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Susceptible Role of Saccharin Mixture in Induction of Inflammation Through Action on Interleukin-10 and its Receptor

Sodium cyclamate and saccharin mixture is a common artificial sweetener used as a food additive and it was found to be accompanied with increase relevance of inflammation including IBD. The causes of IBD are unknown, but many immune, genetic and environmental factors play a role as causative agents of that disease. The consumption of artificial sweeteners was related to the appearance of inflammation including IBD. The present study was aimed to evaluate the effect of sodium cyclamate and saccharin mixture as artificial sweeteners on immune system in albino mice through assessment of IL-10 cytokine and its receptor. Fifty male albino mice grouped into control group (n=20) receive only tap water and treated groups (n=30) received 60 mg/kg body weight sodium cyclamate and saccharin mixture in tab water for 12 weeks. Mice were sacrificed twice at the 6th and the 12th weeks. Collected blood measured low concentration of IL-10 cytokine by the sandwich ELISA. While, expression levels of IL-10R1 and IL-10R2 were assessed in colorectal tissue samples using Real time PCR. The results demonstrate significantly overexpression of IL-10R1 and IL-10R2 at 6th week than 12th week treated mice was recorded. Also, more congestion of RBCs, focal aggregation, focal necrosis, and focal infiltrations between glands in the lamina propria at 12th week treated group than 6th week treated group were observed. In conclusion, sodium cyclamate and saccharin mixture induced inflammation that may be risk for IBD by alteration in gene expressions of IL-10R1 and IL-10R2 in male albino mice.

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Health Care Facility Network Efficiency and Location Crucial for Ebola Treatment Outcome

Background: The application of network analysis in public health research is gaining popularity with the belief that health problems are a product of complex social, political and economic causes. Organisational networks can be used in public health to design and evaluate public health programs. There have been multiple studies in the past relating to public health organisations and HIV/AIDS using organisational networking method. Here we use social network analysis to analyse the association between the network positions of health care facilities and the treatment outcome of Ebola patients from these health care facilities in Sierra Leone. Methods: We extracted and later analysed treatment outcome data obtained from the Case Report Forms (CRF) of 117 Ebola patients who sought Ebola treatment at the Kenema Government Hospital from June 2014 to April 2015. For ego network purpose, we considered each Ebola referral health care facility as an ego. Poisson regression analysis was used to determine the association between Ebola mortality rates in a health care facility and the ego’s structural holes. Results: The median age, length of stay during Ebola treatment, and the period it takes an Ebola patient to survive treatment following from onset of signs and symptoms were 20 (IQR=17.5 years), 15 (IQR=11 days) and 7 (IQR=5.3 days) respectively. There were differences in ego, network efficiency, effective size and constraint for the factors associated with mortality rates for Ebola patients treated at the Kenema Government Hospital. Conclusion: Establishing non-redundant contacts within a health care facility network and expanding their locations can reduce Ebola mortality rates during outbreak.

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Opposing SMAD-6 and SMAD-7 Expression Profiles Correlate with the Sensitivity of Multiple Myeloma Cells to Bone Morphogenetic Protein (BMP)-2

Objective: Multiple myeloma (MM) is a hematologic disease characterized by hyper-proliferation of antibody secreting B-cells. One of the most severe accompanying symptoms in MM is the destruction of bone tissue. Thus, the use of bone morphogenetic proteins (BMPs) for MM treatment seems to be a good option since these proteins are capable to induce formation of bone tissue in vivo and additionally can suppress cell proliferation of malignant Bcells. But, the different BMP family members vary in their biological activities also in terms of donor specific differences of addressed cells. In this study we analyzed signal transduction of two different TGFβ family members, BMP2 and GDF5, in different MM cell lines.Methods: Ten MM cell lines were stimulated either with BMP2 or GDF5 and cell proliferation was analyzed by WST-1 assays. Receptor expression levels were determined by qRT-PCR for relevant BMP receptors. SMAD-1/5/8 phosphorylation was analyzed by Western blot and correlated to the expression levels of inhibitory (i)-SMADs, SMAD-6 and SMAD-7 proteins, respectively.Results: Only three out of ten investigated cell lines were BMP2 responsive, one of which was additionally sensitive to GDF5. Depending on the expression of the required receptors the different cell lines could be divided into three subgroups. The first group expressed all receptor chains which are crucial for proper signal transduction and was ligand sensitive, the second also expressed the required receptors, but appeared ligand-resistant. The third subgroup instead missed at least one or more essential receptor rendering these cells also resistant to ligand exposure. Western blot analyses addressing phosphorylated SMAD-1/5/8 proteins revealed that the second group showed no or at least extremely reduced levels of SMAD-1/5/8 phosphorylation levels upon ligand exposure. Furthermore, Western blot analyses also showed that non-responsive cells expressed the inhibitory SMAD-7 protein at high levels prior to ligand stimulation. In contrast, the BMP2 responsive cells did not express SMAD-7 but instead expressed SMAD-6 at high levels prior to ligand stimulation.Conclusion: Aside of the expression of essential receptors, further factors are decisive for proper BMP signal transduction in MM cells such as the individual expression levels of SMAD-6 and SMAD-7 in unstimulated cells. The conspicuous opposing basal expression levels of either SMAD-6 or SMAD-7 might be used as prediction whether a particular MM cell line appears ligand-responsive or ligand-resistant.

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