Different degradation rates of nanofiber vascular grafts in small and large animal models

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.     

Weill-Marchesani syndrome - possible linkage of the autosomal dominant form to 15q21.1

Weill-Marchesani syndrome comprises short stature, brachydactyly, microspherophakia, glaucoma, and ectopia lentis is regarded as an autosomal recessive trait (McKusick 277600). We present two families each with affected individuals in 3 generations demonstrating autosomal dominant inheritance of Weill-Marchesani syndrome. Linkage analysis in these 2 families suggests a gene for Weill-Marchesani syndrome maps to 15q21.1. The dislocated lenses and connective tissue disorder in these families suggests that fibrillin-1 and microfibril-associated protein 1, which both map to 15q21.1, are candidate genes for Weill-Marchesani syndrome. Immunohistochemistry staining of skin sections from family 1 showed an apparent decrease in fibrillin staining compared to control individuals. © 1996 Wiley-Liss, Inc.     

Osteoglophonic dysplasia: Review and further delineation of the syndrome

We report on a boy with clinical and radiologic findings of osteoglophonic dysplasia. He had craniostenosis, “bizarre,” expansile cystic lesions in the diaphyses, delayed tooth eruption, and progressive rib expansion typical of the syndrome. Initially delayed psychomotor development with later normal intelligence, early feeding and breathing difficulty, and speech delay are also characteristic of the disorder. Manifestations, not previously reported in osteoglophonic dysplasia, present in the propositus are spontaneous fractures resulting in pseudoarthroses through cystic and dysplastic foci in his proximal femoral shafts and right humerus, pretibial dimples, hypospadias, marked rib expansion, and absence of significant vertebral abnormality. These findings expand the spectrum of osteoglophonic dysplasia. © 1996 Wiley-Liss, Inc.     

Radiological features of Adenomatoid odontogenic tumor: Report of a maxillary case and a mandibular one

We present two cases of AOT, the first case concerns a 23‐year‐old patient with an AOT located in the maxilla and the second case involves a 37‐year‐old patient presenting an AOT with mandibular localization.     

Acanthosis nigricans

Acanthosis nigricans (AN) is a well-defined skin disorder characterized by velvety hyperkeratotic macules that can be accompanied by various degrees of pigmentation. Other manifestations of AN are marked papillomatous growths and deep skin markings. These changes can affect the entire skin but preferentially are observed in the axilla, neck, genitals, and oral cavity. The presence of AN around and within the oral cavity as well as its well-known association with internal malignant conditions, especially adenocarcinoma of the stomach, and/or its association with insulin resistance, has prompted this review article, which emphasizes the oral manifestations of AN.     

Pilot study of oxygen transport rate of banked red blood cells

Background and Objectives  Dynamic oximetry provides a new way to assess the effect of blood storage on the oxygen transport rate (OTR).
Materials and Methods  In dynamic oximetry, the rate at which oxyhemoglobin becomes deoxyhemoglobin is measured optically, thereby, indirectly measuring the rate at which oxygen leaves the red blood cell (RBC) making it available for transfer to tissues. Extending the physiologic diffusion time in an in vitro apparatus, consisting of a diffusion system and gas exchanger capable of controlling the surface area and the time of exposure for oxygenation and deoxygenation, makes OTR measurement feasible. Eight normal blood donor units, collected in adenine, dextrose, sorbitol, sodium chloride and mannitol , were stored for 8 weeks under standard conditions and serially sampled for OTR.
Results  We report that the OTR at the time of blood bank donation appears to be singular for each donor, that the interdonor differences are maintained over time, and that the individual OTR increased 1·72-fold (95% CI 1·51, 1·95) over 8 weeks, adjusting for sex, age and plasma cholesterol level.
Conclusion  Oxygen transport rate increases during storage; blood units with similar haemoglobin content may have significant differences in OTR. Studies examining blood parameters at the time of donation and blood storage on patient outcomes should consider measuring OTR, as it may contribute to differences in observed efficacy of tissue oxygenation.     

Glioma Cell Migration on Three-dimensional Nanofiber Scaffolds Is Regulated by Substrate Topography and Abolished by Inhibition of STAT3 Signaling

A hallmark of malignant gliomas is their ability to disperse through neural tissue, leading to long-term failure of all known therapies. Identifying new antimigratory targets could reduce glioma recurrence and improve therapeutic efficacy, but screens based on conventional migration assays are hampered by the limited ability of these assays to reproduce native cell motility. Here, we have analyzed the motility, gene expression, and sensitivity to migration inhibitors of glioma cells cultured on scaffolds formed by submicron-sized fibers (nanofibers) mimicking the neural topography. Glioma cells cultured on aligned nanofiber scaffolds reproduced the elongated morphology of cells migrating in white matter tissue and were highly sensitive to myosin II inhibition but only moderately affected by stress fiber disruption. In contrast, the same cells displayed a flat morphology and opposite sensitivity to myosin II and actin inhibition when cultured on conventional tissue culture polystyrene. Gene expression analysis indicated a correlation between migration on aligned nanofibers and increased STAT3 signaling, a known driver of glioma progression. Accordingly, cell migration out of glioblastoma-derived neurospheres and tumor explants was reduced by STAT3 inhibitors at subtoxic concentrations. Remarkably, these inhibitors were ineffective when tested at the same concentrations in a conventional two-dimensional migration assay. We conclude that migration of glioma cells is regulated by topographical cues that affect cell adhesion and gene expression. Cell migration analysis using nanofiber scaffolds could be used to reproduce native mechanisms of migration and to identify antimigratory strategies not disclosed by other in vitro models.     

Noncovalent binding of a mitomycin C metabolite, 2,7-diaminomitosene, to duplex DNA

The major metabolite of mitomycin C, 2,7-diaminomitosene (DAM), interacts noncovalently with DNA. This was supported by ultraviolet-visible spectrum changes upon mixing with DNA and ethidium bromide displacement from DNA, measured as fluorescence changes. Moreover, DAM bound to DNA sufficiently strongly to hold DNA in a double stranded conformation under denaturing gel electrophoresis conditions commonly used to measure mitomycin C cross-links. These data show that generation of DAM and interaction with DNA represent a potential additional mechanism of DNA damage induced by mitomycin C.