Studies on Formulation and Evaluation of Ethyl Cellulose Based Extended Release Metformin Hydrochloride Matrix Tablets

Monolithic matrix tablets of metformin hydrochloride were formulated as extended release tablets by employing ethyl cellulose polymer and the extended release characterization of the formulated tablets was investigated.  Extended release matrix tablets containing 500 mg metformin hydrochloride were developed by changing concentration of drug :  polymer (EC) in the ratio of 5:1, 5:2, 5:3 and 5:4 by direct compression.  Formulations were optimized based on the acceptable tablet properties invitro and invivo drug release.  The resulting formulations produced robust tablets with optimum hardness, weight variation, drug content and low friability.  The result of invitro and invivo drug release studies indicated that formulation (drug:polymer =5:3), is the most successful of the study and exhibited constant and extended release of metformin hydrochloride 99-100.5% release at the end of 10 h compared with reference standard.  Further, the formulation F3 was subjected to exposure at room and accelerated condition to stability studies.  A decrease in release of the drug was observed on increasing polymer ratio at certain level.  Before tablet compression, the resulting formulation blends were evaluated for angle of repose, bulk density, % porosity, % compressibility index and drug polymer compatibility study of drug and excipients.  The t25, t50 and t90 drug release values was calculated from selected formulation F3 on every month of stability studies and comparision of both room and accelerated condition by statistical t-test, there is no difference between storage temperature. The formulation F3 was showed similar invitro and invivo drug release when compared to marketed sustained release tablet (F5M)

Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats

Objective: Fluorophore-labeled contrast imaging agents are moving toward clinical use for a number of applications. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate. Methods: Male and female Sprague–Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; Indocyanine Green was used as a comparative control. Animals were injected with varying doses of the test and control articles and observed for up to 14 days. Clinical chemistry, hematological, and pharmacokinetic analyses were performed on subgroups of animals. Organs were analyzed for content of the test article. Tissues were analyzed microscopically for pathological changes. Results: Based on hematologic, clinical chemistry, and histopathologic evaluation, single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5, and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. Conclusion: A dose of 20 mg/kg was identified as the no observed adverse effect level following IV or ID routes of administration of IRDye 800CW

Elevated serum levels of soluble CD154 in children with juvenile idiopathic arthritis

<p>Abstract</p> <p>Objective</p> <p>Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines.</p> <p>Methods</p> <p>Serum from 77 children with JIA and 81 pediatric controls was analyzed for interleukin (IL)1β, IL2, IL4, IL5, IL6, IL8, IL10, IL12, IL13, sCD154, interferon-γ (IFNγ), soluble IL2 receptor (sIL2R), and tumor necrosis factor-α (TNFα), using the Luminex Multi-Analyte Profiling system. Differences in levels of cytokines between cases and controls were analyzed. Logistic regression was also performed.</p> <p>Results</p> <p>sCD154 was significantly elevated in cases compared to controls (p < 0.0001). IL1β, IL5, IL6, IL8, IL13, IFNγ, sIL2R, and TNFα were also significantly elevated in JIA. Levels of sCD154 were highly correlated with IL1β, IL6, IL8, and TNFα (p < 0.0001). Logistic regression analysis suggested that IL6 (odds ratio (OR): 1.4, p < 0.0001), sCD154 (OR: 1.1, p < 0.0001), and TNFα (OR: 1.1, p < 0.005) were positively associated with JIA, while IL10 (OR: 0.5, p < 0.002) was protective. sCD154 was elevated in all JIA subtypes, with highest levels among more severe subtypes. IL1β, IL6, IL8, sIL2R and TNFα were also elevated in several JIA subtypes.</p> <p>Conclusion</p> <p>Serum levels of sCD154, IL1β, IL6, IL8, sIL2R and TNFα are elevated in most JIA subtypes, suggesting a major role for sCD154, and these cytokines and cytokine receptors in the pathogenesis of JIA.</p

Bordetella Adenylate Cyclase Toxin Mobilizes Its β2 Integrin Receptor into Lipid Rafts to Accomplish Translocation across Target Cell Membrane in Two Steps

Bordetella adenylate cyclase toxin (CyaA) binds the αMβ2 integrin (CD11b/CD18, Mac-1, or CR3) of myeloid phagocytes and delivers into their cytosol an adenylate cyclase (AC) enzyme that converts ATP into the key signaling molecule cAMP. We show that penetration of the AC domain across cell membrane proceeds in two steps. It starts by membrane insertion of a toxin ‘translocation intermediate’, which can be ‘locked’ in the membrane by the 3D1 antibody blocking AC domain translocation. Insertion of the ‘intermediate’ permeabilizes cells for influx of extracellular calcium ions and thus activates calpain-mediated cleavage of the talin tether. Recruitment of the integrin-CyaA complex into lipid rafts follows and the cholesterol-rich lipid environment promotes translocation of the AC domain across cell membrane. AC translocation into cells was inhibited upon raft disruption by cholesterol depletion, or when CyaA mobilization into rafts was blocked by inhibition of talin processing. Furthermore, CyaA mutants unable to mobilize calcium into cells failed to relocate into lipid rafts, and failed to translocate the AC domain across cell membrane, unless rescued by Ca2+ influx promoted in trans by ionomycin or another CyaA protein. Hence, by mobilizing calcium ions into phagocytes, the ‘translocation intermediate’ promotes toxin piggybacking on integrin into lipid rafts and enables AC enzyme delivery into host cytosol

Cervical epidural steroid injections in the management of cervical radiculitis: interlaminar versus transforaminal. A review

There has been recent concern regarding the safety of cervical epidural steroid injections. The decision to proceed with treatment requires balancing the risk and benefits. This article is an in depth review of the efficacy, complications, and technique of both interlaminar and transforaminal cervical epidural steroid injections in the management of cervical radiculitis

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field