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Istvan Foldi, Niki Anthoney, Neale Harrison, Monique Gangloff, Brett Verstak, Mohanakarthik Ponnadai Nallasivan, Samaher AlAhmed, Bangfu Zhu, Mark Phizacklea, Maria Losada-Perez, Marta Moreira, Nicholas J Gay, Alicia Hidalgo
Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75(NTR) receptors and cell death via p75(NTR) and Sortilin. Drosophila NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism...
April 3, 2017: Journal of Cell Biology
Moriteru Asano, Takenori Hitaka, Takashi Imada, Masami Yamada, Megumi Morimoto, Hiromi Shinohara, Takahito Hara, Masuo Yamaoka, Takashi Santou, Masaharu Nakayama, Yumi Imai, Noriyuki Habuka, Jason Yano, Keith Wilson, Hisashi Fujita, Atsushi Hasuoka
We recently reported a class of novel tissue-selective androgen receptor modulators (SARMs), represented by a naphthalene derivative A. However, their pharmacokinetic (PK) profiles were poor due to low metabolic stability. To improve the PK profiles, we modified the hydroxypyrrolidine and benzonitrile substituents of 4-(pyrrolidin-1-yl)benzonitrile derivative B, which had a comparable potency as that of compound A. This optimization led us to further modifications, which improved metabolic stability while maintaining potent androgen agonistic activity...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
Mario Thevis, Wilhelm Schänzer
The class of selective androgen receptor modulators (SARMs) has been the subject of intense and dedicated clinical research over the past two decades. Potential therapeutic applications of SARMs are manifold and focus particularly on the treatment of conditions manifesting in muscle loss such as general sarcopenia, cancer-associated cachexia, muscular dystrophy, etc. Consequently, based on the substantial muscle- and bone-anabolic properties of SARMs, these agents constitute substances with significant potential for misuse in sport and have therefore been added to the Word Anti-Doping Agency's (WADA's) Prohibited List in 2008...
January 27, 2017: Molecular and Cellular Endocrinology
Gökmen Kurt, Ayşe Tuba Altuğ, Gökhan Türker, Banu Kiliç, Erdem Kiliç, Alper Alkan
AIM: The aim of the present study was to compare the effects of surgical and nonsurgical rapid maxillary expansion (RME) in skeletally mature patients. MATERIALS AND METHODS: Surgically assisted rapid maxillary expansion (SARME) was used in 18 patients (2 males, 16 females) with a mean age of 19.90 years. Two nonsurgical RME groups were constructed to compare the expansion changes of SARME. Eighteen patients in maximum pubertal peak (12 males, 6 females) with a mean age of 13...
January 27, 2017: Journal of Craniofacial Surgery
Thomas Jensen, Maria Rodrigo-Domingo
OBJECTIVE: To assess nasal septum deviation after surgically assisted rapid maxillary expansion (SARME) with or without intraoperative releasing of the nasal septum. STUDY DESIGN: A total of 20 consecutive adult patients with transverse maxillary deficiency underwent SARME with intraoperative releasing (n = 10) or nonreleasing (n = 10) of the nasal septum. Cone beam computed tomography scans were obtained immediately after surgery (T1), after the end of distraction (T2), and 6 months after SARME (T3)...
March 2017: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Sara Divari, Enrica Berio, Paola Pregel, Alessandra Sereno, Luca Chiesa, Radmila Pavlovic, Sara Panseri, Toine F H Bovee, Bartolomeo Biolatti, Francesca T Cannizzo
The present study describes different effects of the selective androgen receptor modulator (SARM) nandrolone phenylpropionate (Nandrosol) and the β-agonist ractopamine administration in veal calves, and it investigates different strategies applied to trace these molecules. Morphological changes of gonads and accessory glands attributed to androgen effects, such as testicular atrophy, seminiferous tubule diameter reduction and hyperplasia of prostate epithelium, were detected, although SARMs are not described to cause these lesions...
April 15, 2017: Food Chemistry
J P de Gijt, A Gül, S T H Tjoa, E B Wolvius, K G H van der Wal, M J Koudstaal
Surgically-assisted rapid maxillary expansion (SARME) is a technique used to widen the maxilla, and we present the results of our long-term follow up (6.5 years). Seventeen patients who had been treated with SARME and prospectively followed were invited for long-term follow up using dental casts and posteroanterior cephalograms. The following measurements were made on the dental casts: transverse distances at canine, premolar, and molar level, length of the arch, and width and depth of the palate at premolar and molar level...
January 2017: British Journal of Oral & Maxillofacial Surgery
Nora Cesbron, Alexandre Sydor, Mylène Penot, Stéphanie Prevost, Bruno Le Bizec, Gaud Dervilly-Pinel
Selective androgen receptor modulators (SARMs) are a novel class of androgen receptor ligands. They are intended to exhibit the same kind of effects as androgenic drugs, like anabolic steroids, but be much more selective in their action, targeting particular tissues without any undesirable effects on others. While the main applications of these synthetic substances are for therapeutic purposes, they also have a high potential for misuse in veterinary practice and the sporting world. In order to guarantee for consumers with food from animal origin that it is free from any residues of such compounds, analytical strategies are required to ensure safe food and also to enable fair trade between producers...
April 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Dante Rojas, Gaud Dervilly-Pinel, Nora Cesbron, Mylène Penot, Alexandre Sydor, Stéphanie Prévost, Bruno Le Bizec
Besides their development for therapeutic purposes, non-steroidal selective androgen receptor modulators (non-steroidal SARMs) are also known to impact growth-associated pathways as ligands of androgenic receptors (AR). They present a potential for abuse in sports and food-producing animals as an interesting alternative to anabolic androgenic steroids (AAS). These compounds are easily available and could therefore be (mis)used in livestock production as growth promoters. To prevent such practices, dedicated analytical strategies should be developed for specific and sensitive detection of these compounds in biological matrices...
October 11, 2016: Drug Testing and Analysis
Christian Görgens, Sven Guddat, Andreas Thomas, Philipp Wachsmuth, Anne-Katrin Orlovius, Gerd Sigmund, Mario Thevis, Wilhelm Schänzer
So far, in sports drug testing compounds of different classes are processed and measured using different screening procedures. The constantly increasing number of samples in doping analysis, as well as the large number of substances with doping related, pharmacological effects require the development of even more powerful assays than those already employed in sports drug testing, indispensably with reduced sample preparation procedures. The analysis of native urine samples after direct injection provides a promising analytical approach, which thereby possesses a broad applicability to many different compounds and their metabolites, without a time-consuming sample preparation...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
Suriyan Ponnusamy, Ryan D Sullivan, Thirumagal Thiyagarajan, Heather Tillmann, Robert H Getzenberg, Ramesh Narayanan
Stress urinary incontinence (SUI), a prevalent condition, is represented by an involuntary leakage of urine that results, at least in part, from weakened or damaged pelvic floor muscles and is triggered by physical stress. Current treatment options are limited with no oral therapies available. The pelvic floor is rich in androgen receptor and molecules with anabolic activity including selective androgen receptor modulators (SARMs) may serve as therapeutic options for individuals with SUI. In this study, two SARMs (GTx-024 and GTx-027) were evaluated in a post-menopausal animal model in order to determine their effect on pelvic floor muscles...
September 28, 2016: Journal of Cellular Biochemistry
Yu Gong, Lin Zou, Dongzhi Cen, Wei Chao, Dunjin Chen
Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens...
December 2016: Inflammation
Christopher Wu, Jason R Kovac
There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states...
October 2016: Current Urology Reports
Mohammad Zandi, Amirfarhang Miresmaeili, Ali Heidari, Arash Lamei
PURPOSE: To evaluate and compare the short-term skeletal and dental changes following surgically assisted rapid maxillary expansion (SARME) with or without pterygomaxillary disjunction (PTMD) using cone beam computed tomography (CBCT). MATERIAL AND METHODS: In present study, a total of 15 consecutive patients with transverse maxillary deficiency underwent SARME without PTMD. This prospective group was compared to one arm of a randomized controlled clinical trial the authors of present study published in 2014, in which 15 patients underwent SARME with PTMD...
September 2016: Journal of Cranio-maxillo-facial Surgery
Vishnu Lal Sharma, Sonal Gupta, Gopal Gupta
Proliferation of the smooth muscle and epithelial cells within the prostatic transition zone in older men leads to benign prostatic hyperplasia (BPH) which is hallmarked by the troublesome lower urinary tract symptoms. The affair responsible for the initiation and promotion of disease is still unresolved. Alpha blockers and 5α-reductase inhibitors are used as management options for relief of the dynamic and static components respectively. Combination therapy including both the alpha blocker and 5α-reductase inhibitors is emerging as inclusive parcel for treatment...
June 30, 2016: Mini Reviews in Medicinal Chemistry
Felix Kunz, Christian Linz, Gregor Baunach, Hartmut Böhm, Philipp Meyer-Marcotty
OBJECTIVES: The purpose of this work was to compare the patterns of expansion resulting from a tooth-borne hyrax appliance and a bone-borne transpalatal distractor in patients treated by surgically assisted rapid maxillary expansion (SARME). METHODS: A total of 28 patients with transverse maxillary hypoplasia were treated by SARME, using a hyrax appliance in 12 and a transpalatal distractor in 16 cases. Before and after palatal expansion, an impression of each maxilla was taken...
September 2016: Journal of Orofacial Orthopedics, Fortschritte der Kieferorthopädie
Andreas Lagojda, Dirk Kuehne, Oliver Krug, Andreas Thomas, Tina Wigger, Uwe Karst, Wilhelm Schänzer, Mario Thevis
Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus...
2016: European Journal of Mass Spectrometry
Kenta Watanabe, Michiko Hirata, Tsukasa Tominari, Chiho Matsumoto, Yasuyuki Endo, Gillian Murphy, Hideaki Nagase, Masaki Inada, Chisato Miyaura
Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321...
September 9, 2016: Biochemical and Biophysical Research Communications
Toshihiko Yanase
In recent years, the drugs, which show anabolic, effect on bone and muscle without stimulating prostate has been developed. They show tissue-specific selective androgen actions and called selective androgen receptor modulators(SARMs). The development of drug targeting bone and muscle in male is very promising as a treatment tool for osteoporosis and sarcopenia in the near future. The clinical study is under going especially in the field of cachexia associated with cancer, but unfortunately there is no drug in the current market at present...
July 2016: Clinical Calcium
O Tšuiko, M Nõukas, O Žilina, K Hensen, J S Tapanainen, R Mägi, M Kals, P A Kivistik, K Haller-Kikkatalo, A Salumets, A Kurg
STUDY QUESTION: Can spontaneous premature ovarian failure (POF) patients derived from population-based biobanks reveal the association between copy number variations (CNVs) and POF? SUMMARY ANSWER: CNVs can hamper the functional capacity of ovaries by disrupting key genes and pathways essential for proper ovarian function. WHAT IS KNOWN ALREADY: POF is defined as the cessation of ovarian function before the age of 40 years. POF is a major reason for female infertility, although its cause remains largely unknown...
August 2016: Human Reproduction
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