Why do people die. Why is it believed that people most often die in the morning

Why did the woman die from alcoholism? How do men die from alcoholism? What are the main causes of such deaths? All these questions are worth knowing the answers to. Alcohol is a highly toxic substance, with its constant use in the body, irreversible changes occur, which adversely affects the human condition as a whole. Gradual poisoning of the body provokes the development of diseases, which can often end in death. Death after drinking alcohol-containing drinks is the result of a gradual toxic effect of alcohol on the body or is associated with its ability to quickly worsen a person's health in chronic diseases and various hidden pathologies.

Leading causes of death from alcohol addiction

Important! Death from alcohol is one of the main causes of sudden death for many apparently healthy men, with no obvious signs of intoxication.

How can you die from alcoholism? Death from alcohol abuse can be due to various reasons. In acute pancreatitis, a person's heart can stop abruptly. The cause of death will also be a blood clot, breaking off and blocking the blood supply while drinking alcohol. Often the cause of death is the use of a lethal dose of alcohol - in this case, a fatal outcome is usually observed the next day.

Diseases

According to statistics from the World Health Organization, about 4% of the world's population die from alcoholism and alcohol-induced diseases of the internal organs every year, now it is approximately 2.5 million people. Such cases include:

• At least 1/5 of alcohol-related deaths are due to various oncological diseases that were provoked by alcohol;
• About 16% of drinking people die from liver disease, most of all die from cirrhosis;
• Approximately 14% of deaths are due to alcohol-induced cardiovascular disease;
• 18% of deaths are associated with other chronic diseases and pathologies that are aggravated due to alcohol poisoning.

The harmful effect of alcohol is noted when taking ethanol in any volume, and regular alcohol intoxication causes diseases of many internal organs, of which the greatest danger is:

• Heart disease - myocardial dystrophy, arrhythmia;
• Nervous system - polyneuropathy, myopathy, hepatic encephalopathy, epileptiform seizures;
• Diseases of the digestive tract - pancreatitis, stomach ulcers, esophageal reflux, liver failure;
• Genitourinary system - acute urinary retention, nephritis, sexual disorders;
• Pneumonia;
• Bone fractures.

Alcohol consumption leads to disorders of purine, carbohydrate metabolism, exacerbates gout, diabetes, and destroys the immune system.

Accidents

According to WHO statistics, about 30% of drunken deaths are due to accidents. Here are just some examples of how people die from alcohol at the same time:

• Hit by various vehicles (cars, trams, trains, and so on);
• Falling from height;
• Hypothermia or overheating;
• Gassing;
• Improper handling of all kinds of household appliances;
• Death in fires;
• Drowning.

When the dose of alcohol was large enough, intoxication came a long time ago, the person no longer feels the change in the conditions around him - temperature, altitude, obstacles. Reflexes are dulled and in this state any ridiculous accident can occur. Alcoholic suicides are slightly less common. Psychoses caused by alcohol abuse can provoke alcoholics to many actions, including suicide.

Medications

Alcohol and drugs often do not go well with each other. Alcoholic beverages (including beer) can make drugs either simply ineffective or change their effect in the most unpredictable way. For fatal poisoning in this case, it is enough to mix alcohol with drugs:

• Sleeping pills - can lead to drowsiness, coma or death;
• Cardiovascular- seriously increases the risk of developing vascular insufficiency;
• Antipyretic- provokes ulcerative lesions of the gastrointestinal tract;
• Diuretic - stimulates the development of pancreatitis and heart failure;
• Analgesics - increases tachycardia;
• Antibiotics - enhances the destructive effect of toxins on the body.

Avoiding alcoholic beverages while undergoing any medication treatment can often be vital. However, every year a certain number of people for some reason forget about this simple rule.

Surrogates

A high price, a beautiful bottle and a label are not always signs of really high-quality alcohol. Even in reputable stores, products based on methyl alcohol (methanol) can be sold, and it is much more dangerous than ordinary ethanol. These are just some of the detrimental features of its effect on the human body:

• Vision suffers greatly from methanol, up to blindness;
• Methyl alcohol causes severe poisoning of the body;
• Methanol leads to intoxication many times faster, and much more damage to health is caused.

Methyl alcohol as a deadly substitute for ethyl alcohol is used in industry; it is prohibited in food production, because it is extremely harmful to the human body. But some alcoholics and such qualities do not stop him from drinking dubious drinks.

Important! Due to the fact that methanol-based alcohol does not visually differ from high-quality alcohol, dangerous drinks are successfully sold, but this is mostly observed on the market in the low price segment.

Weakened immunity, which is inherent in all alcoholics, leads to the fact that they have increased susceptibility to various infections. With alcoholism, a person often dies already extremely ill, while experiencing unimaginable torment. And for which of the above reasons this will happen - with the aggravation of alcoholism, it becomes no longer so important, because in the end a person almost completely loses touch with reality. Therefore, it is necessary to solve problems with alcohol as soon as they appear, so as not to lead to irreversible consequences.

How not to die from alcohol poisoning?

How not to die from alcohol poisoning? Poor health in the morning after excessive drinking of alcohol is an indicator of the beginning of the development of addiction to alcohol. Depending on the symptoms, the subsequent reaction of the body is different, including death. Vomiting blood may well be a sign of a stomach ulcer, and pain in the heart is a sign of a heart attack. With severe pain, you should not try to cope with it with willpower and various folk remedies. Fainting, fever or pressure, worsening headache - all these symptoms should cause a person to immediately seek professional medical help. It is impossible to be inactive with a strong heartbeat, dizziness, confused consciousness, painful repeated vomiting.

These symptoms may not be signs of intoxication, but be an acute reaction of the body to any disease. With renal colic, pain can be relieved only by intravenous administration of painkillers, other methods will not help here, especially if it is bilateral pain, acute urinary retention, repeated vomiting. Warming procedures such as warm baths, warming compresses at the site of pain will not give an effect. With acute urinary retention, all attempts on their own to help the patient will only lead to an increase in his suffering. For first aid, it is necessary to make a catheterization of the bladder. With symptoms of heart failure or hepatic coma, you should immediately call an ambulance.

You should not joke with health in the position of alcohol poisoning, and at the first signs of intoxication, you must begin to act, and not wait until everything “passes by itself”. An alcoholic may not feel the aggravation of his condition, which is why alcohol poisoning with a fatal outcome is so common among people dependent on alcohol. The probability of death from alcoholism can be called the first and one of the main reasons right now to give up drinking and start leading a healthy lifestyle.

The atmosphere on our planet, the distance to the sun, and many other incredible coincidences have led to the fact that life on Earth can exist as we know it. We take all this for granted, and we, hurrying to work or relaxing at a table in a cafe, do not find anything surprising in our existence. But all good things come to an end. One day the Earth will become unfit to support the life we ​​know. It may not happen for millions of years. But astrophysics tells us that a catastrophe can happen at any moment. And scientists have found many reasons why the Earth can become lifeless.

1) The core of the planet will cool down

The earth is surrounded by a magnetic field called the magnetosphere, which protects us from the solar wind.
This field is created by the rotation of the planet, which causes the liquid iron-nickel shell (outer core) to move around the solid metal core (inner core), forming a giant magnetic generator.
The magnetosphere deflects energy particles emitted by the sun, changing their size and shape.
If the core of the planet cools, then we will lose our magnetosphere - as well as protection from the solar wind, because of which it will gradually spread the Earth's atmosphere throughout space.
Mars, which once had water and an atmosphere, suffered just such a fate a few million years ago, and it turned into the dry and lifeless world as we know it now.

2) There will be an expansion of the Sun

The sun, and especially our distance to it, is perhaps the most important factor that made life possible.
However, the Sun is a star. And the stars are dying.
Right now, the Sun is in the middle of its life cycle, constantly turning hydrogen into helium through fusion reactions.
But it can't last forever. In a few billion years, the Sun's core will run out of hydrogen, and it will begin to process helium.
Due to the fact that the processing of helium gives much more energy, the Sun will begin to expand, and possibly pull the Earth towards itself.
We will burn and evaporate.
Either that, or the expansion of the sun opposite, will push the Earth away, it will descend from its orbit and will be doomed to wander through space as a wandering planet - a dead piece of cold stone.

3) Earth will collide with a wanderer planet

There are many planets in space that move freely through it, and do not revolve around a star. Planets are quite often thrown out of their star systems during their formation.
Recent calculations show that the number of wandering planets in the Milky Way outnumbers the number of stars by 100,000 times.
One of these planets could approach Earth and dangerously destabilize its orbit.
Or a rogue planet could collide with Earth. And this has already happened - about 4.5 million years ago, a small planet collided with a larger one, which formed the Earth and the Moon as we know them.

4) Earth will collide with an asteroid

Hollywood is very fond of such scenarios.
Stones from outer space can be very destructive - one of them destroyed the dinosaurs. Although, of course, in order to completely destroy the planet, much more asteroids are needed.
But it can still happen. For example, in the hundreds of millions of years since the formation of the Earth, asteroids have collided with it very often. The impacts were so strong that the oceans boiled for years and the air temperature was over 500 degrees Celsius. Life on Earth then was single-celled, and was presented in the form of especially heat-resistant microbes. Most modern life forms would not have endured such a thing.

5) The Earth can get close to a wandering black hole

Black holes are perhaps the second most popular cause of planetary death in Hollywood. It's easy to see why.
They are mysterious and scary. Even their name sounds creepy.
We don't know much about black holes, but we do know that they are so massive that not even light can escape their event horizon.
Scientists also know that there are black holes freely traveling through space. So it is possible that one of them can visit the solar system.
If light can't escape a black hole, then Earth certainly can't. There are two theories about what happens to the planet after it crosses the point of no return of a sufficiently large black hole. A smaller one will simply stretch (as the astrophysicists say, “spaghettifies”) the planet.
Some physicists say that beyond the event horizon, atoms will stretch until they are completely annihilated.
Others - that we will end up in another part of the universe, or even in another dimension.
But even if the black hole doesn't pull the Earth into it, if it gets close enough it can cause earthquakes and other natural disasters or disrupt the planet's orbit so that we either leave the solar system or fall into the sun.

6) Earth will be destroyed by a burst of gamma radiation

Gamma-ray bursts (or simply gamma-ray bursts) are among the most powerful phenomena in the universe.
Many of them are the result of the collapse of a star during its death. One short burst can contain more energy than the Sun can generate in its entire lifetime.
Such a powerful flow of energy can deprive the Earth of the ozone layer, making us defenseless against dangerous ultraviolet radiation, and start the mechanism of rapid global cooling.
A gamma-ray burst that hit the Earth 440 million years ago could have been the cause of the first mass extinction.
But fortunately, David Thompson, deputy head of the Gamma Ray Observation Project, said that gamma ray bursts are actually not very dangerous.
He said the chance of the Earth being hit by a gamma-ray burst is about the same as "the chance of me meeting a polar bear in my closet."

7) The universe will fall apart in its last "Big Rip"

This is something that can destroy the entire universe, not just the Earth.
The bottom line is this: an unknown force called dark energy is causing the universe to expand faster and faster.
If the expansion continues (which is very possible), in 22 billion years, the interatomic bonds will weaken, and all matter in the universe will gradually dissipate in the form of energy.
But if we assume that the Big Rip does not happen, then what can happen after a global catastrophe that humanity will not survive?
It is possible that some microbes will survive, from which life will then develop again.
But if the destruction is absolute, then, as a last resort, we can hope that somewhere in the universe there is another intelligent life that can give us the last honors.

EXPERIMENTAL ARTICLES

UDC 577.15:576.367

Acadesine causes non-apoptotic death of tumor cells

V. A. Glazunova1*, K. V. Lobanov2, R. S. Shakulov2, A. S. Mironov2, A. A. Shtil1 N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, 115478, Moscow, Kashirskoe ., 24

■State Research Institute of Genetics and Breeding of Industrial Microorganisms, 1, Dorozhny pr-d, Moscow, 117545 *E-mail: [email protected] Received December 27, 2012

ABSTRACT The effect of acadesine (5-aminoimidazole-4-carboxamide-1-0-O-ribofuranoside) on tumor and non-tumor cells of various species and tissue origin was studied. It has been established that acadesine causes non-apoptotic death of tumor cells; the sensitivity of non-tumor cells to the action of this compound is significantly lower. Acadesine causes the death of tumor cells with a drug resistance phenotype due to the expression of the P-glycoprotein transporter and inactivation of the proapoptotic p53 protein. A necessary condition for cell death is the activity of adenosine transporters, while the function of AMP-activated protein kinase is not required. The predominant death of tumor cells under the action of acadesine and the peculiarities of the mechanism of its cytotoxicity determine the prospects of this compound as an antitumor agent. keywords acadesine, cell death, tumor cells.

introduction

Acadesine (5-aminoimidazole-4-carboxamide-1-P-O-ribofuranoside, AICAR) is in clinical trials for the treatment of chronic lymphocytic leukemia. An important property of acadesine is its predominant toxicity to tumor cells with less pronounced damage to non-tumor cells. It was previously shown that acadesine is able to stimulate AMP-activated protein kinase (AMPK), an important regulator of cellular energy balance that controls fatty acid oxidation, glucose metabolism, protein, fatty acid, and cholesterol synthesis. The mechanism of action of acadesine is due to its phosphorylation by adenosine kinase with the formation of ZMP (5-amino-4-imidazolecarboxamidribotide) - an intermediate product of de novo synthesis of purine bases. ZMP, mimicking the metabolic effects of AMP, is able to activate AMPK. The antitumor effect of acadesine is associated with the induction of apoptosis. At the same time, there are data on non-apoptotic cell death and an AMPK-independent mechanism of action of acadesine on tumor cells.

In this work, the effect of acadesine on mammalian cells was studied. It has been shown that acadesine causes the death of tumor cells of various tissues.

of non-origin, including cells resistant to a number of antitumor agents. The mechanisms of cell death differ from apoptosis; their important feature is the need for adenosine transport. Non-tumor cells are less sensitive to the action of acadesine. The selectivity of the cytotoxic effect and the peculiarities of the mechanisms of tumor cell death may be important factors determining the prospects for using acadesine in tumor therapy.

experimental part

The following human cell lines were used in the experiments: HCT116 (colon adenocarcinoma), HCT116p53KO (isogenic subline in which p53 does not function), K562 (promyelocytic leukemia), K562/4 (subline obtained after selection for survival in the presence of doxorubicin; expressed multidrug resistance protein (MDR) P-glycoprotein; Pgp), MCF-7 (breast adenocarcinoma), MCF-7Dox (subline after selection for survival in the presence of doxorubicin; Pgp-mediated MDR phenotype), fibroblast culture PPF-2, blood lymphocytes from healthy donors, as well as mouse cells: P388 (lymphocytic leukemia) and Sp2 / 0 (myeloma). Reagents were purchased from PanEco, Russia (unless otherwise noted). The cells were cultured in

Dulbecco's modified Eagle's medium supplemented with 5% fetal calf serum (Bio-Whittaker, Austria), 2 mM L-glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin at 37°C, 5% CO2 in a humidified atmosphere. Cultures in the logarithmic phase of growth were used in the experiments. Lymphocytes were isolated from the peripheral blood of donors by centrifugation in a ficoll-urographin density gradient (d = 1.077 g/cm3).

Acadesine was obtained in GosNIIGenetika by microbiological method using the original recombinant strain. In addition, the cytotoxicity of acadesine from Sigma was evaluated. The same company purchased dipyridamole, an adenosine receptor inhibitor, 5-iodotubercidin, an adenosine kinase inhibitor that prevents the conversion of acadesine to ZMP, and zVAD-fmk (carbobenzoxyvalylalanyl-aspartyl-fluoromethylketone), a pan-caspase inhibitor. All compounds were dissolved in dimethyl sulfoxide or water (10-20 mm) and stored at -20°C. On the day of the experiment, dilutions of the drug were prepared in the culture medium. To assess the cytotoxicity of acadesine, we used the MTT test, cell staining with propidium iodide and annexin V conjugated with fluorescein isothiocyanate (FITC), determination

cell cycle in flow cytometry and electrophoretic analysis of the integrity of genomic DNA. In some experiments, the reference drug was the alkyl cationic glycerolipid gas-P-(4-[(2-ethoxy-3-octadecyloxy)prop-1-yloxycarbonyl]butyl)-N-methylimidazolium iodide, an apoptosis inducer.

RESULTS AND DISCUSSION

Preferential sensitivity of tumor cells to acadesine

In preliminary experiments, we found that the microbiologically prepared preparation of acadesine and commercial acadesine are identical in terms of physicochemical properties, purity, storage stability, and cytotoxicity (data not shown). For further research, acadesine obtained by the author was used. In table. Figure 1 shows the cytotoxicity of acadesine for transformed and non-transformed cells (cultivated or freshly isolated) of various species and tissue origin.

From the data presented in table. 1, it follows that the most sensitive to the action of acadesine

Table 1. Cytotoxicity of acadesine for mammalian cells

^tags Acadesine, mM

G G.125 G.25 G.5 1.G 2.G

K562 1GG* 1GG 70 46 9 G

P388 1GG 36 30 20 9 G

Sp2/0 1GG 34 29 14 G G

K562/4 1GG 1GG 72 42 8 G

MCF-7 1GG 1GG 82 50 15 2

MCF-7Dox 1GG 1GG 86 48 17 1

HCT116 1GG 1GG 50 36 23G

HCT116p53KO 1GG 1GG 54 34 25G

PPF-2, proliferating 1GG 1GG 1GG 96 96 86

PPF-2, non-proliferating** 1GG 1GG 1GG 1GG 95 92

Donor lymphocytes 1GG 1GG 1GG 98 94 90

Note. The results of the MTT test after 72 hours of cell incubation are presented. "The survival of cells incubated without acadesine was taken as 100%. Each value is the average of five independent experiments, standard deviation< 0%. ""Пролиферацию фибробластов останавливали культивированием клеток до монослоя (контактное торможение деления клеток).

P388 cells (mouse leukemia) and Sp2/0 (mouse myeloma): at an acadesine concentration of 0.125 mM, ~1/3 of the cell population survives. Other transformed cell lines studied also die under the action of submillimolar concentrations of acadesine. It is important that the cytotoxicity of acadesine is practically the same in the case of the K562 leukemic line and its subline with Pgp-mediated MDR (K562/4). The same is true for the MCF-7 breast adenocarcinoma line and the MDR subline (Table 1). A comparison of the cytotoxicity of acadesine against the HCT116 line and the HCT116p53KO subline (resistant to a number of DNA-damaging antitumor compounds) showed that inactivation of the proapoptotic p53 protein does not lead to an increase in cell survival in the presence of acadesine.

The significantly higher survival rate of non-tumor cells in the presence of acadesine is equally important: the death of donor lymphocytes and non-transformed fibroblasts was practically absent even under the action of acadesine at millimolar concentrations for 72 h of continuous exposure (Table 1). Thus, acadesine causes predominant death of transformed cells (suspension and epithelial), including sublines resistant to other antitumor compounds. Non-tumor cells are damaged by acadesine to a much lesser extent. These features make it promising to use acadesine as an antitumor agent. However, for this it is important to establish the mechanisms of acadesine toxicity to tumor cells.

Acadesine causes non-apoptotic cell death

The effect of acadesine on the distribution of ploidy of colon adenocarcinoma HCT116 cells was studied by flow cytometry. 24 h after the addition of acadesine (0.25 mM), the accumulation of cells in the S phase was determined, and after 48 h (Fig. 1), mass cell death was determined (the area to the left of the G1 peak; hypodiploid nuclei).

Accumulation of fragmented DNA may be a sign of apoptotic cell death if DNA cleavage occurs in internucleosome spaces, as seen from the formation of a set of 140-170 bp fragments. with electrophoresis. To test this possibility, DNA integrity was determined in HCT116 cells treated with acadesine. It turned out that acadesine, in contrast to the reference drug, an alkyl cationic glycerolipid, does not lead to the appearance of a “ladder” of DNA fragments characteristic of apoptosis (Fig. 2).

Fluorescence

Rice. Fig. 1. Distribution of HCT116 cells by cycle phases under the action of 0.4 mM acadesine. A - intact cells; B - accumulation in phase S after 24 hours; B - accumulation in the region of sub^1 after 48 hours

An argument in favor of the non-apoptotic mechanism of HCT116 cell death under the action of acadesine is the results of cell staining with annexin U-FITC and propidium iodide (Fig. 3). Annexin Y binds phosphatidylserine on the plasma membrane (translocation of phosphatidylserine from the inner lipid layer of the membrane

Rice. 2. DNA integrity in HCT116 cells.

1 - Intact cells;

2 - acadesine, 0.4 mM, 24 h;

3 - alkyl cationic glycerolipid, 6 μM, 24 h (method control)

Rice. 3. Staining of HCT116 cells with annexin V-FITC and propidium iodide. Pseudo-colors: red - intact cells; violet - acadesine (0.4 mM, 24 h); blue - alkyl cationic glycerolipid (method control; see caption to Fig. 2)

in the external is considered a sign of apoptosis). Propidium iodide is able to penetrate into cells undergoing necrosis (violation of the integrity of the plasma membrane). HCT116 cells treated with acadesine (0.4 mM, 24 h) did not stain with annexin V-FITC; on the contrary, the cells accumulated propidium iodide (Fig. 3), suggesting a necrotic component of the death mechanism. Similar results were obtained when registering necrotic cells using trypan blue (data not shown). Possibly, disruption of the integrity of the plasma membrane is a late event in acadesine-induced cell death. The reference drug, an alkyl cationic glycerolipid, induced an increase in annexin V-positive cells characteristic of apoptosis (Fig. 3).

Since apoptotic cell death suggests an active role for caspases, the effect of the pan-caspase inhibitor zVAD-fmk on acadesine cytotoxicity was studied. HCT116 cells were incubated with 200 μM zVAD-fmk for 30 min, after which acadesine was added to the cultures and incubation continued for 24 h. The presence of zVAD-fmk did not reduce cell death, which confirms the conclusion about the non-apoptotic mechanism of acadesine cytotoxicity.

Interaction with adenosine receptors is necessary for the death of tumor cells under the action of acadesine

Transfer of acadesine from the extracellular environment to cells can be carried out by adenosine transporters. We studied the effect of dipyridamole, an inhibitor of these transporters, on the cytotoxicity of acadesine in the P388 cell line. It turned out that, in the presence of dipyridamole, cells are insensitive even to relatively high (up to 0.8 mM) concentrations of acadesine (Table 2).

To elucidate the role of the acadesine-NMP-AMPK metabolic pathway in the cytotoxicity of acadesine

Table 2 Cytotoxicity of acadesine in combination with dipyridamole or 5-iodotubercidin

Exposure to Acadesine, mM

0 0.08 0.1 0.2 0.4 0.8

Akadesin 100* 79 Z8 ZZ 20 18

Acadesine + dipyridamole, 5 μM 100 100 99 99 100 101

Acadesine + 5-iodotubercidin, 0.05 μM 100 76 Z9 Z1 22 16

* Survival (%) of P388 leukemia cells according to the MTT test after incubation for 72 hours.

(its phosphorylation by adenosine kinase to form ZMP and activate AMPK) cells were incubated with acadesine and the adenosine kinase inhibitor 5-iodotubercidin. The inhibitor did not affect the cytotoxicity of acadesine (Table 2). This suggests that cell death in response to acadesine is not due to ZMP formation and AMPK activation.

Thus, the study of the mechanisms of acadesine cytotoxicity revealed a number of features indicating the nontrivial nature of the pharmacological effects of this compound. Acadesine causes the death of cultured tumor cells with a significantly less pronounced effect on non-tumor cells. Acadesine is toxic to cells with molecular determinants of drug resistance - Pgp expression and non-functioning p53. It is important to emphasize the non-apoptotic nature of tumor cell death under the action of acadesine. These results allow us to regard acadesine as a specific reagent for studying the mechanisms of tumor cell death and as a promising drug candidate.

The question of the intracellular target of acadesine, the interaction with which causes the death of tumor cells, remains open. We have shown that the condition for cell death is the functioning of adenosine transporters, while AMPK activation is not required. It is reasonable to assume that tumors expressing these adenosine transporters and receptors will be most sensitive to acadesine. The role of purine base transport in cell death is not well understood; analysis of the differential expression of adenosine transporters and receptors in tumors of various types is required. It is likely that the increased expression of these molecules will be a new molecular marker of tumor sensitivity to acadesine and a criterion for selecting patients for appropriate therapy.

The work was supported by the Ministry of Education and Science of the Russian Federation (State Contract No. 16.N08.12.1010), and also partially supported by the Dynasty Foundation for Non-Commercial Programs.

BIBLIOGRAPHY

1. Academician. AICA Riboside, ARA 100, Arasine, GP 1 110.

Drugs R D. 2008. V. 9. No. 3. P. 169-175.

2. Jose C., Bellance N., Chatelain E.H., Benard G., Nouette-Gaulain K., Rossignol R. // Mitochondrion. 2012. V. 12. P. 100-109.

3. Jose C., Hebert-Chatelain E., Bellance N., Larendra A., Su M., Nouette-Gaulain K., Rossignol R. // Biochim. Biophys. acta. 2011. V. 1807. P. 707-718.

4. van den Neste E., van den Berghe G., Bontemps F. // Expert Opin. Invest. drugs. 2010. V. 19. No. 4. P. 571-578.

5. Javaux F., Vincent M.F., Wagner D.R., van den Berghe G. // Biochem. J. 1995. V. 305. P. 913-919.

6. Merrill G.F., Kurth E.J., Hardie D.G., Winder W.W. // Endocrinol. Metab. 1997. V. 273. No. 6. P. 1107-1112.

7. Su R.Y., Chao Y., Chen T.Y., Huang D.Y., Lin W.W. // Mol. cancer therapy. 2007. V. 6. No. 5. P. 1562-1571.

8. Theodoropoulou S., Kolovou P.E., Morizane Y., Kayama M., Nicolaou F., Miller J.W., Gragoudas E., Ksander B.R., Vavvas D.G. // FASEB. 2010. V. 24. P. 2620-2630.

9. The Handbook of Metabolomics. Methods in Pharmacology and Toxicology / Eds Whei-Mei Fan T. et al. 2012. V. 17. P. 439-480.

10. Walker J., Jijon H.B., Diaz H., Salehi P., Churchill T., Madsen K.L. // Biochem. J. 2005. V. 385. P. 485-491.

11. Campas C., Santidrian A.F., Domingo A., Gil J. // Leukemia. 2005. V. 19. P. 292-294.

12. Lopez J.M., Santidrian A.F., Campas C., Gil J. // Biochem. J. 2003. V. 70. P. 1027-1032.

13. Guigas B., Sakamoto K., Taleux N., Reyna S.M., Musi N., Viollet B., Hue L. // IUBMB Life. 2009. V. 61. No. 1. P. 18-26.

14. Lobanov K.V., Errais Lopez L., Korolkova N.V., Tyaglov B.V., Glazunov A.V., Shakulov R.S., Mironov A.S. // Acta Naturae. 2011. T. 3. No. 2 (9). pp. 83-93.

15. Lysenkova L.N., Turchin K.F., Korolev A.M., Bykov E.E., Danilenko V.N., Bekker O.B., Trenin A.S., Elizarov S.M., Dezhenkova L.G., Shtil A.A., Preobrazhenskaya M.N. // J. Antibiotics. (Tokyo). 2012. V. 65. No. 8. P. 405-411.

16. V. S. Simonova, A. V. Samusenko, N. A. Filippova, A. N. Tevyashova, L. S. Lyniv, G. I. Kulik, V. F. Chekhun, and A. A. Shtil’ . // Bull. exp. biol. honey. 2005. V. 4. S. 451-455.

17. Markova A.A., Plyavnik N.V., Pletneva M.V., Serebrennikova G.A., Shtil A.A. // Wedge. oncohematol. 2012. V. 5. No. 2.

18. Shchekotikhin A.E., Glazunova V.A., Dezhenkova L.G., Shevtsova E.K., Traven’ V.F., Balzarini J., Huang H.-S., Shtil A.A., Preobrazhenskaya M.N. // EUR. J. Med. Chem. 2011. V. 46. P. 213-218.

19. Gadalla A.E., Pearson T., Currie A.J., Dale N., Hawley S.A., Sheehan M., Hirst W., Michel A.D., Randall A., Hardie D.G., Frenguelli B.G. // J. Neurochem. 2004. V. 88. P. 1272-1282.

Why are people dying? This question once worried the minds of sages, priests, rulers and monks, just as it still worries many doctors, biologists, geneticists, and religious figures. Why people die early (and early is for someone at 20, and for another - at 80 or 90) is a rhetorical question. There are several points of view, everyone is free to adhere to the one that is closer to him.

What is death?

Why are people dying? Everything is simple and cynical - because the world works this way, and nothing else. There are stages of appearance or birth, development and growth, flourishing or maturity, aging or fading and death. These stages are lived by every living being - this is how they teach in biology lessons at school. But besides this, these same stages are also characteristic of any processes and objects of inanimate nature, and even social institutions. It's all about the duration of the transition from one stage of life to another. It can be said with complete certainty that nothing in the physical world exists forever.

Man is no exception. The laws of the universe apply to a reasonable person (Homo Sapiens), who is still significantly different from his predecessors (Neanderthal or Homo sapiens, Homo erectus), and from animals. All people are born, grow and develop, multiply, grow old and eventually die. It turns out that death is the end of life, but not its opposite. If we talk about the opposite of death as a process, then rather, it will be a birth.

So why is a person born and dying? Just because that's the way the world works. Because the old must give way to the new, remaining in the past. A person comes from nowhere and goes nowhere, it turns out that life is just a flash, a moment in eternity.

Death in terms of religious teachings

Why must people die? From the point of view of many religious teachings, death is by no means an end. Absolutely all world religions claim that there is something invisible, eternal and indestructible in a person. It is the mental sheath, the soul, while the body is the physical sheath.

Each person, according to religion, comes into this world to fulfill a certain mission, the work of a lifetime, which each has its own. Someone is destined to atone for the sins of past lives and in this life to beg or get sick, someone receives a reward for their past great (from a moral point of view) accomplishments, for example, helping the hungry and destitute, and may not worry about satisfying their basic needs for this life, to develop spiritually.

Then the soul returns back to the Creator - each religion calls him differently. In Islam, for example, this is Allah, in Hinduism - Ishvara, in Orthodoxy - God the Father, God the Son and the Holy Spirit, but Buddhism rejects the idea of ​​the existence of a single God. In paganism, the ancient world and the Proto-Indo-European religion, the Demiurge was the father of all living things, the creator and creator.

According to the religious concept, death is a transition from one state to another, a birth into a new life. After death, the soul does not die, but continues to exist, only outside the physical (earthly) body. In different teachings, ideas about what happens after death are different, but all religions agree that death is not the end.

Scientific end of life

From the point of view of modern science, death is a mechanism invented by nature, which ensures the change of generations and protects the planet from overpopulation. Death is a stop of all biological processes that take place in the human body during life. But there are a lot of reasons for this stop. People die not only from diseases, but also from accidents or at the hands of other people. If all this can be avoided, then the person dies of old age, that is, a natural death.

What is natural death?

Natural death is the death of a person from old age. What does it mean? With age, cell activity decreases, all processes occurring in the body begin to fade. Immunologists argue that natural death occurs for the reason that autoimmune processes begin to take effect.

Normally, at a young and mature age, the human body is "encoded" to fight against death. This is expressed, for example, in the fact that after drinking an excessive amount of alcohol, a person becomes ill. The body reacts to the poison and tries to remove it as soon as possible, sends signals that such drinks should not be consumed. Not only the human consciousness wants to live, but also the body, so the body normally fights infections, poisons and other negative influences on its own.

Over the years, and sometimes even at a young age due to various diseases, autoimmune processes begin to develop. The immune system ceases to recognize foreign objects, it begins to take "ours" for "aliens". That is, the body begins to self-destruct, attack its own cells. This is how natural death from old age is explained.

Leading causes of death

Why do people die young or just prematurely? This happens, as mentioned above, due to accidents, diseases or at the hands of other people. According to WHO, the majority of people (54%) die due to causes, the list of which can be limited to 10 points. Thus, stroke and coronary heart disease take the most human lives - these are the leading causes of death in the world. In second place is COPD (obstructive pulmonary disease). Next - cancer of the lungs, trachea and bronchi, diabetes, lower respiratory tract infections, diarrheal diseases, tuberculosis, HIV / AIDS and ... road accidents.

Why do people sometimes die in their sleep?

Why do people die in their sleep? Indeed, many people leave this world in a dream: a person falls asleep and never wakes up. This is explained quite simply and logically. A person spends a third of his life in a dream, so that passing away at the time of such a rest is a phenomenon as natural as death in reality. There is a very scientific explanation for this fact. Cardiologists say that during sleep or just in a horizontal position, it increases the flow of venous blood to the heart, so that the muscle needs more oxygen, and the diseased heart does its job poorly and cannot withstand the load. That is why it is recommended that the patient not be laid down during an attack, but left in a half-sitting position.

premature death

Why do people die prematurely? In addition to accidents, various illnesses, and other factors, doctors list sudden and unexplained death syndrome among the causes. Sometimes it happens that a relatively healthy young person dies. From what? In such cases, the cause is explained precisely by this syndrome, the nature of which is not completely clear to modern science. It is known that men are more susceptible to this syndrome than women. Age - from 20 to 49 years. In addition, this happens more often with Mongoloids than with representatives of other races. Most often, sudden death syndrome is not called those cases that can be attributed to alcohol, drug or smoking abuse, excess weight and disease. Moreover, the autopsy, as a rule, does not give any explanation. Witnesses claim that a person who died of SIDS would suddenly begin to sniffle, moan, gasp and die in their sleep. If a person was awakened, within the next hour or day (in 94% of cases), he still died.

Why Russia is dying

Why do people die in Russia? The causes of death in Russia largely correspond to those presented by WHO. Most people die from diseases of the circulatory system, ischemia and strokes, neoplasms, respiratory and digestive diseases.

According to the definition of the World Health Organization, sudden death includes cases of death of practically healthy persons or patients whose condition was considered quite satisfactory. It is obvious that the majority of people have certain deviations in the state of health, which do not have a significant impact on everyday life and do not reduce its quality. In other words, pathological changes on the part of organs and systems, if they exist in such people, are stubbornly compensated. Such representatives of humanity are classified as "practically healthy". It is in this group that the most common phenomenon is encountered, which scientists called sudden death. In this phrase, it is surprising not the second word (all people die sooner or later), but the first. Sudden is an unexpected death that occurs without any warning, in the midst of complete well-being. This catastrophe is not amenable to any prediction so far. She does not have harbingers and signs that could alert doctors. Studying numerous, more and more frequent cases of sudden death, experts came to the conclusion that this event always has vascular causes, which makes it possible to classify it as a vascular accident.

A prominent businessman with a typical Georgian surname, one of the heirs of the wealth of the collapsed Soviet Union, had already endured all the hardships of the division of property and lived a healthy and proper life in London. He probably had enough money for a full medical examination, and personal doctors would not miss even a suspicious heart murmur. Death came suddenly and completely unexpectedly. He was in his early 50s. An autopsy found no cause of death.

There are no exact statistics on sudden death, since there is no generally accepted definition of this concept. However, it is estimated that every 60-75 seconds in the US, 1 person dies from sudden cardiac arrest. The problem of sudden cardiac death, which has attracted the attention of cardiologists for many decades, has risen sharply again in recent years, when large population studies conducted by the World Health Organization have demonstrated an increasing frequency of sudden death among the adult, and not only the adult population. It turned out that cases of sudden death are not so rare, and this problem requires close study.

During post-mortem examination (autopsy) of the dead, as a rule, it is not possible to detect signs of damage to the heart or blood vessels that could explain the sudden circulatory arrest. Another feature of sudden death is that, if timely assistance is provided, such patients can be revived, and in practice this happens quite often. Usually, resuscitation (resuscitation) is performed through artificial respiration and closed heart massage. Sometimes, to restore blood circulation, it is enough to hit the chest with a fist - in the region of the heart. If a catastrophe occurs in a medical institution or in the presence of ambulance service doctors, then a high-voltage electric current discharge is used to restore blood circulation - defibrillation.

Sudden death, which is based on pathological changes in the heart, is commonly called sudden cardiac death. Cardiac causes account for the bulk of sudden deaths. The basis for such a judgment is the statistical data indicating that pathological changes in the heart are noted, even if the victim has never complained about his state of health. Atherosclerosis of the coronary arteries can be found in more than half of the people who died as a result of sudden circulatory arrest. Scars on the heart muscle, which indicate a previous heart attack, and an increase in the mass of the heart are found in 40-70% of cases. Such obvious causes as fresh blood clots in the coronary arteries in sudden cardiac death can be found extremely rarely. With a careful study (it is clear that all cases of sudden death serve as the basis for a careful study), it is almost always possible to detect some kind of pathology. However, that doesn't make sudden death any less mysterious. After all, all changes in the heart and blood vessels exist and form for a long time, and death comes suddenly and completely unexpectedly. The latest methods for studying the cardiovascular system (ultrasound scanning, spiral computed tomography) detect the smallest changes in blood vessels and the heart without any opening of the body. And these data show that certain changes can be found in almost all people, who, fortunately, for the most part live safely into old age.

Since no damage to the cardiovascular system can be detected in cases of sudden death, it remains to be assumed that this catastrophe is associated with a dysfunction, and not with a change in the structure of the heart. This assumption was confirmed with the development and introduction into clinical practice of methods for long-term monitoring of the work of the heart (ECG registration for hours and days). It became clear that sudden death most often (65-80%) is directly related to ventricular fibrillation.

Ventricular fibrillation - very frequent (up to 200 or more in 1 minute), erratic contraction of the ventricles of the heart - flutter. Flutter is not accompanied by effective contractions of the heart, so the latter ceases to perform its main, pumping, function. Blood circulation stops, death occurs. Sudden ventricular tachycardia - an increase in ventricular contractions of the heart to 120-150 beats per minute - dramatically increases the load on the myocardium, quickly depletes its reserves, which leads to circulatory arrest.

Here is what the breakdown of a normal rhythm into a state of ventricular flutter looks like on an electrocardiogram:

As a rule, trembling is followed by a complete cardiac arrest due to the depletion of its energy reserves. But fibrillation cannot be considered the cause of sudden death; rather, it is its mechanism.
It is generally accepted that the most important causative factor in sudden cardiac death is acute myocardial ischemia - a violation of the blood supply to the heart muscle due to spasm or blockage of the coronary arteries. That's right: it is commonly believed, because nothing else comes to mind when experts consider the heart as an organ that consumes blood like an engine that consumes fuel. Indeed, oxygen starvation leads to disturbances in the ability of the heart muscle to contract, increases sensitivity to irritation, which contributes to rhythm disturbances. It has been established that disturbances in the nervous regulation of the work of the heart (imbalance of autonomic tone) can lead to rhythm disruption. It is precisely known that stress contributes to the occurrence of arrhythmias - hormones change the excitability of the heart muscle. It is also known that the lack of potassium and magnesium has a significant impact on the work of the heart and under certain conditions can lead to its stop. There is no doubt that some medicinal substances, toxic factors (for example, alcohol) can lead to damage to the conduction system of the heart or contribute to impaired myocardial contractility. But, with all the clarity of individual mechanisms of violations of the normal functioning of the heart, many cases of sudden death do not receive a satisfactory explanation. Let us recall at least the regularly repeated cases of death of young athletes.

24-year-old French tennis player Mathieu Montcourt, who on the night of Tuesday July 7, 2008 was found dead in his apartment in the suburbs of Paris, died of cardiac arrest.

As a rule, in this group of well-trained, well-developed physically young people, medical supervision is fairly well established. It is unlikely that among professional athletes who have managed to achieve extraordinary success with their physical efforts, there are people suffering from serious diseases of the heart and blood vessels. It is even more difficult to imagine coronary insufficiency in people who regularly endure huge physical exertion. The relatively high statistics of sudden death among athletes can only be explained by obvious overloads or the use of pharmacological agents that increase physical endurance (doping). According to statistics, in young people, sudden death is most often associated with sports (about 20%) or occurs during sleep (30%). The high frequency of cardiac arrest during sleep convincingly refutes the coronary nature of sudden death. If not in all cases, then in a significant part of them. During sleep, physiological rhythm changes occur, which are characterized by bradycardia - a decrease in heart rate to 55-60 beats per minute. In trained athletes, this frequency is even lower.

V. Turchinsky, an outstanding athlete and simply a handsome person who promotes and leads a healthy lifestyle, suddenly falls and dies before reaching the age of 50.

Several newspaper lines are honored with suddenly deceased famous athletes, politicians, artists. But many such disasters happen to ordinary people who are not written about in the newspapers.
- He after all was perfectly healthy! - the shocked relatives and acquaintances are amazed for several days. But the inexorable persuasiveness of what happened soon makes one believe the facts: if he died, then he was sick.

Sudden death significantly more often overtakes another category of patients - persons suffering from mental illness. Researchers attribute this phenomenon to the use of psychotropic drugs, most of which affect the conduction system of the heart.

It is known that alcoholics are prone to sudden death. Everything is more or less clear here: ethyl alcohol destroys the myocardium and the conduction system of the heart. One day, deprived of energy and rhythmic control, the heart simply stops after another drinking bout.

It would seem that now the circle of victims has been determined: the risk group is made up of people with heart diseases that do not manifest themselves until a certain time, athletes for whom physical overload is part of their lifestyle, and numerous representatives of the population who abuse alcohol or drugs.

But in this series, deaths of young children stand apart - sudden infant mortality syndrome. British scientists, who studied 325 such cases, came to the conclusion that most often the danger occurs at the 13th week of life. Almost always, the death of an infant occurs in a dream; more often this happens in the cold season and when the baby is lying on his stomach. Some researchers link the sudden death of infants with smells (perfumes, tobacco smoke).

With all the clarity of the relationship between risk factors and tragic cases of sudden death, the majority of people who died suddenly have never had these factors. Sudden death made a habit of visiting quite healthy people.