Effect of Pt doping on the critical temperature and upper critical field in YNi2-xPtxB2C (x=0-0.2)

We investigate the evolution of superconducting properties by doping non-magnetic impurity in single crystals of YNi2-xPtxB2C (x=0-0.2). With increasing Pt doping the critical temperature (Tc) monotonically decreases from 15.85K and saturates to a value ~13K for x>0.14. However, unlike conventional s-wave superconductors, the upper critical field (HC2) along both crystallographic directions a and c decreases with increasing Pt doping. Specific heat measurements show that the density of states (N(EF)) at the Fermi level (EF) and the Debye temperatures (Theta_D) in this series remains constant within the error bars of our measurement. We explain our results based on the increase in intraband scattering in the multiband superconductor YNi2B2C.Comment: ps file with figure

Resummed transverse momentum distribution of pseudo-scalar Higgs boson at NNLOA_A+NNLL

In this article we have studied the transverse momentum distribution of the pseudo-scalar Higgs boson at the Large Hadron Collider (LHC). The small \pt region which provides the bulk of the cross section is not accessible to fixed order perturbation theory due to the presence of large logarithms in the series. Using the universal infrared behaviour of the QCD we resum these large logarithms up to next-to-next-to-leading logarithmic (NNLL) accuracy. We observe a significant reduction in theoretical uncertainties due to the unphysical scales at NNLL level compared to the previous order. We present the $p_T$ distribution matched to NNLO$_A$+NNLL, valid for the whole $p_T$ region and provide a detailed phenomenological study in the context of both 14 TeV and 13 TeV LHC using different choices of masses, scales and parton distribution functions which will be useful for the search of such particle at the LHC in near future.Comment: 20 pages, 8 figures, 2 table

Trypanosomatid Aquaporins: Roles in Physiology and Drug Response

In the class Kinetoplastida, we find an order of parasitic protozoans classified as Trypanosomatids. Three major pathogens form part of this order, Trypanosoma cruzi, Trypanosoma brucei, and Leishmania, which are responsible for disease and fatalities in millions of humans worldwide, especially in non-industrialized countries in tropical and sub-tropical regions. In order to develop new drugs and treatments, the physiology of these pathogenic protozoans has been studied in detail, specifically the significance of membrane transporters in host parasites interactions. Aquaporins and Aquaglyceroporins (AQPs) are a part of the major intrinsic proteins (MIPs) super-family. AQPs are characterized for their ability to facilitate the diffusion of water (aquaporin), glycerol (aquaglyceroporin), and other small-uncharged solutes. Furthermore, AQPs have been shown to allow the ubiquitous passage of some metalloids, such as trivalent arsenic and antimony. These trivalent metalloids are the active ingredient of a number of chemotherapeutic agents used against certain cancers and protozoan parasitic infections. Recently, the importance of the AQPs not only in osmotic adaptations but also as a factor in drug resistance of the trypanosomatid parasites has been reported. In this review, we will describe the physiological functions of aquaporins and their effect in drug response across the different trypanosomatids

Enhancement of solubility of Metaclopramide using solid dispersion technique with different carriers (HPβCD, PVP K-30)

Modern drug discovery has led to the development of drug molecules that exhibit high lipophilicity and poor water solubility, which leads to problematic bioavailability. Approaches have thus been made to enhance dissolution of poorly water soluble drugs through modifications and creation of specific formulations. Metaclopramide is an antiemetic and gastroprokinetic agent, commonly used to treat nausea and vomiting. It is absorbed well after oral administration but a significant first pass effect in some human patients may reduce systemic bioavailability to 30%.The Metaclopramide base is thus modified from Metaclopramide hydrochloride to enhance solubility .This has been achieved by the formulating in solid dispersion since Metaclopramide is poorly water soluble. Though it is absorbed well after oral administration, a significant first pass effect in some patients reduces systemic bioavailability, which can cause adverse side effects. This solid dispersion has then been used through transdermal drug delivery. Enhancement of solubility of poorly water soluble drug by solid dispersion may be attributed to particles modified characters such as particle size reduction, improved wettability, higher porosity, decreased lattice energy, amorphous state. The main objective thus includes modification of drug Metaclopramide  hydrochloride to Metaclopramide base, preparation of solid dispersion of modified Metaclopramide  base drug which has poor water solubility, experimental analysis of Metaclopramide base drug and solid dispersion products with carriers. Keywords: solubility, Metaclopramide, solid dispersion, carriers, HPβCD, PVP K-3

Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species

BERBERINE HYDROCHLORIDE COULD PROVE TO BE A PROMISING BULLET AGAINST CLOSTRIDIUM DIFFICILE INFECTION: A PRELIMINARY STUDY FROM SOUTH INDIA

Objective: Recurrent Clostridium difficile infection (CDI) and the emergence of strains with reduced susceptibility to metronidazole and vancomycinwarrants alternative therapy. Hence, we tested the potential efficacy of the natural compound berberine hydrochloride (BBRHCl) against toxigenicC. difficile.Methods: Three representative polymerase chain reaction confirmed, toxin-positive strains were included in the study. Pulsed-field gel electrophoresis(PFGE) profile and antibiogram of the strains were analyzed along with 10 other toxin positive isolates. Efficacy of BBRHCl against toxigenic C. difficilewas determined using agar diffusion by punch well method.Results: PFGE grouped the test strains into three clusters with unique susceptibility pattern toward standard antibiotics. BBRHCl was efficaciousagainst the test strains at a concentration ranging between 6.25 μg/ml and 10 mg/ml. BBRHCl's breakpoint point inhibitory zone diameter wasequivalent (p<0.001) to the epidemiological cutoff values for teicoplanin, vancomycin and 2% black seed oil. Although the predicted concentration ofBBRHCl for breakpoint zone diameter equivalent to European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff value formetronidazole was observed to fall outside the tested concentration range; it was still within the safe dosage for humans.Conclusion: The present study is promising in considering BBRHCl as a potent substitute or adjunct not only for metronidazole, vancomycin andteicoplanin but also for natural compounds like 2% black seed oil for managing resistant cases of CDI. Owing to BBRHCl's direct antibacterial and antiinflammatoryaction, further investigations will aid in the proper characterization of the therapeutic effects of similar plant compounds, to developsafe and effective drugs against the epidemiological outbreak of CDI

Formulation Development to Enhance the Solubility of Metoclopramide Base Drug by Solid Dispersion and Evaluation of Transdermal Film

Aims & Objectives: The present work deals with the modification of controlled release dosage form of poorly water soluble drug (Metoclopramide hydrochloride) in order to improve the bioavailability and to control drug release for a longer period of time by the aid of solid dispersion. Methods: Various binary combination of MET-solid dispersion was prepared with different carriers such as HPβCD, PVP K30 and PLX-188 by solvent evaporation technique and then the aqueous solubility, dissolution study and phase solubility study was performed. DSC analysis is performed to carry out for metoclopramide loaded solid dispersion, physical mixture & also for pure drug to analyze the crystalline and amorphous nature of compounds. Results and Discussion:  The saturation solubility of Metoclopramide with various carriers at different pH was performed and found that in pH 5.5 (solubility is 5553.2µg/ml), pH 6.8 (3363.3µ/ml), pH 7.4 (1367.3µg/ml) at 37oC. In dissolution study of solid dispersion (5:1) of different carriers in DDW, the Cumulative % dissolution is found in the order of PVP K30>PLX-Met>HPβCD-Met & in pH 7.4, in the order of PLX-Met>PVP K30>HPβCD-Met. DSC thermogram of Metoclopramide base showed a sharp endothermic peak at its melting point (147oC) which exhibits in crystalline form complying with that of Metoclopramide hydrochloride form, melting point was found to be 850C.  In the ex-vivo study of several transdermal patches, patch C [SD of MET: HPβCD (1:5)] showed the controlled release and permeation of drug. Conclusion: Poor solubility of new chemical entities being a well known problem for past few decades despite the imbalance between significant research efforts & few successful marketed formulations, the solid dispersion proves to hold a key position among all the various formulation strategies to enhance the aqueous solubility & dissolution rate and thereby the bioavailability of  poorly aqueous solubility of drug. Keywords: Bioavailability,DSC, Metoclopramide hydrochloride, solid dispersion, HPβCD

Review on Solubility enhancement of Metoclopramide base by solid dispersion technique for Transdermal drug delivery system

Modern drug discovery has led to the development of drug molecules that exhibit high lipophilicity and poor water solubility, which leads to problematic bioavailability. Approaches have thus been made to enhance dissolution of poorly water soluble drugs through modifications and creation of specific formulations. Metoclopramide is an antiemetic and gastroprokinetic agent, commonly used to treat nausea and vomiting. It is absorbed well after oral administration but a significant first pass effect in some human patients may reduce systemic bioavailability to 30%.The Metoclopramide base is thus modified from Metoclopramide hydrochloride to enhance solubility .This has been achieved by the formulating in solid dispersion since Metoclopramide is poorly water soluble. Though it is absorbed well after oral administration,a significant first pass effect in some patients reduces systemic bioavailability, which can cause adverse side effects. This solid dispersion has then been used through transdermal drug delivery. Enhancement of solubility of poorly water soluble drug by solid dispersion may be attributed to particles modified characters such as particle size reduction, improved wettability, higher porosity, decreased lattice energy, amorphous state. Transdermal drug delivery system has a lot of advantages such as bypassing hepatic first pass, avoidance of risks of I.V therapy, enhancing therapeutic efficiency and others but limitations like skin irritations are also prevalent. Keywords: Solid dispersion, Metoclopramide, solubility, bioavailability, transdermal drug delivery system

Genomic characterization of antibiotic resistance‐encoding genes in clinical isolates of Vibrio cholerae non‐O1/non‐O139 strains from Kolkata, India: generation of novel types of genomic islands containing plural antibiotic resistance genes

Non‐O1/non‐O139 nontoxigenic Vibrio cholerae associated with cholera‐like diarrhea has been reported in Kolkata, India. However, the property involved in the pathogenicity of these strains has remained unclear. The character of 25 non‐O1/non‐O139 nontoxigenic V. cholerae isolated during 8 years from 2007 to 2014 in Kolkata was examined. Determination of the serogroup showed that the serogroups O6, O10, O35, O36, O39, and O70 were represented by two strains in each serogroup, and the remaining isolates belonged to different serogroups. To clarify the character of antibiotic resistance of these isolates, an antibiotic resistance test and the gene analysis were performed. According to antimicrobial drug susceptibility testing, 13 strains were classified as drug resistant. Among them, 10 strains were quinolone resistant and 6 of the 13 strains were resistant to more than three antibiotics. To define the genetic background of the antibiotic character of these strains, whole‐genome sequences of these strains were determined. From the analysis of these sequences, it becomes clear that all quinolone resistance isolates have mutations in quinolone resistance‐determining regions. Further research on the genome sequence showed that four strains possess Class 1 integrons in their genomes, and that three of the four integrons are found to be located in their genomic islands. These genomic islands are novel types. This indicates that various integrons containing drug resistance genes are spreading among V. cholerae non‐O1/non‐O139 strains through the action of newly generated genomic islands