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Biomedical subjects

N H Antia

Publications and source records attributed to N H Antia.

At least 19 recordsLinked to original sources

Schwann cell extracellular matrix protein production is modulated by Mycobacterium leprae and macrophage secretory products.

Extracellular matrix (ECM) protein deposition is an important feature of leprous nerves, where Schwann cells (SCs) and macrophages are the main hosts for Mycobacterium leprae. Since, SCs are involved in the synthesis of ECM proteins and its production is regulated by macrophage secretory factors, the present study aimed to determine in vitro, the effect of M. leprae infection and macrophage secretory products on secretion of ECM proteins by SCs in two strains of mice, Swiss White (SW) and C57BL/6, that are known to differ in their nerve pathology and macrophage functions in response to infection. Following six days of M. leprae infection, SCs from SW mice responded with increased secretion of 14C-leucine radiolabelled proteins and a concomitant increase in laminin and collagens type I, III and IV, as determined by enzyme-linked immunosorbent assay. In contrast infected C57BL/6 SCs responded with decreased secretion of total proteins and fibronectin. Exposure of SCs to macrophage conditioned medium resulted in decreased ECM protein secretion in both strains of mice. This decrease was a function of protein breakdown by macrophage derived proteases and also active regulation by macrophage secreted cytokines. A similar effect of M. leprae and macrophage secretory products on SC metabolism in leprous nerves would have major ramifications on damage and repair activities. In addition ECM proteins would also influence the composition of the infiltrating cell population in lepromatous and tuberculoid nerves.

Animals

Expression of mycobacterial antigens on murine dissociated Schwann cells infected with Mycobacterium leprae.

Mycobacterial antigens were detected in a cell surface ELISA on murine dissociated Schwann cells infected with Mycobacterium leprae. The time kinetics of expression and its refractoriness to modulation with monensin suggests that the antigens are likely to be integrated into the membrane during bacterial entry. This may be partially responsible for the defective Schwann cell functions leading to subsequent peripheral nerve damage.

Animals

Higher incidence of viable Mycobacterium leprae within the nerve as compared to skin among multibacillary leprosy patients released from multidrug therapy.

As identified by a significant growth in the footpads of immunosuppressed mice, the incidence of viable bacteria in a group of 26 multibacillary (BL-LL) patients released from multidrug (MDT) treatment was found to be two times more in the nerves (46%) as compared to skin (23%). Evidently there was a positive correlation between the overall bacterial load and the incidence of viable organisms. Bacterial growth was also observed in two out of five cases where neither the skin nor the nerve homogenate had shown any presence of acid-fast bacilli. Histopathology of biopsies, skin as well as nerve, including those having viable bacteria did not show any features of active disease.

Adolescent

Nerve growth factor production and expression of p75 by Schwann cells and neurofibroblasts in response to M. leprae infection and macrophage secretory products.

This study describes the changes occurring in vitro in nerve growth factor (NGF) production and expression of p75 by murine Schwann cells and neurofibroblasts, following infection with Mycobacterium leprae and in the presence of macrophage secretory products, using a semiquantitative ELISA. These parameters are compared in two strains of mice, Swiss White (SW) and C57B1/6, as they differ in their response to M. leprae infection; C57B1/6 is the 'resistant' strain. On infection, NGF levels remained unaltered in Schwann cells from both strains, while fibroblasts from C57B1/6 strain showed an increase in NGF production. Expression of p75 by Schwann cells was decreased on infection in both strains of mice. In vivo, this opposing effect of infection on NGF production and p75 expression by Schwann cells and neurofibroblasts may result in suboptimal amounts of NGF reaching neurons of the affected leprous nerves. Macrophage secretory products suppressed the production of NGF by infected neurofibroblasts from SW strain mice and the expression of p75 in Schwann cells from both strains. These results indicate that macrophages do not assist in nerve repair in leprosy and the differences in response to macrophage secretory products in the two strains suggests that different mechanisms of nerve repair operate in SW and C57B1/6 mice and presumably in lepromatous and tuberculoid patients.

Animals

Primary resistance to single and multiple drugs in leprosy--a mouse footpad study.

Skin biopsy homogenates obtained from three cases of lepromatous leprosy with no prior history of antileprosy treatment were tested in the mouse footpad for the sensitivity of Mycobacterium leprae to multiple drugs. One of the inocula was sensitive to all the three drugs tested using the highest concentration each of DDS 0.01 g%, RFP 0.03 g% and CLF 0.01 g%. The 2nd inocula showed growth in the presence of 0.01 g% DDS only. While the 3rd inocula (Pt. KU) tested resistant to all the three drugs in the first, i.e. man to mouse, as well as in the second passage, i.e. mouse to mouse.

Adult

Views on the sustenance of resistant Mycobacterium tuberculosis in the environment.

Microbial resistance to conventional as well as newly introduced drugs is a hallmark feature of several infectious diseases, notably tuberculosis. It is hypothesized that the greater the selective pressure exerted by increasingly potent drugs, the more rapidly is an organism able to adapt to a drug-containing environment. The roles of drug-containing environments, and the immunological status of the host and bacterial molecular mechanisms of development of drug resistance to Mycobacterium tuberculosis have been examined and examples cited for implementation of modified drug regimens in tuberculosis-control programmes. The views expressed, albeit restricted to Mycobacterium tuberculosis, encourage consideration of drug regimens on a disease evolution basis as well as understanding of the natural rules that govern development and sustenance of drug resistance in the microbial world.

Antitubercular Agents

Vascular surgery of the posterior tibial compartment for plantar ulceration in leprosy.

Traditional surgical decompression of the posterior tibial nerve yields equivocal results. The authors postulate that the posterior tibial artery is the most compromised structure in the neurovascular compartment and that the best surgical results in healing of plantar ulcers are achieved by the rechannelling of the blood flow in the posterior tibial artery during posterior tibial neurovascular compartment surgery. This procedure has been of benefit to patients with plantar ulcers of greater than 7-10 years' duration in whom all other modes of healing had failed. It has been undertaken as an outpatient procedure under local anaesthesia, supported by postoperative vasodilator drugs. The use of tourniquet, antibiotics and surgical interference with the ulcer per se was eschewed. A report of 156 patients is presented with follow-up of up to 6 years for the earlier cases.

Follow-Up Studies

Keyhole surgery.

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Developing Countries

Immunohistological localization of mycobacterial antigens within the peripheral nerves of treated leprosy patients and their significance to nerve damage in leprosy.

The presence and distribution of Mycobacterium leprae-specific and cross-reacting antigens within the peripheral nerves of multidrug-treated patients with leprosy was investigated to gain a better understanding of the mechanism of nerve damage and the effect of multidrug therapy (MDT) on it. There was no specific qualitative difference in the type of antigens in the leprosy spectrum. However, our results indicate that there may be differential handling of antigens by the macrophages as compared to Schwann cells. This could play a key role in the pathogenesis of the disease. Multidrug treatment is effective in arresting the progression of the disease process as well as in reducing the viable bacterial load, both in borderline lepromatous and lepromatous (MB) and borderline tuberculoid and tuberculoid (PB) cases. However, the presence of M. leprae antigens in all the multidrug-treated MB nerve lesions and 87% of PB nerve lesions suggest that the antigens persist for a prolonged period. Hence, the risk of immunological reaction and antigen-associated silent nerve damage may continue even after majority of M. leprae were killed. The findings give further support to the view that most of the nerve damage is due to bacterial antigens.

Adolescent