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<p><strong>Purpose: </strong>Habitual aerobic exercise improves vascular function; however, the acute vascular response to exercise is poorly understood. The present investigation compared the time course of acute changes in vascular function following two different types of aerobic exercise. <strong>Methods: </strong>Ten untrained males (23 ± 2 yrs) completed one bout of sustained moderate-intensity cycling (END) (30 mins at 55% peak power) or high-intensity interval (HIT) cycling (10 one-minute intervals at 80% peak power) on different days. Endothelium-dependent dilation was assessed by brachial artery flow-mediated dilation (baFMD) at baseline, immediately post-exercise, 1 hour post-exercise and 24 hours post-exercise. Endothelium-independent dilation was assessed via nitroglycerin (NTG) at all time points, except 1 hour post-exercise. <strong>Results:</strong> baFMD values were not significantly different between END and HIT at any time point. Immediately post-exercise baFMD values were unchanged from baseline. 1 Hour post-exercise, relative (p £ 0.001) and absolute (p £ 0.05) baFMD values were attenuated compared to all other time points for both HIT (%FMD baseline: 5.9 ± 2.3%; 1 hour post-exercise: 2.5 ± 1.5%) and END (%FMD baseline: 6.8 ± 2.4%; 1 hour post-exercise: 2.6 ± 1.9%). Relative (p £ 0.05) and absolute (p £ 0.05) NTG responses were attenuated immediately post-exercise compared to baseline for both HIT (%NTG baseline: 18.8 ± 4.4%; immediately post-exercise: 12.3 ± 3.1%) and END (%NTG baseline: 18.3 ± 3.1%; immediately post-exercise: 10.9 ± 4.9%). <strong>Conclusions: </strong>Immediately post-exercise, endothelium-dependent dilation is maintained; but reduced 1 hour following exercise cessation. Similar acute vascular responses are found following HIT and END.</p> / Master of Science in Kinesiology

The development of new innovations in explosives was an important part of the industrialization process from the mid-nineteenth century. The establishment of the world´s first nitroglycerin factory – Nitroglycerin Aktiebolaget (NA) in Stockholm in 1864 started a process replacing gunpowder with nitroglycerin and from 1868 by the safer invention dynamite. This affected both the long-term relationships between the mining industry and the powder mills and the demand from new industries for efficient and safe explosives. Even though the explosives industry was a small industry, it was of great importance for many other industries and for economic transformation. With dynamite and its successors, society also faced new risks. As a result, an extensive legislation was developed at an early stage which was supplemented with further supervision from a government authority in various organizations from 1895. The aim of the thesis is to investigate and analyze the major decision-making processes of the Swedish civilian explosives industry during the period 1858-1950. The purpose of the work is to contribute to gaining knowledge about how the society´s regulation of different industries has evolved and how state and private actors have acted in the development of new regulations. The work is structured around three main questions. The first question is about how the Swedish explosives industry developed during the period. How did the technological development of the industry and the explosives look like and had this any impact on the questions the actors within the industry drove? The second question is about how the dynamite industry was regulated. What did the regulations contain and how was the control organized? How did rights and obligations look like and how was the industry affected by this? The third question concerns the regulatory process itself. How and why did the regulations change and which actors were involved in the various changes? How did the Government and the actors act and can we see shifts over time between their different roles and interests? The study concludes that NA was the actor that, by using different methods, managed to gain the greatest influence over the regulatory process. Although the traditional established powder mill industry competed with NA at an early stage, it was nevertheless the initial, high-tech company that was involved in creating new national regulations in negotiation with the regulating authorities. This was a process of regulatory capture where NA, by combining both direct and indirect capture methods, managed to gain influence over regulations in the long run. A parallel but slightly different characteristic of this regulatory capture process is risk minimization for the public. Despite the occurrence of regulatory capture the regulations developed in a kind of a co-regulation system where the regulators became dependent on NA to provide the technical and practical expertise needed to build the necessary regulatory framework.

The goal of this project was to develop a rapid separation and detection method for analyzing organic compounds in smokeless powders and then test its applicability on gunshot residue (GSR) samples. In this project, a total of 20 common smokeless powder additives and their decomposition products were separated by ultra performance liquid chromatography (UPLC) and confirmed by tandem mass spectrometry (MS/MS) using multiple reaction monitoring mode (MRM). Some of the targeted compounds included diphenylamines, centralites, nitrotoluenes, nitroglycerin, and various phthalates. The compounds were ionized in the MS source using simultaneous positive and negative electrospray ionization (ESI) with negative atmospheric pressure chemical ionization (APCI) in order to detect all compounds in a single analysis. The developed UPLC/MS/MS method was applied to commercially available smokeless powders and gunshot residue samples recovered from the hands of shooters, spent cartridges, and smokeless powder retrieved from unfired cartridges. Distinct compositions were identified for smokeless powders from different manufacturers and from separate manufacturing lots. The procedure also produced specific chemical profiles when tested on gunshot residues from different manufacturers. Overall, this thesis represents the development of a rapid and reproducible procedure capable of simultaneously detecting the widest possible range of components present in organic gunshot residue.

Indiana University-Purdue University Indianapolis (IUPUI) / Pipe bombs are a common form of improvised explosive device, due in part to their ease of construction. Despite their simplistic nature, the lethality of pipe bombs should not be dismissed. Due to the risk of harm and their commonality, research into the pipe bomb deflagration process and subsequent chemical analysis is necessary. The laboratory examination of pipe bomb fragments begins with a visual examination. While this is presumptive in nature, hypotheses formed here can lead to subsequent confirmatory exams. The purpose of this study was to measure the mass and velocity of pipe bomb fragments using high speed video. These values were used to discern any trends in container type (PVC or black/galvanized steel), energetic filler (Pyrodex or double base smokeless powder), and ambient temperature (13°C and -8°C). The results show patterns based on container type, energetic filler, and temperature. The second stage of a laboratory exam is chemical analysis to identify any explosive that may be present. Legality calls for identification only, not quantitation. The purpose of this study is to quantitate the amount of explosive residue on post-blast pipe bomb fragments. By doing so, the instrumental sensitivities required for this type of analysis will be known. Additionally, a distribution of the residue will be mapped to provide insight into the deflagration process of a device. This project used a novel sampling technique called total vaporization solid phase microextraction. The method was optimized for nitroglycerin, the main energetic in double base smokeless powder. Detection limits are in the part per billion range. Results show that the concentration of residue is not uniform, and the highest concentration is located on the endcaps regardless of container type. Total vaporization solid phase microextraction was also applied to automotive racing samples of interest to the National Hot Rod Association. The purpose of this project is two-fold; safety of the race teams in the form of dragstrip adhesive consistency and monitoring in the form of fuel testing for illegal adulteration. A suite of analyses, including gas chromatography mass spectrometry, infrared spectroscopy, and evaporation rate, were developed for the testing of dragstrip adhesives. Gas chromatography mass spectrometry methods were developed for both nitromethane based fuel as well as racing gasolines. Analyses of fuel from post-race cars were able to detect evidence of adulteration. Not only was a novel technique developed and optimized, but it was successfully implemented in the analysis of two different analytes, explosive residue and racing gasoline. TV-SPME shows tremendous promise for the future in its ability to analyze a broad spectrum of analytes.

<p>Mnogi lekovi registrovani za razne druge indikacije mogu da deluju selektivno na tumorske receptore, signalne puteve, metaboličke procese, bioenergetske faktore, enzime, proteine, gene koji reguli&scaron;u proliferaciju, apoptozu i neoangiogenezu tumora ne pogađajući ove procese kod zdravih ćelija. Uvođenje novih lekova je izrazito dug, složen i skup proces istraživanja. Kori&scaron;ćenjem principa otkrivanja antikancerskog efekta kod već registrovanih lekova za druge indikacije, direktno se utiče na skraćivanje vremena i tro&scaron;kova istraživanja. Eksperimentalno je ispitana efikasnost antitumorskog delovanja mebendazola, metformina, itrakonazola, diklofenaka, nitroglicerina i deoksiholne kiseline na fibrosarkom hrčka izazvan BHK21/C13 tumorskom ćelijskom linijom praćenjem veličine i histologije lečenih tumora. Eksperimentalno je ispitana mogućnost primene deoksiholne kiseline, nitroglicerina, kofeina i itrakonazola kao adjuvansa u kombinaciji sa pojedinim ispitivanim lekovima (metformin, itrakonazol, diklofenak) za lečenje fibrosarkoma hrčka. Kako je ispitivanje vr&scaron;eno na mladuncima imladim hrčkovima i kako su sarkomi najče&scaron;ći u dečijem uzrastu, definisanje potencijalne antikancerske uloge ispitivanih lekova se odnosi prvenstveno na njihovu primenu u pedijatriji. Pokazano je da metformin, kombinacije metformina sa kofeinom, metformina sa itrakonazolom i metformina sa nitroglicerinom deluju u pogledu svih ispitivanih parametara tumora antitumorski na fibrosarkom hrčka. Kofein, itrakonazol i nitroglicerin pojačavaju antitumorsko dejstvo metformina na fibrosarkom hrčka. Tokom svih eksperimenata realizovanih u okviru ove disertacije, pokazalo se da nije bilo delotvornog tretmana, koji ne sadrži metformin.</p> / <p>Many drugs registered for various other indications can act selectively to tumor receptors, signaling pathways, metabolic processes, bioenergetic factors, enzymes, proteins, genes that regulate proliferation, apoptosis, and neoangiogenesis of the tumor without affecting these processes in the healthy cells. The introduction of new drugs is a very long, complex and expensive process of research. Using the principle of detecting the anticancer effect in already registered drugs for other indications, directly affects the reduction of time and cost of research. The efficacy of mebendazole, metformin, itraconazole, diclofenac, nitroglycerin and deoxycholic acid antitumor activity on hamster fibrosarcinoma induced experimentally by the BHK21/C13 tumor cell line was tested by monitoring the size and histology of the treated tumors. The possibility of using deoxycholic acid, nitroglycerin, caffeine and itraconazole as an adjuvant in combination with investigated drugs (metformin, itraconazole, diclofenac) for the treatment of hamster fibrosarcoma has been experimentally tested. As the examination was carried out on young cubs and young hamsters and that sarcomas are the most common in childhood, defining the potential anti-cancer role of the investigated drugs relates primarily to their application in pediatrics. Metformin, combinations of metformin with caffeine, metformin with itraconazole and metformin with nitroglycerin have shown antitumor action on the hamster fibrosarcoma in terms of all tested tumor parameters. Caffeine, itraconazole and nitroglycerin increase the antitumor effect of metformin on the hamster fibrosarcoma. During all the experiments carried out within this dissertation, there has been no effective treatment, which does not contain metformin.</p>

Organic nitrates, such as nitroglycerine (NTG), are widely used for their potent vasodilator capacity in the management of coronary artery disease and heart failure. Unfortunately, their beneficial effect is rapidly lost due to the development of nitrate tolerance, which is translated by an impaired vasorelaxation to NTG and an increased oxidative stress production. Although the mechanisms of the development of nitrate tolerance are still not fully elucidated, much interest has been focused in treating nitrate-receiving patients together with other drugs in order to overcome the development of nitrate tolerance. The Nitric Oxide generating enzyme, eNOS, and the superoxide anion generating enzyme, NAD(P)H oxidase, have been suggested to play a role in the development of nitrate tolerance. The aim of this study was to analyse the underlying mechanism by which ramipril, an ACE inhibitor and rosuvastatin, a new molecule of the statin class, are able to protect against the development of nitrate tolerance in the aortas isolated from rats, wild-type (wt) and eNOS-/- mice. <p>These results show that ramipril as well as rosuvastatin are able to protect against the development of nitrate tolerance in the wt and eNOS-/- mice aortas suggesting that eNOS is not necessary for their protective effect. The aortas from nitrate tolerant rats and mice showed a significant increase in the NAD(P)H oxidase activation compared to the aortas from the control and from the co-treated ramipril+NTG or rosuvastatin+NTG animals. In line with these findings were the results obtained by RT-PCR analysis: the mRNA expression of the different subunits of the NAD(P)H oxidase, such as gp91phox, p22phox, were significantly decreased after rosuvastatin or ramipril treatment in wt and eNOS-/- mice aortas. Apocynin, the NAD(P)H oxidase inhibitor was also able to inhibit the development of nitrate tolerance in the rat and mouse aortas. <p>In conclusion, these results suggest that rosuvastatin and ramipril are able to protect against the development of nitrate tolerance by counteracting the nitrate-induced oxidative stress. The mechanism of protection involves a direct interaction with the NAD(P)H oxidase pathway and seems to be completely independent of the eNOS pathway. <p> / Doctorat en sciences pharmaceutiques / info:eu-repo/semantics/nonPublished

<p>У овој дисертацији испитивана су антитуморска дејства антихипергликемијског лека метформина, вазодилататорног лека нитроглицерина, и комбинација ових лекова са дијагностичким средством 2-деокси-D-глукозом и/или радио и хемио сензибилизатором кофеином на хуманим културама аденокарцинома плућа (A549), колоректалног карцинома (HT29), аденокарцинома цервикса (HeLa), као и на контролној ћелијској култури нормалних фибробласта плућа (МRC 5). In vitro испитивање утицаја метформина, нитроглицерина, 2-деокси-D-глукозе и кофеина на проли- ферацију ћелија карцинома грлића материце (HeLa), ћелијској култури аденокарциномa плућа (A549) и ћелијској линији карцинома дебелог црева (HT29). Ћелије у експоненцијалној фази раста третиране су растућим концентрацијама метформина, нитроглицерина и 2-деокси-D-глукозе и утврдила се дозна зависност цитотоксичног ефекта. Метформин, кофеин и 2-деокси-D-глукоза су утицали на смањење процента преживљавања туморских ћелија, док је применом нитроглицерина овај ефекат изостао, иако у експериментима код истовремене примене нитроглицерина и кофеина постоји пад процента преживелих ћелија. Најпотентнији ефекат је постигнут код истовремене примене метформина и кофеина, док је разлог за одсуство снажног цитотоксичног ефекта метформина и 2-деокси-D-глукозе код комбиноване примене молекуларни механизам деловања појединачних супстанци. Снажан пролиферативни ефекат је евидентиран применом метформина и кофена на здравим фибробластима плућа.</p> / <p>U ovoj disertaciji ispitivana su antitumorska dejstva antihiperglikemijskog leka metformina, vazodilatatornog leka nitroglicerina, i kombinacija ovih lekova sa dijagnostičkim sredstvom 2-deoksi-D-glukozom i/ili radio i hemio senzibilizatorom kofeinom na humanim kulturama adenokarcinoma pluća (A549), kolorektalnog karcinoma (HT29), adenokarcinoma cerviksa (HeLa), kao i na kontrolnoj ćelijskoj kulturi normalnih fibroblasta pluća (MRC 5). In vitro ispitivanje uticaja metformina, nitroglicerina, 2-deoksi-D-glukoze i kofeina na proli- feraciju ćelija karcinoma grlića materice (HeLa), ćelijskoj kulturi adenokarcinoma pluća (A549) i ćelijskoj liniji karcinoma debelog creva (HT29). Ćelije u eksponencijalnoj fazi rasta tretirane su rastućim koncentracijama metformina, nitroglicerina i 2-deoksi-D-glukoze i utvrdila se dozna zavisnost citotoksičnog efekta. Metformin, kofein i 2-deoksi-D-glukoza su uticali na smanjenje procenta preživljavanja tumorskih ćelija, dok je primenom nitroglicerina ovaj efekat izostao, iako u eksperimentima kod istovremene primene nitroglicerina i kofeina postoji pad procenta preživelih ćelija. Najpotentniji efekat je postignut kod istovremene primene metformina i kofeina, dok je razlog za odsustvo snažnog citotoksičnog efekta metformina i 2-deoksi-D-glukoze kod kombinovane primene molekularni mehanizam delovanja pojedinačnih supstanci. Snažan proliferativni efekat je evidentiran primenom metformina i kofena na zdravim fibroblastima pluća.</p> / <p>In this dissertation, the anti-cancer effects of an antihyperglycaemic agent of metformin, a vasodilator drug nitroglycerin, and a combination of these drugs with a 2-deoxy-D-glucose diagnostic agent and / or radio and hemio sensitizer with caffeine on human cultures of adenocarcinoma of the lungs (A549), colorectal carcinoma (HT29), cervix adenocarcinoma (HeLa), as well as on the control cell culture of normal fibroblasts of the lungs (MRC 5). An in vitro study of the effects of metformin, nitroglycerin, 2-deoxy-D-glucose and caffeine on the proliferation of cervical cancer cells (HeLa), cell culture of the lung adenocarcinoma (A549), and colon cancer of the colon (HT29). The cells at the exponential growth stage were treated with rising concentrations of metformin, nitroglycerin and 2-deoxy-D-glucose, and the cytotoxic effect was determined. Metformin, caffeine, and 2-deoxy-D-glucose reduced the number of tumor cells, while nitroglycerin did not it could be concluded. Although there is a decrease in survival in experiments with the simultaneous administration of nitroglycerin and caffeine, the most effective effect is achieved in the simultaneous use of metformin and caffeine, while the reason for the absence of a potent cytotoxic effect of metformin and -deoxy-D-glucose is the molecular mechanism of the action of individual substances. The most significant effect was achieved with the simultaneous administration of metformin and caffeine to the cell culture of lung adenocarcinoma. A potent proliferative effect was recorded using metformin and 2-deoxy-Dglucose on healthy lung fibroblasts.</p>