290 research outputs found

    Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres.

    Get PDF
    The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue vapreotide and maintenance of sustained plasma levels over 2–4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1–15 and 10–70 μm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40–80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC6h–14d (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors

    Candida interface keratitis after deep anterior lamellar keratoplasty: Clinical, microbiologic, histopathologic, and confocal microscopic reports

    Get PDF
    PURPOSE: To report the clinical, histopathologic, microbiologic, and confocal microscopic features of Candida keratitis after deep anterior lamellar keratoplasty (DALK). METHODS: We performed clinical, confocal scan, microbiologic and histopathologic examinations on two corneas from 2 young patients who underwent DALK for keratoconus. RESULTS: The first patient presented with asymptomatic white to cream-colored interface deposits 2 months after DALK. The confocal scan disclosed clusters of hyperreflective, fine granular deposits at the region of interface, with no evidence of inflammation or hyphaelike structures. The clinical presumption of possible "epithelial downgrowth" was suggested, and because of the progression of these lesions, irrigation of the interface was considered. Finally, penetrating keratoplasty was performed because of a rupture in the Descemet membrane. Histopathologic examination of the cornea disclosed yeastlike structures within the interface area. The microbiologic results of the irrigation fluid showed Candida glabrata. The second patient presented with a symptomatic infiltration of the inferior interface close to the suture site 2.5 months after DALK. The confocal scan showed foci of inflammation with clusters of hyperreflective round-shaped structures that resembled epithelial cells. Clinically, there was a suggestion of epithelial downgrowth, and subsequently, penetrating keratoplasty was performed because of the progression of the lesion. Histopathologic examination of the cornea disclosed an acute and chronic granulomatous keratitis caused by yeastlike structures. The microbiologic results revealed infection with Candida albicans. CONCLUSIONS: These are the first reported occurrences of interface Candida keratitis after DALK and with different confocal features. The clinical and the confocal features of interface Candida keratitis may be similar to those seen in epithelial downgrowth, which may postpone correct diagnosis and treatment. Candida keratitis should be considered in cases of interface deposits after any form of lamellar keratoplasty. © 2007 Lippincott Williams & Wilkins, Inc

    Radiological profile of anemia on unenhanced MDCT of the thorax.

    Get PDF
    Our aim was to investigate the diagnostic value of unenhanced MDCT in anemic patients. Fifty consecutive patients with proven anemia and 50 nonanemic matched group for age, sex and body mass index were evaluated. In either group, hemoglobin levels were assessed no more than 24 h from an unenhanced CT of the thorax. For each patient, the presence of a hyperattenuating aortic wall (aortic ring sign) and/or dense interventricular septum (subjective parameters) were identified by two radiologists who were blinded to the laboratory findings. Furthermore, the aortic CT attenuation values (objective parameter) were also obtained and correlated with the hemoglobin levels. The sensitivity and specificity in detecting anemia were calculated for each variable, and ROC analysis was generated for subjective and objective parameters. Subjective image analysis revealed that the aortic ring sign was more sensitive than the interventricular septum sign for anemia detection (84% vs. 72%), whereas this latter sign was more specific (100% vs. 92%). A good correlation (r = 0.60) was observed between the aortic CT attenuation values and the hemoglobin levels in the whole study population. Using a threshold of < or = 35 HU for anemia diagnosis, the sensitivity and specificity of aortic CT attenuation value were 84% and 94%, respectively, with the largest area under the curve (0.89) among all diagnostic criteria. However, the best trade-off between sensitivity (80%) and specificity (100%) was obtained from combining both subjective and objective analysis. Interpreting anemia upon unnenhanced MDCT of the thorax is quite feasible. A diagnostic approach that considers both subjective and objective analysis offers the best trade-off between sensitivity and specificity

    Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

    Get PDF
    This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

    Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

    Get PDF
    Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

    Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

    Get PDF
    A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters
    corecore