Optimization of Ibuprofen Loaded Nanostructured Lipid Carrier (NLC) Using Response Surface Methodology (RSM): Preparation and Invitro Evaluation

The present work describes a study on “optimization of ibuprofen loaded nano structured lipid carrier (NLC) using response surface methodology (RSM): preparation and in vitro evaluation” Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body. This drug was selected for the study because it has good percutaneous absorption and appears to be more active as anti inflammatory activity and is well tolerated. Nano structured lipid carrier was formulated by high speed homogenization method which was found to be simple and economic. Excipients (lipids) used in the study was economic and safe. Effect of various factors on the formulation can be studied by the Box-Behnken design. With the use of desirability plots minor change in the formulation is possible for the required response. It is evidence from the FTIR spectrum shows that the lipids ( solid lipid ) used in the NLC formulations were compatible with the drug Ibuprofen. In vitro release studies of the formulations were carried out across the dialysis membrane using a diffusion cell. Among all the formulations, the release was highest for the formulation NLC F1 as 98.63% in 12 hours diffusion study. It also shows lowest particle size , better entrapment efficiency and high zeta potential value, hence NLC-IBU F1 was concluded as optimized formulation. The optimized nano structured lipid carrier IBU-NLC formulations was dispersed into gel. The polymers namely Carbopol-940 were used as gelling agent for formulation of gels and studied for their drug permeation from the NLC- gel formulations. Carbopol gels were transparent, non-greasy and smooth on application. The pH of the formulations ranged from 6.5 to 7.1. The spreadability data ranges from 4.3-5.5 gm-cm/sec. The drug content was found to be 90-94%. The pH, spreadability and drug content were good and up to the acceptable range. The in vitro diffusion study of NLC gel formulation were carried out across the skin membrane using Franz diffusion cell. It shows good permeation into skin for prolonged release of 12 hours than the marketed gel formulation . From this investigation, it was concluded that formulation F1 was concluded as best formulation . It could be concluded that NLCs may play an important role in controlling the release of Ibuprofen from NLCs as well as targeting of drug to the skin. The amount of drug retained in the skin for NLC based gel was found to be significantly higher as compared to marketed formulation. The dermal retention of Ibuprofen was attributed to the increased contact with corneocytes, skin occlusion and sustained release owing to the properties of NLCs. Due to their small particle size, NLC make closer contact with the superficial junctions of corneocytes clusters and furrows present between corneocyte islands and favour accumulation for several hours , allowing sustained drug release. Therefore, it can be concluded that the Ibuprofen NLCs gel formulation can be used to extend the duration of drug release and as an efficient topical drug delivery carrier for chronic treatment of inflammation

Idle Object Detection in Video for Banking ATM Applications

Abstract: This study proposes a method to detect idle object and applies it for analysis of suspicious events. Partitioning and Normalized Cross Correlation (PNCC) based algorithm is proposed for the detection of moving object. This algorithm takes less processing time, which increases the speed and also the detection rate. In this an approach is proposed for the detection and tracking of moving object in an image sequence. Two consecutive frames from image sequence are partitioned into four quadrants and then the Normalized Cross Correlation (NCC) is applied to each sub frame. The sub frame which has minimum value of NCC, indicates the presence of moving object. The proposed system is going to use the suspicious tracking of human behaviour in video surveillance and it is mainly used for security purpose in ATM application. The suspicious object's visual properties so that it can be accurately segmented from videos. After analyzing its subsequent motion features, different abnormal events like robbery can be effectively detected from videos. The suspicious action in ATM are many, such as using mobile phones, multiple persons trying to access the ATM machine in same time, kicking of each other, idle object and it shows event corresponding to Vandalism and robbery. In proposed system, idle object detection is used to identify by using PNCC algorithm with P-filter (Particle) and by extracting the features of the object in an enhanced way by using the curvelet based transformation

Experimental Assessment on Latent Fingerprint Matching Using Affine Transformation

Abstract-In forensics latent fingerprint identification is critical importance to identifying suspects: latent fingerprints are invisible fingerprint impressions left by fingers on surfaces of objects. The proposed algorithm uses a robust alignment algorithm (mixture contour and Orientation based Descriptor) to align fingerprints and to get the similarity score between fingerprints by considering minutiae points and ridge orientation field information.The texture-based descriptors (local binary patterns and local phase quantization), address important issues related to the dissimilarity representation, such as the impact of the number of references used for verification and identification. However, the overlapped region shape similarity retrieved from minutiae spatial distribution information provides additional important criteria. After finding the overlapping region of a possible affine transform, we can measure to find the shape dissimilarity via the application of the shape context to all interior points.TheHybrid matching algorithm, is to prune outlier minutiae pairs, and secondly to provide more information to use in similarity evaluation

Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity.

Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET) whole-genome sequencing, we analyzed 15 gastric cancers (GCs) from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT). Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H(+) leakage, and the fusion might contribute to invasiveness once a cell is transformed. Cell Rep 2015 Jul 14; 12(2):272-285

Functional annotations of diabetes nephropathy susceptibility loci through analysis of genome-wide renal gene expression in rat models of diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Hyperglycaemia in diabetes mellitus (DM) alters gene expression regulation in various organs and contributes to long term vascular and renal complications. We aimed to generate novel renal genome-wide gene transcription data in rat models of diabetes in order to test the responsiveness to hyperglycaemia and renal structural changes of positional candidate genes at selected diabetic nephropathy (DN) susceptibility loci.</p> <p>Methods</p> <p>Both Affymetrix and Illumina technologies were used to identify significant quantitative changes in the abundance of over 15,000 transcripts in kidney of models of spontaneous (genetically determined) mild hyperglycaemia and insulin resistance (Goto-Kakizaki-GK) and experimentally induced severe hyperglycaemia (Wistar-Kyoto-WKY rats injected with streptozotocin [STZ]).</p> <p>Results</p> <p>Different patterns of transcription regulation in the two rat models of diabetes likely underlie the roles of genetic variants and hyperglycaemia severity. The impact of prolonged hyperglycaemia on gene expression changes was more profound in STZ-WKY rats than in GK rats and involved largely different sets of genes. These included genes already tested in genetic studies of DN and a large number of protein coding sequences of unknown function which can be considered as functional and, when they map to DN loci, positional candidates for DN. Further expression analysis of rat orthologs of human DN positional candidate genes provided functional annotations of known and novel genes that are responsive to hyperglycaemia and may contribute to renal functional and/or structural alterations.</p> <p>Conclusion</p> <p>Combining transcriptomics in animal models and comparative genomics provides important information to improve functional annotations of disease susceptibility loci in humans and experimental support for testing candidate genes in human genetics.</p

Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology

Environmentally Realistic Exposure to the Herbicide Atrazine Alters Some Sexually Selected Traits in Male Guppies

Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the number of courtship displays performed. Atrazine exposure also reduced aggression towards competing males in the context of mate competition. In the wild, exposure levels vary among individuals because of differential distribution of the pollutants across habitats; hence, differently impacted males often compete for the same mates. Disrupted mating signals can reduce reproductive success as females avoid mating with perceptibly suboptimal males. Less aggressive males are at a competitive disadvantage and lose access to females. This study highlights the effects of atrazine on ecologically relevant mating signals and behaviors in exposed wildlife. Altered reproductive traits have important implications for population dynamics, evolutionary patterns, and conservation of wildlife species

Claudins in renal physiology and disease

The tight junction forms the paracellular permeability barrier in all epithelia, including the renal tubule. Claudins are a family of tight junction membrane proteins with four transmembrane domains that form the paracellular pore and barrier. Their first extracellular domain appears to be important for determining selectivity. A number of claudin isoforms have been found to be important in renal tubule function, both in adults and in neonates. Familial hypomagnesemic hypercalciuria with nephrocalcinosis is an autosomal recessive syndrome characterized by impaired reabsorption of Mg and Ca in the thick ascending limb of Henle's loop. Mutations in claudin-16 and 19 can both cause this syndrome, but the pathophysiological mechanism remains controversial

Organization of multiprotein complexes at cell–cell junctions

The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease