What are gallstones?
Gallstones are a common aliment among adults and will on average affect 15 % of the British population; and disproportionally affect women 2-3 times more frequently than men. The risk of developing gallstones increases with age. Most people with gallstones, will not manifest symptoms. Symptoms will only manifest in cases, where the gallstones form a blockage in the common bile duct, preventing the flow of bile from the gallbladder to the small intestine. This happens in about 20 % of cases. Symptoms will often manifest following a meal and can persist for hours. Symptoms are severe pain, below the right ribcage, radiating towards the back or the shoulder, nausea or vomiting, and restlessness brought on by pain. Furthermore, some patients can experience yellow discolouring of skin and eyes (jaundice), pale stools and dark urine.
Gallstones are associated with certain complications, such as inflammation of the gallbladder and acute inflammation of the pancreas, both of which are extremely severe conditions. Treatment is therefore essential. Presently, gallstones are most commonly treated with laparoscopic cholecystectomy, while the pain is managed through analgesic medication. It is possible to live without one’s gallbladder, and in patients whom have had their gallbladder removed, bile is continuously emptied into the small intestine, rather than only occurring after a meal.
In 80 % of patients with gallstones, the stones are composed of cholesterol and calcium salts. Gallstones are caused by an imbalance in the composition of the bile, which can, among other factors, be caused by an increased intake of fat. This leads to a higher concentration of cholesterol, which in turn leads to the formation of cholesterol crystals. These crystals can, eventually, grow into gallstones, that can form a blockage in the common bile duct and cause severe pain.
New medicinal treatment tested on mice
Researches have examined the effect of a specific receptor found, among other locations, in the cells of the gallbladder and liver. This receptor is located in the nucleus of the cells and can up- or downregulate the cells ability of synthesise certain proteins, that are essential to their metabolism. The receptor is called Constitutive Androstane Receptor (CAR) and perform a key role for the concentration of fatty acids and cholesterol in bile.
Researchers have discovered a drug with the ability to stimulate this receptor. They have performed drug trails on mice; where half the test-subjects were given the drug, and the other half did not receive the drug. The mice were fed with either regular mouse feed or a diet rich in fat, which stimulate the formation of gallstones.
Over a two-week period, the mice were given weekly injections with or without the CAR-activating drug, the researchers were able to present promising data for the new drug’s ability to prevent and treat gallstones. The results showed that of the mice, that were given and fatty diet but did not receive the CAR-activating drug, 97,7 % developed gallstones; compared to only 33,3 % of mice that received the drug in addition to a fatty diet. The mice, that were not given the treatment, had gallbladders filled with gallstones, composed of cholesterol crystals, and developed inflammations in the gallbladder wall. In contrast, mice that received the treatment exhibited transparent bile, free of cholesterol crystals, and showed no sign of inflammation in the gallbladder wall. An additional benefit of the treatment, was that the mice displayed an increased conversion of cholesterol to bile salts and an increase in reabsorption of bile salts in the small intestine.
Given that gallstones are a frequent ailment, associated with a high-energy diet, type 2 diabetes, and obesity; a reliable method of prevention and treatment of the ailment would be especially desirable. The researchers suggest that, if the same effect can be replicated in humans, it might be possible to fabricate a pill or injection, capable of preventing and treating gallstones; something which would be especially relevant for high-risk patients. Furthermore, would hospitals be able to save funds, by having to perform fewer operations, and fewer patients would have to undergo the inherent risks associated with surgery.
