PubMed Health⌕ Search

Biomedical subjects

A Gallacher

Publications and source records attributed to A Gallacher.

7 recordsLinked to original sources

Local carboplatin delivery and tissue distribution in livers after radiofrequency ablation.

This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.

Animals↗

A mechanism of action for non-steroidal anti-inflammatory agents in calcium pyrophosphate dihydrate (CPPD) crystal induced arthritis.

The acute inflammatory response to calcium pyrophosphate dihydrate crystals follows the meeting of neutrophils and crystals. The ensuing phagocytosis leads to the generation of a glycoprotein chemotactically active for neutrophils and to the release of lysosomal enzymes. Indomethacin and phenylbutazone, at therapeutic concentrations, impaired phagocytosis of the crystals and generation of chemotactic factor activity. Colchicine had no effect upon phagocytosis but significantly impaired the appearance of chemotactic factor activity.

Arthritis↗

Calcium pyrophosphate dihydrate (CPPD) crystal-induced chemotactic factor: subcellular localization, role of protein synthesis and phagocytosis.

A factor with chemotactic properties for polymorphonuclear leukocytes appears in their lysosomal fraction following phagocytosis of CCPD crystals. The factor, whose appearance was blocked by inhibition of protein synthesis, was estimated to have a molecular weight of 8,400 daltons. Inhibition of crystal phagocytosis by cytochalasin B was also shown to inhibit the generation of chemotactic factor activity, indicating that ingestion of the crystals by the cell is essential for the generation of the CPPD crystal-induced chemotactic factor. This latter finding provides a clue in the understanding of the development and termination of the acute pseudogout attack.

Calcium Pyrophosphate↗

Urate crystal-induced chemotactic factor: isolation and partial characterization.

A factor with chemotactic properties for neutrophils and mononuclear cells was extracted from the lysosomal fraction of both human and rabbit neutrophils that had been allowed to phagocytose monosodium urate crystals. The chemotactic factor was found to be a glycoprotein with a mol wt of 8,400 daltons. The factor is heat labile and has chemotactic activity for human as well as rabbit cells. Preincubation of the cells with the urate induced chemotactic factor or with complement activated plasma prevents the cell from migrating chemotactically when challenged with either factor in the chemotactic chamber. The chemotactic factor induces release of lysosomal enzymes for cytochalasin B treated human neutrophils.

Glucuronidase↗

Studies on crystal-induced chemotactic factor. II. Role of phagocytosis.

The interaction of polymorphonuclear leukocytes (PMN's) and urate crystal leads to the formation of a chemotactic factor. The purpose of this study was to determine the need for ingestion of crystals by the cells in the generation of the chemotactic factor. Our studies showed that when PMN's were incubated with cytochalasin B, an inhibitor of phagocytosis, and urate crystals, no chemotactic activity appeared in the lysosomal extract of the cells. Likewise, no chemotactic activity was present in the media of PMN's incubated with crystals although lysosomal enzyme activity was increased. These findings indicate that phagocytosis is required for chemotactic activity to appear. Our studies also show that cytochalasin B increases the release of lysosomal enzyme B-glucuronidase but not of cytoplasmic enzyme lactic dehydrogenase from PMN's when the cell encounters urate crystals.

Animals↗

Fluorimetric method for the detection of anti-DNA antibodies in serum.

A method for the detection of native anti-DNA antibodies in serum is described. The method is based on the reactivity of fluorescein isothiocyanate with DNA, forming a complex capable of combining with anti-DNA antibodies. The fluorescein content of the precipitated fluorescein-DNA anti-DNA complex is then measured in a fluorometer. The assay is accurate, highly reproducible, and inexpensive to perform. Comparative studies performed with the Farr assay show the fluorimetric method to be more sensitive in detecting anti-DNA antibodies in the serum of SLE patients.

Antibodies, Antinuclear↗