Pyrazinamide is a commonly used first-line antitubercular drug. Gastric-related adverse drug reactions are common with pyrazinamide. Dermatological manifestations due to pyrazinamide are rare. This study aimed find out the dermatological manifestations/adverse drug reaction (ADR) due to pyrazinamide. We reported a case of maculopapular rash caused by pyrazinamide in a patient on antituberculosis treatment using structured questionnaires. The patient developed maculopapular rashes on receiving combination antituberculosis treatment. The rashes disappeared after stopping the suspected drug. The patient was rechallenged with pyrazinamide, which led to reappearance of a similar type of rash. The causality, preventability, and severity were assessed using the Naranjo algorithm and Hartwig scale. Since pyrazinamide is a commonly used drug in tuberculosis and which is a common infectious disease in developing countries, with the similar reports, we can predict early case detection and can prevent the occurrence of similar reactions in future.
Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity.
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