Experimental Bearing Capacity Determination of Bonded Rock Bolts

Import 26/02/2015Diplomová práce se zabývá únosností tmelených horninových svorníků a jejím experimentální stanovením. Tato práce analyzuje a poukazuje na možné způsoby porušení, které vznikají zatížením v těsné blízkosti svorníkové tyče a to především v prstenci tmele na kontaktech svorník – tmel a tmel – hornina. V teoretické části byl navržen způsob měření a stanovení pevnostních a deformačních charakteristik tahem zatížených tmelených svorníků napodobujících zatížení v kořenové délce svorníkové výztuže. V praktické části byly pak navržené postupy uskutečněny sérií laboratorních zkoušek. Výstupem z provedených zkoušek je pracovně-deformační charakteristika tmelené svorníkové výztuže zvoleného testovaného materiálu.The thesis focuses on the bearing capacity of bonded rock bolts and experimental determination of this capacity. Possible ways of failure, which is caused by the load near the rock bolt, especially in the circular ring of the grout and between the rock bolt - the grout and between the grout - the rock, are analysed. The theoretical part includes design of measuring and assessment of strength and deformation characteristics on drawn rock bolts as it simulates the load in the root length of bolt reinforcement. This theory was applied in the laboratory tests and presents the practical part of the thesis. In conclusion, the load - deformation characteristics of bonded rock bolt reinforcement made from chosen material are stated.224 - Katedra geotechniky a podzemního stavitelstvívýborn

Low levels of IgM antibodies recognizing oxidation-specific epitopes are associated with human non-alcoholic fatty liver disease

Background: Lipid oxidation of membrane phospholipids is accompanied by the formation of oxidation-specific epitopes (OSE). These epitopes are recognized by specific antibodies and represent danger-associated molecular patterns that are generated during chronic inflammatory processes. In a murine model for hepatic inflammation during non-alcoholic fatty liver disease (NAFLD), increased antibody levels targeting OSE were found to be protective. Here, our aim was to determine an association between OSE-specific antibody titers and NAFLD in humans. Methods: IgM and IgG levels with specificity for various OSE were assessed in the plasma of patients with NAFLD (n = 71) and healthy controls (n = 68). Antibody titers were comprehensively analyzed in patients with NAFLD after classification by histological evaluation of liver biopsies. Statistical analysis was performed to determine significant correlations and odds ratios. To study the specificity for NAFLD, plasma antibody titers were measured in patients with hepatitis C (n = 40) and inflammatory bowel disease (n = 62). Results: IgM titers against OSE were lower in patients with NAFLD compared to controls. Further biopsy-based classification of patients with NAFLD did not show any difference in IgM levels. Plasma IgM titers towards the P1 mimotope demonstrated an inverse correlation with markers for obesity, systemic inflammation, and liver damage. In contrast, hepatitis C and increased disease activity during inflammatory bowel disease was not associated with reduced IgM titers. Conclusions: Our data highlight the importance of immune recognition of OSE by IgM antibodies in the pathophysiology of NAFLD

The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice.

<p>BACKGROUND & AIMS: Non-alcoholic steatohepatitis is characterized by hepatic steatosis with inflammation. Although steatosis is benign and reversible, inflammation can increase liver damage. Hepatic inflammation has been associated with accumulation of cholesterol in lysosomes of Kupffer cells. 27-Hydroxycholesterol (27HC), a derivative of cholesterol formed by CYP27A1, can mobilize cholesterol from the lysosomes to the cytoplasm. We investigated whether 27HC can change the intracellular distribution cholesterol and reduce hepatic inflammation in mice. METHODS: We transplanted bone marrow from irradiated wild-type or Cyp27a1(-/-) mice to mice that do not express the low density lipoprotein receptor (Ldlr(-/-)), which are hyperlipidemic; 9 weeks later, mice were fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 3 months. In a separate experiment, Ldlr(-/-) mice were given subcutaneous injections of 27HC and placed on regular chow or HFC diets for 3 weeks. Blood and liver tissues samples were collected and analyzed for intracellular cholesterol distribution and inflammation. RESULTS: In Ldlr(-/-) mice that received bone marrow transplants from Cyp27a1(-/-) mice, lysosomes of Kupfer cells had a greater accumulation of cholesterol than those of mice that received bone marrow from wild-type mice, after the HFC diet. Liver histology and gene expression analyses showed increased inflammation and liver damage in mice given bone marrow transplants from Cyp27a1(-/-) mice and placed on the HFC diet. Administration of 27HC to Ldlr(-/-) mice, following the HFC diet, reduced the accumulation of lysosomal cholesterol and hepatic inflammation, compared with mice that were not given 27HC. CONCLUSIONS: Accumulation of cholesterol in lysosomes of Kupfer cells promotes hepatic inflammation in mice. The cholesterol derivative 27HC reduces accumulation of cholesterol in lysosomes and might be used to treat non-alcoholic steatohepatitis.</p>

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis

A global action agenda for turning the tide on fatty liver disease

Background and Aims: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. Approach and Results: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of “agree” responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% “agree”). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. Conclusions: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.publishedVersio

Comment on Flatscher et al. Impact of Mediterranean Diet on Lipid Composition in the Colaus-PsyColaus Study. <i>Nutrients</i> 2023, <i>15</i>, 4659

With great interest, we read the article by Flatscher et al [...

The role of ectopic adipose tissue:benefit or deleterious overflow?

Ectopic adipose tissues (EAT) are present adjacent to many organs and have predominantly been described in overweight and obesity. They have been suggested to be related to fatty acid overflow and to have harmful effects. The objective of this semi-comprehensive review is to explore whether EAT may play a supportive role rather than interfering with its function, when the adjacent organ is challenged metabolically and functionally. EAT are present adhered to different tissues or organs, including lymph nodes, heart, kidney, ovaries and joints. In this review, we only focused on epicardial, perinodal, and peritumoral fat since these locations have been studied in more detail. Evidence was found that EAT volume significantly increased, associated with chronic metabolic challenges of the corresponding tissue. In vitro evidence revealed transfer of fatty acids from peritumoral and perinodal fat to the adjacent tissue. Cytokine expression in these EAT is upregulated when the adjacent tissue is challenged. In these tissues, glycolysis is enhanced, whereas fatty acid oxidation is increased. Together with more direct evidence, this shows that glucose is oxidized to a lesser degree, but used to support anabolic metabolism of the adjacent tissue. In these situations, browning occurs, resulting from upregulation of anabolic metabolism, stimulated by uncoupling proteins 1 and 2 and possibly 3. In conclusion, the evidence found is fragmented but the available data support the view that accumulation and browning of adipocytes adjacent to the investigated organs or tissues may be a normal physiological response promoting healing and (patho)physiological growth

How we manage patients with hereditary haemochromatosis

A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment. Recent publications suggest that erythrocytapheresis, as a more individualized treatment, can provide a good balance between effectiveness, tolerability and costs. Other treatments like oral chelators and proton pomp inhibitors, which are used in selected patients, create the possibility to further individualize treatment of hereditary haemochromatosis. In the future, hepcidin-targeted therapy could provide a more fundamental approach to treatment