Major Channels Involved in Neuropsychiatric Disorders and Therapeutic Perspectives.

Major channels involved in neuropsychiatric disorders and therapeutic perspectives.

Front Genet. 2013; 4: 76
Imbrici P, Camerino DC, Tricarico D

Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription, and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders (BPDs) or schizophrenia. Moreover, point mutations in calcium, sodium, and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium, and potassium channels in BPD, schizophrenia, and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests. HubMed – drug

Therapy’s Shadow: A Short History of the Study of Resistance to Cancer Chemotherapy.

Front Pharmacol. 2013; 4: 58
Keating P, Cambrosio A, Nelson NC, Mogoutov A, Cointet JP

This article traces the history of research on resistance to drug therapy in oncology using scientometric techniques and qualitative analysis. Using co-citation analysis, we generate maps to visualize subdomains in resistance research in two time periods, 1975-1990 and 1995-2010. These maps reveal two historical trends in resistance research: first, a shift in focus from generic mechanisms of resistance to chemotherapy to a focus on resistance to targeted therapies and molecular mechanisms of oncogenesis; and second, a movement away from an almost exclusive reliance on animal and cell models and toward the generation of knowledge about resistance through clinical trial work. A close reading of highly cited articles within each subdomain cluster reveals specific points of transition from one regime to the other, in particular the failure of several promising theories of resistance to be translated into clinical insights and the emergence of interest in resistance to a new generation of targeted agents such as imatinib and trastuzumab. We argue that the study of resistance in the oncology field has thus become more integrated with research into cancer therapy – rather than constituting it as a separate domain of study, as it has done in the past, contemporary research treats resistance as the flip side to treatment, as therapy’s shadow. HubMed – drug

Role of DNA Repair Pathways in Response to Zidovudine-induced DNA Damage in Immortalized Human Liver THLE2 Cells.

Int J Biomed Sci. 2013 Mar; 9(1): 18-25
Wu Q, Beland FA, Chang CW, Fang JL

The nucleoside reverse transcriptase inhibitor zidovudine (3′-azido-3′-dexoythymidine, AZT) can be incorporated into DNA and cause DNA damage. Previously, we determined that the human hepatocellular carcinoma HepG2 cells are more susceptible to AZT-induced toxicities than the immortalized normal human liver THLE2 cells and the nucleotide excision repair (NER) pathway plays an essential role in the response to AZT-induced DNA damage. We have now investigated if the effects of AZT treatment on the expression levels of genes related to DNA damage and repair pathways contribute to the differences in sensitivity to AZT treatment between HepG2 cells and THLE2 cells. Of total 84 genes related to DNA damage and repair, two, five, and six genes were up-regulated more than 1.5-fold at 50, 500, and 2,500 µM AZT groups compared with that of control THLE2 cells. Seven genes showed a decreased expression of more than 1.5-fold following the 2,500 µM AZT treatment. Two-sided multivariate analysis of variance indicated that the change in expression of genes involved in apoptosis, cell cycle, and DNA repair pathways was significant only at 2,500 µM AZT. Statistically significant dose-related increases were identified in XPC gene expression and GTF2H1 protein level after the AZT treatments, which implicated the NER pathway in response to the DNA damage induced by AZT. In contrast, AZT treatment did not alter significantly the expression of the APE1 gene or the levels of APE1 protein. These results indicate that the NER repair pathway is involved in AZT-induced DNA damage response in immortalized human hepatic THLE2 cells. HubMed – drug

Liquid chromatographic determination of linagliptin in bulk, in plasma and in its pharmaceutical preparation.

Int J Biomed Sci. 2012 Sep; 8(3): 209-14
El-Bagary RI, Elkady EF, Ayoub BM

In this work, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of linagliptin (LNG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile(20:80, v/v) at a flow rate of 1 mL min(-1). Two detection techniques have been applied either UV detection at 299 nm in the first method or fluorometric detection at 239 nm for excitation and 355 nm for emission in the second method. Chromatographic separation in the two methods was achieved on a Symmetry(®) cyanide column (150 mm × 4.6 mm, 5 ?m). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 2.5-80 ?g mL(-1) for LNG in bulk and 2.5-15 ?g mL(-1) for LNG in plasma with the first method and 5-160 ?g mL(-1) for LNG in bulk with the second method. The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drug in its pharmaceutical preparation. HubMed – drug