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A model of angiogenesis in the mouse cornea.

PURPOSE: The study of angiogenesis depends on reliable and reproducible models for the stimulation of a neovascular response. The purpose of this research was to develop such a model of angiogenesis in the mouse cornea. METHODS: Uniformly sized Hydron pellets containing either basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) and sucralfate were prepared and implanted into the stroma mouse cornea adjacent to the temporal limbus. RESULTS: Neovascularization of the corneal stroma began on day 3 and was sustained through day 8. The bFGF-induced neovascularization was consistent and dose dependent in C57B1/6, as well as in severe combined immune deficient, beige natural killer cell-deficient, and nude mouse strains. Biomicroscopic and histologic examination of bFGF- and VEGF-induced angiogenesis was notable for the absence of corneal edema or substantial inflammation. CONCLUSIONS: This noninflammatory model of corneal neovascularization is especially advantageous because it is reproducible, economical, and facilitates investigation of angiogenesis in various murine tumor models as well as in genetically defined murine strains.

Animals↗

Cell-substratum interactions mediate oncogene-induced phenotype of lung cancer cells.

In vivo and in vitro studies have linked small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells along a differentiation continuum. The transition of a SCLC toward a NSCLC phenotype is modeled in culture by the simultaneous overexpression of myc and ras genes in cultured SCLC cells. A major phenotypic distinction between SCLC and NSCLC in culture is that SCLC cells usually grow in floating aggregates, whereas NSCLC cells and myc- plus ras-expressing SCLC cells grow as adherent spreading monolayers like other epithelial cells. The present studies examine how myc, ras, cell aggregation, and attachment to laminin may interact to modulate transitions between the SCLC and NSCLC phenotypes. We find that myc-expressing SCLC cells, which normally grow as anchorage-independent cells in plastic flasks, will adhere to laminin and exhibit an epithelial morphology. In this setting, the cells express both NSCLC and SCLC markers, thus resembling a tumor type previously termed NSCLC with neuroendocrine features. Anchorage-dependent SCLC cells simultaneously expressing the myc family and an exogenous ras oncogene move further toward the NSCLC phenotype than the above myc-expressing cells. However, forced suspension of such cells restores the expression of neuroendocrine SCLC features. These studies indicate that cell environment, as much as gene expression events, profoundly affects aspects of the SCLC cell phenotype.

Basic Helix-Loop-Helix Proteins↗

Ridge preservation using HTR synthetic bone following tooth extraction.

Use of HTR (synthetic bone graft material) has been described to make tooth extraction a more controlled, regimented procedure. Strict adherence to surgical technique, with emphasis on appropriate suturing, is necessary to produce consistently successful results. A variation of an interrupted suture technique, the double-mattress stitch, is described in detail to achieve these results. This suturing method is replicable and applicable to most areas of the mouth. This technique is more challenging (but not impossible) to perform in areas that are difficult to access, such as in maxillary third molar regions. This stitch is essential for closing the extraction site and containing the graft material during initial healing. An ideal bone graft material should prevent postextraction osteitis, and maintain bone in the extraction area and proximal to this site. HTR satisfied these requirements.

Alveolar Bone Loss↗

Cultivation of keratinocytes on poly HEMA and their migration after inversion.

This study demonstrates how the pretreatment of poly HEMA disks with bovine serum influences the adhesion of human keratinocytes in vitro. The ability of these cells to migrate from poly HEMA disks to a polystyrene petri dish surface colonized with irradiated 3T3 cells is also evaluated. The stimulatory effect of 24-h preincubation of the poly HEMA disks with bovine serum on the keratinocyte adhesion and growth was dependent on the concentration of the serum used. The keratinocytes migrated from the poly HEMA disks to polystyrene colonized with irradiated 3T3 cells. The numerous cells which migrated from the poly HEMA were positive for cytokeratin 10 (suprabasal layers) after 3 weeks and for cytokeratin 1 (cornified layer) after 1 month. These results seem to be encouraging for further experiments with respect to clinical application.

Animals↗

[Biological compatibility of soft contact lens materials (HEMA) (author's transl)].

After implanting a disc (0,25 mm thickness and 1,5 mm diameter) of soft contact lens materials ("Soflens", "Hydroflex", "Hydron") in the anterior chamber of rabbits through a lancet incision, the reactions of iris, aqueous and cornea were observed for six months at regular intervals with slit lamp photograph. At the place where the disc touched the iris one could see during half a year periodic hyperaemia iridis and foreign-substance-granuloma of the iris. The cause of these reactions is a toxin in the HEMA. The reactions are more intense than with PMMA.

Animals↗

Implantation of PHEMA keratoprostheses after alkali burns in rabbit eyes.

PURPOSE: We have previously examined histologically the healing of a PHEMA core-and-skirt keratoprosthesis (the Chirila KPro) as a full-thickness implant in healthy animal corneas. The present study was carried out to determine whether a diseased cornea could also generate biocolonization of the skirt region of a KPro. METHODS: Ten KPros were placed as full-thickness corneal implants under conjunctival flaps in 10 alkali-burned rabbit corneas. Histological findings at intervals from 2 weeks to 6 months postoperatively were compared with earlier findings in 10 rabbits that had received identical KPros without prior alkali injury. RESULTS: Despite severe corneal injury and the reduced keratocyte population present, there were no clinically detected complications in 60%. Histological findings established that, compared with healthy host tissue, skirt biocolonization and KPro-cornea healing after an alkali burn were impaired, with evidence of epithelial downgrowth in 40%. One animal required euthanasia earlier than the planned end point, but no KPro extrusions occurred. CONCLUSION: Biocolonization of a KPro skirt is reduced but not prevented in an alkali-induced corneal inflammation model. Although no extrusions occurred, close follow-up and anticollagenolytic medication would be required to minimize the complication rate.

Animals↗

Contact lens induced peripheral ulcers during hydrogel contact lens wear.

PURPOSE: Ulcerative keratitis is the most serious adverse response associated with contact lens wear. However, some reports of microbial keratitis in the literature may refer to a less severe form of corneal ulceration, which we have termed contact lens induced peripheral ulcers (CLPU). METHODS: We present details of 11 cases of CLPU which occurred in clinical trials at our research unit. RESULTS: CLPU episodes are characterized by a single, small (< 2 mm diameter) circular lesion in the corneal mid-periphery or periphery, involving a focal loss of the full thickness of the epithelium associated with subepithelial stromal infiltrates. Patient symptoms may include ocular irritation, pain, photophobia, and lacrimation. They are usually associated with the use of hydrogel extended wear contact lenses. The lesions are self-limiting, typically healing within 7 days without treatment. After resolution, a small circular scar remains, which does not affect vision because of its peripheral location. The etiology of CLPU is unclear. In our studies, the incidence of CLPU was similar in conventional (2.9% per patient year) and disposable (2.0% per patient year) hydrogel extended wear, but lower during intermittent extended wear (1.6% per patient year); only one case occurred during daily wear (< 0.5% per patient year). CONCLUSIONS: A conservative approach to patient management of all suspected cases of corneal ulceration is encouraged. However, we suggest that future reports of ulcerative keratitis associated with various lens types and wearing schedules should differentiate between potentially devastating microbial keratitis and the relatively innocuous peripheral ulceration described in this paper.

Adult↗

Overnight corneal swelling in symptomatic and asymptomatic contact lens wearers.

PURPOSE: High corneal swelling with contact lens wear may be a predictor of patient failure in overnight contact lens use. This study evaluated whether contact lens wearers who had previously experienced corneal inflammation showed greater corneal swelling following a single occasion of overnight contact lens use compared with matched controls. METHODS: Forty-four subjects were evaluated: 9 wearers who had experienced contact lens associated acute red eye (CLARE); 9 controls; 13 subjects who had experienced contact lens induced peripheral ulcer (CLPU); and 13 controls. Controls were matched to cases for age, gender, wear experience and refractive error. Subjects wore bilateral disposable contact lenses overnight. Central corneal thickness was measured optically using a Holden-Payor pachometer at baseline, on eye opening, and 1, 2, and 4 hours later. RESULTS: There was no significant difference in overnight corneal swelling between CLARE subjects (7.6 +/- 2.3%) and controls (7.0 +/- 2.3%) (P = 0.57). Similarly, there was no significant difference in overnight corneal swelling between CLPU subjects (7.7 +/- 2.2%) and controls (7.8 +/- 2.6%) (P = 0.89). Deswell rate was similar in all groups. CONCLUSIONS: There was no apparent predisposition for higher overnight corneal swelling or altered deswell rate after one night of lens wear in subjects who had previously experienced contact lens related corneal inflammation.

Adult↗

The use of a particulate, microporous, calcified copolymer as a ridge maintenance device in dogs.

HTR polymer Synthetic Bone was found to be an osteoconductive, biocompatible, reliable nonresorbable matrix ridge maintenance material (Ridge Preservation). When used as socket implants immediately after the extraction of teeth over a one-year period in 16 beagle dogs, HTR was observed clinically and radiographically and compared with controls (unimplanted, sutured) extraction sites. As the control areas resorbed, the stability and effectiveness of the synthetic bone material in the operative sites became more clearly delineated. Quantitative analyses could not be made using radiographic techniques, but radiographs supported by subjective clinical observations as well as study casts taken of the height and width of the implanted areas, showed greater ridge retention compared with controls. Histological sections demonstrated dense laminar bone gradually forming into and around the HTR particulate material.

Alveolar Bone Loss↗

Recyclable characteristics of hyaluronate-polyhydroxyethyl acrylate blend hydrogel for controlled releases.

Hyaluronate-hydroxyethyl acrylate blend hydrogels which have a wide range of composition and characteristics were investigated. Glycidyl methacrylate derivatized hyaluronate (GMA-HA) were synthesized by coupling GMA to hyaluronate (HA) in the presence of a photoinduced initiator for polymerization. By copolymerizing radically GMA-HA and hydroxyethyl acrylate (HEA) under various compositions (weight ratios of HEA and GMA-HA: 1-20), GMA-HA hydrogels could be prepared in wide ranges of characteristics. These HA-PHEA gels possessed the feature that the dried ones recovered completely to the original swelling states on repeated runs, i.e. recyclable gels. The water contents of these hydrogels in equilibrium swellings in water (W(w)) were 0.99-0.86, and their viscoelastic properties were measured by a creep. The spontaneous elastic moduli were 1.05x10(5)-1.94x10(5) N m(-2), and they were mechanically tough. Their effective charge densities were estimated from the partition coefficients of sodium benzoate (NaBA) and decreased from -0.033 to -0.044 mol dm(-3) with increasing contents of HEA. Release of NaBA was studied, and the diffusion coefficients were found to be from 6.95x10(-10) to 0.12x10(-10) m(2) s(-1) with increasing the ratio of HEA. Their diffusion coefficients were found to be much less than the values estimated from the lattice model.

Acrylates↗