[Spontaneous remission of acromegaly and Cushing's disease in older patients. Report of two cases]. / Remisión espontánea de acromegalia y enfermedad de Cushing en adultos mayores. Casos clínicos.

Pituitary diseases such as acromegaly and Cushing's disease require surgical or medical therapy. In some functioning pituitary tumors, a spontaneous remission of hormonal hypersecretion is observed, mainly associated to apoplexy or pituitary infarction. We report the evolution of two female patients older than 70 years at the time of diagnosis, with multiple comorbidities. In case 1, acromegaly was diagnosed at 74 years of age. Sellar CT scan showed a 10-mm adenoma. During her follow-up, IGF1 levels remained normal. Nine years later, a magnetic resonance (MR) showed a 7-mm adenoma. In case 2, clinical and biochemical diagnosis of Cushing's disease was done being 71 years old. Sellar MR showed a 6-mm adenoma. Three years later, urinary cortisol normalized with no changes in adenoma at MR. Seven years later, she remains without clinical or biochemical signs of hypercortisolism. In both cases, no signs of hemorrhage were observed at MR.

Remisión espontánea de acromegalia y enfermedad de Cushing en adultos mayores: casos clínicos / Spontaneous remission of acromegaly and Cushing's disease in older patients: report of two cases

Pituitary diseases such as acromegaly and Cushing's disease require surgical or medical therapy. In some functioning pituitary tumors, a spontaneous remission of hormonal hypersecretion is observed, mainly associated to apoplexy or pituitary infarction. We report the evolution of two female patients older than 70 years at the time of diagnosis, with multiple comorbidities. In case 1, acromegaly was diagnosed at 74 years of age. Sellar CT scan showed a 10-mm adenoma. During her follow-up, IGF1 levels remained normal. Nine years later, a magnetic resonance (MR) showed a 7-mm adenoma. In case 2, clinical and biochemical diagnosis of Cushing's disease was done being 71 years old. Sellar MR showed a 6-mm adenoma. Three years later, urinary cortisol normalized with no changes in adenoma at MR. Seven years later, she remains without clinical or biochemical signs of hypercortisolism. In both cases, no signs of hemorrhage were observed at MR.

[Consensus statement of the Chilean endocrinological society on the role of bariatric surgery in type 2 diabetes]. / Rol de la cirugía bariátrica/metabólica en el manejo de la diabetes mellitus 2. Consenso SOCHED/SCCBM.

Diabetes Mellitus (DM) and obesity are a public health problem in Chile. Bariatric surgery is the most effective treatment alternative to achieve a significant and sustained weight reduction in patients with morbid obesity. The results of controlled clinical trials indicate that, compared to medical treatment, surgery for obese patients with DM2 allows a better control of blood glucose and cardiovascular risk factors, reduces the need for medications and increases the likelihood for remission. Consensus conferences and clinical practice guidelines support bariatric surgery as an option to treat DM2 in Class III Obesity (Body Mass Index (BMI) > 40) regardless of the glycemic control and the complexity of pharmacological treatment and in Class II Obesity (BMI 35-39,9) with inadequate glycemic control despite optimal pharmacological treatment and lifestyle. However, surgical indication for patients with DM2 and BMI between 30-34.9, the most prevalent sub-group, is only suggested. The Chilean Societies of Endocrinology and Diabetes and of Bariatric and Metabolic Surgery decided to generate a consensus regarding the importance of other factors related to DM2 that would allow a better selection of candidates for surgery, particularly when weight does not constitute an indication. Considering the national reality, we also need a statement regarding the selection and characteristics of the surgical procedure as well as the role of the diabetologist in the multidisciplinary team.

[False negative spect parathyroid scintigraphy with sestamibi in patients with primary hyperparathyroidism]. / Análisis de falsos negativos en la cintigrafía SPECT de paratiroides con sestamibi en pacientes con hiperparatiroidismo primario sometidos a cirugía entre 2008-2015 en hospital universitario.

BACKGROUND: 99mTc-sestamibi parathyroid SPECT scintigraphy is a useful tool in the pre-operative study of hyperparathyroidism. False negatives (FN) have been reported in 5.7-14% of the examinations. AIM: To characterize 99mTc-sestamibi FN in cases referred for primary hyperparathyroidism (PHP) to a university hospital. MATERIAL AND METHODS: Descriptive retrospective analysis. We included patients with PHP, studied with SPECT scintigraphy, operated at our center between 2008 and 2015. Clinical and surgical data were recorded; biopsies of the FN were blindly reviewed by one pathologist. RESULTS: One hundred twenty one scintigraphies fulfilled the inclusion criteria. Seven (5.8%) were negative and 114 positive. There was no difference in age, sex and PTH levels between FN and true positive scintigraphies. At surgery, one FN case had two hyperplasic glands and two cases had ectopic glands. Pathology reported adenoma in three cases, hyperplasia in three and carcinoma in one. The largest diameter of the lesion was lower in FN (1.3 and 2.1 cm respectively, p = 0.02) and the proportion of adenomas was higher in true positive cases (29% and 75% respectively; p < 0.01). The interval between scintigraphy and parathyroidectomy was greater in FN with a median of 92 days (range 20 days-3.2 years, p < 0.01). The percentage of oxyphilic cells observed was similar in both groups. CONCLUSIONS: FN parathyroid SPECT scintigraphies in PHP are uncommon. They corresponded to lesions under the equipment's resolution limit and resulted in longer time lags between scintigraphy and surgery.

Análisis de falsos negativos en la cintigrafía SPECT de paratiroides con sestamibi en pacientes con hiperparatiroidismo primario sometidos a cirugía entre 2008-2015 en hospital universitario / False negative spect parathyroid scintigraphy with sestamibi in patients with primary hyperparathyroidism

Background: 99mTc-sestamibi parathyroid SPECT scintigraphy is a useful tool in the pre-operative study of hyperparathyroidism. False negatives (FN) have been reported in 5.7-14% of the examinations. Aim: To characterize 99mTc-sestamibi FN in cases referred for primary hyperparathyroidism (PHP) to a university hospital. Material and Methods: Descriptive retrospective analysis. We included patients with PHP, studied with SPECT scintigraphy, operated at our center between 2008 and 2015. Clinical and surgical data were recorded; biopsies of the FN were blindly reviewed by one pathologist. Results: One hundred twenty one scintigraphies fulfilled the inclusion criteria. Seven (5.8%) were negative and 114 positive. There was no difference in age, sex and PTH levels between FN and true positive scintigraphies. At surgery, one FN case had two hyperplasic glands and two cases had ectopic glands. Pathology reported adenoma in three cases, hyperplasia in three and carcinoma in one. The largest diameter of the lesion was lower in FN (1.3 and 2.1 cm respectively, p = 0.02) and the proportion of adenomas was higher in true positive cases (29% and 75% respectively; p < 0.01). The interval between scintigraphy and parathyroidectomy was greater in FN with a median of 92 days (range 20 days-3.2 years, p < 0.01). The percentage of oxyphilic cells observed was similar in both groups. Conclusions: FN parathyroid SPECT scintigraphies in PHP are uncommon. They corresponded to lesions under the equipment's resolution limit and resulted in longer time lags between scintigraphy and surgery.

Evaluación de parámetros clínicos y de laboratorio relacionados con el diagnóstico de insulino resistencia / Evaluation of clinical and laboratory parameters related to the diagnosis of insulin resistance

The evaluation of insulin resistance (IR) in clinical practice is based on the determination of fasting insulin (I0) and insulin level after 2 hours in an oral glucose tolerance test (OGT). However, there are not adequate cutoff points to discriminate IR patients. Objectives: to evaluate the reliability of insulin levels in the diagnosis of IR using the intravenous insulin tolerance test (IVITT) as the gold standard. Patients and Method: The OGT and IVITT of patients who participated as cases or controls in research protocols were analyzed. We excluded those cases with fasting glycemia over126 mg/dl. Results: 128 cases, 111 F, 17 M; Age: 40.3 +/- 14.8 years; BMI: 33 +/- 8 kg/m2; Waist circumference, M: 100.3 +/- 9.4 cm, F: 96 +/- 15 cm. According to IVITT (KITT), 103 (80.5 percent) were IR (KITT < 4.5 percent) and 25 (19.5 percent) were non IR (KITT > 4.5 percent). Fasting (G0) and 120 minutes after glucose challenge glycemia (G120), I0 and I120, HOMA and area under the glycemia and insulin curve, were significantly higher in the IR, as the same as, hypertension and acanthosis nigricans features (p < 0.05). According to G120, 45 cases (35.2 percent) had glucose intolerance, 9 (7 percent) diabetes and 74 (57.8 percent) were normals. In addition to G0, only IVITT was significantly different among the 3 groups (p = 0.025), identifying most insulin resistant subjects. The sensitivity and specificity for a cutoff point of I120 at 60 µIU/mL, were 30 percent and 88 percent, respectively. Conclusion: Baseline and 120 minutes post glucose charge insulin levels and HOMA, do not discriminate insulin resistant subjects, especially when there is fasting or post-stimulus hyperglycemia. Therefore, they are not recommended for individual diagnosis or therapeutic decisions

Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study.

BACKGROUND: Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients. METHODS: The diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.I.N.I.) and Hamilton depression scale (HAM-D17), respectively. Euthyroid patients were treated with placebo (one week) followed by fluoxetine (20 mg) (two months). Severity of depression was re-evaluated after placebo, three weeks and two months of fluoxetine treatments. Placebo response was defined as HAM-D17 score reductions of at least 25% and to < 15. Early response and response were reductions of at least 50% after three weeks and two months, and remission with ≤ 7 after two months. Plasma TSH, free-T4, circadian salivary cortisol levels and cortisol suppression by dexamethasone were evaluated. Seven genetic polymorphisms located in the Corticotrophin-releasing-hormone-receptor-1 (rs242939, rs242941, rs1876828), Corticotrophin-releasing-hormone-receptor-2 (rs2270007), Glucocorticoid-receptor (rs41423247), FK506-binding-protein-5 (rs1360780), and Arginine-vasopressin (rs3729965) genes were determined. Association analyses between response to placebo/fluoxetine and polymorphism were performed by chi-square or Fisher exact test. Cortisol levels were compared by t-test, ANOVA and the general linear model for repeated measures. RESULTS: 208 depressed patients were recruited, 187 of whom were euthyroid. Placebo responders, fluoxetine responders and remitters exhibited significantly lower circadian cortisol levels than those who did not respond (p-values of 0.014, 0.008 and 0.021 respectively). Patients who abandoned treatment before the third week also exhibited a trend to low cortisol levels (p = 0.057). The polymorphisms rs242939 (CRHR1) and rs2270007 (CRHR2) were not in Hardy-Weinberg equilibrium. Only the rs242939 polymorphism (CRHR1) exhibited association with early response (three weeks) to fluoxetine (p-value = 0.043). No other association between outcomes and polymorphisms was observed. CONCLUSIONS: These results support the clinical relevance of low salivary cortisol levels as a predictor of antidepressant response, either to placebo or to fluoxetine. Only one polymorphism in the CRHR1 gene was associated with the early response. Other factors may be involved in antidepressant response, although further studies are needed to identify them.

[Bone mineral density disminution post Roux-Y bypass surgery]. / Disminución de masa ósea post-cirugía bariátrica con by-pass en Y de Roux.

INTRODUCTION: Bariatric surgery has important metabolic complications such as bone mass loss. GOAL: To assess bone mineral density (BMD) after Roux-en-Y gastric by-pass (RYGB) in patients under standard calcium and vitamin D supplementation. METHOD: In patients with morbid obesity submitted to RYGB, 76 women and 22 men of diverse age, all with standard nutritional instruction including vitamin D and calcium, we measured BMD with a dual X-ray densitometer. They had lumbar spine and hips measurement 2-3 years post-surgery. Twenty females were followed up with BMD until of a mean of 54 months. Using World Health Organization (WHO) criteria's, values were compared with young controls and same age and sex population, evaluating osteopenia and osteoporosis. RESULTS: Inverse correlation was observed between BMD and age; positive between BMD and body mass index as well as with preoperative weight excess. In women younger than 45 years, we observed a diminished BMD in 26.8% of them, with no cases of osteoporosis. In older females, BMD was decreased in 65.7% (p = 0.0011); corresponding to 45.7% of osteopenia and 20% osteoporosis, more frequent in lumbar spine. In the female's subgroup followed longer, BMD diminished progressively mainly in left hip. In men, there was 36% of osteopenia and 14% of osteoporosis. CONCLUSION: Patients from both genders and diverse ages after BPYR presented osteopenia and osteoporosis, despite early supplement prescription of calcium and vitamin D. We consider important to perform serial BMD measurements and also to individualize therapy with risk factors control.

Introducción: La cirugía bariátrica tiene complicaciones metabólicas importantes como la pérdida de masa ósea. Objetivo: Evaluar la densidad mineral ósea (DMO) posterior a by-pass gástrico en Y de Roux (BPYR) en pacientes con indicación de suplemento estándar de calcio y vitamina D. Método: En pacientes con BPYR por obesidad mórbida, 76 mujeres y 22 hombres de diversa edad, con instrucción nutricional, suplemento de calcio y vitamina D, se midió la DMO en columna lumbar y caderas con densitómetro radiológico de doble haz 2 a 3 años post-cirugía. Veinte mujeres fueron seguidas con DMO hasta 54 meses en promedio. Según criterios de Organización Mundial de la Salud (OMS), se comparó con población control joven y de su edad según sexo, evaluando osteopenia y osteoporosis. Resultados: Hubo correlación negativa de DMO con edad; positiva de DMO con índice de masa corporal y con exceso de peso preoperatorio. En mujeres menores de 45 años, se observó disminución de DMO en 26,8%, sin casos de osteoporosis y en 65,7% en las mayores de 45 años (p = 0,0011), correspondiendo a 45,7% de osteopenia y 20% de osteoporosis, predominantemente en columna lumbar. El subgrupo de mujeres con mayor seguimiento, presentó disminución progresiva de DMO, especialmente en cadera izquierda. En hombres se observó 36% de osteopenia y 14% de osteoporosis. Conclusión: Pacientes de ambos sexos y diversa edad, despues de un BPYR, presentaron osteopenia y osteoporosis, a pesar de suplemento precoz de calcio y vitamina D. Consideramos importante medir DMO seriada, individualizando terapias y controlando factores de riesgo.

Disminución de masa ósea post-cirugía bariátrica con by-pass en Y de Roux / Bone mineral density disminution post y de roux by-pass surgery

Introducción: La cirugía bariátrica tiene complicaciones metabólicas importantes como la pérdida de masa ósea. Objetivo: Evaluar la densidad mineral ósea (DMO) posterior a by-pass gástrico en Y de Roux (BPYR) en pacientes con indicación de suplemento estándar de calcio y vitamina D. Método: En pacientes con BPYR por obesidad mórbida, 76 mujeres y 22 hombres de diversa edad, con instrucción nutricional, suplemento de calcio y vitamina D, se midió la DMO en columna lumbar y caderas con densitómetro radiológico de doble haz 2 a 3 años post-cirugía. Veinte mujeres fueron seguidas con DMO hasta 54 meses en promedio. Según criterios de Organización Mundial de la Salud (OMS), se comparó con población control joven y de su edad según sexo, evaluando osteopenia y osteoporosis. Resultados: Hubo correlación negativa de DMO con edad; positiva de DMO con índice de masa corporal y con exceso de peso preoperatorio. En mujeres menores de 45 años, se observó disminución de DMO en 26,8%, sin casos de osteoporosis y en 65,7% en las mayores de 45 años (p = 0,0011), correspondiendo a 45,7% de osteopenia y 20% de osteoporosis, predominantemente en columna lumbar. El subgrupo de mujeres con mayor seguimiento, presentó disminución progresiva de DMO, especialmente en cadera izquierda. En hombres se observó 36% de osteopenia y 14% de osteoporosis. Conclusión: Pacientes de ambos sexos y diversa edad, despues de un BPYR, presentaron osteopenia y osteoporosis, a pesar de suplemento precoz de calcio y vitamina D. Consideramos importante medir DMO seriada, individualizando terapias y controlando factores de riesgo (AU)

INTRODUCTION: Bariatric surgery has important metabolic complications such as bone mass loss. GOAL: To assess bone mineral density (BMD) after Roux-en-Y gastric by-pass (RYGB) in patients under standard calcium and vitamin D supplementation. METHOD: In patients with morbid obesity submitted to RYGB, 76 women and 22 men of diverse age, all with standard nutritional instruction including vitamin D and calcium, we measured BMD with a dual X-ray densitometer. They had lumbar spine and hips measurement 2-3 years post-surgery. Twenty females were followed up with BMD until of a mean of 54 months. Using World Health Organization (WHO) criteria's, values were compared with young controls and same age and sex population, evaluating osteopenia and osteoporosis. RESULTS: Inverse correlation was observed between BMD and age; positive between BMD and body mass index as well as with preoperative weight excess. In women younger than 45 years, we observed a diminished BMD in 26.8% of them, with no cases of osteoporosis. In older females, BMD was decreased in 65.7% (p = 0.0011); corresponding to 45.7% of osteopenia and 20% osteoporosis, more frequent in lumbar spine. In the female's subgroup followed longer, BMD diminished progressively mainly in left hip. In men, there was 36% of osteopenia and 14% of osteoporosis. CONCLUSION :Patients from both genders and diverse ages after BPYR presented osteopenia and osteoporosis, despite early supplement prescription of calcium and vitamin D. We consider important to perform serial BMD measurements and also to individualize therapy with risk factors control (AU)

[Frequency of positive anti thyroid peroxidase antibody titers among normal individuals]. / Alta frecuencia de anticuerpos anti-tiroperoxidasa (ATPO) positivos en sujetos adultos, sin patología tiroidea conocida, de Santiago de Chile.

BACKGROUND: Anti-thyroid peroxidase antibodies have a pathogenic role in Hashimoto thyroiditis. Between 10 and 19% of individuals without thyroid disease, have positive titers of these antibodies. AIM: To study the frequency of positive titers of anti-thyroid peroxidase antibodies in healthy individuals. MATERIAL AND METHODS: A blood sample, to measure anti-thyroid peroxidase antibodies and thyroid stimulating hormone (TSH) by chemoluminiscense assay, was obtained from 67women and 62 men aged 45 +/- 14years, without a personal or familiar history of thyroid diseases and normal thyroid palpation. The cutoff point of the manufacturer to consider positive a titer of anti-thyroid peroxidase antibodies was set at 35 IU/ml. RESULTS: Twenty-eight women and 28 men had positive antibody titers (43% of the sample). Subjects in the upper tercile of anti-thyroid peroxidase antibody titers had a higher TSH than those in the second tercile, although within normal limits (1.73 +/- 0.74 and 1.37 +/- 0.59 mlU/L, respectively p = 0.02) CONCLUSIONS: Forty three percent of the studied subjects without personal or familial history of thyroid diseases had positive titers of anti-thyroid peroxidase antibodies. Further prospective studies should evaluate whether this observation discloses an increase in thyroid autoimmune disease in a population with increased iodine intake.

Alta frecuencia de anticuerpos anti-tiroperoxidasa (ATPO) positivos en sujetos adultos, sin patología tiroidea conocida, de Santiago de Chile / Frequency of positive anti thyroid peroxidase antibody titers among normal individuals

Background: Anti-thyroid peroxidase antibodies have a pathogenic role in Hashimoto thyroiditis. Between 10 and 19 percent of individuals without thyroid disease, have positive titers of these antibodies. Aim: To study the frequency of positive titers of anti-thyroid peroxidase antibodies in healthy individuals. Material and Methods: A blood sample, to measure anti-thyroid peroxidase antibodies and thyroid stimulating hormone (TSH) by chemoluminiscense assay, was obtained from 67women and 62 men aged 45 ± 14years, without a personal or familiar history of thyroid diseases and normal thyroid palpation. The cutoff point of the manufacturer to consider positive a titer of anti-thyroid peroxidase antibodies was set at 35 IU/ml. Results: Twenty-eight women and 28 men had positive antibody titers (43 percent of the sample). Subjects in the upper tercile of anti-thyroid peroxidase antibody titers had a higher TSH than those in the second tercile, although within normal limits (1.73 ± 0.74 and 1.37 ± 0.59 mlU/L, respectively p = 0.02) Conclusions: Forty three percent of the studied subjects without personal or familial history of thyroid diseases had positive titers of anti-thyroid peroxidase antibodies. Further prospective studies should evaluate whether this observation discloses an increase in thyroid autoimmune disease in a population with increased iodine intake.

Decreased liver fatty acid delta-6 and delta-5 desaturase activity in obese patients.

Steatosis in obese nonalcoholic fatty liver disease (NAFLD) patients is a clinicopathological condition associated with depletion of n-3 polyunsaturated fatty acids (PUFA), a feature that may be related to PUFA desaturation. Liver Delta-6 and Delta-5 desaturase (Delta-6D and Delta-5D) activities, homeostasis model assessment of insulin resistance (HOMA(IR)), and ferric reducing ability of plasma (FRAP) were evaluated in 13 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 15 nonobese patients who underwent laparoscopic cholecystectomy (controls). Liver Delta-6D and Delta-5D activities in obese patients were 87% and 66% lower than controls (P < 0.001), respectively, with a 62% diminution in the Delta-6D/Delta-5D activity ratio (P < 0.02). Delta-6D inversely correlated with both HOMA(IR) (r = -0.70, P < 0.0001) and oxidative stress assessed as the reciprocal value of FRAP (r = -0.40, P < 0.05). Delta-5D negatively correlated with HOMA(IR) (r = -0.48, P < 0.01) but not with FRAP(-1) (r = -0.13, not significant). In conclusion, liver PUFA desaturation is diminished in obese NAFLD patients, in association with underlying insulin resistance and oxidative stress, which may play a role in altering lipid metabolism favoring fatty infiltration.

Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion.

Sterol receptor element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) mRNA expression was assessed in liver as signaling mechanisms associated with steatosis in obese patients. Liver SREBP-1c and PPAR-alpha mRNA (RT-PCR), fatty acid synthase (FAS) and carnitine palmitoyltransferase-1a (CPT-1a) mRNA (real-time RT-PCR), and n-3 long-chain polyunsaturated fatty acid (LCPUFA)(GLC) contents, plasma adiponectin levels (RIA), and insulin resistance (IR) evolution (HOMA) were evaluated in 11 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 8 non-obese subjects who underwent laparoscopic cholecystectomy (controls). Liver SREBP-1c and FAS mRNA levels were 33% and 70% higher than control values (P<0.05), respectively, whereas those of PPAR-alpha and CPT-1a were 16% and 65% lower (P<0.05), respectively, with a significant 62% enhancement in the SREBP-1c/PPAR-alpha ratio. Liver n-3 LCPUFA levels were 53% lower in obese patients who also showed IR and hipoadiponectinemia over controls (P<0.05). IR negatively correlated with both the hepatic content of n-3 LCPUFA (r=-0.55; P<0.01) and the plasma levels of adiponectin (r=-0.62; P<0.005). Liver SREBP-1c/PPAR-alpha ratio and n-3 LCPUFA showed a negative correlation (r=-0.48; P<0.02) and positive associations with either HOMA (r=0.75; P<0.0001) or serum insulin levels (r=0.69; P<0.001). In conclusion, liver up-regulation of SREBP-1c and down-regulation of PPAR-alpha occur in obese patients, with enhancement in the SREBP-1c/PPAR-alpha ratio associated with n-3 LCPUFA depletion and IR, a condition that may favor lipogenesis over FA oxidation thereby leading to steatosis.

Liver NF-kappaB and AP-1 DNA binding in obese patients.

Oxidative stress and insulin resistance (IR) are major contributors in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in the progression from steatosis to nonalcoholic steatohepatitis (NASH). Our aim was to assess nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation and Toll-like receptor 4 (TLR4) expression as signaling mechanisms related to liver injury in obese NAFLD patients, and examined potential correlations among them, oxidative stress, and IR. Liver NF-kappaB and AP-1 (electromobility shift assay (EMSA)), TLR4 expression (western blot), ferric reducing ability of plasma (FRAP), and IR evolution (HOMA) were evaluated in 17 obese patients who underwent subtotal gastrectomy with gastro-jejunal anastomosis in Roux-en-Y and 10 nonobese subjects who underwent laparoscopic cholecystectomy (controls). Liver NF-kappaB and AP-1 DNA binding were markedly increased in NASH patients (n = 9; P < 0.05) compared to controls, without significant changes in NAFLD patients with steatosis (n = 8), whereas TLR4 expression was comparable between groups. Hepatic NF-kappaB activation was positively correlated with that of AP-1 (r = 0.79; P < 0.0001); both liver NF-kappaB and AP-1 DNA binding were inversely associated with FRAP (r = -0.43 and r = -0.40, respectively; P < 0.05) and directly correlated with HOMA (r = 0.66 and r = 0.62, respectively, P < 0.001). Data presented show enhanced liver activation of the proinflammatory transcription factors NF-kappaB and AP-1 in obese patients with NASH, parameters that are significantly associated to oxidative stress and IR.

Evaluation of the effect of caloric restriction on serum BDNF in overweight and obese subjects: preliminary evidences.

UNLABELLED: Brain-derived neurotrophic factor (BDNF) has emerged as a new element related with insulin resistance and obesity. OBJECTIVE: To evaluate the effect of a 3-month reduced-calorie diet (RCD) on serum BDNF concentrations in overweight and obese subjects. SUBJECTS: Seventeen healthy overweight and obese subjects of both sexes (24 - 48 years, BMI 34.6 +/- 1.1 kg/m2). METHODS: Anthropometry, oral glucose tolerance test (OGTT), lipid levels, and serum BDNF were measured at baseline and at the end of the third month. Reduced-calorie diet was defined as a 25% reduction in energy intake composed of: 55% carbohydrates, 20% proteins, and 25% fat (less than 10% saturated fat and over 10% nonsaturated fat). Refined sugar was not allowed. RESULTS: There was a significant decrease in BMI, waist circumference, body fat percentage, fasting glucose, post-OGTT glucose levels, area under the curve of glucose, and HOMA2-IR after 3 months of RCD. Serum BDNF showed a significant increase (3.97 +/- 0.87 to 6.75 +/- 1.62 ng/ml, P = 0.02). Final serum BDNF correlated negatively with weight (r = -0.51, P = 0.03), and basal post-OGTT insulin correlated positively with final serum BDNF (r = 0.48, P = 0.04). CONCLUSIONS: Serum BDNF increases in insulin-resistant overweight and obese subjects after three months on a RCD. This observation could indicate that BDNF may be modulated in humans through diet composition.

[Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas]. / Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia.

BACKGROUND: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. AIM: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the plurihormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. MATERIAL AND METHODS: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. RESULTS: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6+/-3.3%. There were no differences in the expression of this marker between mono or plurihormonal tumors. The expression was neither associated with extrasellar extension. CONCLUSIONS: Half of GH producing pituitary adenomas are plurihormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.

Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia / Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas

Background: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. Aim: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the pluríhormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. Material and methods: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. Results: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6±3.3 percent. There were no differences in the expression of this marker between mono or pluríhormonal tumors. The expression was neither associated with extrasellar extensión. Conclusions: Half of GH producing pituitary adenomas are pluríhormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.