Pathways

Blue diaper syndrome is a recessive metabolic disorder that has not yet been determined to be X-linked or autosomal. This syndrome is caused by a mutation in the large neutral amino acids transporter small subunit 1 protein, which allows tryptophan, among other amino acids, to be reabsorbed in the kidneys. The excess tryptophan found in the intestine is digested by bacteria which excrete indole, which can undergo oxidation to produce indigo blue. This is seen in the diapers of infants affected by blue diaper syndrome, due to the increased levels of indole in their urine or feces. Other symptoms can include bacterial infections, damage to various parts of the eye, hypercalcemia, and impaired kidney function due to this. Treatment can include a calcium restricted diet in order to prevent hypercalcemia, and a tryptophan restricted diet to prevent all systems. If bacterial infections are common, antibiotics may be prescribed.

Boceprevir is a hepatitis C virus NS3/4A protease inhibitor used in combination with other medications to treat chronic hepatitis C genotype 1 infection. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. Boceprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Boceprevir inhibits NS3/4A protease, which is an enzyme that cleaves the heptatitis C virus polyprotein downstream of the NS3 proteolytic site, which generates nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins are required in viral RNA replication, therefore because of the inhibition of their formation, RNA replication cannot occur. Because RNA replication does not occur, the mature virion is unable to form.

Boceprevir is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Boceprevir passes through the liver and is then excreted from the body mainly through the kidney.

Bopindolol (also known as Sandonorm) is a selective β1 adrenergic receptor antagonist (beta blocker), which can be used for treatment of high blood pressure (hypertension) and irregular heartbeats (arrhythmias). Bopindolol also has the ability to mild intrinsic sympathomimetic activity (ISA) with effective range of dosage. Adrenaline (also known as epinephrine) can activate β1 adrenergic receptor so that the heart rate and output will be increased. Renin is a hormone that generated from kidney, which could lead to constriction of blood vessels. Beta blockers could efficiently prohibit renin release.

Bopindolol is a non-cardioselective beta blocker and the ester prodrug of pinolol. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, bopindolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, bopindolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like bopindolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Bopindolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis. Some side effects of using bopindolol may include chest pain, tingling, numbness, and shortness of breath.

Bopindolol is a non-cardioselective beta blocker and the ester prodrug of pinolol. It can be administered orally, where it passes through hepatic portal circulation, and enters the bloodstream and travels to act on cardiomyocytes. In bronchial and vascular smooth muscle, bopindolol can compete with epinephrine for beta-2 adrenergic receptors. By competing with catecholamines for adrenergic receptors, it inhibits sympathetic stimulation of the heart. The reduction of neurotransmitters binding to beta receptor proteins in the heart inhibits adenylate cyclase type 1. Because adenylate cyclase type 1 typically activates cAMP synthesis, which in turn activates PKA production, which then activates SRC and nitric oxide synthase, its inhibition causes the inhibition of cAMP, PKA, SRC and nitric oxide synthase signaling. Following this chain of reactions, we see that the inhibition of nitric oxide synthase reduces nitric oxide production outside the cell which results in vasoconstriction. On a different end of this reaction chain, the inhibition of SRC in essence causes the activation of Caspase 3 and Caspase 9. This Caspase cascade leads to cell apoptosis. The net result of all these reactions is a decreased sympathetic effect on cardiac cells, causing the heart rate to slow and arterial blood pressure to lower; thus, bopindolol administration and binding reduces resting heart rate, cardiac output, afterload, blood pressure and orthostatic hypotension. By prolonging diastolic time, it can prevent re-infarction. One potentially less than desirable effect of non-selective beta blockers like bopindolol is the bronchoconstrictive effect exerted by antagonizing beta-2 adrenergic receptors in the lungs. Clinically, it is used to increase atrioventricular block to treat supraventricular dysrhythmias. Bopindolol also reduce sympathetic activity and is used to treat hypertension, angina, migraine headaches, and hypertrophic subaortic stenosis.