Biophysical Techniques of Transcutaneous Drug Sampling and Drug Delivery

Monitoring the time course of drug in the skin is critical for determining the frequency and dose of drug administration from safety and efficacy perspectives. Intermittent blood sampling is used as a surrogate for approximating concentration of drugs in the tissues, which leads to blood loss and discomfort to patients. A novel noninvasive technique called “Electroporation and transcutaneous sampling” (ETS) was developed for estimating the drug concentration in the skin extracellular fluid. The application of ETS technique in studying dermatokinetics of cephalexin, ciprofloxacin, and 8-methoxypsoralen was investigated. The results demonstrated the ability of ETS technique in dermatokinetic studies of drugs with different physicochemical properties. ETS technique was also found to be a promising method for noninvasive estimation of blood glucose levels. Two novel techniques were developed for enhancing the transdermal delivery of drugs. “ChilDrive”, a technique of combining regional cutaneous hypothermia with iontophoresis was used for enhancing the bioavailability of transdermally administered drug in the deeper musculoskeletal tissue like synovial fluid. The bioavailability of drugs in the synovial fluid of knee joint was enhanced by ?6-12-fold and ?2-4-fold by ChilDrive when compared to passive and iontophoretic transdermal drug delivery. Magnetophoresis, a technique of enhancing transdermal drug delivery by application of magnetic field was developed. The mechanistic studies demonstrated that transdermal magnetophoresis of drugs was due to contribution of multiple factors such as magnetorepulsion, magnetohydrokinesis and magnetically enhanced partition coefficient. Magnetophoretic patch system was designed and pharmacokinetic studies were performed. Magnetophoresis resulted in higher dermal bioavailability of drugs compared to passive transdermal drug delivery. It was also found from the in vitro studies that combination of chemical enhancers would further enhance the efficiency of magnetophoretically mediated drug delivery enhancement

Medical Data Analytics for Secure Multi-party-primarily based Cloud Computing utilizing Homomorphic Encryption

Cloud computing has emerged as a vibrant part of today's modern world, providing computer services such as data storage, managing and processing via the internet. For the most part, cloud applications emphasize a multi-tenant structure to provide support for several customers in a single instance. A multi-tenancy situation involving the allocation of resources in cloud storage and the risks associated with it, in which confidentiality or integrity may be compromised. Homomorphic encryption is one such technique which guarantees to franchise in safeguarding information under cryptographic domain. The proposed modified Algebra Homomorphic Encryption scheme based on updated ElGamal (AHEE) encryption scheme is designed in such a way that the cloud administrators do not obtain any information about the medical data. This scheme is quantitatively evaluated using metrics such as encryption time and decryption time. The experimental results using UCI Machine Learning Repository ECG data set show that the proposed scheme achieved shorter encryption time of 6.61 ms and decryption time of 5.94 ms and also analyze this secured datum using big data analytics

Medical Data Analytics for Secure Multi-party-primarily based Cloud Computing utilizing Homomorphic Encryption

692-698Cloud computing has emerged as a vibrant part of today's modern world, providing computer services such as data storage, managing and processing via the internet. For the most part, cloud applications emphasize a multi-tenant structure to provide support for several customers in a single instance. A multi-tenancy situation involving the allocation of resources in cloud storage and the risks associated with it, in which confidentiality or integrity may be compromised. Homomorphic encryption is one such technique which guarantees to franchise in safeguarding information under cryptographic domain. The proposed modified Algebra Homomorphic Encryption scheme based on updated ElGamal (AHEE) encryption scheme is designed in such a way that the cloud administrators do not obtain any information about the medical data. This scheme is quantitatively evaluated using metrics such as encryption time and decryption time. The experimental results using UCI Machine Learning Repository ECG data set show that the proposed scheme achieved shorter encryption time of 6.61 ms and decryption time of 5.94 ms and also analyze this secured datum using big data analytics

Amyloid and intracellular accumulation of BRI2

Familial British dementia (FBD) and familial Danish dementia (FDD) are caused by mutations in the BRI2 gene. These diseases are characterized clinically by progressive dementia and ataxia and neuropathologically by amyloid deposits and neurofibrillary tangles. Herein, we investigate BRI2 protein accumulation in FBD, FDD, Alzheimer disease and Gerstmann-Sträussler-Scheinker disease. In FBD and FDD, we observed reduced processing of the mutant BRI2 pro-protein, which was found accumulating intracellularly in the Golgi of neurons and glial cells. In addition, we observed an accumulation of a mature form of BRI2 protein in dystrophic neurites, surrounding amyloid cores. Accumulation of BRI2 was also observed in dystrophic neurites of Alzheimer disease and Gerstmann-Sträussler-Scheinker disease cases. Although it remains to be determined whether intracellular accumulation of BRI2 may lead to cell damage in these degenerative diseases, our study provides new insights into the role of mutant BRI2 in the pathogenesis of FBD and FDD and implicates BRI2 as a potential indicator of neuritic damage in diseases characterized by cerebral amyloid deposition

A Real-time Vehicular Visible Light Communications for Smart Transportation

In this paper, we demonstrate a real time vehicular visible light communications prototype using Raspberry Pi's for switching of light emitting diodes, signal processing and detection at the receiver side. The low cost system is attractive offering a communication link span of up to 12 m with error free transmission at a data rate of 9.6 kbps, as it shows good performance in the communication distance achieved

Chronic agmatine treatment prevents olanzapine-induced obesity and metabolic dysregulation in female rats

Antipsychotic-induced obesity affects millions of people and is a serious health condition worldwide. Olanzapine is the most widely prescribed antipsychotic agent with high obesogenic potential. However, the exact mechanism by which it causes its metabolic dysregulation remains poorly understood. In this study, we investigated the effect of agmatine in olanzapine-induced metabolic derangements in Female Sprague-Dawley rats. Repeated olanzapine administration for 28 days increased body weight while treatment with agmatine from days 15 to 28 prevented the body weight gain induced by olanzapine without any alteration in food intake. Repeated agmatine treatment decreased the elevated feeding efficiency and adiposity index, as well as improved dysregulated lipid metabolism induced by olanzapine. Increased activity of fatty acid synthase (FAS) and decreased expression of carnitine palmitoyl transferase-1 (CPT-1) were detected in chronic olanzapine-treated rats. Although agmatine treatment did not alter FAS activity, it increased CPT-1 activity. It is possible that the inhibitory effect of agmatine on weight gain and adiposity might be associated with increased mitochondrial fatty acid oxidation and energy expenditure in olanzapine-treated rats. We suggest that agmatine can be explored for the prevention of obesity complications associated with chronic antipsychotic treatment

Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons

Neurogenesis of projection neurons requires that axons be initiated, extended, and connected. Differences in the expression of axon growth and guidance genes must drive these events, but comprehensively characterizing these differences in a single neuronal type has not been accomplished. Guided by a catalog of gene expression in olfactory sensory neurons (OSNs), in situ hybridization and immunohistochemistry revealed that Cxcr4 and Dbn1 , two axon initiation genes, marked the developmental transition from basal progenitor cells to immature OSNs in the olfactory epithelium. The CXCR4 immunoreactivity of these nascent OSNs overlapped partially with markers of proliferation of basal progenitor cells and partially with immunoreactivity for GAP43, the canonical marker of immature OSNs. Intracellular guidance cue signaling transcripts Ablim1, Crmp1, Dypsl2, Dpysl3, Dpysl5, Gap43, Marcskl1, and Stmn1–4 were specific to, or much more abundant in, the immature OSN layer. Receptors that mediate axonal inhibition or repulsion tended to be expressed in both immature and mature OSNs ( Plxna1, Plxna4, Nrp2, Efna5 ) or specifically in mature OSNs ( Plxna3, Unc5b, Efna3, Epha5, Epha7 ), although some were specific to immature OSNs ( Plxnb1, Plxnb2, Plxdc2, Nrp1 ). Cell adhesion molecules were expressed either by both immature and mature OSNs ( Dscam, Ncam1, Ncam2, Nrxn1 ) or solely by immature OSNs ( Chl1, Nfasc1, Dscaml1 ). Given the loss of intracellular signaling protein expression, the continued expression of guidance cue receptors in mature OSNs is consistent with a change in the role of these receptors, perhaps to sending signals back to the cell body and nucleus. © 2010 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106698/1/22497_ftp.pd

Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections

The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response

Sensory perception requires accurate encoding of stimulus information by sensory receptor cells. We identified NCKX4, a potassium-dependent Na(+)/Ca(2+) exchanger, as being necessary for rapid response termination and proper adaptation of vertebrate olfactory sensory neurons (OSNs). Nckx4(-/-) (also known as Slc24a4) mouse OSNs displayed substantially prolonged responses and stronger adaptation. Single-cell electrophysiological analyses revealed that the majority of Na(+)-dependent Ca(2+) exchange in OSNs relevant to sensory transduction is a result of NCKX4 and that Nckx4(-/-) mouse OSNs are deficient in encoding action potentials on repeated stimulation. Olfactory-specific Nckx4(-/-) mice had lower body weights and a reduced ability to locate an odorous source. These results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception