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Self-emulsifying system for improving drug dissolution and bioavailability: in vitro/in vivo evaluationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study focuses on enhancement of the dissolution and oral absorption of poorly water-soluble etodolac. A self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant, and co-surfactant for oral administration was formulated. The SEDDS formulations were optimized by evaluating their ability to self-emulsifying when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimized formulation of SEDDS was selected for bioavailability assessment in rabbits. Also, the anti-inflammatory effect of SEDDS formulation was determined in rats, co...
Source: Drug Development Research - November 20, 2009 Category: Drugs & Pharmacology Authors: Nahla S. Barakat Source Type: journals

Enhanced bioavailability and antihistamine effects by transdermal administration of loratadine gels containing an enhancer in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present study examined the feasibility of transdermal administration of loratadine gels containing an enhancer to rats by comparing the pharmacokinetic parameters of loratadine after transdermal, oral, or intravenous administration. Transdermal administration of loratadine gel (12 mg/kg applied to the abdominal skin) with an enhancer produced a significantly higher plasma concentration of loratadine than the loratadine gel without the enhancer (control). The average areas under the serum concentration-time curves (AUC) was 929±148 h·ng/ml for oral administration, and 3,318±530.9 h·ng/ml for intravenous administrati...
Source: Drug Development Research - November 19, 2009 Category: Drugs & Pharmacology Authors: Cheong-Weon Cho, Jun-Shik Choi, Sang-Chul Shin Source Type: journals

Anti-diabetic effect of standardized extract of Potentilla discolor Bunge and identification of its active componentsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report the anti-diabetic effect of P. discolor on normal and alloxan-induced diabetic mice, as well as the possible constituents and mechanism responsible for this activity. We found that the standardized extract of P. discolor (EPD) had little effect on the glucose levels of normal mice, while a dose-dependent hypoglycemic effect was observed in diabetic mice. Glucose tolerance test data indicated that there was a significantly higher rate of glucose disposal after EPD treatment. Phytochemical characterization indicated that the major components of EPD were triterpenes and flavonoids that could inhibit the activity of ...
Source: Drug Development Research - November 19, 2009 Category: Drugs & Pharmacology Authors: Jie Yang, Hong Chen, Li Zhang, Qiang Wang, Mao-Xiang Lai Source Type: journals

Effect of the antidepressant paroxetine on Ca2+ movement in PC3 human prostate cancer cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study explored whether paroxetine changed basal [Ca2+]i levels in suspended PC3 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Paroxetine at concentrations between 10-150 µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 55% by removing extracellular Ca2+. Paroxetine-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin, 2,5-di-tert-butylhy...
Source: Drug Development Research - November 19, 2009 Category: Drugs & Pharmacology Authors: Chih Chuan Pan, Daih-Huang Kuo, Pochuen Shieh, Fu-An Chen, Chun-Chi Kuo, Chung-Ren Jan Source Type: journals

Cathelicidin peptide SMAP-29: comprehensive review of its properties and potential as a novel class of antibioticsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sheep myeloid antimicrobial peptide of 29 amino acids (SMAP-29) is one of the most potent antimicrobial peptides known, with a broad spectrum of activity against bacteria, fungi, and viruses. It has also been shown to prevent infections in animals. SMAP-29 is an [alpha]-helical cathelicidin that acts rapidly to permeabilize membranes of susceptible organisms. However, it is also cytotoxic and hemolytic to mammalian cells. In this review, all published data on inhibition constants and hemolytic activities of SMAP-29 are brought together for the first time, including data for the peptide of 28 residues that lacks the C-termi...
Source: Drug Development Research - October 31, 2009 Category: Drugs & Pharmacology Authors: Raymond M. Dawson, Chun-Qiang Liu Source Type: journals

Diclofenac acid: a free-radical-scavenger to protect DNA against radical-induced oxidationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The present work focused on the antioxidant effects of diclofenac acid (DaH) and its sodium salt (DaNaH) on the radical-induced oxidation of DNA. 2,2[prime]-Azobis(2-amidinopropane) dihydrochloride (AAPH) was used as radical initiator to oxidize naked DNA sodium salt, followed by the determination of thiobarbituric acid reactive substance (TBARS). DaH and DaNaH also interacted with two other radicals: 2,2[prime]-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS+.) and 2,2[prime]-diphenyl-1-picrylhydrazyl (DPPH). DaH and DaNaH produce a concentration-dependent protection of DNA. Kinetic studies established t...
Source: Drug Development Research - September 15, 2009 Category: Drugs & Pharmacology Authors: You-Zhi Tang, Zai-Qun Liu Source Type: journals

The brain angiotensin IV/AT4 receptor system as a new target for the treatment of Alzheimer's diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The brain renin-angiotensin system (RAS) regulates several physiologies including blood pressure, body sodium and water balance, cyclicity of reproductive hormones and related sexual behaviors, and the release of pituitary gland hormones. These physiologies are under the control of the angiotensin II (AngII)/AT1 receptor subtype system. The AngII/AT2 receptor subtype system is expressed during fetal development and is less abundant in the adult. This system appears to oppose growth responses facilitated by activation of the AT1 receptor. There is a growing list of nontraditional physiologies mediated by the most recently d...
Source: Drug Development Research - September 15, 2009 Category: Drugs & Pharmacology Authors: John W. Wright, Joseph W. Harding Source Type: journals

Nonprofit organizations and pharmaceutical research and developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Not-for-profit or nonprofit organizations (NPOs) are playing an increasingly important role in providing solutions to the significant challenges faced by both large pharmaceutical and smaller biotechnology companies in today's world. NPOs chartered for the public benefit are common in the United States and in selected other parts of the world. The largest NPOs in the U.S. with bioscience programs include Battelle, the Midwest Research Institute, the Research Triangle Institute, Southern Research, and SRI International. To provide a perspective on NPO business models, 10 SRI case studies spanning a broad range of technical ...
Source: Drug Development Research - September 15, 2009 Category: Drugs & Pharmacology Authors: Walter H. Moos, Jon C. Mirsalis Source Type: journals

Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study explored whether capsaicin changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Capsaicin at concentrations between 10-100 µM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 80% by removing extracellular Ca2+. Capsacin induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid and the non-selective Ca2+ entry blocker La3+, but not by store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and protei...
Source: Drug Development Research - September 15, 2009 Category: Drugs & Pharmacology Authors: Jeng-Hsien Yeh, Jenn-Kuen Lee, Jyh-Seng Wang, Mei-Yin Yeh, Yu-Lin Yang, Jau-Shyang Huang, Wen-Teng Chang, Daih-Huang Kuo, Pochuen Shieh, Fu-An Chen, Chun-Chi Kuo, Chung-Ren Jan Source Type: journals

Tat-mediated peptide intervention in analgesia and anesthesiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Membrane-permeable peptide carriers are attractive drug delivery tools. Among such carriers, the protein transduction domain (PTD) of the human immunodeficiency virus-type 1 Tat protein is most frequently used and has been successfully shown to deliver a large variety of cargoes. The Tat PTD can facilitate the uptake of large, biologically active molecules into mammalian cells; recent studies have shown that it can mediate the delivery of different cargoes into tissues throughout a living organism. Given that the Tat PTD-mediated delivery is size-independent, this technology could make previously non-applicable large molec...
Source: Drug Development Research - September 15, 2009 Category: Drugs & Pharmacology Authors: Feng Tao, Roger A. Johns Source Type: journals

Synergistic interaction between tramadol and dipyrone in thermal paw stimulation model in the ratEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Dipyrone, also known as metamizol, and tramadol are drugs that are widely used for the treatment of pain; however, side effects can limit their use. As dipyrone and tramadol produce side effects that are dose dependent, it seems appropriate to combine these drugs to reduce their dose requirements and, consequently, side effects. The purpose of this study was to evaluate whether dipyrone and tramadol produce antihyperalgesic effects in the thermal paw stimulation model in the rat, and whether there is a synergistic interaction between them. Using this model, dose-response curves were constructed for dipyrone (10-178 mg/kg, ...
Source: Drug Development Research - September 14, 2009 Category: Drugs & Pharmacology Authors: Juan Rodríguez-Silverio, Jesús Arrieta, Francisco J. Flores-Murrieta Tags: Research Articles Source Type: journals

Development and use of methylnaltrexone, a peripherally acting opioid antagonist, to treat side effects related to opioid useEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Opioid medications are used extensively as potent analgesics for treating moderate to severe pain. Although opioids offer reliable pain relief, their use is associated with a number of adverse effects, especially constipation. Conventional measures for ameliorating opioid-induced adverse effects are often insufficient. Thus, reducing the severity of these adverse effects is of utmost importance for patients who require the benefits of opioid analgesics. Since opioids mediate pain-relieving and adverse effects through the same classes of receptors, i.e., mu, delta, and kappa, it has been challenging to dissociate beneficial...
Source: Drug Development Research - August 31, 2009 Category: Drugs & Pharmacology Authors: Chun-Su Yuan, Joseph F. Foss, Wade A. Williams, Jonathan Moss Tags: Research Overview Source Type: journals

Preparation of carboxy-PEG-PLA nanoparticles loaded with camptothecin and their body distribution in solid tumor-bearing miceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Carboxy-polyethylene glycol-poly(DL-lactic acid) block copolymer was synthesized by reductive amination of carboxy-polyethylene glycol-amine and aldehyde-ended poly(DL-lactic acid). The obtained product, PA-PEG-CB, composed of pure carboxy-polyethylene glycol-poly(DL-lactic acid) block copolymer and poly(DL-lactic acid), was used to prepare nanoparticles loaded with camptothecin (CPT), designated CPT-NP. CPT-NP with 500-600 nm and approximately 1% (w/w) drug content were obtained by emulsification/evaporation, while nanoparticles with a drug content of only less than 0.1% (w/w) were prepared by dialysis. CPT-NP produced by...
Source: Drug Development Research - July 16, 2009 Category: Drugs & Pharmacology Authors: Kennichi Ueki, Hiraku Onishi, Masanaho Sasatsu, Yoshiharu Machida Source Type: journals

Effect of CJX2, an amlodipine derivative, combined with verapamil on P-glycoprotein efflux function in vitroEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In an effort to inhibit P-glycoprotein (P-gp) efflux function with greater activity and less side effects, the combined effect of CJX2 and verapamil (Ver) was evaluated isobolographically in fixed ratio combinations of 1:1, 1:2, 1:4, 1:8, and 1:10 in doxorubicin-resistant human myelogenous leukemia (K562/DOX ) cells and rat brain microvessel endothelial cells (RBMEC). The results displayed that mixtures of both drugs at the fixed ratios of 1:1, 1:2, 1:4, 1:8, and 1:10 exerted synergistic interactions, indicating that when the two blockers that bind P-gp on separate membrane sites were combined, each contributes to the over...
Source: Drug Development Research - July 15, 2009 Category: Drugs & Pharmacology Authors: Bian-Sheng Ji, Ming Li, Ling He Tags: Research Articles Source Type: journals

3D-QSAR studies of cytotoxic heterocyclic quinones using calculated reduction potentialEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most quinones with 2-4 fused aromatic rings exhibit cytostatic activity via DNA intercalation that causes enzyme blockade and reading errors during the replication process. The redox activity of quinones plays a role in the DNA cleavage mediated by oxygen or sulfur radicals. To develop novel anticancer agents based on nitrogen-containing heterocyclic quinones, pharmacophore models of representative molecules with high activity were generated using Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database (GALAHAD). A series of compounds were aligned to the selected pharmacophore model and the 3D-quan...
Source: Drug Development Research - July 15, 2009 Category: Drugs & Pharmacology Authors: Yoonji Lee, Seoeun Kim, Hee-Kyung Rhee, Kyung-Eun Doh, Junhee Park, Chong-Ock Lee, Sun Choi, Hea-Young Park Choo Tags: Research Articles Source Type: journals

Protective effect of curcumin, a Curcuma longa constituent, in early colonic inflammation in ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Curcumin, a polyphenol derived from the plant, Curcuma longa, has a variety of pharmacological effects, including chemotherapeutic, anti-inflammatory, antiangiogenic, and antioxidant activities. To gain a better understanding of the effects and mechanisms of action of curcumin on the acute injury caused by intra-colonic administration of acetic acid (AA) in rats, inflammation was assessed by histology and myeloperoxidase activity (MPO; an index of neutrophil infiltration in the mucosa); Th1 and Th2 cytokine production; histological and histochemical analysis of the lesions; nitrite production in colon mucosa; and the expre...
Source: Drug Development Research - July 15, 2009 Category: Drugs & Pharmacology Authors: Juan Manuel Sánchez-Calvo, Isabel Villegas, Susana Sánchez-Fidalgo, Laura Camacho-Barquero, Elena Talero, Virginia Motilva, Catalina Alarcón de la Lastra Tags: Research Articles Source Type: journals

Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti-inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH-triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling age...
Source: Drug Development Research - July 15, 2009 Category: Drugs & Pharmacology Authors: A.S. Manjappa, Basavaraj K. Nanjwade, F.V. Manvi, R.S.R. Murthy Tags: Research Articles Source Type: journals

Pharmacological efficacy and safety profile of taranabant in preclinical speciesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Taranabant is a highly selective and potent cannabinoid CB1 receptor inverse agonist. We compared the pharmacological properties of taranabant with another inverse agonist, rimonabant, and determined the preclinical safety margins of taranabant. In vitro studies demonstrated that taranabant is [sim]10-fold more potent than rimonabant at the CB1 receptor, and taranabant is more selective based on off-target in vitro screening. In vivo efficacy studies demonstrated that taranabant is [sim]10-fold more potent than rimonabant in diet-induced obese rats. In repeat-dose toxicological studies, taranabant did not cause mortality i...
Source: Drug Development Research - July 15, 2009 Category: Drugs & Pharmacology Authors: T.M. Fong, L.P. Shearman, D.S. Stribling, J. Shu, J. Lao, C.R.-R. Huang, J.C. Xiao, C.-P. Shen, J. Tyszkiewicz, A.M. Strack, C. DeMaula, M.-F. Hubert, A. Galijatovic-Idrizbegovic, R. Owen, A.C. Huber, C.L. Lanning Tags: Research Articles Source Type: journals

The evaluation of a biodegradable dental chip containing chlorhexidine in chitosan base as a targeted drug delivery in the management of chronic periodontitis in patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Chlorhexidine is one of the commonly used agents in the treatment of periodontitis. In the present study, a biodegradable dental chip of chitosan containing chlorhexidine was evaluated both in vitro and in vivo, as a targeted drug delivery system in patients of chronic periodontitis. Thirty patients having localized periodontal pockets [ge]5 mm were selected. At baseline, the experimental patients received full mouth scaling and root planing followed by placement of a chlorhexidine chip. The placebo group received plain chitosan chips, and conventional scaling and root planing were performed for the control group. Measurem...
Source: Drug Development Research - June 21, 2009 Category: Drugs & Pharmacology Authors: M.V. Jothi, K.M. Bhat, P.K. Pratibha, G.S. Bhat Tags: Research Articles Source Type: journals

Synergistic antiallodynic interaction of the metamizol-gabapentin combinationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study was designed to evaluate the possible antiallodynic interaction between metamizol and gabapentin in rats submitted to L5/L6 spinal nerve ligation. Metamizol, gabapentin, or a combination of both drugs were assessed after oral and intrathecal administration in neuropathic rats. Metamizol partially reduced tactile allodynia after intrathecal, but not oral, administration. Conversely, gabapentin reduced tactile allodynia in a dose-dependent manner after both administration routes. Oral administration of a constant dose of metamizol (600 mg/kg) significantly increased the gabapentin-induced antiallodynic effect. Mor...
Source: Drug Development Research - June 21, 2009 Category: Drugs & Pharmacology Authors: Luis F. Ortega-Varela, Jorge E. Herrera, Nadia L. Caram-Salas, Hector I. Rocha-Gonzalez, Jorge E. Torres-López, Vinicio Granados-Soto Tags: Research Articles Source Type: journals

Scopoletin induces apoptosis of fibroblast-like synoviocytes from adjuvant arthritis rats by a mitochondrial-dependent pathwayEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Scopoletin is a naturally occurring coumarin compound found in many medicinal plants, such as Erycibe obtusifolia Benth and Aster tataricus. Our previous studies have demonstrated that this compound could ameliorate adjuvant-induced arthritis in a rat model of human rheumatoid arthritis (RA). Since the proliferation of fibroblast-like synoviocytes (FLS) plays a pivotal role in the formation and growth of pannus, which leads to subsequent joint destruction in RA, we examined the effects of scopoletin on FLS apoptosis. Primary FLS from adjuvant arthritis rats were purified and cultured, and then treated with increasing conce...
Source: Drug Development Research - June 21, 2009 Category: Drugs & Pharmacology Authors: Ying Li, Yue Dai, Mei Liu, Rong Pan, Yubin Luo, Yufeng Xia, Xiaofeng Xia Tags: Research Articles Source Type: journals

Nonylphenol-induced cytosolic Ca2+ elevation and death in renal tubular cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Nonylphenol is an environmental endocrine disrupter. The effect of nonylphenol on intracellular free Ca2+ levels ([Ca2+]i) and viability in Madin-Darby canine kidney (MDCK) cells was explored. Nonylphenol increased [Ca2+]i in a concentration-dependent manner (EC50[sim]0.8 [mu]M). Nonylphenol-induced Mn2+ entry demonstrated Ca2+ influx and removal of extracellular Ca2+ partly decreased the [Ca2+]i rise. The [Ca2+]i rise was inhibited by the protein kinase C activator, phorbol 13-myristate acetate (PMA) but not by L-type Ca2+ channel blockers. In Ca2+-free medium, nonylphenol-induced [Ca2+]i rise was partly inhibited by pret...
Source: Drug Development Research - June 21, 2009 Category: Drugs & Pharmacology Authors: Jeng-Yu Tsai, Chorng-Chih Huang, He-Hsiung Cheng, Ko-Long Lin, Wei-Chuan Liao, Chung-Ren Jan Tags: Research Articles Source Type: journals

Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Solid dispersions (SDs) of aloe-emodin (AE) and polyethylene glycol 6000 (PEG6000) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) and evaluated for solubility and in vitro release. The oral bioavailability of AE from SD in rats was compared with the crystalline drug. Plasma concentrations of AE were determined by HPLC. After administration of crystalline AE (35 mg·kg-1) in rats, the AUC0-600 and Cmax were 393.6±77.1 mg·min·l-1 and 1.87±0.30 mg·l-1, respectively. For the PEG6000 SD of AE, AUC0-600 and Cmax were boosted to 1310...
Source: Drug Development Research - June 21, 2009 Category: Drugs & Pharmacology Authors: Hao-gang Duan, Yu-hui Wei, Bo-xia Li, Hong-yan Qin, Xin-an Wu Tags: Research Articles Source Type: journals

Smart planner: radically accelerating R&D to combat a biothreatEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conventional R&D processes are ill-suited to biothreats and biothreat preparation because they are intended to support risk-averse decisions for patients and are designed for longer expected development times. The Smart Planner tool is a risk visualization framework developed to help contingency and R&D planners quantify and balance risk, uncertainty, and time. The tool incorporates the following capabilities: (1) visualization of the risks of inaction; (2) identification of critical areas of uncertainty where new information can really make a difference; (3) decision support for (i) development and treatment options and (...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Andrew T. Chadwick, Roger A. Edwards Tags: Research Commentary Source Type: journals

Tools for planning and coordinating development of medical countermeasures in the public sectorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In spite of significant increases in biodefense spending in the 7 years since the 2001 anthrax attacks, the United States may not yet be fully prepared to respond effectively to many potential biothreats. The principal reasons appear to be that: (1) the problem is extremely complex, and the metrics for success are often unclear; (2) although the US Congress has allocated substantial resources for this effort, these funds are insufficient for the task as initially conceived, i.e., "one drug for each bug;" and (3) there is insufficient coordination among the many agencies working to achieve the goal of protecting the nation ...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Ian Manger, Jay Pearson, Richard Winegar, Lynne Gilfillan Tags: Research Overviews Source Type: journals

Accelerating botulism therapeutic product development in the Department of DefenseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Coordinated small-molecule drug discovery research efforts for the treatment of botulism by the public sector, especially the U.S. Department of Defense (DoD) and Department of Health and Human Services (DHHS), began in the 1990s and represent a significant resource investment. Organization of an effective botulism therapeutic drug program, however, presents formidable technical and logistical challenges. Seven distinct BoNT serotypes are known, each representing a different target. Moreover, BoNT exerts its action inside peripheral cholinergic neurons, and some serotypes may persist functionally within nerve cells for wee...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Andrea M. Stahl, Michael Adler, Charles B. Millard, Lynne Gilfillan Tags: Research Overviews Source Type: journals

Using a systems biology approach to dissect parasite-host interactionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The reductionist approach to biology has allowed us to understand the cell at a component level. But in recent years, with the deluge of genome-derived and empirically obtained data, we must interpret biological complexity holistically. Thus, systems biology research allows us to connect the seemingly independent elements in biological networks. Protozoan parasites in the genus Leishmania cause clinically distinct diseases in humans with visceral, cutaneous, and mucocutaneous pathologies. In this article, we take the example of Leishmania parasites and their interactions with the vertebrate host as a model to generate a gl...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Rajeev Vaidyanathan, Krishna Kodukula Tags: Research Overviews Source Type: journals

Manufacturing a rapid biologic responseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There are two major components in making new biologic medical countermeasures available for bio-defense and pandemic response: (1) the detection/discovery of effective countermeasures, and (2) their subsequent Process Development (PD) and manufacture. PD and manufacturing, however, are often the most costly and time-consuming parts of the process, potentially taking years and costing hundreds of millions to billions of dollars. To address these long timelines, governments have historically stockpiled countermeasures for known biothreats. Unfortunately, this kind of stockpiling is very expensive, and does not provide protec...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Peter W. Latham Tags: Research Overviews Source Type: journals

Developing technologies in biodefense research: computational drug designEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of small-molecule drugs to counter the threat of bioterrorism will differ from classical drug discovery because it will be impossible to evaluate efficacy in clinical trials for many agents. This difference focuses biodefense on the identification of multiple drug candidates for each threat organism so that multiple treatments can be mounted simultaneously when needed to maximize the probability of success. Accordingly, drug discovery will become the rate- and cost-limiting phase of the overall drug development process. We address the potential of computational chemistry to optimize efficiency and efficacy ...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Matthew Clark, Sia Meshkat, George Talbot, Zenon Konteatis, Jennifer Ludington, Jinming Zou, Steven J. Freedman, Jeffrey S. Wiseman Tags: Research Overviews Source Type: journals

U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The United States Army (USA) under the auspices of the Medical Research and Material Command (USAMRMC) and the Defense Threat Reduction Agency (DTRA) sponsored several major efforts to develop an effective medical countermeasure against botulinum neurotoxin (BoNT). This review focuses on the U.S. Army's research and development efforts for a BoNT therapeutic over the period from 1975-2007. Two antitoxin preparations: Human botulism immunoglobulin (BIG) and Botulism Immune Globulin F(ab')2 Heptavalent Equine (BIGHE) were administered to humans and shown to possess acceptable efficacy and safety levels. BIGHE was deployed in...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Joseph C. Larsen Tags: Research Commentary Source Type: journals

Identification of novel cellular targets for therapeutic intervention against Ebola virus infection by siRNA screeningEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
While much progress has been made in developing drugs against a few prominent viruses such as HIV, few examples exist for emerging infectious agents. In some cases, broad spectrum anti-viral drugs, such as ribavirin, are effective, but for some groups of viruses, these show little efficacy in animal models. Traditional methods focus on screening small molecule libraries to identify drugs that target virus factors, with the intention that side-effects to the host can be minimized. However, this greatly limits potential drug targets and virus genes can rapidly mutate to avoid drug action. Recent advances in siRNA gene-target...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Andrey A. Kolokoltsov, Mohammad F. Saeed, Alexander N. Freiberg, Michael R. Holbrook, Robert A. Davey Tags: Research Article Source Type: journals

Toward RNA interference-based therapy for filovirus infectionsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ebola (EBOV) and Marburg (MARV) viruses, of the family filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates (NHPs) with mortality rates of up to 90%. Infection is thought to occur through mucous membranes or breaks in the skin after contact with infected animal tissue or body fluids of infected individuals. Beyond naturally occurring outbreaks, the potential use of these viruses in acts of bioterrorism remains a public health and national security concern. EBOV and MARV are classified as category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). To date, there are no lice...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Kevin B. Spurgers, Lynn S. Silvestri, Kelly L. Warfield, Sina Bavari Tags: Research Overview Source Type: journals

Conducting biodefense-related research in a highly regulated academic environmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this article, we discuss the impact of regulations pertaining to national security and quality control on scientific inquiry, especially as it relates to performing research in an academic setting. Specifically, the increasing burden of regulatory requirements on programs investigating select agents has negatively impacted the extent and quality of the research on these microbes, despite the fact that funds for these programs have become more readily available. Most of these regulations were created and are enforced to control access to a limited number of microbial agents considered to be the greatest threat to civilia...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Ashok K. Chopra, Johnny W. Peterson Tags: Research Commentaries Source Type: journals

Maximizing the use of Project Bioshield contracting opportunitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article explores the often complicated relationship between agency policymakers and the contracting officers that are charged with executing agency procurements. In particular, the article explores the role of the contracting officer in maximizing the use of streamlined contracting practices under the Project BioShield Act of 2004 (Public Law 108-276). Project BioShield, which is implemented through the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services (DHHS), is designed to encourage procurement activity that protects Americans against a chemical, biolog...
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Dana B. Pashkoff, John M. Clerici Tags: Research Commentaries Source Type: journals

Developing medical countermeasures: from BioShield to BARDAEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article examines U.S. government efforts in the MCM field and prospects for the future. Drug Dev Res 70:224-233, 2009. © 2009 Wiley-Liss, Inc. (Source: Drug Development Research)
Source: Drug Development Research - June 12, 2009 Category: Drugs & Pharmacology Authors: Jonathan B. Tucker Tags: Research Commentaries Source Type: journals

Development of medical countermeasures for biodefense: how far have we come in seven years?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No Abstract (Source: Drug Development Research)
Source: Drug Development Research - June 1, 2009 Category: Drugs & Pharmacology Authors: Lynne Gilfillan Tags: Preface Source Type: journals

Adaptivity in drug discovery and developmentEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The development of novel drugs is becoming increasingly challenging, inefficient, and costly, as acknowledged by all major stakeholders of pharmaceutical products. Adaptive designs have attracted considerable attention in recent years, as they promise an increase in efficiency of the drug development process by making better use of the observed data. The key idea of adaptive designs is to use data accumulating from an ongoing experiment to decide on how to modify certain design aspects and better address the question(s) of interest and/or adjust for incorrect assumptions. When planned carefully and applied in appropriate s...
Source: Drug Development Research - May 1, 2009 Category: Drugs & Pharmacology Authors: Frank Bretz, Michael Branson, Carl-Fredrik Burman, Christy Chuang-Stein, Christopher S. Coffey Tags: Research Overview Source Type: journals

In vitro and in vivo evaluation of novel implantable collagen-chitosan-soybean phosphatidylcholine composite film for the sustained delivery of mitomycin CEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An implantable mitomycin C (MMC) delivery system (MMC-film), incorporating polylactide (PLA)-MMC nanoparticles in a composite film from blends of collagen-chitosan-soybean phosphatidylcholine (SPC) with a mass ratio of 4:1:1, was developed and evaluated. PLA-MMC nanoparticles were prepared using an improved emulsion/solvent evaporation technique and then dispersed uniformly within the film to result in a final MMC loading content of 0.8 mg/cm2. Drug release studies were performed in pH 7.4 PBS at 37°C with drug analysis using UV/vis spectrometer at 366 nm. The MMC-film exhibited more fractional drug release and a longer t...
Source: Drug Development Research - April 20, 2009 Category: Drugs & Pharmacology Authors: Zhenqing Hou, Qian Sun, Qian Wang, Jing Han, Yuqian Wang, Qiqing Zhang Tags: Research Articles Source Type: journals

Development of an inhibitory antibody fragment to human tissue factor using phage display technologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tissue factor is involved in the etiology of thrombotic diseases initiating the thrombosis associated with the inflammation that occurs during infection. The prevention of blood coagulation and inflammation is of primary importance in a number of pathological situations. A single-chain variable antibody fragment of molecular weight of 26 kD that inhibits the action of human tissue factor was selected by phage display technology, purified and tested for its tissue factor inhibitory effect, purified on a protein A column, and its purity evaluated on SDS-PAGE. The effects of the antibody fragment on prothrombin times, Factor ...
Source: Drug Development Research - April 20, 2009 Category: Drugs & Pharmacology Authors: S.M. Meiring, J. Vermeulen, P.N. Badenhorst Tags: Research Articles Source Type: journals

Anti-angiogenic potential of scopoletin is associated with the inhibition of ERK1/2 activationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiogenesis plays an important role in many diseases, such as cancer, rheumatoid arthritis, and diabetic retinopathy. Specific inhibitors of angiogenesis are therefore expected to be potential candidate therapeutics for these disorders. Recently, several naturally occurring coumarins and synthetic analogues have proved to hinder new vessel formation. The present study was undertaken to investigate the effects of scopoletin, a phenolic coumarin compound with various biological activities on endothelial cell activation and resultant angiogenesis. Scopoletin had no cytotoxic effect on endothelial cells at the concentrations ...
Source: Drug Development Research - April 8, 2009 Category: Drugs & Pharmacology Authors: Rong Pan, Yue Dai, Jian Yang, Ying Li, Xiujuan Yao, Yufeng Xia Tags: Research Articles Source Type: journals

Effects of (-)-carveol and HPMC on the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide formulations in normotensive New Zealand rabbitsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The objective of the current study was to maximize the ocular bioavailability of the carbonic anhydrase inhibitor, dorzolamide hydrochloride (DZD) via (a) enhancement of DZD corneal transport using terpene enhancers, (b) reducing pre-corneal loss of the installed dose via increased formulation viscosity, and (c) assessment of the in vivo intraocular pressure (IOP) lowering effects of test formulations using rabbit. DZD was formulated as a 2% ophthalmic solution containing different concentrations of HPMC as a viscosity improving agent (VIA), and (-)-carveol as a corneal penetration enhancer. The transport of DZD from test ...
Source: Drug Development Research - March 19, 2009 Category: Drugs & Pharmacology Authors: Mohsen I. Afouna, Ala'a Khedr, Adnan Al-Marzoqi Tags: Research Articles Source Type: journals

Alzheimer's disease: a light at the end of the tunnel?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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Source: Drug Development Research - March 1, 2009 Category: Drugs & Pharmacology Authors: Albert J. Robichaud, David P. Rotella Tags: Preface Source Type: journals

5-HT6 antagonists as potential treatment for cognitive dysfunctionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Among the potential therapeutic targets for the development of cognitive enhancers for AD and schizophrenia, the 5-HT6 receptor is of especial interest based on its localization, pharmacology, and recent behavioral data showing that 5-HT6 receptor blockade improves cognition in a number of rodent behavioral models. It is localized almost exclusively in the CNS, in areas important for learning and memory, while atypical antipsychotics and tricyclic antidepressants bind with high affinity to this target. 5-HT6 receptor antagonism enhances neurotransmission at cholinergic and glutamatergic neurons, as well as in other pathway...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Kevin G. Liu, Albert J. Robichaud Tags: Research Overviews Source Type: journals

Advances in the development of kinase inhibitor therapeutics for Alzheimer's diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pharmaceutical approaches to slow the progression of Alzheimer's disease (AD) have focused primarily on reducing production or increasing clearance of amyloid [beta] peptide (A[beta]). Recent clinical trial results question the efficacy of targeting A[beta] for treatment of mild to moderate AD, highlighting the need for alternate approaches. With the marketing of eight kinase inhibitors for oncology indications as of 2008 (Gleevec®, Tarceva®, Nexavar®, Sutent®, Rapamune®, Sprycel®, Tasigna®, and Tykerb®) and current clinical trials of more than 150 others for a number of indications, the progress that has been made...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Mary J. Savage, Diane E. Gingrich Tags: Research Overviews Source Type: journals

Small molecule inhibitors of A[beta]-aggregation and neurotoxicityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of A[beta] peptide, neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau, and a deficit of cholinergic neurons in the basal forebrain. Presently, only symptomatic therapies are available for the treatment of AD and these therapies have a limited time frame of utility. Amyloid disorders represent the effects of chronic A[beta] production and are not a secondary pathological effect caused by a distant trigger; therefore targeting A[beta] is a viable pursuit. In this review, we will discuss the various small molecule...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Cheryl A. Hawkes, Vivian Ng, JoAnne McLaurin Tags: Research Article Source Type: journals

Progress toward the development of a viable BACE-1 inhibitorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive formation of insoluble amyloid plaque and fibrillary tangles. Plaques are extracellular constructs consisting primarily of A[beta]42 derived from the catabolism of [beta]-amyloid precursor protein (APP). [beta]-Secretase (BACE-1) is the enzyme responsible for the initiatory cleavage event in APP catabolism. The central role of BACE-1 in the production of A[beta]42 has made it an attractive target for drug development. However, the development of BACE-1 inhibitors has been hampered by difficulty in identifying inhibitors with acceptable...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Shawn J. Stachel Tags: Research Overviews Source Type: journals

[gamma]-secretase inhibitors for the treatment of Alzheimer's diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alzheimer's disease is a neurodegenerative disorder manifested by cognitive and memory deterioration, impairment of language, and other activities of daily life. Two major pathological hallmarks are characteristics of Alzheimer's disease: intracellular neurofibrillary tangles and extracellular amyloid plaques. The amyloid plaque is mainly comprised of aggregated form of the 40-42 residue amyloid [beta]-peptide (A[beta]). The accumulation and deposition of A[beta] eventually lead to neuronal damage and cell death. A[beta] peptides are generated from a large precursor protein (APP) by [beta]-secretase (BACE) and [gamma]-secr...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Wen-Lian Wu, Lili Zhang Tags: Research Overviews Source Type: journals

Structure and modeling in the design of [beta]- and [gamma]-secretase inhibitorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This review discusses the involvement of structure and modeling in the design of [beta]-secretase (BACE-1) and [gamma]-secretase inhibitors as putative Alzheimer's Disease therapeutics. The early and broad availability of structural information for BACE-1, a membrane-tethered aspartyl protease, has led to the use of in silico methods in the overall design and optimization process. However, for [gamma]-secretase, an integral membrane protein, the lack of a detailed 3D structure has limited the application of computational methods. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. (Source: Drug Development Research)
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: M. Katharine Holloway, Peter Hunt, Georgia B. McGaughey Tags: Research Overviews Source Type: journals

Translational medicine perspective in development of disease modifying therapies for Alzheimer's disease: biomarkers to buy down the riskEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of age-related dementia. Currently available pharmacologic therapies, including acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists, only treat symptoms and do not address the underlying neurodegeneration. In addition to potentially improve the accuracy of diagnosis, biomarkers serve important roles for the development of putative disease-modifying drugs for AD. In this article, we review the existing and emerging areas of biomarker research and development for AD. Biochemical biomarkers in ...
Source: Drug Development Research - February 27, 2009 Category: Drugs & Pharmacology Authors: Hong I. Wan, Orest Hurko, Mark Day, J. Lynn Rutkowski Tags: Research Overviews Source Type: journals