Acne vulgaris causes a considerable amount of psychosocial stress. There are unfounded beliefs surrounding acne and unawareness of treatment options available.
The NS2B cofactor is critical for proteolytic activation of the flavivirus NS3 protease. To elucidate the mechanism involved in NS2B-mediated activation of NS3 protease, molecular dynamic simulation, principal component analysis, molecular docking, mutagenesis, and bioassay studies were carried out on both the dengue virus NS3pro and NS2B-NS3pro systems. The results revealed that the NS2B-NS3pro complex is more rigid than NS3pro alone due to its robust hydrogen bond and hydrophobic interaction networks within the complex. These potent networks lead to remodeling of the secondary and tertiary structures of the protease that facilitates cleavage sequence recognition and binding of substrates. The cofactor is also essential for proper domain motion that contributes to substrate binding. Hence, the NS2B cofactor plays a dual role in enzyme activation by facilitating the refolding of the NS3pro domain as well as being directly involved in substrate binding/interactions. Kinetic analyses indicated for the first time that Glu92 and Asp50 in NS2B and Gln27, Gln35, and Arg54 in NS3pro may provide secondary interaction points for substrate binding. These new insights on the mechanistic contributions of the NS2B cofactor to NS3 activation may be utilized to refine current computer-based search strategies to raise the quality of candidate molecules identified as potent inhibitors against flaviviruses.The spectrum of clinical manifestations caused by the dengue virus, namely, dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, are increasing in severity and present major threats to global health. In the tropics and subtropical regions, the fatality rate ranges between 1 and 10% of more than 1 million cases of dengue hemorrhagic fever every year. With exacerbation of disease infection rates aided by global warming, growing urbanization, and rapid expansion of international trade and travel, the virus is now endemic in more than 100 countries and threatens more than a quarter of the world's population. Currently, there is no vaccine or effective therapeutic agent available to protect against or cure acute dengue viral infections.Dengue viruses are members of the Flaviviridae family. They are small, enveloped positive-sense RNA viruses transmitted by Aedes aegypti and Aedes albopictus mosquitoes (6). Dengue virus type 2 (DEN2), the most prevalent of the four serotypes, contains a single-stranded RNA and encodes a large single polyprotein precursor of 3,391 amino acid residues which consists of three structural proteins (C, prM, and E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (16). Processing of the polyprotein precursor to release mature viral proteins is mediated co-and posttranslationally by host proteases and the virus-encoded two-component protease NS2B-NS3pro (8). Thus, the essential role of NS2B-NS3pro for viral replication makes it an attractive target for the development of effective antiviral drug inhibitors with therapeutic applications against dengue hemorrhagic feve...
Introduction: Cryotherapy with liquid nitrogen is an effective, safe and convenient form of treatment for plantar warts. EMLA® cream (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%) is a topical local anaesthetic agent that has proven to be effective and well tolerated in the relief of pain associated with various minor interventions in numerous clinical settings. Materials and Methods: In a single-centre, double-blind, randomised placebo-controlled study, 64 subjects were randomised into 2 groups. The subjects had a thick layer of EMLA® cream or placebo cream applied to pared plantar wart(s) and onto the surrounding margin of 1 mm to 2 mm under occlusion for 60 minutes prior to receiving cryotherapy. The pain of cryotherapy was evaluated by the subjects using a self-administered Visual Analogue Scale (VAS) immediately after the cryotherapy. Results: There was no statistical difference between the mean VAS score for EMLA® cream (47.0 ± 21.4 mm) and placebo (48.9 ± 22.0 mm). Those with more than 1 wart had a significantly higher VAS score than those with only 1 wart (59.1 ± 21.8 vs. 44.3 ± 20.4, P <0.05) but this did not affect the therapeutic effect of EMLA® cream prior to cryotherapy. Conclusion: We conclude that the application of EMLA® cream prior to cryotherapy does not reduce the pain associated with cryotherapy. Key words: Anaesthetic, Pain, Wart
Acne vulgaris causes a considerable amount of psychosocial stress. There are unfounded beliefs surrounding acne and unawareness of treatment options available.
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