SR 16584

Laparoscopic Silastic Ring Mini-Gastric Bypass (SR-MGBP): Up to 11-Year Results from a Single Centre.[Pubmed:28378207]

Obes Surg. 2017 Sep;27(9):2229-2234.

BACKGROUND: Bariatric surgery is well established as an effective method for treating obesity and its related comorbidities. The laparoscopic mini-gastric bypass (MGBP) represents a simpler alternative to a Roux-en-Y gastric bypass (RYGBP). The placement of a silastic ring (SR) may enhance excess weight loss and minimize weight regain. This study reports long-term results from a cohort of patients undergoing a SR-MGBP in a single centre. METHODS: Long-term outcomes (up to 11 years) in a cohort of 156 patients undergoing surgery between August 2005 and January 2008 were analysed. A combination of follow-up questionnaires and electronic hospital records were used to assess weight loss, comorbidity resolution and complications. RESULTS: A total of 156 patients (mean body mass index 46 kg/m(2)) underwent surgery. Ninety-two patients responded to the follow-up questionnaires. Computer-based hospital information was available on a total of 139 patients. Mean percent excess weight loss (%EWL) at 11 years was 84.3%. Comorbidity resolution, determined by medication use, showed a reduction in diabetes (21.8% to 7.1%), hypertension (37.2% to 21.4%) and hypercholesterolaemia (40.4% to 13.4%). Five of 139 patients (3.6%) had SR problems needing removal. Two other patients had the SR changed to a bigger size and a further two had endoscopic removal of the SR for erosion. Of the 139 patients, 9.4% required conversion to a Roux-en-Y gastric bypass (RYGBP). The number of patients on anti-reflux medications increased from 5.1% to 44.6% at 11 years. There were two deaths unrelated to surgery. CONCLUSIONS: SR-MGBP appears to be a safe and effective operation for the morbidly obese. It is durable, with good weight loss at up to 11 years post-surgery. The SR can easily be removed or exchanged for another size and is reasonable to consider when performing a MGBP. Concerns about bile reflux appear to be well founded, and some patients who are poorly controlled medically will require revision.

Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester.[Pubmed:28373285]

J Biol Chem. 2017 May 26;292(21):8864-8873.

Reverse cholesterol transport (transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver) is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process: "gobbling," i.e. one-step transfer of all HDL-CE to the cell and "nibbling," multiple successive cycles of SR-B1-HDL association during which a few CEs transfer to the cell. Concurrently, we compared cellular uptake of apoAI with that of apoAII, which is more lipophilic than apoAI, using HDL-[(3)H]CE labeled with [(125)I]apoAI or [(125)I]apoAII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR(-/-)) with (CHO-SR-B1) and without SR-B1 overexpression and in human Huh7 hepatocytes. Relative to CE, both apoAI and apoAII were excluded from uptake by all cells. However, apoAII was more highly excluded from uptake (2-4x) than apoAI. To distinguish gobbling versus nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size-exclusion chromatography, and the distribution of apoAI, apoAII, cholesterol, and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e. nibbling, with the concurrent release of lipid-free apoAI; apoAII was retained in an HDL remnant. Our data support an SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apoAI, leaving an apoAII-rich remnant.

VEGF-A Regulates Cellular Localization of SR-BI as Well as Transendothelial Transport of HDL but Not LDL.[Pubmed:28360088]

Arterioscler Thromb Vasc Biol. 2017 May;37(5):794-803.

OBJECTIVE: Low- and high-density lipoproteins (LDL and HDL) must pass the endothelial layer to exert pro- and antiatherogenic activities, respectively, within the vascular wall. However, the rate-limiting factors that mediate transendothelial transport of lipoproteins are yet little known. Therefore, we performed a high-throughput screen with kinase drug inhibitors to identify modulators of transendothelial LDL and HDL transport. APPROACH AND RESULTS: Microscopy-based high-content screening was performed by incubating human aortic endothelial cells with 141 kinase-inhibiting drugs and fluorescent-labeled LDL or HDL. Inhibitors of vascular endothelial growth factor (VEGF) receptors (VEGFR) significantly decreased the uptake of HDL but not LDL. Silencing of VEGF receptor 2 significantly decreased cellular binding, association, and transendothelial transport of (125)I-HDL but not (125)I-LDL. RNA interference with VEGF receptor 1 or VEGF receptor 3 had no effect. Binding, uptake, and transport of HDL but not LDL were strongly reduced in the absence of VEGF-A from the cell culture medium and were restored by the addition of VEGF-A. The restoring effect of VEGF-A on endothelial binding, uptake, and transport of HDL was abrogated by pharmacological inhibition of phosphatidyl-inositol 3 kinase/protein kinase B or p38 mitogen-activated protein kinase, as well as silencing of scavenger receptor BI. Moreover, the presence of VEGF-A was found to be a prerequisite for the localization of scavenger receptor BI in the plasma membrane of endothelial cells. CONCLUSIONS: The identification of VEGF as a regulatory factor of transendothelial transport of HDL but not LDL supports the concept that the endothelium is a specific and, hence, druggable barrier for the entry of lipoproteins into the vascular wall.

Potential plant growth-promoting strain Bacillus sp. SR-2-1/1 decolorized azo dyes through NADH-ubiquinone:oxidoreductase activity.[Pubmed:28365345]

Bioresour Technol. 2017 Jul;235:176-184.

In this study, a bacterial strain SR-2-1/1 was isolated from textile wastewater-irrigated soil for its concurrent potential of plant growth promotion and azo-dye decolorization. Analysis of 16S rRNA gene sequence confirmed its identity as Bacillus sp. The strain tolerated high concentrations (i.e. up to 1000mgL(-1)) of metals (Ni(2+), Cd(2+), Co(2+), Zn(2+), and Cr(6+)) and efficiently decolorized the azo dyes (i.e. reactive black-5, reactive red-120, direct blue-1 and congo red). It also demonstrated considerable in vitro phosphate solubilizing and 1-aminocyclopropane-1-carboxylic acid deaminase abilities at high metal and salt levels. Bioinformatics analysis of its 537bp azoreductase gene and deduced protein revealed that it decolorized azo dyes through NADH-ubiquinone:oxidoreductase enzyme activity. The deduced protein was predicted structurally and functionally different to those of its closely related database proteins. Thus, the strain SR-2-1/1 is a powerful bioinoculant for bioremediation of textile wastewater contaminated soils in addition to stimulation of plant growth.

Novel alpha3beta4 nicotinic acetylcholine receptor-selective ligands. Discovery, structure-activity studies, and pharmacological evaluation.[Pubmed:20979364]

J Med Chem. 2010 Nov 25;53(22):8187-91.

Antagonist activity at the alpha3beta4 nicotinic acetylcholine receptor (nAChR) is thought to contribute to the antiaddictive properties of several compounds. However, truly selective ligands for the alpha3beta4 nAChR have not been available. We report the discovery and SAR of a novel class of compounds that bind to the alpha3beta4 nAChR and have no measurable affinity for the alpha4beta2 or alpha7 subtype. In functional assays the lead compound antagonized epibatidine-induced Ca(2+) flux in alpha3beta4-transfected cells in a noncompetitive manner.