Spinigerin induces apoptotic like cell death in a caspase independent manner in Leishmania donovani.

Antimicrobial peptides (AMPs) are multifunctional components of the innate immune system. Chemotherapeutic agents used for treatment of visceral leishmaniasis (VL) are now threatened due to the emergence of acquired drug resistance and toxicity. AMPs are attractive alternative to conventional pharmaceuticals. In this study, first time we explored the antileishmanial activity of spinigerin originally derived from Pseudacanthotermes spiniger. Leishmania donovani promastigotes present apoptosis-like cell death upon exposure to spinigerin (IC50, 150 µM). The infection rate was reduced by 20% upon exposure to 150 µM spinigerin but no cytotoxicity on host macrophages was observed. Elevation of intracellular ROS level and down-regulation of two ROS detoxifying enzymes, ascorbate peroxidase (APx) and trypanothione reductase (TR) suggested essential role of ROS machinery during spinigerin mediated cell death. About 97% cell population was found to be Annexin-V positive; 44% cells being highly Annexin-V positive. Moreover, we observed morphological changes like cell rounding, nuclear condensation, oligonucleosomal DNA degradation and TUNEL positive cells without loss of membrane integrity upon spinigerin exposure, suggests apoptosis-like death. Interestingly, collapse in mitochondrial membrane potential and increased level of intracellular ROS and calcium were not associated with caspase like activity. Computational analysis suggests spiningerin interacts with trypanothione reductase and thus probably interferes its function to detoxify the toxic ROS level. Therefore, spinigerin induces apoptosis-like cell death in L. donovani in a caspase-independent manner. The study elucidates the antileishmanial property of spinigerin that may be considered for future chemotherapeutic option alone or adjunct with other drug regimens for improved treatment of visceral leishmaniasis.

Qualitative and quantitative analysis of seized street drug samples and identification of source.

In this paper we describe the identification of constituents of the illicit drugs seized from different regions of eastern India by GC-MS. The constituents were identified to be heroin, acetyl morphine, morphine and acetyl codeine. Quantitative estimation of the constituents were made by GC-MS and HPTLC. In view of non-availability of the authentic samples of drugs of different origin, nothing positive can be said about the origin of illicit drug samples. The possibility of isotopic substitution, an important method for identification of source, was examined from the comparison of the intensity of different (ion) peaks 369 (heroin, m/z=369), 370, 371 and 372 using selective ion monitoring mode. No isotopic substitution in the constituents was observed. Attempts were made to identify the source of the illicit samples from heroin/acetylcodeine ratios in the way described in the literature.

A 5-year safety and efficacy evaluation with fibrel in the correction of cutaneous scars following one or two treatments.

In a multicenter clinical trial 300 patients were treated with Fibrel, 4 weeks following a negative skin test, for the correction of cutaneous scars. Fibrel treatment was restricted to one or two implants in a maximum of four scars. The scar corrections were evaluated by the physician, the patient, and also via an objective photogrammetric method. At the end of 1 year the percentage of scars with moderate, marked, or complete correction were 65, 63.3, and 85.8% according to physician, patient, and photogrammetric evaluations, respectively. A cohort of 111 patients were followed for up to 2 years and 87 patients were followed up to 5 years postimplantation. The physician and patient evaluations showed 55.1 and 50.6%, respectively, of the scars in the moderate, marked, or complete correction category at the end of 5 years with only one or two treatments. Safety evaluations included tests for antinuclear antibodies, rheumatoid factor, and presence of antibodies to Fibrel and their crossreactivity to human collagen I and III. These tests did not show any causal relationship to Fibrel treatments and the patients did not have any untoward immunologic symptoms. The data from these patients demonstrate that one or two Fibrel treatments are effective in maintaining greater than 50% correction of depressed cutaneous scars up to 5 years with negligible adverse sequelae and no untoward immunologic symptoms.