Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.Lisinopril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Perindopril: An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure.Enalaprilat: The active metabolite of ENALAPRIL and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.Antihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.Angiotensin II Type 1 Receptor Blockers: Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.Cilazapril: One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Teprotide: A synthetic nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) which is identical to the peptide from the venom of the snake, Bothrops jararaca. It inhibits kininase II and ANGIOTENSIN I and has been proposed as an antihypertensive agent.Renin-Angiotensin System: A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.Hypertension: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.ThiazepinesBlood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.TetrazolesRenin: A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.Diuretics: Agents that promote the excretion of urine through their effects on kidney function.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Imidazolidines: Compounds based on reduced IMIDAZOLINES which contain no double bonds in the ring.Angioedema: Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.Tetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.3-Mercaptopropionic Acid: An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.Drug Therapy, Combination: Therapy with two or more separate preparations given for a combined effect.Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.Biphenyl CompoundsFosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat.Rats, Inbred SHR: A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke.Saralasin: An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Hyperkalemia: Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Angiotensins: Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Sodium Chloride Symporter Inhibitors: Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.Aldosterone: A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent.Hypertension, Renal: Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Benzazepines: Compounds with BENZENE fused to AZEPINES.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Diabetic Nephropathies: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.Mineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.Rats, Inbred WKY: A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Amlodipine: A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)Hypertension, Renovascular: Hypertension due to RENAL ARTERY OBSTRUCTION or compression.Mopidamol: A phosphodiesterase inhibitor which inhibits platelet aggregation. Formerly used as an antineoplastic.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Dipeptides: Peptides composed of two amino acid units.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Albuminuria: The presence of albumin in the urine, an indicator of KIDNEY DISEASES.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.CreatinineMyocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Oligohydramnios: A condition of abnormally low AMNIOTIC FLUID volume. Principal causes include malformations of fetal URINARY TRACT; FETAL GROWTH RETARDATION; GESTATIONAL HYPERTENSION; nicotine poisoning; and PROLONGED PREGNANCY.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Cough: A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs.Fumarates: Compounds based on fumaric acid.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Oligopeptides: Peptides composed of between two and twelve amino acids.Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Renal Circulation: The circulation of the BLOOD through the vessels of the KIDNEY.Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Angiotensinogen: An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.Receptor, Angiotensin, Type 2: An angiotensin receptor subtype that is expressed at high levels in fetal tissues. Many effects of the angiotensin type 2 receptor such as VASODILATION and sodium loss are the opposite of that of the ANGIOTENSIN TYPE 1 RECEPTOR.Nephrectomy: Excision of kidney.Drug Utilization Review: Formal programs for assessing drug prescription against some standard. Drug utilization review may consider clinical appropriateness, cost effectiveness, and, in some cases, outcomes. Review is usually retrospective, but some analysis may be done before drugs are dispensed (as in computer systems which advise physicians when prescriptions are entered). Drug utilization review is mandated for Medicaid programs beginning in 1993.Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Secondary Prevention: The prevention of recurrences or exacerbations of a disease or complications of its therapy.Randomized Controlled Trials as Topic: Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Receptor, Bradykinin B1: A subtype of BRADYKININ RECEPTOR that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Digitalis: A genus of toxic herbaceous Eurasian plants of the Plantaginaceae which yield cardiotonic DIGITALIS GLYCOSIDES. The most useful species are Digitalis lanata and D. purpurea.Cyclohexanones: Cyclohexane ring substituted by one or more ketones in any position.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Practice Guidelines as Topic: Directions or principles presenting current or future rules of policy for assisting health care practitioners in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Doxazosin: A prazosin-related compound that is a selective alpha-1-adrenergic blocker.Digoxin: A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)Organ Size: The measurement of an organ in volume, mass, or heaviness.Angiotensin II Type 2 Receptor Blockers: Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Atenolol: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Diet, Sodium-Restricted: A diet which contains very little sodium chloride. It is prescribed by some for hypertension and for edematous states. (Dorland, 27th ed)Drug Utilization: The utilization of drugs as reported in individual hospital studies, FDA studies, marketing, or consumption, etc. This includes drug stockpiling, and patient drug profiles.Guideline Adherence: Conformity in fulfilling or following official, recognized, or institutional requirements, guidelines, recommendations, protocols, pathways, or other standards.Neprilysin: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.Hypotension: Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Aminopeptidases: A subclass of EXOPEPTIDASES that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Systole: Period of contraction of the HEART, especially of the HEART VENTRICLES.Bicyclo CompoundsEndothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Indapamide: A benzamide-sulfonamide-indole derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS.Benzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Cross-Over Studies: Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. (Last, A Dictionary of Epidemiology, 2d ed)PyridazinesEndothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)Sulfinpyrazone: A uricosuric drug that is used to reduce the serum urate levels in gout therapy. It lacks anti-inflammatory, analgesic, and diuretic properties.Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Cardiology: The study of the heart, its physiology, and its functions.Heart: The hollow, muscular organ that maintains the circulation of the blood.Nephrotic Syndrome: A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.Benzothiadiazines: Heterocyclic compounds of a ring with SULFUR and two NITROGEN atoms fused to a BENZENE ring. Members inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.Renal Insufficiency: Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77).Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.Amides: Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Acute Kidney Injury: Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.IndolizinesHypertension, Malignant: A condition of markedly elevated BLOOD PRESSURE with DIASTOLIC PRESSURE usually greater than 120 mm Hg. Malignant hypertension is characterized by widespread vascular damage, PAPILLEDEMA, retinopathy, HYPERTENSIVE ENCEPHALOPATHY, and renal dysfunction.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Sodium, Dietary: Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Fees, Pharmaceutical: Amounts charged to the patient or third-party payer for medication. It includes the pharmacist's professional fee and cost of ingredients, containers, etc.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Cardiomyopathy, Dilated: A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.Physician's Practice Patterns: Patterns of practice related to diagnosis and treatment as especially influenced by cost of the service requested and provided.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi.Glomerulonephritis, IGA: A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Sodium: A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS.Dihydralazine: 1,4-Dihydrazinophthalazine. An antihypertensive agent with actions and uses similar to those of HYDRALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p354)Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Metoprolol: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.United StatesCardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Thiazolidines: Reduced (protonated) form of THIAZOLES. They can be oxidized to THIAZOLIDINEDIONES.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Evidence-Based Medicine: An approach of practicing medicine with the goal to improve and evaluate patient care. It requires the judicious integration of best research evidence with the patient's values to make decisions about medical care. This method is to help physicians make proper diagnosis, devise best testing plan, choose best treatment and methods of disease prevention, as well as develop guidelines for large groups of patients with the same disease. (from JAMA 296 (9), 2006)Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Drug Prescriptions: Directions written for the obtaining and use of DRUGS.Coronary Artery Disease: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.Glomerulosclerosis, Focal Segmental: A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Renal Artery Obstruction: Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Diabetes Complications: Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE.Drinking: The consumption of liquids.Aorta: The main trunk of the systemic arteries.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.

The interaction of rhodium(II) carboxylates with enzymes. (1/39504)

The effect of rhodium(II) acetate, propionate, and methoxyacetate on the activity of 17 enzymes was evaluated. The enzymes were preincubated with the rhodium(II) complexes in order to detect irreversible inhibition. All enzymes that have essential sulfhydryl groups in or near their active site were found to be irreversibly inhibited. Those enzymes without essential sulfhydryl groups were not affected. In each case, the rate of inactivation closely paralleled the observed toxicity and antitumor activity of rhodium(II) carboxylates; that is, rhodium(II) propionate greater than rhodium(II) acetate greater than rhodium(II) methoxyacetate. In addition, those enzymes that have been demonstrated to be most sensitive to established sulfhydryl inhibitors, such as glyceraldehyde-3-phosphate dehydrogenase, were also most sensitive to rhodium(II) carboxylate inactivation. Proton nuclear magnetic resonance measurements made during the titration of rhodium(II) acetate with cysteine showed that breakdown of the carboxylate cage occurred as a result of reaction with this sulfhydryl-containing amino acid.  (+info)

Does gill boundary layer carbonic anhydrase contribute to carbon dioxide excretion: a comparison between dogfish (Squalus acanthias) and rainbow trout (Oncorhynchus mykiss). (2/39504)

In vivo experiments were conducted on spiny dogfish (Squalus acanthias) and rainbow trout (Oncorhynchus mykiss) in sea water to determine the potential role of externally oriented or gill boundary layer carbonic anhydrase in carbon dioxide excretion. This was accomplished by assessing pH changes in expired water using a stopped-flow apparatus. In dogfish, expired water was in acid-base disequilibrium as indicated by a pronounced acidification (delta pH=-0.11+/-0.01; N=22; mean +/- s.e.m.) during the period of stopped flow; inspired water, however, was in acid-base equilibrium (delta pH=-0.002+/-0.01; N=22). The acid-base disequilibrium in expired water was abolished (delta pH=-0.005+/-0.01; N=6) by the addition of bovine carbonic anhydrase (5 mg l-1) to the external medium. Addition of the carbonic anhydrase inhibitor acetazolamide (1 mmol l-1) to the water significantly reduced the magnitude of the pH disequilibrium (from -0.133+/-0.03 to -0.063+/-0.02; N=4). However, after correcting for the increased buffering capacity of the water caused by acetazolamide, the acid-base disequilibrium during stopped flow was unaffected by this treatment (control delta [H+]=99.8+/-22.8 micromol l-1; acetazolamide delta [H+]=81.3+/-21.5 micromol l-1). In rainbow trout, expired water displayed an acid-base disequilibrium (delta pH=0.09+/-0.01; N=6) that also was abolished by the application of external carbonic anhydrase (delta pH=0.02+/-0.01). The origin of the expired water acid-base disequilibrium was investigated further in dogfish. Intravascular injection of acetazolamide (40 mg kg-1) to inhibit internal carbonic anhydrase activity non-specifically and thus CO2 excretion significantly diminished the extent of the expired water disequilibrium pH after 30 min (from -0.123+/-0.01 to -0.065+/-0.01; N=6). Selective inhibition of extracellular carbonic anhydrase activity using a low intravascular dose (1.3 mg kg-1) of the inhibitor benzolamide caused a significant reduction in the acid-base disequilibrium after 5 min (from -0.11+/-0.01 to -0.07+/-0. 01; N=14). These results demonstrate that the expired water acid-base disequilibrium originates, at least in part, from excretory CO2 and that extracellular carbonic anhydrase in dogfish may have a significant role in carbon dioxide excretion. However, externally oriented carbonic anhydrase (if present in dogfish) plays no role in catalysing the hydration of the excretory CO2 in water flowing over the gills and thus is unlikely to facilitate CO2 excretion.  (+info)

A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. (3/39504)

Mouse cytomegalovirus (MCMV) early gene expression interferes with the major histocompatibility complex class I (MHC class I) pathway of antigen presentation. Here we identify a 48 kDa type I transmembrane glycoprotein encoded by the MCMV early gene m06, which tightly binds to properly folded beta2-microglobulin (beta2m)-associated MHC class I molecules in the endoplasmic reticulum (ER). This association is mediated by the lumenal/transmembrane part of the protein. gp48-MHC class I complexes are transported out of the ER, pass the Golgi, but instead of being expressed on the cell surface, they are redirected to the endocytic route and rapidly degraded in a Lamp-1(+) compartment. As a result, m06-expressing cells are impaired in presenting antigenic peptides to CD8(+) T cells. The cytoplasmic tail of gp48 contains two di-leucine motifs. Mutation of the membrane-proximal di-leucine motif of gp48 restored surface expression of MHC class I, while mutation of the distal one had no effect. The results establish a novel viral mechanism for downregulation of MHC class I molecules by directly binding surface-destined MHC complexes and exploiting the cellular di-leucine sorting machinery for lysosomal degradation.  (+info)

p50(cdc37) acting in concert with Hsp90 is required for Raf-1 function. (4/39504)

Genetic screens in Drosophila have identified p50(cdc37) to be an essential component of the sevenless receptor/mitogen-activated kinase protein (MAPK) signaling pathway, but neither the function nor the target of p50(cdc37) in this pathway has been defined. In this study, we examined the role of p50(cdc37) and its Hsp90 chaperone partner in Raf/Mek/MAPK signaling biochemically. We found that coexpression of wild-type p50(cdc37) with Raf-1 resulted in robust and dose-dependent activation of Raf-1 in Sf9 cells. In addition, p50(cdc37) greatly potentiated v-Src-mediated Raf-1 activation. Moreover, we found that p50(cdc37) is the primary determinant of Hsp90 recruitment to Raf-1. Overexpression of a p50(cdc37) mutant which is unable to recruit Hsp90 into the Raf-1 complex inhibited Raf-1 and MAPK activation by growth factors. Similarly, pretreatment with geldanamycin (GA), an Hsp90-specific inhibitor, prevented both the association of Raf-1 with the p50(cdc37)-Hsp90 heterodimer and Raf-1 kinase activation by serum. Activation of Raf-1 via baculovirus coexpression with oncogenic Src or Ras in Sf9 cells was also strongly inhibited by dominant negative p50(cdc37) or by GA. Thus, formation of a ternary Raf-1-p50(cdc37)-Hsp90 complex is crucial for Raf-1 activity and MAPK pathway signaling. These results provide the first biochemical evidence for the requirement of the p50(cdc37)-Hsp90 complex in protein kinase regulation and for Raf-1 function in particular.  (+info)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (5/39504)

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules.  (+info)

Cell growth inhibition by farnesyltransferase inhibitors is mediated by gain of geranylgeranylated RhoB. (6/39504)

Recent results have shown that the ability of farnesyltransferase inhibitors (FTIs) to inhibit malignant cell transformation and Ras prenylation can be separated. We proposed previously that farnesylated Rho proteins are important targets for alternation by FTIs, based on studies of RhoB (the FTI-Rho hypothesis). Cells treated with FTIs exhibit a loss of farnesylated RhoB but a gain of geranylgeranylated RhoB (RhoB-GG), which is associated with loss of growth-promoting activity. In this study, we tested whether the gain of RhoB-GG elicited by FTI treatment was sufficient to mediate FTI-induced cell growth inhibition. In support of this hypothesis, when expressed in Ras-transformed cells RhoB-GG induced phenotypic reversion, cell growth inhibition, and activation of the cell cycle kinase inhibitor p21WAF1. RhoB-GG did not affect the phenotype or growth of normal cells. These effects were similar to FTI treatment insofar as they were all induced in transformed cells but not in normal cells. RhoB-GG did not promote anoikis of Ras-transformed cells, implying that this response to FTIs involves loss-of-function effects. Our findings corroborate the FTI-Rho hypothesis and demonstrate that gain-of-function effects on Rho are part of the drug mechanism. Gain of RhoB-GG may explain how FTIs inhibit the growth of human tumor cells that lack Ras mutations.  (+info)

Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor. (7/39504)

Neu differentiation factors (NDFs), or neuregulins, are epidermal growth factor-like growth factors which bind to two tyrosine kinase receptors, ErbB-3 and ErbB-4. The transcription of several genes is regulated by neuregulins, including genes encoding specific subunits of the acetylcholine receptor at the neuromuscular junction. Here, we have examined the promoter of the acetylcholine receptor epsilon subunit and delineated a minimal CA-rich sequence which mediates transcriptional activation by NDF (NDF-response element [NRE]). Using gel mobility shift analysis with an NRE oligonucleotide, we detected two complexes that are induced by treatment with neuregulin and other growth factors and identified Sp1, a constitutively expressed zinc finger phosphoprotein, as a component of one of these complexes. Phosphatase treatment, two-dimensional gel electrophoresis, and an in-gel kinase assay indicated that Sp1 is phosphorylated by a 60-kDa kinase in response to NDF-induced signals. Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus.  (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (8/39504)

To investigate the mode of action of the p16(INK4a) tumor suppressor protein, we have established U2-OS cells in which the expression of p16(INK4a) can be regulated by addition or removal of isopropyl-beta-D-thiogalactopyranoside. As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. However, induction of p16(INK4a) also causes marked inhibition of CDK2 activity. In the case of cyclin E-CDK2, this is brought about by reassortment of cyclin, CDK, and CDK-inhibitor complexes, particularly those involving p27(KIP1). Size fractionation of the cellular lysates reveals that a substantial proportion of CDK4 participates in active kinase complexes of around 200 kDa. Upon induction of p16(INK4a), this complex is partly dissociated, and the majority of CDK4 is found in lower-molecular-weight fractions consistent with the formation of a binary complex with p16(INK4a). Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 by p27(KIP1) and p21(CIP1). Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6.  (+info)

*Moexipril

... hydrochloride is a potent orally active nonsulfhydryl angiotensin converting enzyme inhibitor (ACE inhibitor) which ... Chrysant, S. G. (1998). "Vascular remodeling: The role of angiotensin-converting enzyme inhibitors". American Heart Journal. ... "Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity ... AN IMPORTANT INTERMEDIATE IN THE SYNTHESIS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS". Organic Preparations and Procedures ...

*Quinapril

... (marketed under the brand name Accupril by Pfizer) is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used ... Quinapril inhibits angiotensin converting enzyme, an enzyme which catalyses the formation of angiotensin II from its precursor ... Impaired renal and liver function Patients with a history of angioedema related to previous treatment with an ACE inhibitor ...

*Teprotide

It is an angiotensin converting enzyme inhibitor (ACE inhibitor), which inhibits the conversion of angiotensin I to angiotensin ... "Angiotensin-converting enzyme inhibitors from the venom of bothrops jararaca. Isolation, elucidation of structure, and ... "History of the design of captopril and related inhibitors of angiotensin converting enzyme". Hypertension. 17 (4): 589-592. doi ... Many ACE inhibitors have been developed since this time but this was the start of them. Ferreira, Sergio (February 1965). "A ...

*Angiotensin II receptor blocker

Gales BJ, Bailey EK, Reed AN, Gales MA (February 2010). "Angiotensin-converting enzyme inhibitors and angiotensin receptor ... In addition, there is also a small risk of cross-reactivity in patients having experienced angioedema with ACE inhibitor ... and are thus only rarely associated with the persistent dry cough and/or angioedema that limit ACE inhibitor therapy.[citation ... of the main rationales for the use of this class is the avoidance of dry cough and/or angioedema associated with ACE inhibitor ...

*Captopril challenge test

... an angiotensin converting enzyme inhibitor. It is used to assist in the diagnosis of renal artery stenosis. It is not generally ...

*Renin inhibitor

Between the two lobes, deep within the enzyme, resides the active site, and its catalytic activity is due to two aspartic acid ... Consequently, renin inhibitors prevent the formation of Ang I and Ang II. Renin inhibitors may also prevent Ang-(1-7), Ang-(1-9 ... Example of binding to the renin inhibitor: Aliskiren is a peptide-like renin inhibitor and, unlike most, it is rather ... Pepstatin was found to be a potent competitive inhibitor of most aspartic proteases, but a weak inhibitor of renin. Originally ...

*Enzyme inhibitor

Database of drugs and enzyme inhibitors BRENDA, Database of enzymes giving lists of known inhibitors for each entry Enzymes, ... This new inhibitor is then used to try to obtain a structure of the enzyme in an inhibitor/enzyme complex to show how the ... An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an enzyme's activity can ... The most common uses for enzyme inhibitors are as drugs to treat disease. Many of these inhibitors target a human enzyme and ...

*Captopril

... , sold under the trade name Capoten, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of ... Brown, NJ; Vaughan, DE (1998). "Angiotensin-converting enzyme inhibitors". Circulation. 97 (14): 1411-20. doi:10.1161/01.cir. ... "collected-product inhibitor" of the converting enzyme. Captopril was developed from this peptide after it was found via QSAR- ... "Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents". Science. ...

*Bioorthogonal chemistry

... enzyme inhibitors, etc. The chemical reporter must not alter the structure of the substrate dramatically to avoid affecting its ... Additionally, it is likely that they are metabolized in vitro by cytochrome P450 enzymes. The kinetics of the reactions are ...

*Polyestradiol phosphate

"Synthetic high molecular weight enzyme inhibitors. I. Polymeric phosphates of phloretin and related compounds" (PDF). Acta Chem ... Research has found that PEP acts as an inhibitor of alkaline phosphatase in vitro, and it is thought that PEP may inhibit its ... Estradiol is metabolized primarily in the liver by CYP3A4 and other cytochrome P450 enzymes, and is metabolized to a lesser ... 17β-diphosphate acted as an inhibitor of kidney alkaline phosphatase. When the same scientists wanted to synthesize simple ...

*Antinutrient

Some proteins can also be antinutrients, such as the trypsin inhibitors and lectins found in legumes. These enzyme inhibitors ... For example, Bowman-Birk trypsin inhibitor is found in soybeans. Lipase inhibitors interfere with enzymes, such as human ... Amylase inhibitors, like lipase inhibitors, have been used as a diet aid and obesity treatment. Amylase inhibitors are present ... Amylase inhibitors prevent the action of enzymes that break the glycosidic bonds of starches and other complex carbohydrates, ...

*Enzyme modulator

An enzyme modulator is a type of drug which modulates enzymes. They include enzyme inhibitors and enzyme inducers. In an ... In the homogeneous assay, an enzyme modulator (antibody, inhibitor or receptor for the enzyme) is covalently linked to the ... Practice and Theory of Enzyme Immunoassays. Elsevier. p. 382. ISBN 9780080858845. Retrieved 22 January 2015. ... homogenous assay, "an enzyme modulator ... is covalently linked to the ligand which competes with free ligand from the test ...

*Enzyme activator

... s are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. ... In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate ... Enzyme inducer Effector (biology) Kurland IJ, Pilkis SJ (1995). "Covalent control of 6-phosphofructo-2-kinase/fructose-2,6- ... These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an ...

*ACE inhibitor

An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of ... Previous angioedema associated with ACE inhibitor therapy Hypersensitivity to ACE inhibitors ACE inhibitors should be used with ... Ajayi AA, Campbell BC, Howie CA, Reid JL (1985). "Acute and Chronic Effects of the Converting Enzyme Inhibitors Enalapril and ... van Vark LC, Bertrand M, Akkerhuis KM, Brugts JJ, Fox K, Mourad JJ, Boersma E. "Angiotensin-converting enzyme inhibitors reduce ...

*Fatty acid amide hydrolase

Minkkilä A, Saario S, Nevalainen T (2010). "Discovery and development of endocannabinoid-hydrolyzing enzyme inhibitors". ... a large number of irreversible and reversible inhibitors of this enzyme have been developed. Some of the more significant ... and include non-covalent inhibitor complexes and covalent adducts. Endocannabinoid enhancer Endocannabinoid reuptake inhibitor ... In vivo, FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of ...

*Dynamic combinatorial chemistry

"Bivalent enzyme inhibitors discovered using dynamic covalent chemistry". Chem. Eur. J. 18 (34): 10562-10570. doi:10.1002/chem. ... Leung, I. K. H.; Brown Jr, T.; Schofield, C. J.; Claridge, T. D. W. (May 2011). "An approach to enzyme inhibition employing ... Enzyme-catalysed reversible reactions, such as protease-catalysed amide bond formation/hydrolysis reactions and the aldolase- ... Yang, Z.; Fang, Z.; He, W.; Wang, Z.; Gang, H.; Tian, Q.; Guo, K. (Apr 2016). "Identification of inhibitors for vascular ...

*Β-Lactamase inhibitor

β-lactamase inhibitors expand the useful spectrum of these β-lactam antibiotics by inhibiting the β-lactamase enzymes produced ... Watson ID, Stewart MJ, Platt DJ (1988). "Clinical pharmacokinetics of enzyme inhibitors in antimicrobial chemotherapy". Clin ... Boron based transition state inhibitors or BATSIs are very potent group of beta-lactamase inhibitors. A screen of a series of ... that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. ...

*Redback spider

Angiotensin-converting-enzyme inhibitors, or ACE inhibitors, are a class of widely-prescribed medications used in hypertension ... Sweitzer, Nancy K. (2003). "What Is an Angiotensin Converting Enzyme Inhibitor?". Circulation. 108 (3): e16-18. doi:10.1161/01. ... It contains a complex mixture of cellular constituents, enzymes and a number of high-molecular-weight toxins, including insect ... as have small peptides that inhibit angiotensin-1-converting enzyme; the venom of the redback, although little-studied, likely ...

*Aspergillomarasmine A

Antivirals and Enzyme Inhibitors. Elsevier. p. 499. ISBN 9780080858487. Retrieved 27 June 2014. Matsuura, Akihiro; Hiroshi ... "Pharmacological profiles of aspergillomarasmines as endothelin converting enzyme inhibitors". The Japanese Journal of ... It can inhibit endothelin converting enzymes even in the live rat, probably by chelating metals required by metalloproteases. ...

*Desorption/ionization on silicon

Reaction monitoring can be used to screen enzyme inhibitors. Atmospheric pressure DIOS was shown to be an effective tool for ...

*Lisinopril

... is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood ... Lisinopril is an ACE Inhibitor, meaning it blocks the actions of angiotensin converting enzyme (ACE) in the renin-angiotensin- ... John Wiley & Sons, Apr 3, 2013 ISBN 9781118354469 Menard J and Patchett A. "Angiotensin-Converting Enzyme Inhibitors". pp. 14- ... 1980). "A new class of angiotensin-converting enzyme inhibitors". Nature. 288 (5788): 280-3. Bibcode:1980Natur.288..280P. doi: ...

*Nicotinamide adenine dinucleotide

Other drugs are not enzyme inhibitors, but instead activate enzymes involved in NAD+ metabolism. Sirtuins are a particularly ... by designing enzyme inhibitors or activators based on its structure that change the activity of NAD-dependent enzymes, and by ... this can be exploited in enzyme kinetics to give information about the enzyme's mechanism. This is done by mixing an enzyme ... This radical then reacts with NADH, to produce adducts that are very potent inhibitors of the enzymes enoyl-acyl carrier ...

*Natural product

These include the angiotensin-converting enzyme inhibitor captopril. Captopril is based on the peptidic bradykinin potentiating ... Enzymes in turn are composed of amino acids and often non-peptidic cofactors that are essential for enzyme function. The basic ... they possess enzymes that are functional under quite unusual conditions. These enzymes are of potential use in the food, ... Its mechanism of action is inhibition of the cyclooxygenase (COX) enzyme. Another notable example is opium is extracted from ...

*Ecallantide

"Ecallantide for the acute treatment of Angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, ... HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a ... "Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors". American Journal of Health-System ... It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through ...

*Lenvatinib

No relevant interactions with enzyme inhibitors and inducers are expected. Lenvatinib acts as a multiple kinase inhibitor. It ... Non-enzymatic metabolization also occurs, resulting in a low potential for interactions with enzyme inhibitors and inducers. ... and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases. Lenvatinib is approved (since 2015) for ... Lenvatinib is metabolized by the liver enzyme CYP3A4 to desmethyl-lenvatinib (M2). M2 and lenvatinib itself are oxidized by ...

*Phage display

It is used for finding new ligands (enzyme inhibitors, receptor agonists and antagonists) to target proteins. The technique is ... Lunder M, Bratkovic T, Kreft S, Strukelj B (July 2005). "Peptide inhibitor of pancreatic lipase selected by phage display using ... "Affinity selection to papain yields potent peptide inhibitors of cathepsins L, B, H, and K". Biochem. Biophys. Res. Commun. 332 ...

*Kynurenine 3-monooxygenase

Administration of potent enzyme inhibitors has demonstrated promising pharmacological results. Specifically, genetic ... This enzyme belongs to the family of oxidoreductases, to be specific, those acting on paired donors, with O2 as the oxidant. ... Tautomerization yields 3-hydroxy-L-kynurenine in complex with the enzyme (E Fl HOH-P). Dissociation of 3-hydroxy-L-kynurenine ... Currently, most research on the kynurenine 3-monooxygenase enzyme has been focused primarily on rat models and in yeast, both ...
Genotoxin-based DNA-damaging agents and cell-cycle inhibitors cause damage to DNA, activating checkpoints and inducing apoptosis in nearly all of the proliferating cells. Even though severe side effects are associated with these therapies, they are the most effective therapies in early stages of cancer. However, as cancer progresses, cancer cells accumulate more mutations, abrogating checkpoint functions and apoptosis-inducing programs, making them resistant to genotoxin-based treatments. More recently developed "targeted" therapies use drugs that inhibit specific gene or mutated gene products whose activities are important in cancer development and growth in particular types of cancer. Generally they are less toxic, yet their effects can be very dramatic, shrinking tumors within days. However, there are many practical problems with this approach. For example, inactivating one oncogene with its many variants may not be possible with just one targeted drug (1). Moreover, choosing just one ...
ZSTK474 is a novel orally applicable phosphoinositide 3-kinase-specific inhibitor that strongly inhibits cancer cell proliferation. Combination treatment using X-rays then ZSTK474 given orally for 8 days, starting 24h post-irradiation, significantly enhanced cell growth inhibition. The combined effect was also observed for clonogenic survival with continuous ZSTK474 treatment. Western blot analysis showed enhanced phosphorylation of Akt and GSK-3β by X-irradiation, whereas phosphorylation was inhibited by ZSTK474 treatment alone. Treatment with ZSTK474 after X-irradiation also inhibited phosphorylation, and remarkably inhibited xenograft tumor growth.
It is now understood that the cyclo-oxygenase enzyme system that produces prostaglandins consists of at least two basic isoforms-cyclo-oxygenase 1 and cyclo-oxygenase 2.5 The cyclo-oxygenase 1 enzyme performs "housekeeping" duties, maintaining a normal gastrointestinal mucosa and renal blood flow. Cyclo-oxygenase 2 (the inducible form) is seen in inflammation, the brain, and colon cancer cells. Description of the structure of human recombinant cyclo-oxygenase 2 and its interaction with non-steroidal anti-inflammatory drugs has enabled highly specific inhibitors to be developed.6 The effectiveness and low incidence of gastrointestinal or renal side effects of drugs such as the preferential … ...
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Exceptions to a long-held rule against chemically bonding to biological targets are powering new cancer medicines, finds Andy Extance
1C87: Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B.
1C86: Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B.
Effect of different inhibitors on GR staining of γ/δ T cells treated with platelet supernatant fluid. Bovine lymphocytes were treated with neuraminidase (0.
UCSF researchers have invented a novel method to generate covalent macromolecular inhibitors. This strategy allows a peptide inhibitor to bind to its target protein specifically and irreversibly through proximity-enabled bioreactivity.
Get an answer for Analysis of a compound known to contain only Mg, P,and O gives this analysis.21.8% Mg, 27.7% P, 50.5% OWhat is its empirical formula? and find homework help for other Science questions at eNotes
R.D. Sheldon, J. Padilla, M.H. Laughlin, FACSM, R.S. Rector. Departments of Internal Medicine-Gastroenterology and Hepatology, Nutrition and Exercise Physiology, and Biomedical Science, University of Missouri, Columbia, MO, and Harry S Truman Memorial VA Hospital, Columbia, MO.
PI3K/Akt/mTOR inhibitors effect on CXCL12-induced MCL cell migration and invasionA, Primary MCL cells were preincubated with 5 μM everolimus, 1 μM NVP-BEZ235
Proton Inhibitor Effect - 28 images - Proton Inhibitor, Peptic Ulcer Disease From Ph To Hp By Dr G Muntingh Ppt, Standard American Diet Food Talk 4 You, Proton Inhibitor Side Effects Nexium Lawsuit, Libbey Eurotext Magnesium Research Effect Of
This study provided evidence that l-NMMA, an NOS inhibitor, attenuated the ACh-induced ICa decrease in a cAMP-stimulated condition due to forskolin, and that l-NMMA did not potentiate ICa when IBMX, a nonselective inhibitor in several PDEs, raised the cAMP level. Because the presence of NADPH-diaphorase assay and the expression of ecNOS protein (130 kDa) were identified in isolated rat cardiac myocytes, it is possible that inhibition of NOS blocks the cholinergic attenuation of ICa in a cAMP-stimulated condition and that this blocking action is mediated by inhibition of cGMP-stimulated cAMP-PDE, which can hydrolyze cAMP. This hypothesis was further confirmed by evidence demonstrating that both forskolin and milrinone potentiated the effect of l-NMMA on ICa, whereas the ICa response to l-NMMA was not significantly altered by application of 8-Br-cGMP.. NADPH-diaphorase and NOS activities are thought to reflect different properties of the same enzyme (Hope et al., 1991), but NADPH-diaphorase assay ...
Caspase 9 Inhibitor Drug Detection Kit(Caspase 9抑制剂药物检测试剂盒)(ab102497)快速简单的测定Caspase 9的抑制剂。 适合高通量实验。
Caspase 5 Inhibitor Drug Detection Kit(Caspase 5抑制剂药物检测试剂盒)(ab102493)快速简单的测定Caspase 5的抑制剂。 适合高通量实验。
InvivoGen provides a collection of inhibitors for different pathways: Signal Transduction Inhibitors, Protein Kinase inhibitors, Epigenetic Inhibitors, Heat Shock Protein Inhibitors, DNA Synthesis Inhibitors
KBP-7018: Tri‐kinase inhibitor (blocks PDGFR, RET, and c‐KIT at nM concentrations) targeting fibrotic disease, especially idiopathic pulmonary fibrosis ...
A highly selective inhibitor of phosphatidylinositol 3-kinase (IC50 values are 0.31, 0.73, 1.06 and 6.60μM for PI 3-Kβ, PI 3-Kα, PI 3-Kδ and PI 3-Kγ respectively). Inhibits proliferation and induces apoptosis in human colon cancer cells in vitro and in vivo. ...
Angiotensin converting enzyme inhibitors cause cough in some patients, but the mechanism of this effect is not known. Six patients in whom these inhibitors had caused cough and a further two patients in whom they were suspected to have caused worsening of bronchial asthma were studied. Nine patients in whom angiotensin converting enzyme inhibitors had not been associated with cough served as controls. In the controls lung function and bronchial reactivity were measured once; for the study patients these and the cough index were measured twice before rechallenge for two weeks with an angiotensin enzyme inhibitor and once afterwards. Rechallenge with drug for two weeks caused a significant decrease in the mean concentration of histamine causing a 35% fall in airways conductance and a significant increase in the cough index. Patients with cough showed bronchial hyperactivity compared with the controls, which increased after rechallenge with the inhibitors.. Cough associated with converting enzyme ...
One misconception that slips its way past most of us is the belief that soy was consumed for many years by Asian cultures and that they are among the most healthy, so if we consume soy now, we should all be fine. While this is true, there is a glaring difference between how ancient Asia prepared soy and how we do today. That key difference: fermenting the soy.. Un-fermented soybeans, what we mainly eat today, contain large quantities of natural toxins or "anti-nutrients". Some of the most important to avoid are potent enzyme inhibitors that block the action of trypsin and other enzymes needed for protein digestion. These inhibitors are tightly folded proteins that do not deactivate during the cooking process. Without being deactivated, they have the ability to produce serious gastric distress, reduce protein digestion and chronic deficiencies in amino acid uptake. Several tests were done on animals that showed diets high in trypsin inhibitors cause enlargement and pathological conditions of the ...
Ramace (Ramipril) belongs to a group of drugs called ACE Inhibitors.It work by interrupting a chemical pathway, ACE Inhibitors cause relaxation of the bodys blood vessels, and increase the excretion of salt and water in the urine.
Compare competitive and noncompetitive in terms of A) how Km is effected in presence of inhibitor, B) how Vmax is effected in presence of inhibitor, C) where inhibitor would bind to the enzyme.
A controversial class of anti-inflammatory drugs -- the COX-2 inhibitors -- increase the risk of cardiovascular disease by blocking a key protective substance, researchers reported.
Mercks recall of rofecoxib, a COX-2 inhibitor drug for arthritis, raises the question of whether similar drugs might also increase the risk of heart attack.
Effects of Nerve Growth Factor and Nitric Oxide Synthase Inhibitors on Amyloid Precursor Protein mRNA Levels and Protein Stability
BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing |160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with
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Du, XJ, Bobik, A, Little, PJ, Esler, MD and Dart, AM (1997) Role of Ca2+ in metabolic inhibition-induced norepinephrine release in rat brain synaptosomes. Circulation Research, 80 2: 179-188. ...
Capot Chemical CAS# 13515-97-4, DL-Alanine methyl ester hydrochloride. 13515-97-4 MSDS,ROS,13515-97-4 MOA,COA,SPECS,pecifications,1H-NMR,GHS,CAT #10905;Methyl DL-2-aminopropanoate hydrochloride
Dl-valine methyl ester hydrochloride/ACM5619056 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
With $208,000 in funds from FRAXA Research Foundation, Dr. Richard Jope and his team at the University of Miami tested whether newly developed, highly specific inhibitors of GSK3 can reduce behavioral abnormalities in fragile X mice.. Read more ...
Hypertension is the second leading primary cause of end-stage renal disease;however, considerable variation exists with respect to the relative risk of hyperten...
Activation of NF-κB signaling is increasingly being recognized as a key mechanism for tumorigenesis and is thought to act mainly by conferring apoptosis resistance to transformed cells. In this report, we used a well characterized combined in vitro/in vivo model of mammary carcinogenesis (EpRas) to determine the function of NF-κB in the regulation of epithelial plasticity and metastasis. First, we showed that NF-κB activity is required together with oncogenic Ras for efficient protection of mammary epithelial cells from TGF-β-induced apoptosis, as a prerequisite for these cells to undergo an EMT toward an invasive, metastatic tumor phenotype. Second, NF-κB can, in part, induce EMT in Ras-transformed cells in the absence of TGF-β, suggesting that NF-κB signaling can mediate important aspects of TGF-β signaling essential for inducing EMT. Third, NF-κB activity is necessary for cells to be maintained in a mesenchymal state, as its inhibition causes reversal of EMT; and finally, in ...
Product Number , 58089751. CAS Number , 5874-57-7. EC , Molecular Formula , -. Molecular Weight , 155.58. Storage Temp , Harmonized Tariff code , Signal Word , ...
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Purpose Metabolism, and especially glucose uptake, is normally an integral quantitative cell characteristic thats associated with cancer tumor initiation and development closely. advantages within the various other available blood sugar tracers, such as for example 2-DG or the radiolabel isotope FDG, including INCB8761 its low comparative cost, convenience of high temporal and spatial quality (on the single-cell level), insufficient ionizing radiation, as well as the nondestructive nature enabling immediate monitoring of blood sugar transport in live cells. Furthermore, we developed another independent method of directly measure the distribution of blood sugar uptake on the single-cell level that utilizes the energy of high-content computerized microscopy (HCAM), cell-cytometric picture evaluation (via in DMSO. Likewise, split plates had been treated and ready with Erlotinib at the same concentrations. Cells had been incubated with medications for another INCB8761 24 h Cish3 under regular ...
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Pfizer was undertaking a research programme to develop a series of centrally-active and selective neuronal nitric oxide synthase (nNOS) inhibitors based on a
At present children who have bone marrow or combined bone marrow and extramedullary relapses of acute leukemia while on therapy have 5-20% of long-term survival. Newer, targeted agents need to be identified and integrated into the present cytotoxic chemotherapy regimens. Biologically targeted cancer agents, including signal transduction inhibitors like mammalian target of rapamycin inhibitors (MTIs), have shown great promise in treating hematologic malignancies. A Phase 1 trial of sirolimus (an MTI) alone performed at CHOP has been well tolerated with no DLTs and has evidence of hitting the biologic target. While signal transduction inhibitors may be efficacious as single agents, it is more likely that these targeted agents will demonstrate greater efficacy in combination with other cytotoxic agents.Based upon pre-clinical humanized ALL mouse models we propose to study the toxicity and efficacy of adding sirolimus to oral methotrexate in relapsed and refractory patients.. Patients , 25 years of ...
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Creative Peptides offers Glycine methyl ester hydrochloride for your research. We also provide custom peptide synthesis, process development, GMP manufacturing.
Increased basal ET-1 release by NOS inhibitor was observed in only 2 of 9 studies with static cultures36,37 (Figure). Furthermore, in these 2 studies, the increased ET-1 release was determined after prolonged incubation with NOS inhibitor (ie, 637 and 24 hours36). Thus, the observed ET-1 release36,37 is not reflective of possible acute negative regulation of ET-1 release by NO.. Other studies failed to demonstrate increased ET-1 release after extended incubation (3-24 hours) with NOS inhibitor27,35,38-41 (Figure). Importantly, the general inability of NOS inhibitor to increase ET-1 release does not seem to be because of the failure of NOS inhibitor to decrease NO because NOS inhibitor for 8 hours decreased basal NO by 75% but did not increase ET-1 release41 (Figure; Figure S1).. The effect of NO inactivation on basal ET-1 release was also examined with oxyhemoglobin, which binds NO38,39,42,43 (Figure). Although exposure to oxyhemoglobin for 1 to 24 hours increased ET-1 release, it is likely that ...
The Receptor Tyrosine Kinase (RTK) Met influences behaviour of several cancers by controlling growth, survival and metastasis. Recently, compartmentalisation of signals generated by RTKs, due to their endocytosis / trafficking, has emerged as a major determinant of various cell functions. The aim of my project was to study oncogenic Met signalling in relation to endosomal trafficking and to determine the consequences of such spatial changes on tumour cell growth and migration in vitro and in vivo. The model studied was NIH3T3 cells stably transfected with Wild type (Wt) Met or with three distinct mutants reported in human cancers. I found that two activating mutations in the kinase domain are highly tumorigenic in vivo. Using functional assays and tumour growth experiments, I demonstrated that one mutant is highly sensitive to Met specific tyrosine kinase inhibitors (TKI) while another is resistant. Such results suggested that therapeutical approaches to these mutants should be different. ...
Using molecular modeling approach, potential antibacterial agents with triazole core were proposed. A moderate to weak level of antibacterial activity in most of the compounds have been observed, with best minimal inhibitory concentration (MIC) value of 0.003 mg/mL, as shown by the 15 against S. epidermidis. Studied compounds were also submitted to the antifungal assay. The best antifungal activity was detected for 16 with MIC at 0.125 and 0.25 mg/mL against C. albicans and C. parapsilosis, respectively.
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Zinc atom in PDB 1zef: Structure of Alkaline Phosphatase From Human Placenta in Complex With Its Uncompetitive Inhibitor L-Phe
American Health & Drug Benefits® examines drug and other healthcare intervention value from the separate and unified vantage points of each stakeholder group to the process: payers, purchasers, providers, patients, manufacturers, regulators, distributors, and evaluators. Directly or indirectly, all parties to healthcare benefits influence policy and demand satisfaction of their interests.
PRAVACHOL® PravastatinSodium Tablets CONTRAINDICATIONS: Hypersensitivityto any component of this medication. Active liver disease or unexplained, persistent elevations in liver function tests (see WARNINGS).Pregnancy and lactation. Atherosclerosisis a chronic process and discontinuationof lipid-loweringdrugs during pregnancyshould have little impact on the outcome of long-term therapy of primary hypercholesterolemia.Cholesteroland other products of cholesterol biosynthesis are essential components for fetal development (including synthesis of steroids and cell membranes). Since HMG-CoAreductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologicallyactive substances derived from cholesterol, they may cause fetal harm when administered to pregnant women. Therefore,HMG-CoAreductase inhibitorsare contraindicated during pregnancyand innursing mothers. Pravastatinshould be administered to women of childbearing age onlywhen such patients are highlyunlikely to ...
Lapatinib is classified as a signal transduction inhibitor - tyrosine kinase inhibitor, inhibitor of EGFR and HER2. Lapatinib is marketed as Tykerb and is used in the treatment of metastatic breast cancer that is HER-2 positive. The drug may also be used in combination with other chemotherapy drugs or for the treatment of other cancers.
Some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. There are no current data on whether this autonomic failure presents in humans at clinically used doses. We will test the hypothesis that Akt inhibition causes an acute decrease in sympathetic tone and lowers blood pressure ...
Reiter, K.; Polzer, H.; Krupka, C.; Maiser, A.; Vick, B.; Rothenberg-Thurley, M.; Metzeler, K. H.; Doerfel, D.; Salih, H. R.; Jung, G.; Noessner, E.; Jeremias, I.; Hiddemann, W.; Leonhardt, H.; Spiekermann, K.; Subklewe, M.; Greif, P. A. ...
Serum alpha-thiol protease inhibitor concentrations in health and disease.: Serum alpha-thiol protease inhibitor (alpha-TPI) concentration was assayed by radial
Purpose Metabolism, and especially glucose uptake, is normally an integral quantitative cell characteristic thats associated with cancer tumor initiation and development closely. advantages within the various other available blood sugar tracers, such as for example 2-DG or the radiolabel isotope FDG, including INCB8761 its low comparative cost, convenience of high temporal and spatial quality (on the single-cell level), insufficient ionizing radiation, as well as the nondestructive nature enabling immediate monitoring of blood sugar transport in live cells. Furthermore, we developed another independent method of directly measure the distribution of blood sugar uptake on the single-cell level that utilizes the energy of high-content computerized microscopy (HCAM), cell-cytometric picture evaluation (via in DMSO. Likewise, split plates had been treated and ready with Erlotinib at the same concentrations. Cells had been incubated with medications for another INCB8761 24 h Cish3 under regular ...
BioAssay record AID 919 submitted by NCGC: Concentration-Response Counterscreen for Redox Active Inhibitors of Caspase-7: Summary.
Kyowa Hakko Kirin is developing a series of orally active inhibitors of tyrosine kinases for the treatment of cancer. The rationale for the development of the
NU7441, also known as KU-57788, is a highly potent and selective DNA-PK inhibitor (IC50=14 nM), exhibiting ATP-competitive inhibition kinetics. NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB.
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TY - JOUR. T1 - Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. AU - Zujewski, J.. AU - Horak, I. D.. AU - Bol, C. J.. AU - Woestenborghs, R.. AU - Bowden, C.. AU - End, D. W.. AU - Piotrovsky, V. K.. AU - Chiao, J.. AU - Belly, R. T.. AU - Todd, A.. AU - Kopp, W. C.. AU - Kohler, D. R.. AU - Chow, C.. AU - Noone, M.. AU - Hakim, F. T.. AU - Larkin, G.. AU - Gress, R. E.. AU - Nussenblatt, R. B.. AU - Kremer, A. B.. AU - Cowan, K. H.. PY - 2000/2/1. Y1 - 2000/2/1. N2 - Purpose: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. Patients and Methods: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to ...
How is Nitric Oxide Synthase Inhibitor NG-Monomethyl-L-Arginine abbreviated? L-NMMA stands for Nitric Oxide Synthase Inhibitor NG-Monomethyl-L-Arginine. L-NMMA is defined as Nitric Oxide Synthase Inhibitor NG-Monomethyl-L-Arginine rarely.
Title: Signal Transduction Inhibitors as Radiosensitizers. VOLUME: 2 ISSUE: 6. Author(s): A. Tenzer, D. Zingg, O. Riesterer, V. Vuong, S. Bodis and M. Pruschy. Affiliation:Laboratory for Molecular Radiobiology, Dept. Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland.. Abstract: DNA double strand breaks are the pivotal cellular damage induced by ionizing radiation. A plethora of molecular and cellular processes are activated as part of the cellular stress response that result in cell cycle arrest and induction of the DNA-repair machinery to restore the damage of DNA or to activate a cell death program. However ionizing radiation also initiates signal transduction cascades that are generated at cellular sites distant from and independent of DNA-damage. These signaling processes are similar to hormone activated growth factor receptor controlled signal transduction cascades and represent interesting targets for anticancer treatment modalities combining ionizing radiation ...
Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to citrulline and nitric oxide (NO). The expression of this enzyme is associated with both physiology and pathophysiology conditions, depending on cell types and expression level. In spinal motoneurons, it is de novo synthesized after ventral root avulsion. Potential roles of NOS expression on motoneuron survival were extensively studied whereas effects of NOS in neuronal regeneration are under-explored. In this study, a peripheral nerve was implanted to the cervical segment where the ventral roots were avulsed in adult SD rats. Isoform specific NOS inhibitor was soaked in gel foam and topically applied on the lesioned site. After 2, 4 and 8 weeks, the rats were sacrificed and spinal cords were harvested. Samples were and cut into 40 micrometer thick sections and examined under microscope. Majority of the cells survived after nerve implantation as compared to 50% cell lose in control group without implantation at 4 weeks. The ...
TY - JOUR. T1 - Screening-based discovery of drug-like O-GlcNAcase inhibitor scaffolds. AU - Dorfmueller,Helge C.. AU - van Aalten,Daan M. F.. PY - 2010/2/19. Y1 - 2010/2/19. N2 - O-GlcNAcylation is an essential posttranslational modification in metazoa. Modulation of O-GlcNAc levels with small molecule inhibitors of O-GlcNAc hydrolase (OGA) is a useful strategy to probe the role of this modification in a range of cellular processes. Here we report the discovery of novel, low molecular weight and drug-like O-GlcNAcase inhibitor scaffolds by high-throughput screening. Kinetic and X-ray crystallographic analyses of the binding modes with human/bacterial O-GlcNAcases identify some of these as competitive inhibitors. Comparative kinetic experiments with the mechanistically related human lysosomal hexosaminidases reveal that three of the inhibitor scaffolds show selectivity towards human OGA. These scaffolds provide attractive starting points for the development of non-carbohydrate, drug-like OGA ...
Nitric oxide synthase inhibition improves contractile economy in rat hindlimb muscles perfused in situ at matched convective oxygen ...
[150 Pages Report] Check for Discount on 2016 Global and Chinese Dl-Serine Methyl Ester Hydrochloride (CAS 1358433) Industry Market Research Report report by Prof Research. The Global and Chinese Dl-Serine Methyl Ester Hydrochloride Industry,...
The report generally describes d-leucine methyl ester hydrochloride, examines its uses, production methods, patents. D-Leucine methyl ester hydrochloride
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Significant pharmaceutical innovations and progresses have occurred in oncology treatments and patients management. Recent signal transduction inhibitor agents having a strong anti-tumour specificity are able to disrupt signal pathways mediating cancer cell proliferation and efficiently prevent tumour growth. Signal transduction inhibitors include imatinib, sunitinib, nilotinib, dasatinib, sorafenib and other tyrosine kinase blockers currently under investigation. But other chemotherapeutic drugs such as antimetabolites (methotrexate, 5-Fluorouracil), mitotic spindle inhibitors (vincristine, vinorelbine), antibiotic inhibitors of topoisomerases (etoposide, topotecan) etc. are also increasingly used in oncology. As a consequence, cancer patients are living longer, and the amount of consumption of these classes of drugs has grown accordingly. In parallel, the amount of anticancer drug residues released into the environment has increased. Indeed, most anticancer drugs are eliminated by urines or ...
Collagen activates platelets through a tyrosine kinase-dependent pathway, involving phospholipase Cgamma2. Functional responses such as aggregation and secretion induced by collagen are potentiated by preincubation with thrombopoietin (TPO). In this study, we show that collagen and thrombopoietin activate the phosphatidylinositol 3-kinase (PI 3-kinase) pathway and that this contributes to their respective actions. The structurally distinct inhibitors of PI 3-kinase, wortmannin, and LY294002, completely inhibit formation of phosphatidylinositol 3,4,5-trisphosphate by collagen. This leads to a substantial reduction in the formation of inositol phosphates and phosphatidic acid, 2 indices of PLC activity, and the consequent inhibition of intracellular Ca(++) [Ca(++)](i), aggregation and secretion. Potentiation of the collagen response by TPO is prevented in the presence of wortmannin and LY294002. However, when the 2 PI 3-kinase inhibitors are given after the addition of TPO but before the collagen,
Author Summary Myocardial ischemia, commonly observed when arteries supplying the heart become occluded, results when cardiac tissue receives inadequate blood perfusion. In order to minimize the amount of cardiac damage, ischemic tissue must be reperfused. However, reperfusion can result in deleterious effects that leave the heart muscle sicker than if the ischemia had been allowed to continue. Examples of these reperfusion injuries include lethal arrhythmias and an increased region of cell death. Some of the early events that result in reperfusion injury include changes in pH and an overload of sodium inside the cell. During reperfusion, the sodium-proton exchanger (NHE) removes protons from the cell in an effort to restore normal pH, in turn importing sodium ions. Many strategies have been attempted to prevent reperfusion injury, including inhibition of the NHE, with little clinical effect. Using a mathematical model that we developed to study ischemia and reperfusion in cardiac cells, we found that
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Increasing resistance to chemotherapeutic regimes remains a serious problem in the treatment of acute myeloid leukaemia. We have shown that phosphatidylinositol (PI) 3-kinase inhibition significantly sensitises the AML derived cell line, HL60 to chemotherapeutic drug- and Fas-induced apoptosis. PI3-kinase inhibition significantly potentiates cytotoxic drug-induced c-jun N-terminal kinase (JNK) activation, reported to be a requirement for apoptosis. However, JNK inhibition does not enhance cell viability following treatment with drug and inhibitor. Furthermore, PI3-kinase inhibition significantly increases sensitivity to apoptosis mediated by an exogenous receptor agonist, again by a JNK independent mechanism. These results suggest that PI3-kinase inhibitors could be of significant therapeutic importance, lowering the threshold for apoptosis induced by both chemotherapy and cell-mediated immune response.
We conducted an experimental study to assess the effect of a novel anti-inflammatory agent on vascular inflammation, over 3 months, in stable atherosclerotic patients receiving statin therapy. Despite a negative primary endpoint, we demonstrated that losmapimod reduced arterial inflammation, as measured by FDG-PET/CT imaging in the most active discrete segments (pre-defined as a TBR of ≥1.6) of selected arteries, suggesting influence predominantly in the most inflamed areas. Complementing this finding, there was a shift in the distribution of active segments using our frequency analysis. The modest vascular effects were accompanied by significant reductions in circulating inflammatory biomarkers, in line with previous results using this compound (8), and in visceral fat FDG uptake.. A linear correlation in a previous small study between TBR vessel average (which ranged from approximately 1.0 to 4.0) and the tissue level of macrophage marker CD68 (11) drove the decision on our primary endpoint. ...
[65 Pages Report] Check for Discount on DL-2-Amino-n-butyric acid methyl ester hydrochloride Global Market and Forecast Research report by ChemReport. DescriptionWe provide independent and unbiased information on manufacturers, prices, production...
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UCL Discovery is UCLs open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.
Proteasome inhibitors have significant promise as components of novel combination therapies to treat multidrug-resistant malaria, according to a study published June 6 in the open-access journal PLOS Pathogens by David Fidock, Caroline Ng, and Barbara Stokes of Columbia University Irving Medical Center, Matthew Bogyo of Stanford University School of Medicine, and colleagues.
Background 15-hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. Principal Findings To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing |160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with
Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Inhibitors decrease the rates that enzymes bind to substrates and convert them to products Three types of inhibition competitive uncompetitive noncompetitivemixed and reaction with no inhibitor are compared for an enzyme reaction that obeys MichaelisndashMenten kinetics Substrate concentration is plotted versus time for a continuous stirredtank reactor CSTR and for a batch reactor Change the inhib
We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy). Sprague-Dawley rats were
One misconception that slips its way past most of us is the belief that soy was consumed for many years by Asian cultures and that they are among the most healthy, so if we consume soy now, we should all be fine. While this is true, there is a glaring difference between how ancient Asia prepared soy and how we do today. That key difference: fermenting the soy.. Un-fermented soybeans, what we mainly eat today, contain large quantities of natural toxins or "anti-nutrients". Some of the most important to avoid are potent enzyme inhibitors that block the action of trypsin and other enzymes needed for protein digestion. These inhibitors are tightly folded proteins that do not deactivate during the cooking process. Without being deactivated, they have the ability to produce serious gastric distress, reduce protein digestion and chronic deficiencies in amino acid uptake. Several tests were done on animals that showed diets high in trypsin inhibitors cause enlargement and pathological conditions of the ...
This study is a single-armed, open-label, single-center phase II trial of signal transduction inhibitor number 571 (STI-571) systemic therapy in selecti
423 Most human breast cancers are reported to be refractory to transforming growth factor beta 1 (TGFβ1) mediated growth regulation while producing large amounts of TGFβ1 (reviewed in Cancer Metastasis Rev 20 (1-2):133, 2001). Ionizing radiation (IR) activates TGFβ1 through a redox mechanism (Radiat Res 166:839-48, 2006) Our recent studies show that TGFβ1 depletion in irradiated epithelial cells compromises ataxia telengiectasia mutated (ATM) kinase activity and autophosphorylation, leading to reduced phosphorylation of critical DNA damage transducers γH2AX, Chk2, p53 and Rad17, abrogation of the cell cycle block and apoptosis (Cancer Res 66 (22):10861, 2006). Radiosensitivity is increased as a result in both Tgfβ1 null murine epithelial cells and non-malignant human epithelial cells in which TGFβ signaling is inhibited. Therefore, we hypothesized that TGFβ inhibition might increase clonogenic cell death in irradiated cancer cells. We first established the relative TGFβ1 sensitivity in ...
A new study suggests that combining two experimental anticancer peptide agents might simultaneously block formation of new tumor blood vessels while also inhibiting the growth of tumor cells. This early test of the two agents in a breast cancer model suggests that the double hit can stifle tumor progression, avoid drug resistance and cause few…
Dl-phenylalanine tert-butyl ester hydrochloride/AFI75898474 can be provided in Alfa Chemistry. We are dedicated to provide our customers the best products and services.
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2-methylsulfanyl-4,5-dihydro-1H-imidazole chemical properties, What are the chemical properties of 2-methylsulfanyl-4,5-dihydro-1H-imidazole 20112-79-2, What are the physical properties of 2-methylsulfanyl-4,5-dihydro-1H-imidazole ect.
The first fragment-derived drug approved, vemurafenib, illustrated how quickly FBDD could move: just six years from the start of the program to approval. In contrast, venetoclax is the culmination of a program that has been running for more than two decades; Steve Fesik and his colleagues at Abbott published the X-ray and NMR structure of the protein BCL-xL back in 1996! The original SAR by NMR work was done on this protein, leading to ABT-263, which hits both BCL-xL and BCL-2. Subsequent work revealed that a selective BCL-2 inhibitor might be preferable in some cases, and further medicinal chemistry led to venetoclax ...
A molecular strategy that could make a much larger variety of tumors treatable with PARP inhibitors, a promising new class of cancer drugs, has been demonstrated
Sigma-Aldrich offers Aldrich-687065, 4-(4-Fluorophenyl)-1H-imidazole for your research needs. Find product specific information including CAS, MSDS, protocols and references.
In recent years, aldehyde oxidase (AO) has continued to grow as an important enzyme in drug metabolism. Herein, we have focused primarily on the inhibition kinetics of AO and also developing tools to better understand AO ...
|p|BYK 49187 is a potent inhibitor of PARP-1 and PARP-2 with pIC50 value pIC50 values of 8.36 and 7.50 for cell-free recombinant PARP-1 and murine PARP-2 respectively [1].|br /|Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a numb
1. This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L-NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. 2. Repeated administration of intrathecal morphine (15 micrograms), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co-administration of ketorolac (30 and 45 micrograms) or S(+) ibuprofen (10 micrograms) with morphine (15 micrograms) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L-NAME (100 micrograms) exerted weaker effects. Administration of S(+) but not R(-) ibuprofen (10 mg kg-1) had similar effects on systemic administration of morphine (15 mg kg-1). 3. Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not
There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with eitherL-NAME orL-NAME together with the superoxide scavenger Tempol, or together withL-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by ...
Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinica
The tyrosine kinase inhibitor herbimycin A was found to block NF-kappa B stimulation in response to interleukin-1 and phorbol 12-myristate 13-acetate in EL4.NOB-1 thymoma cells and phorbol 12-myristate 13-acetate in Jurkat T lymphoma cells. The effect appeared not to involve inhibition of tyrosine kinase activation as neither interleukin-1 nor phorbol 12-myristate 13-acetate induced major changes in tyrosine phosphorylation in EL4.NOB-1 or Jurkat cells, respectively. Herbimycin A did not interfere with I kappa B-alpha degradation, and in unstimulated cells, it modified NF-kappa B prior to chemical dissociation with sodium deoxycholate. Because herbimycin A is thiol-reactive, we suspected that the target was the p50 subunit of NF-kappa B, which has a key thiol at cysteine 62. Herbimycin A inhibited DNA binding when added to nuclear extracts prepared from stimulated cells, which were shown to contain high levels of p50. Incubation of herbimycin A with 2-mercaptoethanol attenuated the effect. ...
BACKGROUND: Clinical and experimental data indicate that early failure of intraportally grafted islets is caused by inflammation including secretion of cytokines and nitric oxide. Direct inducible nitric oxide synthase suppression may avoid detrimental effects associated with steroid administration. We compared the efficiency of selective and unselective inducible nitric oxide synthase inhibitors with dexamethasone to suppress nitric oxide generation after intraportal islet xenotransplantation into nude rats. METHODS: Nonfasting serum glucose levels were daily evaluated after intraportal transplantation of 4000 freshly isolated pig islets into diabetic nude rats (85 mg/kg streptozotocin) either sham-treated with saline (n=21) or continuously infused for 7 days with L-NG-monomethyl-arginine (n=7), S-methyl-isothiourea (n=15), or S-(2-aminoethyl)-isothiourea (n=19) in a dosage of 240, 100, or 50 mg/kg/day, respectively. Dexamethasone was injected i.p. twice as a daily bolus of 20 mg/kg (n=10) starting 1
Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A "double-hemorrhage" canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography.. Secondary branches of both untreated basilar arteries (inner diameter, 324 +/- 11 microns; n = 12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328 +/- 12 microns; n = 12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer.. In untreated arteries, 10(-11) to 10(-7) M vasopressin, 10(-10) to 10(-6) M bradykinin, and 10(-9) to 10(-6) M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10(-6) and 3 x 10(-4) M the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced ...

Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary...Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary...

BACKGROUND Cilazapril is a novel angiotensin converting enzyme inhibitor with antiproliferative effects in the rat model after ... Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary ... Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary ... Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary ...
more infohttp://circ.ahajournals.org/content/86/1/100

Hydrochlorothiazide 12.5 - Hydrochlorothiazide 12.5 mg * Dr. Rigamontis BlogHydrochlorothiazide 12.5 - Hydrochlorothiazide 12.5 mg * Dr. Rigamonti's Blog

Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Exacerbation or activation of ... Zestoretic, pharmacologic Category, angiotensin-Converting Enzyme (ACE) Inhibitor, antihypertensive. The adverse reaction ... Drug interactions Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) ... May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. ...
more infohttp://www.drrigamonti.com/blog-2/

Can I take amlodipine with perindopril - Drug DetailsCan I take amlodipine with perindopril - Drug Details

Perindopril belongs to the class of ACE (Angiotensin Converting Enzyme) inhibitors. ACE inhibitors bind and inhibit the ... Principally, ACE inhibitors inhibit the angiotensin-converting enzyme (ACE), an important component of the renin-angiotensin- ... Perindopril is a non sulfhydryl prodrug that belongs to the class of ACE (angiotensin-converting enzyme) inhibitor. The drug is ... angiotensin-converting enzyme (ACE) inhibitor) and Amlodipine (calcium channel blocker). The mode of action of the two drugs is ...
more infohttps://drugsdetails.com/can-i-take-amlodipine-with-perindopril/

Studies of enzyme inhibitors and endochitinase in seeds of jobs tears (Coix lachryna-jobi) - Durham e-ThesesStudies of enzyme inhibitors and endochitinase in seeds of job's tears (Coix lachryna-jobi) - Durham e-Theses

Studies of enzyme inhibitors and endochitinase in seeds of jobs tears (Coix lachryna-jobi) ... Ary, Marta Baccache (1994) Studies of enzyme inhibitors and endochitinase in seeds of jobs tears (Coix lachryna-jobi). ... from the literature this is the first characterization of a plant protein with activity as an enzyme and as an enzyme inhibitor ... A protein inhibitor of locust gut ζ-amylase was purified from seeds of Coix using ammonium sulphate precipitation, affinity ...
more infohttp://etheses.dur.ac.uk/5667/

Enzyme inhibitor - WikipediaEnzyme inhibitor - Wikipedia

Reversible inhibitors[edit]. Types of reversible inhibitors[edit]. Reversible inhibitors attach to enzymes with non-covalent ... An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an enzymes activity can ... This new inhibitor is then used to try to obtain a structure of the enzyme in an inhibitor/enzyme complex to show how the ... Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity ...
more infohttps://en.wikipedia.org/wiki/Enzyme_inhibition

Enzyme inhibitor - WikipediaEnzyme inhibitor - Wikipedia

An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an enzymes activity can ... This new inhibitor is then used to try to obtain a structure of the enzyme in an inhibitor/enzyme complex to show how the ... Reversible inhibitorsEdit. Types of reversible inhibitorsEdit. Reversible inhibitors attach to enzymes with non-covalent ... Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity ...
more infohttps://en.m.wikipedia.org/wiki/Enzyme_inhibitor

Angiotensin converting enzyme inhibitors in pregnancy.  - PubMed - NCBIAngiotensin converting enzyme inhibitors in pregnancy. - PubMed - NCBI

Angiotensin converting enzyme inhibitors in pregnancy.. Mastrobattista JM1.. Author information. 1. Department of Obstetrics, ... Angiotensin converting enzyme (ACE) inhibitors are excellent antihypertensive agents and are becoming widely used as first-line ... This review discusses the mechanism of action of ACE inhibitors and the use of ACE inhibitors in pregnancy both in experimental ... ACE inhibitors used during pregnancy may have untoward effects on the fetus. Based on reports in the literature, one should ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/9201818?dopt=Abstract

Enzyme Inhibitors: Pancreatic Amylase | GreenMedInfoEnzyme Inhibitors: Pancreatic Amylase | GreenMedInfo

Pharmacological Actions : Enzyme Inhibitors: Pancreatic Amylase, Enzyme Inhibitors: Pancreatic Lipase, Pancreato Protective ... Pharmacological Actions : Enzyme Inhibitors: Pancreatic Amylase, Enzyme Inhibitors: Pancreatic Lipase, Pancreato Protective ... Pharmacological Actions : Alpha-amylase inhibitor, Alpha-glucosidase inhibitor , Enzyme Inhibitors: Pancreatic Amylase ... 6 Abstracts with Enzyme Inhibitors: Pancreatic Amylase Research. Filter by Study Type. Animal Study. ...
more infohttps://www.greenmedinfo.com/pharmacological-action/enzyme-inhibitors-pancreatic-amylase

Angiotensin-Converting Enzyme Inhibitors | GreenMedInfoAngiotensin-Converting Enzyme Inhibitors | GreenMedInfo

Pharmacological Actions : Alpha-amylase inhibitor, Alpha-glucosidase inhibitor , Angiotensin-Converting Enzyme Inhibitors, ... Pharmacological Actions : Alpha-amylase inhibitor, Alpha-glucosidase inhibitor , Angiotensin-Converting Enzyme Inhibitors, ... Pharmacological Actions : Angiotensin-Converting Enzyme Inhibitors, Hypotensive, Vascular smooth muscle cell (VSMC) inhibitor ... Pharmacological Actions : Angiotensin-Converting Enzyme Inhibitors, Anti-Angiogenic, Hypotensive, NF-kappaB Inhibitor ...
more infohttp://www.greenmedinfo.com/pharmacological-action/angiotensin-converting-enzyme-inhibitors

Enzyme Inhibitors and Activators | IntechOpenEnzyme Inhibitors and Activators | IntechOpen

We also considered enzyme inhibitors that were used for design of various types of pharmacological drugs and natural inhibitors ... In this chapter, we focused on the properties of enzyme inhibitors and activators. Here we present canonical inhibitor ... Enzyme inhibitors are also useful tool for study of enzymatic reaction as well as for design of new medicine drugs. ... Enzyme inhibitors and activators that modulate the velocity of enzymatic reactions play an important role in the regulation of ...
more infohttps://www.intechopen.com/books/enzyme-inhibitors-and-activators/enzyme-inhibitors-and-activators/

Patent US5147867 - Phosphorus containing enzyme inhibitors - Google PatentsPatent US5147867 - Phosphorus containing enzyme inhibitors - Google Patents

The compounds have dehydropeptidase (DHP) enzyme inhibitor activity. ... Inhibition of the enzyme is gauged by comparison to a standard run containing no inhibitor and is expressed as the inhibitor ... Inhibitors of NAALADase enzyme activity. US6028216 *. Dec 31, 1997. Feb 22, 2000. Guilford Pharmaceuticals Inc.. Asymmetric ... Inhibitors of NAALADase enzyme activity. US5863536 *. Dec 31, 1996. Jan 26, 1999. Guilford Pharmaceuticals Inc.. ...
more infohttp://www.google.com/patents/US5147867?dq=7800613

Molecular Mimetism As An Enzyme InhibitorMolecular Mimetism As An Enzyme Inhibitor

... 05.12.2007. Over time viruses have developed a wide range of varied strategies to ... If the theory is corroborated, this would be another case of molecular mimesis as an enzyme inhibitor technique. The future ... Their experiments show that the protein p56 conceals the part of the UDG enzyme that interacts with the damaged DNA so that ... In order to carry out its function, the UDG enzyme first identifies the damaged DNA by locating uracil residues and then ...
more infohttp://www.innovations-report.com/html/reports/life-sciences/report-99523.html

9780470286265 - Design of Enzyme Inhibitors for | eCampus.com9780470286265 - Design of Enzyme Inhibitors for | eCampus.com

9780470286265 Our cheapest price for Design of Enzyme Inhibitors for Therapeutics is $82.48. Free shipping on all orders over $ ... 3. Covalent enzyme inhibitor in drug discovery and development. Shujaath Mehdi. 4. Preclinomics: Using Enzyme Assays and Rodent ... Design of Enzyme Inhibitors highlights how, what, and where enzymes have become critical in pharmaceutical and biotechnology ... This book provides an overview of new developments in enzyme technology and case studies of new enzyme inhibitor drugs. This ...
more infohttp://www.ecampus.com/design-enzyme-inhibitors-therapeutics/bk/9780470286265

Analysis of Angiotensin-Converting Enzyme Inhibitors in Biological Fluids | SpringerLinkAnalysis of Angiotensin-Converting Enzyme Inhibitors in Biological Fluids | SpringerLink

... inhibitors, diverse analytical methods including HPLC, GC, GC-MS, REI and RIA have been reported. The different analytical ... Rakhit A. (1988) Analysis of Angiotensin-Converting Enzyme Inhibitors in Biological Fluids. In: Reid E., Robinson J.D., Wilson ... During the last 10 years of development of several ACE* inhibitors, diverse analytical methods including HPLC, GC, GC-MS, REI ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4757-9424-3_16

DailyMed - Search Results for Angiotensin-converting Enzyme InhibitorsDailyMed - Search Results for Angiotensin-converting Enzyme Inhibitors

SEARCH RESULTS for: Angiotensin-converting Enzyme Inhibitors [Drug Class] (839 results) * Share : JavaScript needed for Sharing ...
more infohttps://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Angiotensin-converting%20Enzyme%20Inhibitors&searchdb=class

Brief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications | SpringerLinkBrief review: Angiotensin converting enzyme inhibitors and angioedema: anesthetic implications | SpringerLink

Purpose Angiotensin converting enzyme inhibitors (ACEIs) are a group of drugs used to treat hypertension and heart failure, ... Unmasking of acquired autoimmune C1-inhibitor deficiency by an angiotensin-converting enzyme inhibitor. Ann Allergy Asthma ... Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema. Br J Dermatol 1997, 136:153-8.PubMedCrossRefGoogle Scholar ... Recurrent angiotensin-converting enzyme inhibitor-associated angioedema. JAMA 1997; 278:232-3.PubMedCrossRefGoogle Scholar ...
more infohttps://link.springer.com/article/10.1007%2FBF03022528

Untitled | Mechanistic Target Of Rapamycin | Enzyme InhibitorUntitled | Mechanistic Target Of Rapamycin | Enzyme Inhibitor

In this circumstance, a substantial fraction of the total inhibitor is bound to the enzyme during the assay, and therefore ... Copeland, R.A. Evaluation of enzyme inhibitors in drug discovery. A guide for medicinal chemists and pharmacologists. Methods ... 12). We also tested whether a structurally unrelated tRNA synthetase inhibitor, the threonyl-tRNA synthetase inhibitor ... but rather requires an ATP-induced conformational change in the enzyme that allows inhibitor binding. Although we have not ...
more infohttps://www.scribd.com/document/109856700/Untitled

Enzyme inhibitors help reverse scars | Chemical & Engineering NewsEnzyme inhibitors help reverse scars | Chemical & Engineering News

Enzyme inhibitors help reverse scars. Blocking the collagen cross-linking enzyme lysyl oxidase reduces scarring after injury ... Home > Volume 94 Issue 34 > Science & Technology Concentrates > Enzyme inhibitors help reverse scars ... The researchers are now studying the efficacy of inhibitors in animal models and hope to start human trials of topical ... Imaging and biochemical tests on human cells treated with lysyl oxidase inhibitors showed that the agents reduce collagen cross ...
more infohttps://cen.acs.org/articles/94/i34/Enzyme-inhibitors-help-reverse-scars.html

Zinc Enzyme Inhibitors | Springer for Research & DevelopmentZinc Enzyme Inhibitors | Springer for Research & Development

... toxin Clostridium Protozoan carbonic anhydrases Bacterial carbonic anhydrases Tetanus Toxin Anthrax Lethal Factor Inhibitors ...
more infohttps://rd.springer.com/book/10.1007%2F978-3-319-46112-0

Enzyme Inhibitors (A-Z)Enzyme Inhibitors (A-Z)

... enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell ... BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and ... Ubiquitin Activating Enzyme E1 Inhibitor(1). *Ubiquitin Ligase (E3) Inhibitors(9). *Ubiquitin Proteasome Pathway Inhibitors(44) ...
more infohttps://www.biovision.com/products/enzyme-inhibitors/enzyme-inhibitors-a-z.html

Angiotensin Converting Enzyme Inhibitors in Cardiovascular Disease (Expert ConseAngiotensin Converting Enzyme Inhibitors in Cardiovascular Disease (Expert Conse

... nsus Document on) ESC Clinical Practice ... Effects of ACE-inhibitors: Haemodynamic effects, Neurohormonal effects, Antiproliferative effects, Renal effects, Other effects ...
more infohttps://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Angiotensin-Converting-Enzyme-Inhibitors-in-Cardiovascular-Disease-Expert-Conse

Class A beta-lactamases--enzyme-inhibitor interactions and resistance.  - PubMed - NCBIClass A beta-lactamases--enzyme-inhibitor interactions and resistance. - PubMed - NCBI

Class A beta-lactamases--enzyme-inhibitor interactions and resistance.. Yang Y1, Rasmussen BA, Shlaes DM. ... In the face of selective pressure arising from use of either newer cephalosporins or beta-lactam/beta-lactamase inhibitor ... This review focuses on the mechanism of inhibition by these currently marketed beta-lactamase inhibitors and on the mechanism ... This proton donation is probably not required for formation of a favorable leaving group for the sulfone inhibitors sulbactam ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/10511459?dopt=Abstract

Angiotensin-Converting Enzyme Inhibitors for Stroke Prevention | StrokeAngiotensin-Converting Enzyme Inhibitors for Stroke Prevention | Stroke

Angiotensin-Converting Enzyme Inhibitors for Stroke Prevention. Is There HOPE for PROGRESS After LIFE?. Graeme J. Hankey ... Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. ... Lonn EM, Yusuf S, Jha P, Montague TH, Teo KK, Benedict CR, Pitt B. Emerging role of angiotensin-converting enzyme inhibitors in ... Effects of long-term treatment with angiotensin-converting-enzyme inhibitors in the presence or absence of aspirin: a ...
more infohttp://stroke.ahajournals.org/content/34/2/354.full

Enzyme inhibitor combined with chemotherapy delays glioblastoma growth - ScienceBlog.comEnzyme inhibitor combined with chemotherapy delays glioblastoma growth - ScienceBlog.com

... a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and ... The regression seen in this combination therapy of temozolomide and the inhibitor SLC-0111 - which targets the enzyme carbonic ... a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and ... In the face of this hypoxia and acid stress, tumor cells over-produce CA9, a membrane enzyme that converts carbon dioxide and ...
more infohttps://scienceblog.com/499236/enzyme-inhibitor-combined-chemotherapy-delays-glioblastoma-growth/

Angiotensin-Converting Enzyme Inhibitors and Obstructive Sleep ApneaAngiotensin-Converting Enzyme Inhibitors and Obstructive Sleep Apnea

Anglotensin-converting enzyme (ACE) inhibitors may Induce cough and rhinopharyngeal Inflammation. Obstructive sleep apnea (OSA ... before or after withdrawal of ACE Inhibitor treatment. These findings suggest that ACE Inhibitor treatment may contribute to ... Similar findings were observed in 4 other patients with OSA who had ACE Inhibitor-Induced cough. The mean ± SD AHI was 33.8± ...
more infohttp://connection.ebscohost.com/c/articles/19800786/angiotensin-converting-enzyme-inhibitors-obstructive-sleep-apnea
  • Many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology . (wikipedia.org)
  • The regression seen in this combination therapy of temozolomide and the inhibitor SLC-0111 - which targets the enzyme carbonic anhydrase 9, or CA9 - was greater than that seen with either SLC-0111 or temozolomide alone, says research leader Anita Hjelmeland, Ph.D., assistant professor in the Department of Cell, Developmental and Integrative Biology at the University of Alabama at Birmingham . (scienceblog.com)
  • It is known that this enzyme, present in all living organisms, is involved in the DNA repair processes and hence, it avoids mutations in the cellular genome. (innovations-report.com)
  • In the face of selective pressure arising from use of either newer cephalosporins or beta-lactam/beta-lactamase inhibitor combinations, mutations arose among Class A beta-lactamase genes, leading to resistance. (nih.gov)
  • In animal experiments, a human-derived glioblastoma significantly regressed when treated with the combination of an experimental enzyme inhibitor and the standard glioblastoma chemotherapy drug, temozolomide. (scienceblog.com)
  • Here, we have been able to quantitatively reconstruct the complete binding process of the enzyme-inhibitor complex trypsin-benzamidine by performing 495 molecular dynamics simulations of free ligand binding of 100 ns each, 187 of which produced binding events with an rmsd less than 2 Å compared to the crystal structure. (pnas.org)
  • Enzyme inhibitors also occur naturally and are involved in the regulation of metabolism . (wikipedia.org)
  • Clavulanic acid, a naturally occurring clavam, and the penicillanic acid sulfones sulbactam and tazobactam are the inhibitors in clinical use. (nih.gov)
  • In contrast to substrates and irreversible inhibitors, reversible inhibitors generally do not undergo chemical reactions when bound to the enzyme and can be easily removed by dilution or dialysis. (wikipedia.org)
  • This volume reviews important progress on the chemical biology of enzymes in the post-genomic era. (ecampus.com)
  • Design of Enzyme Inhibitors highlights how, what, and where enzymes have become critical in pharmaceutical and biotechnology research. (ecampus.com)
  • Researchmoz added Most up-to-date research on "Global Dissociation Enzyme-Inhibitor Complex Industry 2018, Trends and Forecast Report" to its huge collection of research reports. (openpr.com)
  • These findings suggest that ACE Inhibitor treatment may contribute to OSA by Inducing upper airway Inflammation. (ebscohost.com)
  • The binding paths obtained are able to capture the kinetic pathway of the inhibitor diffusing from solvent (S0) to the bound (S4) state passing through two metastable intermediate states S2 and S3. (pnas.org)
  • The major trypsin inhibitor from seeds of Coix was purified by heat treatment, fractional precipitation with ammonium sulphate, ion-exchange chromatography, gel filtration and preparative reversed-phase HPLC. (dur.ac.uk)
  • Because St. John's wort and dong quai may also cause this problem, taking these herbal supplements during treatment with ACE inhibitors might add to this risk. (memorialhospitaljax.com)
  • Bisdemethoxycurcumin from Curcuma longa rhizome is a potent small molecule inhibitor of human pancreatic α-amylase, a target for type-2 diabetes. (greenmedinfo.com)
  • During the last 10 years of development of several ACE* inhibitors, diverse analytical methods including HPLC, GC, GC-MS, REI and RIA have been reported. (springer.com)
  • Reports of adverse fetal and neonatal effects from the use of ACE inhibitors in pregnancy in both animal and human studies prompted recommendations against their use in human pregnancy by several authors. (nih.gov)
  • Imaging and biochemical tests on human cells treated with lysyl oxidase inhibitors showed that the agents reduce collagen cross-linking, which could make skin look more normal. (acs.org)
  • The researchers are now studying the efficacy of inhibitors in animal models and hope to start human trials of topical nanoformulations in a few years. (acs.org)
  • The sequence exhibited strong similarity with a number of Bowman-Birk inhibitors from legume and cereal seeds. (dur.ac.uk)
  • Rational lead design strategies are being adopted for the design of PfDHFR inhibitors as anti-malarial agents. (eurekaselect.com)
  • In future the rational methods of lead design and lead optimization are expected to increase because sufficient knowledge is already generated on the structural aspects of PfDHFR and its possible inhibitors are already available. (eurekaselect.com)
  • This proton donation is probably not required for formation of a favorable leaving group for the sulfone inhibitors sulbactam and tazobactam. (nih.gov)
  • Site-directed mutagenesis studies confirm the role of Arg244 and its coordinating partners in beta-lactam turnover and in the reactions leading to enzyme inactivation. (nih.gov)