Antibacterial activity of actinomycetes against bacterial pathogens of diabetic foot ulcers

Diabetes mellitus is a serious public health problem worldwide. Diabetic foot ulcers (DFU), a major complication in Type 2 diabetes are one of the major causes of morbidity and mortality around the world. To screen various bacterial pathogens present in diabetic foot ulcers and to determine their antibiotic sensitivity to actinomycetes isolated from various fields of Chandragiri, Tirupati, twenty four actinomycetes isolates were isolated and screened by primary and secondary screening methods to determine potent antibiotic producers by using test organisms. Among 24 isolates, 4 were more potent and they showed varied range of antibacterial activity of pathogens, isolated form diabetic foot ulcers. Four isolates were compared with lenezoid antibiotic. Enterococcus was resistant to lenezoid antibiotic but four actinomycetes inhibited the growth of Enterococi

Study on the Essential Oil of Aerial and Sub-Aerial Parts of Cymbopogon Flexuosus (Nees Ex Steud) Wats.

Cymbopogon flexuosus (Nees ex Steud) Wats commonly known as, East Indian lemongrass a widely grown essential oil plant in the world belongs to the family Poaceae and comprise of 140 species worldwide, found abundantly in tropics and sub-tropic regions of Asia, Africa and America. In India, 45 species are recorded of which the economic importance is C.winterianus, C.flexuosus, C.martinii, C.nardus, C.citratus, C.pendulus, C.jwarancusa and C.khasianus. Aerial and sub-aerial parts of C. flexuosus collected from Himavath Gopala hills, Karnataka, India, were subjected to hydrodistillation for extraction of essential oil. GC and GC-MS analysis were performed to know the chemical composition of the oil. Among the 39 compounds identified in aerial parts of the plant the major compounds were citral (64.98%), 1,7-octadien-3-ol (10.97%), dimethyl oxatricyclo nonanone (9.44%), nerol (2.85%), verbenol (1.77%) and caryophyllene oxide (0.71%). In sub-aerial parts of the plant 33 compounds were identified. The analysis of sub-aerial parts showed a different chemical profile compared to aerial part and possessed citral as the major compound of upto 30.47%. Other compounds in sub-aerial part are Eudesmol (17.82%), Elemol (14.16%), dihydro isopropyl methyl azulene (11.08%), .-cadinene (1.88%), junipene (1.36%), hydroxyalloaromadendrene, juniper camphor (1.12%) and elemene (1.04%)

DEVELOPMENT OF RIVASTIGMINE LOADED SELF ASSEMBLED NANOSTRUCTURES OF NONIONIC SURFACTANTS FOR BRAIN DELIVERY

Objective: Aim of the study is to develop rivastigmine-loaded niosomal in situ gel via the intranasal route to the brain by crossing the Blood-Brain Barrier. For the treatment of Alzheimer’s disease, it provides a speedy onset of action, a faster therapeutic effect, avoidance of the first-pass metabolism, and enhanced bioavailability. Methods: Rivastigmine niosomal in situ nasal gel was developed, refined and tested with the goal of delivering the medicine to the brain via the intranasal route Rivastigmine niosomes were formulated by thin-film hydration technique, optimized using (32) factorial design and characterized for its physicochemical parameters. Rivastigmine-loaded niosomes were further incorporated into Carbopal-934P and HPMC-K4M liquid gelling system to form in situ nasal gel. The resulting solution was evaluated for several parameters including, viscosity at pH 5 and pH 6, gelling capacity and gelling time. Results: Optimized best formulation containing span 60 (A) and cholesterol (B) with (1:0.5) ratio identified from the model developed from Design-Expert®12 software, exhibited Entrapment efficiency (76.5±0.23%), particle size (933.4±0.14 nm), in vitro drug release maximum (68.94±0.26%) at 8th hour and further studied for its characteristics by SEM and TEM showed stable vesicles. Polynomial equations of Y1, Y2, and Y3 were conducted and ANOVA results showed a significant impact (p<0.05) on three levels. In vivo perfusion studies using rat model showed, the niosomes developed has good perfusion compared to pure drug with 27.2% of drug absorption in the brain at the end of 3 h. In vitro permeation of Rivastigmine through the dialysis membrane showed that 60.74% w/w drug permeated after 8 h. The formation of stable vesicles was proved by Zeta potential measurements and SEM analysis. Conclusion: Optimized formulation had greater perfusion and was expected to have a good bioavailability compared to conventional other drug delivery systems

Insights into the Fold Organization of TIM Barrel from Interaction Energy Based Structure Networks

There are many well-known examples of proteins with low sequence similarity, adopting the same structural fold. This aspect of sequence-structure relationship has been extensively studied both experimentally and theoretically, however with limited success. Most of the studies consider remote homology or “sequence conservation” as the basis for their understanding. Recently “interaction energy” based network formalism (Protein Energy Networks (PENs)) was developed to understand the determinants of protein structures. In this paper we have used these PENs to investigate the common non-covalent interactions and their collective features which stabilize the TIM barrel fold. We have also developed a method of aligning PENs in order to understand the spatial conservation of interactions in the fold. We have identified key common interactions responsible for the conservation of the TIM fold, despite high sequence dissimilarity. For instance, the central beta barrel of the TIM fold is stabilized by long-range high energy electrostatic interactions and low-energy contiguous vdW interactions in certain families. The other interfaces like the helix-sheet or the helix-helix seem to be devoid of any high energy conserved interactions. Conserved interactions in the loop regions around the catalytic site of the TIM fold have also been identified, pointing out their significance in both structural and functional evolution. Based on these investigations, we have developed a novel network based phylogenetic analysis for remote homologues, which can perform better than sequence based phylogeny. Such an analysis is more meaningful from both structural and functional evolutionary perspective. We believe that the information obtained through the “interaction conservation” viewpoint and the subsequently developed method of structure network alignment, can shed new light in the fields of fold organization and de novo computational protein design

A Method for Dynamic Characterization and Response Prediction Using Ground Vibration Test(GVT)Data for Unknown Structures.

The Objective Of This Proposed Work Is To Develop A Reliable Method For Dynamic Characterization And Prediction Of Dynamic Response Of Structures Of Known/Unknown Configurations, By Processing The Free Vibration Data Generated Experimentally From The Ground Vibration Tests (GVT)Of The Prototype Vehicles. The Methodology Would Make Use Of The Measured Dynamic Data In Terms Of Mode Shapes, Natural Frequencies, Modal Damping, Point Impedances Etc.And Generate Modal (Scaled) Stiffness And Inertia Information That Will Be Used For Prediction Of Response Characteristics Of The Prototype Structure . With These Objectives, The Present Work Develops The Mathematical Formulation Of The Method, And Demonstrates Its Reliability By Performing The Experiment On A Simple Cantilever Beam To Determine Its Dynamic Characteristics. Results On Scaled Modal Stiffness And Inertia, Generated Through The Method Using Experimental (GVT) Data Show Excellent Agreement With Those Generated By FE And Analytical Models .It Must Be Noted That A Valid Benchmarking Is Performed With The Condition That The Experimental Procedure Is 'Blind' To The Actual Stiffness And Inertia Distributions As Used In FEM Or Analytical Models . Agreement Of The Predicted Response Of The Structure With That From Direct Experiment And Those From The FE And Analytical Models Indicates That This Method Will Be A Promising Tool To Predict The Dynamic And Aeroelastic Characteristics Of Any Prototype Vehicle In The Future. Once The Reliability Of The Method Is Established,It Can Be Extended To Determine The Dynamic And Aeroelastic Characteristics Of All Aircraft For Which Dynamic Characteristics Are Available From A Ground -; Vibration Test (GVT)

NIOSOMES AS AN EMERGING FORMULATION TOOL FOR DRUG DELIVERY-A REVIEW

Nonionic surfactant based vesicles which are uni/multilamellar in structures are called niosomes. These vesicles contains an aqueous interior surrounded by one or more amphiphilic bilayer membrane forming surfactant which separates them from the bulk solution, and are also called as supramolecular aggregates. Niosomes, being an efficient drug delivery system, investigations are carried out to utilize this system to treat various disorders, to promote improved patient compliance, lesser side effects, reduction in dose, lesser dosage frequency, and higher amount of the drug at the particular site so as to lessen an excessive contact with the whole body. The Pharmacokinetic and Pharmacodynamic profile of Niosomal drug delivery system vary for various entrapped drugs. Drugs that are successful in the mitigation or treatment of CNS disorders should cross the BBB to reach the brain, as BBB seems to be an obstacle for a large number of drugs, including CNS active drugs. This article compiles recent techniques for the preparation and characterization of niosomes, the effect of formulation variables on its physicochemical properties and discussed about its effective applications in drug delivery

MutL homologs in restriction-modification systems and the origin of eukaryotic MORC ATPases

The provenance and biochemical roles of eukaryotic MORC proteins have remained poorly understood since the discovery of their prototype MORC1, which is required for meiotic nuclear division in animals. The MORC family contains a combination of a gyrase, histidine kinase, and MutL (GHKL) and S5 domains that together constitute a catalytically active ATPase module. We identify the prokaryotic MORCs and establish that the MORC family belongs to a larger radiation of several families of GHKL proteins (paraMORCs) in prokaryotes. Using contextual information from conserved gene neighborhoods we show that these proteins primarily function in restriction-modification systems, in conjunction with diverse superfamily II DNA helicases and endonucleases. The common ancestor of these GHKL proteins, MutL and topoisomerase ATPase modules appears to have catalyzed structural reorganization of protein complexes and concomitant DNA-superstructure manipulations along with fused or standalone nuclease domains. Furthermore, contextual associations of the prokaryotic MORCs and their relatives suggest that their eukaryotic counterparts are likely to carry out chromatin remodeling by DNA superstructure manipulation in response to epigenetic signals such as histone and DNA methylation

A new family of polymerases related to superfamily A DNA polymerases and T7-like DNA-dependent RNA polymerases

Using sequence profile methods and structural comparisons we characterize a previously unknown family of nucleic acid polymerases in a group of mobile elements from genomes of diverse bacteria, an algal plastid and certain DNA viruses, including the recently reported Sputnik virus. Using contextual information from domain architectures and gene-neighborhoods we present evidence that they are likely to possess both primase and DNA polymerase activity, comparable to the previously reported prim-pol proteins. These newly identified polymerases help in defining the minimal functional core of superfamily A DNA polymerases and related RNA polymerases. Thus, they provide a framework to understand the emergence of both DNA and RNA polymerization activity in this class of enzymes. They also provide evidence that enigmatic DNA viruses, such as Sputnik, might have emerged from mobile elements coding these polymerases