Bee venom destroys HIV and does not destroy adjacent healthy cells. Interesting on the web
More recently, the collection of apitoxin has been labor-intensive with a low yield of useful pharmacological raw materials. The method of "milking" was reminiscent of collecting the poison of a cobra, a viper. A membrane was pulled over the container, forcing the bees to give up the secret, to insert the sting through the membrane. For greater provocation of insects, a rotating drum was used, and sometimes inanimate individuals were simply collected and poisonous glands were separated from them. The first preparation of bee venom was obtained in 1915.
Scientific progress has made it possible to obtain volumes of poison on an industrial scale. The bee is affected by a weak electric shock, its reaction to pain is the release of poison on special glass plates. In nature, a bee dies if the sting, stuck in the body of the enemy, comes off. Under production conditions, the bee is used as a donor many times.
In the air space, the poison crystallizes without losing properties, so it can be in the form:
- natural natural liquid;
- dried poison in the form of a powder of a grayish-cream shade;
- in the form of an oil preparation (emulsion), since it is difficult to dissolve in alcohol and does not dissolve in ether;
- lyophilized, that is, in the form of tiny grains of pure white powder.
The bee poisonous secret is highly soluble in water, so it is washed off the substrates when collecting poison or from the stinger, and then evaporated.
Dry poison for a short time absorbs moisture and, collapsing under the action of bacteria, loses its biological properties. Therefore, it is stored in dark hermetically sealed glass containers. In this case, its properties can be preserved for several years.
Composition of apitoxin
Work on the composition of the poison is still ongoing, but it is known that it contains a huge amount of organic and inorganic compounds, most of which are either toxic or promote inflammation and destroy tissues. The ingredients of the poison act synergistically, their interaction reinforcing each other.
Toxins, which are found only in bee venom, act selectively to cell structures. Protein compounds, such as melittin, apamin, and other polypeptides, can destroy cell membranes of a living organism. They are associated mainly with the biological effect of the secret: contraction of smooth muscles, destruction of the membrane of red blood cells, paralysis of the synapse of central and peripheral neurons and cells.
The damaging effect of apitoxin enzymes (especially hyaluronidase and phospholipase) occurs by enzymatic hydrolysis. The substance of the connective tissue dissolves, the poison penetrates deeper.
A strong inflammatory reaction, swelling and pain are provoked by biogenic derivatives of ammonia (histamine, norepinephrine), but they also allow lowering blood pressure and promoting the activity of the excretory organs of the digestive system. Peptide-linked amino acid macromolecules, serapin and terzapin, have a sedative effect, while adolapin blocks the aggregation of red blood cells, preventing the formation of blood clots.
Some components, such as melittin, cause a different response from the size of a single dose of the body. In a small amount, melittin causes inflammation, the average volume stimulates the adrenal cortex, which leads to an anti-inflammatory effect. Large doses are toxic, block the respiratory center, and can lead to cardiac arrest. No wonder they say: "poison in small doses is a medicine." Apitoxin is the strongest immunomodulator and immunostimulant. With a properly calculated treatment regimen, damaged homeostasis can be restored.
Bee venom withstands boiling and freezing, but when it enters the human stomach, it is destroyed by enzymes (pepsin, renpin). Therefore, preparations with apitoxin are intended mainly for surface rubbing (ointments and balms), intradermal injections (sterile solutions), liquid formulations for physiotherapy.
Acting on the ends of the processes of nerve fibers, apitoxin irritates the cells of the nerve centers. There is a stimulation of blood circulation and acceleration of metabolism. In the bone marrow, the production of red blood cells is accelerated, the amount of hemoglobin in the blood increases, and the cholesterol content decreases. Blood viscosity becomes less - this serves as a good prevention of myocardial infarctions and strokes. Increased nervous excitability decreases, the muscle reaction returns to normal, becomes better sleep and increases appetite.
Apitoxin is subcutaneously prescribed for various disorders in the joints and muscles (gout, myositis, arthritis), infringement or inflammation of the nerve (neuralgia, sciatica, osteochondrosis), paralysis (including stroke), diseases of cardio-vascular system(atherosclerosis, angina pectoris, myocardial infarction).
Poison is injected into painful points and reflex areas by sitting down a bee, injecting apitoxin with a syringe, electro and phonophoresis, as well as apimassage.
At various diseases places most sensitive to exposure (pain points) have different localization. In each subsequent session, the number of bees is increased depending on the disease and the individual reaction of the body to apitoxin, bringing it up to 18 - 20 pcs. In one course, from 9 to 21 sessions, held every other day (lasts no more than 15 minutes). Healing practitioners such as N.P. Yorish, K.A. Kuzmina, N.Z. Khismatullina, who practice treatment with bees, use different numbers of bees, bioactive points and the duration of the recovery break.
During the session, the hairy body of the insect is carefully transferred with tweezers or fingers and applied with the abdomen to the clean surface of the reflex zone or bioactive point. The sting gets stuck in the layers of the skin due to the spikes on its surface. Therefore, after 5-10 minutes, the sting is carefully removed and treated with boron petroleum jelly. Under the influence of the poison from the brain, blood flow occurs to the tissues exposed to the poison, for this reason the patient may lose consciousness. After the session, you must lie down for at least half an hour. It is forbidden to be in the open sun, sunbathe and swim, engage in heavy physical labor.
As observations have shown, alcohol has specific antitoxic properties, therefore, during treatment sessions, people refrain from drinking alcoholic beverages. Ascorbic acid, which is part of many fruits and preserves, catalyzes the action of histaminase, neutralizing bacterial toxins. For this reason, it is recommended to follow a dairy-vegetarian diet without spices, pickles and smoked foods.
For various diseases developed its own method of bee stinging. So, sensorineural hearing loss is treated by stinging in the behind-the-ear zone, with stereotoxicosis, bees are planted over parathyroid glands. Although most often insects are forced to sting the outer surfaces of the limbs.
Other types of apitoxin therapy
According to these methods of natural stinging, ampouled poison can be injected with a syringe. In this case, you can clearly dose the intake of the drug, but in this case, the pain from the procedure is greater. Treatment regimens are currently being developed various diseases based on Chinese acupuncture.
A good summarizing result has a combined effect of apitoxin and direct current (electrophoresis), as well as the mutual action of poison and ultrasound (phonophoresis). Basically, physiotherapy is used for radiculitis, arthrosis, polyarthritis.
Apimassage also has a positive effect on the body. Increased blood flow to the diseased organ and relaxation of the muscles under the influence of massage techniques and apitoxin deeply warm up sore spot and give an analgesic effect. After instructions from the apitherapist, the patient independently rub the poison into pain points.
doctor, based medical card the patient, his individual tolerance and bioassays, can combine all methods of apitoxin therapy.
The ancient healer Galen (c. 130-200 AD) advised the use of a mixture of bee venom and honey as a remedy to nourish hair follicles and stimulate hair growth. Since there is a high risk to life in independent attempts to calculate individual doses of both natural bee treatment and the use of pharmaceutical preparations of pure apitoxin, we recommend using pharmaceuticals that have passed clinical trials.
It is important to understand that insect bite treatment and injection medical preparations bee venom except strong therapeutic action It has a strong toxic effect and is strictly prohibited, for example, in tuberculosis, diabetes mellitus, all infectious diseases in the active phase and suppurative processes. Ointments, the composition of which includes bee venom, can be treated independently with individual tolerance this product beekeeping.
Ellie Lobel, 27, was bitten by a tick and contracted Lyme disease. Years later, the woman, tired of fighting the terrible consequences of her illness, decided to give up.
Lyme disease is caused by bacteria Borreliaburgdorferi that enter the body through tick bites. About 300,000 new cases of infection are registered in the United States every year. Virtually none of the sick people die, and most of them recover, provided timely medical care is provided. Antibiotic treatment kills bacteria before they can attack the heart, joints, and nervous system.
But in the spring of 1996, Ellie did not suspect that she needed to pay attention to the characteristic reaction in the form of a rash - the woman thought that she had been bitten by a spider. After that, for three months she suffered from flu-like symptoms and terrible pains that migrated to different parts of the body. Ellie - a healthy, active mother of three - did not know how to recover from this strange disease. She became disabled. “I could barely lift my head off the pillow on my own,” the woman recalls.
The first doctor she went to diagnosed viral disease and reassured her that it would go away on its own. The second doctor said the same. Time passed, Ellie went to the doctors, and each time she was given a new diagnosis - multiple sclerosis, lupus, rheumatoid arthritis, fibromyalgia. No one guessed that the woman's body is affected by bacteria Borrelia. Put correct diagnosis could only more than a year after infection, but by that time it was already too late.
"I went through a variety of treatments one after the other," Ellie says. Her condition steadily worsened. She could not get out of bed herself, was forced to use a wheelchair, noticed a loss of short-term memory and a decrease in intelligence: "Sometimes I got better for a short time, but then I again plunged into this nightmare - and each time the relapses became more and more cruel."
After 15 years of living like this, Ellie gave up. “Nothing helped me anymore, and no one could advise me anything,” she says. “I didn’t care if I lived to see my next birthday. I decided that I had had enough. I just wanted to end this torment.”
Ellie moved to California to die there. And almost died.
Less than a week after moving in, she was attacked by a swarm of Africanized bees - hybrid bees that are large and especially aggressive.
savior bees
Prior to this incident, Ellie had only spent three days in California. "I wanted to take a last breath fresh air, expose your face to the sun and hear the birds singing, she says. “I knew I would die bedridden in three or four months. My condition was quite depressive."
By that time, Ellie was already struggling to stand on her feet without assistance. She hired a male nurse to help her move slowly along the country roads near her new home in Wildomar, which was to be her final resting place.
Before this incident, Ellie was deathly afraid of bees.
Ellie stopped at the collapsed wall when the first bee appeared. The insect, according to her recollections, bit her right on the head. “And all of a sudden there was a whole swarm of bees,” she says.
Her companion ran away. But Ellie could neither run nor even walk on her own: "The bees got tangled in my hair, I heard nothing but their buzzing. And then I thought - now I'm going to die, right here."
Ellie is part of a relatively small group of people - according to various estimates, from 1% to 7% of the world's population - with a very strong allergy to bee venom. When she was two years old, she developed anaphylaxis from a bee sting, a severe reaction of the immune system that can be expressed in swelling, nausea, and constriction. respiratory tract. Then Ellie almost died - she had a respiratory arrest, and she had to be revived with a defibrillator. After that incident, Ellie's mother instilled in her a fear of bees so that she would never again find herself in such life-threatening situations.
Powerful Poison
Bees, as well as some other species of Hymenoptera insects, such as ants and wasps, have a powerful weapon - a multi-component poison. Perhaps the most important of these components is a tiny 26-amino acid peptide known as melitin, which is what causes the burning sensation of a bee sting.
When the body is exposed to high temperatures, cells release inflammatory compounds that activate special channels in receptor neurons known as TRPV1 receptors. As a result, neurons send a signal to the brain that its owner is on fire. Melitin acts on other enzymes in the body that, acting in the same way as inflammatory compounds, also activate TRPV1 receptors.
“I still managed to feel the first five or ten bites,” Ellie recalls. “All I heard was their deafening buzz; I felt how they sting my head, face, neck.”
She continues: “I went limp, raised my hands and covered my face with them, because I didn’t want the bees to sting in my eyes ... And then the bees disappeared.”
Ellie is convinced that bee venom saved her life.
When the swarm finally left, Ellie's man tried to take her to the hospital, but she refused. "It was God who finally decided to put me out of my misery," she told him. "I'll just accept his gift."
"I locked myself in my room and asked him to come the next morning to collect my body."
But Ellie didn't die, not that day, not four months later.
"I can't believe what happened three years ago, I can't believe my recovery," she says. "But all the tests confirm it, and I feel so healthy!"
Ellie is convinced that the bee venom saved her life.
It has long been known that toxins contained in animal venoms that cause harm to humans can also be used for treatment. In Asia, bee venom has been used medicinally for centuries. In traditional Chinese medicine, scorpion venom is considered a powerful drug and is used to treat a wide range of ailments, from eczema to epilepsy. It is said that the Pontic king Mithridates VI, a powerful enemy of the Roman Empire (also known for having studied poisonous plants since childhood), avoided death from a serious wound on the battlefield by stopping the bleeding with the venom of a steppe viper.
"Through millions of years of evolution, insects, these tiny chemical engineers, have created an infinite number of molecules that act on different parts of our nervous system," says Ken Winkel, director of poison research at the University of Melbourne. "The idea is to treat diseases of the nervous system with using these powerful neurotoxins has been discussed for a long time, but we don't have enough knowledge yet to do it effectively and safely for the patient."
According to Ellie, in order to collect one gram of poison, it takes 10,000 bees to pass through the plate.
Despite the abundance of historical evidence in favor of the use of animal poisons in medicinal purposes, in modern medical therapy, their use remained minimal until the beginning of the 21st century, says researcher Glenn King from the University of Queensland in Brisbane, Australia. In 1997, while Ellie was rushing to the doctors, King was dissecting the venom of the deadly Australian funnel-web spider. Now he is one of the leaders in research on the pharmacological properties of animal poisons.
King's team was the first to break down spider venom into components using high performance liquid chromatography. "I was blown away by the results," says King. "Nobody before us had seriously paid attention to this pharmacological gold mine. We were able to decompose the poison into hundreds of individual peptides."
During the 20th century in medical literature periodically there were proposals to use animal poisons in the treatment of various diseases. Tests have shown that such poisons help fight cancer, kill bacteria, and even serve as powerful painkillers - although many experiments were limited to experimental animals. At the time of this writing, only six drugs based on animal venoms have been approved for use. medical use US FDA food products and medicines (another drug - Baltrodibin, created on the basis of the venom of the spear-headed snake - does not have such permission, but is sold outside the United States as a hemostatic agent during surgical operations).
The more we learn about poisons that cause terrible harm to human health, the more we understand how useful they can be from a medical point of view - for example, as in the case of melitin in bee venom.
Action at the molecular level
Melitin is capable of not only causing pain. When dosed correctly, it punches holes in the protective membranes of cells, causing them to explode. In small doses, melitin binds to membranes, activating lipid-degrading enzymes. These enzymes mimic the inflammatory process caused by exposure to elevated temperature. But in more high concentration and under certain conditions, melitin molecules are grouped into rings. They create wide pores in cell membranes, weakening the cell's protective barrier and causing the entire cell to swell and burst like a balloon.
Melitin easily copes with various bacteria and fungi
Due to this property, melitin acts as a powerful antimicrobial agent, easily coping with a variety of bacteria and fungi. However, scientists believe that this useful qualities melitin are not exhausted. They hope it can help fight diseases like HIV, cancer, arthritis, and multiple sclerosis.
For example, researchers at the Washington University School of Medicine in St. Louis, Missouri, found that melitin can destroy the protective membrane of the human immunodeficiency virus without damaging the body's cells. At the same time, the virus has no chance to develop resistance to this threat. “Melitin destroys the inherent physical property of HIV,” lead author Joshua Hood told the press. “In theory, the virus will not be able to adapt to such a scenario. The protective shell is vital for it.” The drug being developed in Missouri was originally developed as a prophylactic vaginal gel, but scientists now hope that nanoparticles “charged” with melitin can in the future be injected into the bloodstream of patients, thus clearing the body of infection.
bacteria killer
But did bee venom really cure Ellie of Lyme disease? The woman agrees that her story does not sound entirely believable. "If someone suggested that I experience bee stings in order to recover, I would consider this person crazy," says Ellie. However, now she has no doubt that it was the poison that helped her heal.
After being bitten, Ellie looked at her watch, waiting for the symptoms of anaphylaxis to appear, but they still did not appear. Instead, three hours later began excruciating pain throughout the body. Even before the disease, Ellie received a natural science education. She believes that her pains were not caused by an allergic reaction to bee venom, but by an allergic process to toxins from dying bacteria, known as the Jarisch-Hexheimer reaction. A similar syndrome is observed in the treatment of severe syphilis. There is a version that certain types bacteria die and secrete toxic substances which in turn cause fever, rash and other symptoms.
Ellie was in pain for three days. And then the pain disappeared.
“All these years I lived in a constant state of semi-coma due to inflammation of the brain caused by Lyme disease,” she says. “But suddenly the fog in my head cleared. I realized that I could think clearly again - for the first time in many years.”
Ellie used apitherapy for a while - treatment with live bees
Now that her mind was clear, Ellie wondered what had happened to her. She did what anyone in her place would have done - she began to search for information on the network. To her dismay, the search turned up no significant results. However, she was able to find a link to a small study conducted in 1997 by scientists from the Rocky Mountain Laboratories in Montana, who found that melitin kills bacteria. Borrelia. The researchers exposed cell cultures to pure melitin and concluded that the substance completely blocked growth. Borrelia. After a more detailed study, they found that shortly after contact with melitin, the bacterium is actually paralyzed - it loses the ability to move, and at this time the peptide acts on its outer membrane. After some time, the membrane begins to disintegrate, and the bacterium dies.
Inspired by her own experience and the findings of researchers, Ellie decided to try apitherapy, a form of treatment using live bees and bee products. She was interested in living bees.
In her apartment, Ellie arranged a special house for bees. She doesn't grow them herself - she orders a batch by mail once a week. Ellie takes the bee with tweezers and gently presses it to one or another part of the body. "Sometimes you have to lightly tap on their sting, but usually they sting willingly," she says.
Ellie started with 10 bee stings a day, three times a week on Mondays, Wednesdays and Fridays. Three years have passed, and after countless bites, Ellie appears to have made a full recovery. She is gradually reducing the number of stings and the frequency of the procedure - in the past eight months, she had the bees sting herself only three times (and once - in an attempt to reduce swelling caused by a fracture, and not due to symptoms caused by Lyme disease). Ellie still keeps bees at home just in case, but for the last year she has mostly gone without them.
New Research
Rare cases like Ellie's serve as a reminder of the powerful potential that animal poisons have. However, translating word of mouth healing legends into actual pharmaceuticals can be a very long and difficult process. "It takes up to 10 years between discovering the pharmacological properties of a substance and obtaining a patent for a drug based on it," says King. "And for every success, there are a dozen failures."
Since the 1997 study, no one has studied bee venom in depth as possible remedy from Lyme disease - until Ellie took care of it.
Bee venom is worth more than gold
She agreed to cooperate with a beekeeping farm that collects bee venom using an electrified glass plate placed at the entrance to the hives - bees pass over the plate on their way out of the hive and back, and harmless to them electric currents stimulate the release of poison from the abdomen. Tiny droplets of poison settle on the glass, which are then collected. According to Ellie, to collect one gram of venom, it takes 10,000 bees to pass through the plate (according to other sources, such as the UN Food and Agriculture Organization, one gram of venom is contained in 1 million bee stings). She emphasizes that this collection method does not harm the health of the bees.
Ellie sends some of the purchased poison - which she says is "worth more than gold" due to the high cost of the humane method of collection - to Eva Sapi, an assistant professor of biology and environmental studies at the University of New Haven who studies Lyme disease.
Sapi's work on the effects of bee venom on Lyme bacteria is ongoing and the results have yet to be published, although she says the preliminary findings from one of her students are "very encouraging." bacteria Borellia can change shape in the body, which is why they are so difficult to destroy. Sapi found that traditional antibiotics don't actually kill bacteria, but simply cause them to mutate into a more latent form. As soon as the patient stops taking antibiotics, the bacteria become active again. In his lab, Sapi is testing various bee venoms on every form the bacterium can take, and so far, research shows that melitin is effective in all cases.
Next, it will be necessary to find out whether melitin has such an effect on bacteria, or whether other substances involved in this process are also contained in bee venom. "In addition, we want to see with high-resolution images what exactly happens when bee venom comes into contact with Borellia", says the researcher.
It is still not known for certain whether the bee venom killed disease bacteria or simply stimulated immune system Ellie
Sapy emphasizes that more data needs to be collected before a decision can be made on the appropriateness of the clinical use of melitin. "There needs to be some animal testing before going into human studies," she says. we are talking about the poison." In addition, it is still not known for certain why the bee venom helped Ellie, including due to the fact that the etiology of the symptoms that she experienced during the treatment remains unclear. "Whether the bee venom turned out to be effective in her case because he killed Borellia or because it stimulated her immune system?” Sapi asks. There is no answer to this question yet.
Be that as it may, animal poisons can be excellent sources of drugs for the treatment of severe neurological diseases, since many of them act specifically on the nervous system of the victim. “In this area, we do not yet have effective drugs,” says Winkel. “In the meantime, tiny living factories live next to us, producing an infinite number of amazing substances…”
No one knows exactly how many poisonous species of animals live on Earth. But it is known about the existence of poisonous jellyfish, snails, insects and even primates. "When asked to suggest the most convincing argument for the need to preserve wildlife, I answer that trying to appeal to her beauty and virginity is the most losing option," says Dr Brian Fry from the University of Queensland. Instead, he said, it should be emphasized that wild nature has a gigantic - and not yet fully explored - potential that can be useful to humanity: "We are talking about a resource, about money. Therefore, protecting nature through its commercialization is the only reasonable approach."
Ellie fully shares this idea. "We still have a lot of research to do on natural poisons," she says. "We need to see what else nature has to offer to help us."
Nanoparticles containing bee venom toxin (melittin) can destroy the human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, scientists from the University of Washington said in a report. medical institute, in the March 2013 issue of the journal Antiviral Therapy. The researchers say their finding is an important step towards creating a vaginal gel that could prevent the spread of HIV infection in the body. HIV is the virus that causes AIDS.
Joshua L. Goode, MD, PhD, scientific director of the medical department, said: "We hope that in places where the HIV virus is spreading very quickly, people could use this gel as a preventive measure to stop the initial infection."
Melittin also destroys some other viruses and malignant tumor cells.
Melittin is a powerful toxin that has been found in bee venom. It can destroy the protective shell of the virus that surrounds the human immunodeficiency virus, like the shell of other viruses. Pure melittin in large quantities can cause significant harm.
Senior author, Samuel A. Wickline, MD, J. Russell Hornsby Professor of Biomedical Sciences, has clearly demonstrated that nanoparticles fueled with melittin have anti-cancer properties and have the ability to kill tumor cells. The use of bee venom in antitumor therapy is not an innovation; in 2004, Croatian scientists published in the journal Science of Nutrition and Agriculture that bee products, including bee venom, may well find their use in the treatment and prevention of cancer.
Healthy cells, however, remain intact - scientists have proven that nanoparticles filled with melittin do not harm normal, healthy cells. Protective bumpers have been added to the surface of the nanoparticles so that when they come into contact with normal cells (which tend to be much larger), the nanoparticles bounce off rather than attach to them.
HIV virus cells are much smaller than nanoparticles, and they fit between bumpers. When HIV encounters nanoparticles, it penetrates between the bumpers and comes into direct contact with their surface, which is coated with bee toxin, which in turn destroys the virus.
Goode explained: “Melittin on the nanoparticles fuses with the viral envelope. Melittin forms small pores, similar to an attack complex, and breaks the shell, extracting the virus from it.
While most anti-HIV drugs work by keeping the virus from replicating, this drug works by vital part its structures. The problem of influencing the ability of the pathogen is reproduced in that it does not stop it from spreading the infection. Some varieties of HIV have found a way to bypass the drugs that block its spread, and despite taking these drugs, it still spreads in the body.
Good says, "We're working on physical properties that are inherent in the HIV virus. Theoretically, the virus has no way to adapt to this impact. The virus must have a protective coating of a two-layer membrane." Melittin nanoparticles can prevent the penetration of HIV infection and, at the same time, treat an existing HIV infection in the body.
Goode believes that melittin loaded into nanoparticles has potential in two types of treatment:
- Vaginal gel to prevent the spread of HIV infection in the body.
- Treatment of pre-existing HIV infection, i.e. individually pharmacoresistant treatment.
In theory, if the nanoparticles are injected into a patient's bloodstream, they should be able to clear the blood of HIV infection.
Goode said: “The core particle we use in these experiments was developed many years ago as an artificial blood product. It doesn't do a very good job of delivering oxygen, but it circulates well in the body and gives us a good platform that we can use to fight different kinds of infections."
Melittin randomly attacks bilayer membranes, making it a powerful agent used in drug therapy other than treating HIV infection. Hepatitis B and C viruses, among a number of other viruses, are based on the same type of protective shell and can be destroyed by injecting melittin loaded with nanoparticles into the body.
The gel also has the potential to affect sperm, the researchers explain using it as a possible contraceptive.
Goode said: “We have also observed this process in couples where only one of the partners has HIV infection and they really want to have children. These particles themselves are safe for sperm, for the same reason they are perfectly safe for vaginal cells.”
This study was conducted on cells in the laboratory. At the same time, nanoparticles are easy to produce, and a sufficient number of particles can certainly be provided for future human research.
Latest HIV Research
Over the past few years, scientists have made great strides in improving the treatment of HIV/AIDS and developing strategies for the prevention of this disease.
Researchers at the Johns Hopkins Children's Center, the University of Mississippi Medical Center, and the University of Massachusetts Medical School reported that a baby treated with antiretroviral therapy was functionally cured thirty hours after birth. functional treatment means that no viral replication was detected in the body after antiretroviral therapy.
Developing antiretroviral therapy for HIV worth the extra cost - researchers at Harvard University in the US reported that scaling up antiretroviral therapy in a remote province of South Africa (KwaZulu-Natal) reduced the risk of transmitting the HIV virus to sexual partners by 96%.
- and non-small cell lung cancer. These types are diagnosed based on how the cells look under a microscope. Based on the established type, treatment options are selected. To understand disease prognosis and survival, here are the US open source statistics for 2014 for both types of lung cancer together: New cases (prognosis: 224,210 Predicted deaths: 159,260 Let's take a closer look at both types, specifics and treatment options. "> Lung Cancer 4
- in the US in 2014: New cases: 232,670 Deaths: 40,000 Breast cancer is the most common non-skin cancer among women in the US (open sources estimate that 62,570 cases of pre-invasive diseases (in situ, 232,670 new cases of invasive disease, and 40,000 deaths.Thus, less than one in six women diagnosed with breast cancer dies from the disease.In comparison, about 72,330 American women are estimated to die from lung cancer in 2014. Breast Cancer glands in men (yes, yes, there is such a thing. It accounts for 1% of all cases of breast cancer and mortality from this disease. Widespread screening has increased the incidence of breast cancer and changed the characteristics of the detected cancer. Why did it increase? Yes, because the use of modern methods has made it possible to detect incidence of low-risk cancer, premalignant lesions, and ductal cancer in situ (DCIS. Population-based studies from the US and UK show an increase in DCIS and the incidence of invasive breast cancer since 1970, this is due to widespread hormone therapy in postmenopausal women and mammography. In the last decade, women have abstained from the use of postmenopausal hormones and the incidence of breast cancer has decreased, but not to the level that can be achieved with widespread use mammography. Risk and protective factors Increasing age is the most important risk factor for breast cancer. Other risk factors for breast cancer include the following: Family history o Underlying genetic susceptibility Sexual mutations in the BRCA1 and BRCA2 genes, and other breast cancer susceptibility genes Alcohol consumption Breast tissue density (mammographic) Estrogen (endogenous: o Menstrual history (onset of menses) / Late menopause o No history of childbirth o Older age at first birth History of hormone therapy: o Combination estrogen and progestin (HRT Oral contraception Obesity Lack of exercise Personal history of breast cancer Personal history of proliferative forms benign diseases breast radiation exposure of the breast Of all women with breast cancer, 5% to 10% may have germline mutations in the BRCA1 and BRCA2 genes. Studies have shown that specific BRCA1 and BRCA2 mutations are more common among Jewish women. Men who carry the BRCA2 mutation also have an increased risk of developing breast cancer. Mutations in both the BRCA1 gene and BRCA2 also create an increased risk of developing ovarian cancer or other primary cancers. Once BRCA1 or BRCA2 mutations have been identified, it is desirable for other family members to get genetic counseling and testing. Protective factors and measures to reduce the risk of developing breast cancer include the following: Use of estrogen (especially after a hysterectomy) Establishing an exercise habit Early pregnancy Breast-feeding Selective estrogen receptor modulators (SERMs) Aromatase inhibitors or inactivators Reduced risk of mastectomy Reduced risk of oophorectomy or ovariectomy Screening Clinical trials have found that screening asymptomatic women with mammography, with or without clinical examination breast cancer, reduces mortality from breast cancer. Diagnosis In case breast cancer is suspected, the patient usually has to go through the following steps: Confirmation of the diagnosis. Assessment of the stage of the disease. The choice of therapy. Next tests and procedures used to diagnose breast cancer: Mammography. Ultrasound. Breast magnetic resonance imaging (MRI, if clinically indicated. Biopsy. Contralateral breast cancer Pathologically, breast cancer can be multicentric and bilateral. risk of primary breast cancer in the contralateral breast ranges from 3% to 10%, although endocrine therapy may reduce this risk Development of second breast cancer is associated with an increased risk of distant recurrence When a BRCA1/BRCA2 gene mutation has been diagnosed in before the age of 40 years, the risk of second breast cancer in the next 25 years reaches almost 50%.Patients diagnosed with breast cancer should have bilateral mammography at the time of diagnosis to rule out synchronous disease.The role of MRI in contralateral breast cancer screening and monitoring of women treated with breast preservation therapy continues to evolve. Because the elevated level detection of possible disease on mammography has been demonstrated, the selective use of MRI for adjunctive screening occurs more frequently, despite the absence of randomized controlled data. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation is recommended prior to initiating treatment. Whether this increase in the rate of disease detection will lead to improved treatment outcomes is unknown. Prognostic factors Breast cancer is usually treated with various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Conclusions and selection of therapy may be influenced by the following clinical and pathological features (based on conventional histology and immunohistochemistry): Patient's climacteric status. Disease stage. Grade of the primary tumor. Tumor status depending on the status of estrogen receptors (ER and progesterone receptors (PR. Histological types). Breast cancer is classified into different histological types, some of which are of prognostic value.For example, favorable histological types include colloidal, medullary, and tubular cancer.The use of molecular profiling in breast cancer includes the following: ER and PR status testing. HER2/Neu status Based on these results, breast cancer is classified as: Hormone receptor positive HER2 positive Triple negative (ER, PR and HER2/Neu negative Although some rare hereditary mutations, such as BRCA1 and BRCA2, predispose to the development of breast cancer in carriers of the mutation, but prognostic data for carriers of the BRCA1 /BRCA2 mutation are controversial; these women are simply at greater risk of developing second breast cancer. But it is not certain that this can happen. Hormone Replacement Therapy After careful consideration, patients with severe symptoms may be treated with hormone replacement therapy. Follow-up The frequency of follow-up and the appropriateness of screening after completion of primary treatment for stage I, stage II, or stage III breast cancer remain controversial. Data from randomized trials show that periodic follow-up with bone scans, liver ultrasound, radiography chest and blood tests for liver function does not improve survival or quality of life at all compared to routine physical exams. Even when these tests allow early detection of recurrence of the disease, this does not affect the survival of patients. Based on these data, limited follow-up and annual mammography for asymptomatic patients treated for stage I to III breast cancer may be an acceptable follow-up. More detailed information in articles: "> Mammary cancer5
- , ureters, and proximal urethra are lined with a specialized mucous membrane called transitional epithelium (also called urothelium. Most cancers that form in the bladder, renal pelvis, ureters, and proximal urethra are transitional cell carcinomas (also called urothelial carcinomas, derived from transitional epithelium. Transitional cell carcinoma of the bladder can be low-grade or high-grade: Low-grade bladder cancer often recurs in the bladder after treatment, but rarely invades the muscular walls of the bladder or spreads to others parts of the body Patients rarely die from low-grade bladder cancer High-grade bladder cancer usually recurs in the bladder and also has a strong tendency to invade the muscular walls of the bladder and spread to other parts of the body High-grade bladder cancer is considered more aggressive than low-grade bladder cancer and are much more likely to die Almost all deaths from bladder cancer are due to high-grade cancers Bladder cancer is also divided into muscle-invasive and non-muscle-invasive disease based on invasion into the muscular mucosa (also referred to as the detrusor mucosa, which is located deep in the muscular wall of the bladder. Muscle-invasive disease is much more likely to spread to other parts of the body and is usually treated either by removing the bladder or treating the bladder with radiation and chemotherapy. As noted above, high-grade cancers are much more likely to be muscle-invasive cancers than low-grade cancers. Thus, muscle-invasive cancer is generally considered to be more aggressive than non-muscle-invasive cancer. Non-muscle invasive disease can often be treated by removing the tumor using a transurethral approach, and sometimes by chemotherapy or other procedures in which a drug is injected into the bladder through a catheter to help fight the cancer. Cancer can occur in the bladder in conditions of chronic inflammation, such as a bladder infection caused by the parasite haematobium Schistosoma, or as a result of squamous metaplasia; The incidence of squamous cell bladder cancer is higher in chronically inflammatory conditions than otherwise. In addition to transitional carcinoma and squamous cell carcinoma, adenocarcinoma, small cell carcinoma, and sarcoma can form in the bladder. In the United States, transitional cell carcinomas make up the vast majority (over 90% of bladder cancers. However, a significant number of transitional carcinomas have areas of squamous or other differentiation. Carcinogenesis and Risk Factors There is strong evidence that carcinogens influence the onset and development of bladder cancer. The most common risk factor for developing bladder cancer is cigarette smoking. It is estimated that up to half of all bladder cancers are caused by smoking and that smoking increases one's risk of developing bladder cancer by two to four times the baseline risk. Smokers with a less functional N-acetyltransferase-2 polymorphism (known as a slow acetylator) have a higher risk of developing bladder cancer compared to other smokers, apparently due to a reduced ability to detoxify carcinogens. Some occupational exposures have also been associated with bladder cancer, and higher rates of bladder cancer have been reported due to textile dyes and rubber in the tire industry; artists; leather workers; shoemakers; and aluminum-, iron-, and steelworkers. bladder carcinogens include beta-naphthylamine, 4-aminobiphenyl, and benzidine.Although these chemicals are now generally banned in Western countries , many other chemicals that are still in use are also suspected of initiating bladder cancer. Exposure to the chemotherapy agent cyclophosphamide has also been associated with an increased risk of bladder cancer. Chronic urinary tract infections and infections caused by the parasite S. haematobium are also associated with an increased risk of bladder cancer, and often squamous cell carcinoma. Chronic inflammation is believed to play a key role in the process of carcinogenesis under these conditions. Clinical features Bladder cancer usually presents with simple or microscopic hematuria. Less commonly, patients may complain of frequent urination, nocturia, and dysuria, symptoms that are more common in patients with carcinoma. Patients with urothelial cancer of the upper urinary tract may experience pain due to tumor obstruction. It is important to note that urothelial carcinoma is often multifocal, necessitating examination of the entire urothelium if a tumor is found. In patients with bladder cancer, imaging of the upper urinary tract is essential for diagnosis and follow-up. This can be achieved with ureteroscopy, retrograde pyelogram in cystoscopy, intravenous pyelogram, or computed tomography (CT urogram). In addition, patients with transitional cell carcinoma of the upper urinary tract are at high risk of developing bladder cancer; these patients need periodic cystoscopy and observation of the opposite upper urinary tract Diagnosis When bladder cancer is suspected, the most useful diagnostic test is cystoscopy Radiological examination such as computed tomography or ultrasound is not sensitive enough to be useful in detecting bladder cancer Cystoscopy may be performed in the urology If cancer is found during cystoscopy, the patient is usually scheduled for a bimanual examination under anesthesia and a repeat cystoscopy in the operating room so that transurethral resection of the tumor and/or biopsy can be performed.Survival In patients who die from bladder cancer , almost always there are metastases from the bladder to other organs. Low-grade bladder cancer rarely grows into the muscular wall of the bladder and rarely metastasizes, so patients with low-grade (stage I bladder cancer) very rarely die from cancer. However, they may experience multiple recurrences, which must be resected. Nearly all deaths from bladder cancer occur among patients with high grade disease, which has a much greater potential to invade deep into the muscular walls of the bladder and spread to other organs. Approximately 70% to 80% of patients with newly diagnosed bladder cancer have superficial bladder tumors (i.e. stage Ta, TIS, or T1). The prognosis of these patients depends largely on the grade of the tumor. Patients with tumors high degree malignancies have a significant risk of dying from cancer, even if it is not a muscle-invasive cancer. Those patients with high-grade tumors who are diagnosed with superficial, non-muscle-invasive bladder cancer in most cases have a high chance of being cured, and even in the presence of muscle-invasive disease, sometimes the patient can be cured. Studies have shown that in some patients with distant metastases, oncologists have achieved a long-term complete response after treatment with a combination chemotherapy regimen, although in most of these patients, metastases are limited to their lymph nodes. Secondary Bladder Cancer Bladder cancer tends to recur even if it is non-invasive at the time of diagnosis. Therefore, it is standard practice to conduct surveillance of the urinary tract after a diagnosis of bladder cancer has been made. However, studies have not yet been conducted to assess whether observation affects progression rates, survival, or quality of life; although there are clinical trials to determine the optimal follow-up schedule. Urothelial carcinoma is believed to reflect a so-called field defect in which the cancer is due to genetic mutations that are widely present in the patient's bladder or throughout the urothelium. Thus, people who have had a resected bladder tumor often subsequently have ongoing tumors in the bladder, often in locations other than the primary tumor. Similarly, but less frequently, they may develop tumors in the upper urinary tract (i.e., in the renal pelvis or ureters. An alternative explanation for these patterns of recurrence is that cancer cells that are destroyed when the tumor is resected may be reimplanted in another location in the urothelium.Support for this second theory, that tumors are more likely to recur lower than backwards from initial cancer. Upper urinary tract cancer is more likely to recur in the bladder than bladder cancer will replicate in the upper urinary tract. The rest in the following articles: "> bladder cancer4
- and an increased risk of metastatic disease. The degree of differentiation (determining the stage of tumor development has an important influence on the natural history of this disease and on the choice of treatment. An increase in cases of endometrial cancer has been found in connection with prolonged, unopposed exposure to estrogen (increased levels. In contrast, combination therapy (estrogen + progesterone prevents the increased risk of endometrial cancer associated with the lack of resistance to the effects of specific estrogen.Getting a diagnosis is not the best time.However, you should be aware - endometrial cancer is a treatable disease.Watch the symptoms and everything will be fine!In some patients, it can play a role endometrial cancer "activator" a prior history of complex hyperplasia with atypia An increase in endometrial cancer has also been found in association with tamoxifen treatment of breast cancer. According to researchers, this is due to the estrogenic effect of tamoxifen on the endometrium. Because of this increase, patients who patients on tamoxifen therapy should be required to undergo regular pelvic examinations and be alert to any abnormal uterine bleeding. Histopathology The spread of malignant endometrial cancer cells depends in part on the degree of cellular differentiation. Well-differentiated tumors tend to limit their spread to the surface of the uterine mucosa; myometrial expansion occurs less frequently. In patients with poorly differentiated tumors, invasion of the myometrium is much more common. Invasion of the myometrium is often a precursor to lymph node involvement and distant metastases, and often depends on the degree of differentiation. Metastasis occurs in the usual way. Spread to the pelvic and para-aortic nodes is common. When distant metastases occur, it most often occurs in: Lungs. Inguinal and supraclavicular nodes. Liver. Bones. Brain. Vagina. Prognostic factors Another factor that is associated with ectopic and nodular tumor spread is the involvement of the capillary-lymphatic space in the histological examination. Three prognostic groupings clinical stage I were made possible by careful operational staging. Patients with a stage 1 tumor involving only the endometrium and no evidence of intraperitoneal disease (i.e. adnexal extension) are at low risk (">Endometrial Cancer 4
- Apitherapy. / Khismatullina N.3. - Perm: Mobile, 2005. - 296 p.
- Guide to apitherapy (treatment bee venom, honey, propolis, pollen and other bee products) for doctors, medical students and beekeepers / E. A. Ludyansky. - Vologda: [PF "Polygraphist"], 1994. - 462 p.
2 The chemical composition of bee venom according to the book of Khismatullina N.Z.
2.1 Composition of bee venom
Dried bee venom is a multi-component mixture of inorganic and organic substances. Poison Organic Substances:- carbohydrates;
- fats;
- proteins;
- peptides;
- amino acids;
- biogenic amines;
- aromatic and aliphatic compounds, etc.
If the dried poison is 30-45% of the native secretion, then the main part of the dry matter of the poison is represented by proteins and peptides - about 80% minerals, remaining after burning the poison at 500-600°C, make up 2-4% of the dry weight of the poison. The composition of bee venom according to various sources is presented in the table.
| Content in poison, % | Molecular |||
|---|---|---|---|
| 1. Ferromones (volatile substances) | |||
| ethyl acetate Isoamyl acetate n-amyl acetate, etc. (more than 20 volatile components identified in total) | 4÷8 88 |||
| 2. Proteins (enzymes) | |||
| Hyauronidase | 1÷3 41000|||
| Phospholipase A2 | 10÷12 15800 129|||
| Mesophospholipase | 1 22000|||
| Acid phosphatase (phosphomonoesterase) | 1 55000|||
| Alpha glucosidase | 0.6 170000|||
| 3. Peptides (polypeptides) | |||
| Melittin | 40÷50 120000 (tetramer) pH above 9|||
| Melittin F | 0.01|||
| Apamin | 1÷3 2036 18|||
| MSD (peptide 401) | 1÷2 2593 22|||
| Sekapin | 0.5÷2 3000 25|||
| Tertiapine | 1 2500 21|||
| Profireplaces | 1÷3 600|||
| Cardiopep | 1940|||
| Adolapin | 11000|||
| Protease inhibitors | 15800, 8500|||
| Other peptides | 13÷15 less than 600|||
| 4. Biologically active amines | |||
| Histamine | 0.5÷2 111|||
| Dopamine | 0.2÷1 189.7|||
| Norepinephrine | 0.1÷0.5 169|||
| Serotonin | 176|||
| 5. Sugar | |||
| Glucose Fructose |
2
180
|||
| 6.Lipids | |||
| Phospholipids | 52 700|||
| 7. Amino acids | |||
| Free amino acids | 1 700|||
| 8. Mineral composition (from 30-45% dry residue and 2-4% ash) | |||
| Carbon | 43.6|||
| Hydrogen | 7.1|||
| Nitrogen | 13.6|||
| Nitrogen | 2.6|||
| Phosphorus Magnesium Calcium Copper etc. |
33.1
|||
The chemical composition of the poison is the result of the biochemical evolution of compounds with pronounced biological properties. Poison ingredients have a strict specialization, but act synergistically, complementing and reinforcing each other.
Pheromones are biologically active substances secreted by bees into the environment and are a means of intraspecific signaling. They are signaling substances great importance, primarily for the protective behavior of bees. Distinguish between sex pheromones, anxiety, gathering, etc.
Bee venom toxins (peptides, polypeptides) are low-molecular protein compounds, the structure of which is unique, they are species-specific and are intended for toxic action.
Enzymes, (enzymes) contained in bee venom can be considered as agents that damage tissue structures by enzymatic hydrolysis. The main enzymes that make up bee venom and determine a number of its most important effects are:- phospholipase A2;
- hyaluronidase;
- acid phosphatase;
- a-glucosidase;
- lysophospholipase(phospholipase B is an obsolete name, the modern one is phospholipase L);
2.2 Properties of the components of bee venom
| Name (action) |
Properties | ||
|---|---|---|---|
| Melittin (reduces the surface tension of cells and their organelles) | Different degrees of destruction of cell membranes of erythrocytes, basophils, mast cells and lysosome membranes. Cytolysis of basophils and mast cells is accompanied by the release of serotonin, bradykinin and histamine. It enhances the synthesis of various classes of prostaglandins from arachidonic acid. Increases the tone of smooth muscles (mainly the gastrointestinal tract and striated muscles), which is associated with the release of histamine from mast cells and basophils. Reduces the activity of thromboplastin. Stimulates the production of adrenocorticotropic hormone (ACTH). It binds to biologically active cellular substances. Inhibits the immune response by stimulating adrenal hormones. It limits the access of oxygen to tissues, ensures the implementation of radioprotective action in case of radiation injury. Reduces blood pressure. Anti-inflammatory properties. It has a vasodilating effect, protects blood vessels from atherosclerotic changes. Therapeutic doses increase tone. Anticoagulant action. With an increase in the release of glucocorticosteroids by the adrenal cortex, an anti-inflammatory effect. Antibacterial action, inhibits the growth of gram-positive bacteria. antirheumatic properties. High doses cause blockade of the sympathetic ganglia (lowering blood pressure). Higher doses impair non-muscular transmission and induce the opposite. Effect. local inflammatory response. Large doses cause hemolytic anemia and the appearance of hemoglobin in the urine, bronchospasm.|||
| MSD (peptide 401) | It causes degranulation of only mast cells with the release of histamine, serotonin and heparin. The mechanism of histamine release is fundamentally different from the corresponding process in immediate allergic reactions. Stimulates ACTH - the synthetic function of the pituitary gland. Hypotensive effect, increased permeability of the capillary wall. Anti-inflammatory effect No allergic properties were found. Less toxic bee venom ingredient|||
| Adolapin | It has endorphin-like activity, disrupts inter-inaptic transmission. It inhibits cyclooxygenase and lipoxygenase, reduces and slows down the biosynthesis of prostaglandins, directly affects the inflammatory focus. Analgesic and anti-inflammatory effects. Combination of central and peripheral analgesic effect Low allergenicity|||
| secalin | Moderate sedative and hypothermic effect Exceptionally low toxicity|||
| Tertiapine | Inhibits Ca2+-binding protein calmodulin, which regulates the activity of a large number of Ca2+-dependent enzymes Pronounced presynaptic effect on the neuromuscular apparatus|||
| Protease inhibitors | They inhibit the action of proteolytic enzymes of the glandular secretion of bees, blood and tissues of the stung organism, retain the activity of the protein-peptide complex of the poison. They inhibit the activity of trypsin They have anti-inflammatory properties, which are due to the inhibition of some proteolytic enzymes involved in the development of the inflammatory process, delay the movement of certain types of leukocytes Non-toxic|||
| Cardiopep | Affects the course of heart failure Antiarrhythmic action, similar in severity to β-blockers|||
| Phospholipase A2 (the most stable bee venom enzyme) | It affects structural phospholipids (phosphoglycerides), which are part of biological membranes, mitochondria, disrupts cellular functions. It forms biologically active lysolecithin from lecithin, inhibits the activity of tissue dehydrogenases and thrombokinases, inhibits oxidative phosphorylation, has neurotropic properties, disrupts the release of mediators from presynaptic terminals, inhibits the thermal coagulation of egg yolk. Decreased blood clotting under the influence of bee venom (hemolytic activity). Hydrolytic function and transacylase activity Structural poison, antigenic and allergenic substrate, enhances the anticoagulant effect of melittin|||
| Hyaluronidase (glycoprotein), the most active enzyme of mucopol and saccharides | Causes decay hyaluronic acid, which determines the barrier functions of the main intercellular substance. Destroys tissues and promotes the spread of the active principles of the poison in the body due to increased permeability blood vessels. Biological role is reduced to ensuring the penetration of the poison into human tissues with subsequent resorption into the blood Accelerates the resorption of hematomas, adhesions, scars, restores patency fallopian tubes. The property of the enzyme has a positive value in the case of application in the form of skin ointments and liniments Pronounced antigenic and allergenic properties|||
| Dopamine (dopamine) | Specific neurotransmitter for dopamine receptors, stimulates α- and β-adrenergic receptors, increases cardiac output Causes a small change in blood pressure, as well as strength and heart rate without increasing total peripheral resistance. Unlike epinephrine and norepinephrine, it reduces renal blood flow and diuresis|||
| Histamine | Contained in the body in a bound form. Released during inflammatory and allergic reactions, anaphylactic shock. Causes pain in mammals and humans. Hormonal action, mediator functions. Causes expansion of capillaries, increases their permeability and contraction of smooth muscles important role in the development of allergic reactions|||
| Norepinephrine | In the body, it is formed from dopamine and is a precursor of adrenaline. Hormone of the human adrenal medulla Participates in the transmission of nerve impulses in the peripheral nerve endings and synapses of the central nervous system, acts as an α1-adrenergic agonist on the adrenergic receptors of the muscles of blood vessels, causes their narrowing, which leads to an increase in blood pressure|||
Melittin is a peptide component with a characteristic molecular structure that combines hydrophobic and hydrophilic properties. The melittin molecule, due to its surface-active properties, is able to integrate its hydrophobic part into bilayer lipid structures, which contributes to their modification and lysis with the participation of enzymes.
Melittin combines the properties of a substance with pro- and anti-inflammatory effects. Inflammatory action (local reaction) is the result of its direct action on membrane permeability, accumulation of biologically active substances and prostaglandin synthesis. The anti-inflammatory effect (systemic) is provided by ACTH and manifests itself with the introduction of relatively high doses (0.05-2 μg / ml). Toxic doses(10mkg/ml and more) depress the central nervous system, respiratory center and release of adrenaline, increase blood pressure (due to a sharp increase in the concentration of glucocorticosteroids), cause cardiac arrhythmia. Melittin is a weak antigen and allergen, strengthens lysosomal membranes.
Apamin is a low molecular weight bee venom peptide capable of actively modifying the ion channels of the cell membrane, which is accompanied by characteristic changes in the functional state of cells and organs.
MSD (peptide 401), a stronger degranulating and histamine releasing agent. If phospholipase and melittin release biogenic amines from mast cells, damaging the cell membrane and destroying their organelles, then the action of the MSD peptide is based on a different mechanism. It belongs to the group of specific histamine-releasing agents. The main effect is the ability to cause degranulation of mast cells with the release of histamine, serotonin and heparin.
3 The chemical composition of bee venom according to the book of Ludyansky E.A.
3.1 Composition of bee venom. Properties of the components of bee venom
Macromolecular substances consist of phospholipase A and B, hyaluronidase, acid phosphatase and others.
Hyaluronidase - an enzyme that destroys polysaccharides that are part of the connective tissue and cell membranes, is heat-resistant, has allergic properties. Helps to increase the permeability of cells and tissues. Enzyme activity is smoothed out by heparin and blood serum. Smoothes out scar tissue. It breaks down blood and tissue structures, damages mitochondrial membranes and blocks the conduction of the structures of the nervous system. Phospholipase A converts phospholipids into toxic compounds (hemolytic poison), as a result of which it disrupts the processes of tissue respiration, is the most active antigen and allergen. Phospholipase cleaves lecithin and cephalin from phospholipids, which reduces surface tension. Chapolini found that this enzyme (2% of the composition of the poison) consists of 183 amino acid residues, to which sugars adjoin. Exim activation occurs in the presence of sodium chloride and iron.
Lipophospholipase(phospholipase B), in turn, converts toxic lysolecithin into non-toxic compounds, thereby reducing the activity of phospholipase A (St. Shkenderov).
Acid phosphatase- a complex protein such as glycoproteins, heat-resistant, non-toxic, together with alpha-glucosidase provides hypersensitivity to bee venom. Alpha-glucosidase with a molecular weight of 170,000 is sensitive to high temperature, non-toxic.
The composition of bee venom includes 18 of the 20 essential amino acids (alanine, valine, glycocol, leucine, isoleucine, serine, trionine, lysine, arginine, glutamic and aspartic acid, tryptophan, proline, tyrosine, cystine, methionine, phenylalanine, histidine). Even Paracelsus wrote that the effect of bee venom depends on the dose. Small doses of poison, getting into the blood, compensate for the deficiency of amino acids, therefore the best option apitherapy bee stinging. Methionine activates the action of hormones, vitamins, enzymes, lowers cholesterol levels. Histidine has a positive effect on fat metabolism, improves the condition of a patient with atherosclerosis. Peptides belong to low molecular weight compounds. These chemicals play an important role in human body, stimulating various biochemical processes, participating in protein, fat, hormonal, mineral, water and other types of metabolism. They consist of a chain of amino acids produced by APUD cells. According to V.E. Klush (1987), T.V. Dokukina et al. (1989) and others, peptides enhance the activity of the cells of the central nervous system, impulses are more intensely conducted along the pathways and the peripheral nervous system. According to B.N. Orlov (1988), bee venom peptides provide such a versatile effect.
RD Seifulla et al. (1988) showed that peptides are analogues with antagonists of various hypothalamic factors. The leading peptide in bee venom is melittin (55%).(Neiman and Gaberman 1952, Gaberman 1964).
Mellittin consists of 26 amino acids, stimulates the activity of the adrenal-pituitary system, increases the level of cortisol in the blood plasma, immunosuppressant, improves the formation specific antibodies, binds and removes products of inflammatory reactions, small doses of melittin increase the formation of CATP in the liver and stimulate the glands internal secretion which reduces the inflammatory response. Mellitin acts antibacterially, especially on gram-positive microbes. Shipman and Cole from San Francisco in 1967 established the radioprotective action of melittin. 60% of mice, which were previously injected with large doses of poison and then subjected to intense x-ray radiation, remained alive. BN Orlov showed the ganglioblocking effect of this peptide.
Mellitin increases muscle contractility, reduces the surface tension of solutions, mediating reactions through prostaglandins E1 and E2. Mellitin is bound by elements of the reticuloendothelial tissue, so subcutaneous administration of the poison is more toxic than intravenous.
Art. Shkenderov and Ts. Ivanov (1985) found that mellitin weakens the inflammatory action of lysosomes, which somewhat contradicts the generally accepted data on the effect of mellitin on inflammation. They also revealed the stimulating effect of the peptide on bone marrow function. However, it should be noted that the researchers worked with small dilutions of melittin.
In 1937, Feldberg and Calloway established that bee venom releases endogenous histamine. NV Korneva showed that microcirculation and reactivity of skin capillaries change under the influence of histamine. Melittin and phospholipase A affect not only erythrocytes, but also leukocytes.
B.N. Orlov et al. (1983) found that intravenous administration of melittin at a dose of 0.1-0.5 mg/kg reduces the tone of the vessels of the systemic circulation, increases the pulse filling of the vessels of the brain and extremities, and improves the functional state of the myocardium. Small doses of melittin reduced blood viscosity.
Apamia (2% of the composition of bee venom) consists of 18 amino acids with a molecular weight of 2036. The structure was discovered in parallel by Gaberman and R.A. Schipolini in 1967. In 1975, French researchers isolated pure apamin Apamine consists of 18 amino acids, the peptide has an alkaline character. Molecular weight 2036 (St. Shkenderov and Ts. Ivanov, 1985).
Apamin causes increased motor activity. Due to its small size, apamin easily passes through the blood-brain barrier. When introduced into the cerebral ventricles, the activity of the peptide increases by 100-10,000 times. Apamin strongly excites the central and peripheral nervous system, the system of the adrenal cortex - the pituitary gland (increase in the level of adrenaline, cortisol, blood pressure). It is a stimulant of the reticulo-limbic structures. (St. Shkenderov). Apamin protects whey proteins from denaturation, which is much stronger nonsteroidal group. It inhibits serotonin inflammation, histaglobin and serum complex activity, which affects immune processes. The peptide does not cause allergies, provides an anti-inflammatory effect (R. Ovcharov et al. 1983).
Apamin increases the permeability of the blood-brain barrier. Small amounts of the peptide excite the nervous system (W. Sporri and M. Yentsch, 1973), increase motor activity, stimulate the formation of biogenic amines (norepinephrine, serotonin, dopamine). Apamin blocks the inflammatory response from external influence, protects whey proteins from denaturation, acts like non-steroidal anti-inflammatory drugs. This is due to proteases that inhibit the action of trypsin, thrombin, papain. Its action is similar to trazilol. This peptide stimulates cells that produce antibodies (St. Shkenderov) strengthens immunocompetent cells. Apamin inhibits inhibitory processes in the central nervous system, stimulates the mesencephalic and hypothalamic zones of the brain.
G. Weissman (1973) showed that experimental arthritis can be cured only by apamin. R. Ovcharov et al. (1976) found that apamin inhibits the action of serotonin, mucoproteins, haptaglobin, which explains its anti-inflammatory effect.
MSD-peptide (peptide 401) was isolated by Breithaupt and Gaberman in 1968, consists of 22 amino acids with a molecular weight of 2588, has an alkaline character. This peptide releases endogenous histamine from mast cells and is blocked by papaverine. MSD-peptide increases capillary permeability and causes local edema. Like apamin, it irritates the nervous system, has an anti-inflammatory effect (1000 times stronger than hydrocortisone). When administered intravenously, it blocks any experimental inflammation. It is the leading anti-inflammatory peptide in bee venom(Billingham), stabilizes the function of the endothelium of blood vessels, which becomes insensitive to inflammation. The leading mechanism is analgesic, acts like indomethacin. The activity of enzymes that provide inflammatory reactions (cyclooxygenase and lipoxygenase) is inhibited due to the suspension of the release of prostaglandins and the hemotoxic effect. It has antiaggregant action. The therapeutic index of this substance is from 5000 to 7000, while traditional analgesics are 30-50. Opiate number 80, i.e. 80 times stronger than opium. Adolapine is the first exogenous peptide that acts like endorphins on all the analyzing systems of the brain. Protein inhibitors - peptides that affect trypsin and other proteases, formed in a fraction of a second, releasing histamine.
In the laboratory of acad. YuA.Ovchinnikova (1980) isolated a low molecular weight component - tertiapine, which had a presynaptic effect.
In 1971, a peptide was isolated from bee venom, which causes the hibernation of fruit flies and slows down their growth.
In 1976, melittia R and secapin reduce body temperature and calm the central nervous system.
J. Sein (1983) reported on the isolation of the peptide cardiopep with antiarrhythmic action as a beta-blocking adrenolytic.
Inorganic acids are isolated in bee venom: formic, hydrochloric, orthophosphoric and acetylcholine, which provide a burning sensation when stinging. NP Yorish (1978) showed that bee venom acetylcholine helps in the treatment of paralysis. P.Pochinkova et al. (1971) found that bee venom injected with ultrasound inhibits cholinesterase.
The poison contains trace elements: phosphorus, copper, calcium, magnesium, their number is less than in honey.
