Phenolase inhibitors.
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Biomedical subjects
Publications and source records attributed to K Prabhakaran.
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Previous results had shown that the human leprosy bacilli possess a phenoloxidase, which, when compared with the enzyme from mammalian and plant sources, seemed unique in the range of substrates utilized and in the nature of the products formed. The effect of several inhibitors on the enzyme in Mycobacterium leprae was tested. Compounds which bind copper were found to be more effective than substrate analogues. Diethyldithiocarbamate penetrated the bacillus and completely suppressed its phenolase activity. Diasone (a derivative of diaminodiphenylsulfone used in the treatment of leprosy) proved to be a potent inhibitor of phenoloxidase of mammalian and plant origin. However, it was less efficient in the case of M. leprae. A biochemical peculiarity of M. leprae was observed in its ability to metabolize mimosine and penicillamine. These compounds produced total inhibition of tyrosinase in melanoma extract and of mushroom tyrosinase. Nontoxic inhibitors of phenoloxidase in the leprosy bacilli may be of value in developing a rational approach to chemotherapy of the disease.
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Experiments were conducted on the substrate specificity of phenoloxidase in Mycobacterium leprae, by using various phenolic compounds. Comparative studies were carried out with the enzyme from mammalian and plant sources. The phenolase of M. leprae was found to be similar to the enzyme of plant origin in oxidizing a variety of substrates; it was different from the mammalian enzyme, which has a limited substrate specificity. The findings confirmed that phenoloxidase is a specific property of M. leprae and is not a result of adsorption of host-tissue enzymes. The method used in separation of bacilli from infected tissues was evaluated for its effect on the viability of the organisms. This was tested by using M. lepraemurium as a model. The preparative procedure was found to have no adverse effect on the ability of the organisms to multiply in the mouse foot-pad. Several inhibitors of phenoloxidase have been tested-both substrate analogues and compounds which bind copper in the enzyme. Substances binding copper were found to be more effective. Since phenolase has been found to be a characteristic metabolic activity in M. leprae, nontoxic inhibitors of the enzyme offer possibilities of developing a rational chemotherapy of leprosy.
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The Mitrofanoff procedure is a versatile technique that is successfully used in achieving continent urinary diversion for a wide variety of urological conditions. Appendix and usable segment of ureter are commonly employed for this purpose and provide desirable results. This communication describes a teenage girl with lumbosacral agenesis and neurogenic bladder in whom Meckel's diverticulum was successfully used for the Mitrofanoff procedure.
My first contact with Dr. Dharmendra was through correspondence. While working for Ph.D., I wrote to him that a section in his book "Notes on Leprosy" was ambiguous. Instead of ignoring the letter, he replied, agreeing to clarify it in the revised edition. I went to work at Carville at the invitation of Dr. Kirchheimer, who had seen my Ph.D. thesis. Dr. Dharmendra visited Carville to receive the Damien-Dutton award and stayed there for a few days. Carville is an isolated place with no public transportation. I used to take him for afternoon drives to the countryside around Carville. He published some of our papers in Leprosy in India and later in Indian Journal of Leprosy. He was very prompt in acknowledging receipt of manuscripts and suggesting any changes to be made. He also reprinted in the Journal several of our papers published elsewhere, and also a lecture I gave at a meeting of the Japanese Leprosy Association. During one of my visits to India, Dr. M. C. Vaidya had arranged a talk by me at the All India Institute of Medical Sciences, New Delhi. At the invitation of Dr. Dharmendra, I visited him in his home. We used to exchange new year cards and letters. He wrote to me about his eye infection and consequent loss of sight in one eye. He asked me to write an editorial for an issue of Indian Journal of Leprosy (January 1989). The last time I met him was during the International Leprosy Congress held in New Delhi.
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Very little information is available on the basic biology of Mycobacterium leprae. It is not known why the organism fails to grow in bacteriological media or in cell cultures and why it has an unusual predilection for certain tissues in the human host where cells derived from the neural crest occur (e.g. skin, peripheral nerves adrenal medulla). Biochemical studies have revealed that M. Leprae contains an unusual form of the enzyme diphenoloxidase which has not been detected in other mycobacteria. The presence of a specific glutamic acid decarboxylase in the organism has been demonstrated. Although a few enzymes of glycolysis and tricarboxylic acid cycle have been investigated, nothing characteristic of the bacterium has been discovered, and how M. leprae derives energy for its survival and proliferation still remains obscure.
The effects of acute auditory stress on certain biochemical parameters like blood corticosterone, total cholesterol, triglyceride, Serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) were studied in albino rats. A significant increase was observed in the blood level of corticosterone, total cholesterol, SGOT and SGPT while a marked reduction was noticed in the Sr. triglyceride level. These data indicate that noise could be a potent stressor and cause disturbances in the biochemical parameters of the body. It is presumed that most of the effects are indirect, being manifested through the activation of autonomic nervous system which liberates catecholamines and hypothalamo pituitary adrenal axis responsible for the liberation of corticosteroids.
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