19 research outputs found

    Experimental Investigation on Soil Stabilisation Using Rubber Crumbs on Expansive Soil

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    To withstand the load soil is the basic foundation for the structure. Weak in the strength, high degree of expansion and contraction due to the presence of montmorilonite minerals causes differential settlement in a structure which leads to failure in the black cotton soil. To increase the engineering properties and to make it suitable for the construction purpose it is required to stabilize the soil. It can be done by various methods such as by using lime, cement, textile effluent, plastic, etc. In this study the stabilization is carried out by using increasing percentage of rubber crumbs along with lime under suitable test. The main objective is to increase the CBR value

    A case report of dengue haemorrhagic fever during the peripartum period: challenges in management and a case of vertical dengue transmission

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    Abstract Background Incidence of Dengue infection is on the increase in Sri Lanka with it being associated with significant maternal and neonatal morbidity in pregnancy. Case presentation A 33-year-old pregnant woman at 38 weeks of gestation, presented with acute onset of fever, was later diagnosed with Dengue illness. Due to the emergence of warning symptoms and signs and rapidly dropping platelet count, the baby was delivered by urgent caesarian section. She went into the critical phase during the postoperative period and due to concealed bleeding, required blood transfusion. On the 5th day of life, the neonate was also diagnosed with possible dengue by vertical transmission and required blood and PLT transfusions for recovery. Conclusions This case report illustrates how a high index of suspicion, early diagnosis, close monitoring, timely intervention and critical consideration of physiological changes of pregnancy when interpreting clinical situation, led to achieving a successful outcome

    Mucosal Tolerance to a Combination of ApoB and HSP60 Peptides Controls Plaque Progression and Stabilizes Vulnerable Plaque in Apob<sup>tm2Sgy</sup>Ldlr<sup>tm1Her</sup>/J Mice

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    <div><p>Oral tolerance to auto antigens reduces the development of atherosclerosis in mouse models. However, the effect of immune tolerance to multiple self antigenic peptides in plaque progression and stabilization is not known. We studied the protective effect of mucosal tolerance to peptides from apolipoprotein B (ApoB; 661–680) and heat shock protein 60 (HSP60; 153–163), in combination with diet, in the prevention of atherosclerotic lesion progression and plaque stabilization in ApoB<sup>tm25gy</sup>LDLr<sup>tm1Her</sup> mice. We found that oral administration of five doses of a combination of ApoB and HSP60 peptides (20 µg/mice/dose) induced tolerance to both the peptides and reduced early plaque development by 39.9% better than the individual peptides (ApoB = 28.7%;HSP60 = 26.8%)(P<0.001). Oral tolerance to combination of peptides along with diet modification arrested plaque progression by 37.6% which was associated with increases in T-regulatory cell and transforming growth factor-β expression in the plaque and peripheral circulation. Reduced macrophage infiltration and tumor necrosis factor-α expression in the plaque was also observed. Tolerance with continued hypercholesterolemia resulted in 60.8% reduction in necrotic core area suggesting plaque stabilization, which was supported by reduction in apoptosis and increased efferocytosis demonstrated by greater expression of receptor tyrosine kinase Mer (MerTK) in the plaque. Tolerance to the two peptides also reduced the expression of matrix metalloproteinase 9, tissue factor, calprotectin, and increased its collagen content. Our study suggests that oral tolerance to ApoB and HSP60 peptide combination induces CD4<sup>+</sup> CTLA4<sup>+</sup> Tregs and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Tregs secreting TGF-β, which inhibit pathogenic T cell response to both peptides thus reducing the development and progression of atherosclerosis and provides evidence for plaque stabilization in ApoB<sup>tm25gy</sup>LDLr<sup>tm1Her</sup> mice.</p> </div

    Oral Tolerance with Continued Hypercholesterolemia Stabilizes Vulnerable Plaque.

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    <p>A. Experimental design. B. Representative photomicrographs of plaque area stained with EVG and its quantitative analysis in aortic sinus of 26 week old ApoB<sup>tm25gy</sup>LDLr<sup>tm1Her</sup> mice (n = 10 per group). Scale bar represents 200 µm C. Percentage of acellular necrotic core area in total plaque area. *P = 0.012 D. Representative photomicrographs showing double immunofluorescence staining of aortic sinus sections with CD4 (green) and Foxp3 (red). Scale bar represents 50 µm. Enlarged region to show double immune staining. Scale bar represents 6.25 µm. Right panel: Number of CD4-positive cells/mm<sup>2</sup> and CD4+ Foxp3+ cells/mm<sup>2</sup> (n = 9per group). ***P<0.001. E. Percentage of CD25<sup>+</sup>Foxp3<sup>+</sup> cells (*P<0.009) and CTLA-4 (NS) within the CD4 population in spleen (n = 6 per group). F. Expression of mRNA of Foxp3 (***P = 0.003), CTLA-4 (P = NS), and TGF-β (**P = 0.005) in the ascending aorta quantified by RT-PCR and normalized to GAPDH. Fold-changes in their expression in ApoB+HSP60-tolerized mice relative to controls (n = 4 per group).</p

    Oral Administration of ApoB+HSP60 Peptides Induces Tolerance to Both Peptides and attenuates inflammation.

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    <p>A. Flow cytometry analysis: Percentage of CD25<sup>+</sup>Foxp3<sup>+</sup> cells (*P = 0.035) and CTLA-4<sup>+</sup>cells (**P<0.0001) within the CD4 population in spleen at the end of the study (n = 6 per group). B. Relative mRNA expression of IFN-γ (*** P<0.001), TGF-β (*** P<0.005), Foxp3 (*** P<0.005), and CTLA-4(*** P<0.005) in the ascending aorta quantified by RT-PCR analysis and normalized to GAPDH. Fold-changes in their expression in ApoB+HSP60-tolerized mice relative to controls are shown (n = 5 per group). C. Splenic effector cells were generated from ApoB/Ldlr<sup>−/−</sup> mice immunized subcutaneously with the peptides. Addition of purified Treg cells from oral tolerant mice is indicated at different ratios to effector cells. Proliferation of effector-cell alone is indicated by the white bar; proliferation index represents the percentage carboxyfluorescein succinimidyl ester reduction in culture stimulated with ApoB or HSP60 peptides (10 µg/mL) relative to unstimulated culture (n = 4 per group). *P<0.05 D. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with CD68 (red) and its quantitative analysis (n = 10 per group). *P = 0.02. E. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with TNF-α (red) and its quantitative analysis (n = 6 per group). *P = 0.04. F. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with TGF-β (red) and its quantitative analysis (n = 6 per group). *P = 0.03. Scale bar represents 50 µm for the immunofluorescence staining.</p

    Oral Tolerance to ApoB+HSP60 peptides in Combination with Diet Modification Arrests Plaque Progression.

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    <p>A. Experimental design. B. Representative photomicrographs of EVG stained plaque area and its quantitative analysis in aortic sinus of 26 week old ApoB<sup>tm25gy</sup>LDLr<sup>tm1Her</sup> mice (n = 10 per group) *P = 0.01 for APOB+HSP60 tolerized animals compared to KLH. Scale bar represents 200 µm. C. Percentage of CD25<sup>+</sup>Foxp3<sup>+</sup> cells (*P = 0.011) and CTLA-4<sup>+</sup>cells (**P = 0.005) within the CD4 population in spleen (n = 6 per group). D. Expression of mRNA of Foxp3 (**P = 0.003), CTLA-4 (***P<0.001), and TGF-β (***P<0.002) in the ascending aorta were quantified by RT-PCR analysis and normalized to GAPDH. Fold-changes in their expression in ApoB+HSP60-tolerized mice relative to controls (n = 5 per group). E. Representative photomicrographs showing double immunofluorescence staining of aortic sinus sections with CD4 (green) and Foxp3 (red). Scale bar represents 50 µm. Enlarged region to show double immune staining. Scale bar represents 6.25 µm. Lower panel: Number of CD4-positive cells/mm<sup>2</sup> and CD4+ Foxp3+ cells/mm<sup>2</sup> (n = 9 per group), ***P<0.001.</p

    Model Depicting Oral Tolerance-Induced Prevention and Stabilization of Atherosclerotic Lesion Development.

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    <p>Oral administration of peptides (ApoB+HSP60) induces a regulatory T-cell response, which is maintained for 10 weeks and results in prevention of early atherosclerotic lesions. Oral administration of peptides in mice with established lesions in combination with diet modification also induces a Treg-cell response with an increase in CD4+CD25+Foxp3 T cells, CTLA-4 expression, and increased TGF-secretion in the lesion and the peripheral circulation. It is likely that both CTLA-4- and TGF-mediated suppression are required for early lesion reduction and inhibition of plaque progression. With continuous hypercholesterolemia, the CTLA-4 expression remains unaltered, while there is an increase in Foxp3 and TGF expression in tolerized mice. We propose that the TGF-mediated decrease in inflammatory activity results in plaque stabilization.</p

    Reduction in Plaque Vulnerability Markers in Tolerized Mice.

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    <p>A. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with MMP9 (red) and its quantitative analysis (n = 10 per group). *P = 0.035 B. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with tissue factor (red) and its quantitative analysis (n = 6 per group). *P = 0.028 C. Representative photomicrographs showing immunofluorescence staining of aortic sinus sections with calprotectin (MRP8/14) (red) and its quantitative analysis (n = 6 per group). *P = 0.045 D. Representative photomicrographs of aortic sinus sections stained with alizarin-red S. (n = 6 per group) Arrows indicate calcium depositions and its quantitative analysis. *P = 0.018. Scale bar represents 150 µm. E. Representative photomicrographs of aortic sinus sections stained with Masson’s trichrome and its quantitative analysis (n = 8 per group). **P = 0.002. Lower photomicrograph shows picrosirius staining for collagen content Scale bar represents 200 µm. Scale bar represents 50 µm for the immunofluorescence staining.</p
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