Pyridines

Publication Title: 
Investigative Ophthalmology & Visual Science

PURPOSE: To investigate the migratory and contractile behavior of isolated human corneal fibroblasts in fibrillar collagen matrices. METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin. Cells were plated at low density on top of or within 100-microm-thick fibrillar collagen lattices. After 18 hours to 7 days, time-lapse imaging was performed.

Author(s): 
Vishwanath, Mridula
Ma, Lisha
Otey, Carol A.
Jester, James V.
Petroll, W. Matthew
Publication Title: 
Molecular Pharmacology

The epigenetic down-regulation of genes is emerging as a possible underlying mechanism of the GABAergic neuron dysfunction in schizophrenia. For example, evidence has been presented to show that the promoters associated with reelin and GAD67 are down-regulated as a consequence of DNA methyltransferase (DNMT)-mediated hypermethylation. Using neuronal progenitor cells to study this regulation, we have previously demonstrated that DNMT inhibitors coordinately increase reelin and GAD67 mRNAs.

Author(s): 
Kundakovic, Marija
Chen, Ying
Guidotti, Alessandro
Grayson, Dennis R.
Publication Title: 
Nature Neuroscience

Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown.

Author(s): 
Kurita, Mitsumasa
Holloway, Terrell
GarcÌa-Bea, Aintzane
Kozlenkov, Alexey
Friedman, Allyson K.
Moreno, JosÈ L.
Heshmati, Mitra
Golden, Sam A.
Kennedy, Pamela J.
Takahashi, Nagahide
Dietz, David M.
Mocci, Giuseppe
Gabilondo, Ane M.
Hanks, James
Umali, Adrienne
Callado, Luis F.
Gallitano, Amelia L.
Neve, Rachael L.
Shen, Li
Buxbaum, Joseph D.
Han, Ming-Hu
Nestler, Eric J.
Meana, J. Javier
Russo, Scott J.
Gonz·lez-Maeso, Javier
Publication Title: 
Clinical Pharmacology and Therapeutics

After a 16-week clinical trial of a new anti-inflammatory drug, the participants were given a factual test to determine whether they had understood and remembered the information given them when consent was solicited. They filled out a questionnaire about their reasons for volunteering and their views on clinical studies and on medical practice in general. Demographic information was also obtained. Two thirds of the participants did not remember that they had been informed about potential risk (gastrointestinal ulceration).

Author(s): 
Hassar, M.
Weintraub, M.
Publication Title: 
British Journal of Clinical Pharmacology

1 A new imidazo-pyridine hypnotic (zolpidem 10 mg and 20 mg) was compared with placebo as premedication before general anaesthesia in female patients undergoing minor gynaecological surgery. Efficacy and tolerance before and after anaesthesia were assessed. Psychomotor testing was used to study recovery from anaesthesia. 2 Both doses of zolpidem produced good sedation pre-operatively but only the higher dose was associated with anterograde amnesia. 3 Premorbid anxiety scores were low in the group of patients studied and were unaffected by either dose of zolpidem.

Author(s): 
Cashman, J. N.
Power, S. J.
Jones, R. M.
Publication Title: 
Methods and Findings in Experimental and Clinical Pharmacology

The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general signs and behavior in mice. TU-199 (300 mg/kg p.o.) decreased locomotor activity 3 h after administration in mice.

Author(s): 
Kakinoki, B.
Ono, C.
Yamazaki, N.
Chikamatsu, N.
Wakatsuki, D.
Uchiyama, K.
Morinaka, Y.
Publication Title: 
Indian Journal of Experimental Biology

Pentobarbitone-induced hypnosis test was used as an animal model to explore the role of BR-16A, a polyherbal formulation in sleep. Pentobarbitone produces quick sleep latency (onset) and prolongation of total sleep time (duration). Sleep latency and total sleep time were used as a parameters for the evaluation. BR-16A potentiated the effect of triazolam (0.1 mg/kg, ip) and alprazolam (0.25 mg/kg, ip). Melatonin (5.0 mg/kg, ip) and zolpidem (0.5 mg/kg, ip) did not produce any significant effect on sleep parameters.

Author(s): 
Kumar, Anil
Kulkarni, S. K.
Publication Title: 
The International Journal of Clinical and Experimental Hypnosis

This study evaluated the benefits of add-on hypnotherapy in patients with chronic PTSD. Thirty-two PTSD patients treated by SSRI antidepressants and supportive psychotherapy were randomized to 2 groups: 15 patients in the first group received Zolpidem 10 mg nightly for 14 nights, and 17 patients in the hypnotherapy group were treated by symptom-oriented hypnotherapy, twice-a-week 1.5-hour sessions for 2 weeks.

Author(s): 
Abramowitz, Eitan G.
Barak, Yoram
Ben-Avi, Irit
Knobler, Haim Y.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

With >1 million deaths annually, mostly among children in sub-Saharan Africa, malaria poses one of the most critical challenges in medicine today. Although introduction of the artemisinin class of antimalarial drugs has offered a temporary solution to the problem of drug resistance, new antimalarial drugs are needed to ensure effective control of the disease in the future. Herein, we have investigated members of the methionine aminopeptidase family as potential antimalarial targets.

Author(s): 
Chen, Xiaochun
Chong, Curtis R.
Shi, Lirong
Yoshimoto, Tadashi
Sullivan, David J.
Liu, Jun O.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency.

Author(s): 
Biagini, Giancarlo A.
Fisher, Nicholas
Shone, Alison E.
Mubaraki, Murad A.
Srivastava, Abhishek
Hill, Alisdair
Antoine, Thomas
Warman, Ashley J.
Davies, Jill
Pidathala, Chandrakala
Amewu, Richard K.
Leung, Suet C.
Sharma, Raman
Gibbons, Peter
Hong, David W.
Pacorel, Bénédicte
Lawrenson, Alexandre S.
Charoensutthivarakul, Sitthivut
Taylor, Lee
Berger, Olivier
Mbekeani, Alison
Stocks, Paul A.
Nixon, Gemma L.
Chadwick, James
Hemingway, Janet
Delves, Michael J.
Sinden, Robert E.
Zeeman, Anne-Marie
Kocken, Clemens H. M.
Berry, Neil G.
O'Neill, Paul M.
Ward, Stephen A.

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