muramidase and Leprosy

Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Dapsone; Disease Models, Animal; Drug Resistance, Microbial; Foot; gamma-Globulins; Glucocorticoids; Humans; Immunosuppressive Agents; Immunotherapy; Leprosy; Mice; Muramidase; Mycobacterium leprae; Phenazines; Sulfonamides; Sulfones; Thalidomide; Thioacetazone

To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile.. 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits.. In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses.. In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile.. CTRI/2013/07/003802.

Topics: Administration, Topical; Adult; Aged; Conjunctiva; Double-Blind Method; Dry Eye Syndromes; Electrophoresis, Polyacrylamide Gel; Eye Infections, Bacterial; Eye Proteins; Female; Fetal Blood; Humans; Lactoferrin; Leprosy; Male; Middle Aged; Muramidase; Prospective Studies; Proteomics; Serum; Tears

Topics: Animals; Anti-Bacterial Agents; Clinical Trials as Topic; Dapsone; Disease Models, Animal; Drug Resistance, Microbial; Foot; gamma-Globulins; Glucocorticoids; Humans; Immunosuppressive Agents; Immunotherapy; Leprosy; Mice; Muramidase; Mycobacterium leprae; Phenazines; Sulfonamides; Sulfones; Thalidomide; Thioacetazone

The objective of the present study was to investigate the correlation between macrophage activity and apoptosis in the polar forms of leprosy because the immunopathological phenomena involved in these forms are still poorly understood. For this purpose, 29 skin biopsy samples obtained from patients with the polar forms of leprosy were analyzed. Macrophage activity and apoptosis were evaluated by immunohistochemistry using lysozyme, CD68, iNOS and caspase 3 as markers. The nonparametric Mann-Whitney test and Spearman's linear correlation test were used for statistical analysis. The results suggest that the apoptosis rate is under the direct influence of macrophage activity in lesions of patients with the tuberculoid form. In contrast, in lepromatous lesions other factors seem to induce programmed cell death, possibly TGF-beta. Further studies are necessary to identify additional factors involved in the immunopathogenesis of leprosy.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Biopsy; Caspase 3; Humans; Immunohistochemistry; Leprosy; Macrophages; Microscopy; Muramidase; Nitric Oxide Synthase Type II; Skin

In the defense against Mycobacterium leprae, macrophages play an essential part in the mechanism of bacterial lysis but require the presence of cytokines such as interleukin 2 and gamma interferon from lymphocytes in order to effectively kill the organisms in any number. While there have been many studies of the lymphocytes in lesions of leprosy, less attention has been given to the immunohistochemical characterization of the macrophage populations. In this study, the cutaneous lesions of 69 patients with leprosy (42 lepromatous, 5 mid-borderline, and 22 tuberculoid) were evaluated by immunohistochemistry for the expression of S100 protein, CD1a, CD68, muramidase, HLA-DR, and Factor 13a. The macrophages from lesions of polar, subpolar, and borderline lepromatous leprosy patients expressed S100 protein intensely and constantly. In contrast, the lesions of polar and subpolar tuberculoid leprosy had very few cells that were immunoreactive for S100 protein ('S100+') in the granulomas in the dermis. The macrophages in all lesions were reactive for CD68 and muramidase. In paraffin sections, macrophages of lepromatous lesions failed to stain for HLA-DR, whereas in tuberculoid lesions, they were strongly positive for HLA-DR. Three patients with histoid leprosy (relapse lesions) had lesions that were strongly positive for Factor 13a and were negative for S100 protein ('S100-'). Given the possible chemotactic and migration inhibition effects of the calcium-binding proteins of the S100 family, these data suggest a possibly important role for S100 protein in the accumulation of macrophages in lepromatous leprosy, and also reveal infection of Factor 13a + dermal dendritic cells in histoid leprosy.

Topics: Antigens, CD; Antigens, CD1; Antigens, Differentiation, Myelomonocytic; Dendritic Cells; Humans; Immunohistochemistry; Leprosy; Leprosy, Borderline; Leprosy, Lepromatous; Leprosy, Tuberculoid; Macrophages; Muramidase; S100 Proteins; Transglutaminases

Active tuberculosis (TB) and leprosy are difficult to diagnose early because there are few organisms to detect and the specific immune response does not distinguish between active and inactive disease. We developed an immunoassay for lysozyme to see whether serum lysozyme levels could be used to identify individuals with clinical leprosy or TB. The immunoassay for lysozyme proved superior to standard enzyme assays that were less sensitive and reliable. The lysozyme assay was compared with assays for antibodies to Mycobacterium tuberculosis lipoarabinomannan (LAM) and M. leprae phenolic glycolipid-1. The sera tested were from Ethiopian leprosy (paucibacillary and multibacillary) and TB patients and from healthy Ethiopian and U.S. controls. The lysozyme assay was able to detect more of the individuals with TB (sensitivity, 100% for 19 patients) or leprosy (sensitivity, 86% for 36 patients) than either antibody assay. In particular, lysozyme levels were raised in a higher proportion of the paucibacillary leprosy patients (83% of 17), for whom the antibody assays were less sensitive; the LAM IgG and the phenolic glycolipid-1 IgM levels were raised in only 62 and 44% of 16 patients, respectively. The data suggest that lysozyme measurements may be useful in the diagnosis of mycobacterial infections and other chronic infectious granulomatoses.

Topics: Antibodies, Bacterial; Antigens, Bacterial; Glycolipids; HIV Infections; Humans; Immunoassay; Leprosy; Lipopolysaccharides; Muramidase; Tuberculosis

The levels and distribution of lysozyme-positive cells and exudate were studied in leprosy lesions through the spectrum, in untreated and treated patients, in relapse and in reactions. Altogether 124 skin biopsies were examined by the immunoperoxidase technique. Monocytes, neutrophil-polymorphs and mast cells were the most conspicuous cells seen. Lysozyme proved to be a useful means of indexing renewal of these cells in the lesions. Peak numbers of monocytes were seen in lesions of active lepromatous leprosy (LL) and of tuberculoid leprosy (TT), at poles of opposite immunological performance. In TT the stimulus for recruitment was delayed hypersensitivity (DH). A decline in DH from TT towards the middle of the spectrum, mid-borderline, was accompanied by a fall in monocyte level. Furthermore, reacting lesions due to enhanced DH also had increased numbers of monocytes. On the other hand reactions associated with immunological deterioration were similar to active lepromatous leprosy (LL) and monocyte influx was raised in response to the stimulus of free multiplication of bacilli in both cases. In TT delayed hypersensitivity acted also to promote the rapid transformation of monocytes to epithelioid and giant cells all of which were strongly positive for lysozyme. This was in contrast to much lower levels in histologically similar macrophage-epithelioid cells of BT granulomas. Lysozyme synthesis was not seen in macrophages after ingestion of M. leprae. Early foamy change was made conspicuous by lysozyme deposited in phagocytic vacuoles, but old foam cells in regressing lepromas were negative. Lysozyme bound to dead extracellular M. leprae but not to viable or intracellular organisms. Dead bacilli or immune complexes appeared to be the stimulus for neutrophil-polymorph recruitment, mainly in reactions.

Topics: Granuloma; Humans; Hypersensitivity, Delayed; Leprosy; Monocytes; Muramidase; Neutrophils; Skin

Using the immunoperoxidase staining method, tissue muramidase (lysozyme) activity was studied in 34 nerve biopsies from leprosy patients and compared to findings in the skin. In a majority of lepromatous and borderline-lepromatous leprosy patients, the enzyme was seen to form a saccular pattern within the cells; whereas a granular pattern was found at the tuberculoid end of the leprosy spectrum, as well as during reversal reactions. Indeed, the most intense enzymatic activity was found in four patients with reversal reactions. Compared to the skin, muramidase activity was found to be more intense and persisted longer in the nerves. Successful antileprosy treatment reduced the enzymatic activity in both the nerves and the skin, but more so in the skin. Schwann cells and axons did not show muramidase activity, indicating that the muramidase-positive cells are not of neuronal origin. Our results suggest that a high percentage of mononuclear cells infiltrating the peripheral nerves in leprosy are derived from blood monocytes. The function of tissue muramidase in leprosy is not yet clear. Its peculiar intracellular distribution pattern in the different forms of leprosy, however, warrants further study to elucidate its role in the pathogenesis of the disease.

Topics: Adolescent; Adult; Dapsone; Female; Humans; Leprosy; Male; Middle Aged; Muramidase; Radial Nerve; Sural Nerve

We have found that 26 of 54 (48%) untreated patients with leprosy had serum migration inhibitory activity, and that this was present in tuberculoid, borderline, and lepromatous forms of the disease. Patients with active recreational states; i.e., reversal reactions, Lucio's reaction, or erythema nodosum leprosum, were particularly apt to have this inhibitory activity. The prevalence of inhibitory activity did not vary significantly with treatment, dinitrochlorobenzene responsiveness, tuberculin responsiveness, or serum lysozyme levels.

Topics: Dapsone; Dinitrochlorobenzene; Humans; Hypersensitivity, Delayed; Leprosy; Macrophage Migration-Inhibitory Factors; Molecular Weight; Muramidase; Prednisone; Thalidomide

Lysozyme concentrations have been estimated in 47 patients with lepromatous leprosy and in 50 healthy people by a single radial immunodiffusion technique using monospecific antiserum against human lysozyme. In healthy people the mean tear lysozyme concentration was 1.34 mg/ml. In leprosy patients the mean tear lysozyme concentration was 1.0 mg/ml. Anterior uveitis per se did not appear to alter the lysozyme concentration in tears.

Topics: Female; Humans; Leprosy; Male; Muramidase; Tears

The muramidase content of reactive cells in the lesions of human foreign body reactions, lepromatous and tuberculoid leprosy, sarcoidosis, tuberculosis, and granulomatous hepatitis, was assessed using specific anti-human muramidase antiserum and a peroxidase-anti-peroxidase marker system. Epithelioid and giant cells in sarcoidosis, tuberculosis, granulomatous hepatitis, and tuberculoid leprosy all showed the presence of muramidase in their cytoplasm. The muramidase content of macrophages in foreign body reactions and lepromatous leprosy varied and most multinucleate cells in these lesions gave a negative reaction. Possibly varying rates of muramidase secretion may account for these differences.

Topics: Cytoplasm; Foreign-Body Reaction; Hepatitis; Humans; Leprosy; Lung; Lymph Nodes; Muramidase; Sarcoidosis; Tuberculosis

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Kenya; Leprosy; Male; Middle Aged; Muramidase; Neoplasms

Serum lysozyme was assessed in 43 healthy subjects and 183 leprosy patients. Significantly elevated level of lysozyme was observed in sera of leprosy patients as compared to normal individuals. The enzyme levels in leprosy of different types showed elevations in following order, Erythema Nodosum Leprosum (ENL) greater than Lepromatous greater than Borderline greater than Tuberculoid. Enzyme levels in patients with inactive stage were lower than in untreated patients. The serum lysozyme level correlated well with the activity disease in leprosy--clinically and bacteriologically. Thus the estimation of serum lysozyme can be used as one of the parameters of activity of the disease.

Topics: Adolescent; Adult; Aged; Dapsone; Erythema Nodosum; Female; Humans; Leprosy; Male; Middle Aged; Muramidase

Topics: Animals; Armadillos; Blood Proteins; Leprosy; Muramidase; Mycobacterium Infections; Peptidyl-Dipeptidase A; Transcobalamins; Xenarthra

Serum amyloid protein (SAA) appears to be the precursor of amyloid protein AA, the non-immunoglobulin fibril protein of secondary amyloidosis. Since amyloidosis is known to occur in high frequency associated with lepromatous leprosy (LL), we have examined the SAA levels in untreated LL patients and compared them to the levels observed in patients with tuberculoid leprosy (TT) and a large number observed in healthy controls. We found that SAA is markedly elevated in LL when compared to TT and controls. No clear correlation could be established with C-reactive protein, a well-documented acute phase reactant, or serum lysozyme levels that reflect the presence of monocyte activity. This study showed that SAA levels in leprosy do not appear to be a reflection of inflammatory activity or monocyte turnover. Whether amyloidosis will be more prevalent in patients who have higher SAA levels remains to be determined.

Topics: Amyloid; C-Reactive Protein; Humans; Leprosy; Muramidase; Serum Amyloid A Protein

Lysozyme activities of skin granulomas of 24 patients in leprosy were studied. Lepra cells of all 15 lepromatous leprosy showed strong lysozyme activity in cytoplasma. In the specimens stained with lysozyme and Ziehl-Neelsen's carbolfuchsin double stain conspicuous lysozyme activity around M. leprae were observed. One borderline case was negative. Lysozyme of epithelioid cells and giant cells of 10 tuberculoid types were completely negative. These results suggest that lysozyme plays only a small role in the disposal of M. leprae in macrophages and other mechanisms than bacteriolytic function of lysozyme are responsible for the defence against these bacilli.

Topics: Humans; Leprosy; Macrophages; Muramidase; Mycobacterium leprae; Skin

Mean serum lysozyme values were found to be elevated in untreated leprosy patients. Statistically significant elevations were present in each of the three major categories of leprosy, tuberculoid, borderline, and lepromatous. Values were particularly high in patients with severe reversal reactions or Lucio's phenomenon. Prolonged sulfone therapy was associated with a fall in serum lysozyme values. With an immunoperoxidase method to localize lysozyme in leprous tissues, two distinct staining patterns were found, granular and saccular. The grandular pattern of lysozymal staining was found in epithelioid cells and in giant cells, and the intensity of staining showed a positive correlation with serum lysozyme levels. Conversely, a saccular pattern of lysozymal staining was found in lepromatous histiocytes, buth the intensity of staining was unrelated to serum lysozyme levels; the saccular structures contained dense aggregates of Mycobacterium leprae. These two patterns of staining probably represent different functional responses of monocyte-derived granuloma cells, whereas the serum levels reflect, to a varying degree, both the absolute number of such cells and the rate of secretory activity of this cell population as a whole.

Topics: Adolescent; Adult; Aged; Dapsone; Histiocytes; Humans; Leprosy; Middle Aged; Muramidase; Radiation-Protective Agents; Thalidomide

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Amino Acids; Blood Proteins; Globulins; Humans; Immunoglobulins; Leprosy; Lysosomes; Muramidase; Proteins