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Bardoxolone Methyl
Bardoxolone methyl (also known as “RTA 402”, “CDDO-methyl ester”, CDDO-Me, and more formally methyl bardoxolonate) is an experimental and orally-bioavailable semi-synthetic triterpenoid, based on the scaffold of the natural product oleanolic acid. Pre-clinical studies indicate that the compound acts as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway. A phase 3 clinical trial evaluating bardoxolone methyl for the treatment of chro nic kidney disease (CKD) was terminated in October 2012 after patients treated with the drug were found to have experienced a higher rate of heart-related adverse events, including heart failure, hospitalizations, and deaths. An advisory committee meeting of experts voted unanimously that bardoxolone methyl was not effective in slowing the progression of chronic kidney disease in Alport syndrome and that its benefits did not outweigh its risks. A Complete Response Letter from FDA stated a similar opinion. Clinical dev ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bioavailable
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via routes other than intravenous, its bioavailability is generally lower than that of intravenous due to intestinal endothelium absorption and first-pass metabolism. Thereby, mathematically, bioavailability equals the ratio of comparing the area under the plasma drug concentration curve versus time (AUC) for the extravascular formulation to the AUC for the intravascular formulation. AUC is used because AUC is proportional to the dose that has entered the systemic circulation. Bioavailability of a drug is an average value; to take population variability into account, deviation range is shown as ±. To ensure that the drug taker who has poor absorption is dosed appropriately, the bottom value of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NQO1
NAD(P)H dehydrogenase uinone1 is an enzyme that in humans is encoded by the ''NQO1'' gene. This protein-coding gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a 2-electron reductase (enzyme). This FAD-binding protein forms homodimers and performs two-electron reduction of quinones to hydroquinones and of other redox dyes. It has a preference for short-chain acceptor quinones, such as ubiquinone, benzoquinone, juglone and duroquinone. This gene has an important paralog NQO2. This protein is located in the cytosol. NQO1 enzyme expression can be induced by dioxin and inhibited by dicoumarol. Function This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This enzyme facilitates the two electron reduction of quinone to hydroquinone. NQO1-mediated two electron reduction of quinone to hydroquinone thereby indirectly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kidney Diseases
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option. Chronic kidney disease is defined as prolonged kidney abnormalities (functional and/or structural in nature) that last for more than three months. Acute kidney disease is now termed acute kidney injury and is marked by the sudden reduction in kidney function over seven days. In 2007, about one in eight A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
KEAP1
Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the ''Keap1'' gene. Structure Keap1 has four discrete protein domains. The N-terminal Broad complex, Tramtrack and Bric-à-Brac (BTB) domain contains the Cys151 residue, which is one of the important cysteines in stress sensing. The intervening region (IVR) domain contains two critical cysteine residues, Cys273 and Cys288, which are a second group of cysteines important for stress sensing. A double glycine repeat (DGR) and C-terminal region (CTR) domains collaborate to form a β-propeller structure, which is where Keap1 interacts with Nrf2. Interactions Keap1 has been shown to interact with Nrf2, a master regulator of the antioxidant response, which is important for the amelioration of oxidative stress. Under quiescent conditions, Nrf2 is anchored in the cytoplasm through binding to Keap1, which, in turn, facilitates the ubiquitination and subsequent proteolysis of Nrf2. Such sequestratio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Brain Natriuretic Peptide
Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. Along with NT-proBNP, BNP is one of two natriuretic peptides. The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid N-terminal fragment in the prohormone called NT-proBNP (BNPT), which is biologically inactive. Once released, BNP binds to and activates the atrial natriuretic factor receptor NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing. The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as wel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Heart Failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is measured by the severity of symptoms during exercise. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease. Common causes of heart failure include coronary artery disease, heart attack, high blood pressure, atrial fibrillation, valvular heart disease, excessive alcohol consumption, infection, and cardiomyopathy. These cause heart failure by altering ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Post-hoc Analyses
In a scientific study, post hoc analysis (from Latin '' post hoc'', "after this") consists of statistical analyses that were specified after the data were seen. They are usually used to uncover specific differences between three or more group means when an analysis of variance (ANOVA) test is significant. This typically creates a multiple testing problem because each potential analysis is effectively a statistical test. Multiple testing procedures are sometimes used to compensate, but that is often difficult or impossible to do precisely. Post hoc analysis that is conducted and interpreted without adequate consideration of this problem is sometimes called ''data dredging'' by critics because the statistical associations that it finds are often spurious. Common post hoc tests Some common post hoc tests include: {{Cite web , last=Pamplona , first=Fabricio , date=2022-07-28 , title=Post Hoc Analysis: Process and types of tests , url=https://mindthegraph.com/blog/post-hoc-analysis/ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase 3 Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over severa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. AEs in patients participating in clinical trials must be reported to the study sponsor and if required could be reported to the local ethics committee. Adverse events categorized as "serious" (results in death, illness requiring hospitalization, events deemed life-threatening, results in persistent or significant incapacity, a congenital anomaly, birth defect or medically important condition) must be reported to the regulatory authorities immediately, whereas non-serious adverse events are ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Clinical Endpoint
Clinical endpoints or clinical outcomes are Outcome measure, outcome measures referring to occurrence of disease, symptom, Medical sign, sign or laboratory abnormality constituting a target outcome in clinical trial, clinical research trials. The term may also refer to any disease or sign that strongly motivates withdrawal of an individual or entity from the trial, then often termed a ''humane (clinical) endpoint''. The primary endpoint of a clinical trial is the endpoint for which the trial is statistical power, powered. Secondary endpoints are additional endpoints, preferably also pre-specified, for which the trial may not be powered. Surrogate endpoint, Surrogate endpoints are trial endpoints that have outcomes that substitute for a clinical endpoint, often because studying the clinical endpoint is difficult, for example using an increase in blood pressure as a surrogate for death by cardiovascular disease, where strong evidence of a causal link exists. Scope In a general sens ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Controlled Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase 2 Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over severa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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