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Biomedical subjects

F J Papatheofanis

Publications and source records attributed to F J Papatheofanis.

33 records · Page 2Linked to original sources

Polymorphonuclear leukocyte degranulation with exposure to polymethylmethacrylate nanoparticles.

Polymethylmethacrylate (PMMA) is clinically employed in a wide range of orthopaedic procedures. The etiology of the inflammatory reaction of recipient tissues to PMMA remains unresolved. Classically, polymorphonuclear leukocytes (PMNs) release cytoplasmic lysosomal granules when exposed to a variety of proinflammatory stimuli. Such degranulation contributes, and partially defines, the local tissue reaction to this foreign material. In the present investigation, PMMA particles (50-60 nm) were mixed with human PMNs, and the amount of lactate dehydrogenase, lysozyme, and beta-glucuronidase released from the cells was quantitated. In all cases, a dose-dependent increase in degranulation followed the addition of increasing amounts of PMMA to the PMNs. In addition, the migration of PMNs was diminished in a dose-dependent manner with exposure to increasing amounts of the cement. These results suggested that PMMA stimulates the release of leukocyte lysosomal contents and alters the migration characteristics of these cells in a manner that is consistent with the local inflammatory reaction to this cement.

Biocompatible Materials↗

Biochemical changes in knee joint articular cartilage after cemented prosthetic hip hemiarthroplasty in dogs.

Biochemical changes in the distal femoral articular cartilage (knee joint) after cemented prosthetic replacement of the femoral head were determined. Femurs from dogs (n = 10) that had undergone cobalt-chromium prosthetic hip hemiarthroplasty (6-8 months postoperatively) were analyzed for articular cartilage lipids in the distal femur. The quantity of phosphatidylserine increased from 0.59 +/- 0.14 mg (uninvolved) to 1.52 +/- 0.23 mg (hemiarthroplasty) lipid phosphorus/100 g tissue, and the quantity of arachidonic acid in the articular cartilage increased from 0.23 +/- 0.07 mg (uninvolved) to 2.07 +/- 0.29 mg/100 g tissue (hemiarthroplasty). Likewise, hydroxyproline content was higher in the recipient femurs (77.4 +/- 1.58 micrograms/mg cartilage) versus uninvolved femurs (71.8 +/- 1.03 micrograms/mg cartilage); the activity of acid phosphatase was greater in the recipient distal femoral cartilage as compared with the uninvolved femur, 0.07 +/- 0.01 and 0.06 +/- 0.02 mol hydrolyzed per kilogram per hour, respectively, and the hexosamine content was lower in the recipient femur knee cartilage versus knee cartilage from uninvolved femurs, 54.5 +/- 1.51 and 63.1 +/- 1.37 micrograms/mg cartilage, respectively. These biochemical changes may suggest degeneration of the knee joint articular cartilage after cemented hip hemiarthroplasty.

Acid Phosphatase↗

Use of calcium channel antagonists as magnetoprotective agents.

Human polymorphonuclear leukocytes (PMNs) exhibited a time-dependent (0 to 60 min) increase in the release of lysozyme and lactate dehydrogenase (degranulation) when exposed to a static (direct current) magnetic field of 0.1 Tesla. When 1 X 10(6) PMNs were treated with the calcium channel antagonists diltiazem, nifedipine, and verapamil before exposure to a magnetic field, no significant change in degranulation was detected compared to control and sham-exposed PMNs that were similarly treated. Likewise, magnetic field-induced inhibition of cell migration was prevented with the addition of these antagonists. Such changes in degranulation and cell migration occurred in a dose-dependent manner. These results indicated that these agents protected PMNs exposed to a magnetic field, and the damage to the cells that is mediated by magnetic field-stimulated Ca2+ influx might be preventable. In this regard, pharmaceutical agents might prove useful in protection against injurious electromagnetic field exposure.

Calcium Channel Blockers↗

Cytotoxicity of alkyl-2-cyanoacrylate adhesives.

The cytotoxicity of methyl- and isobutyl-2-cyanoacrylate adhesives was determined using a rat polymorphonuclear leukocyte suspension. Cell degranulation increased and migration decreased on addition of the alkyl-2-cyanoacrylates to the suspension in a concentration-dependent manner. When acetylsalicylic acid or indomethacin, inhibitors of prostaglandin H synthase, were present, the cytotoxicity observed on addition of the adhesives to the leukocytes decreased up to eightfold in a dose-dependent manner as detected by trypan blue exclusion. Likewise, glutathione peroxidase and superoxide dismutase lowered such cytotoxicity resulting from the cyanoacrylates up to eight- and sevenfold, respectively. The data suggested that the adhesives may have generated lipid hydroperoxides that activated prostaglandin and thromboxane biosynthesis, and participated in membranal oxidation and lysis. Such a mechanism may contribute to understanding the thrombotic events associated with the necrosis observed on application of these adhesives to tissues in vivo.

Animals↗

Surgical repair of rabbit tibia osteotomy using isobutyl-2-cyanoacrylate.

Isobutyl-2-cyanoacrylate was employed in the surgical repair of the osteotomized rabbit tibia in vivo. Union occurred at 24.3 +/- 3.1 days postoperatively when the adhesive had been used, compared with 35.5 +/- 3.6 days when no intervention was implemented. Healing of the osteotomy was not aided by external fixation or immobilization in either case. The results indicate the feasibility of using isobutyl-2-cyanoacrylate in the repair of load-bearing bones.

Animals↗

Prothrombotic cytotoxicity of cyanoacrylate tissue adhesive.

Alkyl-2-cyanoacrylates exhibit properties suggestive of their use as surgical adhesives; however, their cytotoxic and proinflammatory properties have prevented their widespread application. The question of whether cyanoacrylate cytotoxicity may be due to eicosanoid production was investigated. Endothelial cells from rats were exposed to increased concentrations of isobutyl-2-cyanoacrylate. The products from this exposure promoted enhanced, concentration-dependent thromboxane biosynthesis as detected by platelet aggregation. When platelets were pretreated with 1-carboxyheptylimidazole (2.0 mM), an inhibitor of thromboxane biosynthesis, up to 80% less aggregation was observed. Such aggregation was inhibited using 1-carboxyheptylimidazole in a dose-dependent manner. Treatment of endothelial cells with isobutyl-2-cyanoacrylate and 1-carboxyheptylimidazole did not significantly alter the amount of platelet aggregation. A soluble metabolite of isobutyl-2-cyanoacrylate appeared to activate platelet aggregation. The cytotoxicity associated with the surgical use of alkyl-2-cyanoacrylates may be mediated by enhanced local thromboxane production.

Adenosine Diphosphate↗

Contribution of hydroxyapatite to the tensile strength of the isobutyl-2-cyanoacrylate-bone bond.

The bonding strength between bone and alpha-2-cyanoacrylate polymers, with or without the addition of powdered hydroxyapatite, was determined. The tensile strength of a bone-cyanoacrylate bond was measured for each polymer: 4.31 +/- 0.88 MPa (methyl-), 5.74 +/- 0.62 MPa (ethyl-), and 8.33 +/- 0.41 MPa (isobutyl-). The tensile strength of the isobutyl-2-cyanoacrylate bond increased to 12.03 +/- 0.72 MPa with the addition of 10% (w/v) hydroxyapatite before decreasing to 7.89 +/- 0.58 MPa on addition of 15% (w/v) hydroxyapatite. An optimal concentration of hydroxyapatite significantly increased the tensile strength of a bone-cyanocacrylate bond in vitro in a manner comparable to reinforced bone replacement materials.

Animals↗

Acid and alkaline phosphatase activity in bone following intense magnetic field irradiation of short duration.

Consideration of the biological effects of electromagnetic radiation is particularly important with regard to bone metabolism. Magnetic fields have been applied to the treatment of bone fractures, and similar fields are employed in the visualization of skeletal structures through magnetic resonance imaging (MRI). The present investigation addressed the effect of MRI-intensity (1 Tesla) magnetic fields on enzymatic indices of bone metabolism. Mice were exposed to intense static (direct current) magnetic fields for 30 min on each of 10 successive days. After this exposure regimen the primary spongiosum of the humerus was assayed for acid and alkaline phosphatase activity. No significant difference was detected in tissue levels of either enzyme in bones from control (n = 10), sham-exposed (n = 10), and magnetic field-exposed (n = 10) mice. These results suggested that the effects of magnetic field irradiation do not appear to involve modification of the activities of regulatory enzymes in bone.

Acid Phosphatase↗

Short-term effect of exposure to intense magnetic fields on hematologic indices of bone metabolism.

Magnetic resonance imaging (MRI) is a useful tool in the diagnosis and management of orthopedic disease. Previous reports indicate that magnetic fields of MRI intensity stimulate bone growth in vivo. We investigated the question of whether exposure to intense magnetic fields modified ionic and enzymatic constituents of the circulatory system. Mice were exposed to a static (direct current) magnetic field (1 Tesla) for 30 minutes on each of ten consecutive days. No significant difference in blood alkaline phosphatase, acid phosphatase, calcium ion concentration, and phosphate ion concentration was detected between control, sham-exposed, and magnetic field-exposed mice. These results suggest that exposure to intense magnetic fields does not alter physiological mechanisms of bone mineralization.

Animals↗

Biochemical diagnosis of genetic disorders of the osseous skeleton.

Genetic diseases of the skeletal system are difficult to accurately diagnose. Changes in the chemical structure of collagen significantly modify the structure of collagen in bone. The ratio of collagen hydration to hydroxylation reflects specific features of the collagen structure. The hypothesis proposes to use this ratio in the diagnosis of diseases of the skeleton.

Bone Diseases↗

Experimental use of adhesives in the repair of transverse fractures of the rat and rabbit.

In this preliminary study, the feasibility of fixing fractured bones was explored using the ethyl and isobutyl 2-cyano-acrylates, prepolymerized barnacle cement, and fibrin glue. Adequate cohesive strength cannot be obtained when lipids are present on the surface to be joined by alkyl 2-cyanoacrylates. Oxidized regenerated cellulose gauze soaked in a highly concentrated fibrinogen solution was inserted into the partially hollowed fracture ends to arrest the flow of oozing blood from the medullary canal. Anhydrous ether was used to sponge off any residual lipid from the bone surfaces. The displaced fracture ends were aligned and narrow strips of bone were secured around the fracture line resulting in a barrel stave arrangement. Roentgenograms indicated successful reduction of transverse (midshaft) fractures in eight rat (femur) and seven rabbit (tibia) models. In some cases, casts were used as supplementary fixation. Using the ethyl and isobutyl 2-cyanoacrylates, reduced fractures were maintained in a stable position for up to five and six days, respectively. Further study of the 2-cyanoacrylates is recommended. By using a standardized surgical method for testing the usefulness of future adhesives in vivo, consistent interpretation of results will be facilitated.

Animals↗

Mathematical analysis of contribution of bone remodeling to adhesive performance.

The alkyl-2-cyanoacrylates have been used to repair tissues such as bone. The failure of bonding observed with the application of such adhesives is attributable to a variety of factors including the aqueous environment of the bond. A mathematical analysis of the contribution of the aqueous environment to bonding performance is elaborated. Mathematical modeling may accurately approximate experimental variables that contribute to the performance of biomaterials.

Body Water↗