Insulin Autoimmune Syndrome
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Insulin Autoimmune Syndrome
Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia also known as Hirata's disease, was first described by Hirata in Japan in 1970. Signs and symptoms Affected patients are usually adults, experiencing multiple episodes of spontaneous hypoglycemia with neuroglycopenic symptoms. Causes The cause of IAS is not clearly understood. However, interaction of disulfide bond in the insulin molecule with sulfhydryl group drugs such as methimazole, carbimazole, captopril, isoniazid, hydralazine, imipenem, and also with lipoic acid has been suggested. Drug-induced autoimmunization is evidenced by insulin autoantibodies appearing a few weeks after the intake of drug containing the sulfhydryl group. Additionally, IAS has a significant genetic predisposition as its association with specific HLA class has been observed . Pathophysiology Following a meal, glucose concentration in the bloodstream rises, providing a stimulus for insulin secretion. Autoantibodies b ...
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Hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly. The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol. Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumo ...
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Neuroglycopenic
Neuroglycopenia is a shortage of glucose (glycopenia) in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged or recurrent neuroglycopenia can result in loss of consciousness, damage to the brain, and eventual death. Signs and symptoms *Abnormal mentation, impaired judgment *Nonspecific dysphoria, anxiety, moodiness, depression, crying, fear of dying, suicidal thoughts *Negativism, irritability, belligerence, combativeness, rage *Personality change, emotional lability * Fatigue, weakness, apathy, lethargy, daydreaming *Confusion, amnesia, dizziness, delirium * Staring, "glassy" look, blurred vision, double vision *Automatic behavior *Difficulty speaking, slurred speech *Ataxia, incoordination, sometimes mistaken for "drunkenness" *Focal or general motor deficit, paralysis, hemiparesis * Paresthesia, headache * Stupor, coma, abnormal breathing * Generalized or focal seizures *Plasma glucose 2 ...
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Methimazole
Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism. This includes Graves disease, toxic multinodular goiter, and thyrotoxic crisis. It is taken by mouth. Full effects may take a few weeks to occur. Common side effects include itchiness, hair loss, nausea, muscle pain, swelling, and abdominal pain. Severe side effects may include low blood cell counts, liver failure, and vasculitis. Use is not recommended during the first trimester of pregnancy due to the risk of congenital anomalies, but it may be used in the second trimester or third trimester. It may be used during breastfeeding. Those who developed significant side effects may also have problems with propylthiouracil. Thiamazole is a thioamide and works by decreasing the production of thyroid hormones. Thiamazole was approved for medical use in the United States in 1950. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. It i ...
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Carbimazole
Carbimazole (brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodinating and coupling the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine). It is on the World Health Organization's List of Essential Medicines. Medical uses Medical therapy for hyperthyroidism typically involves either titrating the dose of carbimazole until the patient becomes euthyroid or maintaining a high dose of carbimazole to suppress endogenous thyroid production, and then replacing thyroid hormone with levothyroxine ("block and replace"). Treatment is usually given for 18–24 months followed by a trial withdraw. The onset of anti-thyroid effect is rapid but the onset of clinical effects on thyroid hormone levels in the blood is much slower. This is because the large s ...
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Captopril
Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inhibitor found for the treatment of hypertension. It does not cause fatigue as associated with beta-blockers. Due to the adverse drug event of causing hyperkalemia, as seen with most ACE Inhibitors, the medication is usually paired with a diuretic. Captopril was patented in 1976 and approved for medical use in 1980. Structure–activity relationship Captopril has an L-proline group which allows for it to be more bioavailable within oral formulations. The thiol moiety within the molecule has been associated with two significance adverse effects: the hapten or immune response. This immune response, also known as agranulocytosis, can explain the adverse drug events which may be seen in captopril with the allergic response, which would be: hi ...
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Isoniazid
Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For latent tuberculosis it is often used by itself. It may also be used for atypical types of mycobacteria, such as '' M. avium'', '' M. kansasii'', and '' M. xenopi''. It is usually taken by mouth but may be used by injection into muscle. Common side effects include increased blood levels of liver enzymes and numbness in the hands and feet. Serious side effects may include liver inflammation and acute liver failure. It is unclear if use during pregnancy is safe for the baby. Use during breastfeeding is likely safe. Pyridoxine may be given to reduce the risk of side effects. Isoniazid works in part by disrupting the formation of the bacteria's cell wall which results in cell death. Isoniazid was first made in 1952. It is on the World ...
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Hydralazine
Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours. Common side effects include headache and fast heart rate. It is not recommended in people with coronary artery disease or in those with rheumatic heart disease that affects the mitral valve. In those with kidney disease a low dose is recommended. Hydralazine is in the vasodilator family of medications, so it is believed to work by causing the dilation of blood vessels. Hydralazine was discovered while scientists at Ciba were looking for a treatment for malaria. It was patented in 1949. It is ...
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Imipenem
Imipenem (trade name Primaxin among others) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enzymes produced by many multiple drug-resistant Gram-negative bacteria, thus play a key role in the treatment of infections not readily treated with other antibiotics. Imipenem was patented in 1975 and approved for medical use in 1985. It was discovered via a lengthy trial-and-error search for a more stable version of the natural product thienamycin, which is produced by the bacterium '' Streptomyces cattleya''. Thienamycin has antibacterial activity, but is unstable in aqueous solution, so impractical to administer to patients. Imipenem has a broad spectrum of activity against aerobic and anaerobic, Gram-positive and Gram-negative bacteria. It is particularly important for its activity against ''Pseudomonas aeruginosa'' and the ''Enterococc ...
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Lipoic Acid
Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is also manufactured and is available as a dietary supplement in some countries where it is marketed as an antioxidant, and is available as a pharmaceutical drug in other countries. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. Only the (''R'')-(+)-enantiomer (RLA) exists in nature and is essential for aerobic metabolism because RLA is an essential cofactor of many enzyme complexes. Physical and chemical properties Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA), and thioctic acid is an organosulfur compound derived from octanoic acid. LA contains two sulfur atoms (at C6 and C8) connected by a disulfide bond and is thus considered to be oxidized althou ...
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Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially o ...
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Autoantibodies
An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Production Antibodies are produced by B cells in two ways: (i) randomly, and (ii) in response to a foreign protein or substance within the body. Initially, one B cell produces one specific kind of antibody. In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion. Normally, the immune system is able to recognize and ignore the body's own healthy proteins, cells, and tissues, and to not overreact to non-threatening substances in the environment, such as foods. Sometimes, the immune system ceases to recognize one or more of the body's normal constituents as "self," leading to production of pathological autoantibodies. Autoantibodies may also play a nonpathological role; for instance they m ...
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C-peptide
The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum levels can be used to Differential diagnosis, distinguish between different conditions with similar clinical features. In the insulin synthesis pathway, first preproinsulin is translocated into the endoplasmic reticulum of beta cells of the pancreas with an A-chain, a C-peptide, a B-chain, and a signal peptide, signal sequence. The signal sequence is cleaved from the N-terminus of the peptide by a signal peptidase, leaving proinsulin. After proinsulin is packaged into vesicles in the Golgi apparatus (beta-granules), the C-peptide is removed, leaving the A-chain and B-chain bound together by disulfide bonds, that constitute the insulin molecule. History Proinsulin C-peptide was first described in 1967 in connection with the discovery of the ...
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