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Biomedical subjects

C Eriksson

Publications and source records attributed to C Eriksson.

10 recordsLinked to original sources

Effects of glutathione-modulating agents on the covalent binding and toxicity of dichlobenil in the mouse olfactory mucosa.

Twenty-four hours following injection of a single dose of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in C57Bl/6 mice a steep dose-response curve for the histopathological toxicity in the olfactory mucosa was observed. Four hours following injection of a toxic dose of [ring-14C]dichlobenil (12 mg/kg) the covalent binding in the olfactory mucosa was 26 times higher than that in the liver. A dose-dependent decrease of nonprotein sulfhydryls (mainly glutathione, GSH) in the olfactory mucosa was observed 2.5 hr following injection of dichlobenil (6, 12, 25 mg/kg). The synthetic GSH precursor N-acetyl-L-cysteine decreased both the dichlobenil-induced toxicity and the covalent binding, whereas N-acetyl-D-cysteine had no effect. No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed. In mice given the GSH-depleting agent phorone and a subtoxic dose of dichlobenil (6 mg/kg), an extensive toxicity and an increased covalent binding in the olfactory mucosa were demonstrated. Autoradiography showed no change in the distribution of covalent [14C]dichlobenil binding to nontarget tissues of phorone-treated mice. In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa. Hence, the level of GSH appears to be of importance for the dichlobenil-induced toxicity in the olfactory mucosa.

Acetylcysteine

Tissue-binding and toxicity of compounds structurally related to the herbicide dichlobenil in the mouse olfactory mucosa.

The herbicides dichlobenil (2,6-dichlorobenzonitrile), chlorthiamid (2,6-dichlorothiobenzamide) and their environmental degradation product 2,6-dichlorobenzamide are irreversibly bound and toxic to the olfactory mucosa following single injections in mice (Brandt et al., Toxicology and Applied Pharmacology 1990, 103, 491-501; Brittebo et al., Fundamental and Applied Toxicology 1991, 17, 92-102). In the present study, autoradiography showed an irreversible binding of radioactivity in the olfactory mucosa (preferentially in the Bowman's glands) in C57Bl/6 mice treated with the 14C-labelled analogues [14C]2,6-difluorobenzonitrile ([14C]DFBN) and [14C]2,6-difluorobenzamide ([14C]DFBA). Therefore the toxicity of DFBN, DFBA and of some structurally related compounds including benzonitrile (BN) and the herbicides bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and ioxynil (3,5-diiodo-4-hydroxybenzonitrile) in the mouse olfactory mucosa was examined. No histopathological changes in the olfactory mucosa or in the liver were observed following a single ip dose of any of these compounds [0.145 mmol/kg (all compounds); 0.58 mmol/kg (DFBN, DFBA and BN)]. Also in mice treated with the glutathione-depleting agent phorone, none of these compounds induced any histopathological changes in the olfactory mucosa. The covalent binding of [14C]DFBN in the olfactory mucosa was 16 times lower than an equimolar toxic dose of [14C]dichlobenil, suggesting a low rate of metabolic activation of DFBN in the olfactory mucosa or a low reactivity of the DFBN metabolites formed. The results of this study thus show that single doses of DFBN, DFBA, BN, IX and BX, compounds structurally related to the potent olfactory toxicant dichlobenil, do not elicit acute toxicity in the olfactory mucosa of mice.

Animals

Affinity chromatography of lipoxygenases.

A number of aminohexyl agarose derivatives of unsaturated fatty acids have been prepared and evaluated as materials for the affinity chromatography of soybean and pea lipoxygenases. A practical method for a one-stage purification of soybean lipoxygenase-1, with a purification factor of 16, is described, using either linolenate or docosa-4,7,10,13,16,19-hexaenoate as ligands. Results show that alleged competitive inhibitors do not cause sharp elution from the affinity column, and that there is an increasing specificity of binding and sharpness of elution as the proportion of unsaturation in the ligand is increased. These results are discussed in terms of the relative importance of the types of bonding involved in enzyme-substrate binding.

Chromatography, Affinity

Preliminary clinical evaluation of the effect of small electrical currents on the healing of jaw fractures.

A clinical investigation has been carried out into the effect of small electrical currents on the healing of mandibular fractures. Electrical stimulation of fracture healing was carried out in 40 patients with a direct current of 10 or 20 microamperes delivered through a platinum electrode. An equal number of patients with similar fractures were selected as controls. Rate of repair was assessed by measuring the mobility of the fracture. Serum phosphatase and calcium were regularly measured at intervals in both groups after reduction and suggested that alkaline phosphatase activity increased in the stimulated group. The repair process was enhanced in the electrically stimulated fractures compared to the controls in the first 10-14 days after reduction.

Alkaline Phosphatase

Bone mineral and surface charge.

A triple association has been observed between a high negative surface charge, bone morphogenetic activity, and in vitro recalcificaiton in implants of demineralized bone matrix. Proplast fills with bony tissue when implanted in the body and shows the same triple association. The higher the negative surface charge, the greater is the mass of new bone induced and the higher degree of mineralization when placed in a calcifying solution in vitro. Further investigations are necessary to determine whether in implants of demineralized bone, a high negative surface charge may cause the formation of discrete calcium deposits or whether it triggers the invading primitive cells to differnetiate and produce bone, or both.

Animals

Some factors affecting bone formation: a review.

Two separate methods exist at present to induce new bone formation. One utilises the implantation of specific materials, which may be of biological or non-biological origin. The other is based on the finding that bony tissue responds to very small electrical currents by stimulating osteogenesis at the negative electrode. This article discusses these methods in detail.

Animals

Bone morphogenesis and surface charge.

The electrophoretic mobility of variously treated bone specimens, with and without bone morphogenetic activity, has been measured in physiological solutions. The Bone Morphogenetic Principle appears to be associated with a minimum negative surface charge on the implant that corresponds to that of normal undemineralized cortical bone in saline. Demineralization of cortical bone in 0.6 N HCI at 2 degrees consistently increases the bone negative surface charge, and biologically produces an implant with morphogenetic activity. It is suggested that through the mediation of the positively charges ionic layer surrounding the negative implant that the negatively charged mesenchymal cell is able to reside in very close contact with the surfaces of the implant. The binding force can be expected to be directly proportional to the degree of negativity of the implant. However, implants with a positive zeta potentaial will be surrounded by ions with a net negative charge so discouraging the stable positioning of mesenchymal cells in close contact with the implant. The negative surface charge corresponding to that of untreated cortical bone is apparently borderline in permitting such a close contact for a sufficiently long period of time for differentiation to follow.

Bone Development