<b><i>Introduction:</i></b> Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. <b><i>Materials and Methods:</i></b> This is a prospective pilot study including patients (<i>n</i> = 21) with PHH after RYGB, matched by age and gender with healthy controls (<i>n</i> = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. <b><i>Results:</i></b> OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, <i>p</i> &#x3c; 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, <i>p</i> = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, <i>p</i> &#x3c; 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (<i>p</i> &#x3c; 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. <b><i>Conclusion:</i></b> Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.

Four new chiral coordination polymers (CPs), {[Cu(HL n )MeOH]•NO 3 } ∞ (n = 1−4), were obtained using a chiral building block synthesized from the condensation reaction of L-or D-valine with an imidazole aldehyde. These CPs crystallize in a noncentrosymmetric space group P2 1 2 1 2 1 , evidencing that the chirality of the α-amino acid valine is transferred to the structure of the coordination polymer. Moreover, the CPs present a 1D structure with a Cu(II) cation in a square base pyramid geometry formed by two units of chiral ligand and a methanol molecule. The magnetic measurement and theoretical calculations show that the Cu(II) spin carriers are magnetically communicated through the carboxylate bridge, presenting a 1D ferromagnetic chain behavior. Furthermore, four new stable molecular compounds [Cu(HL n )-DMSO] + (n = 1−4), sharing the same chiral building block of CPs, were characterized by circular dichroism (CD). The theoretical electronic excited states of the molecular compounds reproduce the CD experimental spectra showing that the intrinsic chiral activity of the α-amino acid Schiff base is transferred to the Cu(II) centers. Remarkably, using crystal engineering tools, a family of chiral coordination compounds was obtained and analyzed combining several experimental and theoretical approaches, leading to a robust understanding of its chemical and physical properties.

Objective: To evaluate the impact of patient follicular environment with oxidative stress on oocyte quality. Methods: Patients on fertility treatment with either advanced maternal age or endometriosis were asked to donate follicular fluid collected during ovum pick-up. Follicular fluid (FF) was added (20%, 10% and 5%; %V/V) to in vitro maturation (IVM) medium with mouse oocytes. Following maturation culture, the oocytes were assessed for meiosis reinitiation. In a second setup, coenzyme Q10 was added to culture medium with FF. In addition to assessing meiotic maturation, a subset of oocytes was assessed for spindle structure and chromosome alignment. Results: Supplementation of IVM medium with FF of patients of advanced maternal age (with or without antioxidants) did not have an effect on the maturation capacity of mouse oocytes. However, the addition of FF of individuals with endometriosis (without antioxidants) in the two highest concentrations affected oocyte maturation (61.5% & 57.0% maturation) compared with the lowest concentration (89.2% maturation) ( p <0.05). Supplementation of medium with coenzyme Q10 did not improve the maturation rate of oocytes exposed to the FF of individuals with endometriosis (28.5±13.7%) ( p <0.05). Nevertheless, preliminary analysis of spindle abnormality and chromosome alignment revealed that oocytes resuming meiosis in the presence of FF of patients with endometriosis displayed aberrant spindle morphology and chromosomal misalignment. Conclusion: The follicular environment of patients with endometriosis severely affected oocyte (nuclear) maturation. In vitro maturation in the presence of coenzyme Q10 appears to be a tool for rescuing oocytes exposed to such follicular environment.

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex®improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex®is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.

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