Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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Adenoviral transfer of the murine oncostatin M gene suppresses dextran-sodium sulfate-induced colitis.

The use of biologics has promising potential in the treatment of inflammation. Studies with cultured cells and mouse models of disease have ascribed proinflammatory and anti-inflammatory functions to oncostatin M (OSM) and the related cytokine, interleukin-6 (IL-6). Here, we examined the effect of systemic administration of adenoviral (Ad) vectors encoding either murine OSM (AdMuOSM) or murine IL-6 (AdMuIL-6) in a mouse model of colitis. BALB/c mice were treated with a 5-day course of 4% dextran-sodium sulfate (DSS) water with or without administration of adenoviral vectors (i.p. or i.m. at 10(7) plaque-forming units [pfu]) given as a cotreatment or therapy. The deletion variant of the adenovirus served as a control for adenoviral infection. Colitis was assessed by (1) morphology (damage score, macrophage infiltration, apoptosis) and (2) function (myeloperoxidase activity and Ussing chamber analysis of epithelial ion transport). Infection with adenovirus alone did not affect colonic form or function. AdMuOSM (either i.p. or i.m.) significantly reduced the severity of the DSS-induced colitis. There was less damage, reduced macrophage infiltration, fewer apoptotic bodies, and a significant improvement in stimulated ion transport in colonic tissues from the treated mice. No benefit of AdMuIL-6 treatment was observed in this model system. Thus, systemic administration of AdMuOSM given as a cotreatment and to a lesser extent as a therapy was found to be of benefit in DSS-induced colitis, a murine model of inflammatory bowel disease (IBD).     

Ultrastructural immunocytochemical studies of the localization and distribution of somatostatin, calcitonin, calcitonin gene-related peptide, and substance P in the bat thyroid follicle

Electron microscope immunocytochemistry was used to determine the intracellular localization and distribution among follicular elements of four peptides: calcitonin, somatostatin, calcitonin gene-related peptide (CGRP), and substance P in the thyroid glands of bats captured in the prehibernation phase of their annual life cycle. Previous studies have shown that this period of the hibernation-activity cycle is characterized by the accumulation and storage of secretory granules in parafollicular cells. Sites of binding of primary antisera to each of the four peptides were identified by means of affinity-purified secondary antisera directly coupled to colloidal gold particles. Calcitonin and somatostatin immunoreactivities were found in all parafollicular cells examined and in every secretory granule within these cells. CGRP was also found in all parafollicular cells examined (n = 75) but only in about half of their secretory granules. In contrast to these peptides, substance P immunoreactivity was not found in any parafollicular cells, but was localized exclusively in nerve endings within the basement membrane of the follicle.     

Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed in Panama

To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.     

A chromosome No. 2 abnormality in a child with a few congenital defects*

An abnormal chromosome No. 2 was found in the case of a child with an imperforate anus, a recto-vaginal fistula, unilateral atresia of the inner canal, and deformity of the external ear. G-banding studies revealed an insertion of a segment of the short arm into the long arm in one of the chromosomes No. 2 of the proband, the apparent result of a de novo phenomenon of chromosome rearrangement.     

Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro

Candida albicans must penetrate the endothelial cell lining of the vasculature to invade the deep tissues during a hematogenously disseminated infection. We compared 27 C. albicans mutants with their wild-type parent for their capacity to damage endothelial cells in vitro and cause a lethal infection in mice following tail vein inoculation. Of 10 mutants with significantly impaired capacity to damage endothelial cells, all had attenuated virulence. Therefore, the endothelial cell damage assay can be used as a screen to identify some virulence factors relevant to hematogenously disseminated candidiasis.