EFFECT OF EFFERVESCENCE IN COMBINATION WITH SUPERDISINTEGRANTS IN THE FORMULATION OF PROPRANOLOL HCL ORAL DISINTEGRATING TABLETS

ABSTRACTObjective: The current research work is intended to formulate propranolol HCl (PLH) as orally disintegrating tablet (ODT). It is also intending to checkthe superiority in a combination of superdisintegrants and effervescent mixture than the use of superdisintegrants alone by a direct compressiontechnique. To fasten the onset of action and thereby enhancing the bioavailability of PLH in comparison to its conventional tablets.Methods: Standard calibration curve of PLH was obtained in pH 6.8 phosphate buffer by spectrophotometric method, drug-excipient compatibilitystudies were carried by Fourier transform infrared (FT-IR) studies. All the formulations were evaluated for pre and postcompression studies.Accelerated stability studies were carried out up to 6 months for the optimized formulation, EF3.Results and Discussion: Superdisintegrants used in the study are compatible with PLH. Pre- and post-compression parameters were within theacceptable limits for all formulations. In vitro dissolution kinetic studies indicate the release of PLH from ODT increases as the concentration ofsuperdisintegrants as well as the ratio of citric acid: NaHCO3 of effervescent mixture increases. Formulations with an effervescent mixture are havingrapid disintegration and dissolution rate when compared to the formulations with superdisintegrants alone. The order of superdisintegrants inenhancing the dissolution rate of PLH is crospovidone (CPV) > croscarmellose sodium (CCS) > sodium starch glycolate (SSG). Formulation, EF3 (10%CPV and 1:3, citric acid: NaHCO3 ratio, respectively) had the highest dissolution efficiency at 10 minutes (DE10=82.74%); the first order dissolutionrate constant (K1=0.141/minutes) with a regression coefficient (r2=0.974) and lesser time for 90% of drug release (t90=4 minutes), was considered asthe optimal ODT in this study. Formulation EF3, passed the test for stability.Conclusion: Hence, an effective PLH ODT was formulated by the direct compression technique with disintegration by combination of superdisintegrantsand effervescent mixture, will fasten the onset of action and enhances the bioavailability of PLH in comparison to its conventional tablets.Keywords: Propranolol HCl, Orally disintegrating tablet, Sodium starch glycolate, Croscarmellose sodium, Crospovidone, Direct compression, In vitrodissolution studies

Dynamical spin-flip susceptibility for a strongly interacting ultracold Fermi gas

The Stoner model predicts that a two-component Fermi gas at increasing repulsive interactions undergoes a ferromagnetic transition. Using the random-phase approximation we study the dynamical properties of the interacting Fermi gas. For an atomic Fermi gas under harmonic confinement we show that the transverse (spin-flip) dynamical susceptibility displays a clear signature of the ferromagnetic phase in a magnon peak emerging from the Stoner particle-hole continuum. The dynamical spin susceptibilities could be experimentally explored via spin-dependent Bragg spectroscopy.Comment: 4 pages, 3 figure

Low-energy Scheduling Algorithms for Wearable Fall Pre-impact Detection System

ABSTRACT In this paper, novel low-energy static and dynamic scheduling algorithms with low computational complexities for heterogeneous multiprocessor systems are proposed. Since battery life of the system plays a critical role in wearable embedded systems, the algorithms are useful for energy consumption reduction in Body Area Network (BAN)-based wearable multiprocessor systems in healthcare applications. Our developed BAN-based fall pre-impact detection system is used in this investigation. Based on simulation results using the algorithms, it is found that the battery life can be extended up to 41.6 percent more of its normal life without the algorithms

An Exact Formula for the Average Run Length to False Alarm of the Generalized Shiryaev-Roberts Procedure for Change-Point Detection under Exponential Observations

We derive analytically an exact closed-form formula for the standard minimax Average Run Length (ARL) to false alarm delivered by the Generalized Shiryaev-Roberts (GSR) change-point detection procedure devised to detect a shift in the baseline mean of a sequence of independent exponentially distributed observations. Specifically, the formula is found through direct solution of the respective integral (renewal) equation, and is a general result in that the GSR procedure's headstart is not restricted to a bounded range, nor is there a "ceiling" value for the detection threshold. Apart from the theoretical significance (in change-point detection, exact closed-form performance formulae are typically either difficult or impossible to get, especially for the GSR procedure), the obtained formula is also useful to a practitioner: in cases of practical interest, the formula is a function linear in both the detection threshold and the headstart, and, therefore, the ARL to false alarm of the GSR procedure can be easily computed.Comment: 9 pages; Accepted for publication in Proceedings of the 12-th German-Polish Workshop on Stochastic Models, Statistics and Their Application

Social learning against data falsification in sensor networks

Sensor networks generate large amounts of geographically-distributed data. The conventional approach to exploit this data is to first gather it in a special node that then performs processing and inference. However, what happens if this node is destroyed, or even worst, if it is hijacked? To explore this problem, in this work we consider a smart attacker who can take control of critical nodes within the network and use them to inject false information. In order to face this critical security thread, we propose a novel scheme that enables data aggregation and decision-making over networks based on social learning, where the sensor nodes act resembling how agents make decisions in social networks. Our results suggest that social learning enables high network resilience, even when a significant portion of the nodes have been compromised by the attacker

Regulation of DNA Repair Mechanism in Human Glioma Xenograft Cells both In Vitro and In Vivo in Nude Mice

Glioblastoma Multiforme (GBM) is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR) are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ) repair mechanism plays a major role in double strand break (DSB) repair in mammalian cells.Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU) and MMP9-cathepsin B (pMC) shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls.Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential of MMP9, uPAR and cathepsin B shRNA in the treatment of glioma from clinical stand point

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

Tuftsin Promotes an Anti-Inflammatory Switch and Attenuates Symptoms in Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a demyelinating autoimmune disease mediated by infiltration of T cells into the central nervous system after compromise of the blood-brain barrier. We have previously shown that administration of tuftsin, a macrophage/microglial activator, dramatically improves the clinical course of experimental autoimmune encephalomyelitis (EAE), a well-established animal model for MS. Tuftsin administration correlates with upregulation of the immunosuppressive Helper-2 Tcell (Th2) cytokine transcription factor GATA-3. We now show that tuftsin-mediated microglial activation results in shifting microglia to an anti-inflammatory phenotype. Moreover, the T cell phenotype is shifted towards immunoprotection after exposure to tuftsin-treated activated microglia; specifically, downregulation of pro-inflammatory Th1 responses is triggered in conjunction with upregulation of Th2-specific responses and expansion of immunosuppressive regulatory T cells (Tregs). Finally, tuftsin-shifted T cells, delivered into animals via adoptive transfer, reverse the pathology observed in mice with established EAE. Taken together, our findings demonstrate that tuftsin decreases the proinflammatory environment of EAE and may represent a therapeutic opportunity for treatment of MS

Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

Abstract: The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins