2,534 research outputs found

    Razvoj i vrednovanje mikrospužvastih sustava etilceluloze i ksantan gume za kontroliranu perkutanu isporuku diklofenak natrija

    Get PDF
    In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared by the double emulsification technique and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to the skin. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their yield (79.1–88.5 %), drug entrapment efficiency (50.0–64.1 %), and mean particle diameter (181–255 µm). Compared to the microsponges with high drug/polymer ratio (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by 19.9 % and 17.0 %, respectively, for the microsponges prepared at low and intermediate drug/polymer ratios. When an equivalent amount of pure drug (not entrapped into microsponges) was dispersed into the gel base and the flux was compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce the flux by 33.3 %. Whether the drug was dispersed either in un-entrapped or entrapped form into the gel base, the drug permeation through rat skin followed Higuchi\u27s diffusion kinetic model. The microsponges prepared at the lowest drug/polymer ratio exhibited a comparatively slower drug permeation profile and were hence considered most suitable for controlled drug delivery application. FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous nature of the drug in these microsponges. The gel containing these optimized microsponges was comparable to that of a commercial gel formulation and did not show serious dermal reactions. Hence, the microsponge system obtained at the lowest drug/polymer ratio could be useful for controlled release of diclofenac sodium to the skin.U radu su opisani mikrospužvasti sustavi s etilcelulozom i ksantan gumom pripravljeni metodom dvostruke emulzifikacije i dispergirani u podlogu s karbopol gelom za kontrolirano oslobađanje diklofenak natrija na kožu. Elektronska pretražna mikroskopija potvrdila je poroznu, sferičnu strukturu mikrospužvastih sustava. Povećanjem omjera lijeka i polimera (0,4:1, 0,6:1, 0,8:1, m/m) povećalo se iskorištenje (79,1–88,5 %), količina uklopljenog lijeka (50,0–64,1 %) i srednji promjer čestica (181–255 µm). Prolaz uklopljenog lijeka kroz izrezane komade kože štakora smanjio se za 19,9 %, odnosno 17,0 %, kada se omjer lijeka i polimera smanjio s visokog (0,8:1, m/m) na niski i srednji. Oslobađanje iz mikrospužvastih struktura s omjerom lijeka i polimera 0,8:1 (m/m) smanjeno je za 33,3 % u odnosu na oslobađanje ekvivalentne količina lijeka koji nije uklopljen već samo dispergiran u geliranu podlogu. Ako je lijek bio dispergiran kao neuklopljen ili kao uklopljen u geliranu podlogu, permeacija lijeka kroz kožu štakora slijedila je Higuchijev difuzijski kinetički model. Mikrospužvaste strukture pripravljene uz najniži omjer lijeka i polimera pokazale su sporiji permeacijski profil pa ih smatramo najpovoljnijima za kontrolirano oslobađanje lijeka. FTIR spektroskopija i DSC analiza pokazale su da je lijek u mikrospružvastim sustavima stabilan i amorfan. Gel s optimiranim mikrospužvastim sustavom sličan je komercijalnom gelu i ne pokazuje ozbiljne kožne reakcije. Sustav pripravljen s najnižim omjerom lijeka i polimera mogao bi biti pogodan za kontrolirano oslobađanje diklofenak natrija na kožu

    pH dependent chemical stability and release of methotrexate from a novel nanoceramic carrier

    Get PDF
    Considering the pH dependent chemical stability of anticancer drug methotrexate (MTX), the present communication reports a new approach for intercalation of the same in a nanoceramic vehicle, magnesium aluminium layered double hydroxide (LDH), by ex situ anion exchange method at pH 7.00, using 0.3 M ammonium acetate solution for dissolution of the drug. This simple method ensures maximum stability of the drug at the above said pH, with no degradation byproduct (e.g., N-10-methyl folic acid formed due to alkaline hydrolysis) under the given experimental conditions, compared to the similar approach, using 0.1 M sodium hydroxide solution, reported in our earlier work. Importantly, the above method leads to an enhanced drug loading of 32.3 wt%, compared to our previous reports. The cumulative release profile of MTX from LDH-MTX formulation in phosphate buffer saline (PBS) at pH 7.4 exhibited burst release initially which was taken care of by imparting a unique coating of poly(D,L-lactideco-glycolide, PLGA) on the LDH-MTX nanostructure that reduces the toxicity due to local accumulation. Hence, the superiority of the above for use in cancer chemotherapy, over the conventional drug-polymer system has been established w.r.t the drug release profile and a possible hypothesis of the same has been suggested. The half maximal inhibitory concentration (IC50) of the MTX drug used in this study has been determined and the same has been used to estimate the time dependent (24, 48, 72 and 96 h) efficacy of the MTX loaded samples with/without polymer coating, on human colon tumour cells (HCT-116)

    Solitonic supersymmetry restoration

    Full text link
    Q-balls are a possible feature of any model with a conserved, global U(1) symmetry and no massless, charged scalars. It is shown that for a broad class of models of metastable supersymmetry breaking they are extremely influential on the vacuum lifetime and make seemingly viable vacua catastrophically short lived. A net charge asymmetry is not required as there is often a significant range of parameter space where statistical fluctuations alone are sufficient. This effect is examined for two supersymmetry breaking scenarios. It is found that models of minimal gauge mediation (which necessarily have a messenger number U(1)) undergo a rapid, supersymmetry restoring phase transition unless the messenger mass is greater than 10^8 GeV. Similarly the ISS model, in the context of direct mediation, quickly decays unless the perturbative superpotential coupling is greater than the Standard Model gauge couplings.Comment: 17 pages, 3 figures, minor comments added, accepted for publication in JHE

    Dynamical completions of generalized O'Raifeartaigh models

    Get PDF
    We present gauge theory completions of Wess-Zumino models admitting supersymmetry breaking vacua with spontaneously broken R-symmetry. Our models are simple deformations of generalized ITIY models, a supersymmetric theory with gauge group Sp(N), N+1 flavors plus singlets, with a modified tree level superpotential which explicitly breaks (part of) the global symmetry. Depending on the nature of the deformation, we obtain effective O'Raifeartaigh-like models whose pseudomoduli space is locally stable in a neighborhood of the origin of field space, or in a region not including it. Hence, once embedded in direct gauge mediation scenarios, our models can give low energy spectra with either suppressed or unsuppressed gaugino mass.Comment: 21 pages, 1 figure; v3: reference adde

    Does the magnetization transfer effect bias chemical exchange saturation transfer effects? Quantifying chemical exchange saturation transfer in the presence of magnetization transfer

    Get PDF
    Purpose Chemical exchange saturation transfer (CEST) is an MRI technique sensitive to the presence of low‐concentration solute protons exchanging with water. However, magnetization transfer (MT) effects also arise when large semisolid molecules interact with water, which biases CEST parameter estimates if quantitative models do not account for macromolecular effects. This study establishes under what conditions this bias is significant and demonstrates how using an appropriate model provides more accurate quantitative CEST measurements. Methods CEST and MT data were acquired in phantoms containing bovine serum albumin and agarose. Several quantitative CEST and MT models were used with the phantom data to demonstrate how underfitting can influence estimates of the CEST effect. CEST and MT data were acquired in healthy volunteers, and a two‐pool model was fit in vivo and in vitro, whereas removing increasing amounts of CEST data to show biases in the CEST analysis also corrupts MT parameter estimates. Results When all significant CEST/MT effects were included, the derived parameter estimates for each CEST/MT pool significantly correlated (P < .05) with bovine serum albumin/agarose concentration; minimal or negative correlations were found with underfitted data. Additionally, a bootstrap analysis demonstrated that significant biases occur in MT parameter estimates (P < .001) when unmodeled CEST data are included in the analysis. Conclusions These results indicate that current practices of simultaneously fitting both CEST and MT effects in model‐based analyses can lead to significant bias in all parameter estimates unless a sufficiently detailed model is utilized. Therefore, care must be taken when quantifying CEST and MT effects in vivo by properly modeling data to minimize these biases

    Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and <b>youth</b>. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard."</p> <p>Methods</p> <p>The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA.</p> <p>Results</p> <p>Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis.</p> <p>Conclusions</p> <p>Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.</p

    Tree Level Metastability and Gauge Mediation in Baryon Deformed SQCD

    Full text link
    We investigate supersymmetric QCD with gauge group SU(2) and a baryon deformation to the superpotential. The existence of an uplifted vacuum at the origin with tree level metastability is demonstrated. When this model is implemented in a direct gauge mediation scenario we therefore find gaugino masses which are comparable to sfermion masses and parameterised by an effective number of messengers 1/8. All deformations are well motivated by appealing to the electric theory and an R-symmetry. This R-symmetry is explicitly broken by the same term responsible for supersymmetry breaking. Moreover, the model does not suffer from the Landau pole problem and we find that it can be described in terms of just two scales: the weak scale and a high scale like the Planck or GUT scale. The model can be tested by searching for new particles at the TeV scale charged under the visible sector gauge group.Comment: 17 pages, 7 figures, updated reference

    Global distribution of two fungal pathogens threatening endangered sea turtles

    Get PDF
    This work was supported by grants of Ministerio de Ciencia e Innovación, Spain (CGL2009-10032, CGL2012-32934). J.M.S.R was supported by PhD fellowship of the CSIC (JAEPre 0901804). The Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council supported P.V.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Thanks Machalilla National Park in Ecuador, Pacuare Nature Reserve in Costa Rica, Foundations Natura 2000 in Cape Verde and Equilibrio Azul in Ecuador, Dr. Jesus Muñoz, Dr. Ian Bell, Dr. Juan Patiño for help and technical support during samplingPeer reviewedPublisher PD
    corecore