Collagen membrane/fleece composite film reduces adhesions in the presence of bleeding in a rabbit uterine horn model.

OBJECTIVE: Determination of efficacy in presence of bleeding of CDS, a collagen/membrane fleece composite, in a rabbit uterine horn simple abrasion model. DESIGN: Randomized, controlled, and blinded study involving standard abrasion of the uterine horns with induction of moderate mesouterine bleeding. SETTING: Research laboratory. PATIENT(S): New Zealand White rabbits. INTERVENTION(S): No treatment (surgical control), CDS film, or INTERCEED barrier (negative reference control). MAIN OUTCOME MEASURE(S) AND RESULT(S): The extent (percent length uterine horn) with adhesions was assessed after 29 or 30 days. Adhesions formed in surgical controls to an extent (85.6% +/- 4.6%) consistent with historic data for this model. INTERCEED failed to reduce adhesions (78.1% +/- 7.7%) indicating that the test conditions of inadequate hemostasis were validated. CDS film, despite this inadequate hemostasis, reduced the extent of adhesions (31% +/- 7.4%; P<.01). Both the tenacity (P=.0008) and degree of uterine convolution (P=.000003) was reduced by CDS film but not by INTERCEED. CONCLUSION(S): Under conditions of inadequate hemostasis CDS effected a reduction in adhesion development. CDS may be useful adjuvant for procedures where hemostasis is difficult to achieve.

Synthetic epikeratoplasty in rhesus monkeys with human type IV collagen.

Human type IV collagen discs were found to support proliferation and adhesion of rabbit corneal epithelial cells in tissue culture. To assess the biocompatibility of this synthetic collagen for epikeratoplasty, seven eyes of seven rhesus monkeys underwent epikeratoplasty with lenticules made of human type IV collagen. Eye rubbing by the animals expulsed two of the lenticules and caused failure of two to epithelialize completely. The remaining three lenticules epithelialized, remained clear, and caused no adverse effects on the eye. Two of these lenticules developed focal areas of subepithelial thinning 3 months postoperatively and the third lenticule has remained stable for 30 months. The presence of epithelial attachment components at the epithelial-lenticule interface was demonstrated by immunolocalization. Histopathologic and ultrastructural examination revealed focal areas of epithelial invasion and degradation of the lenticule. Neutral proteases were detected in the thinning region of one specimen. Human type IV collagen supports epithelialization in vivo and may have potential as a biomaterial for epikeratoplasty, but the stability of the material must be improved.

[Human collagen IV lenses and epikeratoplasy in monkeys. Study of epithelial cicatrization]. / Lentilles de collagène IV humain et épikératoplastie chez le singe. Etude de la cicatrisation de l'épithélium.

A previous study showed the good tolerance of the human type IV collagen lenses implanted by epikeratoplasty in 8 monkeys. It also showed type IV collagen is a good material for the reepithelialization. But we have been interested in the stability of the epithelial healing. The ultrastructural study found anchoring structures. However these were inconstant. So the authors try to understand better the mechanisms of this synthesis of the anchoring structures and describe the future ways of this experimental study.

[Epikeratoplasty without sutures using collagen IV lens in monkeys: description of the surgical technic]. / Epikératoplastie sans suture avec lentille de Collagène IV chez le singe: description de la technique chirurgicale.

The authors describe their original epikeratoplasty technic without sutures which is compatible with the use of collagen IV lens. They describe the first four observations of primates operated on using this technic. At first the epithelium is removed at the cornea center and a trepanation is made of 4 mm diameter and 0.1 mm depth. The bottom of the trepanation is then cut horizontally, and the periphery of the lens is put in the cornea stroma. Later the epithelium will recover the collagen lens. The lens is perfectly set in the cornea. We don't use any suture and so we avoid astigmatism and neovascularisation. The follow-up consisted of biomicroscopic examination photography, specular microscopy, pachymetry, photokeratoscopy (Nidek System) tonometry and histology. Clinical observance showed a perfect lens tolerance. The cornea is immediately transparent and within a week epithelial cells recovered the lens of three animals out of four. The photokeratoscopy study proved the important cornea refraction modification. This technic is reversible and the lens can be exchanged. A study of histology has begun and already shows a pluristratified epithelium. Further studies will test the biomaterial stability and ultra structural relations between the collagen IV lens and epithelial cells.

Biocompatibility of human collagen type IV intracorneal implants.

A new biomaterial made from human placental collagen type IV has been developed in corneal inlays for refractive keratoplasty. Eight dogs received intracorneal lenses to investigate biocompatibility. Postoperative follow-up observation of 2 years revealed that the eyes remained clear and without inflammatory reaction. Endothelial cells were unaltered. Histological and ultrastructural studies showed no signs of inflammation, ulceration, or encapsulation. No fibroblastic activity was evident at the lens stroma interface.

[Viscous human collagen IV. Physical properties and experimental tolerance]. / Le collagène IV visqueux d'origine humaine. Propriétés physiques et tolérance expérimentale.

Viscous solutions of collagen IV have been used experimentally on rabbits and monkeys. The physical properties of the solution allow a first class visco-surgery. Tolerance is studied: degradation and absorption in the anterior chamber, intraocular pressure, endothelial effects, biological sensitivity. Good tolerance and mechanical properties are said excellent and use during human surgery has started.

[A trial use of lenses of human placental collagen in epikeratoplasty procedures]. / Essai d'utilisation de lenticules en collagène placentaire humain dans la technique de l'épikératoplastie.

Epikeratoplasty is a refractive surgery procedure described by Werblin and Kaufman which is simple, effective and reversible. However its development is hampered by the need of human corneas. We evaluated this procedure in rabbits and monkeys using lenticules of human collagen. The collagen is obtained from frozen human placentas, washed and subjected to pepsin digestion; it is contained in the supernatant of centrifugation and can be isolated by a physico-chemical treatment. 15 days after surgery the lenses of 14 rabbits were completely covered with a layer of epithelial cells. 6 months after surgery, the eyes of 14 monkeys were quiet and the lenses were covered with an epithelium made up of 2 to 5 layers of cells. The lens exhibited no inflammatory infiltration and there was no inflammatory reaction around the lens. These studies are still preliminary and longer term tests are necessary. These initial results are very encouraging, prompting us to develop the use of this type of material in refractive surgery.

Modulation of the immune response by plasma protease inhibitors III. Alpha 1-antichymotrypsin inhibits human natural killing and antibody-dependent cell-mediated cytotoxicity.

The effects of alpha 1-antichymotrypsin (AChy), a serum protease inhibitor, on two parameters of the cellular immune response, natural killing (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC), were tested. Both NK and ADCC were inhibited by the protein in a dose-dependent fashion. Our results suggest that this protease inhibitor binds to the surface of NK and ADCC target cells and neutralizes the lytic signal passed between the effector and target.

Modulation of the immune response by plasma protease inhibitors. II. Alpha 2-macroglobulin subunits inhibit natural killer cell cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

In two different cytolytic assays, dose-dependent inhibition of antibody-dependent cell-mediated cytotoxicity and natural killing by alpha 2-macroglobulin (alpha 2m) and its subunits was observed. Alpha 2m subunits were approximately four times more inhibitory in both assays than the native alpha 2m molecule on a molar basis. Analysis of trypsin protein esterase activity demonstrated that alpha 2 subunits were four times more active than the parent molecule.