Learning about ezetimibe.📜📜📜

Ezetimibe was the first drug to inhibit cholesterol absorption in the gut. It can be combined with statins to enhance the ability to lower cholesterol levels. It is widely used clinically. The following will introduce the relevant knowledge about ezetimibe.

1. The mechanism of ezetimibe.

Ezetimibe is converted to ezetimibe-glucuronide in the intestinal tract. Ezetimibe-glucuronide acts at the brush border of intestinal epithelial cells. It inhibits the activity of the sterol carrier transporter NPC1L1, thereby reducing intestinal absorption of cholesterol.

Dosage: Once a day, 10mg ezetimibe each time. Ezetimibe can be taken any time of the day. It can also be taken on an empty stomach or with food.

2. The enterohepatic circulation of ezetimibe.

First, ezetimibe is converted to ezetimibe-glucuronide in the intestine. It then travels from the portal vein to the liver and from the liver to the bile. Finally it goes back into the intestines. Enterohepatic circulation maintains ezetimibe-glucuronide in the brush border of intestinal epithelial cells. It can inhibit the intestinal absorption of cholesterol. In addition, enterohepatic circulation can also slow the elimination of ezetimibe-glucuronide. Its half-life is 22 hours.

3. The lipid-lowering intensity of ezetimibe.

Cholesterol in the human body can be divided into endogenous synthesis by the body and exogenous absorption in the diet. About 2/3 of cholesterol is synthesized endogenously and 1/3 of cholesterol is absorbed exogenously. 

Ezetimibe alone can reduce low-density lipoprotein cholesterol (LDL-C) by about 20%. 

	Total cholesterol (TC)	Low-density lipoprotein cholesterol (LDL-C)	High-density lipoprotein cholesterol (HDL-C)	Triglycerides (TG)
Ezetimibe	13%↓	18%↓	8%↓	1%↑
Pravastatin	17%↓	25%↓	8%↓	7%↑
Simvastatin	26%↓	36%↓	17%↓	7%↑
Atorvastatin	32%↓	44%↓	25%↓	4%↑

From the above table, it can be seen that statins have stronger lipid-lowering intensity than ezetimibe. Therefore, ezetimibe is often used in combination with statins to further reduce LDL-C.

	Lipid-lowering treatment plan	Reduced levels of LDL-C
Monotherapy	Ezetimibe	20%
	Moderate-intensity statins (eg, simvastatin, pravastatin)	30%
	High-intensity statins (eg, atorvastatin, rosuvastatin)	50%
	PCSK9 inhibitors (eg, evolocumab, alirocumab)	60%
Combination therapy	High-intensity statin + Ezetimibe	65%
	High-intensity statin + PCSK9 inhibitor	75%
	High-intensity statin + PCSK9 inhibitors + Ezetimibe	85%

4. Adverse reactions.

Because ezetimibe is not metabolized by CYP450 enzymes, it is less likely to have drug interactions. Ezetimibe was well tolerated and safe. Its adverse effects are mild and mostly transient. Its main adverse reactions are gastrointestinal discomfort and headache. In addition, side effects such as muscle pain and increased transaminases can occur when it is used in combination with statins.

Read More

Repeated damage to cells can cause cancer, so do muscle cells?💪💪💪

Chronic injury and inflammation are major risk factors for cancer. Carcinogenic factors such as eating hot food, drinking hot tea, smoking, and air pollution are all due to their repeated damage to human tissues. But why does repeated tissue damage lead to cancer? Although the mechanism of this carcinogenesis is complex, one of the more easily understood reasons is that the repair of damaged tissue requires cell division. Every time a cell divides, a gene may mutate. Repeated tissue damage increases the number of cell divisions, which increases the probability of mutation into an oncogene. At this time, fitness enthusiasts may think that muscle fibers are constantly damaged and repaired during muscle exercise. Will it also increase the risk of cancer?

Does muscle building increase the chance of a genetic mutation?

Its answer is of course not. Muscle building does not increase your risk of cancer. The main reason is that with or without exercise, muscle tissue rarely develops tumors. Lung cancer, breast cancer, liver cancer, etc. are all common, but muscle cancer is rare. It is because the muscle tissue rarely develops tumors. Although this does not mean that muscle tissue is completely tumor-free, for example, rhabdomyosarcoma is a tumor with muscle tissue characteristics. However, it is not caused by muscle building. Rhabdomyosarcoma is a common childhood tumor. Congenital or early developmental genetic mutations are its main cause. Adults over the age of 30 generally do not have rhabdomyosarcoma. 

Why do muscles rarely get cancer?

Long-term muscle building can lead to repeated muscle growth and injury, but why do muscles rarely get cancer? Because of the special structure of skeletal muscle, it has its own anti-cancer function. 

The structure of muscle.

As it can be seen from the above figure, a skeletal muscle cell is also called a muscle fiber. It has two main features:

1. Most cells in the human body generally have only one nucleus. However, a myofibroblast will have many nuclei. It belongs to multinucleated cells.
2. Muscle cells, which are multinucleated cells, do not divide and proliferate by themselves. They do not go from one muscle fiber directly to two muscle fibers.

So how does muscle training make muscles stronger without splitting muscle fibers? This makes muscles stronger both by making the muscle cells bigger and by fusing more muscle cells. Muscles tend to get bigger because each muscle fiber cell gets bigger, not because there are more of them. Myofibroblasts use nutrients in the body to synthesize more protein when stimulated by exercise. It makes muscle cells larger, but does not proliferate. 

Muscle building

How do muscles repair after muscle damage?

Muscle stem cells are responsible for muscle repair. Although myofibroblasts cannot divide and proliferate, muscle stem cells can. Muscle stem cells usually only attach to the surface of muscle fibers and do not proliferate. Muscle stem cells are activated if the muscle is growing or repairing damage. They divide and proliferate to create new muscle cells. Most stem cell divisions produce new cells that fuse with old myofibroblasts and repair damaged muscle fibers. The rest retain the properties of muscle stem cells and attach to the surface of muscle fibers.

Muscle Repair.

Why doesn't the division and proliferation of muscle stem cells increase cancer risk?

One of the main reasons is that most muscle stem cells fuse into muscle fibers after they divide and proliferate. When these stem cells fuse into muscle fibers, they lose their ability to divide and proliferate. They do not accumulate mutations. Although a single muscle stem cell division may lead to cancer-causing mutations, one mutation is not enough to generate cancer cells. Adults generally need to accumulate multiple mutations to form cancer cells. And in many cases, specific mutation types and sequences are required to cause cancer. The process is also relatively long. And when a muscle stem cell has an oncogene mutation, it is quickly fused into the muscle fiber. Even if the muscle is damaged by the next exercise, it will not divide and grow again. Normally, it does not accumulate into cancer cells and cause cancer. This biological feature is the anticancer function of skeletal muscle. In addition, a number of studies have shown that regular muscle training does not increase cancer risk but significantly reduces cancer incidence.

Read More

Drinking water like this is bad for your body.😖😖😖

Many people know that drinking more water is good for the body. Many people know that drinking more water is good for the body. However, drinking water indiscriminately can be harmful to the body's organs and the damage is not immediately reflected. It can cause long-term damage to your body without even noticing it. Therefore, here are some bad drinking habits, so that you can change your drinking habits in time.

Too cold water is bad for the stomach and intestines.

With summer approaching, many people like to drink cold water. Drinking it can refresh you when you are sleepy, and it can cool down quickly after exercising. This is very refreshing. However, if a person suddenly drinks too cold water, the smooth muscles of the stomach and intestines will spasm, and the blood vessels will suddenly contract. It may cause stomach and intestinal dysfunction, indigestion, constipation and other problems. Especially during or after exercise, these problems are more likely to be caused. 

When a person is exercising, the functions of various organs in the human body will be adjusted due to the exercise. The functions of exercise-related tissues and organs such as the heart, lungs and muscles will be enhanced. Organs involved in metabolism or energy storage, such as the gastrointestinal tract, are also weakened. The rate of gastric emptying is also reduced. In addition, a person's body temperature rises during and after exercise. At this time, if you drink too much or drink too cold water quickly, it will not only easily cause gastrointestinal disorders, but also cause water retention in the stomach. It can cause nausea, stomach pain, bloating, indigestion and constipation.

Drinking water too fast is bad for the heart.

The heart pumps blood throughout the body through the contraction of the myocardium, and returns the blood to the heart through the relaxation of the myocardium. However, as people age, the function of the heart also declines. After the function of the heart declines, its ability to withstand sudden stimuli will also decrease. Even small stimuli, such as drinking water quickly, can damage the heart due to the increased burden. Especially with a lot of people who are thirsty after a bath, they drink water instantly and quickly. It is very dangerous. Heart rate generally rises right after taking a shower. If you drink water quickly at this time, too much water will enter the blood vessels. This water can make the heart more burdened. People with poor heart function, patients with cardiovascular disease and the elderly may experience symptoms such as palpitation and sweating.

Drinking too little water is bad for your kidneys and bladder.

Drinking too little water can reduce urination. Decreased urination can cause the following:

Decreased urine output and increased urine concentration can saturate or supersaturate calcium phosphate, calcium oxalate, and uric acid in urine. They can precipitate as crystalline particles in the urine. These crystals continue to accumulate and eventually form kidney stones or bladder stones.

Decreased urination prevents bacteria from being excreted in time. It can easily cause acute cystitis, urinary tract infection, etc., especially in women. Because the female urethra is relatively short. External bacteria can easily pass through the infected urethra to the bladder.

If the weather is hot, people sweat more and drink too little water, which increases the risk of infection and urinary tract stones.

In addition, if you don't drink enough water for a long time, your body will be dehydrated. It also increases the risk of urinary system cancers.

Drinking too hot water is bad for the esophagus.

Many people drink some hot water to relieve discomfort when they feel uncomfortable. However, too hot water can actually harm our esophagus. The mucosal epithelial layer on the esophagus is very soft and thin. When hot water directly touches the mucosal epithelial layers, it is easy to burn them and cause breakage, ulceration, and bleeding. The mucosal epithelium generally repairs damaged tissue quickly. However, if the mucosal epithelium is often badly stimulated, it will easily appear some cells with abnormal functions and morphology due to frequent repair and proliferation, and then evolve into tumor cells. Although the maximum temperature that the mouth and esophagus can tolerate is 50 to 60 ^oC, the optimal temperature for food to be eaten by the human body is 10 to 40 ^oC. Therefore, food or water that is too hot should be ingested after it has cooled slightly. 

Read More