Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main advantage of the triphasic oral contraceptive (OC) is its reduced corticosteroid content, which is accompanied by a reduction in metabolic impact. Triphasic pills differ according to their components and according to whether or not their estrogen dose is constant. The Triella pill has a constant dose of 35 mcg ethinyl estradiol (EE) and a dose of norethisterone that increases from .50 to 1 mg, while Triquilar-Trinordiol mimics the preovulatory estrogen peak while also varying the progestin content. In a study of 22,728 cycles, the Pearl index was only .06/100 woman years for triphasic pills. Comparisons with existing monophasic pills indicate that triphasics may offer improved cycle control, but the fact should be emphasized to patients that cycle control is an inappropriate criterion for choice of pills. Metabolic effects or possible carcinogenic effects are more important qualities. Triphasic pills have been found to improve acne, not to affect weight or blood pressure, and to reduce the frequency of headaches, nervousness, and breast tenderness. Studies have shown that triphasics containing levonorgestrel produce minimal effects on lipid metabolism, while less rigorous studies on triphasics containing norethisterone have also yielded favorable results. It is true however that knowledge of the relationship between alterations in plasma cholesterol caused by Triella use and the etiology of certain diseases remains incomplete. Low dose triphasic pills appear to have fewer deleterious effects on glucose metabolism than higher dose pills, but they are not entirely without effect and should not be prescribed for women at risk of developing diabetes. Studies examining modifications of the intima and coagulation factors have given reassuring results, and neither triphasics with levonorgestrel nor those with norethisterone modify the blood pressure. Triphasics entail a reduction in the levels of estradiol and testosterone and a slight increase of plasma renin activity but no modification in plasma aldosterone. The subtle effects on the gonodotropic axis are considered especially fitting for young women in whom post-pill ovulatory function is preserved. Endometrial biopsies show that the state of the endometrium with OC use is not well understood and highly variable. The triphasic pill approaches as closely as possible the normal physiology of the endometrium while still suppressing ovulation.
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PMID:[The triphasic pill]. 1228 Feb 9

Epigenetic mechanisms might play a role in the pathophysiology of hypertension, a major risk factor for cardiovascular disease and renal failure. We aimed to systematically review studies investigating the association between epigenetic marks (global, candidate-gene or genome-wide methylation of DNA, and histone modifications) and blood pressure or hypertension. Five bibliographic databases were searched until the 7th of December 2018. Of 2984 identified references, 26 articles based on 25 unique studies met our inclusion criteria, which involved a total of 28,382 participants. The five studies that assessed global DNA methylation generally found lower methylation levels with higher systolic blood pressure, diastolic blood pressure, and/or presence of hypertension. Eighteen candidate-gene studies reported, in total, 16 differentially methylated genes, including renin-angiotensin-system-related genes (ACE promoter and AGTR1) and genes involved in sodium homeostasis and extracellular fluid volume maintenance system (NET promoter, SCNN1A, and ADD1). Between the three identified epigenome-wide association studies (EWAS), lower methylation levels of SULF1, EHMT2, and SKOR2 were found in hypertensive patients as compared with normotensive subjects, and lower methylation levels of PHGDH, SLC7A11, and TSPAN2 were associated with higher systolic and diastolic blood pressure. In summary, the most convincing evidence has been reported from candidate-gene studies, which show reproducible epigenetic changes in the interconnected renin-angiotensin and inflammatory systems. Our study highlights gaps in the literature on the role of histone modifications in blood pressure and the need to conduct high-quality studies, in particular, hypothesis-generating studies that may help to elucidate new molecular mechanisms.
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PMID:The role of DNA methylation and histone modifications in blood pressure: a systematic review. 3145 12

Background and objectives: Bradykinin-mediated angioedema (AE) induced by antihypertensive drugs primarily affect the head and neck region and may occur even after several years of uneventful treatment. Many facts about the clinical course remain unknown. Diagnosis is not easy, as the clinical appearance resembles allergic AE. No specific diagnostic markers are known and no officially approved treatment is currently available. Methods: All patients who presented to the ORL department between 2010 and 2016 with acute AE were included. Those with a history of renin-angiotensin-aldosterone system (RAAS) blocker intake were defined as RAE and their pathophysiological characteristics and clinical course of the disease were analyzed. Results: A total of 84 patients (median age of 71 years) with RAE was identified. The majority (80%) was on ACE inhibition. The oral cavity was most often affected. Nearly 60% were medicated for more than 1 year before AE occurred. RAE occurred more often during the morning hours. The necessity for emergency intubation and/or tracheostomy was nine times higher in patients with acute RAE compared to patients with AE due to other reasons. Conclusions: Event-free, long-term therapy with an RAAS blocker before the first development of edema does not exclude RAE. RAE is associated with an increased risk for emergency airway management. Abbreviations ACE: Angiotensin Converting Enzyme; ACEi AE: ACE inhibitor-induced angioedema; AE: Angioedema; ARB: Angiotensin II receptor 1 blocker; C1 INH: C1 Inhibitor; CI: Confidence Interval; CRP: C-reactive protein; DPP IV: Dipeptidyl peptidase IV; ENT: Ear, Nose and Throat; HAE: Hereditary Angioedema; ICD 10: International Statistical Classification of Diseases and Related Health Problems, 10th Edition; OR: Odds Ratio; ORL: Otorhinolaryngology; RAAS: Renin-Angiotensin-Aldosterone System; RAE: RAAS-blocker-induced angioedema.
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PMID:Clinical features of angioedema induced by renin-angiotensin-aldosterone system inhibition: a retrospective analysis of 84 patients. 3200 48