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https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#1
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28924114/long-interval-cytapheresis-as-a-novel-therapeutic-strategy-leading-to-dosage-reduction-and-discontinuation-of-steroids-in-steroid-dependent-ulcerative-colitis
#2
Masahiro Iizuka, Takeshi Etou, Makoto Kumagai, Atsushi Matsuoka, Yuka Numata, Shiho Sagara
Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28923543/selective-glucocorticoid-receptor-modulation-inhibits-cytokine-responses-in-a-canine-model-of-mild-endotoxemia
#3
J Bartko, U Derhaschnig, T Neels, G H Nabozny, C Harcken, J Leuschner, F De Vries, B Jilma
Selective glucocorticoid receptor modulators (GRMs) promise to reduce adverse events of glucocorticoids while maintaining anti-inflammatory potency. The present study tested the anti-inflammatory activity of two novel non-steroidal GRMs (GRM1: BI 607812 BS, GRM2: BI 653048 BS*H3PO4) in comparison to prednisolone in a canine model of low dose endotoxemia. This study compared the anti-inflammatory and pharmacokinetic profile of escalating daily oral doses of GRM1 (1, 2.5, 5 and 10mg/kg) and GRM2 (0.1, 0.25 and 1mg/kg) with prednisolone (0...
September 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28920065/the-influence-of-sex-steroid-hormones-on-the-response-to-trauma-and-burn-injury
#4
REVIEW
K Al-Tarrah, N Moiemen, J M Lord
Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure. Regardless of the type and severity of injury, gender dimorphism in outcomes following trauma have been reported, with females having lower mortality than males, suggesting that sex steroid hormones (SSH) play an important role in the response of body systems to trauma. In addition, several clinical and experimental studies have demonstrated the effects of SSH on the clinical course and outcomes following injury...
2017: Burns and trauma
https://www.readbyqxmd.com/read/28919755/synthetic-high-density-lipoprotein-nanodisks-for-targeted-withalongolide-delivery-to-adrenocortical-carcinoma
#5
Rui Kuai, Chitra Subramanian, Peter T White, Barbara N Timmermann, James J Moon, Mark S Cohen, Anna Schwendeman
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs), which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative - withalongolide A 4,19,27-triacetate (WGA-TA) - which has shown potent antitumor efficacy, but poor aqueous solubility...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28919448/review-7%C3%AE-hydroxypregnenolone-regulating-locomotor-behavior-identified-in-the-brain-and-pineal-gland-across-vertebrates
#6
REVIEW
Kazuyoshi Tsutsui, Shogo Haraguchi, Hubert Vaudry
The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. Based on extensive studies on neurosteroids over the past thirty years, it is now accepted that neurosteroidogenesis in the brain is a conserved property across vertebrates. However, the formation of bioactive neurosteroids in the brain is still incompletely elucidated in vertebrates. In fact, we recently identified 7 α -hydroxypregnenolone (7 α -OH PREG) as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates...
September 14, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28919152/erector-spinae-plane-esp-block-in-the-management-of-post-thoracotomy-pain-syndrome-a-case-series
#7
Mauricio Forero, Manikandan Rajarathinam, Sanjib Adhikary, Ki Jinn Chin
BACKGROUND AND AIMS: Post thoracotomy pain syndrome (PTPS) remains a common complication of thoracic surgery with significant impact on patients' quality of life. Management usually involves a multidisciplinary approach that includes oral and topical analgesics, performing appropriate interventional techniques, and coordinating additional care such as physiotherapy, psychotherapy and rehabilitation. A variety of interventional procedures have been described to treat PTPS that is inadequately managed with systemic or topical analgesics...
September 11, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/28918115/the-interplay-of-endocrine-therapy-steroid-pathways-and-therapeutic-resistance-importance-of-androgen-in-breast-carcinoma
#8
REVIEW
Kiyoshi Takagi, Yasuhiro Miki, Takanori Ishida, Hironobu Sasano, Takashi Suzuki
A great majority of breast carcinomas expresses estrogen receptor (ER) and estrogens have crucial roles in the progress of breast carcinomas. Endocrine therapy targeting ER and/or intratumoral estrogen production significantly improved clinical outcomes of the patients with ER-positive breast carcinomas. However, resistance to endocrine therapy is often observed and significant number of patients will recur after the treatment. In addition, treatment for the patients with triple-negative breast carcinomas (negative for all ER, progesterone receptor (PR) and HER2) are limited to cytotoxic chemotherapy and novel therapeutic targets need to be identified...
September 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28912031/hormones-and-the-coolidge-effect
#9
REVIEW
Elisa Ventura-Aquino, Alonso Fernández-Guasti, Raúl G Paredes
The Coolidge effect is the renewal of sexual behavior after the presentation of a novel sexual partner and possibly occurs as the result of habituation and dishabituation processes. This re-motivation to copulate is well studied in males and is commonly related to sexual satiety, which involves several neurobiological changes in steroid receptors and their mRNA expression in the CNS. On the other hand, there are few reports studying sexual novelty in females and have been limited to behavioral aspects. Here we report that the levels of rat proceptive behavior, a sign of sexual motivation, declines after 4 h of continuous mating, particularly in females that were unable to regulate the time of mating...
September 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28899802/the-new-targeted-therapy-in-systemic-lupus-erythematosus-is-the-glass-half-full-or-half-empty
#10
REVIEW
Andrea Doria, Ricard Cervera, Mariele Gatto, Gamal Chehab, Matthias Schneider
Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage. In this viewpoint, the authors summarize their views for a "half-full or half-empty" glass on targeted therapy in SLE. The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28895370/eosinophilic-esophagitis-current-evidence-based-diagnosis-and-treatment-in-children-and-adults
#11
Alfredo J Lucendo
Eosinophilic esophagitis (EoE) is a disease caused by an immune response to food antigens in contact with the esophageal mucosa that has arisen as a common disorder in current clinical practice. Its diagnosis is defined by the combination of symptoms of esophageal dysfunction and inflammation of the esophageal mucosa predominantly by eosinophils. Its chronic course and frequent progression to subepithelial fibrosis leading to strictures and narrow-caliber esophagus indicate the need for treatment. Information provided by recent clinical trials and systematic reviews allowed for the development of new clinical guidelines, endorsed by several European scientific societies...
September 11, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28894020/transcription-factor-oswrky53-positively-regulates-brassinosteroid-signaling-and-plant-architecture
#12
Xiaojie Tian, Xiufeng Li, Wenjia Zhou, Yuekun Ren, Zhenyu Wang, Zhiqi Liu, Jiaqi Tang, Hongning Tong, Jun Fang, Qingyun Bu
Brassinosteroids (BRs) are a class of steroid hormones regulating multiple aspects of plant growth, development, and adaptation. Compared with extensive studies in Arabidopsis, the mechanism of BR signaling in rice is less understood. Here, we identified OsWRKY53, a transcription factor involved in defense responses, as an important regulator of rice BR signaling. Phenotypic analyses showed that OsWRKY53 overexpression led to enlarged leaf angles and increased grain size, in contrast to the erect leaves and smaller seeds in oswrky53 mutant...
September 11, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28889957/pathophysiology-of-preterm-labor-with-intact-membranes
#13
REVIEW
Asha N Talati, David N Hackney, Sam Mesiano
Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor...
September 7, 2017: Seminars in Perinatology
https://www.readbyqxmd.com/read/28889921/pd-1-checkpoint-inhibition-toxicities-and-management
#14
REVIEW
Andrew W Hahn, David M Gill, Neeraj Agarwal, Benjamin L Maughan
PURPOSE: With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. MATERIALS AND METHODS: In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab...
September 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28888822/discovery-of-novel-steroidal-histamine-h3-receptor-antagonists-inverse-agonists
#15
Istvan Ledneczki, Pál Tapolcsányi, Eszter Gábor, János Éles, István Greiner, Éva Schmidt, Zsolt Némethy, Rita Soukupné Kedves, Ottilia Balázs, Viktor Román, György Lévay, Sándor Mahó
Emerging from an HTS campaign, novel steroid-based histamine H3 receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H3 receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28888712/simultaneous-optimization-of-ph-and-binary-organic-composition-by-grid-form-modeling-of-the-retention-behavior-in-reversed-phase-ultra-high-performance-liquid-chromatography
#16
Tsukasa Sasaki, Kenichiro Todoroki, Toshimasa Toyo'oka
A novel computer-assisted methodology for the simultaneous optimization of aqueous pH and binary organic eluent composition through a broad range of analytical conditions of reversed-phase ultra high-performance liquid chromatography is proposed. Two of nonlinear prediction models were employed to fit into the retention time (tR) on a linear gradient elution with a predefined slope. One model was derived from Bernoulli-type probability distribution to predict the value of tR against the pH value of the aqueous eluent...
September 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28888424/novel-patient-missense-mutations-in-the-hsd17b10-gene-affect-dehydrogenase-and-mitochondrial-trna-modification-functions-of-the-encoded-protein
#17
Stephanie Oerum, Martine Roovers, Michael Leichsenring, Cécile Acquaviva-Bourdain, Frauke Beermann, Corinne Gemperle-Britschgi, Alain Fouilhoux, Anne Korwitz-Reichelt, Henry J Bailey, Louis Droogmans, Udo Oppermann, Jörn Oliver Sass, Wyatt W Yue
MRPP2 (also known as HSD10/SDR5C1) is a multifunctional protein that harbours both catalytic and non-catalytic functions. The protein belongs to the short-chain dehydrogenase/reductases (SDR) family and is involved in the catabolism of isoleucine in vivo and steroid metabolism in vitro. MRPP2 also moonlights in a complex with the MRPP1 (also known as TRMT10C) protein for N1-methylation of purines at position 9 of mitochondrial tRNA, and in a complex with MRPP1 and MRPP3 (also known as PRORP) proteins for 5'-end processing of mitochondrial precursor tRNA...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28881288/hydroxytriazole-derivatives-as-potent-and-selective-aldo-keto-reductase-1c3-akr1c3-inhibitors-discovered-by-bioisosteric-scaffold-hopping-approach
#18
Agnese C Pippione, Alessandro Giraudo, Davide Bonanni, Irene M Carnovale, Elisabetta Marini, Clara Cena, Annalisa Costale, Daniele Zonari, Klaus Pors, Maria Sadiq, Donatella Boschi, Simonetta Oliaro-Bosso, Marco L Lolli
The aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy. Although AKR1C3 is a promising drug target, no AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid, a non-steroidal anti-inflammatory drug, is known to potently inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. To diminish off-target effects, we have applied a scaffold hopping strategy replacing the benzoic acid moiety of flufenamic acid with an acidic hydroxyazolecarbonylic scaffold...
August 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28880396/drug-repurposing-to-treat-asthma-and-allergic-disorders-progress-and-prospects
#19
REVIEW
Robert L Kruse, Kristine Vanijcharoenkarn
Allergy and atopic asthma have continued to become more prevalent in modern society despite the advent of new treatments, representing a major global health problem. Common medications such as antihistamines and steroids may have undesirable long-term side effects and lack efficacy in some resistant patients. Biologic medications are increasingly given to treat resistant patients, but they can represent high costs, complex dosing and management, and are not widely available around the world. The field needs new, cheap and convenient treatment options in order to bring better symptom relief to patients...
September 7, 2017: Allergy
https://www.readbyqxmd.com/read/28879428/difficult-to-treat-idiopathic-nephrotic-syndrome-established-drugs-open-questions-and-future-options
#20
REVIEW
Markus J Kemper, Lisa Valentin, Michael van Husen
The idiopathic nephrotic syndrome in childhood can be classified according to the International Study of Kidney Disease in Children (ISKDC) based on the response to steroids. Typically, steroid-sensitive nephrotic syndrome (SSNS) is characterised by minimal changes in disease (MCD) histology, whereas in steroid-resistant nephrotic syndrome (SRNS) focal segmental glomerulosclerosis (FSGS) is the most prevalent lesion. Patients with SSNS may develop frequent relapses and/or steroid dependency, which can be difficult to treat...
September 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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