Three independent assay methods were used to investigate the activities of antimicrobial peptides (human and rabbit defensins and protegrin from porcine leukocytes) against Mycobacterium tuberculosis in vitro. M. tuberculosis H37Ra was cultured in the presence of human neutrophil peptide 1, synthetic rabbit neutrophil peptide 1, or porcine protegrin 1 at 37؇C for 6 to 48 h, and antimycobacterial activity was measured by CFU assay. These peptides at a concentration of 50 g/ml showed significant antibacterial effects on M. tuberculosis after 24 and 48 h of incubation (85.9 to 97.5% at 24 h and 91.6 to 99.4% at 48 h). A radiometric method and a radial diffusion assay confirmed these observations. Antibacterial activity against M. tuberculosis was independent of calcium (1.0 mM) or magnesium (1.0 mM) and not inhibited by sodium chloride (100 mM). The optimal pH for antibacterial activity against M. tuberculosis was greater than 4.0. Three clinical isolates of M. tuberculosis were also studied, and these peptides showed 86.3 to 99.0% reduction in CFU of these organisms. Morphological studies using scanning electron microscopy showed that defensins caused lesions on the surface of H37Ra. These observations suggest that antimicrobial peptides such as defensins and protegrins may represent an important component of the host defense mechanism against M. tuberculosis and offer a potential new approach to therapy. Mycobacterium tuberculosis is still a leading cause of worldwide disease morbidity and is responsible for more deaths each year than any other single pathogen (32). In addition, the AIDS epidemic has exacerbated the problem. Interest in tuberculosis has been rekindled by the recent resurgence of cases both in the United States and worldwide. The increasing number of multidrug-resistant M. tuberculosis isolates that can be exceedingly difficult and expensive to treat is of particular concern (17). The combination of the increased frequency of infection due to M. tuberculosis and the increase in multidrugresistant M. tuberculosis isolates in patients with AIDS has raised a great deal of concern across the country. Defensins are endogenous antimicrobial peptides (AMPs) that contain 29 to 35 amino acid residues (27). These peptides were first recognized in rabbit and guinea pig neutrophils and in rabbit alveolar macrophages as ''lysosomal cationic proteins'' with antimicrobial properties (42, 43). Much earlier, calf thymus peptide (7) and lysozyme (34) were shown to inhibit the growth of pathogenic mycobacteria. More than 15 mammalian defensins derived from five species have been purified and sequenced, and human neutrophils were found to contain four defensin peptides (15). Defensins have been shown to possess antifungal (10), antibacterial (13, 16, 37), and antiviral (4) activities in vitro. We have previously demonstrated that the defensins human neutrophil peptide 1 (HNP-1), HNP-2, and HNP-3 have activity against Mycobacterium avium-Mycobacterium intracellulare (33). More recently, we have synthesized rabbit neutr...
Turmix is beneficial and effective in reducing burning sensation in early OSMF patients.
A 60-year-old male presented with a complaint of a slow growing, solitary, midline swelling in the region of chin, which had a duration of 5 years. There was a history of removal of lower front teeth, followed by trauma to the chin and discolouration of the lower front teeth. A single, oval, sub mental lymph node was palpable and it was nontender, firm in consistency and freely movable. Extra oral examination revealed obliteration of the mentolabial sulcus and slight fullness of the chin region [Table/ Fig-1]. It had extended superiorly from vermillion border of the upper lip, inferiorly obliterated the mentolabial sulcus and mediolaterally 2 cm from the midline, i.e., upto the corner of the mouth. Skin over the swelling and skin surrounding the swelling appeared to be normal, with no local rise in temperature. The swelling was non-tender and no visible or palpable pulsations were encountered. Intraoral examination revealed a solitary, well-defined roughly oval swelling of size 5×4 cm in the anterior region of the mandible extending from the mesial aspect of 33 to the mesial aspect of 44, inferiorly obliterating the vestibule and superiorly upto the level of occlusion above the alveolar crest [Table/ Fig-2]. The mucosa over the swelling and which surrounded the swelling appeared to be normal, with smooth surface texture. The swelling was non-tender, non-pulsatile and it showed cystic consistency. Teeth 31, 32, 41,42 and 43 were missing [Table/ Fig-3]. Bilateral Angle's class I molar relationship was observed and 44 appeared to be displaced mesioligullay. Although stains and calculi were present, there was no evidence of active periodontitis. 2 ml of straw coloured serosanguinous fluid was obtained upon aspiration and it showed the presence of cholesterol crystals. Radiograph of the mandibular anterior region showed a mixed radiolucent radiopaque lesion in the region of missing 31,32,41,42 and 43, extended from the mesial aspect of 33 to the mesial aspect of 44 [Table /Fig-4]. The lesion consisted of an oval radiolucency that was surrounded by a thin cortical line near the inferior aspect of the lesion with two discrete areas of calcifications within the radiolucency [Table /Fig-5]. The radiodensity of the calcifications was not similar to that of either enamel or dentin. Routine laboratory findings were within normal limits. Based on the above said findings, a provisional diagnosis of residual cyst with calcifications and differential diagnoses of other mixed radiolucent radiopaque lesions like traumatic bone cyst, focal cement-osseous dysplasia and periapical cement-osseous dysplasia (PCOD) were considered. Although, the common presentation patterns of these lesions, like location, site, gender, age distributions and radiographic appearances were specific, a histopathologic examination was done to establish a definitive diagnosis.Patient was referred to the Department of Oral and Maxillofacial Surgery, where an incisional biopsy was performed after obtaining ABSTRACTA residual cyst, as the name implies, is a r...
We have recently demonstrated that the calmodulin antagonist trifluoperazine has antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv susceptible and resistant to isoniazid. It is now shown that trifluoperazine at a concentration of 50 micrograms ml-1 when added to the cells along with the labelled precursors inhibited the incorporation of [14C]acetate into lipids (63%) and uptake of [14C]glycine (74%) and [3H]thymidine (52%) by whole cells of M. tuberculosis H37Rv by 6 h of exposure. After 48 h, the inhibition was 87%, 97% and 74%, respectively. However, when the drug was added to cells taking up and metabolizing the labelled precursors at a later point (3 h for [14C]acetate and [3H]thymidine and 12 h for [14C]glycine) it inhibited completely the uptake of all the precursors, at least up to 24 h. The onset of inhibitory action was very rapid, i.e. 3 h. It is suggested that trifluoperazine has multiple sites of action and acts probably by affecting the synthesis of lipids, proteins and DNA.
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