Most species of the genus Bifidobacterium contain the gene cluster PFNA, which is presumably involved in the species-specific communication between bacteria and their hosts. The gene cluster PFNA consists of five genes including fn3 , which codes for a protein containing two fibronectin type III domains. Each fibronectin domain contains sites similar to cytokine-binding sites of human receptors. Based on this finding we assumed that this protein would bind specifically to human cytokines in vitro . We cloned a fragment of the fn3 gene (1503 bp; 501 aa) containing two fibronectin domains, from the strain B. longum subsp. longum GT15. After cloning the fragment into the expression vector pET16b and expressing it in E. coli , the protein product was purified to a homogenous state for further analysis. Using the immunoferment method, we tested the purified fragment’s ability to bind the following human cytokines: IL-1β, IL-6, IL-10, TNFα. We developed a sandwich ELISA system to detect any specific interactions between the purified protein and any of the studied cytokines. We found that the purified protein fragment only binds to TNFα.
BackgroundE.coli type II L-asparaginase is widely used for treatment of acute lymphoblastic leukemia. However, serious side effects such as allergic or hypersensitivity reactions are common for L-asparaginase treatment. Methods for minimizing immune response on L-asparaginase treatment in human include bioengeneering of less immunogenic version of the enzyme or utilizing the homologous enzymes of different origin. To rationalize these approaches we compared immunogenicity of L-asparaginases from five bacterial organisms and performed sequence-structure analysis of the presumable epitope regions.MethodsIgG and IgM immune response in C57B16 mice after immunization with Wollinella succinogenes type II (WsA), Yersinia pseudotuberculosis type II (YpA), Erwinia carotovora type II (EwA), and Rhodospirillum rubrum type I (RrA) and Escherichia coli type II (EcA) L-asparaginases was evaluated using standard ELISA method. The comparative bioinformatics analysis of structure and sequence of the bacterial L-asparaginases presumable epitope regions was performed.ResultsWe showed different immunogenic properties of five studied L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin as a second-line treatment. Studied L-asparaginases might be placed in the following order based on the immunogenicity level: YpA > RrA, WsA ≥ EwA > EcA. Most significant cross-immunogenicity was shown between EcA and YpA. We propose that a long N-terminus of YpA enzyme enriched with charged aminoacids and tryptophan could be a reason of higher immunogenicity of YpA in comparison with other considered enzymes. Although the recognized structural and sequence differences in putative epitope regions among five considered L-asparaginases does not fully explain experimental observation of the immunogenicity of the enzymes, the performed analysis set the foundation for further research in this direction.ConclusionsThe performed studies showed different immunogenic properties of L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin. The preferable enzymes for the second line treatment are WsA, RrA, or EwA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2125-4) contains supplementary material, which is available to authorized users.
Objective: comparative assessment of the economic effect of oral vinorelbine when used as indicated, taking into consideration the new registered price.Material and methods. A clinical-economic study was performed to compare active platinum-containing chemotherapy regimens of the first line for stage IV non-small-cell lung cancer with oral vinorelbine and pemetrexed as well as first-line chemotherapy regimens for metastatic breast cancer presented with oral vinorelbine and ixabepilone alone. A systematic search for information in medical databases was carried out, the cost estimate was made out in accordance with the recommendations of The Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. The direct medical costs were estimated, formed on the basis of the dosage, frequency and dosage regimen of the compared drugs, based on the data of the State Register of maximum selling prices, clinical guidelines for the studied nosologies, and instructions for medical use. The comparison of the economic effect of the studied drugs was carried out in pairs using the cost minimization method with a sensitivity analysis. Further, the calculations of the amounts of reimbursement of medical care provided were made using each of the compared drugs. An economic assessment of the economic effect of oral vinorelbine was carried out taking into consideration the change in the price of the drug and a budget impact analysis with a sensitivity analysis.Results. It was determined that the use of oral vinorelbine provides financial savings for a medical organization at the amount of 246,042.34 rubles per 6 cycles of chemotherapy for each patient with stage IV non-small-cell lung cancer compared with the use of pemetrexed, and 558,659.32 rubles per year – for the treatment of each patient with metastatic breast cancer compared with ixabepilone. The results of the budget impact analysis showed that the indication of oral vinorelbine saved 3,287,470.56 rubles for the budget fund considering the change in the cost of 1 mg of the drug for a hypothetical population of patients with stage IV non-small-cell lung cancer in 1000 people. This would create the possibility of therapy for additional 15 patients with this diagnosis. The indication of oral vinorelbine in first-line chemotherapy of metastatic breast cancer for a similar target population would save 18,355,043.96 rubles for the budget fund, which makes it possible to treat 15 more patients with this diagnosis.Conclusion. The use of oral vinorelbine is associated with the saving of financial resources of a medical organization. In addition, the reimbursement for medical care provided from the compulsory medical insurance funds when using regimens with oral vinorelbine is primarily lower than for comparison drugs. Thus, the use of regimens with oral vinorelbine is more beneficial for the payer (the Federal Compulsory Health Insurance Fund) and for the medical organization. The change in the cost of the drug is associated with an increase in the availability of medical care for patients with stage IV non-small-cell lung cancer and patients with metastatic breast cancer.
Due its high efficacy, prestance (amlodipine + perindopril) is a pharmacoeconomically preferred alternative only to the conventional therapy for hypertension even if the least costly generics are used, in both the short and medium term.
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