Therapeutic and immunomodulatory activities of short-course treatment of murine visceral leishmaniasis with KALSOME™10, a new liposomal amphotericin B

Visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent, East Africa and South America. Since the conventional antileishmanial drugs have many limitations we evaluated a new ergosterol rich liposomal amphotericin B formulation, KALSOME™10 for its leishmanicidal efficacy, tolerability and immunomodulatory activity. Normal healthy mice were treated with 3.5 mg/kg single and 7.5 mg/kg single and double doses ofKALSOME™10. Liver and kidney function tests were performed fourteen days after treatment. Next, normal mice were infected with Leishmania donovani amastigotes. Two months post infection they were treated with the above mentioned doses of KALSOME™10 and sacrificed one month after treatment for estimation of parasite burden in the liver and spleen by Limiting Dilution Assay. Leishmanial antigen stimulated splenocyte culture supernatants were collected for cytokine detection through ELISA. Flow cytometric studies were performed on normal animals treated with KALSOME™10, Amphotericin B (AmB) and AmBiosome to compare their immunomodulatory activities. The drug was found to induce no hepato- or nephrotoxicities at the studied doses. Moreover, at all doses, it led to significant reduction in parasite burden in two month infected BALB/c mice, with 7.5 mg/kg double dose resulting in almost complete clearance of parasites from both liver and spleen. Interestingly, the drug at 7.5 mg/kg double dose could almost completely inhibit the secretion of disease promoting cytokines, IL-10 and TGFβ, and significantly elevate the levels of IFNγ and IL-12, cytokines required for control of the disease. Mice treated with KALSOME™10 showed elevated levels of IFNγ and suppressed IL-10 secretion from both CD4+ and CD8+ subsets of T cells, as well as from culture supernatants of splenocytes, compared to that of normal, AmB and AmBisome treated animal Treatment of infected mice with 7.5 mg/kg double dose of KALSOME™10 was safe and effective in clearing the parasites from the sites of infection. The drug maintains the inherent immunomodulatory activities of AmB by effectively suppressing disease promoting cytokines IL-10 and TGFβ, thereby boosting IL-12 and IFNγ levels. This emphasizes KALSOME™10 as a promising drug alternative for lifelong protection from VL

Appraisal of Noise Level Dissemination Surrounding Mining and Industrial Areas of Keonjhar, Odisha: a Comprehensive Approach Using Noise Mapping

Noise mapping is a well-established practice among the European nations, and it has been follow for almost two decades. Recently, as per guidelines of the Directorate General of Mines Safety (DGMS), India, noise mapping has been made mandatory in the mining expanses. This study is an effort to map the noise levels in nearby areas of mines in the northern Keonjhar district. The motive of this study is to quantify the existing A-weighted time-average sound level (LAeq, T) in the study area to probe its effects on the human dwellings and noise sensitive areas with the probability of future development of the mines, roads, and industrial and commercial zone. The LAeq, T was measured at 39 identified locations, including industrial, commercial, residential, and sensitive zones, 15 open cast mines, 3 major highways, and 3 haulage roads. With the utilisation of Predictor LimA Software and other GIS tools, the worked out data is mapped and noise contours are developed for the visualisation and identification of the extent and distribution of sound levels across the study area. This investigation discloses that the present noise level at 60% of the locations in silence and residential zone exposed to significantly high noise levels surpasses the prescribed limit of Central Pollution Control Board (CPCB), India. The observed day and night time LAeq, T level of both zones ranged between 43.2–62.2 dB(A) and 30.5–53.4 dB(A), respectively, whereas, the average Ldn values vary between 32.7 and 51.2 dB(A). The extensive mobility of heavy vehicles adjoining the sensitive areas and a nearby plethora of open cast mines is the leading cause of exceeded noise levels. The study divulges that the delicate establishments like schools and hospitals are susceptible to high noise levels throughout the day and night. A correlation between observed and software predicted values gives R2 of 0.605 for Ld, 0.217 for Ln, and 0.524 for Ldn. Finally, the mitigation measure is proposed and demonstrated using a contour map showing a significant reduction in the noise levels by 0–5.3 dB(A)

Appraisal of Noise Level Dissemination Surrounding Mining and Industrial Areas of Keonjhar, Odisha: a Comprehensive Approach Using Noise Mapping

Noise mapping is a well-established practice among the European nations, and it has been follow for almost two decades. Recently, as per guidelines of the Directorate General of Mines Safety (DGMS), India, noise mapping has been made mandatory in the mining expanses. This study is an effort to map the noise levels in nearby areas of mines in the northern Keonjhar district. The motive of this study is to quantify the existing A-weighted time-average sound level (LAeq, T) in the study area to probe its effects on the human dwellings and noise sensitive areas with the probability of future development of the mines, roads, and industrial and commercial zone. The LAeq, T was measured at 39 identified locations, including industrial, commercial, residential, and sensitive zones, 15 open cast mines, 3 major highways, and 3 haulage roads. With the utilisation of Predictor LimA Software and other GIS tools, the worked out data is mapped and noise contours are developed for the visualisation and identification of the extent and distribution of sound levels across the study area. This investigation discloses that the present noise level at 60% of the locations in silence and residential zone exposed to significantly high noise levels surpasses the prescribed limit of Central Pollution Control Board (CPCB), India. The observed day and night time LAeq, T level of both zones ranged between 43.2–62.2 dB(A) and 30.5–53.4 dB(A), respectively, whereas, the average Ldn values vary between 32.7 and 51.2 dB(A). The extensive mobility of heavy vehicles adjoining the sensitive areas and a nearby plethora of open cast mines is the leading cause of exceeded noise levels. The study divulges that the delicate establishments like schools and hospitals are susceptible to high noise levels throughout the day and night. A correlation between observed and software predicted values gives R2 of 0.605 for Ld, 0.217 for Ln, and 0.524 for Ldn. Finally, the mitigation measure is proposed and demonstrated using a contour map showing a significant reduction in the noise levels by 0–5.3 dB(A)