RESUMO
This study reports the use of a purified form of the enzyme collagenase (Nucleolysin) to effect dissolution of the normal nucleus pulposus in a series of dogs and monkeys. A consistent dissolution effect has been observed. The toxicity of the enzyme to surrounding local tissues has been studied in the same species with an indication of safety in all areas other than intrathecal administration. A margin of safety in intrathecal administration between the effective dose and toxic dose has been suggested in the monkey. Mice LD50 studies and systemic toxicity studies in dogs show a satisfactory margin of safety for this enzyme. Guinea pig studies show no significant antigenicity.
Assuntos
Disco Intervertebral/efeitos dos fármacos , Colagenase Microbiana/toxicidade , Adulto , Animais , Dor nas Costas/enzimologia , Cães , Haplorrinos , Humanos , Injeções/métodos , Injeções Espinhais/efeitos adversos , Disco Intervertebral/enzimologia , Macaca fascicularis , Macaca mulatta , Colagenase Microbiana/administração & dosagem , Colagenase Microbiana/farmacologiaRESUMO
A new subclass of mouse IgG for which we propose the name IgG3 has been shown to have a mol wt of 150,000 consistent with an L(2)H(2) structure, and is present in normal mouse serum at a concentration of 0.1-0.2 mg/ml. Its molecular weight, low carbohydrate content, glycopeptide analysis, and C-terminal analysis are all typical of the IgG class. The intact protein had a strong tendency to form noncovalent aggregates with itself which were dissociable in acid. Upon papain digestion an Fab fragment of 47,000 mole wt was generated along with an Fc fragment which was insoluble at neutral pH. As for its biology, the protein did not fix complement, was not cytophilic for gammaG2 receptor sites on macrophages, and did not show passive cutaneous anaphylaxis. It was very efficiently transported across the placenta so that its concentration in the newborn was twice that in the serum of the mother, compared to the concentration of IgG1 and IgG2 proteins which were only present at one-third the concentration of that found in the serum of the mother. The Fc fragment of this protein reacted with and was solubilized by the staphylococcal A protein which also precipitated the intact immunoglobulin. In addition, the myeloma protein which was the prototype for this gammaG subclass exhibited binding activity for levan which was localized to the Fab fragment.
