RESUMEN

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

RESUMEN

Limited work examining woman's appetite-regulatory response to exercise has been focused on the follicular phase (FP) of the menstrual cycle. This is an important limitation as estradiol (E2) and progesterone (P4) fluctuate across phases with greater concentrations in the luteal phase (LP). OBJECTIVE: To examine the appetite-regulatory response to vigorous-intensity continuous exercise (VICT) in the FP and LP. METHODS: Twelve women completed 30 min of VICT at 80% V˙O2max in the FP and LP. E2, P4, acylated ghrelin, active peptide tyrosine-tyrosine (PYY), active glucagon-like peptide-1 (GLP-1), and appetite perceptions were measured pre-exercise, 0-, 30-, and 90-min post-exercise. Energy intake was recorded for a 2-day period (day before and of each session). A series of two-way repeated measure ANOVA were used to compare all dependent variables. RESULTS: Pre-exercise E2 (P = 0.005, d = 1.00) and P4 (P < 0.001, d = 1.41) concentrations were greater in the LP than the FP and exercise increased both at 0- and 30-min post-exercise (E2: P < 0.009; P4: P < 0.001, d = 0.63). Acylated ghrelin was lower in the FP versus LP at pre-exercise as well as 0-min (P = 0.006, d = 0.97) and 90-min (P = 0.029, d = 0.72) post-exercise. There were no differences of menstrual phase on PYY (P = 0.359, ηp2 = 0.092), GLP-1 (P = 0.226, ηp2 = 0.130), or overall appetite (P = 0.514, ηp2 = 0.066). Energy intake was greater on the day of in the LP versus the FP (P = 0.003, d = 1.2). CONCLUSION: Acylated ghrelin was lower in the FP compared to the LP and though there were no differences in anorexigenic hormones or subjective appetite, energy intake was greater on the day of the session in the LP suggesting important differences across the menstrual cycle where greater concentrations of ovarian hormones in the LP may blunt the exercise response.

Asunto(s)

RESUMEN

Preclinical studies in animal models of obesity and inflammation have shown that oral administration of ARD-101, a potential TAS2R agonist, reduced food intake and body weight and downregulated inflammatory cytokines. We present results from a first-in-human phase 1 randomized, placebo-controlled trial that evaluated safety, pharmacokinetics, and pharmacodynamics of single or multiple ascending doses of oral ARD-101 (40, 100, and 240 mg) in healthy adults. A total of 43 subjects were randomly assigned and dosed to ARD-101 or placebo with 42 subjects completing the study treatment. ARD-101 was found to be >99% restricted to the gut with minimal systemic exposure, demonstrated a favorable safety profile, and was well tolerated at all dose levels. Blood samples taken 1 hour after administration showed that subjects dosed with 240 mg of ARD-101 had elevated circulating levels of several gut peptide hormones. It is postulated that ARD-101 activates enteroendocrine cells to achieve its effects regulating metabolism and inflammation. The phase 1 clinical results demonstrated safety of ARD-101 and indicated activation of gut peptide hormone release in healthy adults. Further clinical trials will evaluate ARD-101 in patients with metabolic and inflammatory disorders.

Asunto(s)

RESUMEN

PURPOSE: Inconsistent evidence exists for greater satiety after medium-chain triglycerides (MCT) or conjugated linoleic acid (CLA) compared to long-chain triglycerides (LCT). Furthermore, the mechanisms are poorly understood and effects in people with a healthy weight and those with overweight/obesity have not been compared. This study aimed to compare appetite responses in these groups and examine the mechanisms behind any differences. METHODS: Fifteen participants with healthy weight (BMI: 22.7 ± 1.9 kg·m-2) and fourteen participants with overweight/obesity (BMI: 30.9 ± 3.9 kg·m-2) consumed a breakfast containing either 23.06 g vegetable oil (CON), 25.00 g MCT oil (MCT), or 6.25 g CLA and 16.80 g vegetable oil (CLA). Appetite, peptide YY (PYY), total ghrelin (TG), ß-hydroxybutyrate, and gastric emptying (GE) were measured throughout. Energy intake was assessed at an ad libitum lunch and throughout the following ~ 36 h. RESULTS: Neither MCT nor CLA decreased ad libitum intake; however MCT decreased day 1 energy intake (P = 0.031) and the 48-h period (P = 0.005) compared to CON. MCT delayed GE (P ≤ 0.01) compared to CON, whereas CLA did not. PYY and TG concentrations were not different (P = 0.743 and P = 0.188, respectively), but MCT increased ß-hydroxybutyrate concentrations compared to CON (P = 0.005) and CLA (P < 0.001). ß-hydroxybutyrate concentrations were higher in participants with overweight/obesity (P = 0.009). CONCLUSION: Consumption of MCT reduces energy intake in the subsequent 48 h, whereas CLA does not. Delayed gastric emptying or increased ß-hydroxybutyrate concentrations may mediate this.

Asunto(s)

RESUMEN

BACKGROUND: Previous research indicated that coeliac disease (CD) is associated with type 1 diabetes mellitus (T1DM). However, the gut-brain axis peptide hormones secretion has not been evaluated so far in patients with CD prior to treatment initiation or under treatment, irrespective of patients having concomitant T1DM or not. The aim of the study was therefore to evaluate these gut hormones at the preprandial levels of patients with CD before and under treatment. METHODS: Of forty-seven CD children, 12 untreated (UCD), 22 treated with gluten-free diet (TCD) and 13 treated CD with coexisting T1DM (DCD), and 18 healthy controls (HC) were enrolled. Preprandial glucagon-like-peptide-1 (GLP-1), glucose-dependent-insulinotropic-polypeptide (GIP), active amylin, acylated ghrelin (AG), leptin, pancreatic polypeptide (PP) and peptide-tyrosine-tyrosine (PYY) were determined with hormone-map-array technology. RESULTS: We found in patients with CD compared with HC that the concentration of (i) GLP-1 was reduced remarkably in all patients with CD (P = 0.008), (ii) GIP was lower in patients with UCD (P = 0.008), (iii) amylin was remarkably reduced (P < 0.01) in all patients with CD, (iv) AG was significantly decreased in patients with DCD (P < 0.01), while (v) leptin, PP and PYY were not significantly different. GIP, GLP-1 and amylin levels correlated positively with insulin concentrations (P < 0.001, P = 0.004 and P < 0.01, respectively) in all patients. Amylin and GIP levels were strongly associated with triglycerides concentrations (P < 0.001, for both peptides) in children with CD. CONCLUSIONS: Our study revealed a different secretion pattern of gut-brain axis hormones in children with CD compared with HC. The alterations in the axis were more pronounced in children with both CD and T1DM.

Asunto(s)