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S R Geed, Sachin Prasad, M K Kureel, R S Singh, B N Rai
The isolated microbial Alcaligenes sp. S3 from the agricultural field was used for the biodegradation of synthetic wastewater containing atrazine. This study was conducted in an alternating aerobic-anoxic lab scale pilot plant. The performance of continuously operated pilot plant was evaluated in three different phases with varying atrazine concentration. The best performance of plant was observed in phase-II. The atrazine (200 mg/L) having COD value 1356 mg/L was used with varying flow rate and 90.56% COD removal was obtained at a flow rate of 300 mL/h on 122th day of operation...
March 13, 2018: Journal of Environmental Management
Jared T Hammill, Daniel C Scott, Jaeki Min, Michele C Connelly, Gloria Holbrook, Fangyi Zhu, Amy Matheny, Lei Yang, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit...
March 16, 2018: Journal of Medicinal Chemistry
Jared T Hammill, Deepak Bhasin, Daniel C Scott, Jaeki Min, Yizhe Chen, Yan Lu, Lei Yang, Ho Shin Kim, Michele C Connelly, Courtney Hammill, Gloria Holbrook, Cynthia Jeffries, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously reported the discovery, validation, and structure-activity relationships of a series of piperidinyl ureas that potently inhibit the DCN1-UBE2M interaction. We demonstrated that compound 7 inhibits both the DCN1-UBE2M protein-protein interaction and DCN1-mediated cullin neddylation in biochemical assays and reduces levels of steady-state cullin neddylation in a squamous carcinoma cell line harboring DCN1 amplification. Although compound 7 exhibits good solubility and permeability, it is rapidly metabolized in microsomal models (CLint = 170 mL/min/kg)...
March 16, 2018: Journal of Medicinal Chemistry
Oscar H L Bing
Ammonia plays a central role in the life and death of all living organisms and has been studied for over one hundred years. Ammonia is necessary for growth and development but it is toxic in excess and, as a result, differing methods of ammonia neutralization have evolved. Following physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is FDA approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia clearance...
March 16, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Nicholette D Palmer, Hayrettin Okut, Fang-Chi Hsu, Maggie C Y Ng, Yii-Der Ida Chen, Mark O Goodarzi, Kent D Taylor, Jill M Norris, Carlos Lorenzo, Jerome I Rotter, Richard N Bergman, Carl D Langefeld, Lynne E Wagenknecht, Donald W Bowden
Context: Metabolomics provides a biochemical fingerprint which, when coupled with clinical phenotypes, can provide insight into physiological processes and disease. Objective: Survey metabolites associated with dynamic and basal measures of glucose homeostasis. Design: Analysis of 733 serum metabolites from the Insulin Resistance Atherosclerosis Family Study. Setting: Community-based. Participants: 1111 Mexican Americans...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Yizi Xia, Ying Chen, Luming Tang, Zheng Wang, Yu Zheng
Acute kidney injury (AKI) is a severe complication of sepsis with a high mortality and morbidity. Pterostilbene (Pte) has been suggested to confer anti-apoptotic and anti-inflammatory effects. In the current study, the effects of Pte on AKI were evaluated in septic mice. Cecal ligation and puncture surgery was performed to induce sepsis. The results suggested that Pte administration significantly decreased the levels of serum urea nitrogen and creatinine, and improved the survival rate of septic mice. Additionally, the renal injury induced by sepsis was attenuated by pterostilbene treatment...
April 2018: Experimental and Therapeutic Medicine
Shuhong Zhang, Guangzhu Yang, Qinghua Ye, Qingping Wu, Jumei Zhang, Yuanbin Huang
Klebsiella pneumoniae is not only a major hospital-acquired pathogen but also an important food-borne pathogen that can cause septicaemia, liver abscesses, and diarrhea in humans. The phenotypic and genotypic characteristics of K. pneumoniae in retail foods have not been thoroughly investigated in China. The objective of this study was to characterize K. pneumoniae isolates through biotyping, serotyping, determination of virulence factors, antibiotic resistance testing, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), and (GTG)5 -PCR molecular typing...
2018: Frontiers in Microbiology
Yi Zhang, Melanie Berghaus, Sean Klein, Kelly Jenkins, Siwen Zhang, Scott A McCallum, Joel Morgan, Roland Winter, Doug Barrick, Catherine A Royer
Many repeat proteins contain capping motifs, which serve to shield the hydrophobic core from solvent and maintain structural integrity. While the role of capping motifs in enhancing the stability and structural integrity of repeat proteins is well-documented, their contribution to folding cooperativity is not. Here we examined the role of capping motifs in defining the folding cooperativity of the leucine rich repeat protein, pp32, by monitoring the pressure and urea induced unfolding of an N-cap deletion mutant, pp32-∆N-cap, and a C-cap destabilization mutant pp32-Y131F/D146L, using residue specific NMR and SAXS...
March 12, 2018: Journal of Molecular Biology
K Isoda, T Nozawa, Y Taira, I Taira, Y Shimizu, I Ishida
Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury...
March 5, 2018: Die Pharmazie
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
Lawrence Mj Best, Yemisi Takwoingi, Sulman Siddique, Abiram Selladurai, Akash Gandhi, Benjamin Low, Mohammad Yaghoobi, Kurinchi Selvan Gurusamy
BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain...
March 15, 2018: Cochrane Database of Systematic Reviews
Asim Badar, Zarina Arif, Khursheed Alam
Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: Nα -amino moiety of a protein N-terminus and the Nɛ -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis...
March 15, 2018: IUBMB Life
W Weinrebe, S Käbe-Frisch, I Füsgen, M Karaman, E Johannsdottir, S Rupp
OBJECTIVE: To compare the efficacy of desmopressin and placebo in independent geriatric outpatients with nocturnal polyuria (NP). METHODS: A prospective, randomized, single-center, national, double blind, placebo-controlled, fixed-dose, parallel group comparative trial was carried out. The study included 110 geriatric outpatients, 55 patients per treatment group using desmopressin acetate nasal spray (strength: 0.1 mg/ml) once daily of 10 μg/spray blast or placebo...
March 14, 2018: Zeitschrift Für Gerontologie und Geriatrie
Thomas Knoepfel, Pascal Furet, Robert Mah, Nicole Buschmann, Catherine Leblanc, Sebastien Ripoche, Diana Graus-Porta, Markus Wartmann, Inga Galuba, Robin A Fairhurst
As part of a project to identify FGFR4 selective inhibitors, scaffold morphing of a 2-formylquinoline amide hit identified series of 2-formylpyridine ureas (2-FPUs) with improved potency and physicochemical properties. In particular, tetrahydronaphthyridine urea analogues with cellular activities below 30 nM have been identified. Consistent with the hypothesized reversible-covalent mechanism of inhibition, the 2-FPUs exhibited slow binding kinetics, and the aldehyde, as the putative electrophile, could be demonstrated to be a key structural element for activity...
March 8, 2018: ACS Medicinal Chemistry Letters
Yanle Guo, Min Zhang, Zhiguang Liu, Xiaofei Tian, Shugang Zhang, Chenhao Zhao, Hao Lu
Previous research into the synthesis of urea-formaldehyde fertilizers was mostly based on orthogonal experimental designs or single factor tests; this led to low precision for synthesis and relatively large ranges of parameters for these processes. To obtain mathematical response models for the synthesis of urea-formaldehyde fertilizers with different nitrogen release properties, a central composite design (CCD) of response surface methodology was used in our research to examine the effects of different reaction times, temperatures, and molar ratios on nitrogen insoluble in either hot or cold water...
March 14, 2018: Scientific Reports
Didem Onk, Fatih Özçelik, Oruç Alper Onk, Murat Günay, Tülin Akarsu Ayazoğlu, Ethem Ünver
BACKGROUND The present study sought to assess the renal and liver protective effect of N-acetylcysteine through NH3 and urea metabolism in patients with chronic obstructive pulmonary disease who were scheduled for coronary artery bypass grafting surgery. MATERIAL AND METHODS Patients with chronic obstructive pulmonary disease (COPD) who were scheduled for coronary artery bypass grafting were divided into 2 groups so as to receive (Group 1, n=35) or not receive (Group 2, n=35) 900 mg/day of n-acetylcysteine for 7 days before the operation starting from their admission to the service by a pulmonologist with the purpose of treating COPD until the day of surgery...
March 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Mohamed Ghanem, Mohamed Zeineldin, Attia Eissa, Eman El Ebissy, Rasha Mohammed, Yassein Abdelraof
The objective of this study was to evaluate the impact of varying degrees of water salinity on the ultrasonographical and histopathological appearance of the liver and kidneys in Barki sheep. Thirty Barki sheep (initial weight, 29.48 ± 0.81 kg) were allocated into three groups (n=10 per group) based on the type of drinking water for 9 months: the tap water (TW) group (350 ppm total dissolved solids [TDS]); the moderate saline water (MSW) group (4557 ppm TDS); and the high saline water (HSW) group (8934 ppm TDS)...
March 14, 2018: Journal of Veterinary Medical Science
Christabel Y L Chan, Kum C Hiong, Mel V Boo, Celine Y L Choo, Wai P Wong, Shit F Chew, Yuen K Ip
Giant clams live in nutrient-poor reef waters of the Indo-Pacific and rely on symbiotic dinoflagellates ( Symbiodinium spp., also known as zooxanthellae) for nutrients. As the symbionts are nitrogen deficient, the host clam has to absorb exogenous nitrogen and supply it to them. This study aimed to demonstrate light-enhanced urea absorption in the fluted giant clam, Tridacna squamosa , and to clone and characterize the urea active transporter, DUR3-like, from its ctenidium (gill). Results indicate that T. squamosa could absorb exogenous urea, and the rate of urea uptake in light was significantly higher than that in darkness...
March 14, 2018: Journal of Experimental Biology
N R Hill, H T Cook, C D Pusey, R M Tarzi
BACKGROUND: Necrotizing glomerular lesions are a feature of severe glomerulonephritis. Unlike apoptosis, cellular necrosis has the potential to release damage-associated proteins into the microenvironment, thereby potentiating inflammation. Until recently necrosis was thought to be an unregulated cellular response to injury. However, recent evidence suggests that under certain circumstances receptor mediated necrosis occurs in response to death ligand signalling, one form of which is termed necroptosis...
March 14, 2018: BMC Nephrology
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