Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) produces more durable glycemic control than sleeve gastrectomy (SG) or intensive medical therapy (IMT). However, the contribution of acylated ghrelin (AG), a gluco-regulatory/appetite hormone, to improve glucose metabolism and body composition in patients with type 2 diabetes (T2D) following RYGB is unknown. DESIGN: STAMPEDE (Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently) was a prospective, randomized controlled trial. SUBJECTS: Fifty-three (body mass index: 36±3 kg m(-2), age: 49±9 years) poorly controlled patients with T2D (HbA1c (glycated hemoglobin): 9.7±2%) were randomized to IMT, IMT+RYGB or IMT+SG and underwent a mixed-meal tolerance test at baseline, 12, and 24 months for evaluation of AG suppression (postprandial minus fasting) and beta-cell function (oral disposition index; glucose-stimulated insulin secretion × Matsuda index). Total/android body fat (dual-energy X-ray absorptiometry) was also assessed. RESULTS: RYGB and SG reduced body fat comparably (15-23 kg) at 12 and 24 months, whereas IMT had no effect. Beta-cell function increased 5.8-fold in RYGB and was greater than IMT at 24 months (P<0.001). However, there was no difference in insulin secretion between SG vs IMT at 24 months (P=0.32). Fasting AG was reduced fourfold following SG (P<0.01) and did not change with RYGB or IMT at 24 months. AG suppression improved more following RYGB than SG or IMT at 24 months (P=0.01 vs SG, P=0.07 vs IMT). At 24 months, AG suppression was associated with increased postprandial glucagon-like peptide-1 (r=-0.32, P<0.02) and decreased android fat (r=0.38; P<0.006). CONCLUSIONS: Enhanced AG suppression persists for up to 2 years after RYGB, and this effect is associated with decreased android obesity and improved insulin secretion. Together, these findings suggest that AG suppression is partly responsible for the improved glucose control after RYGB surgery.

Ghrelin suppression is associated with weight loss and insulin action following gastric bypass surgery at 12 months in obese adults with type 2 diabetes.

Roux-en-Y gastric bypass (RYGB) surgery reverses type 2 diabetes mellitus (T2DM) in approximately 80% of patients. Ghrelin regulates glucose homeostasis, but its role in T2DM remission after RYGB surgery is unclear. Nine obese T2DM subjects underwent a mixed meal tolerance test before and at 1 and 12 months after RYGB surgery. Changes in ghrelin, body weight, glucagon-like polypeptide-1 (GLP-1, glucose tolerance and insulin sensitivity (IS) were measured. At 1 month, body weight, glycaemia and IS were improved, while ghrelin concentrations were reduced (p < 0.05). After 12 months, body weight and fasting glucose were reduced (30 and 16%, respectively; p < 0.05) and IS was enhanced (threefold; p < 0.05). Ghrelin suppression improved by 32% at 12 months (p < 0.05), and this was associated with weight loss (r = 0.72, p = 0.03), enhanced IS (r = -0.78, p = 0.01) and peak postprandial GLP-1 (r = -0.73, p = 0.03). These data suggest that postprandial ghrelin suppression may be part of the mechanism that contributes to diabetes remission after RYGB surgery.

2,2'-Bis{8-[(benzyl-amino)-methyl-idene]-1,6-dihy-droxy-5-isopropyl-3-methyl-naphthalen-7(8H)-one}.

The asymmetric unit of the title compound, C44H44N2O6, contains two independent mol-ecules with similar conformations. The di-hydro-naphthalene ring systems are approximately planar [maximum deviations = 0.036 (2), 0.128 (2), 0.0.24 (2) and 0.075 (2) Å]. The dihedral angle between two di-hydro-naphthalene ring systems is 83.37 (4)° in one mol-ecule and 88.99 (4)° in the other. The carbonyl O atom is linked with the adjacent hy-droxy and imino groups via intra-molecular O-H⋯O and N-H⋯O hydrogen bonds. In the crystal, mol-ecules are linked through O-H⋯O hydrogen bonds into layers parallel to (001), and adjacent layers are further stacked by π-π inter-actions between di-hydro-naphthalene and phenyl rings into a three-dimensional supra-molecular architecture. In the crystal, one of the isopropyl groups is disordered over two positions with an occupancy ratio of 0.684 (8):0.316 (8).

Desoxyhemigossypol 6-methyl ether.

THE TITLE SESQUITERPENE [SYSTEMATIC NAME: 6-methoxy-10-methyl-7-(propan-2-yl)-2-oxatricyclo[6.3.1.0(4,12)]dodeca-1(11),4,6,8(12),9-pentaen-5-ol], C(16)H(18)O(3), was isolated from pathogen-infected stele tissue of Gossypium barbadense. There are two mol-ecules in the asymmetric unit and the dihedral angle between their naphtho-furan systems is 86.48 (2)°. In the crystal, O-H⋯O hydrogen bonds between the hy-droxy groups and etheric O atoms link the mol-ecules into centrosymmetric tetra-mers. These tetra-mers are assembled into (010) layers via stacking inter-actions between the naphtho-furan systems [inter-planar distance 3.473 (3) Å] and short C-H⋯O contacts.

Lacinilene C 7-methyl ether.

The title compound, C16H20O3 [systematic name: 1-hy-droxy-7-meth-oxy-1,6-dimethyl-4-(propan-2-yl)naphthalen-2(1H)-one], is a sesquiterpene isolated from foliar tissues of the cotton plant and is of inter-est with respect to its anti-bacterial properties. Its phenyl ring is ideally planar, and the maximum of deviation in the second ring is 0.386 (3) Å. The hy-droxy group and the methyl group are oriented in an equatorial fashion and axial, respectively, to the second ring. In the crystal, inversion dimers are formed through pairs of O-H⋯O hydrogen bonds. Weak C-H⋯O hydrogen bonds link the dimers into columns along the c axis. These columns form a crystal structure with a crystal packing factor of 0.66.

Bis(7-meth-oxy-1-methyl-4,9-dihydro-3H-ß-carbolinium) tetra-chloridozincate.

In the title compound, (C(13)H(15)N(2)O)(2)[ZnCl(4)], also known as di(harmalinium) tetra-chloridozincate, the Zn(II) atom is in a distorted tetrahedral coordination of the chlorido ligands. In the cation, the meth-oxy and methyl groups are both coplanar with with rings to which they are attached [maximum deviations of 0.232 (4) and 0.259 (4) Å, respectively]. In the crystal, the alkaloid cations and metal complex anions inter-act by way of N-H⋯Cl hydrogen bonds involving each Cl atom, resulting in a network structure.

Bis(acetyl-acetonato-κO,O')(2-amino-1-methyl-1H-benzimidazole-κN)oxido-vanadium(IV).

The title mixed-ligand oxidovanadium(IV) compound, [VO(C(5)H(7)O(2))(2)(C(8)H(9)N(3))], contains a V(IV) atom in a distorted octahedral coordination, which is typical for such complexes. The vanadyl group and the N-heterocyclic ligand are cis to each other. The coordination bond is located at the endocyclic N atom of the benzimidazole ligand. Intra-molecular hydrogen bonds between the exo-NH(2) group H atoms and acetyl-acetonate O atoms stabilize the crystal structure.

Crystal structure of bis-p-anizidinegossypol with an unknown solvate.

The title compound, C44H44N2O8, (systematic name: 1,1',6,6'-tetra-hydroxy-5,5'-diisopropyl-8,8'-bis-{[(4-meth-oxy-phen-yl)iminium-yl]meth-yl}-3,3'-dimethyl-2,2'-bi-naphthalene-7,7'-diolate) has been obtained by the addition of p-anizidine to gossypol dissolved in di-chloro-methane. In the solid state, the title compound exists in the enamine or quinoid form. The two naphthyl moieties are inclined to one another by 72.08 (5)°. The pendant phenyl rings are inclined at 22.26 (14) and 23.86 (13)° to the corresponding naphthyl rings. In the crystal, mol-ecules are incorporated into layers through inversion-related pairs of O-H⋯O inter-actions [graph sets R 2 (2)(20) and R 2 (2)(10)] and translation-related O-H⋯O inter-actions [graph set C(15)]. The packing of these layers in the crystal structure gives rise to channels in the [011] direction, with hydro-phobic inter-actions occurring between adjacent layers. The channels are 5-7 Šwide, and the void volume of each cell is 655 Å(3), corresponding to 26.6% of the cell volume. Disordered guest mol-ecules, probably solvent and water mol-ecules, occupy these voids of the crystal; their contribution to the scattering was removed with the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] of PLATON [Spek (2009 ▸). Acta Cryst. D65, 148-155].

Population growth, trophic level, and reproductive biology of two congeneric archer fishes (Toxotes chatareus, Hamilton 1822 and Toxotes jaculatrix, Pallas 1767) inhabiting Malaysian coastal waters.

Population growth, trophic level, and some aspects of reproductive biology of two congeneric archer fish species, Toxotes chatareus and Toxotes jaculatrix, collected from Johor coastal waters, Malaysia, were studied. Growth pattern by length-weight relationship (W=aL(b)) for the sexes differed, and exhibited positive allometric growth (male, female and combined sexes of T. chatareus; female and combined sexes of T. jaculatrix) and isometric growth (male samples of T. jaculatrix only). Trophic levels of both species were analyzed based on 128 specimens. The results show that, in both species, crustaceans and insects were the most abundant prey items, and among crustaceans the red clawed crab Sesarma bidens and Formicidae family insects were the most represented taxa. The estimated mean trophic levels for T. chatareus and T. jaculatrix were 3.422+/-0.009 and 3.420+/-0.020, respectively, indicating that they are largely carnivores. Fecundity of T. chatareus ranged from 38 354 to 147 185 eggs for females with total length ranging from 14.5 to 22.5 cm and total body weight from 48.7 to 270.2 g, and T. jaculatrix 25 251 to 150 456 eggs for females with total length ranging from 12.2 to 23.0 cm and total body weight from 25.7 to 275.0 g. Differences in values of gonadosomatic and hepatosomatic indexes calculated for both species in this study may have resulted from uneven sample size ranges.

Quantum chemical study of the photocoloration reaction in the napthoxazine series.

Ab initio and semiempirical quantum mechanical calculations were performed to study the electronic spectra of spiroxazine photochromic compounds as well as the corresponding photoisomers. Ground-state geometries were optimized based on density functional theory (DFT). Excitation energies of the different forms were calculated using the time-dependent density functional theory (TD-DFT) method. Semiempirical calculations including configuration interactions were performed to detail the mechanism of ring opening in excited states. On the basis of the obtained potential energy profile, a complete mechanism of photocoloration able to clarify some experimental findings is provided. A correlation of the experimental quantum yield of photocoloration with the calculated properties as a function of substituent effects is proposed.

In vitro chemosensitivity of Plasmodium falciparum to four chloroquine derivatives.

The antimalarial activity of four chloroquine derivatives has been assessed in vitro by the Trager and Jensen technique against the strain of Plasmodium falciparum FCC, 2spp. Monodesethyl-chloroquine possessed a significant activity, reducing the parasitaemia to 5% with 2 nM ml-1 (base). The hydroxy-metabolite showed a slight activity, reducing the parasitaemia to 39.5% with 2 nM ml-1 (base). No activity was found with the amino-metabolite and the pyrrolidinyl chemical derivative. The anti-malarial activity of monodesethyl-chloroquine should be considered for pharmacokinetics and for optimizing chloroquine treatments.