Adenovirus 36 seropositivity is related to the expression of anti-adipogenic lncRNAs GAS5 and MEG3 in adipose tissue obtained from subjects with obesity.

BACKGROUND: Human Adenovirus D-36 (HAdV-D36) promotes adipogenesis in cellular and animal models and may contribute to the development of human obesity. Induction of PPARγ by HAdV-D36 seems to have a central role in the maintenance of adipogenic status. There is limited information about epigenetic mechanisms contributing to this process in human adipose tissue. This study evaluated the expression of lncRNAs (ADINR, GAS5 and MEG3) and miRNAs (miR-18a and miR-140) involved in the adipogenic process in visceral adipose tissue (VAT) of subjects with obesity with previous HAdV-D36 infection (seropositive) and unexposed (seronegative) subjects with obesity. METHODS: Individuals with obesity were grouped according to the presence of antibodies against HAdV-D36 (Seropositive: HAdV-D36[+], n = 29; and Seronegative: HAdV-D36[-], n = 28). Additionally, a group of individuals without obesity (n = 17) was selected as a control group. The HAdV-D36 serology was carried out by ELISA. Biopsies of VAT were obtained during an elective and clinically indicated surgery (bariatric or cholecystectomy). RNA extraction from VAT was performed and the expression of PPARG and non-coding RNAs was evaluated by qPCR. RESULTS: HAdV-D36[+] individuals had lower expression of anti-adipogenic lncRNAs GAS5 (p = 0.016) and MEG3 (p = 0.035) compared with HAdV-D36[-] subjects with obesity. HAdV-D36[+] subjects also presented increased expression of the adipogenic miRNA miR-18a (p = 0.042), which has been reported to be modulated by GAS5 through a RNA sponging mechanism during adipogenic differentiation. Additionally, an inverse correlation of GAS5 with PPARG expression was observed (r = -0.917, p = 0.01). CONCLUSION: Our results suggest that HAdV-D36 is related to non-coding RNAs implicated in adipogenesis, representing a potential mechanism by which previous HAdV-D36 infection could be associated with the long-term maintenance of adipogenic status, probably through the GAS5/miR-18a axis.

Adenovirus 36 seropositivity is related to obesity risk, glycemic control, and leptin levels in Chilean subjects.

BACKGROUND: Adenovirus 36 (Ad-36) has been associated to adiposity in animal and in vitro studies. Ad-36 seropositivity has also been reported to contribute to obesity risk in children and adult populations. We investigated the relationship of Ad-36 serology with obesity and metabolic parameters in a Chilean population. SUBJECTS AND METHODS: Clinical and anthropometric data were obtained and blood samples were drawn from 99 lean (BMI: 18.5-24.9 kg/m2) and 151 obese (BMI > 30 kg/m2) subjects. Laboratory tests included lipid profile as well as glucose, insulin, leptin, and adiponectin levels. Ad-36 seropositivity was evaluated in serum samples by enzyme-linked immunosorbent assay. RESULTS: Seroprevalence of Ad-36 was higher in the obese group (58%) than in lean controls (34%) demonstrating that individuals previously infected with Ad-36 have higher risk of obesity in the study population (OR: 2.67, 95%CI: 1.58-4.51, p < 0.001). Interestingly, Ad-36 was related to lower concentrations of triglycerides and VLDL cholesterol in lean subjects (p = 0.049) and lower leptin in obese individuals (p = 0.014). Previous Ad-36 infection was also related to lower glycemia, insulinemia, and HOMA-IR (p < 0.05) in obese subjects who were not under antidiabetic drugs. CONCLUSIONS: Our results provide evidence of the contribution of previous Ad-36 infection to an increased risk of obesity in adult Chilean population. Ad-36 seropositivity was also associated to lipid profile, glycemic control, and leptin levels in adult Chilean population.

Influence of adenovirus 36 seropositivity on the expression of adipogenic microRNAs in obese subjects.

BACKGROUND: Infection by Adenovirus 36 (Ad-36) has been associated with adipogenesis using cell and animal models, and a high risk of developing obesity has been reported in Ad-36-seropositive individuals. However, molecular mechanisms involved in the maintenance over the years of adipogenesis associated with Ad-36 has not been investigated in human adipose tissue. Epigenetic mechanisms, such as micro-RNAs (miRNAs) that regulate gene expression at the post-transcriptional level, have shown an important role in the development and maintenance of metabolic diseases. AIM: This study investigated the expression of miRNA associated with the adipogenic process in visceral adipose tissue from obese individuals according to Ad-36 serology. METHODS: Obese individuals were separated according to their status of Ad-36 serology in seropositive (Ad-36 (+); n = 29) and seronegative (Ad-36 (-); n = 28) groups. Additionally, a group of lean controls (n = 17) was selected to compare with obese individuals. Biopsies of visceral adipose tissue were obtained to evaluate miRNA and gene expression. The study of Ad-36 serology was carried out by ELISA. The expression of pro-adipogenic (miR-17 and miR-210) and anti-adipogenic (miR-155, miR-130 and miR-27a) miRNAs was evaluated using Taqman advanced miRNA assays by qPCR. The expression of adipogenes encoding LEP, ADIPOQ, and PPARγ was evaluated by Taqman predesigned assays through qPCR. RESULTS: The obese group had higher LEP (p < 0.001) and PPARγ (p = 0.016) expression and lower ADIPOQ expression (p = 0.017), and also had higher expression of miR-210 (p = 0.039), whereas lower expression of miR-155 (p = 0.019) and miR-27a (p = 0.028) as compared to lean controls. Higher PPARγ expression (p = 0.008), but no influence on LEP or ADIPOQ expression was observed in Ad-36 (+) group. Those seropositive individuals also had higher expression of the miR-17 (p = 0.028) and lower levels of miR-155 (p = 0.031) in adipose tissue as compared to seronegative subjects. CONCLUSIONS: Individuals with previous infection by Ad-36 had higher expression of the pro-adipogenic miR-17 and lower expression of the anti-adipogenic miR-155, which could lead to an increased adipogenic status by positively modulating PPARγ expression in adipose tissue from obese subjects.

Ectopic pituitary adenoma of the TSH-secreting sphenoidal sinus with excellent response to somatostatin analogs. Theory of the embryogenesis and literature review from a clinical case.

Ectopic thyrotropin-secreting pituitary adenomas are rare, with only 10 published cases. We report the case of a 52-year-old woman who was referred for primary hypothyroidism, who showed clinical signs of hyperthyroidism and had been under treatment with levothyroxine. Her exams revealed high levels of thyroid stimulating hormone (TSH), at odds with free thyroxin (FT4) and raised triiodothyronine (T3), which remained elevated after medication suspension, suggesting possible central hyperthyroidism. Sellar MRI showed normal pituitary gland, with a mass in the sphenoid sinus of 24 mm. A possible ectopic TSH secreting pituitary tumor of sphenoid sinus was hypothesized. After a intramuscularly (IM) single dose of a sustained-relase of a somatostatin analog (octreotide) 20 mg, plasma levels of thyroid hormones were normalized and a significant tumor reduction was demonstrated in MRI control at 7-weeks' follow-up. The tumor was removed by transsphenoidal endoscopy, and the biopsy confirmed an adenoma with positive immunostaining for TSH and GH. Hyperthyroidism recurrence was observed in hormonal controls 4 weeks after surgery. Treatment with sustained-release octreotide was reinitiated, every 60-days for two years, with normalization of the thyroid hormone profile, but with a residual lesion with the appearance of a tumor in the MRI. A second tumor resection was performed, achieving sustained hormonal cure and no residual tumor lesion at 2-years' follow-up. To our knowledge, this is the first report of an ectopic thyrotropin-secreting pituitary adenoma of the sphenoid sinus. Clinical and laboratory aspects relevant to this entity are reviewed, emphasizing the usefulness of octreotide in the management of the reported case.

A possible association between primary aldosteronism and a lower beta-cell function.

OBJECTIVE: Primary aldosteronism (PA) is the most common secondary cause of hypertension and recently has been implicated as a cause of impaired glucose tolerance. We investigated the glucose insulin sensitivity and insulin secretion in patients with idiopathic primary aldosteronism. DESIGN: Thirty PA patients and 60 essential hypertensive (EH) patients as controls were included, matched (1: 2) by their body mass index (BMI) (29.9 +/- 4.3 versus 29.8 +/- 5.8 m/kg), age (53.7 +/- 9.4 versus 59.9 +/- 8.6 years old) and gender (male/female: 8/22 versus 17/43). In all patients, we measured insulin, total cholesterol, triglycerides, C-peptide and fasting glucose levels. Homeostasis model assessment for insulin resistance (HOMA-IR) and HOMA of pancreatic beta-cell function (HOMA-betaF) indexes were calculated. We also evaluated the response to spironolactone in 19 PA patients. RESULTS: PA patients had higher levels of glucose (5.2 +/- 0.7 versus 4.9 +/- 0.7 mmol/l; P = 0.017). Insulin levels (10.7 +/- 6.5 versus 11.5 +/- 5.8 uUI/ml, P = 0.525) and HOMA-IR (2.51 +/- 1.59 versus 2.45 +/- 1.29 uUI/ml x mmol/l, P = 0.854) were similar in both groups. HOMA-betaF index (138.9 +/- 89.8 versus 179.8 +/- 100.2%, P = 0.049) and C-peptide (0.83 +/- 0.63 versus 1.56 +/- 0.84 ng/dl, P = 0.0001) were lower in PA patients. Potassium was normal in both groups. Negative correlations between serum aldosterone/plasma renin activity (SA/PRA) ratio and HOMA-betaF, and between C-peptide and SA levels were found in all patients. After the spironolactone treatment, we found an increase of C-peptide and insulin levels without changes in HOMA-IR or HOMA-betaF. CONCLUSION: Our results showed differences in glucose metabolism between PA patients and those with hypertension suggesting that these findings could probably be determined by a lower beta-cell function influenced by aldosterone. These findings highlight the importance of aldosterone in glucose metabolism.

Urinary free cortisol is not a biochemical marker of hypertension.

BACKGROUND: Increasing evidence suggests that glucocorticoids might play a role in blood pressure (BP) control. These reports show that cortisol (F) can increase the BP acting on the mineralocorticoid receptor in kidney, brain, heart, and blood vessel. The aim of this study was to evaluate the effects of F in the renal salt and water reabsorption in essential hypertensive patients (EH). METHODS: We studied 364 EH and 102 normotensive (NT) subjects. We obtained 24-h urine to measure urinary free cortisol (UFF) and creatinine (Cr). The upper limit of the UFF/Cr ratio was calculated from NT subjects. Patients with a high UFF/Cr ratio underwent dexamethasone suppression test (DST). Blood samples were used to determine plasma renin activity (PRA), aldosterone (SA), F, cortisone (E), urinary Na/K ratios, adrenocorticotrophic hormone levels, and also to purify lymphocytes for binding assays and genetic analysis. RESULTS: In EH subjects the UFF/Cr and F/E ratios were higher than in normotensives (48.3 microg/g [33.6 to 57.5 microg/g] v 32.6 microg/g [5.6 to 34.6 microg/g], P < .001 and 3.9 microg/g [3.3 to 4.8 microg/g] v 3.0 microg/g [2.4 to 3.6 microg/g], respectively), whereas the SA and PRA levels were similar. The upper limit value for UFF/Cr was set at 51.6 microg/g. The EH patients with high UFF/Cr (123/364, 34%) had lower PRA (1.5 ng/mL/h [0.9 to 2.5 ng/mL/h] v 2.0 ng/mL/h [1.1 to 3.0 ng/mL/h], P = .012, SA levels (7.1 ng/dL [4.1 to 10.5 ng/dL] v 7.9 ng/dL [5.2 to 11.0 ng/dL], P = .045) and Na/K ratios (3.6 [2.8 to 5.8] v 4.0 [3.1 to 6.6], P < or = .05) than those with normal UFF/Cr ratios. We found a slight negative relationship between UFF/Cr and PRA (r = -0.117, P = .031), SA (r = -0.096, P = .058) and Na/K ratios (r = 0.176, P = .059). We did not find significant differences in serum F/E ratios between EH patients with high or normal UFF/Cr (3.9 [3.3 to 5.1] v 3.8 [3.2 to 4.7], P = not significant [NS]) or a correlation between F/E ratio and UFF excretion (r = 0.032, P = NS). We did not find any association between UFF/Cr with systolic BP (P = .349) or diastolic BP (P = .895). Forty EH with the highest UFF/Cr values underwent the DST, which resulted in suppressed serum F in all of them. Binding assays in 4 of 13 EH with the highest UFF/Cr ratio showed a low affinity to dexamethasone (K(d) 13.7 to 33.0 nmol/L). The polymerase chain reaction (PCR) amplification of the GR gene (ligand-binding domain exons) did not show mutations or gross alterations. CONCLUSIONS: We found an EH subpopulation with abnormally high values of UFF but evidence of only a minor mineralocorticoid action, which was not directly related to the BP elevation, suggesting that another alternative mechanism could be triggering the F-induced hypertension. The origin of hypercortisoluria was not elucidated; however, a subtle glucocorticoid resistance was found in some cases.

[Possible pathogenetic role of 11 beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) gene polymorphisms in arterial hypertension]. / Regiones polimórficas del gen 11 beta-hidroxiesteroide deshidrogenasa tipo 1 (11betaHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico.

BACKGROUND: Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11betaHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over-expression of this enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11betaHSD2 impaired patients. Several polymorphisms have been reported in HSDl IB 1 gene (CAI5, CAI9 and InsA83557), which could modify HSDl IB 1 gene expression or activity. AIM: To determine the distribution and prevalence of CAI5, CAI9 and InsA83557 in the HSDl IBl gene, and to correlate these results with biochemical parameters in cortisol/ ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). PATIENTS AND METHODS: We studied 113 EH patients (76 non-obese and 37 obese, with a body mass índex >30 kg/m(2)) and 30 normotensive adults (NT). In each patient, we measured serum levels of E E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8% polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibrium by the Hardy-Weinberg (H-W) equation. RESULTS: We found all three polymorphisms in the EH and the NT group, both in genetic equilibrium. In obese essential hypertensives, the CAI5 polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r = 0.220, p 0.009). The InsA83557polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). CONCLUSIONS: The CAI5 and CAI9 polymorphism correlated with changes in biochemical parameters in HPA and RAA axis of obese essential hypertensives. These changes may result in modifications in the expression of 11betaHSD1, leading to increased cortisol and aldosterone levels independent of ACTH and renin control, respectively.

[Health psychology: a key to understand therapeutic adherence]. / Psicología de la salud: una clave para comprender el fenómeno de la adherencia terapéutica.

The lack of compliance with treatment is a public health problem that affects the patient's quality of life, avoids an objective assessment of therapeutic effectiveness and may even cause death. Non compliance can be considered an one-dimensional problem that only depends of patients's responsibility. However, Health Psychology has generated theoretical models that allow the prediction and understanding of therapeutic compliance. It also expands the responsibility to other agents involved in the therapeutic process, specifically health care providers and health systems.

Factores psicosociales asociados a la adherencia al tratamiento de la diabetes mellitus tipo 2 / Psychosocial factors associated with adherence to treatment of type 2 diabetes mellitus

Se han reportado bajas tasas de adherencia al tratamiento de enfermedades crónicas (50 por ciento). Asimismo, los factores psicosociales estarían relacionados con la adherencia al tratamiento. Con el propósito de identificar la relación que existe entre factores psicosociales y la adherencia al tratamiento de la DM2 en usuarios del sistema de salud pública chileno, se diseñó un estudio no experimental transversal correlacional (n = 50, edad promedio 60,76 años). Se autoadministraron encuestas para evaluar estrés y estilo de afrontamiento, sintomatología depresiva, percepción de apoyo social y adherencia al tratamiento. 40 por ciento de los pacientes presenta valores de hemoglobina glicosilada (Hb1Ac) mayores a 9 por ciento, mientras que un 66 por ciento de los participantes presenta desde moderados a altos niveles de estrés. En promedio durante los últimos 7 días los participantes han cumplido con la dieta general en 4,37 días, han consumido frutas y verduras en 3,14 días y han realizado exámenes de glicemia en 1,1 días. Existe una correlación directa entre el estrés y la hemoglobina glicosilada. El apoyo social y la sintomatología depresiva no se asociaron con la adherencia al tratamiento pero sí con el estrés. Se confirman pobres cifras de adherencia, y la asociación entre alto estrés y altos índices de Hb1Ac.

It is estimated that rates of non-adherence to chronic diseases are around 50 percent. International studies have reported some psychosocial factors related to treatment adherence. The purpose of the present study was to detect the relationship between psychosocial factors and treatment adherence in a sample of Type 2 Diabetics subjects from a public health institution. To this end, a non - experimental transversal correlational study was designed with a 50 DM2 subjects sample, which average age was 60,76 years old. Self-report measures of stress level, coping style, depressive symptoms, social support perception and treatment adherence, were obtained. The results revealed that 40 percent of participants had glycosylated hemoglobin over 9 percent, and 66 percent of them shown moderate to high stress levels. In average during the last 7 days, the participants have accomplished the diet 4,37 days, consumed fruits and vegetables 3,14 days and took glycemia test in 1,1 days. There is a direct correlation between the stress level and concentrations of glycosylated hemoglobin. Unlike stress, social support and depressive symptomatology was not associated with treatment adherence. These results confirm low levels of treatment adherence and high rates of stress in DM2 patients, as well as its association with high levels of glycosylated hemoglobin.

[Psychological factors associated to patient's treatment compliance in Chilean diabetic teenagers]. / Adherencia al tratamiento en adolescentes diabéticos tipo 1 chilenos: una aproximación psicológica.

BACKGROUND: Treatment compliance among patients with type 1 diabetes mellitus, is low in 50% of diabetic teenagers, becoming a social and medical problem. AIM: To determine psycho-social factors associated to treatment compliance among Chilean diabetic type 1 teenagers. PATIENTS AND METHODS: A non experimental study of 61 diabetic teenagers (age 14.9+/-1.9 years, 37 male). The number of blood glucose determinations, socioeconomic level and practice of sports was measured. Psychological tests were applied to analyze self-efficiency, motivation of achievement, self-esteem and knowledge of the illness and its treatment. As a measure of patient compliance, glycosilated hemoglobin (HB1Ac) was measured. RESULTS: Six patients had a good control of diabetes (HB1Ac <7%), 24 had HB1Ac values between 7 and 8.9, and 31 (51%) had values of 9% or more, considered as a poor diabetes control. The intensified insulin treatment scheme, the knowledge of the illness and its treatment and the sense of self-efficiency, were the factors associated with a better compliance with treatment. Teenagers of higher socio-economical levels had a better compliance with treatment. CONCLUSIONS: Fifty percent of Chilean diabetic teenagers in this sample had a poor control of the disease and the variable knowledge about the disease is the better predictor of patient compliance.

Regiones polimórficas del gen 11ß-hidroxiesteroide deshidrogenasa tipo 1 (11ßHSD1) en hipertensión arterial esencial: Posible rol etiopatogénico / Possible pathogenetic role of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) gene polymorphisms in arterial hypertension

Background: Cortisol has been implicated in hypertension and lately reported to be regulated at the pre-receptor level by the 11ßHSD1 enzyme, which converts cortisone (E) to cortisol (F). Over expression ofthis enzyme in adipose tissue could determine an increase in available cortisol that interacts with the mineralocorticoid receptor (MR) in renal, brain and heart tissue, leading to similar hypertensive effects as in 11ßHSD2 impaired patients. Severa! polymorphisms have been reported in HSDl IB 1 gene (CAI5, CAI9 and InsA83557), which could modify HSDl IB 1 gene expression or activity. Aun: To determine the distribution and prevalence of CAI5, CAI9 and InsA83557 in the HSDl IBl gene, and to correlate these results with biochemical parameters in cortisol/ ACTH (HPA) and renin-angiotensin-aldosterone (RAA) axis in patients with essential hypertension (EH). Patients and Methods: We studied 113 EHpatients (76 non-obese and 37 obese, with a body mass índex >30 kg/m²) and 30 normotensive adults (NT). In each patient, we measured serum levéis of E E, serum aldosterone (SA), plasma renin activity (PRA), adrenocorticotrophic hormone (ACTH), the urinary free cortisol/creatinine (UFF/Cr), F/ACTH and SA/PRA ratios. Each polymorphism was studied by PCR and 8 percent polyacrylamide gel electrophoresis. Statistical associations were evaluated by Pearson correlations and the genetic equilibñum by the Hardy-Weinberg (H-W) equation. Results: We found all three polymorphisms in the EH and the NT group, both in genetic equilibñum. In obese essential hypertensives, the CAI5polymorphism showed association with SA/PRA ratio (r =0.189, p =0.012) and F/ACTH (r =0.301, p 0.048); CA19 also showed correlation with F/ACTH in obese EH (r = 0.220, p 0.009). The InsA83557polymorphism correlated with UFF/Cr in both EH (r =0.206; p =0.03), and in obese EH (r =0.354; p =0.05). Conclusions: The CAI5 and CAI9 polymorphism correlated with changes in biochemical parameters...