Context: Although the long-term goal of antihypertensive therapy is to reduce adverse clinical outcomes, the only way to evaluate the efficacy of treatment in an individual is the magnitude of blood pressure (BP) reduction. ACE inhibitors and angiotensin receptor blockers (ARBs) are two drug classes that, by different mechanisms, inhibit the renin-angiotensin- aldosterone system that regulates BP. As these drugs are widely prescribed for hypertension, it is essential to determine and compare their effects on BP, heart rate and tolerability. Objectives: 1) To determine the dose-related effect of ACE inhibitors and ARBs on BP, heart rate and withdrawals due to adverse effects (WDAE), compared with placebo in the treatment of primary hypertension (SBP ≥ 140 mm Hg and/or ≥ DPB 90 mm Hg); and 2) To compare the relative effect on BP, heart rate and WDAE of a) each ACE inhibitor with other ACE inhibitors, b) each ARB with other ARBs, and c) all ACE inhibitors with all ARBs. Methods: Two systematic reviews of published, double-blind, randomized, controlled trials (RCTs) evaluating the BP lowering efficacy of fixed dose monotherapy with an ACE inhibitor or ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension were conducted. Electronic databases were searched for RCTs and similar trial inclusion criteria and methods of analysis were used in both reviews. Results: Ninety two RCTs evaluated the dose-related BP lowering efficacy of 14 ACE inhibitors in 12 954 participants with a baseline BP of 157.1/101.2 mm Hg. Forty six RCTs evaluated the dose-related BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 155.6/101.0 mm Hg. The best estimate of the near maximal trough BP reduction for ACE inhibitors and ARBs was -8/-5 mm Hg and -8/-5 mm Hg, respectively. ACE inhibitors and ARBs do not affect heart rate. The evidence for short-term WDAE (tolerability) was incomplete and weak and did not demonstrate a difference between the two classes of drugs. Conclusion: ACE inhibitors and ARBs are not different individually or as drug classes in BP lowering efficacy.

Thesis (M.S.)--University of Wisconsin, 1965. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 132-136).

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Resultat från epidemiologiska studier har antytt att flavonolrik kakao sänker blodtrycket. Detta sker troligen genom att flavonoider i kakao leder till aktivering av eNOS som sedan katalyserar NO-syntesen i kärlendotel vilket leder till vasodilation och sänkt blodtryck. En nyare studie har funnit att kakao dessutom inhiberar enzymet ACE. Mycket tyder även på att NO-koncentrationen är kopplad till ACE-aktiviteten då dessa faktorer visat sig följa varandra inverst vid varierande doser. Det finns också ett samband mellan ACE-genotyp och serumnivåer av ACE. Någon dosberoende effekt av kakao på blodtrycket har inte påvisats, men ihållande dosering med kakao över en längre period visar på en progressiv sänkning av blodtrycket. Inga biverkningar har rapporterats, men fett och socker i kakao kan leda till diabetes och hjärt-kärlsjukdomar. Syftet med blodtrycksbehandling är prevention av nyss nämnda sjukdomar och adekvat blodtryckssänkning krävs därmed för att en behandling ska kunna övervägas. Än så länge ses endast en signifikant men inte en tillräcklig blodtryckssänkande effekt av kakao. Dessutom saknas studier som visar att kakao förebygger kardiovaskulära händelser, exempelvis hjärtinfarkter. Vidare studier krävs innan kakao kan rekommenderas som behandling.

Heart failure is a condition where the heart is incapable of providing adequate blood supply to different organs in the body. The underlying causes of heart failure is some kind of disorder in the heart function, and require careful diagnostics. The basic symptoms that arise from heart failure is difficulty in breathing, that aggravate when lying down, and fatigue. The patients’ symptoms and impaired quality of life can be in different stages depending on the severity of the heart failure. Heart failure is a present widespread disease with numerical superiority which is more likely to affect elderly patients. Heart failure is a very expensive condition and causes enormous costs for the society. The basic treatment of heart failure consists of ACE-inhibitors in combination with beta blockers and with additional diuretics. If intolerance occurs with ACE-inhibitors, often in the form of dry cough, then treatment with angiotensin receptor inhibitors (ARB) will be used instead. The aim of the study was to find out if additional treatment with ARB in patients diagnosed with heart failure and receiving basic treatment with ACE-inhibitors lead to better health or had any economic advantage. The method used consists of literature search studies in the Pubmed database. The search gave a total of 103 articles of which six were chosen. The criteria for inclusion was that it should be clinical trials which were not older than 14 years and that the studies should be based on humans. Two of the six studies that were chosen were health economic studies. The studies were randomized, double blind, placebo controlled and included a large number of patients. The results from the studies showed that there were no significant improvements on mortality or morbidity, when additional treatment with ARB was given to heart failure patients already receiving treatment with ACE-inhibitors. A decrease in hospital admission was seen, but at the same time there were more adverse events arising that lead to discontinuation of study treatment. The economic studies showed a higher medical service cost when treatment with ARB was added and the reason for this were that ARB drugs were more expensive than ACE-inhibitors. It is concluded that the additional treatment with ARB in patients diagnosed with heart failure and already receiving treatment with ACE-inhibitors had no favorable effect neither from a health perspective or an economic perspective. However, health economic studies that are made from a society point of view are required to be able to draw definite conclusions regarding the economic part.

Context: Although the long-term goal of antihypertensive therapy is to reduce adverse clinical outcomes, the only way to evaluate the efficacy of treatment in an individual is the magnitude of blood pressure (BP) reduction. ACE inhibitors and angiotensin receptor blockers (ARBs) are two drug classes that, by different mechanisms, inhibit the renin-angiotensin- aldosterone system that regulates BP. As these drugs are widely prescribed for hypertension, it is essential to determine and compare their effects on BP, heart rate and tolerability. Objectives: 1) To determine the dose-related effect of ACE inhibitors and ARBs on BP, heart rate and withdrawals due to adverse effects (WDAE), compared with placebo in the treatment of primary hypertension (SBP ≥ 140 mm Hg and/or ≥ DPB 90 mm Hg); and 2) To compare the relative effect on BP, heart rate and WDAE of a) each ACE inhibitor with other ACE inhibitors, b) each ARB with other ARBs, and c) all ACE inhibitors with all ARBs. Methods: Two systematic reviews of published, double-blind, randomized, controlled trials (RCTs) evaluating the BP lowering efficacy of fixed dose monotherapy with an ACE inhibitor or ARB compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension were conducted. Electronic databases were searched for RCTs and similar trial inclusion criteria and methods of analysis were used in both reviews. Results: Ninety two RCTs evaluated the dose-related BP lowering efficacy of 14 ACE inhibitors in 12 954 participants with a baseline BP of 157.1/101.2 mm Hg. Forty six RCTs evaluated the dose-related BP lowering efficacy of 9 ARBs in 13 451 participants with a baseline BP of 155.6/101.0 mm Hg. The best estimate of the near maximal trough BP reduction for ACE inhibitors and ARBs was -8/-5 mm Hg and -8/-5 mm Hg, respectively. ACE inhibitors and ARBs do not affect heart rate. The evidence for short-term WDAE (tolerability) was incomplete and weak and did not demonstrate a difference between the two classes of drugs. Conclusion: ACE inhibitors and ARBs are not different individually or as drug classes in BP lowering efficacy. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

This thesis deals with the design of three labs in the simulation environment OPNET IT Guru. The first lab demonstrates the differences between the RM OSI transport layer protocols - TCP and UDP. The second lab discusses the role of ICMP protocol and its most famous feature - PING. The third lab is devoted to Application Characterization Environment (ACE) module, which is included in OPNET IT Guru. Theoretical background is provided for all of the mentioned topics. All designed labs can be used to teach at the Faculty of Electrical Engineering and Communication of BUT on subjects dealing with network technologies.

Lithium ist noch immer der Goldstandard in der Behandlung der bipolaren Störung und kommt auch in der Behandlung der unipolaren Depression zur Anwendung. Die therapeutische Breite von Lithium ist jedoch gering. Bei zu hohen Spiegeln kann es zu schweren Nebenwirkungen bis hin zu Intoxikationen mit letalem Verlauf kommen. Mit zunehmendem Lebensalter nimmt die renale Lithiumclearance ab. Hinzu kommen somatische Komorbiditäten, welche die renale Lithiumcelarance ebenfalls beeinträchtigen können. Darüber hinaus gibt es eine Vielzahl von Arzneimitteln, welche ebenfalls Einfluss auf den Lithiumspiegel nehmen können. Zu diesen zählen Diuretika, ACE-Hemmer und AT1-Rezeptor-Antagonisten sowie nicht-steroidale Antirheumatika, welche den am häufigsten rezeptierten Medikamente gehören. In einer retrospektiven naturalistischen Studie wurde der Einfluss einer Komedikation aus einem Schleifen- (Furosemid/Torasemid), Thiazid- (HCT) oder kaliumsparenden Diuretikum (Amilorid, Spironolacton, Triamteren), einem ACE-Inhibitor (Captopril, Enalapril, Lisinopril, Ramipril) oder AT1-Rezeptor-Antagonisten (Candesartan, Losartan, Irbesartan, Olmesartan, Valsartan) oder einem nicht-steroidalen Antirheumatikum (Acetylsalicylsäure, Diclofenac, Ibuprofen) auf den dosisbezogenen Lithiumspiegel untersucht. Als Stichprobe dienten 501 Lithiumpatienten, welche stationär im Zentrum für Psychische Gesundheit der Universitätsklinik Würzburg behandelt worden waren (01/2008 – 12/2015). 92 Patienten (18,4 %) nahmen nur eines der aufgeführten Medikamente ein, während 76 (15,1 %) eine Kombination von bis zu 5 Medikamenten erhielten – somit beinhaltete die Komedikation von 33,5 % der Patienten mindestens eines der aufgeführten Medikamente. Als Kontrollgruppe diente eine Stichprobe von 333 Lithiumpatienten ohne entsprechende Komedikation. Altersintrinsische Faktoren (p < 0,001; R2=0,289), die GFR (p < 0,001; R2=0,377) sowie das Geschlecht (p < 0,001; R2=0,406) scheinen den größten Einfluss auf den Lithiumspiegel zu nehmen (ca. 41 %), während für die Komedikation ein geringerer Effekt anzunehmen ist (ca. 4%). Die Ergebnisse sprechen für ein signifikantes Interaktionspotential von Diclofenac und Ibuprofen (p = 0,001). Es ergeben sich auch Hinweise auf ein relevantes Interaktionspotential von Hydrochlorothiazid (p = 0,020). Patienten, welche Acetylsalicylsäure (p < 0,001) oder Allopurinol (p = 0,003) erhalten, scheinen ein Risikokollektiv für erhöhte Lithiumspiegel darzustellen. Die dosisbezogenen Lithiumspiegel der Stichproben mit Einnahme eines ACE-Hemmers/AT1-Rezeptor-Antagonisten und eines Schleifendiuretikums unterschieden sich dagegen nicht signifikant von denen der Kontrollstichprobe ohne Komedikation. Es ist zudem davon auszugehen, dass eine Kombination mehrerer Pharmaka mit Interaktionspotential (p < 0,001) ein höheres Risiko für erhöhte dosisbezogene Lithiumspiegel birgt als eine Monotherapie (p = 0,026) und die Indikation einer solchen sollte daher kritisch geprüft werden. Eine zusätzliche Analyse von 32 Fällen von supratherapeutischen Lithiumserumkonzentrationen von ≥ 1,3 mmol/l (1,3–4,1mmol/l) legt nahe, dass sich ein Großteil von Lithiumintoxikationen durch regelmäßige Spiegelkontrollen und Dosisanpassungen unter Berücksichtigung von Komedikation, Alter und Komorbiditäten sowie Psychoedukation der Patienten vermeiden ließen. / Lithium is still the gold standard in treating bipolar disorder and is indicated in the treatment of unipolar depression as well. Lithium has a narrow therapeutic range. Elevated lithium levels can lead to severe adverse effects and lethal intoxications. With increasing age, lithium clearance decreases. Somatic comorbidities can decrease lithium clearance as well. Moreover, there is a large number of drugs, which can affect lithium clearance. Among those are diuretics, ACE-inhibitors/AT1-receptor-antagonists and non-steroidal anti-inflammatory drugs. All of them belong to the most frequently prescribed drug. Retrospective data of lithium serum levels was analysed in 501 inpatients, who had been treated in the Department of Psychiatry, Psychosomatics and Psychotherapy of the University Hospital of Würzburg (01/2008–12/2015). We wanted to investigate whether comedication of loop diuretics (Furosemide/Torasemide), thiaziddiuretics (Hydrochlorothizide) or potassium-sparing diuretics (Amiloride, Spironolactone, Triamterene), ACE-inhibitor (Captopril, Enalapril, Lisinopril, Ramipril) or AT1-receptor-antagonists (Candesartan, Losartan, Irbesartan, Olmesartan, Valsartan) or non-steroidal anti-inflammatory drugs (Acetylsalicylic acid, Diclofenac, Ibuprofen)affect the serum concentration of lithium. 92 inpatients (18.4 %) received one of the mentioned drugs, whereas 76 inpatients (15.1 %) received a combination of up to 5 drugs – thus a total of 33.5 % of the patients were treated with at least one potentially interacting drug. The control sample consisted of 333 inpatients whithout comedication of any interacting drug. Age intrinsic factors (p < 0.001; R2=0,289), gfr (p < 0.001; R2=0,377), and sex (p < 0.001; R2=0,406) had the greatest impact on serum lithium concentration (41%) whereas the effect of comedication was lower (4%). There is evidence that Diclofenac and Ibuprofen have a significant effect on dose related lithium concentration (p = 0.001). Possibly hydrochlorothiazide does so, too (p = 0.020). Moreover patients receiving Acetylsalicylic acid (p < 0.001) and Allopurinol (p = 0.003) are at higher risk for elevates lithium concentrations. Dose related lithium levels of the samples receiving an ACE-inhibitor/AT1-receptor-antagonist or loop diuretic did not significantly differ from the control sample without interacting comedication. A combination of potentially interacting drugs (p < 0.001) seems to be more critical than taking only one of the investigated drugs (p = 0.026) and thus the indication should be critically considered. An additional analysis of 32 cases with elevated lithium concentrations ≥ 1.3 mmol/l (1.3–4.1mmol/l) indicates, that most lithium intoxications could be avoided by regular measurements of lithium serum concentration and adaption of lithium dosage in regard of comedication, age and comorbidity if indicated and by patients´ psychoeducation.

Culex mosquitoes are known for carrying several harmful viruses in the United States. Culex tarsalis is found in rural as well as some residential areas in the Western United States, so they are under insecticide pressure from both agricultural spraying and vector control. In response to insecticide pressure, mosquitoes can evolve two primary resistance mechanisms: target site insensitivity, as a result of DNA mutation, and elevated levels of detoxifying enzymes (GST, alpha and beta esterases, and P450 oxidases). The two types of target site insensitivity studied here in Cx. tarsalis are kdr, which is a mutation in the para-type voltage gated sodium channel and ace-1, which is a mutation in acetylcholinesterase gene. This study focused on a population of Cx. tarsalis in Sutter County, where insecticide use shifted from sumithrin to Naled over the course of the summer. The goal of this study was to determine if there was resistance to insecticides and characterize the mechanisms of resistance. Mosquitoes were separated into resistance levels based on CDC bottle bioassay results using Naled, sumithrin, and permethrin insecticides. Mosquitoes were used to test for elevated levels of detoxifying enzymes and genetic qPCR testing for either kdr and ace-1 mutations. Bottle bioassay results suggest Cx. tarsalis populations from Sutter County are mostly resistant to pyrethroids while not being resistant to organophosphates. Enzymatic assays suggest high concentrations or activities of detoxifying enzymes are commonly seen in resistant individuals, occasionally elevated levels of multiple enzymes within an individual. The ace-1 mutation was seen in a single susceptible individual (0.036%). Either one or two kdr alleles were present in every single semi-resistant or resistant mosquito tested.

This study aims to analyse the relationship between the design and implementation of an Advanced Certificate in Education (ACE) in Mathematical Literacy (ML) (reskilling) program and the development of teacher identities. This study confirms that teacher learning in an in‐service context is a social process that demands a social‐cultural perspective and therefore Wenger’s theory was used in this study. This study illustrates that teachers’ participation in an ACE ML community of practice involved the complex intersection of various components of learning: meaning (learning as experience), practice (learning as doing) and community (learning as belonging) when development of teacher identities takes place. The course was also designed in such a way as to promote a changing way of being. The emerging identities were different in each individual as identity is influenced by the past, the present and the future according to Wenger. The study reveals that when meaning of the subject ML is gained, the meaning can be translated into changed classroom practice. These result in fostering a specific identity influenced by the ACE ML course’s attempts to support the development of understanding in relation to the meaning of ML. This leads to a change in classroom practice and ultimately a change in teachers’ way of ‘being’. This resonates with Wenger’s claim that the four learning components are deeply interconnected and mutually defined. The new trajectories that teachers developed can be grouped into three categories: • Where teachers back grounded their previous identities and fore grounded their ML identities. • Where the teachers added their ML identity to their existing identity, leaving them with a dual identity, the one they had before their involvement in the ACE ML course and the ML identity. • Where those teachers whose existing identity stayed strong, and their ML identity was still developing or was less strong.