PEG Conjugated PAMAM Dendrimers with a Anti- HIV Drug Stavudine for prolong release

The present investigation was aimed to design polyamidoamine (PAMAM) dendrimer having polyethylene glycol grafts as novel drug carrier. In this study we successfully synthesized and conjugated PEGylated PAMAM dendrimers with anti HIV drug stavudine. Hemolytic toxicity studies were carried out for PEGylated PAMAM dendrimers which showed that haemolysis of cell was very negligible in PEGylated PAMAM dendrimers. Moreover surface were characterization of PEGylated PAMAM dendrimers was carried out TEM micrographs. Further physiochemical and physiological parameter such as UV, DSC, drug entrapment and drug release were carried out for PEGylated and non PEGylated PAMAM dendrimers. Drug loading, drug release and toxicity are better for PEGylated PAMAM dendrimers

Prolonged Drug Delivery System of PEGylated PAMAM Dendrimers with a Anti-HIV Drug

Polyamidoamine (PAMAM) dendrimers is a new non viral drug carrier. However their high surface toxicity limits PAMAM dendrimers application in drug delivery. The purpose of present work was aimed to developing and exploring PEGylated G4 and G5 PAMAM dendrimers for anti HIV drug lamivudine. In this study we successfully prepared G4 and G5 PAMAM dendrimers with ethylene diamine core and PEGylated with MPEG for surface modifications. Further physiochemical and physiological parameter such as UV, IR, TEM, DSC, drug entrapment, drug release and hemolytic toxicity of both PEGylated and non PEGylated PAMAM dendrimers were determined and compared. Here the PEGylation of PAMAM dendrimers reduce the surface toxicity and increase the drug loading capacity of PAMAM dendrimers. Moreover PEGylated PAMAM dendrimers had released then drug in controlled and prolonged time. Hence the PEGylated PAMAM dendrimers were found as suitable drug delivery carrier for anti HIV drug lamivudine

Normal Induction but Attenuated Progression of Germinal Center Responses in BAFF and BAFF-R Signaling–Deficient Mice

The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the B cell–activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary B cell survival and development. A role for this cytokine in antigen-driven B cell responses has been suggested but current data in this regard are limited. A BAFF receptor expressed by B cells (BAFF-R/BR3) is defective in A/WySnJ mice which exhibit a phenotype similar to BAFF-deficient (BAFF−/−) animals. Here, we show that although GC responses can be efficiently induced in both A/WySnJ and BAFF−/− mice, these responses are not sustained. In BAFF−/− mice, this response is rapidly attenuated and accompanied by perturbed follicular dendritic cell development and immune complex trapping. In contrast, analysis of the A/WySnJ GC response revealed a B cell autonomous proliferative defect associated with reduced or undetectable Ki67 nuclear proliferation antigen expression by GC B cells at all stages of the response. These data demonstrate a multifaceted role for the BAFF pathway in regulating GC progression

Therapeutic implications of recombinant human erythropoietin in anaemic related clinical manifestations

The introduction of recombinant human erythropoietin (RHUEPO) has revolutionised the treatment strategies for patients suffering with anaemia of chronic renal disease and chronic heart failure. Clinical studies and several observational evidences have demonstrated that RHUEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infection and preoperative therapies. The successful treatment of all the anaemic related malfunctions with recombinant human erythropoietin (RHUEPO) has become a standard treatment tool for dialysis patients and as an interesting therapeutic option for several forms of non-renal anaemia. As a conesquence of both, RHUEPO has achieved the highest annual sales worldwide and the potential of it increases its scope in the future prospective also

Identification of promising lines for yield from IR64/Akihikari Recombinant Inbred Lines under low nitrogen

Not AvailableFor identification of lines with promising yield under low nitrogen (N), a total of 117 Recombinant Inbred Lines (RILs) derived from IR64, an improved and released variety in Akihikari as recurrent parent, were evaluated for two seasons dry (Rabi) 2014 and wet (Kharif) 2015 under field with low and recommended N. The difference between the mean yields of the low and recommended N in both seasons was not significant indicating the differential genotypic response under low and recommended N and the difference between the means of season was about 30%, indicating the role of the season in determining the yield under differential N. Out of 50 promising lines identified for low and recommended N, six promising lines were identified with yields ranging from 11.2 ± 0.65 to 18.3 ± 1.06 (Dry 2014) and 7.1 ± 0.41 to 15.4 ± 0.89 (Wet 2015) under low N suggesting the possibility of evaluation of the mapping populations as a promising strategy for the identification of breeding lines with promising yield under low N.Not Availabl

Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model

Molecular characterization of antibody immunity and human antibody discovery is mainly carried out using peripheral memory B cells, and occasionally plasmablasts, that express B cell receptors (BCRs) on their cell surface. Despite the importance of plasma cells (PCs) as the dominant source of circulating antibodies in serum, PCs are rarely utilized because they do not express surface BCRs and cannot be analyzed using antigen-based fluorescence-activated cell sorting. Here, we studied the antibodies encoded by the entire mature B cell populations, including PCs, and compared the antibody repertoires of bone marrow and spleen compartments elicited by immunization in a human immunoglobulin transgenic mouse strain. To circumvent prior technical limitations for analysis of plasma cells, we applied single-cell antibody heavy and light chain gene capture from the entire mature B cell repertoires followed by yeast display functional analysis using a cytokine as a model immunogen. We performed affinity-based sorting of antibody yeast display libraries and large-scale next-generation sequencing analyses to follow antibody lineage performance, with experimental validation of 76 monoclonal antibodies against the cytokine antigen that identified three antibodies with exquisite double-digit picomolar binding affinity. We observed that spleen B cell populations generated higher affinity antibodies compared to bone marrow PCs and that antigen-specific splenic B cells had higher average levels of somatic hypermutation. A degree of clonal overlap was also observed between bone marrow and spleen antibody repertoires, indicating common origins of certain clones across lymphoid compartments. These data demonstrate a new capacity to functionally analyze antigen-specific B cell populations of different lymphoid organs, including PCs, for high-affinity antibody discovery and detailed fundamental studies of antibody immunity

Critical exponents and equation of state of the three-dimensional Heisenberg universality class

We improve the theoretical estimates of the critical exponents for the three-dimensional Heisenberg universality class. We find gamma=1.3960(9), nu=0.7112(5), eta=0.0375(5), alpha=-0.1336(15), beta=0.3689(3), and delta=4.783(3). We consider an improved lattice phi^4 Hamiltonian with suppressed leading scaling corrections. Our results are obtained by combining Monte Carlo simulations based on finite-size scaling methods and high-temperature expansions. The critical exponents are computed from high-temperature expansions specialized to the phi^4 improved model. By the same technique we determine the coefficients of the small-magnetization expansion of the equation of state. This expansion is extended analytically by means of approximate parametric representations, obtaining the equation of state in the whole critical region. We also determine a number of universal amplitude ratios.Comment: 40 pages, final version. In publication in Phys. Rev.

Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

<p>Abstract</p> <p>Background</p> <p>BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP). BSEP disease is associated with an increased risk of hepatobiliary cancer.</p> <p>Case Presentation</p> <p>A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat.</p> <p>Conclusions</p> <p>Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.</p

Increasing Trends of Leptospirosis in Northern India: A Clinico-Epidemiological Study

Leptospirosis is often not suspected by physicians in patients with acute febrile illnesses reporting from supposedly “non-endemic areas,” including north India. Clinical manifestations are protean, and complications can affect most organ systems, including liver, kidneys, lungs, and the central nervous system. Timely diagnosis and specific therapy can reduce severity of illness and, in turn, mortality. In this study conducted at a tertiary care center in north India, we find how a much-neglected disease entity has emerged as a major cause of acute febrile illness in a so called “non-endemic area.” Incidence is increasing yearly. The majority of patients were from a rural background, and were farmers or farm labourers. Poor hygiene, contact with animals, rat infestation of houses, and contact with stagnant dirty water are the major determinants of disease. Apart from the usual symptoms of intermittent fever with chill and rigor, hepatosplenomegaly, renal decompensation, muscle pain and tenderness, and conjunctival suffusion, signs and symptoms indicating involvement of the respiratory and central nervous systems were also commonly observed. Severe complications resulting in mortality do occur and is especially due to late suspicion among primary level physicians, and the resulting inappropriate therapy