Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

Fate of micelles and quantum dots in cells.

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.     

Prognostic significance of cytochemical analysis of leukemic M2 blasts

Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR),i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.     

Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells.

Honeybee venom hyaluronidase (Api m 2) is a major glycoprotein allergen. Previous studies have indicated that recombinant Api m 2 expressed in insect cells has enzyme activity and IgE binding comparable with that of native Api m 2. In contrast, Api m 2 expressed in Escherichia coli does not. In this study, we characterized the carbohydrate side chains of Api m 2 expressed in insect cells, and compared our data with the established carbohydrate structure of native Api m 2. We assessed both the monosaccharide and the oligosaccharide content of recombinant Api m 2 using fluorophore-assisted carbohydrate electrophoresis and HPLC. To identify the amino acid residues at which glycosylation occurs, we digested recombinant Api m 2 with endoproteinase Glu-C and identified the fragments that contained carbohydrate by specific staining. Recombinant Api m 2 expressed in insect cells contains N-acetylglucosamine, mannose, and fucose, as well as trace amounts of glucose and galactose, and the oligosaccharide analysis is consistent with heterogeneous oligosaccharide chains consisting of two to seven monosaccharides. No sialic acid or N-acetylgalactosamine were detected. These results are similar to published data for native Api m 2, although some monosaccharide components appear to be absent in the recombinant protein. Analysis of proteolytic digests indicates that of the four candidate N-glycosylation sites, carbohydrate chains are attached at asparagines 115 and 263. Recombinant Api m 2 expressed in insect cells has enzymic activity and IgE binding comparable with the native protein, and its carbohydrate composition is very similar.     

Intravenous Infusion of RMP-7 Increases Ocular Uptake of Ganciclovir

Purpose. The ability of intravenous (i.v.) infusions of the bradykinin agonist, RMP-7, to permeabilize the blood-ocular barriers (BOB) to the antiviral agent ganciclovir was investigated in guinea-pigs. Methods. Different i.v. dosing regimens included pre-treatment with RMP-7 (0.2 g/kg/min for 5 min) followed by either [³H]-ganciclovir (1 Ci/0.2 ml/min) alone, and/or co-infusion with RMP-7 and [³H]-ganciclovir. At specific times the animals were sacrificed, their eyes removed, and the retina and lens epithelium dissected and analyzed for the amount of radioactivity. Results. Using the ratio of tissue vs. integrated plasma radioactivity concentration, a two-fold increase in ganciclovir steady-state levels were observed in the retina as well as lens epithelium following RMP-7 pretreatment. Peak uptake effects were achieved with a 4.5 min ganciclovir infusion. Neither longer infusions of ganciclovir alone, nor co-infusions of RMP-7 and ganciclovir further enhanced the uptake effects. Kinetic analysis indicated that RMP-7 increased the rate of ganciclovir entry (K _IN) in studied ocular tissues, while the efflux of drug (K _OUT) was not affected by this treatment. Finally, ganciclovir retina:plasma ratios elevated by RMP-7 pre-treatment, remained higher than control ratios within 60 min following cessation of 4.5 min ganciclovir infusion. Conclusions. These data offer further evidence that BOB and in particular the blood-retinal barrier can be permeabilized via bradykinin receptor stimulation. As the i.v. infusions of RMP-7 enhanced the retinal uptake of ganciclovir, it is suggested that a combination of RMP-7 and ganciclovir may provide a novel approach for treating cytomegalo-virus retinis.     

Diverticulum of the stomach

Gastric diverticula are very rare and usually asymptomatic diseases. Clinical symptoms may include haemorrhage, mild discomfort and pain in upper abdomen. They are most frequently diagnosed incidentally during X-Ray examinations. In symptomatic diverticulum of gastric fundus was diagnosed roentgenographically and endoscopically and was successfully cured surgically.