Bile Acids and Salts
Cholagogues and Choleretics
Gas Chromatography-Mass Spectrometry
Receptors, Cytoplasmic and Nuclear
Chromatography, Thin Layer
Lipid Metabolism, Inborn Errors
Hydroxymethylglutaryl CoA Reductases
Chromatography, High Pressure Liquid
Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. (1/469)Samples of serum, bile, and urine were collected simultaneously from patients with cholestasis of varying aetiology and from patients with cirrhosis; their bile acid composition was determined by gas/liquid chromatography and mass spectrometry. In cholestasis, the patterns in all three body fluids differed consistently and strikingly. In serum, cholic acid was the major bile acid and most bile acids (greater than 93%) were unsulphated, whereas, in urine, chenodeoxycholic was the major bile acid, and the majority of bile acids (greater than 60%) were sulphated. Secondary bile acids were virtually absent in bile, serum, and urine. The total amount of bile acids excreted for 24 hours correlated highly with the concentration of serum bile acids; in patients with complete obstruction, urinary excretion averaged 71-6 mg/24 h. In cirrhotic patients, serum bile acids were less raised, and chenodeoxycholic acid was the predominant acid. In healthy controls, serum bile acids were consistently richer in chenodeoxycholic acid than biliary bile acids, and no bile acids were present in urine. No unusual monohydroxy bile acids were present in patients with primary biliary cirrhosis, but, in several patients, there was a considerable amount of hyocholic acid present in the urinary bile acids. The analyses of individual bile acids in serum and urine did not appear to provide helpful information in the differential diagnosis of cholestasis. Thus, in cholestasis, conjugation of chenodeoxycholic acid with sulphate becomes a major biochemical pathway, urine becomes a major route of bile acid excretion, and abnormal bile acids are formed. (+info)
Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis. (2/469)Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation. (+info)
PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella spp. (3/469)As enteric pathogens, Salmonella spp. are resistant to the actions of bile. Salmonella typhimurium and Salmonella typhi strains were examined to better define the bile resistance phenotype. The MICs of bile for wild-type S. typhimurium and S. typhi were 18 and 12%, respectively, and pretreatment of log-phase S. typhimurium with 15% bile dramatically increased bile resistance. Mutant strains of S. typhimurium and S. typhi lacking the virulence regulator PhoP-PhoQ were killed at significantly lower bile concentrations than wild-type strains, while strains with constitutively active PhoP were able to survive prolonged incubation with bile at concentrations of >60%. PhoP-PhoQ was shown to mediate resistance specifically to the bile components deoxycholate and conjugated forms of chenodeoxycholate, and the protective effect was not generalized to other membrane-active agents. Growth of both S. typhimurium and S. typhi in bile and in deoxycholate resulted in the induction or repression of a number of proteins, many of which appeared identical to PhoP-PhoQ-activated or -repressed products. The PhoP-PhoQ regulon was not induced by bile, nor did any of the 21 PhoP-activated or -repressed genes tested play a role in bile resistance. However, of the PhoP-activated or -repressed genes tested, two (prgC and prgH) were transcriptionally repressed by bile in the medium independent of PhoP-PhoQ. These data suggest that salmonellae can sense and respond to bile to increase resistance and that this response likely includes proteins that are members of the PhoP regulon. These bile- and PhoP-PhoQ-regulated products may play an important role in the survival of Salmonella spp. in the intestine or gallbladder. (+info)
The effect of bile salts and calcium on isolated rat liver mitochondria. (4/469)Intact mitochondria were incubated with and without calcium in solutions of chenodeoxycholate, ursodeoxycholate, or their conjugates. Glutamate dehydrogenase, protein and phospholipid release were measured. Alterations in membrane and organelle structure were investigated by electron paramagnetic resonance spectroscopy. Chenodeoxycholate enhanced enzyme liberation, solubilized protein and phospholipid, and increased protein spin label mobility and the polarity of the hydrophobic membrane interior, whereas ursodeoxycholate and its conjugates did not damage mitochondria. Preincubation with ursodeoxycholate or its conjugate tauroursodeoxycholate for 20 min partially prevented damage by chenodeoxycholate. Extended preincubation even with 1 mM ursodeoxycholate could no longer prevent structural damage. Calcium (from 0.01 mM upward) augmented the damaging effect of chenodeoxycholate (0.15-0.5 mM). The combined action of 0.01 mM calcium and 0.15 mM chenodeoxycholate was reversed by ursodeoxycholate only, not by its conjugates tauroursodeoxycholate and glycoursodeoxycholate. In conclusion, ursodeoxycholate partially prevents chenodeoxycholate-induced glutamate dehydrogenase release from liver cell mitochondria by membrane stabilization. This holds for shorter times and at concentrations below 0.5 mM only, indicating that the different constitution of protein-rich mitochondrial membranes does not allow optimal stabilization such as has been seen in phospholipid- and cholesterol-rich hepatocyte cell membranes, investigated previously. (+info)
Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. (5/469)We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with CD or PMA and these effects were inhibited by curcumin. Treatment with CD or PMA increased binding of AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above effects on gene expression, we found that curcumin directly inhibited the activity of COX-2. These data provide new insights into the anticancer properties of curcumin. (+info)
Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine. (6/469)Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model. (+info)
Identification of a nuclear receptor for bile acids. (7/469)Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport. (+info)
Bile acids: natural ligands for an orphan nuclear receptor. (8/469)Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis. (+info)
Cholelithiasis is a common condition that affects millions of people worldwide. It can occur at any age but is more common in adults over 40 years old. Women are more likely to develop cholelithiasis than men, especially during pregnancy or after childbirth.
The symptoms of cholelithiasis can vary depending on the size and location of the gallstones. Some people may not experience any symptoms at all, while others may have:
* Abdominal pain, especially in the upper right side of the abdomen
* Nausea and vomiting
* Shaking or chills
* Loss of appetite
* Yellowing of the skin and eyes (jaundice)
If left untreated, cholelithiasis can lead to complications such as inflammation of the gallbladder (cholangitis), infection of the bile ducts (biliary sepsis), or blockage of the common bile duct. These complications can be life-threatening and require immediate medical attention.
The diagnosis of cholelithiasis is usually made through a combination of imaging tests such as ultrasound, CT scan, or MRI, and blood tests to check for signs of inflammation and liver function. Treatment options for cholelithiasis include:
* Watchful waiting: If the gallstones are small and not causing any symptoms, doctors may recommend monitoring the condition without immediate treatment.
* Medications: Oral medications such as bile salts or ursodiol can dissolve small gallstones and relieve symptoms.
* Laparoscopic cholecystectomy: A minimally invasive surgical procedure to remove the gallbladder through small incisions.
* Open cholecystectomy: An open surgery to remove the gallbladder, usually performed when the gallstones are large or there are other complications.
It is important to seek medical attention if you experience any symptoms of cholelithiasis, as early diagnosis and treatment can help prevent complications and improve outcomes.
The hallmark feature of CTX is the presence of xanthomas, which are fatty deposits that accumulate in the brain and spinal cord. These deposits can cause inflammation and damage to the surrounding tissue, leading to a range of neurological symptoms.
CTX is usually diagnosed through a combination of clinical evaluation, imaging studies such as MRI or CT scans, and laboratory tests to identify the genetic mutations responsible for the condition. There is currently no cure for CTX, but treatment options may include medications to manage seizures and other symptoms, as well as surgery to remove xanthomas in some cases.
The most common form of xanthomatosis is called familial hypercholesterolemia, which is caused by a deficiency of low-density lipoprotein (LDL) receptors in the body. This results in high levels of LDL cholesterol in the blood, which can lead to the accumulation of cholesterol and other lipids in the skin, eyes, and other tissues.
Other forms of xanthomatosis include:
* Familial apo A-1 deficiency: This is a rare disorder caused by a deficiency of apolipoprotein A-1 (apoA-1), a protein that plays a critical role in the transportation of triglycerides and cholesterol in the blood.
* familial hyperlipidemia: This is a group of rare genetic disorders that are characterized by high levels of lipids in the blood, including cholesterol and triglycerides.
* Chylomicronemia: This is a rare disorder caused by a deficiency of lipoprotein lipase, an enzyme that breaks down triglycerides in the blood.
The symptoms of xanthomatosis vary depending on the specific form of the condition and the organs affected. They may include:
* Yellowish deposits (xanthomas) on the skin, particularly on the elbows, knees, and buttocks
* Deposits in the eyes (corneal arcus)
* Fatty liver disease
* High levels of cholesterol and triglycerides in the blood
* Abdominal pain
* Weight loss
Treatment for xanthomatosis typically involves managing the underlying genetic disorder, which may involve dietary changes, medication, or other therapies. In some cases, surgery may be necessary to remove affected tissue.
In summary, xanthomatosis is a group of rare genetic disorders that are characterized by deposits of lipids in the skin and other organs. The symptoms and treatment vary depending on the specific form of the condition.
There are several types of cholestasis, including:
1. Obstructive cholestasis: This occurs when there is a blockage in the bile ducts, preventing bile from flowing freely from the liver.
2. Metabolic cholestasis: This is caused by a problem with the metabolism of bile acids in the liver.
3. Inflammatory cholestasis: This occurs when there is inflammation in the liver, which can cause scarring and impair bile flow.
4. Idiopathic cholestasis: This type of cholestasis has no identifiable cause.
Treatment for cholestasis depends on the underlying cause, but may include medications to improve bile flow, dissolve gallstones, or reduce inflammation. In severe cases, a liver transplant may be necessary. Early diagnosis and treatment can help to manage symptoms and prevent complications of cholestasis.
The most common types of biliary fistulas are:
1. Bile duct-enteric fistula: This type of fistula connects the bile ducts to the small intestine.
2. Bile duct-skin fistula: This type of fistula connects the bile ducts to the skin, which can lead to a bile leak and infection.
3. Bile duct-liver fistula: This type of fistula connects the bile ducts to the liver, which can cause bleeding and infection.
Symptoms of biliary fistula may include:
* Jaundice (yellowing of the skin and whites of the eyes)
* Pale or clay-colored stools
* Dark urine
* Loss of appetite
* Weight loss
Diagnosis of biliary fistula is typically made through a combination of imaging tests such as endoscopy, CT scan, and MRI. Treatment options for biliary fistula include:
1. Endoscopic therapy: This may involve the use of an endoscope to repair or close off the fistula.
2. Surgery: In some cases, surgery may be necessary to repair or remove the damaged bile ducts.
3. Stent placement: A stent may be placed in the bile ducts to help keep them open and allow for proper drainage.
It is important to seek medical attention if you experience any symptoms of biliary fistula, as it can lead to serious complications such as infection or bleeding.
There are several types of inborn errors of lipid metabolism, each with its own unique set of symptoms and characteristics. Some of the most common include:
* Familial hypercholesterolemia: A condition that causes high levels of low-density lipoprotein (LDL) cholesterol in the blood, which can lead to heart disease and other health problems.
* Fabry disease: A rare genetic disorder that affects the body's ability to break down certain fats, leading to a buildup of toxic substances in the body.
* Gaucher disease: Another rare genetic disorder that affects the body's ability to break down certain lipids, leading to a buildup of toxic substances in the body.
* Lipoid cerebral degeneration: A condition that causes fatty deposits to accumulate in the brain, leading to cognitive decline and other neurological problems.
* Tangier disease: A rare genetic disorder that affects the body's ability to break down certain lipids, leading to a buildup of toxic substances in the body.
Inborn errors of lipid metabolism can be diagnosed through a variety of tests, including blood tests and genetic analysis. Treatment options vary depending on the specific disorder and its severity, but may include dietary changes, medication, and other therapies. With proper treatment and management, many individuals with inborn errors of lipid metabolism can lead active and fulfilling lives.
There are several types of hyperlipidemia, including:
1. High cholesterol: This is the most common type of hyperlipidemia and is characterized by elevated levels of low-density lipoprotein (LDL) cholesterol, also known as "bad" cholesterol.
2. High triglycerides: This type of hyperlipidemia is characterized by elevated levels of triglycerides in the blood. Triglycerides are a type of fat found in the blood that is used for energy.
3. Low high-density lipoprotein (HDL) cholesterol: HDL cholesterol is known as "good" cholesterol because it helps remove excess cholesterol from the bloodstream and transport it to the liver for excretion. Low levels of HDL cholesterol can contribute to hyperlipidemia.
Symptoms of hyperlipidemia may include xanthomas (fatty deposits on the skin), corneal arcus (a cloudy ring around the iris of the eye), and tendon xanthomas (tender lumps under the skin). However, many people with hyperlipidemia have no symptoms at all.
Hyperlipidemia can be diagnosed through a series of blood tests that measure the levels of different types of cholesterol and triglycerides in the blood. Treatment for hyperlipidemia typically involves dietary changes, such as reducing intake of saturated fats and cholesterol, and increasing physical activity. Medications such as statins, fibric acid derivatives, and bile acid sequestrants may also be prescribed to lower cholesterol levels.
In severe cases of hyperlipidemia, atherosclerosis (hardening of the arteries) can occur, which can lead to cardiovascular disease, including heart attacks and strokes. Therefore, it is important to diagnose and treat hyperlipidemia early on to prevent these complications.