The objective of this work was to produce bioactive peptides from the enzymatic hydrolysis of chicken skin proteins that could be used to treat hypertension, oxidative stress and associated health conditions using a metabolomics approach. Enzymatic hydrolysis of chicken thigh and breast muscle skin proteins was carried out using alcalase or a combination of pepsin/pancreatin (PP) at 1–4% enzyme concentrations. Chicken skin protein hydrolysates (CSPH) were each fractionated by membrane ultrafiltration into different molecular weight peptides (<1, 1–3, 3–5 and 5–10 kDa). Investigation of their in vitro antihypertensive and antioxidant activities showed that alcalase hydrolysates had significantly (p < 0.05) higher ACE-inhibitory activity compared to PP hydrolysates. ACE inhibition was inversely related to size of ultrafiltration membrane peptides. Renin-inhibitory activity varied from 15–36%, and was dependent on the type of protease; PP hydrolysates showed significantly (p < 0.05) higher inhibition than alcalase hydrolysates. CSPHs also significantly (p < 0.05) scavenged antioxidant radicals, increasing with enzyme concentration but decreased as peptide size increased. Kinetics studies revealed that peptide-dependent enzyme inhibition pattern was mostly of the mixed-type for both ACE and renin. Short-term (24 hr) oral administration of 100 mg peptides/kg body weight to spontaneously hypertensive rats (SHRs) led to maximum systolic blood pressure (SBP) reduction of –32.67 and –31.33 mmHg after 6 h for chicken thigh skin hydrolysate and chicken breast skin hydrolysate, respectively. During a 6-week feeding trial, CSPH at 1.0 and 0.5% feed substitutions had significant (p<0.05) antihypertensive effects in SHRs (-36 and -31 SBP reductions, respectively). SBP reduction was directly related to lower plasma ACE but not renin activity. Plasma total antioxidant capacity of the rats was also high. Metabolomics analysis revealed several metabolites with significant changes (≥ 2-fold changes, p < 0.05) in urine and plasma of SHRs fed CSPH, such as Symmetric Dimethylarginine (SDMA), N2-acetyl-L-ornithine, buthionine sulfoximine, uric acid, Vitamin E succinate, L-isoleucine and phospholipids which may be considered important biomarkers/pathways for hypertension and oxidative stress. We conclude that CSPHs may be used as ingredients to formulate functional foods and nutraceuticals for the management of oxidative stress and hypertension-related diseases. / October 2015

No description available.

Thesis (Ph.D.). / Written for the Dept. of Epidemiology and Biostatistics. Title from title page of PDF (viewed 2008/05/08). Includes bibliographical references.

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1981. / English, summary and foreword in Dutch. Includes bibliographies.

Class of 2005 Abstract / Objectives: The objectives of this study were to assess the number of antihypertensive prescriptions by therapeutic class including beta-blockers, calcium channel blockers (CCBs), diuretics, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), dispensed in the fiscal years 2002 through 2004. Methods: The project was a retrospective analysis of pharmacy data for medications used to treat hypertension from October 2002 through December 2004 (FY02 through the first quarter of FY05). Drug classes used to treat hypertension were obtained from the VA Integrated Service Network 18 (VISN 18). Within the drug classes, only drugs within the class having at least 100 prescriptions were included for the class. Rates of prescriptions dispensed by quarter over the three-year period of interest were obtained. Descriptive statistics were used to compare the before and after ALLHAT and JNC-7 time periods. Results: After the publication of The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), The Australian National Blood Pressure Study 2 (ANBP2), and Joint National Committee (JNC-7) guidelines, dihydropyridine CCB use declined to from 1.80% to 1.65% and non-dihydropyridine CCB use declined from 0.99% to 0.83% of all prescriptions from the first quarter 2002 to the first quarter 2004. In addition, after the publication of ALLHAT, hydrochlorothiazide use increased from 1.42% to 1.83% and ACE-inhibitor use increased from 4.26% to 4.79% of all prescriptions. Implications: The findings have several implications for encouraging our prescribing patterns to follow national guidelines and clinical studies more closely. Health care providers need to accept some responsibility through continuous education to be able to maintain appropriate therapy.

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No description available.

5 ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Anna Tláskalová Supervisor - specialist: Mgr. Martin Mžik Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Title: LC-HRMS analysis of selected antihypertensive drugs in biological material for compliance assessment About 40 % of Czech population between the ages of 25 and 64 suffer from arterial hypertension. Although an array of effective antihypertensives is available nowadays, optimal blood pressure during treatment is reached by mere 30 % of the patients. This is mainly due to the patients' poor adherence to the treatment, who use their medicaments incorrectly or not at all. The adherence of a patient to the treatment, as well as pharmacokinetics, represent the most significant source of variability of the answer to the treatment and notably influences its outcome. The monitoring of plasmatic levels of antihypertensives is one of the methods of modern medicine which enables both an effective supervision of the incorrectly compensated patients, and the adjustment of dosage scheme. This diploma thesis focuses on development and optimisation of extraction procedures for selected antihypertensives (amiloride, amlodipine, betaxolol, bisoprolol, carvedilol, celiprolol,...

Lau Siu Wai Maggie. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 236-245). / List of Figures --- p.i / List of Tables --- p.viii / List of Abbreviations --- p.x / Abstract --- p.xii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Postulated Pathophysiology of Essential Hypertension --- p.1 / Chapter 1.2 --- Measurement of Cardiac Output (CO) by Transthoracic Electrical Bioimpedance (TEB) and Other Methodologies --- p.6 / Chapter 1.3 --- Measurement of Blood Pressure --- p.10 / Chapter 1.4 --- Use of Antihypertensive Agents in Essential Hypertension --- p.12 / Chapter Chapter 2. --- The Method of Transthoracic Electrical Bioimpedance --- p.15 / Chapter 2.1 --- Introduction --- p.15 / Chapter 2.2 --- Development of Theory --- p.18 / Chapter 2.3 --- Measurements of Haemodynamic Parameters --- p.24 / Chapter 2.4 --- Literature Review - Validity of the Technique --- p.30 / Chapter Chapter 3 --- A Study on Reproducibility of Thoracic Electrical Bioimpedance in Healthy Subjects --- p.39 / Chapter 3.1 --- Objectives --- p.39 / Chapter 3.2 --- Methodology --- p.39 / Chapter 3.2.1 --- Subjects --- p.39 / Chapter 3.2.2 --- Study design --- p.41 / Chapter 3.2.3 --- Non-invasive haemodynamic monitoring --- p.41 / Chapter 3.2.4 --- Blood Pressure Measurement --- p.43 / Chapter 3.2.5 --- Isometric Exercise --- p.43 / Chapter 3.2.6 --- Data analysis --- p.44 / Chapter 3.2.7 --- Statistical analysis --- p.46 / Chapter 3.3 --- Results --- p.50 / Chapter 3.3.1 --- Systolic blood pressure --- p.50 / Chapter 3.3.2 --- Diastolic blood pressure --- p.52 / Chapter 3.3.3 --- Mean arterial pressure --- p.54 / Chapter 3.3.4 --- Heart rate --- p.55 / Chapter 3.3.5 --- Thoracic fluid index --- p.58 / Chapter 3.3.6 --- Stroke index --- p.60 / Chapter 3.3.7 --- Cardiac index --- p.62 / Chapter 3.3.8 --- Systemic vascular resistance index --- p.65 / Chapter 3.4 --- Discussion --- p.70 / Chapter Chapter 4 --- Literature Review --- p.73 / Chapter 4.1 --- Atenolol: Beta-adrenoceptor antagonists with β1-selectivity --- p.73 / Chapter 4.2 --- Pindolol: Beta-adrenoceptor antagonists with ISA --- p.78 / Chapter 4.3 --- Alpha1-adrenoceptor antagonists --- p.81 / Chapter 4.4 --- Angiotensin Converting Enzyme Inhibitors --- p.84 / Chapter 4.5 --- Calcium Channel Blockers --- p.87 / Chapter 4.6 --- Central Alpha Agonist --- p.91 / Chapter 4.7 --- Thiazide Diuretics --- p.94 / Chapter Chapter 5 --- The Integrated Hypertension Study --- p.97 / Chapter 5.1 --- Objectives --- p.97 / Chapter 5.2 --- Methodology --- p.97 / Chapter 5.2.1 --- Subjects --- p.97 / Chapter 5.2.2 --- Study design --- p.109 / Chapter 5.2.3 --- Non-invasive haemodynamic monitoring --- p.110 / Chapter 5.2 4 --- Blood Pressure Measurement --- p.111 / Chapter 5.2.5 --- Isometric Exercise --- p.111 / Chapter 5.2.6 --- Data analysis --- p.111 / Chapter 5.2.7 --- Statistical analysis --- p.112 / Chapter 5.2.8 --- Limitations of the study --- p.113 / Chapter 5.3 --- Results --- p.117 / Chapter 5.3.1 --- Atenolol --- p.117 / Chapter 5.3.2 --- Pindolol --- p.125 / Chapter 5.3.3 --- Doxazosin --- p.132 / Chapter 5.3.4 --- Enalapril --- p.138 / Chapter 5.3.5 --- Nifedipine Retard --- p.145 / Chapter 5.3.6 --- Methyldopa --- p.152 / Chapter 5.3.7 --- Cyclopenthiazide --- p.160 / Chapter 5.4 --- Comparisons of the anti-hypertensive drugs studied --- p.167 / Chapter 5.4.1 --- Baseline values --- p.167 / Chapter 5.4.2 --- Percentage changes after active treatment --- p.170 / Chapter 5.5 --- Discussion --- p.196 / Chapter 5.5.1 --- Atenolol --- p.196 / Chapter 5.5.2 --- Pindolol --- p.199 / Chapter 5.5.3 --- Doxazosin --- p.200 / Chapter 5.5.4 --- Enalapril --- p.202 / Chapter 5.5.5 --- Nifedipine Retard --- p.203 / Chapter 5.5.6 --- Methyldopa --- p.204 / Chapter 5.5.7 --- Cyclopenthiazide --- p.205 / Chapter 5.5.8 --- Comparison of the anti-hypertensive drugs studied --- p.206 / Chapter Chapter 6 --- Acute haemodynamic effects of Atenolol and Pindolol --- p.208 / Chapter 6.1 --- Objectives --- p.208 / Chapter 6.2 --- Methodology --- p.208 / Chapter 6.2.1 --- Subjects --- p.208 / Chapter 6.2.2 --- Study Design --- p.209 / Chapter 6.2.3 --- Statistical analysis --- p.209 / Chapter 6.3 --- Results --- p.211 / Chapter 6.3.1 --- Acute haemodynamic changes of atenolol --- p.211 / Chapter 6.3.2 --- Acute and short-term haemodynamic changes of atenolol --- p.219 / Chapter 6.3.3 --- Acute haemodymmic changes of pindolol --- p.221 / Chapter 6.3.4 --- Acute and short-term haemodymmic changes of pindolol --- p.222 / Chapter 6.3.5 --- Comparison of the acute haemodymmic effects of atenolol and pindolol --- p.226 / Chapter 6.4 --- Discussion --- p.230 / Chapter Chapter 7 --- Conclusion --- p.232 / References --- p.236 / Acknowledgements

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 52-56).