Biomedical subjects

A A Ragab

Publications and source records attributed to A A Ragab.

6 recordsLinked to original sources

PubMed2001

Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice.

Aseptic loosening is the most common cause of orthopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result, 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation. Skeletally mature, adult mice (4-16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening.

Aging↗

PubMed2001

Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclasts.

BACKGROUND: Loosening of orthopaedic implants is mediated by cytokines that elicit bone resorption and are produced in response to phagocytosis of implant-derived wear particles. This accelerated bone resorption could be due to increased osteoclastic activity, survival, or differentiation. Although a number of in vitro studies have shown that wear particles increase osteoclastic activity, the increase was less than twofold in all cases. The objective of the current study was to test the hypothesis that wear particles stimulate bone resorption by inducing osteoclast differentiation. METHODS: Conditioned media were prepared from murine marrow cells or human peripheral blood monocytes incubated in the presence or absence of titanium particles. The effects of conditioned media on osteoclast differentiation were examined with use of a recently developed assay in which osteoclast precursors are co-cultured with mesenchymal support cells. RESULTS: The present study showed that titanium particles induced both murine marrow cells and human peripheral blood monocytes to produce factors that stimulated osteoclast differentiation. The mean increase in osteoclast differentiation was 29.3+/-9.4-fold. The stimulation of osteoclast differentiation led to a parallel increase in bone resorption. The amount of stimulation was regulated in a dose-dependent manner by the concentration of both titanium particles and conditioned media. The stimulation of osteoclast differentiation required interactions between the cells and the particles themselves and, therefore, was not due to metal ions, soluble contaminants released from the particles, or submicrometer particles. In contrast, conditioned media from control cells incubated in the absence of titanium particles had no detectable effect on any of the examined parameters. CONCLUSIONS: The present study showed that titanium particles stimulate in vitro bone resorption primarily by inducing osteoclast differentiation. In contrast, the titanium particles had only small effects on osteoclast activity or survival.

Adult↗

PubMed1999

Measurement and removal of adherent endotoxin from titanium particles and implant surfaces.

Aseptic loosening is thought to be due primarily to osteolysis induced by cytokines and prostaglandins that are produced in response to implant-derived wear particles. Because endotoxin has many of the same effects as have been reported for wear particles, we hypothesized that adherent endotoxin may be responsible for the biological responses induced by wear particles. We demonstrated the presence of significant levels of adherent endotoxin on commonly used preparations of titanium particles as well as on titanium and titanium-alloy implant surfaces. In contrast, supernatants obtained by centrifugation of particle suspensions contained approximately 1% as much endotoxin as did the particles. Therefore, it is erroneous to assume that particles do not contain endotoxin on the basis of data that it cannot be detected in their supernatants or filtrates. These results emphasize the importance of considering the potential role of adherent endotoxin when examining the in vitro effects of wear particles and the in vivo performance of orthopaedic implants. We also developed a protocol that removed more than 99.94% of the adherent endotoxin from the titanium particles without detectably affecting their size or shape. The removal of adherent endotoxin will allow comparison of the biological responses induced by particles with or without adherent endotoxin.

Endotoxins↗

PubMed1999

Clinical and radiographic outcomes of total hip arthroplasty with insertion of an anatomically designed femoral component without cement for the treatment of primary osteoarthritis. A study with a minimum of six years of follow-up.

We evaluated the clinical and radiographic outcomes of 100 consecutive primary total hip arthroplasties in which a proximally coated anatomically designed femoral component was fixed without cement for the treatment of primary osteoarthritis. The minimum duration of follow-up was six years (average, 7.1 years). The eighty-eight patients who had the arthroplasties were followed prospectively with a standard clinical evaluation that involved use of the Harris hip score and a radiographic evaluation based on the criteria of the Hip Society. Bone ingrowth was evaluated with the method of Engh et al. The average age of the patients at the time of the operation was 62.6 years (range, thirty-nine to eighty-four years). Fifty-one patients were men and thirty-seven were women. The average preoperative Harris hip score was 48 points, with an average pain score of 15 points and an average function score of 26 points. Nonmechanical complications that necessitated a revision operation included one deep hematogenous infection, one late periprosthetic fracture, and a 0.5-inch (1.27-centimeter) limb-length discrepancy. At the time of the most recent follow-up, the average Harris hip score was 96 points, with an average pain score of 42 points and an average function score of 45 points. The prevalence of pain in the anterior part of the thigh was 5 percent (five hips). One patient had a revision of the femoral component because of aseptic loosening, and one had a revision of the acetabular component because of recurrent dislocations. Radiographic assessment revealed consistent evidence of proximal bone ingrowth. No complete radiolucent line was identified, except around the stem that had loosened. Twenty-seven femoral components were associated with slight pedestal formation. No osteolytic lesion of the femur was identified. Nonprogressive pelvic osteolysis was identified in four hips, but none of the lesions were more than two millimeters in diameter. None of the acetabular components migrated, and no radiolucent line of more than two millimeters in thickness was seen around any acetabular cup. The data from this study, in which the minimum duration of follow-up was six years, indicate that the anatomically designed prosthesis can provide good results, with low prevalences of pain in the thigh and loosening of the component, in younger, active patients.

Adult↗

PubMed1998

Osteoclast differentiation requires ascorbic acid.

Osteoclast differentiation assays are usually conducted in alpha minimal essential medium (alpha-MEM). We reasoned that determining which components of this media are critical for osteoclast differentiation might provide insight into the mechanisms that regulate osteoclast differentiation. This study demonstrates that ascorbic acid is the crucial component of alpha-MEM that stimulates differentiation of murine osteoclasts in cocultures with murine mesenchymal support cells. Thus, supplementation with ascorbic acid allows osteoclast differentiation to occur in basal MEM media as well as in RPMI-1640 and basal media Eagle (BME) media. The conclusion that osteoclast differentiation is stimulated by ascorbic acid was obtained whether osteoclast differentiation was induced by 1,25-dihydroxyvitamin D3 or parathyroid hormone, whether ST2 or CIMC-2 cells were used as mesenchymal support cells, and whether osteoclast precursors were obtained from spleen or bone marrow. Time course studies revealed that although ascorbic acid only modestly increases the rate at which osteoclast precursors begin to express tartrate-resistant acid phosphatase, it strongly increases the rate at which precursors fuse into mature, multinucleated cells. Moreover, ascorbic acid strongly increases the life span of both osteoclasts and their precursors. The increases in precursor formation, fusion, and life span induced by ascorbic acid are together responsible for the stimulation of osteoclast differentiation by ascorbic acid. Given the known effects of ascorbic acid on differentiation of mesenchymal cells, it may stimulate osteoclast differentiation indirectly by regulating the differentiation state of the mesenchymal cells that support osteoclast differentiation.

Animals↗

PubMed1996

Regional distribution of lead in human milk from Egypt.

Bioaccumulation of lead during chronic exposure and its mobilization and secretion with mother's milk constitute a serious health hazard to the newly born children. Lead levels in human breast milk of 120 Egyptian women representing 20 different governorates throughout Egypt were determined using a graphite furnace Atomic Absorption spectrometer. According to the daily permissible intake (DPI) value established by the WHO of 5.0 micrograms/kg/d in mother's milk, the mean values of lead were around the permissible level in most of the Egyptian governorates. However, lead levels in mother's milk from Alexandria, Assiut and Cairo were significantly higher than the permissible value. Higher lead levels in mother's milk from these governorates may be attributed to heavy automobile traffic using leaded gasoline in addition to the use of lead water pipelines in these areas.

Adult↗