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Anabolic agents

Brendan T Finicle, Vaishali Jayashankar, Aimee L Edinger
While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis...
August 10, 2018: Nature Reviews. Cancer
Andrea V Haas, Meryl S LeBoff
Medications for osteoporosis are classified as either antiresorptive or anabolic. Whereas antiresorptive agents prevent bone resorption, anabolic agents promote new bone formation. Anabolics should be considered in individuals with severe osteoporosis, failure of alternative osteoporosis agents, intolerability or contraindications to other osteoporosis agents, and glucocorticoid-induced osteoporosis. There are currently two approved anabolic therapies, teriparatide and abaloparatide, and a third anabolic agent, romozosumab, is under review by the US Food and Drug Administration...
August 1, 2018: Journal of the Endocrine Society
Yanzhi Liu, Zhenshan Jia, Mohammed P Akhter, Xiang Gao, Xiaobei Wang, Xiaoyan Wang, Gang Zhao, Xin Wei, You Zhou, Xiuli Wang, Curtis W Hartman, Edward V Fehringer, Liao Cui, Dong Wang
Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo...
August 2, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jeffrey P Chmielewski, Sarah C Bowlby, Frances B Wheeler, Lihong Shi, Guangchao Sui, Amanda L Davis, Timothy D Howard, Ralph B D'Agostino, Lance D Miller, S Joseph Sirintrapun, Scott D Cramer, Steven J Kridel
Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on nicotinamide adenine dinucleotide (NAD+) as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD+ also serves as a substrate for poly ADP-ribose polymerases (PARPs), sirtuins, and cyclic ADP-ribose synthases. Dysregulation of the cyclic ADP-ribose synthase CD38, the main NAD'ase in cells, is reported in multiple cancer types. This study demonstrates a novel connection between CD38, modulation of NAD+, and tumor cell metabolism in prostate cancer (PCa)...
August 3, 2018: Molecular Cancer Research: MCR
Joseph Matthew Armstrong, Ross A Avant, Cameron M Charchenko, Mary E Westerman, Matthew J Ziegelmann, Tanner S Miest, Landon W Trost
Background: To describe the impact of supra-physiologic anabolic-androgenic steroid (AAS) use, including agent, dosage, and duration of therapy, on sexual function. Methods: We reviewed data from an online survey of AAS users to evaluate their sexual function on and off AAS. The online survey consisted of questions addressing demographics, anabolic steroid use and patterns, ancillary medications, testosterone (T)-related symptoms while on and off of therapy, as well as sexual function which was assessed using the 5-item, International Index of Erectile Function (IIEF-5)...
June 2018: Translational Andrology and Urology
Lin Li, Mei Lin He, Kai Wang, Yuanshu Zhang
Ruminants are often fed a high-concentrate (HC) diet to meet lactating demands, yet long-term concentrate feeding induces subacute ruminal acidosis (SARA) and leads to a decrease in milk fat. Buffering agent could enhance the acid base buffer capacity and has been used to prevent ruminant rumen SARA and improve the content of milk fat. Therefore, we tested whether a buffering agent increases lipid anabolism in the livers of goats and influences of milk fat synthesis. Twelve Saanen-lactating goats were randomly assigned to two groups: one group received a HC diet (Concentrate : Forage = 60:40, Control) and the other group received the same diet with a buffering agent added (10 g sodium butyrate, C(4)H(7)NaO(2); 10 g sodium bicarbonate, NaHCO(3); BG) over a 20-week experimental period...
July 25, 2018: Physiological Research
Matthew Cohn, Arianna L Gianakos, Kirsten Grueter, Natalie Rosen, Guang-Ting Cong, Joseph M Lane
The prevention and treatment of fragility fractures continuously evolves. Adequate fracture care should involve treating the fracture itself as well as the underlying bone disease. Although effective treatments of osteoporosis are available, a large proportion of patients with fragility fractures are not prescribed anti-osteoporotic medications after their injury. Recent advances in diagnostic tools, medications, and implementation of Fracture Liaison Services (FLS) allow for more effective and comprehensive treatment or fragility fractures...
July 20, 2018: Journal of Orthopaedic Trauma
Amanda L Silveira, Mauro Lúcio G de Oliveira, Diego G Rocha, Sérgio Dracz, Thiago F Borgati, Mary Ane G Lana, Rodinei Augusti, Adriana F Faria
In this work, a GC-MS/MS method was developed for the determination of anabolic-agent residues in bovine urine. The optimized sample preparation was as follows: enzymatic hydrolysis by β-glucuronidase-sulfatase enzyme from Helix pomatia for 16 h at 37.5 °C, liquid-liquid extraction with diethyl ether, solid-phase extraction with HLB and aminopropylsilane cartridges, and microwave-assisted derivatization using 25 μL of MSTFA/NH4 I/ethanethiol and full microwave power for 2 min. The method was validated according to Decision 657/2002/EC, Codex Alimentarius, and Manual da Garantia da Qualidade Analítica guidelines...
August 1, 2018: Journal of Agricultural and Food Chemistry
Christina Vrahnas, Pascal R Buenzli, Thomas A Pearson, Brenda L Pennypacker, Mark J Tobin, Keith R Bambery, Le T Duong, Natalie A Sims
Bone is formed by deposition of a collagen-containing matrix (osteoid) that hardens over time as mineral crystals accrue and are modified; this continues until bone remodeling renews that site. Pharmacological agents for osteoporosis differ in their effects on bone remodeling, and we hypothesized that they may differently modify bone mineral accrual. We, therefore, assessed newly formed bone in mature ovariectomized rabbits treated with the anti-resorptive bisphosphonate alendronate (ALN-100µ g/kg/2×/week), the anabolic parathyroid hormone (PTH (1-34)-15µ g/kg/5×/week), or the experimental anti-resorptive odanacatib (ODN 7...
July 17, 2018: Calcified Tissue International
María Díaz López, Juan José Alegre Sancho, Àngels Martínez-Ferrer
Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered...
July 14, 2018: Reumatología Clinica
Pragati Kushwaha, Ashish Kumar Tripathi, Sampa Gupta, Priyanka Kothari, Akanksha Upadhyay, Naseer Ahmad, Tanuj Sharma, M I Siddiqi, Ritu Trivedi, Koneni V Sashidhara
Twenty-four novel benzofuran-pyran derivatives were synthesized and evaluated for their anti-osteoporotic activity in primary cultures of rat calvarial osteoblasts in vitro. Among all the compounds screened for the alkaline phosphatase activity, three compounds 4e, 4j and 4k showed potent activity at picomolar concentrations in osteoblast differentiating stimulation. Additionally, these compounds were found effective in mineralization, assessed by alizarin red-S staining assay. Compounds were again validated through a series of other in vitro experiments...
June 28, 2018: European Journal of Medicinal Chemistry
Liting Jiang, Wenjie Zhang, Li Wei, Qi Zhou, Guangzheng Yang, Niandong Qian, Yun Tang, Yiming Gao, Xinquan Jiang
The decreased bone mass and impaired osteogenesis capacities that occur with aging may influence the outcome of dental implants. Parathyroid hormone (PTH) (1-34) is an anabolic agent for the treatment of osteoporosis. However, little is known about its effects and mechanisms on vascularized bone regeneration and implant osseointegration in aging. In current study, we adopted both in vivo and in vitro approaches to explore the mechanisms of early actions of PTH (1-34) on the angiogenic and osteogenic microenvironment to enhance implant osseointegration in aged rats...
October 2018: Biomaterials
Joshua Coutinho, Justin B Field, Anupam A Sule
Armour® Thyroid (Forest Pharmaceuticals, LLC; affiliate of Allergan, Dublin, Ireland) is a natural porcine derivative thyroid supplement that is frequently used without physician monitoring by health enthusiasts as a weight loss supplement. Although there are no publications associating Armour Thyroid and major coronary events, significant drug interactions may exist. A 32-year-old male with a history of hypothyroidism, cystic acne, and solitary congenital kidney presented to the emergency room after experiencing crushing substernal chest pain radiating to his left shoulder, accompanied by diaphoresis and shortness of breath...
April 24, 2018: Curēus
Fan Bai, Xuewu Chen, Hui Yang, Hong-Guang Xu
Tumor necrosis factor (TNF) -α plays a crucial role in rheumatoid arthritis (RA)-related bone loss disease. The main mechanism of action of RA induced bone loss is the significant inhibitory effect of TNF-α on osteoblast differentiation. TNF-α inhibits osteoblast differentiation mainly by activating nuclear factor (NF) -κB signaling pathway. Owing to the crucial role of TNF-α and NF-κB in the inhibition of osteoblast differentiation, they are considered as targets for the development of therapeutic drugs...
June 20, 2018: Journal of Craniofacial Surgery
L Pietrogrande, E Raimondo
Abaloparatide is a synthetic 34-amino acid peptide analogue of the 1-34 portion of the human parathyroid hormone-related protein (PTHrP). It has been approved in the U.S. for the treatment of postmenopausal women with osteoporosis at a high risk for fracture. Abaloparatide is an anabolic agent and it seems to have a potent anabolic activity with reduced effects on bone resorption. It reduces the risk of vertebral and nonvertebral fractures, major osteoporotic fractures and clinical fractures, with a significant improvement in bone mineral density at femoral neck, total hip and lumbar spine...
May 2018: Drugs of Today
D Merlotti, M Materozzi, T Picchioni, S Bianciardi, M Alessandri, R Nuti, L Gennari
Osteoporosis is a growing health and health-economic problem due to the increased proportion of elderly people in the population. Basic and clinical advances in research over the past two decades have led to the development of different compounds with antiresorptive or anabolic activity on bone that improved substantially the management of patients with osteoporosis over calcitonin or estrogen replacement. New compounds are in preclinical and clinical development. Areas covered: In this review, the authors review the approaches for the preclinical and clinical development of antiresorptive and anabolic agents for osteoporosis, particularly focusing on the recent advances in technology and in the understanding of skeletal biology, together with their implications on novel osteoporosis drug discovery...
August 2018: Expert Opinion on Drug Discovery
Ana Alonso-Pérez, Eloi Franco-Trepat, María Guillán-Fresco, Alberto Jorge-Mora, Verónica López, Jesús Pino, Oreste Gualillo, Rodolfo Gómez
Inflammation is a process whose main function is to fight against invading pathogens or foreign agents. Nonetheless, it is widely accepted that inflammation takes part in multiple processes in a physiological or pathophysiological context. Among these processes the inflammation has been closely related to bone metabolism. It is well-known that in systemic inflammatory diseases such as rheumatoid arthritis the inflammatory environment contributes to the reduction of the bone mineral density. This has been further evidenced in different animals models of osteoporosis where the deletion of key inflammatory molecules dramatically reduced the bone loss...
2018: Frontiers in Physiology
Deepak H Balani, Henry M Kronenberg
Intermittent PTH-like drugs are the only approved so-called anabolic agent that increases bone mass in both mice and humans. It is well documented that PTH targets mature cells of the osteoblast lineage, with only indirect evidence of its actions on early cells of the osteoblast lineage. Using a triple transgenic mouse model that allowed labeling of very early cells of the osteoblast lineage, we traced the progeny of these into osteoblast lineage in adult mice. These early cells expressed PTH1R and multiplied when PTH (1-34) was administered daily...
May 22, 2018: Bone
Gustav van Niekerk, Anna-Mart Engelbrecht
BACKGROUND: Many of the hallmarks of cancer are not inherently unique to cancer, but rather represent a re-enactment of normal host responses and activities. A vivid example is aerobic glycolysis ('Warburg effect'), which is used not only by cancer cells but also by normal cells that undergo rapid proliferation. A common feature of this metabolic adaptation is a shift in the expression of pyruvate kinase (PK) isoform M1 to isoform M2. Here, we highlight the key role of PKM2 in shifting cancer metabolism between ATP production and biosynthetic processes...
May 24, 2018: Cellular Oncology (Dordrecht)
Daozhong Zhang, Zhijun Tang, Wen Liu
Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function...
June 19, 2018: Accounts of Chemical Research
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