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Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped-hyperglycemic clamp in 15 T2DM and 15 non-diabetic subjects after 2 days and after more chronic (14 days) treatment with empagliflozin. T2DM patients had significantly greater maximal renal glucose transport (TmG) compared to nondiabetic subjects at baseline (459±53 vs 337±25 mg/min, p<0.05). Empagliflozin treatment for 48 hours reduced the TmG in both diabetic and non-diabetic individuals by 44±7% and 53±6%, respectively (both p<0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65±5% and 75±3%, respectively)...
April 20, 2017: Diabetes
Kelsey L Borrell, Christine Cancglin, Brittany L Stinger, Kelsey G DeFrates, Gregory A Caputo, Chun Wu, Timothy D Vaden
The search for biocompatible ionic liquids (ILs) with novel biochemical and biomedical applications has recently gained greater attention. In this report we characterize the effects of two novel amino acid-based aqueous ILs composed of tetramethylguanidinium (TMG) and amino acids on the structure and stability of a widely used red fluorescent protein (mCherry). Our experimental data shows that while the aspartic acid-based IL (TMGAsp) has effects similar to previously-studied conventional ILs (BMIBF4, EMIAc, and TMGAc), the alanine-based IL (TMGAla) has a much stronger destabilization effect on the protein structure...
April 20, 2017: Journal of Physical Chemistry. B
Mun-Young Lee, Dong Kwon Yang, Shang-Jin Kim
Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg(2+) levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg(2+) as the physiologically active form...
March 17, 2017: Biological Trace Element Research
Yoshinori Tsumura, Yu Tsushima, Azusa Tamura, Makiko Hasebe, Masanobu Kanou, Hirotsugu Kato, Tsunefumi Kobayashi
Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues...
2017: PloS One
Atul Narang, Stefan Oehler
The lac (lactose) operon (processes β-galactosides) and the mel (melibiose) operon (processes α-galactosides) of Escherichia coli have a close historical connection. A number of shared substrates and effectors of the permeases and regulatory proteins has been reported over the years. Up to now, β-thiogalactosides like TMG (methyl-β-D-thiogalactopyranoside) and IPTG (isopropyl-β-D-thiogalactopyranoside) are generally not considered inducers of the mel operon. The same is true for β-galactosides like lactose (β-D-galactopyranosyl-(1→4)-D-glucose), which is a substrate, but itself not an inducer of the lac operon...
February 13, 2017: Journal of Bacteriology
Tian Liu, Lei Chen, Yong Zhou, Xi Jiang, Yanwei Duan, Qing Yang
Chitinase-h (Chi-h) is of special interest among insect chitinases due to its exclusive distribution in lepidopteran insects and high sequence identity with bacterial and baculovirus homologs. Here OfChi-h, a Chi-h from Ostrinia furnacalis, was investigated. Crystal structures of both OfChi-h and its complex with chitoheptaose ((GlcN)7) reveal that OfChi-h possesses a long and asymmetric substrate binding cleft, which is a typical characteristics of a processive exo-chitinase. The structural comparison between OfChi-h and its bacterial homolog SmChiA uncovered two phenylalanine-to-tryptophan site variants in OfChi-h at subsites +2 and possibly -7...
February 10, 2017: Journal of Biological Chemistry
Xinpeng Zhang, Weixian Xi, Chen Wang, Maciej Podgórski, Christopher N Bowman
An efficient visible-light-sensitive photobase generator for thiol-Michael addition reactions was synthesized and evaluated. This highly reactive catalyst was designed by protecting a strong base (tetramethyl guanidine, TMG) with a visible-light-responsive group which was a coumarin derivative. The coumarin-coupled TMG was shown to exhibit extraordinary catalytic activity toward initiation of the thiol-Michael reaction, including thiol-Michael addition-based polymerization, upon visible-light irradiation, leading to a stoichiometric reaction of both thiol and vinyl functional groups...
February 16, 2016: ACS Macro Letters
Rieneke Terink, Michael G J Balvers, Maria T Hopman, Renger F Witkamp, Marco Mensink, Jacqueline M T Klein Gunnewiek
Magnesium is essential for optimal sport performance, generating an interest to monitor its status in athletes. However, before measuring magnesium status in blood could become routine, more insight into its diurnal fluctuations and effects of exercise itself is necessary. Therefore, we measured the effect of an acute bout of exercise on ionized (iMg) and total plasma magnesium (tMg) in blood obtained from 18 healthy well-trained endurance athletes (age, 31.1 ± 8.1 yr.; VO2max, 50.9 ± 7.5 ml/kg/min) at multiple time points, and compared this with a resting situation...
December 20, 2016: International Journal of Sport Nutrition and Exercise Metabolism
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
Jinfang Wang, Zhimin Xue, Chuanyu Yan, Zhonghao Li, Tiancheng Mu
In this study, the fine regulation of the dissolution and regeneration of microcrystalline cellulose (MCC) using very low pressure (0-0.2 MPa) CO2 in a mixed solvent of dimethyl sulfoxide (DMSO) and 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU) at a very low temperature (30 °C) was achieved. The solubility of MCC in DMSO/DBU (weight ratio of DMSO WDMSO = 0.90) could reach 9.0% at 30 °C and under CO2 pressure of 0.2 MPa. A similar phenomenon was observed in the mixed solvent DMSO/1,1,3,3-tetramethylguanidine (TMG)...
December 7, 2016: Physical Chemistry Chemical Physics: PCCP
Yating He, Xiaofeng Ma, Daojing Li, Junwei Hao
Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke...
January 1, 2016: Journal of Cerebral Blood Flow and Metabolism
Maria Parkhurst, Alena Gros, Anna Pasetto, Todd Prickett, Jessica S Crystal, Paul Robbins, Steven A Rosenberg
Purpose: The adoptive transfer of lymphocytes genetically modified to express tumor reactive T-cell receptors (TCR) can mediate tumor regression. Some tumor-infiltrating lymphocytes (TIL) recognize somatic mutations expressed only in the patient's tumors, and evidence suggests that clinically effective TILs target tumor-specific neoantigens. Here we attempted to isolate neoantigen-reactive TCRs as a prelude to the treatment of patients with autologous T cells genetically modified to express such TCRs.Experimental Design: Mutations expressed by tumors were identified using whole-exome and RNA sequencing...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jacqulyne P Robichaux, John W Fuseler, Shrusti S Patel, Steven W Kubalak, Adam Hartstone-Rose, Ann F Ramsdell
Left-right (L-R) differences in mammographic parenchymal patterns are an early predictor of breast cancer risk; however, the basis for this asymmetry is unknown. Here, we use retinoid X receptor alpha heterozygous null (RXRα(+/-)) mice to propose a developmental origin: perturbation of coordinated anterior-posterior (A-P) and L-R axial body patterning. We hypothesized that by analogy to somitogenesis-in which retinoic acid (RA) attenuation causes anterior somite pairs to develop L-R asynchronously-that RA pathway perturbation would likewise result in asymmetric mammary development...
December 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Emine Cinici, Nihal Cetin, Bahadir Suleyman, Durdu Altuner, Oguzhan Yarali, Hilal Balta, Ilknur Calik, Levent Tumkaya, Halis Suleyman
AIM: To compare the effects of thiamine pyrophosphate (TPP) and thiamine (TM) in oxidative optic neuropathy in rats induced by ethambutol. METHODS: The animals were divided into four groups: a control group (CG), an ethambutol control (ETC) group, TM plus ethambutol group (TMG), and TPP plus ethambutol group (TPPG). One hour after intraperitoneal administration of TM 20 mg/kg to the TMG group and TPP 20 mg/kg to TPPG group, 30 mg/kg ethambutol was given via gavage to all the groups but the CG...
2016: International Journal of Ophthalmology
Irineu Loturco, Lucas A Pereira, Ronaldo Kobal, Katia Kitamura, Rodrigo Ramírez-Campillo, Vinicius Zanetti, Cesar C Cal Abad, Fabio Y Nakamura
Tensiomyography (TMG) has been used as a simple and non-invasive tool to assess the mechanical properties of skeletal muscles. The TMG-derived velocity of contraction (Vc), which can be calculated from the ratio between maximal radial displacement and the sum of contraction time and delay time, has been proposed for evaluating athletes. However, its sensitivity to training effects and possible relation with changes in soccer players' neuromuscular performance have not yet been addressed. To test this possibility, twenty-two male Brazilian elite soccer players were assessed using TMG-derived Vc, unloaded squat jump, countermovement jump and drop jump at 45 cm, loaded jump squat and linear (20 m) and change of direction (COD) sprint tests, prior to and after an 8-week period, between two consecutive official tournaments, during which the concurrency between endurance and strength-power training commonly impairs neuromuscular capacities...
September 2016: Journal of Sports Science & Medicine
Filip Křemen, Martin Gazvoda, Stanislav Kafka, Karel Proisl, Anna Srholcová, Antonin Klasek, Damijana Urankar, Janez Košmrlj
An unprecedented reactivity of 3-aminoquinoline-2,4-diones is reported. Under basic conditions these compounds undergo molecular rearrangement to furnish 1,4-benzodiazepine-2,5-diones. The transformations take place under mild reaction conditions by using 1,1,3,3-tetramethylguanidine (TMG), NaOEt, or benzyltrimethylammonium hydroxide (Triton B) as a base. A proposed mechanism of the rearrangement and the conformational equilibrium of 1,4-benzodiazepine-2,5-dione rings are discussed.
October 27, 2016: Journal of Organic Chemistry
Wenjun Li, Xiao Zhou, Zhenyan Shi, Yang Liu, Zhantao Liu, Hua Gao
TMG-promoted [3 + 2] organocatalytic 1,3-dipolar cycloaddition reactions of allyl ketones with in situ generated nitrile oxides have been developed. This strategy could generate 3,5-disubstituted isoxazolines in high yields and regioselectivities.
October 10, 2016: Organic & Biomolecular Chemistry
Emily Harrop, Simon Noble, Michelle Edwards, Stephanie Sivell, Barbara Moore, Annmarie Nelson
BACKGROUND: Few studies have explored in depth the experiences of patients with advanced cancer who are participating in clinical investigational medicinal product trials. However, integrated qualitative studies in such trials are needed to enable a broader evaluation of patient experiences in the trial, with important ethical and practical implications for the design and conduct of similar trials and treatment regimes in the future. METHODS: Ten participants were recruited from the control and intervention arms of FRAGMATIC: a non-placebo trial for patients with advanced lung cancer...
July 20, 2016: Trials
Christopher M Zall, John C Linehan, Aaron M Appel
The copper(I) triphosphine complex LCu(MeCN)PF6 (L = 1,1,1-tris(diphenylphosphinomethyl)ethane), which we recently demonstrated is an active catalyst precursor for hydrogenation of CO2 to formate, reacts with H2 in the presence of a base to form a cationic dicopper hydride, [(LCu)2H]PF6. [(LCu)2H](+) is also an active precursor for catalytic CO2 hydrogenation, with equivalent activity to that of LCu(MeCN)(+), and therefore may be a relevant catalytic intermediate. The thermodynamic hydricity of [(LCu)2H](+) was determined to be 41...
August 10, 2016: Journal of the American Chemical Society
Rafaela Muniz de Queiroz, Rashna Madan, Jeremy Chien, Wagner Barbosa Dias, Chad Slawson
O-GlcNAcylation is a dynamic post-translational modification consisting of the addition of a single N-acetylglucosamine sugar to serine and threonine residues in proteins by the enzyme O-linked β-N-acetylglucosamine transferase (OGT), whereas the enzyme O-GlcNAcase (OGA) removes the modification. In cancer, tumor samples present with altered O-GlcNAcylation; however, changes in O-GlcNAcylation are not consistent between tumor types. Interestingly, the tumor suppressor p53 is modified by O-GlcNAc, and most solid tumors contain mutations in p53 leading to the loss of p53 function...
September 2, 2016: Journal of Biological Chemistry
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