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Claudicatio Intermittens (CI) är en kärlsjukdom som yttrar sig i form av perifer smärta och som begränsar ens gångsträcka. Patienter med CI har ett Ankel Brachial Index (ABI) på eller under 0,5. Mikrodialys kan användas för att analysera metaboliter såsom glukos, glycerol, laktat och pyruvat i en muskel. Denna teknik används i denna studie för att se metabolismen i muskeln före och efter Cilostazol Behandling. Syftet är att se om Cilostazol kan förbättra gångsträckan hos  patienter med CI och se om det sker en metabolisk förändring efter 6-8 veckors Cilostazol behandling. Totalt deltog 9 patienter i studien. Undersökningen hade en vilo-, arbets- och en återhämtningsfas. Patienterna fick en mikrodialys kateter insatt i musculus gastrocnemius där metaboliterna insamlades in i mikrovialer för att sedan kunna analyseras. ABI mättes med ankelbrachialmätning. Syrgasmättnad mättes med hjälp av en INVOS mätare. Under arbetsfasen där patienterna fick genomgå ett gångmattetest så noterades Absolute Walking Distance (AWD, eller maximal gångsträcka) och Initial Claudication Distance (ICD, eller gångsträcka utan smärtor). Efter undersökningen fick patienterna gå på en Cilostazol behandling i 6-8 veckor sedan gjordes samma undersökning om igen. Metabolisk skedde i stort sett ingen signifikant skillnad efter Cilostazol behandling. ICD och ABI visade signifikant skillnad efter Cilostazol behandling. En större och mer utvecklad studie hade behövts för att frågeställningen ska besvarar med en större säkerhet men en slutsats kan dras att Cilostazol kan förbättra gångsträckan hos patienter med CI. / Intermittent claudication (CI) is a vascular disease that manifests itself in the form of peripheral pain and limits one's Walking distance. Patients with CI have an Ankle Brachial Index (ABI) of or below 0.5. Microdialysis can be used to analyze metabolites such as glucose, glycerol, lactate and pyruvate in a muscle. This technique is used in this study to see the metabolism in the muscle before and after Cilostazol Treatment. The aim is to see if Cilostazol can improve the walking distance in patients with CI and see if there is a metabolic change after 6-8 weeks of Cilostazol treatment. A total of 9 patients participated in the study. The study had a rest, work and recovery phase. Patients received a microdialysis catheter inserted into the gastrocnemius muscle where the metabolites were collected in to microvials for analysis. ABI was measured with ankle brachial measurement. Oxygen saturation was measured using an INVOS meter. During the work phase where the patients had to undergo a walking mat test, Absolute Walking Distance (AWD, or maximum walking distance) and Initial Claudication Distance (ICD, or walking distance without pain) were noted. After the examination, the patients were given a Cilostazol treatment for 6-8 weeks, then the same examination was performed again. Metabolically, there was virtually no significant difference after Cilostazol treatment. ICD and ABI showed significant difference after Cilostazol treatment. A larger and more developed study would have been needed for the question to be answered with greater certainty but it can be concluded that Cilostazol improves the walking distance in patients with CI.

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Pancreatic cancer is a leading cause of cancer related deaths worldwide and has a low survival rate 1 year after diagnosis. It is therfore important to identify new biomarkers and treatments to improve disease outcome. This experiment investigated the effects of different NOX2 and NOX4 inhibitors on Panc-1 cell lines. Following 48 hours treatment, Cell viability analysis, Caspase 3/7 as well as ROS levels where measured to see how these factors were affected by the treatments. As the PI3K/AKT/mTOR and MAPK/ERK pathways, as well as G6PD and VEGF have been shown to influence cancer metastasis and invasiveness, a gene expression analysis (VEGF, G6PD, AKT2, ERK2) was also conducted. Results obtained showed a general decrease in cell viability with increasing concentrations of inhibitors used. While a general increase in Caspase 3/7 activity was observed, M166-0.6μM treatment showed decreased Caspase 3/7 activity, suggesting that other non-apoptotic cell death pathways such as necrosis could have been at play. A general increase in ROS activity was also observed and unexpected. Gene expression showed an increase in G6PD activity which could mean, the cancer cells increased antioxidant system activity to achieve redox balance due to the increased ROS levels. Some results obtained where unexpected and make it difficult to conclude how the treatments decreased cell viability. The results also suggest that other currently unknown mechanisms were at play in influencing cell viability. Most importantly, the results show that completely inhibiting NOX2 and NOX4 lead to the most significant decrease in cell viability.

Organisms are constantly exposed to microorganisms, some of which can cause disease, and yet, sickness only rarely occurs. Upon infection, the immune system is mobilized to eliminate the threat and re-establish homeostasis. The innate immune system, or “first line of defense”, is responsible for detecting infection and subsequently initiating inflammation. An important mediator of this process is the NLRP3 inflammasome, a molecular hub that coordinates the propagation of the immune response. Specifically, through the secretion of interleukins 1 and 18. These structurally related proteins are known to be secreted via unconventional pathways, however, the specificity of this matter remains inconclusive. One form of secretion suggested was “pyroptosis”, a form of cell death intended to enhance inflammation. The aim of this project was to quantify the secretion of structurally related interleukins-1/18 and evaluate the possible correlation with cell death over time. Samples were collected, interleukin release was quantified using sandwich ELISA and cell viability of stimulated cells was measured using the PrestoBlue assay. During prolonged inflammasome activation, IL-1 and IL-18 showed differences in their patterns of secretion and regulation. IL-1 was eventually downregulated whilst IL-18 maintained a constant increase over time. Strikingly, cell viability remained unchanged over the course of the experiment, demonstrating that pyroptosis is dispensable to the secretion of interleukins 1 and 18. Ultimately, the study of the relationship shared between these processes not only explains how immunity is founded, but also, uncovers the truths behind pathogenesis, how to prevent it and potentially find a cure for certain diseases.

Cancer is considered to be one of the top deadly diseases, characterized by uncontrolled dividing of cells and reprogrammed metabolism. Cancer cells usually use high amounts of glucose, so they can produce the required energy for survival and proliferation, this process is called aerobic glycolysis. Studies have shown the inability of cancer using ketone bodies as fuel to generate ATP, therefore using ketone supplements could be an advantage in the fight of cancer. The aim of this thesis is to investigate the effect of ketone ester HVMN treatment, and investigate possible mechanism of its efficacy. Several methods were implemented, cell viability assay, glycolysis assay, apoptosis assay, and gene expression of several genes. This study showed a decrease in cell viability - when treating PANC-1 with different concentrations of the HVMN ketone ester, a significant decrease was recorded in the treatment concentrations of 5 and 50 mM after 24- and 48-hours. The lactate production was generally high for all concentrations of HVMN ketone ester as well as an increased apoptosis for all concentrations but only significant for treatment concentration of 1mM. The results also showed a significant increase in the expression levels of TFAM and cytochrome c (mt-CO1) indicating a functional mitochondrion. Increase mitochondrial activity suggest that ketogenic treatment HVMN induces a metabolic shift in cancer cells leading to the inhibition of glycolysis pathway, decreasing cell viability and inducing apoptosis.

In this project cancer was viewed as a metabolic disorder. The study focused on the effect of synthetic muscone on PANC-1 cells. Synthetic muscone is a ketone. Some cancers lack the potential to metabolise ketone bodies, mainly due to mitochondrial dysfunction. The Warburg effect is a biochemical phenomenon in which cancer cells favour metabolism through glycolysis instead of oxidative phosphorylation to produce ATP. The cells were treated with various concentrations of muscone for 24 and 48 hours. Three different assays were chosen to assess the effects of the treatment. These included an MTS-Assay to estimate the cell-viability, a Lactate-Glo kit to assess the lactate production after the treatment and Caspase 3/7 assay for the apoptotic effects of the treatment. Lactate is the end product of glycolysis, thus its decrease could be an indication of an effective treatment. Instead, the lactate produced exhibited an increasing tendency. Caspase activity was increased for concentration 500μΜ, whilst no effect was noted for the remaining concentrations tested. Expression of genes involved in glycolysis (HK2, GAPDH & PKM2), apoptotic pathways (CYCS), mitochondrial function (TFAM) and ketolytic activities (BDH1 & OXCT1) were chosen to be tested for a better understanding of the results derived from the assays. The expression of CYCS was in accordance with the findings of the MTS and Caspase assays for concentration 500μΜ, making its investigation promising for future research. Due to time restrictions most experiments were conducted once, thus no safe conclusions could be reached. However, we expect this pilot study to provide valuable insight for future researchers who aim to approach cancer treatment from a metabolic perspective.

No description available.

No description available.