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

Noninvasive Diagnosis of Visceral Leishmaniasis:Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

Visceral leishmaniasis (VL), one of the most prevalent parasitic diseasesin the developing world causes serious health concerns. Post kala-azar dermal leishmaniasis (PKDL) is a skin disease which occurs after treatment as a sequel to VL. Parasitological diagnosis involves invasive tissue aspiration which is tedious and painful. Commercially available immunochromatographic rapid diagnostic test such as rK39-RDT is used for field diagnosis of VL, detects antibodiesin serum samples. Urine sample is however, much easier in collection,storage and handling than serum and would be a better alternative where collection of tissue aspirate or blood is impractical. In this study, we have developed and evaluated the performance of two urine-based diagnostic assays, ELISA and dipstick test, and compared the results with serologicalrK39-RDT. Our study shows the capability of urinebased tests in detecting anti-Leishmania antibodies effectively for both VL and PKDL diagnosis. The ability of dipstick test to demonstrate negative results after six months in 90% of the VL cases after treatment could be useful as a test of clinical cure. Urine-based tests can therefore replace the need for invasive practices and ensure better diagnosi

Human CD8+ T cell cross-reactivity across influenza A, B and C viruses

Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8+ T cells confer cross-protection against IAV strains, however the responses of CD8+ T cells to IBV and ICV are understudied. We investigated the breadth of CD8+ T cell cross-recognition and provide evidence of CD8+ T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8+ T cell epitopes from IBVs that were protective in mice and found memory CD8+ T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8+ T cells displayed tissue-resident memory phenotypes. Notably, CD38+Ki67+CD8+ effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8+ T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines

Kinetics & Mechanism of Oxidation of Diethylenetriaminepentaacetato-cobalt (II) with Hydrogen Peroxide in Aqueous Acidic Medium

289-29

Kinetics & Mechanism of Peroxodisulphate Oxidation of Bis(iminodiacetato)- Cobaltate(II) in Aqueous Acidic Media

1123-112

Inter-petiolar stipules of Galium mollugo L

The inter-petiolar stipules of Galium mollugo are separate, leaf-like in shape and size, and also in the possession of a single trace bundle. Morphogenetical studies at the shoot apex show that the initiation and vascularization of the leaves and stipules are different. Only the leaves bear axillary buds; the leaf-like stipules do not bear them. The foliar foundations by their union form acollar round the axis, from which it separates by the differentiation of a separation layer in its adaxial surface. The glandular hairs also arise from this layer. The axis on its separation shows a wavy contour of its surface. The crest of each initially shallow wave is occupied by a meristem which helps in the development of each ridge. From later behaviour of the apparently single leaf-trace bundle it appears that it is composed of three bundles and the laterals are concerned with the origin of the stipules and their traces

ArF laser photodissociation dynamics of hydroxyacetone: LIF observation of OH and its reaction rate with the parent

Upon photoexcitation at 193 nm, hydroxyacetone dissociation appears to give CH3 and COCH2OH radicals as primary products, and the latter undergoes further dissociation to OH and ketene. Real time LIF observation of OH formation shows a dissociation rate of COCH2OH as (4.6± 0.5)× 106 s-1. There is no significant population (<1%) in excited vibrational levels of OH (X2π ) observed. The rotational state distribution has a Boltzmann temperature of the OH photofragment 380± 40 K. Doppler spectroscopy shows an average translational energy with the OH photofragment as 3.6± 1.3 kcal mol-1. The bimolecular rate constant for OH + hydroxyacetone is (2.8± 0.2) × 10-12 cm3 molecule-1 s-1