scholarly journals The Biochemical Basis of Hydroxymethylglutaryl-CoA Reductase Inhibitors as Neuroprotective Agents in Aneurysmal Subarachnoid Hemorrhage

2010 ◽  
Vol 3 (10) ◽  
pp. 3186-3199 ◽  
Author(s):  
George Kwok Chu Wong ◽  
Wai Sang Poon
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Neuroprotective Agents ◽  
Biochemical Basis ◽  
Reductase Inhibitors ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase

The Natural Products as Hydroxymethylglutaryl-Coa Reductase Inhibitors

2019 ◽  
Vol 16 (10) ◽  
pp. 1130-1137
Author(s):  
Hayrettin Ozan Gulcan ◽  
Serkan Yigitkan ◽  
Ilkay Erdogan Orhan
Keyword(s):  
Natural Products ◽  
Cardiovascular System ◽  
High Cholesterol ◽  
Chemical Structures ◽  
Reductase Inhibitors ◽  
Key Enzyme ◽  
Serious Disease ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase ◽  
Alternative Drugs

High cholesterol and triglyceride levels are mainly related to further generation of lifethreating metabolism disorders including cardiovascular system diseases. Therefore, hypercholesterolemia (i.e., also referred to as hyperlipoproteinemia) is a serious disease state, which must be controlled. Currently, the treatment of hypercholesterolemia is mainly achieved through the employment of statins in the clinic, although there are alternative drugs (e.g., ezetimibe, cholestyramine). In fact, the original statins are natural products directly obtained from fungi-like molds and mushrooms and they are potent inhibitors of hydroxymethylglutaryl-CoA reductase, the key enzyme in the biosynthesis of cholesterol. This review focuses on the first identification of natural statins, their synthetic and semi-synthetic analogues, and the validation of hydroxymethylglutaryl-CoA reductase as a target in the treatment of hypercholesterolemia. Furthermore, other natural products that have been shown to possess the potential to inhibit hydroxymethylglutaryl-CoA reductase are also reviewed with respect to their chemical structures.

STATIN USE WAS NOT ASSOCIATED WITH LESS VASOSPASM OR IMPROVED OUTCOME AFTER SUBARACHNOID HEMORRHAGE

Neurosurgery ◽  
2008 ◽  
Vol 62 (2) ◽  
pp. 422-430 ◽  
Author(s):  
Andreas H. Kramer ◽  
Matthew J. Gurka ◽  
Bart Nathan ◽  
Aaron S. Dumont ◽  
Neal F. Kassell ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Vegetative State ◽  
Treatment Protocol ◽  
Poor Outcome ◽  
Reductase Inhibitors ◽  
Symptomatic Vasospasm ◽  
Endovascular Coil Embolization ◽  
Baseline Characteristics ◽  
Statin Use

Abstract OBJECTIVE The development of delayed ischemia caused by cerebral vasospasm remains a common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. Preliminary studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may decrease the risk of vasospasm, but additional study is required. METHODS Beginning in May 2006, our treatment protocol for patients presenting with subarachnoid hemorrhage was altered to routinely include the use of 80 mg of simvastatin per day for 14 days. Before this time, only patients with other indications for statins were treated. The charts of 203 consecutive patients over a period of 27 months were retrospectively reviewed, and 150 patients were included in the analysis, of whom 71 patients received statins. These patients were compared with 79 untreated patients to determine whether or not the use of statins was associated with a reduction in the occurrence of vasospasm, delayed infarction, or poor outcome (death, vegetative state, or severe disability). RESULTS Patients who were treated with statins and those who were not had similar baseline characteristics, although more patients in the former group were managed with endovascular coil embolization. There were no statistically significant differences in the proportion of patients developing at least moderate radiographic vasospasm (41% with statins versus 42% without, P = 0.91), symptomatic vasospasm (32% with statins versus 25% without, P = 0.34), delayed infarction (23% with statins versus 28% without, P = 0.46), or poor outcome (39% with statins versus 35% without, P = 0.61). After adjustment for differences in baseline characteristics, including the method of aneurysm treatment, statins were still not significantly protective. CONCLUSION The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. If there is a benefit to statin use, it may be smaller than suggested by previous studies. However, further randomized controlled trials are awaited.

scholarly journals Norepinephrine Transporter is Involved in Down-Regulation of β1-Adrenergic Receptors Caused by Adjuvant Arthritis

2009 ◽  
Vol 12 (3) ◽  
pp. 337 ◽  
Author(s):  
John D. Clements ◽  
Fakhreddin Jamali
Keyword(s):  
Calcium Channel ◽  
Adrenergic Receptors ◽  
Adjuvant Arthritis ◽  
Interferon Γ ◽  
Sprague Dawley ◽  
Reductase Inhibitors ◽  
Sprague Dawley Rats ◽  
Heart Homogenate ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase

Purpose. Inflammation in forms of rheumatoid and experimental arthritis cause not only joint pain but also excessive cardiovascular mortality. The condition also reduces response to calcium channel and β-adrenergic (β1-AR) antagonists. For calcium channel inhibitors, the reduced response is shown to be due to the reduced expression of target proteins. Hydroxymethylglutaryl CoA reductase inhibitors (statins) restore response to propranolol and verapamil. We tested the effect of adjuvant arthritis on the norepinephrine (NE) transporter (NET) density since altered sympathetic nervous system innervation has been observed in rheumatoid arthritis. Methods. Male Sprague–Dawley rats were divided into the following groups: Healthy/Placebo, Healthy/Statin, Pre-AA/Placebo, and Pre-AA/Statin (n=7-8/group). On Day 0, to the Pre-AA and Healthy groups, was injected Mycobacterium butyricum or saline, respectively. On Days 4-8, Statin and Placebo groups received either pravastatin (6 mg/kg) or placebo twice daily, respectively. On day 8, heart and blood samples were collected. The density of NET and 1-AR in heart homogenate; NE in plasma and heart and inflammatory mediators (nitrite and interferon-γ) in serum were determined. Results. Inflammation was associated with a significant reduction in both β1-AR and NET density with a positive correlation between the two proteins (r=0.978, p

scholarly journals Hydroxymethylglutaryl-CoA reductase inhibitors (statins) for the treatment of sepsis in adults—Authors’ reply

2019 ◽  
Vol 25 (12) ◽  
pp. 1572-1573
Author(s):  
B. Pertzov ◽  
N. Eliakim-Raz ◽  
H. Atamna ◽  
A.Z. Trestioreanu ◽  
D. Yahav ◽  
...  
Keyword(s):  
Reductase Inhibitors ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase

scholarly journals Statins and Cerebral Hemodynamics

2012 ◽  
Vol 32 (11) ◽  
pp. 1973-1976 ◽  
Author(s):  
Sotirios Giannopoulos ◽  
Aristeidis H Katsanos ◽  
Georgios Tsivgoulis ◽  
Randolph S Marshall
Keyword(s):  
Animal Studies ◽  
Small Vessel Disease ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Hemodynamics ◽  
Clinical Settings ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
Oxide Synthase

HMG-CoA reductase inhibitors (statins) are associated with improved stroke outcome. This observation has been attributed in part to the palliative effect of statins on cerebral hemodynamics and cerebral auto regulation (CA), which are mediated mainly through the upregulation of endothelium nitric oxide synthase (eNOS). Several animal studies indicate that statin pretreatment enhances cerebral blood flow after ischemic stroke, although this finding is not further supported in clinical settings. Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA.

Effect of Hydroxymethylglutaryl-CoA Reductase Inhibitors on the Functional Properties of Erythrocyte Membranes

1993 ◽  
Vol 59 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Rosa Anna Rabini ◽  
Mauro Polenta ◽  
Roberto Staffolani ◽  
Massimo Tocchini ◽  
Roberto Signore ◽  
...  
Keyword(s):  
Functional Properties ◽  
Erythrocyte Membranes ◽  
Reductase Inhibitors ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase

scholarly journals Uso de estatinas e o risco de Diabetes Mellitus tipo 2: Revisão Baseada na Evidência

2016 ◽  
Vol 11 (38) ◽  
pp. 1-8
Author(s):  
Susana Silva ◽  
Nuno Monteiro
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
National Guidelines ◽  
Reductase Inhibitors ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase

Objetivo: Determinar se existe relação entre o uso de estatinas e a incidência de Diabetes Melittus tipo 2 (DM2). Métodos: Foram realizadas pesquisas nas bases de dados National Guidelines Clearinghouse, Cochrane Lybrary, Trip database, PubMed e MedLine utilizando os termos MeSH “Diabetes Mellitus Type 2” e “Hydroxymethylglutaryl-CoA Reductase Inhibitors” (inibidores da HMG-CoA redutase). Foram incluídas revisões sistemáticas e meta-análises e ensaios clínicos aleatorizados e controlados que avaliassem a incidência de DM2 em utilizadores de estatinas, quando comparado com placebo. Resultados: Foram selecionados 10 artigos (1 meta-análise e 9 ensaios clínicos aleatorizados e controlados). A evidência sugere que o uso de estatinas está associado a um aumento da incidência de DM2, principalmente com doses elevadas, em relação ao placebo, na maioria dos estudos avaliados. Conclusão: O risco de incidência de DM2 deve ser considerado, especialmente quando da prescrição de estatinas a indivíduos com baixo risco cardiovascular (SOR A), embora os estudos selecionados apresentem algumas limitações (metodologia heterogênea, sendo a maioria observacional).

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