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  • ISSN: 2379-089X
    Volume 5, Issue 2
    Research Article
    Manish Kumar*, Vipin Saini, Chinmoy Kumar, Shailendra Bhatt, Anuj Malik, and A. Pandurangan
    The aim to develop a locally effective colon targeted therapeutic system in the form of a multiparticulate oral formulation that might provide an improved efficacy with a significant reduction in dose and systemic toxicity and improved quality of life for the treatment of Irritable Bowel Disease (IBD). The formulation of beads develops by inotropic gelation. The effect of various formulation parameters such as ratio of gellan gum and locust bean gum were studied for drug loading, and entrapment efficiency. To retard the drug release in the stomach and achieve a pH dependent release at colonic pH of 7.4 a polymethacrylate base coating carried out by dip coating method. The surface analysis was carried out by scanning electron microscopy (SEM). In vitro analysis of coated formulation shows much retarded release in comparison of uncoated formulation. The in vivo release performance of the developed colon specific formulation was carried out by gammascintigraphy.
    Sweta Sharma, Veejendra Kumar Yadav and Arpita Yadav*
    Recent advances in medicine suggest a combination therapy of immunotherapeutic and chemotherapeutic agents to be clinically successful in treating cancer patients, especially the cases of breast cancer where HER2 receptor is over expressed in about 30% of breast cancers. Recent experimental results indicate that immunotherapy enhances the efficiency of chemotherapeutic drug, perhaps by acting as its carrier. Recent success in crystallizing cyclic peptides inside humanized antibodies led us to demonstrate a plausible mechanism at the molecular level in our previous work. The generalized effort on a database of anticancer agents is described here. While authenticating the generality of the concept, special consideration has been given to drugs with severe side effects. A subset of compounds with severe side effects was chosen from a prepared database of clinically used anticancer drugs. The study depicts internalization of all compounds in antibody utilizing standard docking protocol. Further filtering was done based on more accurate Quantum polarized ligand docking (QPLD) to reconfirm previously identified descriptors for non-covalent carriage of anticancer agents and their delivery at target. Molecular dynamics simulations have been performed on the four best internalized compounds to show smooth carriage and negligible probability of premature expulsion of cargo. Affirmation of identified descriptors for carriage, points out the suitability of these chemotherapeutic agents for combination therapy enhancing their efficacy and reducing side effects. However, these results remain to be verified by in vitro or clinical studies.
    Abaidullah Sajid and Ali Qazi Masroor
    Objective: This study was conducted across 17 sites in nine major cities of Pakistan, to evaluate the safety and effectiveness of orphenadrine/paracetamol combination (Nuberol) in managing the viral symptoms like myalgia and fever among the local population.
    Study design: In this observational, prospective, multicenter study, 300 patients with known prescreened viral infections having myalgia and fever were recruited. While patients with hypersensitivity to the formulation, contra-indication and pregnant, or breastfeeding women were excluded.
    Interventions: The safety evaluation was done as per prescribing information for Nuberol. Myalgia was assessed through the Visual Analogue Scale (VAS), fever was monitored by recording temperature on 24 hourly monitoring chart and safety evaluation started on day 1 of the treatment. As per physician discretion, the treatment therapy was planned (5-10 days) with 2 follow-up visits, screening (visit 1), and after 6-10 days of treatment (visit 2).
    Results: Of 300 recruited patients, 168 (56%) were males and 132 (44%) were females with a mean age of 36.79 ± 13.65 (S.D). According to the results, flu was the most prevalent viral infections 244 (81.3%), among the study sample followed by Chikungunya 36 (12%) and 9 (3%) patients with dengue. The pain intensity and fever were decreased using the therapeutic combination, on visit 1, 203 (67%) patients had mild-moderate pain (VAS, 3-6) and 12 (4%) patients reported severe pain (VAS, 7-8). Upon the follow-up visit (visit 2- after 5-10 days treatment), 239 (80%) patients were having no pain, whereas 59 (19%) patients reported mild pain (VAS, 1-2). While the fever was subsided in almost 297(99.6%) patients in 4-6 hours by visit 2.
    Conclusion: The combination of Orphenadrine/Paracetamol (Nuberol) showed effective and safe in the symptomatic management of myalgia and fever in viral conditions among Pakistani population.
    Jimmy P. Xu, Ashwanth C. Francis, Megan E. Meuser, Marie Mankowski, Roger G. Ptak, Adel A. Rashad, Gregory B. Melikyan, and Simon Cocklin*
    Recent efforts by both academic and pharmaceutical researchers have focused on the HIV-1 capsid (CA) protein as a new therapeutic target. An inter-protomer pocket within the hexamer configuration of the CA, which is also a binding site for key host dependency factors, is the target of the most widely studied CA inhibitor compound PF-3450074 (PF-74). Despite its popularity, PF-74 suffers from properties that limit its usefulness as a lead, most notably it's extremely poor metabolic stability. To minimize unfavorable qualities, we investigated bioisosteric modification of the PF-74 scaffold as a first step in redeveloping this compound. Using a field-based bioisostere identification method, coupled with biochemical and biological assessment, we have created four new compounds that inhibit HIV-1 infection and that bind to the assembled CA hexamer. Detailed mechanism of action studies indicates that the modifications alter the manner in which these new compounds affect HIV-1 capsid core stability, as compared to the parental compound. Further investigations are underway to redevelop these compounds to optimize potency and drug-like characteristics and to deeply define the mechanism of action.
    Alaa E. Ali, Doha Beltagy, Gehan S. Elasala, and Sherif A. Kolkaila*
    ZnII and CdII complexes of barbital, CoII complex of thiouracil and mixed CuII-CoII complex of thiobarbituric acid were prepared and characterized by elemental analyses, IR, electronic spectra and magnetic susceptibility. The results showed that barbital and thiouracil act as bidentate ligands through O and N atoms while in mixed complexes of Cu-Co thiobarbituric acid, four molecules of thiobarbituric acid ligand which act as tri-, tetra- and penta-dentate through O, N and S atoms. Radical scavenging activities of the prepared complexes were studied and the results proved that Zn-barbital complex has the most potent antioxidant activity very close to the values of standard ascorbic acid. Antitumor and antimicrobial activities of the tested compounds were measured using SRB assay for breast cancer and liver cancer. Zn-barbital complex showed good results as antibacterial and antifungal agents.
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