Burden of Silicosis among stone crushing workers in India.

BACKGROUND: In North India, the mining industry is disorganized and profit-driven. It predisposes its workers towards the development of silicosis. Haryana, a major North Indian state, has developed a compensation-rehabilitation policy for mining workers. AIMS: This study is the review of the policy's functioning and limitation from the first 4 years of implementation. METHODS: The labour department does surveillance of workers in the mining industry. All suspected cases of silicosis are evaluated by a multidisciplinary team. Based on the final diagnosis, the compensation is decided. RESULTS: Nearly 5000 workers were screened, and 729 appeared before the medical board. Of these 729, 465 were having silicosis, and their data are presented here (data of 7 patients were missing). All workers were males. The mean age was 44.54 ± 9.6 years, and the mean exposure (work experience) was 17.25 ± 6.7 years. Most of the workers were between the age of 40 and 50 years and had exposure for 10-20 years. Chest radiography examination showed that progressive massive fibrosis (large size type C opacities) was the most common type of presentation (23%). Smaller opacities (p, q, r and s, t, u) were combined for further analysis, given their similar prognostic significance. It was found that age and experience both had a linear and significant correlation with the severity of lung involvement. CONCLUSIONS: Nearly a quarter of subjects were suffering from the worst type of lung involvement at screening itself. The policy has laid a foundation for the welfare of workers, but there is still a long way to go.

In vitro evaluation of combination of polyenes with EDTA against Aspergillus spp. by different methods (FICI and CI Model).

AIMS: We investigated in vitro activity of polyene drugs (amphotericin B, Amp B; and nystatin, NYS;) in combination with ethylene diamine tetra acetic acid (EDTA) against 8 pathogenic isolates of Aspergillus spp. METHODS AND RESULTS: The intensity of the drug interactions was assessed using Fractional Inhibitory Concentration Index (FICI) model and Combination Index (CI) model. The interactions were further confirmed by time-kill curve study. The best combination ratio was subjected for toxicity analysis by MTT and haemolytic assay. A significant synergy was found between each of two polyenes with EDTA against Aspergillus fumigatus and Aspergillus flavus at one ratio four. The FICI ranged from 0·29 to 0·38 against A. fumigatus and A. flavus. The FICI value ranged from 0·78 to 1·26 showed no interaction against Aspergillus niger. The CI value (0·21-0·30) and time-kill curve analysis also confirmed synergistic interaction. Antagonism was not detected. There was reduction in toxicity of Amp B and NYS when used with EDTA. CONCLUSIONS: Subsequently, the chelating agent (EDTA) can be used in combination with Amp B and NYS with increased antifungal potential and reduced toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: To emphasize new development in antifungal drug discovery, combination therapy can be used as a tool box to expand drug development.

Inhibition of conidiophore development in Aspergillus fumigatus by an Escherichia coli DH5α strain, a promising antifungal candidate against aspergillosis.

The opportunistic human pathogen Aspergillus fumigatus produces a massive number of asexual spores (conidia) as the primary means of dispersal, survival, genome protection and infection of hosts. In this report, we investigated secretory and cytosolic proteins of non-pathogenic bacterial species (mostly belonging to human microbiome) for antifungal potential against A. fumigatus, A. flavus and A. niger. Our preliminary results revealed that cytosolic proteins of E. coli DH5α were most active and the less toxic against various pathogenic isolates of A. fumigatus (the major pathogenic species), depicting a minimum inhibitory concentration (MIC) of 62.50 µg/mL, 62.50 µg/mL and 12.50 µg/disc using microbroth dilution assay (MDA), percentage spore germination inhibition assay (PSGI) and disc diffusion assay (DDA), respectively. E. coli protein was non-toxic against human erythrocytes at doses up to 1000 µg/mL as compared to standard drug, amphotericin B which lysed 100% of erythrocytes at a concentration of 37.50 µg/mL. Time kill analysis proved it to be fungicidal in a concentration and time-dependent manner. Scanning electron microscopic studies (SEM) were carried out to prevail what kind of damage it causes to A. fumigatus. SEM results reported that conidiophore (structures forming conidia) development was halted as a major consequence, reducing the number of conidiophores to insignificant values as well as alteration in their morphological attributes. This feature may contribute to the development of new prevention strategies against Aspergillus infections. Hyphal atrophy was also observed, evidenced by shrinking and flattening of hyphal walls and reduced, abrupt hyphal branching. Such actions may effectively reduce the invasive ability of Aspergillus as well as it can sterilize the fungal burden by obstructing the conidiation pathway of A. fumigatus. Hence, E. coli DH5α, being a commensal species, can lead to the development of antifungal molecule with novel targets in fungal metabolism, which will help in combating the antifungal resistance and toxicity associated with current therapy.