Design and characterization of PNVCL-based nanofibers and evaluation of their potential applications as scaffolds for surface drug delivery of hydrophobic drugs

In this work, nanofiber scaffolds for surface drug delivery applications were obtained by electrospinning poly(N-vinylcaprolactam) (PNVCL) and its blends with poly(ε-caprolactone) and poly(N-vinylcaprolactam)-b-poly(ε-caprolactone). The process parameters to obtain smooth and beadless PNVCL fibers were optimized. The average fibers diameter was less than 1 μm, and it was determined by scanning electron microscopy analyses. Their affinity toward water was evaluated by measuring the contact angle with water. The ketoprofen release behavior from the fibers was analyzed using independent and model-dependent approaches. The low values of the release exponent (n < 0.5) obtained for 20 and 42 °C, indicating a Fickian diffusion mechanism for all formulations. Dissolution efficiencies (DEs) revealed the effect of polymer composition, methodology used in the electrospinning process, and temperature on the release rate of ketoprofen. PNVCL/poly(N-vinylcaprolactam)-b-poly(ε-caprolactone)-based nanofibers showed greater ability to control the in vitro release of ketoprofen, in view of reduced kinetic constant and DE, making this material promising system for controlling release of hydrophobic drugs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48472.     

The influence of oxygen partial pressure on growth of the (Hg,Re)-1223 intergrain junction

Hg/sub 0.82/Re/sub 0.18/Ba/sub 2/Ca/sub 2/Cu/sub 3/O/sub 8+/spl delta// polycrystalline samples were successfully obtained by using different oxygen partial pressure in the annealing treatment of the precursor ceramic. The doping state was confirmed by X-ray powder diffraction pattern analysis and by observing distinct thermopower values at room temperature. Also, the intergrain regions have shown an improvement in the critical current density when using the precursor preparation with 10% O/sub 2/ and 90% Ar (optimal doped). The optimal doped sample has presented the highest /spl alpha/ exponent of the J/sub c//spl prop/[1-(T/T/sub c/)/sup 2/]/sup /spl alpha// dependence. For the case of (Hg,Re)-1223 polycrystalline superconductor applications, the /spl alpha/ exponent can be used as a junction quality parameter.     

Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.     

Cure of malignant ascites and generation of protective immunity by monoclonal antibody-targeted activation of a glucuronide prodrug in rats

We examined the in vivo efficacy of targeting beta-glucuronidase (betaG) to activate a glucuronide prodrug (BHAMG) of p-hydroxyaniline mustard (pHAM) at hepatoma ascites in Sprague-Dawley rats. Injection i.p. of 500 microg RH1-betaG, a conjugate formed between recombinant betaG and monoclonal antibody RH1 with specificity for an antigen expressed on AS-30D rat hepatoma cells, into rats bearing AS-30D ascites resulted in the accumulation of 54 microg conjugate per 10(9) tumor cells after 2 hr. Ascites fluid and serum contained 0.53 and 0 microg/ml, respectively, RH1-betaG 2 hr after injection of the conjugate. Conjugate binding to AS-30D cells was heterogeneous and non-saturated, as determined by flow cytometry. BHAMG was less toxic than pHAM to SD rats based on measures of animal mortality, weight loss and hematological toxicity. Treatment of rats bearing established hepatoma ascites with 500 microg RH1-betaG followed 2 hr later with a single i.p. injection of 30 mg/kg BHAMG or 3 i.p. injections of 10 mg/kg BHAMG 2, 3 and 4 hr later resulted in the cure of 6/8 and 8/8 animals, respectively. Treatment with BHAMG or pHAM alone did not produce cures, whereas treatment with a control antibody-betaG conjugate and BHAMG produced significantly greater hematological toxicity compared to treatment with RH1-betaG and BHAMG. All cured rats were completely protected from rechallenge with 2 x 10(7) AS-30D cells, indicating that successful treatment of animals induced protective immunity.     

Partial congenital defect of the left pericardium: angiographic diagnosis and treatment by thoracoscopic pericardiectomy: case report

Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed.     

Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

The effects of the composition of bacteriological growth media on the light output in a chemiluminometric assay of beta-galactosidase in Escherichia coli using 1,2-dioxetane substrates has been studied. In this assay a basic conflict exists between conditions that promote optimal bacterial growth and those conducive to maximal chemiluminescence. Common medium ingredients such as yeast or beef extract, protein hydrolysates and lactose suppress light emission and/or lead to high backgrounds. Quenching of light emission is probably partly due to light absorption by medium ingredients such as oxgall, and partly to interference with the reaction triggering the chemiluminescent process. Elevated backgrounds are caused by the presence of high concentrations of protein hydrolysates, which interact with the alkali in the accelerator solution. Only two purposely developed media, i.e. ILM and Colicult are shown to reconcile the requirements of growth support with that of optimal luminescent properties.