A Review on “Churg-Strauss Vasculitisâ€Â

Churg-Strauss syndrome (CSS) is a systemic disorder characterized by asthma, transient pulmonary infiltrates, hypereosinophilia, and systemic vasculitis. Eosinophilicvasculitis may involve multiple organ systems, including the lungs, heart, skin, gastrointestinal tract and nervous system. Thus allergy and angiitis are the two hallmarks of CSS. Conditions in the differential diagnosis of CSS include Wegener's granulomatosis (WG), drug reactions, bronchocentricgranulomatosis, eosinophilic granuloma, fungal and parasitic infections, and malignancy. Onset typically occurs in patients aged from 15 to 70 years.On presentation, patients often have pulmonary infiltrates on chest x-ray, but they may also have sinusitis, neuropathy, constitutional symptoms, or gastrointestinal or cardiac manifestations. It is important to establish a tissue diagnosis by biopsy and exclude other diseases in the differential diagnosis of CSS because treatment differs significantly from that of other eosinophilic lung diseases. Untreated, CSS may have a dire prognosis, but treatment with corticosteroids or cytotoxic agents, or both,usually results in clinical remission. Although the exact etiology of CSS is unknown, this syndrome is likely believed to represent an autoimmune process because of the prominence of allergic features and the presence of immune complexes, heightened T-cell immunity and altered humoral immunity, as shown by elevated immunoglobulin (Ig) E and rheumatoid factor. Treatment consists of glucocorticoid (GC)-monotherapy, data on outcome and affectivity is lacking on other immunosuppressive regimens such as cyclophosphamide (CP) or GC plus CP. Treatment with INF-alpha has been effective in patients refractory to GC plus CP

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activatio

Modeling complex metabolic reactions, ecological systems, and financial and legal networks with MIANN models based on Markov-Wiener node descriptors

[Abstract] The use of numerical parameters in Complex Network analysis is expanding to new fields of application. At a molecular level, we can use them to describe the molecular structure of chemical entities, protein interactions, or metabolic networks. However, the applications are not restricted to the world of molecules and can be extended to the study of macroscopic nonliving systems, organisms, or even legal or social networks. On the other hand, the development of the field of Artificial Intelligence has led to the formulation of computational algorithms whose design is based on the structure and functioning of networks of biological neurons. These algorithms, called Artificial Neural Networks (ANNs), can be useful for the study of complex networks, since the numerical parameters that encode information of the network (for example centralities/node descriptors) can be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely used in chemoinformatics to quantify the molecular structure of drugs and to study complex networks. In this work, we explore for the first time the possibility of using Markov chains to calculate analogues of node distance numbers/W to describe complex networks from the point of view of their nodes. These parameters are called Markov-Wiener node descriptors of order kth (Wk). Please, note that these descriptors are not related to Markov-Wiener stochastic processes. Here, we calculated the Wk(i) values for a very high number of nodes (>100,000) in more than 100 different complex networks using the software MI-NODES. These networks were grouped according to the field of application. Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different organisms. In addition, we analyzed other biological and legal and social networks. These include the Interaction Web Database Biological Networks (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law Network (SFLN). The calculated Wk(i) values were used as inputs for different ANNs in order to discriminate correct node connectivity patterns from incorrect random patterns. The MIANN models obtained present good values of Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84). These preliminary results are very promising from the point of view of a first exploratory study and suggest that the use of these models could be extended to the high-throughput re-evaluation of connectivity in known complex networks (collation)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A Review on “Anti-angiogenic Therapy – Past, Present and Futureâ€Â

Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is a sequence of events that is fundamental to many physiologic and pathologic processes such as cancer, ischemic diseases, and chronic inflammation. With the identification of several proangiogenic molecules such as the vascular endothelial cell growth factor, the fibroblast growth factors (like in FGFs), and the angiopoietins, and the recent description of specific inhibitors of angiogenesis such as platelet factor-4, angiostatin, endostatin, and vasostatin, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications in various pathologies. Whereas inhibition of angiogenesis can prevent diseases with excessive vessel growth such as cancer, diabetes retinopathy, and arthritis, stimulation of angiogenesis would be beneficial in the treatment of diseases such as coronary artery disease and critical limb ischemia in diabetes. In this review we highlight the current knowledge on angiogenesis regulation and report on the recent findings in angiogenesis research and mainly highlight the anti-angiogenic drugs/therapy

X-ray K-absorption spectral studies of some copper (II) mixed ligand complexes with glycine as primary ligand

929-936X-ray K-absorption spectra of some structurally important copper (II) mixed ligand complexes have been recorded using a Cauchois type bent crystal X-ray spectrograph of 0.4m radius. The spectra have been recorded using both solid complexes as well as their aqueous solutions. The observed X-ray absorption parameters e.g., chemical shift, edge-width, shift of the principal absorption maximum and structure of the K-edge have been used to explain the structure of the complexes and also these parameters have been correlated with chemical studies. The changes in the structure of the complexes as they form aqueous solutions have also been interpreted in terms of the X-ray absorption parameters. Further the average metal-ligand bond distances have been estimated from the extended X-ray absorption fine structure (EXAFS). It has been found that the average metal-ligand bond distance increases in the aqueous solution state as compared to that in the solid state

Spectral & Polarographic Studies of Mixed Ligand Complexes of Copper(II) with Valine as a Primary Ligand & Some Amino Acids as Secondary Ligands

224-22

Anomalous Polarographic Behaviour of Some Mixed Ligand Complexes of Copper(II)

87-8

Spectral Correlation of Polarographic Behaviour of Some Mixed Ligand Complexes of Copper(II) with Aminoacids

671-67