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Biomedical subjects

J M Joseph

Publications and source records attributed to J M Joseph.

81 records · Page 5Linked to original sources
PubMedDate not supplied

Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid space: a preclinical study for the treatment of cancer pain.

Chromaffin cells have been shown to release a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. The allogeneic transplantation of chromaffin cells in the subarachnoid space has been shown to alleviate pain in various rodent models and possibly in terminal cancer patients. Because of the shortage of human cadaver donor tissue, we are investigating the possibility of transplanting xenogeneic cells in polymer capsules. In this technique, cells are surrounded by a permselective synthetic membrane whose pores are suitably sized to allow diffusion of nutrients, neurotransmitters and growth factors, but restrict the diffusion of the large molecules of the immune system and prevent contact with immunocompetent cells. The encapsulation technique therefore allows transplantation of xenogeneic tissue between species as well as retrieval of transplanted cells. Previously we have reported that encapsulated bovine chromaffin cells survive and alleviate pain in various rodent models. The purpose of the present study was to assess the feasibility of implanting a human sized device in a large animal model. Adrenals from 5 calves were surgically removed; chromaffin cells were isolated from these glands using a collagenase-based digestion-filtration technique. Cells were loaded into acrylic-based tubular (5 cm long, 920 microns wide) permselective capsules attached to silicone tethers. The capsules were maintained in vitro for at least 7 days following the encapsulation procedure. Nicotine evoked release was analyzed in a defined subgroup from each batch. One capsule was then implanted using a guiding cannula system in the lumbar subarachnoid space of each sheep for 4 (n = 5) and 8 (n = 1) wk. All capsules were retrieved intact by gentle pulling on the silicone tether. Except for one capsule, the evoked catecholamine release of the retrieved capsules was in the same range as that of other capsules from the same cohort that had been maintained in vitro. All retrieved capsules were devoid of host cell reaction. Clusters of viable cells dispersed in an alginate immobilizing matrix were observed throughout all the implanted capsules. This study demonstrates the feasibility of transplanting functional encapsulated xenogeneic chromaffin cells into the cerebrospinal fluid of a large animal model using a capsule of appropriate dimensions for human implants. We believe that these results suggest the appropriateness of human clinical trials in patients suffering from refractory terminal cancer pain.

Adrenal Glands↗
PubMedDate not supplied

Photochemical production of hydroxyl radical from aqueous iron(III)-hydroxy complex: determination of its reaction rate constants with some substituted benzenes using deoxyribose-thiobartituric acid assay.

Hydroxyl radical (OH) production, mediated by UV light, from aqueous ferric perchlorate was investigated at low pH using a deoxyribose-thiobarbituric acid (-TBA) assay. The rate of production of OH was found to be dependent on the irradiation time. Addition of suitable substrates such as substituted benzenes can compete for the reaction of OH with deoxyribose, leading to a decreased yield of TBA chromogen formed from the deoxyribose-TBA assay. The second-order rate constants of the added substrates can be determined from such a simple competition kinetic method. The second-order rate constants for the reaction of OH with a number of substituted benzenes were determined using this method and the values were compared with the reported rate constants using pulse radiolysis technique. The values determined using the present method (1 to 8 x 10(9) dm3/mols) are in good agreement with those reported by use of the pulse radiolysis technique. It is proposed that the photoproduction of OH from aqueous ferric perchlorate coupled with deoxyribose-TBA assay is a simple and efficient method for determination of rate constants for the reaction of OH with a variety of substituted benzenes that are known to be organic water contaminants.

Benzene↗