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Nicholas A Tritos

Publications and source records attributed to Nicholas A Tritos.

18 recordsLinked to original sources
PubMed2006

The physiology and potential clinical applications of ghrelin, a novel peptide hormone.

Ghrelin, a peptide hormone originally identified as the endogenous ligand of the growth hormone secretagogue receptor, is secreted primarily from the stomach and secondarily from the small intestine and colon. Ghrelin may also be expressed in the pancreatic islets, hypothalamus, pituitary, and several tissues in the periphery. The growth hormone secretagogue receptor is widely expressed, suggesting diverse physiologic roles for ghrelin. A growing body of evidence suggests that, in addition to its predictable effect on growth hormone secretion, ghrelin has an important role in the short-term regulation of appetite and the long-term regulation of energy balance and glucose homeostasis. Recent studies have implicated ghrelin in the regulation of gastrointestinal, cardiovascular, and immune function and have suggested a role for ghrelin in bone physiology. The identification of obestatin, a novel peptide hormone derived from the same gene as ghrelin, has recently added further complexity to ghrelin physiology. Obestatin appears to have actions opposite of ghrelin on energy homeostasis and gastrointestinal function. Despite the rapid progress, many questions remain unanswered, including the regulation of ghrelin and obestatin secretion, the downstream pathways that mediate their effects, and their precise physiologic endocrine and paracrine roles. This review presents data on ghrelin structure, expression, and function, with emphasis placed on human studies, highlighting areas that require future investigation and providing speculation about potential clinical applications of ghrelin agonists or antagonists.

Appetite Regulation↗
PubMed2005

Effect of raloxifene on aortic elasticity in healthy postmenopausal women.

BACKGROUND: The effect of raloxifene on aortic elasticity in healthy postmenopausal women is unknown. The purpose of the present study was to examine the effect of raloxifene on aortic elasticity and cardiovascular structure and function in healthy postmenopausal women. METHODS: A randomized, crossover, double-blind, placebo-controlled clinical trial was performed. Fourteen healthy postmenopausal women received treatment with raloxifene 60 mg daily and matching placebo for 8 weeks with an 8-week washout period in between the 2 treatment periods. Cardiovascular magnetic resonance imaging was used to assess ascending thoracic and abdominal aortic elasticity and cardiovascular structure and function (left ventricular volumes, ejection fraction, and mass and mitral annular displacement) before and at the end of each treatment period. RESULTS: Administration of raloxifene had no significant effect on either heart rate or systemic blood pressure. Raloxifene treatment was associated with a small decrease of the ascending aorta wall thickness (pretreatment 2.4 +/- 0.3 vs posttreatment 2.2 +/- 0.2 mm, P = .01). Consequently, there was an increase in the Young's elastic modulus after raloxifene treatment at the ascending thoracic aorta but not the abdominal aorta. There were no significant differences in aortic compliance or any cardiac indexes after raloxifene treatment. CONCLUSIONS: Raloxifene administration in healthy postmenopausal women over an 8-week period may decrease the aortic wall thickness but has no significant effects on aortic compliance or cardiac structure and function.

Aorta↗
PubMed2004

Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone.

OBJECTIVE: Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin-concentrating hormone (MCH) and the appetite-inhibiting, fat-derived hormone leptin in mediating E2-induced anorexia. RESEARCH METHODS AND PROCEDURES: We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin-deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high-fat diet. RESULTS: We confirmed E2 dose-dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2-implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia. E2-implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2-induced anorexia. High-fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week. DISCUSSION: The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.

Animals↗
PubMed2004

Association between ghrelin and cardiovascular indexes in healthy obese and lean men.

OBJECTIVE: Obesity is an increasingly common condition and is associated with excess morbidity and mortality, including clinical and subclinical cardiac dysfunction. The role of hormones involved in energy homeostasis, including ghrelin and leptin, in cardiovascular function remains incompletely understood. Therefore, we sought to evaluate the association between systemic ghrelin and leptin levels with indexes of cardiovascular structure and function. DESIGN AND MEASUREMENTS: We measured serum ghrelin and leptin levels in 25 clinically healthy obese men and 25 lean controls, using commercially available immunoassays. We also assessed right and left ventricular structure and function using cardiac magnetic resonance imaging. We then investigated the association between serum ghrelin and leptin levels with cardiac indexes, using univariate and multivariate analysis. RESULTS: There was an independent association between serum ghrelin levels and height-adjusted right ventricular mass (r = -0.324, P = 0.026), right ventricular end-diastolic volume (r = -0.363, P = 0.017) and right ventricular end-systolic volume (r = -0.398, P = 0.009) as well as right ventricular ejection fraction (r = 0.317, P = 0.050). There was no significant association between serum ghrelin and indexes of left ventricular structure or function. We also identified an association between serum leptin levels and resting heart rate (r = 0.391, P = 0.002). There was an association between serum leptin and height-adjusted left ventricular mass on univariate, but not on multivariate, analysis. CONCLUSIONS: Serum ghrelin is associated with right ventricular cardiovascular indexes and serum leptin is associated with resting heart rate. These associations indicate a close interaction between the endocrine and cardiovascular systems in obesity.

Adult↗
PubMed2003

Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1alpha) expression in the murine brain.

The peroxisome proliferator activated receptor coactivator 1 alpha (PGC-1alpha) is a nuclear transcriptional coactivator that is expressed in brown adipose tissue, brain, heart and kidney as well as cold-exposed skeletal muscle. In liver, white and brown adipose tissue, PGC-1alpha expression is regulated in a manner suggesting a role in energy homeostasis. To characterize PGC-1alpha expression in the rodent brain and to determine brain PGC-1alpha regulation, we used in situ hybridization histochemistry in C57Bl/6J mice and Sprague-Dawley rats. We found that PGC-1alpha is widely expressed in brain areas, including in the olfactory bulb, cerebral cortex, the diagonal band of Broca, the medial septal nucleus, reticular thalamic nucleus, the striatum and globus pallidus, the hippocampus, the substantia nigra, the mesencephalic nucleus of the trigeminal nerve, the cochlear nucleus and the superior olivary complex. In contrast, PGC-1alpha expression was absent in the hypothalamus. To evaluate PGC-1alpha expression under different physiologic states in these various brain areas, we examined expression with fasting, leptin treatment and cold exposure (4 h at 4 degrees C) and found no change, nor was expression changed in the brain of the leptin-deficient ob/ob mice and the hyperleptinemic UCP-DTA mice. Hence, PGC-1alpha is widely expressed in the rodent brain, but is not regulated by states of caloric deficiency, leptin, obesity or cold exposure. Its functional role in the brain requires further study.

Animals↗
PubMed2003

Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults.

The vascular properties of large vessels in the obese have not been adequately studied. We used cardiovascular magnetic resonance imaging to quantify the cross-sectional area and elastic properties of the ascending thoracic and abdominal aorta in 21 clinically healthy obese young adult men and 25 men who were age-matched lean controls. Obese subjects had greater maximal cross-sectional area of the ascending thoracic aorta (984 +/- 252 vs 786 +/- 109 mm(2), p <0.01) and of the abdominal aorta (415 +/- 71 vs 374 +/- 51 mm(2), p <0.05). When indexed for height the differences persisted, but when indexed for body surface area, a significant difference between groups was found only for the maximal abdominal aortic cross-sectional area. The obese subjects also had decreased abdominal aortic elasticity, characterized by 24% lower compliance (0.0017 +/- 0.0004 vs 0.0021 +/- 0.0005 mm(2)/kPa/mm, p <0.01), 22% higher stiffness index beta (6.0 +/- 1.5 vs 4.9 +/- 0.7, p <0.005), and 41% greater pressure-strain elastic modulus (72 +/- 25 vs 51 +/- 9, p <0.005). At the ascending thoracic aorta, only the pressure-strain elastic modulus was different between obese and lean subjects (85 +/- 42 vs 65 +/- 26 kPa, respectively; p <0.05), corresponding to a 31% difference-but arterial compliance and stiffness index were not significantly different between groups. In clinically healthy young adult obese men, obesity is associated with increased cross-sectional aortic area and decreased aortic elasticity.

Adult↗
PubMed2003

Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery.

OBJECTIVE: We sought to elucidate further the mechanisms leading to weight loss after gastric bypass (GBP) surgery in morbidly obese individuals. Ghrelin is a gastroenteric appetite-stimulating peptide hormone, fasting levels of which decrease with increasing adiposity and increase with diet-induced weight loss. In addition, ghrelin levels rapidly decline postprandially. RESEARCH METHODS AND PROCEDURES: We measured serum ghrelin responses to a 75-g oral glucose tolerance test (OGTT) in 6 subjects who had undergone GBP surgery 1.5 +/- 0.7 years before testing and compared these responses with 6 obese subjects about to undergo GBP surgery, 6 obese nonsurgical subjects (matched for BMI to the post-GBP surgical group), and 5 lean subjects. RESULTS: Despite weight loss induced by the GBP surgery, fasting serum ghrelin levels were significantly lower in the post-GBP surgery group than in the lean subject (by 57%) or pre-GBP surgery (by 45%) group. Serum ghrelin levels during the OGTT were significantly lower in postoperative than in lean, obese pre-GBP surgical, or obese nonsurgical subjects. The magnitude of the decline in serum ghrelin levels between 0 and 120 minutes post-OGTT was significantly smaller in postoperative (by 62%), obese pre-GBP surgical (by 80%), or obese nonsurgical (by 69%) subjects in comparison with lean subjects. DISCUSSION: Serum ghrelin levels in response to OGTT are lower in subjects post-GBP surgery than in either lean or obese subjects. Tonically low serum ghrelin levels may be involved in the mechanisms inducing sustained weight loss after GBP surgery.

Adult↗
PubMed2003

Cardiac structure and function in the obese: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Obesity is a major health problem in the Western world. Among obese subjects cardiac pathology is common, but conventional noninvasive imaging modalities are often suboptimal for detailed evaluation of cardiac structure and function. We investigated whether cardiovascular magnetic resonance imaging (CMR) can better characterize possible cardiac abnormalities associated with obesity, in the absence of other confounding comorbidities. METHODS: In this prospective cross-sectional study, CMR was used to quantify left and right ventricular volumes, ejection fraction, mass, cardiac output, and apical left ventricular rotation in 25 clinically healthy obese men and 25 age-matched lean controls. RESULTS: Obese subjects had higher left ventricular mass (203 +/- 38 g vs. 163 +/- 22 g, p < 0.001), end-diastolic volume (176 +/- 29 mL vs. 156 +/- 25 mL, p < 0.05), and cardiac output (8.2 +/- 1.2 L/min vs. 6.4 +/- 1.3 L/min, p < 0.001). The obese also had increased right ventricular mass (105 +/- 25 g vs. 87 +/- 18 g, p < 0.005) and end-diastolic volume (179 +/- 36 mL vs. 155 +/- 28 mL, p < 0.05). When indexed for height, differences in left and right ventricular mass, and left ventricular end-diastolic volume remained significant. Apical left ventricular rotation and rotational velocity patterns were also different between obese and lean subjects. CONCLUSIONS: Obesity is independently associated with remodeling of the heart. Cardiovascular magnetic resonance imaging identifies subtle cardiac abnormalities and may be the preferred imaging technique to evaluate cardiac structure and function in the obese.

Adult↗
PubMed2003

Cerebrospinal fluid ghrelin is negatively associated with body mass index.

Ghrelin is a 28 amino acid peptide hormone, predominantly expressed in the gastric epithelium and, at a lower level, in the hypothalamus. Although several lines of evidence indicate that ghrelin has a role in appetite regulation, nevertheless the regulation and role of central ghrelin levels remain unclear. To further characterize the role of ghrelin in the regulation of body adiposity, we investigated the association between fasting cerebrospinal fluid (CSF) ghrelin levels and body mass index (BMI) in humans. We consecutively enrolled 19 adults (aged 21-76 yr, 15 females and 4 males), including 4 obese, 7 overweight and 8 lean subjects, who underwent spinal anesthesia during surgery for non-malignant conditions. We found a negative association between fasting CSF ghrelin levels and BMI (r = -0.48, p = 0.035) and a trend towards lower (by 16%) fasting CSF ghrelin levels in the obese (p = 0.06 for the difference between lean and obese subjects). In conclusion, we found a negative association between fasting CSF ghrelin levels and BMI in humans. Our data suggest that central ghrelin may have a role in the regulation of body adiposity in humans, which requires further study to be fully elucidated.

Adult↗
PubMed2002

Serum monocyte chemoattractant protein-1 is increased in chronic autoimmune thyroiditis.

Chemokines are a large family of cytokines, which may be involved in the pathogenesis of a wide variety of inflammatory or autoimmune conditions. The role of chemokines in chronic autoimmune thyroiditis is unknown. We sought to examine the role of CC chemokines in chronic autoimmune thyroiditis. We measured serum levels of CC chemokines, including monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1a and 1b (MIP-1a and MIP-1b) in 32 women with chronic autoimmune thyroiditis in comparison with 2 control groups (33 apparently healthy women and 43 women with benign cold thyroid nodules) by enzyme-linked immunosorbent assay (ELISA). We found a 45% increase in serum MCP-1 levels in women with chronic autoimmune thyroiditis compared with either of the 2 control groups (P =.01). There was no difference in either serum MIP-1a (P =.69) or MIP-1b (P =.81) levels between women with chronic autoimmune thyroiditis and controls. Among women with chronic autoimmune thyroiditis, women with a family history of hypothyroidism had a 59% increase in serum MCP-1 levels compared with women with no family history of hypothyroidism (P =.02). Serum MCP-1 levels were associated with serum levels of antithyroid peroxidase (r =.2, P =.03) (anti-TPO Ab) and antithyroglobulin (r =.2, P =.04) antibodies (anti-TG Ab). There was no association between serum MCP-1 levels and serum free thyroxine index (P =.57), triiodothyronine (T(3)) (P =.47) or thyroid-stimulating hormone (TSH) (P =.47) levels. Serum MCP-1 is increased in women with chronic autoimmune thyroiditis, especially in the presence of a family history of hypothyroidism, indicating a possible pathogenetic role for MCP-1 in this condition.

Adult↗
PubMedDate not supplied

Diagnostic and therapeutic approach to pituitary incidentalomas.

OBJECTIVE: To review data on epidemiology, differential diagnosis, clinical, laboratory, and imaging findings, natural history, and management of incidentally discovered pituitary lesions (pituitary incidentalomas). METHODS: A nonsystematic review was conducted, including articles indexed in Index Medicus that contained reference to incidentally discovered pituitary masses (pituitary incidentalomas). RESULTS: Both autopsy and sensitive neuroimaging studies (including magnetic resonance imaging) suggest that pituitary incidentalomas are common, affecting approximately 10% of the general population. Although typically small (less than 10 mm in greatest diameter) and clinically silent, some pituitary incidentalomas may be hormonally active or cause mass effects by compressing neighboring structures. In addition, a minority of these lesions may grow over time; hence, long-term follow-up is necessary. Therapeutic interventions, including dopamine agonist therapy (in the case of prolactin-secreting adenomas) or transsphenoidal resection, are indicated in the case of pituitary lesions that are hormonally active, cause mass effects, or increase in size. CONCLUSION: Pituitary incidentalomas are common and constitute a heterogeneous group with regard to pathologic features, clinical, laboratory, and imaging characteristics, natural history, and growth potential. Currently available evidence suggests that many hormonally nonfunctioning pituitary incidentalomas causing no mass effects can be safely managed by follow-up surveillance. Nonetheless, more data are needed for further elucidation of the natural history of these lesions and for improvement in accurate and noninvasive diagnosis and in prediction of growth potential of pituitary incidentalomas. Improved understanding of the pathogenesis of this heterogeneous group of lesions may also lead to the development of novel, noninvasive therapeutic agents, rationally designed to interact with well-characterized molecular targets.

Humans↗
PubMedDate not supplied

A case presentation.

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Carcinoma, Papillary↗