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Background: To compare the survival rate of paclitaxel plus cisplatin (PC arm), paclitaxel plus gemcitabine (PG arm) and gemcitabine plus cisplatin (GC arm) in chemotherapy patients with non resectable lung cancer. Methods: This was a retrospective observational study to evaluate chemotherapy response among non resectable lung cancer patients with their survival at cancer center CMH, Dhaka since 01 July 2013 to 31 March 2015. One hundred fifty-four (154) non resectable lung cancer patients were randomly divided into three groups, 50 patients in PC arm, 51 patients in PG arm and 53 patients in GC arm. In PC arm paclitaxel 175 mg/m2 (day 1) with cisplatin 75mg/m2 (day 1), in PG arm Paclitaxel 175 mg/m2 (day 1) with gemcitabine 1000 mg/m2 (days 1 and 8) and in GC arm gemcitabine 1000 mg/m2 (days 1 and 8) with cisplatin 100mg/m2 (day 1). Results: Patients characteristics were similar between the three groups. The overall response rate was 40% in the PC arm,43.1% in the PG arm, 43.4% in the GC arm. The median survival time in PC arm was 8.5 months, in PG arm was 8.8 months, in GC arm was 9.2 months. The major side effect was myelosuppression which accounts 71% patients. The average treatment costs were 57% and 30% lower in PC arm as compared with GC and PG arm respectively. Conclusion: The median survival time, disease free survival time and 1-year survival rate in PC, PG, GC arms without significant difference. Treatment were well tolerable; quality of life parameter was mostly similar but paclitaxel with cisplatin was most cost effective than others chemotherapy regimen. [ABSTRACT FROM AUTHOR]

Electron Paramagnetic Resonance (EPR) spectroscopy coupled with spin traps/probes enables quantitative determination of reactive nitrogen and oxygen species (RNOS). Even with numerous studies using spin probes, the methodology has not been rigorously investigated. The autoxidation of spin probes has been commonly overlooked. Using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH), the present study has tested the effects of metal chelators, temperature, and oxygen content on the autoxidation of spin probes, where an optimized condition is refined for cell studies. The apparent rate of CMH autoxidation under this condition is 7.01 ± 1.60 nM/min, indicating low sensitivity and great variation of the CMH method and that CMH autoxidation rate should be subtracted from the generation rate of CMH-detectable oxidants (simplified as oxidants below) in samples. Oxidants in RAW264.7 cells are detected at an initial rate of 4.0 ± 0.7 pmol/min/106 cells, which is not considered as the rate of basal oxidants generation because the same method has failed to detect oxidant generation from the stimulation of phorbol-12-mysirate-13-acetate (PMA, 0.1 nmol/106 cells) in cells (2.5 ± 0.9 for PMA vs. 2.1 ± 1.5 pmol/min/106 cells for dimethyl sulfoxide (DMSO)-treated cells). In contrast, the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which exhibits minimal autoxidation, reveals differences between PMA and DMSO treatment (0.26 ± 0.09 vs. −0.06 ± 0.12 pmol/min/106 cells), which challenges previous claims that spin probes are more sensitive than spin traps. We have also found that low temperature EPR measurements of frozen samples of CMH autoxidation provide lower signal intensity and greater variation compared to RT measurements of fresh samples. The current study establishes an example for method development of RNOS detection, where experimental details are rigorously considered and tested, and raises questions on the applications of spin probes and spin traps. Image 1 • Method development for the detection of reactive oxygen species. • Electron Paramagnetic Resonance coupled with spin probes and spin traps. • Autoxidation of spin probes must be considered. • Oxidant generation from RAW264.7 cells. • Low temperature measurements provide less intensity and greater variability. [ABSTRACT FROM AUTHOR]

Abstract: In the 1990s, the variability of responses to human immunodeficiency virus (HIV) could only be tracked by phenotypic criteria such as the number of CD4T lymphocytes, the occurrence of opportunistic infection, the disease free survival without treatment. In 1996, the viral load is the leading phenotype for genetic studies. Ever since, thanks to a better understanding of the HIV infection pathophysiology, numerous studies helped to highlight the influence of genetic variability on inter-individual response to this virus. Among the genes having an impact, we can quote the following examples: CCR5, HLA-B and HLA-C genes. Practical applications of genetics in clinical medicine include search for HLA-B*57:01 before abacavir introduction. Recently, an eradicating treatment for HIV disease after bone marrow transplantation with a donor homozygote for a CCR5 gene non-functional variant (CCR5Δ32) has been reported. Interest in genetics of chronic viral infection is not specific to HIV. It has also been used on other viral diseases and it has gained a major place on the management of diseases. [Copyright &y& Elsevier]

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine–Tryptophan–Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.Kidney International (2007) 71, 875–881. doi:10.1038/sj.ki.5002129; published online 21 February 2007 [ABSTRACT FROM AUTHOR]

Abstract: The pathogenesis of food allergy was, in the past, focused on atopy, IgE and auxiliary lymphocytes responsible for class switching. Nevertheless, some allergic reactions induced by foods do not involve IgE. Mechanisms of breaking tolerance and cell mechanisms at the level of the gut mucosa are now better understood. This analysis of the involvement of lymphocytes in food allergy will begin with comments on presentation of antigens in Peyer''s patches, followed by comments on a recognition mechanism involving surface receptors and regulation by chemokines. In association with intestinal immunity, regulatory T cells have a central role in the induction of immunization or tolerance to foods. [Copyright &y& Elsevier]

In order to effectively perceive the huge diversity of antigenic determinants to which it is confronted, the immune system uses referring internal images from self. The major histocompatibility complex constitutes the main reference to self, essential to the operating system of T and NK lymphocytes. It is involved in shaping the T operating repertoire in the thymus, where each differentiating thymocyte, with its TCR interacting with the MHC-peptide self complexes exposed by thymic presenting cells, should answer to both questions: Is it really necessary (positive selection) Is not dangerous (negative selection)? Once in periphery, naive T lymphocytes will undergo an homeostatic control helping their survival through the same contacts between TCR and MHC-peptide self complex than those which allowed the thymic positive selection. In a more hypothetic way, it is possible that contact between a T lymphocyte and the rare foreign MHC-peptide complexes spread at the surface of antigen presenting cell, is not sufficient to initiate its activation. Some arguments exist to involve the MHC-peptide self complexes themselves in the activation process.Finally, the MHC also constitutes a quality referential for the NK lymphocytes. When a somatic cell, infected by a virus or transformed, repress the expression of one or more of its class I HLA alleles, this absence of the self is perceived by the NK lymphocytes which proceed to its elimination through cytolysis. This disposition to sanction the non-self is also used for therapeutic purpose in the case of a non HLA identical allogenic hematopoi¨etic stem cells graft. [Copyright &y& Elsevier]

Function of T and natural killer (NK) lymphocytes is tightly controlled by the balance of activating and inhibitory signals. NK receptors belong to different families: KIRs (“Killer cell Immunoglobulin-like Receptor”) and ILTs (“Immunoglobulin-like Transcript”), mainly inhibitory which binds to HLA class I alleles; C-type lectin NK receptors such as CD94/NKG2A which is inhibitory and binds to HLA-E ; NCR (“Natural Cytotoxicity Receptors”) which directly activate NK cells. These include molecules NKp30, NKp44, NKp46 et NKG2D. Cellular stress (viral and bacterial infections, tumours) may modulate NK function by different mechanisms: decrease in HLA class I molecules expression resulting in the lack of engagement of the inhibitory receptors and ultimately NK cell activation; modulation of CD94/NKG2A inhibitory function through expression of peptides presented by HLA-E as for instance from heat shock proteins; NK activation through NCR expression. Among these, NKG2D is an activating receptor expressed by NK cells and subsets of αβ and γδ and T cells. Major NKG2D ligands in humans are MIC (“MHC class I related”) molecules which are stress-inducible during a viral (CMV) or bacterial infection (M. tuberculosis, E. coli). They may also be expressed by tumors. Therefore, they could play a role in activating NK and/or T lymphocyte responses in these conditions. [Copyright &y& Elsevier]

It is important for the physician to fully understand the basic phenomena of histocompatibility and the specialized functions of a group of genes denominated major histocompatibility complex (MHC) which encode what constitutes the human leucocyte antigen (HLA) system. The HLA system is the most polymorphic known in humans. There are two classes of HLA antigens, class I includes HLA-A, -B and -C. Class II includes HLA-DR. -DQ and -DP. The function of the HLA system is to recognize peptides and exhibit them on the surface of antigen presenting cells, like macrophages, in order to be reviewed by T lymphocytes which will differentiate self from non-self antigens. Due to its extensive polymorphism, HLA antigens themselves constitute antigens capable of activating a powerful immune reaction. HLA class I molecules are also known as the classic transplant antigens, as they were the first discovered when response to human allgrafting was studied. Class II molecules, although discovered later, are in general the most important to match for a successful transplant. Several immunogenetics techniques for studying tissue identity are available in order to ensure full or adequate histocompatibility. These assays can be serologic, such as the classic microlymphocytotoxicity assay, genotypic, employing the polymerase chain reaction, and tissue culture techniques, such as the mixed lymphocyte reaction. In conclusion, adequate histocompatibility between a graft receptor and his or her donor, certified through HLA tissue typing, is essential to guarantee the long-term functioning of the allograft, and the optimal survival of the receptor. [ABSTRACT FROM AUTHOR]

Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration. [ABSTRACT FROM AUTHOR]