Synthesis of novel 3-(1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazol-5(4H)-one as antifungal agents

A novel series of 1,2,3 triazole compounds possessing 1,2,4 oxadiazole ring were efficiently synthesized. Synthesized compounds were evaluated for their in vitro antifungal activities using standard cup plate method. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Compound 11a from the series was more potent than miconazole against Candida albicans (MIC-20) and Aspergillus flavus (MIC-10) whereas equipotent with miconazole against Fusarium oxysporum (MIC-25) and Aspergillus niger (MIC-12.5). Also compound 11h was more potent than miconazole against Candida albicans (MIC-20) and Aspergillus niger (MIC-10) and equipotent with miconazole against Fusarium oxysporum. Compound 11h was equipotent with fluconazole against Aspergillus niger (MIC-10).     

Antimalarials from nature

Malaria is a major public health problem mainly due to the development of resistance by the most lethal causative parasitic species, Plasmodium falciparum to the mainstay drugs like chloroquine. New drugs with unique structures and mechanism of action are urgently required to treat sensitive and drug-resistant strains of malaria. Historically, compounds containing novel structure from natural origin represent a major source for the discovery and development of new drugs for several diseases. This review presents recent advances in antimalarial drug discovery from natural sources, including plant extracts, and compounds isolated from plants, bacteria, fungi and marine organisms. These compounds offer new and novel scaffolds for development as antimalarials. The literature from 1998 to October 2008 is reviewed. The review present literature compilation from plant and marine extracts, alkaloids (naphthylisoquinolines, bisbenzylisoquinolines, protoberberines and aporphines, indoles, manzamines, and miscellaneous alkaloids) terpenes (sesquiterpenes, triterpenes, diterpenes, and miscellaneous terpenes) quassinoids, flavonoids, limonoids, chalcones, peptides, xanthones, quinones and coumarines, and miscellaneous antimalarials from nature. The review also provides an outlook to recent semisynthetic approaches to antimalarial drugs discovered from natural sources.     

Formulation Design and Optimization of Novel Taste Masked Mouth-Dissolving Tablets of Tramadol Having Adequate Mechanical Strength

The purpose of this work was to develop novel taste masked mouth-dissolving tablets of tramadol that overcomes principle drawback of such formulation which is inadequate mechanical strength. Tramadol is an opioid analgesic used for the treatment of moderate to severe pain. Mouth-dissolving tablets offer substantial advantages like rapid onset of action, beneficial for patients having difficulties in swallowing and in conditions where access to water is difficult. The crucial aspect in the formulation of mouth-dissolving tablets is to mask the bitter taste and to minimize the disintegration time while maintaining a good mechanical strength of the tablet. Mouth-dissolving tablets of tramadol are not yet reported in the literature because of its extreme bitter taste. In this work, the bitter taste of Tramadol HCl was masked by forming a complex with an ion exchange resin Tulsion335. The novel combination of a superdisintegrant and a binder that melts near the body temperature was used to formulate mechanically strong tablets that showed fast disintegration. A 3² full factorial design and statistical models were applied to optimize the effect of two factors, i.e., superdisintegrant (crospovidone) and a mouth-melting binder (Gelucire 39/01). It was observed that the responses, i.e., disintegration time and percent friability were affected by both the factors. The statistical models were validated and can be successfully used to prepare optimized taste masked mouth-dissolving tablets of Tramadol HCl with adequate mechanical strength and rapid disintegration.     

Identification and cross-species amplification of EST derived SSR markers in different bamboo species

The availability of expressed sequence data derived from gene discovery programs became an alternative source of mining simple sequence repeat (SSR) and developing inexpensive genetic markers for the crop improvements. In present study, 10 express sequence tags (EST)-SSR markers were identified from Bambusa oldhamii public sequence data base. Transferability to 25 species of Bambusoideae ranged from 30% to 100%. The number of alleles detected per locus ranged from 2 to 10. All the newly identified SSR markers were found to be moderately to highly polymorphic with an average Polymorphic Information Content (PIC) value of 0.54. As these loci represents transcribed region and recorded high level of cross transferability and reliable amplification across the species, demonstrating the utility of these markers for functional and genetic analyses of bamboo species.     

High accuracy decoding of movement target direction in non-human primates based on common spatial patterns of local field potentials

Background

The current development of brain-machine interface technology is limited, among other factors, by concerns about the long-term stability of single- and multi-unit neural signals. In addition, the understanding of the relation between potentially more stable neural signals, such as local field potentials, and motor behavior is still in its early stages.

Methodology/Principal Findings

We tested the hypothesis that spatial correlation patterns of neural data can be used to decode movement target direction. In particular, we examined local field potentials (LFP), which are thought to be more stable over time than single unit activity (SUA). Using LFP recordings from chronically implanted electrodes in the dorsal premotor and primary motor cortex of non-human primates trained to make arm movements in different directions, we made the following observations: (i) it is possible to decode movement target direction with high fidelity from the spatial correlation patterns of neural activity in both primary motor (M1) and dorsal premotor cortex (PMd); (ii) the decoding accuracy of LFP was similar to the decoding accuracy obtained with the set of SUA recorded simultaneously; (iii) directional information varied with the LFP frequency sub-band, being greater in low (0.3–4 Hz) and high (48–200 Hz) frequency bands than in intermediate bands; (iv) the amount of directional information was similar in M1 and PMd; (v) reliable decoding was achieved well in advance of movement onset; and (vi) LFP were relatively stable over a period of one week.

Conclusions/Significance

The results demonstrate that the spatial correlation patterns of LFP signals can be used to decode movement target direction. This finding suggests that parameters of movement, such as target direction, have a stable spatial distribution within primary motor and dorsal premotor cortex, which may be used for brain-machine interfaces.     

JAMA published fewer industry-funded studies after introducing a requirement for independent statistical analysis

Background

JAMA introduced a requirement for independent statistical analysis for industry-funded trials in July 2005. We wanted to see whether this policy affected the number of industry-funded trials published by JAMA.

Methods and Findings

We undertook a retrospective, before-and-after study of published papers. Two investigators independently extracted data from all issues of JAMA published between 1 July 2002 and 30 June 2008 (i.e., three years before and after the policy). They were not blinded to publication date. The randomized controlled trials (RCTs) were classified as industry funded (IF), joint industry/non-commercial funding (J), industry supported (IS) (when manufacturers provided materials only), non-commercial (N) or funding not stated (NS). Findings were compared and discrepancies resolved by discussion or further analysis of the reports. RCTs published in The Lancet and NEJM over the same period were used as a control group. Between July 2002 and July 2008, JAMA published 1,314 papers, of which 311 were RCTs. The number of industry studies (IF, J or IS) fell significantly after the policy (p = 0.02) especially for categories J and IS. However, over the same period, the number of industry studies rose in both The Lancet and NEJM.

Conclusions

After the requirement for independent statistical analysis for industry-funded studies, JAMA published significantly fewer RCTs and significantly fewer industry-funded RCTs. This pattern was not seen in the control journals. This suggests the JAMA policy affected the number of submissions, the acceptance rate, or both. Without analysing the submissions, we cannot check these hypotheses but, assuming the number of published papers is related to the number submitted, our findings suggest that JAMA''s policy may have resulted in a significant reduction in the number of industry-sponsored trials it received and published.     

Antimalarial activities of ring-substituted bioimidazoles

We report in vitro antimalarial activities against chloroquine sensitive and resistant Plasmodium falciparum strains, and in vivo activities against Plasmodium berghei in mice for four series of ring-substituted-L-histidines and histamines.