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Biomedical subjects

M Chvapil

Publications and source records attributed to M Chvapil.

At least 55 records · Page 3Linked to original sources
PubMed1986

Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit.

Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (57Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

Animals↗
PubMed1986

Delivery of antifibroblast agents as adjuncts to filtration surgery--Part II: Delivery of 5-fluorouracil and bleomycin in a collagen implant: pilot study in the rabbit.

A pilot study was performed in order to determine if filtration bleb longevity could be enhanced in rabbits by delivery of 5-fluorouracil or bleomycin in a collagen sponge implant. Results showed that both agents prolonged bleb longevity and lowered intraocular pressure when compared to controls. Bleomycin treated animals had the best bleb appearance and function at the longest postoperative intervals.

Animals↗
PubMed1985

Collagen sponge as vaginal contraceptive barrier: critical summary of seven years of research.

Extensive testing of collagen sponge as a vaginal contraceptive (mechanical and chemical) showed that the original expectations regarding the safety, convenience, and efficacy were not met. The collagen sponge was tested both as a cylinder and as a diaphragm and used as such or impregnated with spermicidal detergent or with zinc salt. The collagen sponge must be larger than 6 cm in diameter in order to serve as a mechanical barrier that will not be dislodged during physical activity. This creates problems with the ease of insertion and with the partners' awareness of the barrier. When the collagen sponge containing ejaculate is left in the vagina greater than 48 hours, it develops an offensive odor. The original acidity of the collagen sponge (pH 3.5, 0.1 mol/L) is soon neutralized by the large volume of alkaline vaginal secretions. In vitro studies showed that up to 10 mg of nonoxynol 9 per milliliter of growth medium did not inhibit the growth of Staphylococcus aureus. These effects, as well as the large surface area of the resilient sponge, present a potential risk for growing staphylococci within the collagen sponge. The capacity of the collagen sponge to absorb a large volume of cervical and vaginal fluid produced two symptoms that were annoying to the volunteers: an awareness of either vaginal dryness during intercourse or, conversely, saturation of the sponge from the vagina. Postcoital studies showed viable spermatozoa in the cervical mucus in 25% of the tests with the nonmedicated cylindrical sponge but in only 6% of tests with the sponge containing nonoxynol 9. The results of clinical trials conducted at four centers support the view that collagen sponge as a vaginal contraceptive barrier method is inconvenient to both partners, not effective enough to compete with present methods of vaginal contraception, and possibly might be unsafe because of the capacity to grow bacteria. Despite the negative end result of this goal-oriented research, we believe that our studies have contributed to a better understanding of vaginal physiologic features, the safety and effectiveness of spermicidal detergents, and the mechanisms of vaginal malodor. Although the acceptability study showed some advantages of the collagen sponge over the rubber diaphragm, the overall acceptability of the collagen sponge diaphragm was no better than that of the rubber diaphragm. For all these reasons, including the possible risk of an increased incidence of toxic shock syndrome, we have discontinued further testing of either type of collagen sponge as a vaginal barrier method.

Collagen↗
PubMed1985

Therapeutic effects of disulfiram in spinal cord contusion of rabbits.

The purpose of the present investigation was to evaluate methods to prevent the development of the immediate and delayed tissue damage in the injured spinal cord by early drug (disulfiram) interference with the molecular mechanism of tissue injury. The edematous inflammation as well as change in the levels and distribution of metallic ions like calcium following spinal cord contusion is known to contribute to the destructive process. A contusion model was applied in the spinal cord of rabbits using a pneumatic impactor. The effect of the systemically administered drug, disulfiram, in the traumatized spinal cord was determined by assaying the tissue water and Ca2+ contents at different locations of the spinal cord. A significant increase in the levels of the assayed parameters at the injured site of the spinal cord is markedly reduced by the pretreatment with disulfiram.

Animals↗
PubMed1985

The control of peritendinous adhesions using topical beta-aminopropionitrile base.

The Lindsay chicken foot tendon model was utilized to test the effect of topically applied beta-aminopropionitrile base upon the tensile strength of peritendinous adhesions following tenolysis of a scarified flexor tendon. The agent reduced by one-third the force required to effect tendon gliding and flexion of the joints in the involved digit. The results show that topical beta-aminopropionitrile is effective in the control of peritendinous adhesions and, therefore, achieves sufficient depth of penetration topically to affect the peritendinous location. No adverse effects of the topically applied agent were demonstrated. The principle of topical therapeutics that may have significant benefits to patients with tendon injuries is demonstrated.

Administration, Topical↗
PubMed1984

Development of topical BAPN delivery system for acute spinal cord injury in dogs.

Topical sustained release of various medications by a subdurally implantable device at the site of spinal cord injury is considered advantageous in the treatment of early symptoms of tissue damage. A typical case is the interference with collagenous scar by beta-aminopropionitrile, inhibiting collagen polymerization. Four materials, silicone, polyethylene, polytetrafluoroethylene (PTFE), and polyacrylonitrile-based hydrogel were evaluated for biocompatibility in subcutaneous implantations. The hydrogel, the least reactive, was then compared with silicone sheets as subcural implants. The histology favored the hydrogel as the most inert material, which was then used for the construction of soft, pliable pouches, releasing the drug through the hydrated wall at a rate controlled by an osmotic pump.

Aminopropionitrile↗
PubMed1984

Identification of the depth of burn injury by collagen stainability.

Heat-denatured collagen in burned skin stains red instead of blue in Masson's trichrome stain. This change in stainability corresponds to the loss of birefringence in slides examined in polarized light. The depth of the abnormal staining of the skin slices was proportional to the time and temperature of the heat exposure. It is concluded that the change in collagen stainability from blue to red relates to the loss of crystallinity or parallel alignment of the collagen fibers. It is further proposed that change in the stainability of collagen in the burns could be used to delineate the depth of the thermal skin injury or the effectiveness of the surgical excision or debridement of the wound by dressing materials.

Animals↗
PubMed1984

Zyderm.

Explore the source record for details and available documents.

Collagen↗
PubMed1983

Some characteristics of collagen-heparin complex.

In various forms of purified collagen (powder of insoluble collagen from bovine skin, fibers from rat tail tendons, membrane from bovine gut), carboxyl groups were activated by carbodiimide to allow covalent binding of heparin. Collagen powder and collagen fibers from rat tail tendons were also incubated in a heparin solution under the same reaction conditions but without carbodiimide present to account for other forms of collagen-heparin interaction. It was found that the linkage of heparin to collagen formed in the presence of carbodiimide is stable, as heparin was minimally extractable by 0.2M buffers with a pH ranging from 5 to 9. Collagen powder incubated with heparin in the absence of carbodiimide released heparin almost completely into Tris buffer of pH 9.0. As a consequence of covalent binding of heparin to collagen, the collagen fibers became more stable as shown by their significantly reduced swelling capacity and significantly increased shrinkage temperature. Collagen fibers interacted with heparin in the absence of carbodiimide also showed some stabilization of their structure, which was, however, significantly less than with carbodiimide reaction. By two independent methods it was shown that heparin linked to collagen by a stable bond retains its anticoagulant activity. It is concluded that, in the presence of carbodiimide, heparin covalently binds to collagen thus forming an antithrombogenic surface. At the same time, collagen is crosslinked. Incubation of collagen in the solution of heparin without carbodiimide also stabilizes collagen structure, but to a significantly lesser degree. Such a linkage is unstable as heparin dissociates and is readily extractable into 0.2M Tris buffers with pH 7-9.

Animals↗
PubMed1983

Healing of skin incision wounds treated with topically applied BAPN free base in the rat.

beta-Aminopropionitrile as free base (BAPN) was applied onto the incised or intact skin of rats at the dose of 5, 20, 100, and 200 microliters for 9 days, twice daily. Breaking strength of the skin wound or intact skin was significantly reduced at doses of 20 microliters and higher; body weight growth was significantly retarded at the two highest dosages. It is concluded that at a given dose (20 microliters) collagen polymerization (evaluated by reduced breaking strength and increased extractability of collagen) was specifically inhibited by BAPN. Furthermore, no evidence of topical or general toxic effects were observed, as reflected in histology, body weight growth, and behavior of the rats. Acute LD50 of BAPN base and fumarate, administered either ip or topically, was determined in mice. While BAPN base in ip administration shows LD50 of 1.15 g/kg, in cutaneous application it is more than 12.8 g/kg. It is suggested that topically applied BAPN base is percutaneously absorbed and affects collagen polymerization in the skin and adjacent tissues.

Administration, Topical↗
PubMed1983

Inhibition of lipid peroxidation in spinal cord homogenates by various drugs.

The extent and kinetic profiles of lipid peroxidation induced with Fe2+-ascorbic acid in a homogenate of spinal cord from greyhound dogs were ascertained by measurement of the formation of malondialdehyde (MDA) and chemiluminescence in the presence of four drugs. Changes in MDA and chemiluminescence were correlated as a function of the activator or inhibitors. The kinetic profiles of chemiluminescence which were observed for 25 min after addition of the activator and individual inhibitors were similar regardless of the type of inhibitor studied. The most effective inhibition was by disulfiram which was approximately 11 and 33 times more effective than two other inhibitors, propyl gallate and promethazine, respectively, and 11,000 times more effective than D-alpha-tocopherol.

Animals↗
PubMed1983

Diffusion characteristics of beta-aminopropionitrile in peripheral nerve.

beta-Aminopropionitrile (beta-APN), a lathyrogen, alters the physical characteristics of fibrous scar tissue and as such may have potential clinical use in treatment of injured spinal cord and peripheral nerve by reducing the physical barrier to axon regeneration. For beta-APN to exert its lathyrogenic effect, it must permeate the injury site and gain access to the developing collagenous scar. To investigate the diffusion characteristics, beta-[14C]APN solution was applied as an immersion bath to rat sciatic nerve using both in vivo and in vitro preparations for intervals of 15 to 90 min. The four experimental groups studied were (a) intact nerve, (b) hemisected nerve, (c) nerve with epineurium removed, and (d) nerve with both epineurium and perineurium removed. The isotope labeling index determined by autoradiography and scintillation counting indicated the perineurium as the primary barrier to significant diffusion of beta-APN in normal nerve. When perineurium was incised or removed, beta-APN entered the endoneurial matrix. beta-APN concentration in the epineurium and perineurium increased with increasing bathing time in vitro; but it decreased markedly after 15 min of in vivo bathing. These findings indicate that topical application of beta-APN to injured peripheral nerve would be a successful method of exposing fibrogenic intraneural tissue to the inhibitory effect on lysyl oxidase enzymes. Continuous application, however, will be necessary because of the rapid beta-APN removal documented in the vivo preparation.

Aminopropionitrile↗
PubMed1983

Zinc transport by the heart lymphatic system after acute myocardial infarction.

Open-chest dog preparations were used to determine divalent cation transport following acute myocardial infarction. Cardiac lymph flow, lymph and plasma protein, zinc, calcium, and magnesium content and hemodynamic measurements were recorded every 20 min before and after coronary artery occlusion in sham operated (N = 4), infarcted (N = 6), and lymph-ablated animals (N = 4). During the 4-hr occlusion period, with constant blood pressure, lymph flow increased from 1.53 +/- 0.25 to 2.15 +/- 0.44 mg/hr (SEM), P less than 0.01. Zinc decreased in plasma from 0.69 +/- 0.10 to 0.41 +/- 0.08 micrograms/ml, P less than 0.01, and in lymph from 0.69 +/- 0.08 to 0.40 +/- 0.02 micrograms/ml, P less than 0.01. Zinc to protein ratio decreased similarly to total zinc in plasma and lymph. Changes in calcium and magnesium were insignificant. Lymph to plasma concentration ratios increased for protein from 0.57 +/- 0.05 to 0.62 +/- 0.02, P less than 0.05, and for zinc from 1.10 +/- 0.26 to 1.21 +/- 0.14, P less than 0.05. Heart lymph clearance (lymph:plasma ratio X lymph flow) steadily rose for protein from 0.31 to 0.06 to 0.50 +/- 0.08, P less than 0.05, and for zinc from 0.59 +/- 0.18 to 0.92 +/- 0.15, P less than 0.05. Lymph and plasma measurements did not change significantly in sham-operated animals. Plasma zinc remained unchanged from baseline after coronary occlusion in all lymph-ablated animals. The increased clearance of protein and zinc suggests that plasma proteins are zinc carriers after acute myocardial infarction and that the reduction of plasma zinc is dependent upon an intact cardiac lymphatic circulation.

Animals↗
PubMed1983

Effect of tanning agent on tissue reaction to tissue implanted collagen sponge.

Pure collagen, isolated from bovine skin, was reconstituted into the form of a sponge in the presence of either glutaraldehyde (GTA) or hexamethylene diisocyanate (DIC). Extensively washed sponges were implanted subcutaneously in rats and harvested 5 and 17 days later. Histology showed that at 5 days, the GTA-crosslinked sponge induced more cellular reaction at the outer layer of the sponge than the DIC-tanned sponge. After 17 days, the cellular infiltration of the GTA-tanned sponge remained at the periphery of the implant while the DIC-tanned sponge was completely infiltrated by inflammatory cells, including fibroblasts. Quantitative morphometry and determination of cellular DNA in sponges harvested at 17 days support the morphological finding. We conclude that GTA-tanned sponges are cytotoxic as evidenced by more pronounced tissue reaction soon after tissue implantation, and no cellular infiltration at later stages into the implant. Hexamethylene diisocyanate seems to be a more adequate tanning agent for sponges designed as a tissue substitute.

Animals↗
PubMed1983

Distribution of disulfiram in brain after carotid ligation in gerbils.

Aiming whether intraperitoneal administration of disulfiram (tetraethyl thiuram disulfide, DS) achieves potentially therapeutic drug concentrations in brain tissue, the behaviour of blood-brain barrier (BBB) to 14C-labelled DS in cerebral ischemia with and without simultaneous administration of dimethylsulfoxide (DMSO) was studied in Mongolian gerbils subjected to left common carotid artery (CCA) occlusion. The results indicated that: (a) the permeability of DS through the BBB was significantly enhanced in the ischemic brain during the initial 30 min duration after DS administration; (b) administration of DMSO increased the entry of DS into the ischemic brain five-fold during the first 30 min and it was significantly higher even at the 60 min sampling period; (3) in general, the content of DS in the brain was quickly reduced with time.

Animals↗
PubMed1983

Topical beta-aminopropionitrile in the treatment of Peyronie's disease.

We treated 9 patients with Peyronie's disease for 1 to 8 years in duration with a 4-week course of beta-aminopropionitrile free base as the pure liquid. The drug was applied topically to the plaques twice daily. Patients were followed with ultrasound imaging of the plaques and saline inflations of the corpora cavernosa with photographic documentation of the deformity. No significant adverse effect was noted. Three patients experienced a subjective response but did not demonstrate objective change on the aforementioned studies. It was concluded that topical beta-aminopropionitrile was not effective in reversing the deformity of Peyronie's disease. Further investigation into specific anti-collagen drugs for the treatment of this condition may be warranted.

Administration, Topical↗