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https://www.readbyqxmd.com/read/28448733/endogenous-meningococcal-endophthalmitis-with-isolated-joint-involvement-in-immunocompetent-adults
#1
Vishal Shah, Anurag Garg, Miles Stanford
PURPOSE: We report two cases of endogenous meningococcal endophthalmitis in immunocompetent adults presenting with unilateral ocular disease and joint involvement. METHODS: A retrospective review of two patients with endogenous endophthalmitis due to Neisseria meningitidis with associated arthropathy was conducted. The clinical presentation, investigations, treatment, and outcomes are presented. RESULTS: Vitreous sampling confirmed Neisseria meningitidis via polymerase chain reaction (PCR) in both cases...
April 27, 2017: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/28438557/the-isozyme-selective-phosphodiesterase-4-inhibitor-abi-4-attenuates-the-effects-of-lipopolysaccharide-in-human-cells-and-rodent-models-of-peripheral-and-cns-inflammation
#2
Joseph R Hedde, Ashley N Hanks, Christopher J Schmidt, Zoë A Hughes
Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50 ∼14 nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32 mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice...
April 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28435519/gt198-psmc3ip-germline-variants-in-early-onset-breast-cancer-patients-from-hereditary-breast-and-ovarian-cancer-families
#3
Stephanie Schubert, Tim Ripperger, Melanie Rood, Anthony Petkidis, Winfried Hofmann, Hildegard Frye-Boukhriss, Marcel Tauscher, Bernd Auber, Ursula Hille-Betz, Thomas Illig, Brigitte Schlegelberger, Doris Steinemann
GT198, located 470 kb downstream of BRCA1, encodes for the nuclear PSMC3-interacting protein, which functions as co-activator of steroid hormone-mediated gene expression, and is involved in RAD51 and DMC1-mediated homologous recombination during DNA repair of double-strand breaks. Recently, germline variants in GT198 have been identified in hereditary breast and ovarian cancer (HBOC) patients, mainly in cases with early-onset. We screened a cohort of 166 BRCA1/2 mutation-negative HBOC patients, of which 56 developed early-onset breast cancer before the age of 36 years, for GT198 variants...
January 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28432813/targeting-on-poly-adp-ribose-polymerase-activity-with-dna-damaging-hybrid-lactam-steroid-alkylators-in-wild-type-and-brca1-mutated-ovarian-cancer-cells
#4
Dimitrios T Trafalis, Aikaterini Polonifi, Panayiotis Dalezis, Nikolaos Nikoleousakos, Sotirios Katsamakas, Vassiliki Sarli
Conjugated lactam-steroid alkylators (LSA), have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemotherapy. Hybrid LSAs combine two active compounds in a single molecule and incorporate modified steroids bearing lactam moiety in one or more steroid rings functioning as vectors for cytotoxic agents. We first describe a novel class of LSAs that generate excellent anticancer activity against UWB1.289 and UWB1.289+BRCA1 human ovarian cancer cell lines...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28432191/gene-expression-effects-of-glucocorticoid-and-mineralocorticoid-receptor-agonists-and-antagonists-on-normal-human-skeletal-muscle
#5
Jessica A Chadwick, James Spencer Hauck, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models...
April 21, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#6
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28428022/cloning-and-identification-of-a-novel-steroid-11%C3%AE-hydroxylase-gene-from-absidia-coerulea
#7
Ruijie Wang, Pengcheng Sui, Xiangjiang Hou, Tong Cao, Longgang Jia, Fuping Lu, Suren Singh, Zhengxiang Wang, Xiaoguang Liu
Steroid 11-hydroxylation by filamentous fungi is a major route for industrial scale production of key intermediates in the synthesis of steroid drugs. Although it is well established that enzymes involved in fungal hydroxylation of steroids are cytochrome P450s (CYP), few fungal steroid hydroxylase genes have been identified. In this study, we identified a novel 11α-hydroxylase gene CYP5311B1 from Absidia coerulea AS3.65 by a combination of transcriptome sequencing, Real-Time qRT-PCR and heterologous expression in Pichia pastoris...
April 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28420099/na%C3%A2-%C2%BAi-k%C3%A2-%C2%BAi-dependent-and-independent-signaling-triggered-by-cardiotonic-steroids-facts-and-artifacts
#8
REVIEW
Sergei N Orlov, Elizaveta A Klimanova, Artem M Tverskoi, Elizaveta A Vladychenskaya, Larisa V Smolyaninova, Olga D Lopina
Na⁺,K⁺-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na⁺ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na⁺i/K⁺i-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death...
April 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28416132/discovery-of-indazole-aldosterone-synthase-cyp11b2-inhibitors-as-potential-treatments-for-hypertension
#9
Scott B Hoyt, Jerry Taylor, Clare London, Amjad Ali, Feroze Ujjainwalla, Jim Tata, Mary Struthers, Doris Cully, Tom Wisniewski, Ning Ren, Charlene Bopp, Andrea Sok, Andreas Verras, Daniel McMasters, Qing Chen, Elaine Tung, Wei Tang, Gino Salituro, Joe Clemas, Gaochao Zhou, Douglas MacNeil, Ruth Duffy, Yusheng Xiong
We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement.
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28413460/early-application-of-low-dose-glucocorticoid-improves-acute-respiratory-distress-syndrome-a-meta-analysis-of-randomized-controlled-trials
#10
Zhi-Gang Yang, Xiao-Li Lei, Xiao-Liang Li
Previous clinical trials have investigated the effect of glucocorticoid therapy in acute respiratory distress syndrome (ARDS), with controversial results, particularly with regard to the early administration of low dose glucocorticoid. The present meta-analysis aimed to assess whether the application of glucocorticoid was able to reduce mortality in patients with ARDS. A literature search was performed using online databases, including MEDLINE, Embase, Cochrane and CNKI regardless of whether the studies were published in English or Chinese...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28408801/effects-of-%C3%AE-d-mannuronic-acid-as-a-novel-non-steroidal-anti-inflammatory-medication-within-immunosuppressive-properties-on-il17-ror%C3%AE-t-il4-and-gata3-gene-expressions-in-rheumatoid-arthritis-patients
#11
Anis Barati, Ahmad Reza Jamshidi, Hossein Ahmadi, Zahra Aghazadeh, Abbas Mirshafiey
Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28407818/-clinical-and-pathological-features-and-the-misdiagnosis-of-childhood-alport-syndrome-a-retrospective-analysis-of-91-cases
#12
Yan-Zhen Chen, Liang-Zhong Sun, Hai-Yan Wang, Xiao-Yun Jiang, Ying Mo, Zhi-Hui Yue, Hua-Mu Chen, Ting Liu, Hong-Rong Lin
OBJECTIVE: To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases...
April 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28406629/first-dual-inhibitors-of-steroid-sulfatase-sts-and-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-17%C3%AE-hsd1-designed-multiple-ligands-as-novel-potential-therapeutics-for-estrogen-dependent-diseases
#13
Mohamed Salah, Ahmed Saad Abdelsamie, Martin Frotscher
STS and 17β-HSD1 are attractive targets for the treatment of estrogen-dependent diseases like endometriosis and breast cancer. The simultaneous inhibition of both enzymes appears more promising than blockage of either protein alone. We describe a designed multiple target approach resulting in highly potent dual inhibitors. The most interesting compound 9 showed nanomolar IC50s for both proteins, membrane permeability and no interference with estrogen receptors. It efficiently reversed E1S- and E1-induced T47D cell proliferation...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28405841/focal-segmental-glomerulosclerosis-and-medullary-nephrocalcinosis-in-children-with-adck4-mutations
#14
Eujin Park, Hee Gyung Kang, Young Hun Choi, Kyoung Bun Lee, Kyung Chul Moon, Hyeon Joo Jeong, Michio Nagata, Hae Il Cheong
BACKGROUND: Mutations in the AarF domain containing kinase 4 gene (ADCK4), one of the novel genes causing steroid-resistant nephrotic syndrome (SRNS), usually manifest as isolated adolescent-onset focal segmental glomerulosclerosis (FSGS). ADCK4 interacts with components of the coenzyme Q10 (CoQ10) biosynthesis pathway. METHODS: The incidence and phenotypes of patients with ADCK4 mutations were investigated in a cohort of Korean pediatric patients with SRNS. RESULTS: Among the 53 patients enrolled in the study the incidence of ADCK4-associated FSGS was 7...
April 12, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28405725/the-posterolateral-approach-for-fluoroscopy-guided-tibiotalar-joint-injection
#15
Vanja Varenika, Jacob Harter, Edwin Chu, Lynne Steinbach
OBJECTIVE: To report a novel technique for tibiotalar joint injection that utilizes a posterolateral approach, including indications and technical considerations. METHODS: The posterolateral approach for tibiotalar injection is similar to that used in posterior subtalar joint injections. Using this technique, the tibiotalar joint space is accessed by directing the needle anterosuperiorly beneath the fibula until the posterior aspect of the talar dome has been reached...
April 12, 2017: Skeletal Radiology
https://www.readbyqxmd.com/read/28405499/combining-therapeutic-antibodies-using-basiliximab-and-etanercept-for-severe-steroid-refractory-acute-graft-versus-host-disease-a-multi-center-prospective-study
#16
Yamin Tan, Haowen Xiao, Depei Wu, Yi Luo, Jianping Lan, Qifa Liu, Kang Yu, Jimin Shi, Jingsong He, Weiyan Zheng, Xiaoyu Lai, Yuanyuan Zhu, Kaili Du, Yishan Ye, Yanmin Zhao, Gaofeng Zheng, Yongxian Hu, Xiaoyan Han, Yanlong Zheng, Guoqing Wei, Zhen Cai, He Huang
Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III-IV) SR-aGVHD with the combination of basiliximab and etanercept...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28401621/mouse-models-of-severe-asthma-understanding-the-mechanisms-of-steroid-resistance-tissue-remodelling-and-disease-exacerbation
#17
REVIEW
Steven Maltby, Hock L Tay, Ming Yang, Paul S Foster
Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e...
April 11, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28399454/detection-of-a-synthetic-sex-steroid-in-the-american-crocodile-crocodylus-acutus-evidence-for-a-novel-environmental-androgen
#18
Christopher M Murray, Mark Merchant, Michael Easter, Sergio Padilla, Davinia B Garrigós, Mahmood Sasa Marin, Craig Guyer
Endocrine-disrupting contaminants (EDC's) are well known to alter sexual differentiation among vertebrates via estrogenic effects during development, particularly in organisms characterized by temperature-dependent sex determination. However, substances producing androgenic effects typically lack potency when tested in laboratory settings and are virtually unstudied in field settings. Here, we assay levels of a synthetic androgen, 17α-methyltestosterone (MT), in a heavily male-biased population of American crocodiles in the Tempisque River Basin of Costa Rica based on the recent hypothesis that this chemical is an EDC in developing crocodilian embryos...
April 5, 2017: Chemosphere
https://www.readbyqxmd.com/read/28397770/prospecting-biotechnologically-relevant-monooxygenases-from-cold-sediment-metagenomes-an-in-silico-approach
#19
Matías A Musumeci, Mariana Lozada, Daniela V Rial, Walter P Mac Cormack, Janet K Jansson, Sara Sjöling, JoLynn Carroll, Hebe M Dionisi
The goal of this work was to identify sequences encoding monooxygenase biocatalysts with novel features by in silico mining an assembled metagenomic dataset of polar and subpolar marine sediments. The targeted enzyme sequences were Baeyer-Villiger and bacterial cytochrome P450 monooxygenases (CYP153). These enzymes have wide-ranging applications, from the synthesis of steroids, antibiotics, mycotoxins and pheromones to the synthesis of monomers for polymerization and anticancer precursors, due to their extraordinary enantio-, regio-, and chemo- selectivity that are valuable features for organic synthesis...
April 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28396535/pregnancy-reprograms-large-conductance-ca-2-activated-k-channel-in-uterine-arteries-roles-of-ten-eleven-translocation-methylcytosine-dioxygenase-1-mediated-active-demethylation
#20
Xiang-Qun Hu, Chiranjib Dasgupta, Man Chen, Daliao Xiao, Xiaohui Huang, Limin Han, Shumei Yang, Zhice Xu, Lubo Zhang
The large-conductance Ca(2+)-activated K(+) (BKCa) channel is of critical importance in pregnancy-mediated increase in uterine artery vasodilation and blood flow. The present study tested the hypothesis that active DNA demethylation plays a key role in pregnancy-induced reprogramming and upregulation of BKCa channel β1 subunit (BKβ1) in uterine arteries. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Pregnancy significantly increased the expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in uterine arteries...
April 10, 2017: Hypertension
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