A Comprehensive Review on Bariatric Endoscopy: Where We Are Now and Where We Are Going.

Background: Obesity is a chronic disease that impairs quality of life and leads to several comorbidities. When conservative therapies fail, bariatric surgical options such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies to induce persistent weight loss. Over the last two decades, bariatric endoscopy has become a valid alternative to surgery in specific settings. Primary bariatric endoscopic therapies: Restrictive gastric procedures, such as intragastric balloons (IGBs) and endoscopic gastroplasty, have been shown to be effective in inducing weight loss compared to diet modifications alone. Endoscopic gastroplasty is usually superior to IGBs in maintaining weight loss in the long-term period, whereas IGBs have an established role as a bridge-to-surgery approach in severely obese patients. IGBs in a minority of patients could be poorly tolerated and require early removal. More recently, novel endoscopic systems have been developed with the combined purpose of inducing weight loss and improving metabolic conditions. Duodenal mucosal resurfacing demonstrated efficacy in this field in its early trials: significant reduction from baseline of HbA1c values and a modest reduction of body weight were observed. Other endoscopic malabsorptive have been developed but need more evidence. For example, a pivotal trial on duodenojejunal bypasses was stopped due to the high rate of severe adverse events (hepatic abscesses). Optimization of these more recent malabsorptive endoscopic procedures could expand the plethora of bariatric patients that could be treated with the intention of improving their metabolic conditions. Revisional bariatric therapies: Weight regain may occur in up to one third of patients after bariatric surgery. Different endoscopic procedures are currently performed after both RYGB and SG in order to modulate post-surgical anatomy. The application of argon plasma coagulation associated with endoscopic full-thickness suturing systems (APC-TORe) and Re-EndoSleeve have shown to be the most effective endoscopic treatments after RYGB and SG, respectively. Both procedures are usually well tolerated and have a very low risk of stricture. However, APC-TORe may sometimes require more than one session to obtain adequate final results. The aim of this review is to explore all the currently available primary and revisional endoscopic bariatric therapies focusing on their efficacy and safety and their potential application in clinical practice.

Zinc Complexes of Cyclodextrin-bearing 8-Hydroxyquinoline Ligands: A Comparative Study.

The mounting evidence supporting the role of metal ions in several diseases has turned metal-ion chelation therapy into a promising treatment strategy. The design of efficient metal-binding ligands requires in-depth knowledge of molecular structure and stability constants of the complexes formed. This paper presents an extensive overview on the stability of zinc(II) and copper(II) complexes of a series of cyclodextrin-8-hydroxyquinoline conjugates. In order to explain the differences observed in the stability constants between the metal complexes of the 6-functionalized and 3-functionalized cyclodextrin isomers, conformational analysis and DFT simulations were also performed. Molecular simulations allowed us to clarify the binding mode and to explain the differences in the stability constants of the metal complexes of these derivatives.

Multifunctional 8-hydroxyquinoline-appended cyclodextrins as new inhibitors of metal-induced protein aggregation.

Mounting evidence suggests a pivotal role of metal imbalances in protein misfolding and amyloid diseases. As such, metal ions represent a promising therapeutic target. In this context, the synthesis of chelators that also contain complementary functionalities to combat the multifactorial nature of neurodegenerative diseases is a highly topical issue. We report two new 8-hydroxyquinoline-appended cyclodextrins and highlight their multifunctional properties, including their Cu(II) and Zn(II) binding abilities, and capacity to act as antioxidants and metal-induced antiaggregants. In particular, the latter property has been applied in the development of an effective assay that exploits the formation of amyloid fibrils when ß-lactoglobulin A is heated in the presence of metal ions.