Emerging Subspecialties in Neurology: Clinical Development.

Emerging Subspecialties in Neurology: Clinical development.

Filed under: Drug and Alcohol Rehabilitation

Neurology. 2013 Jan 1; 80(1): e4-7
Guptill JT, Dupuis RE, D’Cruz O

Therapeutic development includes the activities necessary to bring a new medicinal compound (chemical or biologic) or medical device to market. Following drug discovery or development of a new device, successful preclinical studies result in an Investigational New Drug (IND) application (United States only; Clinical Trials Exemption Certificate in the United Kingdom). Once the IND is filed, a team-driven process begins that tests the efficacy and safety of a new therapeutic in humans. This process, known as clinical development, has traditionally been divided into 4 phases, with large-scale phase 3 pivotal trials in patients with a specific disease leading to registration and postmarketing studies.(1).
HubMed – drug

 

Aurintricarboxylic Acid Ameliorates Experimental Autoimmune Encephalomyelitis by Blocking Chemokine-Mediated Pathogenic Cell Migration and Infiltration.

Filed under: Drug and Alcohol Rehabilitation

J Immunol. 2012 Dec 24;
Zhang F, Wei W, Chai H, Xie X

Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Overactivation of CD4(+) T cells, especially the Th1 and Th17 subpopulations, is thought to be the direct cause of this disease. Aurintricarboxylic acid (ATA), an inhibitor of protein-nucleic acid interaction, has been reported to block with the JAK/STAT signaling pathway that is critical for Th cell differentiation. In this study, we discovered that ATA treatment significantly reduces the clinical score of EAE, but it does not directly inhibit the differentiation of Th1 and Th17 cells in vitro. ATA was found to block the chemotaxis and accumulation of dendritic cells in the spleen of EAE mice before the onset of the disease and to reduce the percentage of Th1 and Th17 cells in the spleen. Further study revealed that ATA also blocks the infiltration of pathogenic T cells into the CNS and blocks the onset of passive EAE. ATA was found to inhibit the functions of many chemokine receptors. By blocking chemokine-mediated migration of dendritic cells and pathogenic T cells, ATA alleviates the pathogenesis of EAE and might be used to treat autoimmune diseases, including multiple sclerosis.
HubMed – drug

 

Chemical approaches to studying stem cell biology.

Filed under: Drug and Alcohol Rehabilitation

Cell Res. 2012 Dec 25;
Li W, Jiang K, Wei W, Shi Y, Ding S

Stem cells, including both pluripotent stem cells and multipotent somatic stem cells, hold great potential for interrogating the mechanisms of tissue development, homeostasis and pathology, and for treating numerous devastating diseases. Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology, and to translate stem cells into regenerative medicine. Chemical approaches have recently provided a number of small molecules that can be used to control cell self-renewal, lineage differentiation, reprogramming and regeneration. These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes. Ultimately, this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation.Cell Research advance online publication 25 December 2012; doi:10.1038/cr.2012.182.
HubMed – drug

 

Genipin crosslinked ethyl cellulose-chitosan complex microspheres for anti-tuberculosis delivery.

Filed under: Drug and Alcohol Rehabilitation

Colloids Surf B Biointerfaces. 2012 Nov 22; 103C: 530-537
Feng H, Zhang L, Zhu C

Genipin-crosslinked complex microspheres made of the combination of two polymers, ethyl cellulose and chitosan, were prepared by spray drying method. Rifabutin, an anti-tuberculosis agent was used as a model drug. Effects of various specifications of ethyl cellulose and chitosan, different drug/polymers ratios and crosslinking effect of genipin on complex microspheres and drug release characteristics were compared to obtain optimized manufacturing parameters. The complex microspheres showed a significant different shape as compared to chitosan microspheres. Biphasic release features were observed in the in vitro and in vivo release study, consisting of an initial quick release phase and an extended sustained release phase. Furthermore, pulmonary drug concentrations of rats after administering the complex microspheres were maintained on a therapeutic level for at least 24 days.
HubMed – drug

 

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