Thalidomide Inhibits Adhesion Molecules in Experimental Acute Pancreatitis‐Associated Lung Injury
ABSTRACT
The study evaluated the effect of thalidomide on adhesion molecule expression in acute pancreatitis‐associated lung injury in rats. Acute pancreatitis was induced in rats by retrograde infusion of 5% sodium taurocholate into the bile‐pancreatic duct, and thalidomide (100 mg/kg) was given daily by intragastric route for 8 days before this treatment. Serum lipase (LPS), protein levels in bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and malondialdehyde (MDA) levels in lung were measured. Compared with the acute pancreatitis‐ group, lung histopathology, ...
Source: Drug Development Research - December 1, 2014 Category: Drugs & Pharmacology Authors: Peng Lv, Hong‐Yun Li, Shu‐Sheng Ji, Wen Li, Li‐Juan Fan Tags: Research Article Source Type: research
Inhibition of LPS‐Induced TLR4 Signaling Products in Murine Macrophages by Phenylmethimazole: An Assay Methodology for Screening Potential Phenylmethimazole Analogs
In this study, we carried out a detailed investigation of the effect of C10 on TLR4 and its molecular signaling products in RAW 264.7 macrophages using quantitative real‐time polymerase chain reaction (PCR), ELISA and cell toxicity assays, a set of in vitro assays that may be used to screen future C10 analogs. C10 exhibited an inhibitory effect on TLR4 MyD88‐dependent and MyD88‐independent pathways. Within the TLR4 pathway, C10 inhibited the expression of cytokines, cytokine receptors, kinases, adapter molecules and transcription factors, suggesting a pathway‐wide inhibitory effect. We also found that C10 dose‐de...
Source: Drug Development Research - November 18, 2014 Category: Drugs & Pharmacology Authors: Sudhir P. Deosarkar, Pooja Bhatt, Jessica Gillespie, Douglas J. Goetz, Kelly D. McCall Tags: Research Article Source Type: research
Nobiletin Inhibits PDGF‐BB‐Induced Vascular Smooth Muscle Cell Proliferation and Migration and Attenuates Neointimal Hyperplasia in a Rat Carotid Artery Injury Model
Abstract
The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti‐inflammatory and anti‐oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet‐derived growth factor (PDGF)‐BB‐ stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF‐BB, and...
Source: Drug Development Research - November 1, 2014 Category: Drugs & Pharmacology Authors: Siyu Guan, Qizhu Tang, Wenwei Liu, Rui Zhu, Bin Li Tags: Research Article Source Type: research
Preventive Effect of American Ginseng Against Premature Ovarian Failure in a Rat Model
Abstract
Premature ovarian failure (POF) is defined by the WHO as the loss of physiological ovarian function before the age of 40. The effect of American ginseng and its underlying mechanisms in preventing and treating premature ovarian failure (POF) was studied in female Sprague‐Dawley rats where POF was induced by ip administration of 4‐vinylcyclohexene diepoxide (VCD). Rat behavior, serum hormone levels, ovarian and uterine size, pathological features, and ovarian tissue expression of genes associated with POF were assessed in controls, untreated POF model rats, and POF model rats treated with low‐ (1.125...
Source: Drug Development Research - November 1, 2014 Category: Drugs & Pharmacology Authors: Pengling Ge, Nannan Xing, Yanhai Ren, Lei Zhu, Dongwei Han, Haixue Kuang, Ji Li Tags: Research Article Source Type: research
Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test
Abstract
The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin‐induced nociception. Diacerhein, each of the antiepileptics or a fixed dose‐ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose‐dependent antinociceptive effect when administered by bo...
Source: Drug Development Research - November 1, 2014 Category: Drugs & Pharmacology Authors: Angel Zúñiga‐Romero, Martha Karina Ponce‐Chávez, Marcia Yvette Gauthereau‐Torres, Luis Fernando Ortega‐Varela Tags: Research Article Source Type: research
Antidiabetic Effect of Schisandrae Chinensis Fructus Involves Inhibition of the Sodium Glucose Cotransporter
In this study, SCF was investigated for its effects on sodium glucose cotransporters 1 and 2 (SGLT 1 and 2) expressed in a COS‐7 cell line for its specificity in inhibiting SGLT2, which is a novel mechanism to screen for potential antidiabetic agents. Using a bioassay‐guided fractionation, we then tried to isolate and identify the active fraction(s)/component(s). The ethanol extract of SCF at a concentration of 1 mg/mL significantly inhibited 89% of SGLT1 and 73% of SGLT2 activities in a [14C]‐α‐methyl‐d‐glucopyranoside ([14C]‐AMG) uptake assay. Fractionation of the ethanol extract yielded nine fractions, ...
Source: Drug Development Research - November 1, 2014 Category: Drugs & Pharmacology Authors: Yue Qu, Judy Yuet‐Wa Chan, Chun‐Wai Wong, Ling Cheng, Chuanshan Xu, Albert Wing‐Nang Leung, Clara Bik‐San Lau Tags: Research Article Source Type: research
Comparison of Antidepressant‐Like and Abuse‐Related Effects of Phencyclidine in Rats
Abstract
N‐methyl‐D‐aspartate (NMDA) receptor antagonists, such as ketamine, have emerged as novel candidate treatments for major depressive disorder, but abuse potential of these agents is a concern. The NMDA antagonist phencyclidine has known abuse liability but undefined efficacy as an antidepressant. To further evaluate the relationship between antidepressant‐like and abuse‐related effects of NMDA antagonists, this study evaluated the effects of phencyclidine (1.0–10.0 mg/kg) in male Sprague‐Dawley rats responding under two procedures that have been used to assess antidepressant‐like effects (d...
Source: Drug Development Research - October 15, 2014 Category: Drugs & Pharmacology Authors: Todd M. Hillhouse, Joseph H. Porter, S. Stevens Negus Tags: Research Article Source Type: research
Genetic Findings in Obsessive–Compulsive Disorder Connect to Brain‐Derived Neurotropic Factor and Mammalian Target of Rapamycin Pathways: Implications for Drug Development
Abstract
Traditional pharmacological approaches to the treatment of obsessive–compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1‐MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation a...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Marco Grados, Hyung Mo Sung, Sejin Kim, Siddharth Srivastava Tags: Research Overview Source Type: research
Transcriptomic Studies on Liver Toxicity of Acetaminophen
Abstract
Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen‐induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen‐induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen‐induced acute...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Endrit Toska, Robert Zagorsky, Bryan Figler, Feng Cheng Tags: Research Overview Source Type: research
Computational Approaches for Drug Discovery
Abstract
Cellular proteins are the mediators of multiple organism functions being involved in physiological mechanisms and disease. By discovering lead compounds that affect the function of target proteins, the target diseases or physiological mechanisms can be modulated. Based on knowledge of the ligand–receptor interaction, the chemical structures of leads can be modified to improve efficacy, selectivity and reduce side effects. One rational drug design technology, which enables drug discovery based on knowledge of target structures, functional properties and mechanisms, is computer‐aided drug design (CADD). T...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Che‐Lun Hung, Chi‐Chun Chen Tags: Research Overview Source Type: research
Network Measures for Chemical Library Design
Abstract
In this overview, we examine recent developments in network approaches to drug design. A brief overview of networks is followed by a discussion of how chemical similarity networks and their properties address challenges in drug design. Multiple methods used to assess or enhance chemical diversity for early‐stage drug discovery are discussed, as well as methods that can be used for drug repositioning and ligand polypharmacology. (Source: Drug Development Research)
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Nagamani Sukumar, Michael P. Krein, Ganesh Prabhu, Sudeepto Bhattacharya, Subhabrata Sen Tags: Research Overview Source Type: research
Opportunities and Challenges Provided by Cloud Repositories for Bioinformatics‐Enabled Drug Discovery
Abstract
Strategy, Management and Health Policy
Enabling Technology, Genomics, Proteomics
Healthcare‐related bioinformatics databases are increasingly offering the possibility to maintain, organize, and distribute DNA sequencing data. Different national and international institutions are currently hosting such databases that offer researchers website platforms where they can obtain sequencing data on which they can perform different types of analysis. Until recently, this process remained mostly one‐dimensional, with most analysis concentrated on a limited amount of data. However, newer genome sequencing tech...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Gratien Dalpé, Yann Joly Tags: Commentary Source Type: research
Advancing Cancer Patient Care by Integrating Circulating Tumor Cell Technology to Understand the Spatial and Temporal Dynamics of Cancer
Abstract
Spatial and temporal dynamics of cancer, studied with physical science approaches at critical transition points of the disease can provide insight into the biology of cancer and the evolutionary changes that occur both naturally and in response to therapy. A very promising development in translational cancer medicine has been the emergence of circulating tumor cells (CTC) as minimally invasive “liquid biopsies.” We envision that the future utility of CTC will not simply be confined to enumeration, but also include their routine characterization using a high‐content approach that investigates morphomet...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Mariam Rodriguez‐Lee, Peter Kuhn, David R. Webb Tags: Research Overview Source Type: research
Genetic Findings in Obsessive–Compulsive Disorder Connect to Brain‐Derived Neutrophic Factor and Mammalian Target of Rapamycin Pathways: Implications for Drug Development
Abstract
Traditional pharmacological approaches to the treatment of obsessive–compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1‐MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation a...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Marco Grados, Hyung Mo Sung, Sejin Kim, Siddharth Srivastava Tags: Research Overview Source Type: research
Microarray Gene and miRNA Expression Studies: Looking for New Therapeutic Targets for Frontotemporal Lobar Degeneration
Abstract
Frontotemporal lobar degeneration (FTLD) encompasses a spectrum of neurodegenerative disorders characterized by behavioral, executive and language impairment, with a common overlap with parkinsonism and motor‐neuron disease. Despite an increased understanding of its genetic background and molecular pathophysiology, FTLD is still an orphan disorder and there are currently no effective therapies available. In this brief overview we report the results obtained by several high‐throughput and bioinformatic studies aimed at discovering impairment in the transcriptional profiles in brain and peripheral tissues...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Elena Milanesi, Andrea Pilotto Tags: Research Overview Source Type: research
