Journal of Computer Science & Systems Biology- Open Access www.omicsonline.com Research Article In Silico Prediction of the Tertiary Structure of M. leprae Hsp65 Protein Shows an Unusual Structure in Carboxy-terminal Region

Copyright: © 2008 Rossetti RAM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DNA vaccines have been used with great success in experimental and some clinical therapy. However, the mechanisms of activation of the immune system by these vaccines are not utterly understood yet. Hsp65 is a Mycobacterium leprae chaperone whose gene has been efficiently used as experimental DNA vaccine against tuberculosis and clinical trial against tumor. Since little is know about the three-dimensional (3D) structure of hsp65 and modeling of 3D protein structure can increase the information to improve the knowledge about the mechanism action as well as the design of new DNA vaccine formulation, here we used the bioinformatics to get the design in silico of hsp65 (heat shock protein) molecule. The determination of hsp65 3D structure was obtained by homology using the software Modeller (Eswar et al., 2001). It was used two proteins as models: 1SJP, a 60kDa chaperonin from Mycobacterium tuberculosis in the PDB, and the 1WE3, the crystal structure of the chaperoni

Extracorporeal photopheresis versus standard treatment for acute graft-versus-host disease after haematopoietic stem cell transplantation in paediatric patients

BACKGROUND: Acute graft-versus host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT) occurring in 8% to 59% of the recipients. Currently, the therapeutic mainstay for aGvHD is corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and re-infusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (Issue 9, 2012), MEDLINE/PubMed and EMBASE (Ovid) databases from their inception to 12 September 2012. We searched the reference lists of potentially relevant studies without any language restriction. We searched eight trial registers and four conference proceedings. We also contacted an expert in the field to request information on unpublished study that involves ECP in aGvHD after HSCT. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in paediatric patients with aGvHD after HSCT. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author. MAIN RESULTS: We found no studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the treatment of aGvHD in paediatric patients after HSCT is unknown and its use should be restricted within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone

Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in paediatric patients

BACKGROUND: Chronic graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation occurring in 6% to 65% of the recipients. Currently, the therapeutic mainstay for chronic GvHD are corticosteroids that are frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory chronic GvHD. The therapeutic options in these people include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. OBJECTIVES: To evaluate the effectiveness and safety of ECP for the management of chronic GvHD in children and adolescents after haematopoietic stem cell transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (Issue 9, 2012), MEDLINE and EMBASE databases from their inception to 12 September 2012. We searched the reference lists of potentially relevant studies without any language restriction. We searched eight trial registers and five conference proceedings. We also contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in paediatric patients with chronic GvHD after haematopoietic stem cell transplantation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author. MAIN RESULTS: We found no studies meeting the criteria for inclusion in this review. AUTHORS' CONCLUSIONS: The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs can currently not be evaluated since we have found no such studies. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical grounds in favour of ECP are made, people should be carefully monitored for beneficial and harmful effects and efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP