MicroRNAs in Bone Balance and Osteoporosis
ABSTRACT
Bone is a rigid and dynamic organ that undergoes continuous turnover. Bone homeostasis is maintained by osteoclast‐mediated bone resorption and osteoblast‐mediated bone formation. The interruption of this balance can cause various diseases, including osteoporosis a public health issue due to the rate of hip fracture, the most serious outcome of osteoporosis. The bone loss in osteoporosis results from an increase in bone resorption versus bone formation. Thus, regulation of osteoblast and osteoclast activity is a main focus in the treatment of osteoporosis. MicroRNAs (miRNAs) are a class of single strand...
Source: Drug Development Research - July 27, 2015 Category: Drugs & Pharmacology Authors: Junying Chen, Min Qiu, Ce Dou, Zhen Cao, Shiwu Dong Tags: Research Overview Source Type: research
Carvedilol Attenuates Inflammatory Biomarkers and Oxidative Stress in a Rat Model of Ulcerative Colitis
This study evaluated the effects of the carvedilol, a nonselective β‐adrenoceptor anatgonist with α1‐adrenoceptor antagonist activity, in a rat model of experimentally induced ulcerative colitis (UC). UC was produced using acetic acid (AA) in animals previously treated with carvedilol (30 mg/kg po, qd) for seven days. Mucus content, lipid peroxidation (LPO) products, sulfhydryl groups, antioxidant enzyme activities, proinflammatory cytokines, prostaglandin E2 and nitric oxide levels were measured in colonic tissues and histopathological changes were assessed. LPO and proinflammatory biomarkers were markedly increased...
Source: Drug Development Research - June 25, 2015 Category: Drugs & Pharmacology Authors: Amal J. Fatani, Khaled A. Al‐Hosaini, Mohammed M. Ahmed, Hatem M. Abuohashish, Mihir Y. Parmar, Salim S. Al‐Rejaie Tags: Research Article Source Type: research
Effects of Kramecyne on LPS Induced Chronic Inflammation and Gastric Ulcers
ABSTRACT
Krameria cytisoides is used for the treatment of inflammation, stomach pain, and gastric ulcers. The active ingredient from this plant is a peroxide, kramecyne (KACY) which has anti‐inflammatory effects. The aim of the present study was to evaluate the anti‐inflammatory activities of KACY in lipopolysaccharide (LPS)‐induced systemic chronic inflammation in mice for 60 days, using dexamethasone (DEX) as the positive control, vehicle (the LPS group) as the negative control and the control group (mice without inflammation). KACY did not affect survival, body weight or relative organ weight in mice but it...
Source: Drug Development Research - June 25, 2015 Category: Drugs & Pharmacology Authors: Angel Josabad Alonso‐Castro, Julia Pérez‐Ramos, Ernesto Sánchez‐Mendoza, Cuauhtemoc Pérez‐González, Salud Pérez‐Gutiérrez Tags: Research Article Source Type: research
Bioprotective Carnitinoids: Lipoic Acid, Butyrate, and Mitochondria‐Targeting to Treat Radiation Injury: Mitochondrial Drugs Come of Age
ABSTRACT
Given nuclear‐power‐plant incidents such as the 2011 Japanese Fukushima‐Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic‐driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds describe...
Source: Drug Development Research - June 25, 2015 Category: Drugs & Pharmacology Authors: Kosta Steliou, Douglas V. Faller, Carl A. Pinkert, Michael H. Irwin, Walter H. Moos Tags: Research Article Source Type: research
The Role of miR‐21 in Cancer
ABSTRACT
MicroRNAs (miRNAs) are small endogenous noncoding RNAs that suppress gene expression at the post‐transcriptional level. In the past decade, miRNAs have been extensively studied in a number of different human cancers. MiRNAs have been identified to act both as oncogenes and as tumor suppressors. In addition, miRNAs are associated with the intrinsic resistance of cancer to various forms of therapy, and they are implicated in both tumor progression and metastasis. The characterization of the specific alterations in the patterns of miRNA expression in cancer has great potential for identifying biomarkers for ...
Source: Drug Development Research - June 16, 2015 Category: Drugs & Pharmacology Authors: Susan R. Pfeffer, Chuan He Yang, Lawrence M. Pfeffer Tags: Research Commentary Source Type: research
Effects of Acute and Sustained Pain Manipulations on Performance in a Visual‐Signal Detection Task of Attention in Rats
ABSTRACT
Patients with pain often display cognitive impairment including deficits in attention. The visual‐signal detection task (VSDT) is a behavioral procedure for assessment of attention in rodents. Male Sprague Dawley rats were trained in a VSDT and tested with three different noxious stimuli: (i) intraperitoneal injection of lactic acid; (ii) intraplantar injection of formalin; and (iii) intraplantar injection of complete Freund's adjuvant (CFA). The muscarinic acetylcholine receptor antagonist, scopolamine was also tested as a positive control. Scopolamine (0.01–1.0 mg/kg) dose dependently reduced accuracy...
Source: Drug Development Research - June 16, 2015 Category: Drugs & Pharmacology Authors: Kelen C. Freitas, Todd M. Hillhouse, Michael D. Leitl, Steve S. Negus Tags: Research Article Source Type: research
MicroRNAs and Noncoding RNAs in Hepatic Lipid and Lipoprotein Metabolism: Potential Therapeutic Targets of Metabolic Disorders
ABSTRACT
Noncoding RNAs and microRNAs (miRNAs) represent an important class of regulatory molecules that modulate gene expression. The role of miRNAs in diverse cellular processes such as cancer, apoptosis, cell differentiation, cardiac remodeling, and inflammation has been intensively explored. Recent studies further demonstrated the important roles of miRNAs and noncoding RNAs in modulating a broad spectrum of genes involved in lipid synthesis and metabolic pathways. This overview focuses on the role of miRNAs in hepatic lipid and lipoprotein metabolism and their potential as therapeutic targets for metabolic synd...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Neetu Sud, Jennifer Taher, Qiaozhu Su Tags: Review Source Type: research
MicroRNA‐Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer
ABSTRACT
MicroRNAs (miRs) have been causally implicated in the progression and development of a wide variety of cancers. miRs modulate the activity of key cell signaling networks by regulating the translation of pathway component proteins. Thus, the pharmacological targeting of miRs that regulate cancer cell signaling networks, either by promoting (using miR‐supplementation) or by suppressing (using antisense oligonucleotide‐based strategies) miR activity is an area of intense research. The RAS‐extracellular signal regulated kinase (ERK) pathway represents a major miR‐regulated signaling network that endows ...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Sriganesh B. Sharma, John Michael Ruppert Tags: Review Source Type: research
Small Molecules in the Treatment of Psoriasis
ABSTRACT
Psoriasis is an inflammatory systemic skin disease that affects various parts of the body requiring long‐term management due to its chronic nature. Available treatment options include topical, systemic or biological therapies, which have long‐term limitations associated to toxicity, tolerability and risk for adverse effects requiring its intermittent use and close monitoring. Small molecules modulate proinflammatory cytokines, selectively inhibit signaling pathways and showing potential to treat inflammatory diseases in patients not responding to conventional treatments. Presently, small molecules avail...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Tiago Torres, Paulo Filipe Tags: Review Article Source Type: research
Co‐administration of N‐Acetylcysteine and Acetaminophen Efficiently Blocks Acetaminophen Toxicity
ABSTRACT
Although acetaminophen (APAP) is an effective analgesic and anti‐pyretic, APAP overdose is the most frequent cause of serious, often lethal, drug‐induced hepatotoxicity. Administration of N‐acetyl cysteine (NAC) within 8 hours of APAP overdose effectively mitigates APAP‐induced hepatotoxicity. Thus, preventing APAP toxicity before it occurs by formulating APAP with NAC is logical and, as we show here in a mouse model, is effective in preventing APAP toxicity. Thus, toxic oral APAP doses sufficient to cause severe widespread liver damage do not cause significant damage when administered concurrently ...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Solomon E Owumi, James P Andrus, Leonard A Herzenberg, Leonore A Herzenberg Tags: Research Article Source Type: research
Characterization and Validation of a Canine Pruritic Model
ABSTRACT
The mechanisms mediating canine pruritus are poorly understood with few models due to limited methods for inducing pruritus in dogs. Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in humans and mice. We have developed a canine model of pruritus where CQ reliably induced pruritus in all dogs tested following intravenous administration. This model is presently being used to test antipruritic activity of drug candidate molecules. This publication has been validated in a blinded cross‐over study in eight beagle dogs using the reference standards, oclacitinib and prednisolone, and has...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Gunnar A.K. Aberg, Nada Arulnesan, Gordon T. Bolger, Vincent B. Ciofalo, Kresimir Pucaj Tags: Research Article Source Type: research
Enhancement of Antihyperalgesia by the Coadministration of N‐palmitoylethanolamide and Acetaminophen in Diabetic Rats
The objective of this study was to evaluate the pharmacological antihyperalgesic interaction between N‐palmitoylethanolamide (PEA) and acetaminophen in diabetic rats using the formalin paw test. Streptozotocin (STZ)‐induced diabetic rats received subcutaneous injections in the paw of PEA alone (1–100 μg/paw) or acetaminophen alone (3–300 μg/paw) 15 min before formalin (0.5%) injection. The results revealed concentration‐dependent responses produced by PEA (EC50 = 7.19 ± 0.7 μg/paw) and acetaminophen (EC50 = 57.9 ± 1.9 μg/paw). Isobolographic analysis was used to evaluate the pharmacological ...
Source: Drug Development Research - June 1, 2015 Category: Drugs & Pharmacology Authors: Myrna Déciga‐Campos, Rolffy Ortíz‐Andrade Tags: Research Article Source Type: research
Gastroprotective Properties of Cashew Gum, a Complex Heteropolysaccharide of Anacardium occidentale, in Naproxen‐Induced Gastrointestinal Damage in Rats
ABSTRACT
Long‐term use nonsteroidal anti‐inflammatory drug is associated with gastrointestinal (GI) lesion formation. The aim of this study was to investigate the protective activity of cashew gum (CG), a complex heteropolysaccharide extracted from Anacardium occidentale on naproxen (NAP)‐induced GI damage. Male Wistar rats were pretreated with vehicle or CG (1, 3, 10, and 30 mg/kg, p.o.) twice daily for 2 days; after 1 h, NAP (80 mg/kg, p.o.) was administered. The rats were euthanized on the 2nd day of treatment, 4 h after NAP administration. Stomach lesions were measured using digital calipers. The medial sm...
Source: Drug Development Research - May 11, 2015 Category: Drugs & Pharmacology Authors: Nathalia S. Carvalho, Mônica M. Silva, Renan O. Silva, Lucas A. D. Nicolau, Francisca Beatriz M. Sousa, Samara R. B. Damasceno, Durcilene A. Silva, André L. R. Barbosa, José Roberto S. A. Leite, Jand Venes R. Medeiros Tags: Research Article Source Type: research
Synergism Between Tramadol and Parecoxib in the Orofacial Formalin Test
ABSTRACT
The aim of this study was to evaluate the interaction between tramadol and parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min before formalin (2.5%) injection into the upper lip to characterize the dose–response curve of each individual drug in the orofacial pain test in mice. Once the dose–response curve of each drug was obtained, an experimental effective dose 50 (ED50) value was determined for each drug. The tramadol–parecoxib combination was evaluated in four different groups of animals. Th...
Source: Drug Development Research - May 8, 2015 Category: Drugs & Pharmacology Authors: Mario Alberto Isiordia‐Espinoza, Juan Ramón Zapata‐Morales, Demian Ismael Castañeda‐Santana, Maximiliano de la Rosa‐Coronado, Othoniel Hugo Aragon‐Martinez Tags: Research Article Source Type: research
In Vivo Wound‐Healing Effects of Novel Benzalkonium Chloride‐Loaded Hydrocolloid Wound Dressing
ABSTRACT
The purpose of this study was to evaluate the wound‐healing effects of a novel benzalkonium chloride (BC)‐loaded hydrocolloid wound dressing (HCD). A BC‐loaded HCD was prepared with various constituents using a hot melting method, and its mechanical properties and antimicrobial activities were assessed. The in vivo wound healings of the BC‐loaded HCD in various would models were evaluated in rats compared with a commercial wound dressing, Duoderm™. This BC‐loaded HCD gave better skin adhesion, swelling, mechanical strength, and flexibility compared with the commercial wound dressing. It showed e...
Source: Drug Development Research - May 8, 2015 Category: Drugs & Pharmacology Authors: Sung Giu Jin, Abid Mehmood Yousaf, Sun Woo Jang, Mi‐Won Son, Kyung Soo Kim, Dong‐Wuk Kim, Dong Xun Li, Jong Oh Kim, Chul Soon Yong, Han‐Gon Choi Tags: Research Article Source Type: research
