularly in pediatric patients and aged individuals, because saliva offers a noninvasive and stress-free alternative to serum collection. The aim of this study was to validate a salivary insulin method and to check its clinical application in pediatric patients. Methods Saliva samples were collected from 130 boys and 147 girls aged 6–14 years. Salivary and serum insulin levels were measured with the chemiluminescent automated method Access (Beckman Coulter, Brea, CA, USA). Serum blood glucose levels were measured with the glucose oxidase method in an autoanalyzer. Results The precision profile of the method was determined for six aliquots of different concentrations from pools of saliva, and the coefficients of variation (CV) were 2.4% for 1 μUI/ml, 4% for 0.5, 8.9% for 0.25, 19% for 0.12, 28% for 0.06, and 38% for 0.03 μUI/ml, being the functional sensibility (concentration corresponding to a 20% CV) 0.12 μUI/ml. Insulin recovery was 100.13%. Salivary insulin levels diminished 29.8% in samples stored during 7 days at 2–8 °C. Differences in insulin values were not observed when samples were stored at −20 °C during 7 days. The methods used to measure salivary and serum insulin correlated significantly (r=0.92, P<0.001). However, at levels of serum insulin >20 μUI/ml, this correlation declined (r=0.57, P=0.083). Conclusion The proposed method for salivary insulin measurement showed convenient analytical characteristics.

Life events, cortisol and levels of prostate specific antigen: a story of synergism.

BACKGROUND Previous studies have tested the relationship between stressful life events (LE) and cancer onset, but inconsistent results have been found. One possibility is that the LE-cancer relation may depend on other biological factors pertinent to stress and cancer. METHODS This study examined the relationship between LE and prostate specific antigen (PSA) levels, a tumor marker, and whether cortisol mediates or moderates a LE-PSA relationship. During a voluntary screening for prostate cancer risk, 139 men (mean age=57.3 years) were assessed with the Holmes and Rahe questionnaire about their LE during the past 1-5 years, and their PSA and serum cortisol levels were measured. RESULTS LE and cortisol alone were unrelated to PSA. However, statistically controlling for age, body mass index and the ratio of triglycerides to HDL cholesterol, we found evidence for a synergistic interaction between LE and cortisol. Among men with low cortisol, number of LE were inversely and significantly correlated with PSA (r=-0.265, p<0.05), while in men with high cortisol, number of LE were positively and significantly correlated with PSA (r=0.344, p<0.01). These results more consistently stemmed from the effects of uncontrollable LE. Similar results were found, using a clinically significant PSA cut-off. CONCLUSIONS These results suggest considering the joint effects of psychosocial and biological factors in relation to possible cancer risk, where the hypothalamic pituitary adrenal axis may moderate stress-cancer risk associations.

HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

Tuberculosis (TB) is the leading cause of death among HIV‐positive patients. The decreasing frequencies of terminal effector (TTE) CD8+T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV–TB patients. Here, we aimed to study Mtb‐specific cytotoxicity, IFN‐γ secretion, memory status of CD8+T cells, and their modulation by DHEA during HIV–TB coinfection. CD8+T cells from HIV–TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T‐cell frequencies compared to healthy donors both in total and Mtb‐specific CD8+T cells. Notably, CD8+T cells from HIV–TB patients displayed higher Terminal Effector (TTE) CD45RAdim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD‐1 expression levels on CD8+T cells from HIV–TB patients increased although restricted to the CD27+ population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8+T cells and in vitro DHEA treatment enhanced Mtb‐specific cytotoxic responses and terminal differentiation in CD8+T cells from HIV–TB patients. Our data suggest that HIV–TB coinfection promotes a deficient CD8+ T‐cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8+T‐cell functions during HIV–TB coinfection.

Life events are positively associated with luteinizing hormone in middle age adult men: role of cortisol as a third variable.

Abstract Previous studies have tested the relationship between chronic stress and sex hormones, but inconsistent results have been found. One possibility is that this association may depend on other biological factors. This study examined the relationship between stressful life events (LE) and sex hormones in men, and whether cortisol is involved in this relationship. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 139 healthy men (mean ± SD age, 57.8 ± 5.7 years) were included in this study. Participants were assessed with the Holmes and Rahe questionnaire in relation to their experience of LE during the previous 1–5 years. Salivary and serum cortisol was measured at 08:00–09:00 h, as well as luteinizing hormone (LH), total testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031, respectively). In a multiple regression analysis, LE-sum explained an additional and significant 10.4% of the variance in LH levels, after statistically controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) = 6.61, p < 0.05). Importantly, cortisol interacted with LE in relation to total testosterone. In men with high cortisol values (≥15.4 µg/dl), there was a statistically significant positive relationship between LE number and total testosterone levels (p = 0.05), while LE were unrelated to total testosterone in men with low cortisol. LE correlated with sex hormones, predicting LH values, and in men with high cortisol levels shows a possible moderator effect of cortisol on the relationship between LE and total testosterone.

Evaluation of an automated chemiluminescent immunoassay for salivary cortisol measurement. Utility in the diagnosis of Cushing's syndrome.

Fil: Repetto, Esteban Martin. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Bioquimica Clinica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina