Question: When was James Eugene Kerry born?

Jim Carrey

In the same year, a survey was conducted among filmmakers on the topic: “Who is the most valuable comedian?” According to the survey, Jim ranked fourth [69].


Question: When was James Eugene Kerry born?

Jim Carrey

In the list of the most influential celebrities for 2009, Kerry is ranked 56th with earnings of $30 million [70].


Question: When was James Eugene Kerry born?

Jim Carrey

According to the results of the rating, Jim held:


Question: When was James Eugene Kerry born?

Jim Carrey

50th place — in terms of earnings;


Question: When was James Eugene Kerry born?

Jim Carrey

40th place — in terms of mentioning on the Internet;


Question: When was James Eugene Kerry born?

Jim Carrey

50th place — by press coverage;


Question: When was James Eugene Kerry born?

Jim Carrey

51st place in terms of mentions on television.


Question: When was James Eugene Kerry born?

Jim Carrey

In subsequent years, Kerry was not included in the lists.


Question: When was James Eugene Kerry born?

Jim Carrey

In an interview, Jim admitted that he really wants to win an Oscar:


Question: When was James Eugene Kerry born?

Jim Carrey

... I will be dissatisfied until I find myself in a stream of light in front of the camera with a thank-you speech.


Question: When was James Eugene Kerry born?

Jim Carrey

You know what I'm talking about... I don't know how I'm going to win an Oscar or what I'm going to have to do to get it.


Question: When was James Eugene Kerry born?

Jim Carrey

Yes, I'm so vain!


Question: When was James Eugene Kerry born?

Jim Carrey


Question: When was James Eugene Kerry born?

Jim Carrey


Question: When was James Eugene Kerry born?

Jim Carrey

Giveaways


Question: When was James Eugene Kerry born?

Jim Carrey

As a child, Jim often made fun of his mother, who was afraid of mice in panic: he “lost” the white mouse in the house, which terrified Kathleen [72].


Question: When was James Eugene Kerry born?

Jim Carrey

In 1982, on his twentieth birthday, Jim went on stage naked, hiding behind only a sock [73] [74].


Question: When was James Eugene Kerry born?

Jim Carrey

In 2006, while traveling to the Middle East, trying to get rid of annoying reporters, Jim, who was staying in Taba, moved to Jerusalem.


Question: When was James Eugene Kerry born?

Jim Carrey

In the city of Taba, there lived a man who looked like Kerry himself.


Question: When was James Eugene Kerry born?

Jim Carrey

Hearing about Garfonel (that was the name of the double), he invited him to become “Jim Carrey” for a while — live in a luxury hotel, eat expensive dishes and avoid reporters.


Question: When was James Eugene Kerry born?

Jim Carrey

Nobody noticed the substitution, and this prank was a success [75].


Question: When was James Eugene Kerry born?

Jim Carrey

In 2008, paparazzi filmed Kerry and his ex-girlfriend Jenny McCarthy walking on the beach wearing her swimsuit [76].


Question: When was James Eugene Kerry born?

Jim Carrey

In 2011, Jim appeared in public with a punk hairstyle [77] and also played billiards dressed as a scuba diver at the Gramercy Park Hotel.


Question: When was James Eugene Kerry born?

Jim Carrey


Question: When was James Eugene Kerry born?

Jim Carrey

Nominations and awards


Question: When was James Eugene Kerry born?

Jim Carrey

YearNominationsResult1994MTV Movie AwardsBest Comedy Role (Ace Ventura: Pet Wanted) Nomination1995Golden GlobeListening Actor (Comedy or Musical) (Mask) Nomination1995MTV Movie AwardsBest Comedy Role (Dumb and Dumber) /Best Kiss (Dumb and Dumber) Winner1995MTV Movie AwardsBest Screen Couple (Dumb and Dumber) /Best Dance (Mask) /Best Comedy Actor (Mask) Nomination1996MTV Movie AwardsBest Comedy Role (Ace Ventura: When Nature Calls) /Best Actor (Ace Ventura 2: When Nature Calls) Winner1996MTV Movie AwardsBest Villain ( Batman: Forever) /Best Kiss (Ace Ventura: When Nature Calls) 1997MTV Movie AwardsBest Comedy Role (The Cable Guy) /Best Villain (The Cable Guy) Winner1997MTV Movie AwardsBest Fight ( The Cable Guy) Nomination1998Golden GlobeBest Actor (Comedy or Musical) (Liar, Liar) Nomination1998MTV Movie AwardsBest Comedy Role (Liar, Liar) Winner1999Golden GlobeBest Male role (drama) (The Truman Show) Winner1999MTV Movie AwardsBest Actor (The Truman Show) Winner2000Golden Globes Best Actor (Comedy or Musical) (Man on the Moon) Winner2000mTV Movie AwardsBest Actor (Man on the Moon) Nomination2000Screen Actors GuildBest Actor (Man on the Moon) Nomination2001Golden GlobeListening Actor (Comedy or Musical) (The Grinch Stole Christmas”) Nomination2001MTV Movie AwardsBest Villain (The Grinch Stole Christmas) Winner2001MTV Movie AwardsBest Comedian (Me, Me Again and Irene) Nomination2001People's ChoiceFavorite Comedy ActorWinner2004MTV Movie AwardsBest Comedy Role (Bruce Almighty) /Best Kiss (Bruce Almighty) 2004SDFCSA Best ActorBest Actor (Eternal Sunshine of the Spotless Mind) Winner2005Golden GlobeListening Actor (Comedy or Musical) (Eternal Sunshine of the Spotless Mind) Nomination2005People's ChoiceFavorite Funny Star2005MTV Movie AwardsBest Villain (Lemony Snicket: 33 Misfortunes) Nomination2005 BAFTA Best Actor Best Actor (Eternal Sunshine of the Spotless Mind) Nomination2006MTV Movie AwardSMTV Generation Award Nominations2008Golden Raspberry Worst Actor (Number 23) Nomination2009People's ChoiceFavorite Funny StarNomination2009Children's Choice Favorite Actor (Always Say Yes) /Favorite Animated Film Voice (Horton) Nomination2009MTV Movie AwardsBest Comedy Role (Always Say Yes) Winner2010People's ChoiceFavorite Comedy StarWinner2010Children's Choice Favorite Animated Film Voice (” A Christmas Story”) Winner2011Spike Guys' Choice AwardsFunniest Winner


Question: When was James Eugene Kerry born?

Jim Carrey

In total, he has 22 nominations and 10 MTV Movie Awards (excluding the MTV Generation Award), holding the record for the number of nominations and awards [2].


Question: When was James Eugene Kerry born?

Jim Carrey

Filmography


Question: When was James Eugene Kerry born?

Jim Carrey

Facts


Question: When was James Eugene Kerry born?

Jim Carrey

Jim's height is 187 cm [79].


Question: When was James Eugene Kerry born?

Jim Carrey

His favorite color is green [2].


Question: When was James Eugene Kerry born?

Jim Carrey

Jim is a vegetarian [80].


Question: When was James Eugene Kerry born?

Jim Carrey

He is engaged in Brazilian jiu-jitsu [81].


Question: When was James Eugene Kerry born?

Jim Carrey

One of Kerry's favorite activities is riding a motorcycle [1] [9].


Question: When was James Eugene Kerry born?

Jim Carrey

Despite the fact that Jim insisted on Cannibal Corpse participating in the filming of Ace Ventura and even personally chose the film's song “Hammer Smashed Face” [82], he is not a fan” cannibals” and doesn't like death metal.


Question: When was James Eugene Kerry born?

Jim Carrey

The actor's son-in-law, rock musician Alex Santana, put an end to many years of rumors.


Question: When was James Eugene Kerry born?

Jim Carrey

According to Santana, “this was the first thing he asked Kerry about when he met” [83].


Question: When was James Eugene Kerry born?

Jim Carrey

In 1997, Kerry was named one of the most beautiful people in the world by People magazine [2].


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry has ADHD, which has survived to this day.


Question: When was James Eugene Kerry born?

Jim Carrey


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry wrote himself a fake check for $10 million at the beginning of his career [85].


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry has a star on the Canadian Walk of Fame in Toronto.


Question: When was James Eugene Kerry born?

Jim Carrey

Madame Tussauds Wax Museum has a wax figure of him [86].


Question: When was James Eugene Kerry born?

Jim Carrey

The figure points to a microphone that changes the voice like Jim does in the movies [87].


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry's official website jimcarrey.com won the Webby Awards for Best Official Page in 2010 [88], and in 2011 Kerry won the award for his role as Ronald Reagan in the site connection Funnyordie.com [89].


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry has been to Moscow twice [9].


Question: When was James Eugene Kerry born?

Jim Carrey

Kerry donates money to charity, mainly for the treatment of seriously ill children.


Question: When was James Eugene Kerry born?

Jim Carrey

In 2007, Kerry directed a video message in which he spoke in defense of Nobel Peace Prize winner Aung San Suu Kyi and other victims of repression in Burma. [90]


Question: When was James Eugene Kerry born?

Jim Carrey

In 2017, a short film by David Bushell was released, in which the actor talks about his passion for fine arts (painting and sculpture).


Question: When was James Eugene Kerry born?

Jim Carrey


Question: When was James Eugene Kerry born?

Jim Carrey

Notes


Question: When was James Eugene Kerry born?

Jim Carrey

References


Question: When was James Eugene Kerry born?

Jim Carrey

(Adobe Flash, 9 MB)


Question: When was James Eugene Kerry born?

Jim Carrey

on YouTube


Question: When was James Eugene Kerry born?

Jim Carrey

Data on reviews of film critics and fees are taken from the Kinopoisk website


Question: When was James Eugene Kerry born?

Jim Carrey

Category: Golden Globe Award winners


Question: When was James Eugene Kerry born?

Jim Carrey

Category:Canadian immigrants to the United States


Question: When was James Eugene Kerry born?

Jim Carrey

Category:stand-up comedians from Canada


Question: When was James Eugene Kerry born?

Jim Carrey

Category:American comedians


Question: When was James Eugene Kerry born?

Jim Carrey

Category:American voice actors


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis (Greek: athra, gruel +, hardening [1])


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

- chronic disease of the arteries of the elastic and muscular-elastic type, which occurs as a result of impaired lipid and protein metabolism and is accompanied by the deposition of cholesterol and some fractions lipoproteins in the lumen of blood vessels.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Deposits form in the form of atheromatous plaques.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The subsequent growth of connective tissue in them (sclerosis), and calcification of the vessel wall lead to deformation and narrowing of the lumen up to obturation (blockage of the vessel).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is important to distinguish atherosclerosis from Menkeberg arteriosclerosis, another form of sclerotic lesions of the arteries, which is characterized by the deposition of calcium salts in the middle membrane of the arteries, the diffusion of the lesion ( absence of plaques), the development of aneurysms (and not blockages) of blood vessels.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis of the heart vessels leads to the development of coronary heart disease.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

epidemiology


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

mini|video with subtitles


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The most studied mortality rates from cardiovascular diseases as a manifestation of generalized atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In the Russian Federation, in 2000, the standardized mortality rate from diseases of the circulatory system was 800.9 per 100,000 population.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

For comparison, in France, this figure is 182.8 (the lowest in Europe), in Japan it is 187.4.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It has been proven that reducing the risk of cardiovascular diseases in these countries is not so much due to the quality of medical care, but to lifestyle and nutritional characteristics.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Etiology


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

At the moment, there is no single theory of the occurrence of this disease


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The following options are put forward, as well as their combinations:


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

theory of lipoprotein infiltration — primary accumulation of lipoproteins in the vascular wall,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

theory of endothelial dysfunction — primarily a violation of the protective properties of the endothelium and its mediators,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

autoimmune - primarily a violation of the function of macrophages and leukocytes, their infiltration of the vascular wall,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

monoclonal - the primary occurrence of a pathological clone of smooth muscle cells,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

viral - primary viral damage to the endothelium (herpes, cytomegalovirus, etc. ),


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

peroxide is primarily a violation of the antioxidant system,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

genetic - a hereditary defect of the vascular wall is primary,


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

chlamydia - the primary lesion of the vascular wall by chlamydia, mainly Chlamydia pneumoniae.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

hormonal - an age-related increase in the level of gonadotropic and adrenocorticotropic hormones leads to an increased synthesis of building material for cholesterol hormones.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Risk factors


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

smoking (the most dangerous factor)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

hyperlipoproteinemia (total cholesterol > 5 mmol/L, LDL > 3 mmol/L, LP (a) > 50 mg/dL)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

arterial hypertension (systolic BP > 140 mmHg diastolic BP > 90 mmHg)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

diabetes


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

obesity


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

sedentary lifestyle (physical inactivity)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

emotional overexertion


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

malnutrition


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

hereditary predisposition


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

postmenopause


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

hyperfibrinogenemia


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

homocysteinuria and homocysteinemia


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

hypothyroidism [2]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

According to the European Guidelines on Cardiovascular Disease Prevention, the assessment of leading risk factors is based on a scale SCORE (Systemic Coronary Risk Evaluation).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Currently, on the website of the European Cardiological Society (ESC), the Russified Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) for calculating the risk of developing cardiac vascular diseases.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A more general assessment can be made according to the table below.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Pathogenesis


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The pathogenesis of atherosclerosis is called atherogenesis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It takes place in several stages.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The development of atherosclerotic lesions is a combination of the processes of entering and leaving the intima of lipoproteins and leukocytes, proliferation and death of cells, the formation and restructuring of intercellular substances, as well as vascular growths and calcifications.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

These processes are controlled by a variety of signals, often in different directions.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

More and more data are accumulating on the complex pathogenetic relationship between changes in the function of cells of the vascular wall and leukocytes that have migrated into it and risk factors for atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Accumulation and modification of lipoproteins


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Normally, the intima of the arteries is formed by a unicellular endothelial layer, under which there are smooth muscle cells immersed in the intercellular substance.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The first manifestations of the disease are the so-called lipid spots.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Their appearance is associated with local deposition of lipoproteins in the intima.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Not all lipoproteins have atherogenic properties, but only low (LDL) and very low density (VLDL).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Initially, they accumulate in the intima mainly due to binding to the components of the intercellular substance - proteoglycans.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In places where lipid spots are formed, the predominance of heparan sulfates over two other glycosaminoglycans, keratan sulfates and chondroitin sulfates, plays an important role.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In intima, lipoproteins, especially those associated with proteoglycans, can enter into chemical reactions.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The main role is played by two: oxidation and non-enzymatic glycosylation.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Intima, unlike plasma, contains few antioxidants.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A mixture of oxidized LDL is formed, and both lipids and protein components are oxidized.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

During the oxidation of lipids, hydroperoxides, lysophospholipids, oxysterins and aldehydes are formed (during peroxidation of fatty acids).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Oxidation of apoproteins leads to the rupture of peptide bonds and the connection of the side chains of amino acids (usually the β-amino group of lysine) with the breakdown products of fatty acids (4-hydroxynonenal and malonic) dialdehyde).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Persistent hyperglycemia in diabetes mellitus contributes to non-enzymatic glycosylation of apoproteins and intima's own proteins, which also disrupts their functions and accelerates atherogenesis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Leukocyte migration and xanthoma (foam) cell formation


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The migration of leukocytes, mainly monocytes and lymphocytes, is the second stage in the development of the lipid spot.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Their migration to the intima is provided by receptors located on the endothelium - adhesion molecules.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Particular attention should be paid to the molecules VCAM-1 and ICAM-1 (from the immunoglobulin superfamily) and P-selectins.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Synthesis of adhesion molecules can increase cytokines.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, interleukin-1 (IL-1) and tumor necrosis factor (TNFα) cause or enhance endothelial cell synthesis VCAM-1 and ICAM-1.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In turn, the release of cytokines by cells of the vascular wall is stimulated by modified lipoproteins.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A vicious circle is forming.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The nature of the blood flow also plays a role.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In most parts of the unchanged artery, blood flows laminar, and the resulting forces reduce the expression (manifestation) of adhesion molecules on the surface of endothelial cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Laminar blood flow also contributes to the formation of nitric oxide NO in the endothelium.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition to the vasodilator effect, at a low concentration supported by the endothelium, NO has anti-inflammatory activity, reducing, for example, the synthesis of VCAM-1.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

But in places of branching, laminar current is often disturbed, and this is where atherosclerotic plaques usually appear.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

After adhesion, leukocytes pass through the endothelium and enter the intima.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Lipoproteins can directly increase migration: oxidized LDL contributes to leukocyte chemotaxis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Monocytes are involved in the further formation of the lipid spot.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In intima, monocytes become macrophages, from which lipid-filled xanthoma (foamy) cells appear due to lipoprotein endocytosis receptors mediated by lipoprotein receptors.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Previously, it was assumed that well-known LDL receptors participate in endocytosis, but if these receptors are defective, both in experimental animals and in patients (for example, with familial hypercholesterolemia ) there are still numerous xanthomas and atherosclerotic plaques filled with xanthoma cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition, exogenous cholesterol inhibits the synthesis of these receptors, and there are few of them in hypercholesterolemia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The role of scavenger receptors for macrophages (binding mainly modified lipoproteins) and other receptors for oxidized LDL and small atherogenic VLDL is now assumed.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Some xanthoma cells that have absorbed lipoproteins from the intercellular substance leave the artery wall, thereby preventing the accumulation of lipids in it.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

If the intake of lipoproteins into the intima prevails over their excretion with macrophages (or other pathways), lipids accumulate and as a result, an atherosclerotic plaque is formed.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In the growing plaque, some xanthoma cells undergo apoptosis or necrosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

As a result, a cavity filled with rich lipid masses forms in the center of the plaque, which is typical for the late stages of atherogenesis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Pro- and anti-atherogenic factors


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

When absorbed by modified lipoproteins, macrophages release cytokines and growth factors that promote plaque development.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Some cytokines and growth factors stimulate the division of smooth muscle cells and the synthesis of intercellular substance that accumulates in the plaque.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Other cytokines, especially interferon-γ from activated T-lymphocytes, inhibit smooth muscle cell division and collagen synthesis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Factors such as IL-1 and TNFα cause the production of platelet growth factor and fibroblast growth factor in the intima, which play a role in the further fate of the plaque.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, there is a complex interaction of factors that both accelerate and inhibit atherogenesis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The role of non-protein mediators is also great.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Activated macrophages and vascular wall cells (endothelial and smooth muscle) produce free oxygen radicals that stimulate the proliferation of smooth muscle cells, enhance synthesis cytokines, and also bind NO.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

On the other hand, activated macrophages are capable of synthesizing induced NO synthase.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

This highly active enzyme produces NO in high, potentially toxic concentrations — in contrast to the low concentration of NO created by the constitutive form of the enzyme, endothelial NO synthase .


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition to macrophages, high-density lipoproteins (HDL) are involved in the removal of cholesterol from the affected intima, which ensure the so-called reverse transport of cholesterol.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A clear inverse relationship between the concentration of HDL cholesterol and the risk of coronary heart disease has been proven.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Women of childbearing age have a higher concentration of HDL cholesterol than male peers, and this is largely due to this, women are less likely to suffer from atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The experiment showed that HDL is able to remove cholesterol from xanthoma cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Smooth muscle cell involvement


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

An atherosclerotic plaque develops from a lipid spot, but not all spots become plaques.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

If lipid spots are characterized by the accumulation of xanthoma cells, then plaques are characterized by fibrosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The intercellular substance in the plaque is synthesized mainly by smooth muscle cells, the migration and proliferation of which is probably a critical moment in the formation of a fibrous plaque at the site of accumulation of xanthomas cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Migration to the lipid spot of smooth muscle cells, their proliferation and synthesis of intercellular substance are caused by cytokines and growth factors released under the influence of modified lipoproteins and other substances macrophages and vascular wall cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, platelet growth factor released by activated endothelial cells stimulates the migration of smooth muscle cells from media to intima.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Locally formed growth factors cause the division of both the intima's own smooth muscle cells and cells that came from the media.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

One of the powerful stimulants of collagen synthesis by these cells is the transforming growth factor p. In addition to paracrine (factors come from neighboring cells), autocrine (the factor is produced by the cell itself) regulation of smooth muscle cells also occurs.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

As a result of the changes that occur with them, the transition of the lipid spot into an atherosclerotic plaque containing many smooth muscle cells and intercellular substance is accelerated.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Like macrophages, these cells can enter into apoptosis: it is caused by cytokines that contribute to the development of atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Complicated plaque development


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition to the usual risk factors and the cytokines described above, changes in the blood coagulation system play an important role in the late stages of atherosclerosis development.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Lipid spots do not require damage or desquamation of the endothelium.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

But in the future, microscopic ruptures may occur in it.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Platelet adhesion occurs on the exposed basement membrane, and small platelet thrombi form in these places.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Activated platelets release a number of substances that accelerate fibrosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition to platelet growth factor and transforming growth factor p, low molecular weight mediators, such as serotonin, act on smooth muscle cells.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Usually, these blood clots dissolve without causing any symptoms, and the integrity of the endothelium is restored.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

As the plaque develops, vasa vasorum (vessels of blood vessels) begins to grow abundantly into it.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

New vessels affect the fate of the plaque in several ways.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They create a vast surface for leukocytes to migrate both into and out of the plaque.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition, new vessels are the source of plaque hemorrhage: as with diabetic retinopathy, they are brittle and prone to rupture.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The resulting hemorrhage leads to thrombosis, thrombin appears.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It not only participates in hemostasis, but also affects intimal cells: it stimulates the division of smooth muscle cells and their production of cytokines, and also causes endothelium to synthesize growth factors.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

As a result of hemorrhages, plaques often contain fibrin and hemosiderin.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerotic plaques are often calcified.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Plaques contain calcium-binding proteins osteocalcin and osteopontin and some other proteins characteristic of bone tissue (in particular, proteins that regulate bone morphogenesis).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Clinic


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Clinical manifestations often do not correspond to morphology.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

At a postmortem autopsy, extensive and pronounced atherosclerotic vascular lesions may be a godsend.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Conversely, the clinic of organ ischemia may appear with moderate obliteration of the lumen of the vessel.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A predominant lesion of certain arterial basins is characteristic.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The clinical picture of the disease also depends on this.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The defeat of the coronary arteries gradually leads to coronary insufficiency, manifested by coronary heart disease.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis of the cerebral arteries causes either transient cerebral ischemia or strokes.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Damage to the arteries of the extremities is the cause of intermittent claudication and dry gangrene.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis of the mesenteric arteries leads to ischemia and intestinal infarction (mesenteric thrombosis).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is also possible to damage the renal arteries with the formation of the Goldblatt kidney.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Even within individual arterial basins, focal lesions are characteristic - involving typical areas and the safety of neighboring ones.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, in the vessels of the heart, occlusion most often occurs in the proximal part of the anterior interventricular branch of the left coronary artery.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Another typical localization is the proximal renal artery and carotid bifurcation.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Some arteries, such as the internal thoracic arteries, are rarely affected, despite the proximity to the coronary arteries both in location and structure.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atheroscleretic plaques often occur in arterial bifurcations, where blood flow is uneven; in other words, local hemodynamics play a role in the location of the plaques (see pathogenesis).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Diagnostics


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Diagnosis of diseases associated with atherosclerosis includes:


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Interviewing the patient and clarifying the symptoms of the disease: symptoms of coronary heart disease, symptoms of cerebral circulation disorders, intermittent claudication, symptoms of abdominal toad, etc.;


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

General examination of the patient: signs of aging of the body, listening to systolic murmur in the aortic focus; palpation of all arteries accessible to palpation is mandatory: aorta, external iliac arteries, general femoral arteries, popliteal arteries, arteries of the rear foot and posterior tibial artery, radial and ulnar arteries, carotid arteries.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

determination of systolic murmur over auscultatory points of arteries.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

if there is a suspicion of damage to the arterial bed of the lower extremities, the definition of the capillary response.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Determination of cholesterol concentration in the blood and determination of blood lipid balance;


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

X-ray examination of the chest organs, X-ray endovascular examination methods;


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Ultrasound examination of the heart and organs of the abdominal cavity and retroperitoneal space;


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Doppler sonography of the vessels of the extremities or, what could be better, ultrasound duplex and triplex scanning of the arteries of the brachiocephalic region, arteries of the lower extremities, the aorto-iliac segment, and also a transcranial doppler.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

diagnosis of arterial wall stiffness [3], including volume sphygmography [4] and determination of cardio-ankle vascular index (CAVI) [5]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Treatments


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The treatment regimen for atherosclerosis considers both drug and non-drug methods.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Non-drug methods for the correction of hyperlipidemia


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

To achieve an adequate effect, the duration of such treatment should be at least 6 months.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The following points are key in the therapy regimen (see Fig. Risk factors):


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

quitting smoking


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

moderate alcohol consumption [6]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

anti-atherosclerotic diet - for example, “Mediterranean”: oil rich in polyunsaturated fatty acids (Omega-3): linseed, rapeseed or olive oil.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Of alcohol, only table wine up to 150 ml per day (but it is better to completely give up alcohol, as it is a risk factor for stroke).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Refusal of bread made from high-grade flour, eating wholemeal bread without yeast (on hop or raisin sourdough), not a day without fruits and vegetables.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

active lifestyle — regular dosed physical activity.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

maintaining psychological and physical comfort


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

weight loss


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Drug therapy


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It includes the correction of hypertension (especially systolic blood pressure), diabetes mellitus, metabolic syndrome.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

However, the most significant is the normalization of the lipid spectrum.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The drugs used for this purpose are divided into four main groups:


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

I — inhibiting cholesterol absorption


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

II - reducing the synthesis of cholesterol and triglycerides in the liver and reducing their concentration in the blood plasma


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

III — increasing catabolism and excretion of atherogenic lipids and lipoproteins


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IV — additional


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Since 2012, a drug has been sold in Russia that treats vascular atherosclerosis with the help of local gene therapy [7].


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The first group


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IA — anion exchange resins (cholestyramine, gemfibrozil).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Cholesterol is adsorbed on themselves.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They are not absorbed or destroyed in the gastrointestinal tract.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The peak efficiency is achieved after a month of use.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The effect lasts 2-4 weeks after cancellation.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Disadvantages: adsorb and other substances - drugs, vitamins, trace elements.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

May be the cause of dyspepsia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

In addition, special studies indicate that the severity of atherosclerosis does not correlate in any way with plasma cholesterol levels, and plaque cholesterol is not plasma, but endothelial cholesterol origin, that is, it is not deposited on the vascular wall from the bloodstream, but is its own pathological metabolite.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IB - vegetable sorbents (guarem, β-sitosterol).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They prevent the absorption of cholesterol in the intestine.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is necessary to drink with a large (at least 200 ml) amount of liquid.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They can also cause dyspepsia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IC — AC-CoA transferase blocker in development and testing.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, it will be possible to reduce the esterification of cholesterol in enterocytes, and as a result, block the capture in the intestine.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

However, it is well known that most (about 2/3) of organ cholesterol is of endogenous origin, and the “lack” of nutritional cholesterol is easily compensated by its endogenous synthesis from acetate .


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thus, the fight against alimentary and/or plasma cholesterol as such is a meaningless and unsafe measure that does not improve the prognosis for this disease in any way.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The second group


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IIA — inhibitors of 3-OH-3-methylgluratyl CoA reductase (HMG-CoA reductase).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They're statins.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The most popular (and expensive) group of drugs.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Representatives in order of increasing effect: lovastatin (mevacor, medostatin, apecstatin), simvastatin (zocor, vasilip, symbor), fluvastatin (leskol), pravastatin (lipostate, pravachol) and cerivastatin ( lipobay), atorvastatin (liprimar, torvacard) and rosuvastatin (crestor).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

However, as the main effect increases, the risk of side effects also partially increases.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Among them: myopathy, rhabdomyolysis up to the development of renal failure, especially in combination with fibrates and nicotinic acid, hepatotoxicity, impotence, alopecia, dyspepsia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

They can not be combined with alcohol, used in children, pregnant and lactating, patients with liver damage.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Caution for patients after coronary artery bypass surgery.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IIB - fibroic acid derivatives (fibrates): clofibrate (miscleron), bezafibrate (bezalip), cyprofibrate (lipanor), fenofibrate (trikor).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Complications when using these drugs can be: myositis, allergies, dyspepsia, cholelithiasis in clofibrate.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Therefore, these drugs of previous generations are now practically not used.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Basically, a derivative of phenofibroic acid or a new generation of fibrates is now widely used: fenofibrate.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Fenofibrate has a higher safety profile and a relatively low incidence of side effects.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is most effective to use fenofibrate in the treatment of patients with type 2 diabetes mellitus, which is characterized by an increase in triglycerides, a decrease in HDL and a moderate increase in LDL.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Fenofibrate also reduces the number of small dense LDL, the most atherogenic LDL.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Along with this, when taking fenofibrate, there is a decrease not only in macrovascular complications (coronary heart disease, myocardial infarction), but also in such disabling microvascular complications as retinopathy, polyneuropathy, nephropathy and lower limb amputations in diabetes.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

For more intensive treatment of atherosclerosis, it is recommended to combine the use of statins and fenofibrate.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IIC — nicotinic acid (enduracin).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is undesirable to use in diabetes mellitus.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Side effects: itchy skin, hyperemia, dyspepsia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IID — reducing sterol synthesis — probucol (phenbutol)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The third group


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unsaturated fatty acids: linetol, lipostabil, tribuspamine, polyspoin, thioctic acid (octolipen, thiogamma, thiolepta), omacor, eiconol.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Caution: may increase the effect of hypoglycemic drugs.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Group 4


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Endotheliotropic drugs (feeding the endothelium).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Reduce cholesterol levels in sex.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Pyricarbate (parmidine, anginin), synthetic analogues of prostacyclin (misoprostol, vasoprostane), policosanol [8], vitamins A, E (Aevit), C.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Preparations under testing


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Cyclodextrin, which has demonstrated the dissolution of cholesterol crystals [9], and successful treatment of atherosclerosis on a mouse model can dissolve cholesterol by removing it from plaques [10].


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Since cyclodextrin is known to be safe for humans, this drug is currently a potential candidate for testing in sick people for the treatment of atherosclerosis [11].


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A peptide called AC-he18a-NH2 (under clinical development known as AEM-28) has been found to have an amazing ability to lower cholesterol and triglycerides, and also has anti-inflammatory properties.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Moreover, unlike statins and PCSK-9 inhibitors, it can lower cholesterol by binding to heparan sulfate proteoglycans (HSPG).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

It is currently undergoing phase 1a/1b clinical trials and has shown acceptable tolerability and, most importantly, promising efficacy.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

[12] [13]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Antisense drugs, such as ISIS-APO (a) Rx and its more powerful analogue ISIS-APO (a) -LRx, which inhibit the translation of apolipoprotein (a) mRNA, can reduce plasma levels of apo (a) /Lp (a) and oxidized forms of phospholipids (OxPl) associated with them by 86% and 93%, respectively [14] [15].


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Surgical correction


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Artery surgeries can be open (endarterectomy), when the plaque is removed or the tortuosity is straightened by open surgery, or endovascular - dilatation of the artery with balloon catheters with stents placed at the site of the narrowing of the artery that prevent vessel reocclusion (transluminal balloon angioplasty and artery stenting).


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The choice of method depends on the location and prevalence of narrowing or closing the lumen of the artery.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

History


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1755 - Geller introduces the term “atheroma” to describe vascular lesions


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1761 — and a little later (1829) and Cruveilher describe the characteristic seals of the arteries during autopsy


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1833 — Lobstein introduces the concept of “arteriosclerosis”


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1892 - Virchow proposes the term “endarteritis deformans nodosa”


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1904 — Marchand first introduces the concept of “atherosclerosis” to refer to a special type of arteriosclerosis


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1908 — Ignatovsky and Saltykov experimentally reproduced atherosclerosis in rabbits for the first time, feeding them milk and eggs


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1912 - Russian pathologist Anichkov, Nikolai Nikolaevich (later academician of the Academy of Sciences and the Academy of Medical Sciences of the USSR, President of the Academy of Medical Sciences of the USSR) and student Khalatov, Semyon Sergeevich (later professor, pathophysiologist) who helped him for the first time created a classic rabbit model of this disease, feeding animals with pure cholesterol dissolved in sunflower oil


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1913 — Anichkov, Nikolai Nikolaevich created an infiltration theory of morphogenesis of atherosclerosis, the essence of which is the staged penetration (infiltration) of blood plasma lipids into the inner membrane arteries followed by the formation of a connective tissue “capsule” around lipid deposits (part of this “capsule” in the form of a fibrous tire creates an atherosclerotic plaque)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1924 — Anichkov, Nikolai Nikolaevich formulated a combination theory of the pathogenesis of atherosclerosis, which includes such factors as: disorders of lipid metabolism, hypertension, local (non-lipid) vascular lesions, etc.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1964 — K. Bloch (USA) and F. Lineen (Germany) awarded the Nobel Prize for research on cholesterol metabolism and regulation


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1964 — The European Atherosclerosis Society (EAS) was founded


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

1985 — M. S. Brown and J.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Goldstein (both USA) awarded the Nobel Prize for research on cholesterol metabolism and regulation


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

2007 — The first Anichkov EAS Prize was awarded to Professor Göran Hansson, Sweden.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

The EAS website says: “This prestigious Prize (Anitschkow Prize), awarded annually by EAS, recognizes outstanding research in the field of atherosclerosis and linked metabolic disturbances. The recipient of the Prize receives the Anitschkow Medal, an award of ten thousand euros, and is invited to present the Anitschkow Lecture as part of the Opening Ceremony at EAS Congress”.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Since then, 8 winners of this award have been known (http://www.eas-society.org/?page=anitschkow)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

2013 — international conference “Centenary of the Infiltration Theory of Atherosclerosis by Academician N. N. Anichkova”, St. Petersburg


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

2016 — Symposium of the International Society for the Study of Atherosclerosis “Anichkov Days”.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Saint Petersburg


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

2016 — Coordinated opinion of Russian experts on the assessment of arterial stiffness in clinical practice [16]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Literature


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Great medical encyclopedia.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Tom 2.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M.: Soviet Encyclopedia, 1975


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Cardiology in diagrams and tables.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M.: Practice, 1996


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Federal guidelines for physicians on the use of medicines.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Issue 2.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M., 2001


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Comparative pathophysiological aspects of energy supply to the vascular wall/Yu.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IN. Byts, V. P. Pishak, A. IN. Ataman//Chernivtsi: Prut, 1999


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Internal medicine according to Tinsley and Harry.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Tom 2.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M.: Practice, 2002


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Thromboangiitis obliterans.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

AND. AND. Zatevakhin, R. YU.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Yudin.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M., 2002


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

L. Rakov V. N. Kolesnikov//New Pharmacy.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2002.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 6


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Anti-atherosclerotic drugs/N. G. Preferanskaya//Russian Medical Journal.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2002.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 5


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Non-drug methods for correcting hyperlipidemia/D. M. Aronov//Attending physician.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2002.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 7-8


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis: clinical significance and prevention possibility/Marzevich//Attending physician.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2004.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 2


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Endothelial dysfunction in individuals with heredity burdened by atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

//Cardiology.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2004.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 1 (vol. 44)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

New European recommendations for the prevention of cardiovascular diseases caused by atherosclerosis /Perova//Cardiology.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2004.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 1 (vol. 44)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Atherosclerosis is the main theories of development/Mkrtchyan//Diabetes.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A way of life.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2004.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— No. 6


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Mortality from diseases of the circulatory system in Russia and economically developed countries/Kharchenkov.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

I.//Russian Journal of Cardiology.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 2005, № 2 [17]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

A pioneer in pathology.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

On the occasion of the 125th anniversary of the birth of academician N. N. Anichkova.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— Bulletin of the Russian Academy of Sciences, 2010, vol.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— P. 1005-1012;


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Ilyinsky B.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

IN. Prevention, early diagnosis and treatment of atherosclerosis.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— M.: Medicine, 1977.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— Circulation of 120,000 copies


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

— 167 p.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Coordinated opinion of Russian experts on the assessment of arterial stiffness in clinical practice 2016 [16]


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Notes


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

References


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) training film


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) — Website of the Republican Center for Atherosclerosis


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) — “Science and Life”, 2000, No. 10.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) — article by Professor J. WELL. Rapoport


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) — Author cardiologist, k.M.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

n.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Veselkova N. S. (article)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Unknown parameter |deadlink= ignored (|dead-url= suggested) (help) (Step 1 and 2) — Author cardiologist, k.m.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

n.


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Veselkova N. S. (article)


Question: Are children diagnosed with atherosclerosis?

Atherosclerosis

Category:Vascular diseases


Question: How is HIV deciphered?

HIV infection

This article is about the disease.


Question: How is HIV deciphered?

HIV infection

The causative agent of the disease is the article human immunodeficiency virus.


Question: How is HIV deciphered?

HIV infection

HIV infection is a slowly progressing disease [1] caused by the human immunodeficiency virus (HIV) [2] [3].


Question: How is HIV deciphered?

HIV infection

The virus infects cells of the immune system that have CD4 receptors on their surface: T-helpers, monocytes, macrophages, Langerhans cells [4], dendritic cells, microglia cells [5].


Question: How is HIV deciphered?

HIV infection

As a result, the immune system is depressed, acquired immune deficiency syndrome (AIDS) develops, the patient's body loses the ability to protect itself from infections and tumors, and secondary opportunistic diseases that are not typical for people with normal immune status [6] [7] [8] [9] [10] [11].


Question: How is HIV deciphered?

HIV infection

Without medical intervention, opportunistic diseases cause death on average 9-11 years after infection (depending on the virus subtype) [8].


Question: How is HIV deciphered?

HIV infection

The average life expectancy at the AIDS stage is about nine months [12] [13].


Question: How is HIV deciphered?

HIV infection

When performing antiretroviral therapy, the patient's life expectancy is 70—80 years [14] [15] [16].


Question: How is HIV deciphered?

HIV infection

The rate of development of HIV infection depends on many factors, including the status of the immune system [17] [18], age (elderly people have an increased risk of rapid development of the disease compared to more young people), virus strain, co-infections with other viruses, good nutrition, therapy [19].


Question: How is HIV deciphered?

HIV infection

An insufficient level of medical care and the presence of concomitant infectious diseases, for example, tuberculosis, cause a predisposition to the fleeting development of the disease [13] [20] [21].


Question: How is HIV deciphered?

HIV infection

Etiology and pathogenesis


Question: How is HIV deciphered?

HIV infection

Human immunodeficiency virus


Question: How is HIV deciphered?

HIV infection

HIV infection is caused by the human immunodeficiency virus, which belongs to the family of retroviruses [22], the genus of lentiviruses.


Question: How is HIV deciphered?

HIV infection

The HIV genome is represented by ribonucleic acid and undergoes reverse transcription in the infected cell.


Question: How is HIV deciphered?

HIV infection

HIV affects human blood cells that have CD4 receptors on their surface: T-lymphocytes, macrophages and dendritic cells [23] [24] [25].


Question: How is HIV deciphered?

HIV infection

Virus-infected T-lymphocytes die due to virus destruction, apoptosis, or destruction by cytotoxic T-lymphocytes.


Question: How is HIV deciphered?

HIV infection

After the number of CD4+ T-lymphocytes falls below 200 in one microliter of blood, the cellular immunity system ceases to protect the body [26].


Question: How is HIV deciphered?

HIV infection

The virus envelope consists of a two-layer lipid membrane into which a number of proteins are embedded, for example, transmembrane glycoprotein gp41 and surface glycoprotein gp120 [27] :293-294, 296.


Question: How is HIV deciphered?

HIV infection

Inside the “core” of the virus, consisting of the matrix protein p17 and the capsid protein p24, there are two single-stranded molecules of genomic RNA and a number of enzymes: reverse transcriptase, integrase and protease.


Question: How is HIV deciphered?

HIV infection

Genetic factors of HIV immunity


Question: How is HIV deciphered?

HIV infection

Heredity plays an important role in the development of HIV infection, people homozygous on the CCR5-Δ32 allele have genetically determined resistance to some HIV serotypes [28] A mutation in the CCR2 gene leads to AIDS development delay [29] [30].


Question: How is HIV deciphered?

HIV infection

HIV is characterized by significant genetic diversity, and strains with different rates of development of the disease are described.


Question: How is HIV deciphered?

HIV infection

[31] [32] [33]


Question: How is HIV deciphered?

HIV infection

Individuals with mutations in the CCR5 coreceptors of M-tropic strains of the virus are not susceptible to M-tropic HIV-1 strains, but become infected with T-tropic strains [34] [35].


Question: How is HIV deciphered?

HIV infection

HLA-BW4 homozygosity is a protective factor against disease progression.


Question: How is HIV deciphered?

HIV infection

In heterozygotes at HLA class I loci, immunodeficiency develops more slowly than homozygotes [36].


Question: How is HIV deciphered?

HIV infection

Studies have shown that carriers of HLA-B14, B27, B51, B57 and C8 progresses more slowly, while carriers of HLA-A23, B37 and B49 develop immunodeficiency rapidly [37] [38].


Question: How is HIV deciphered?

HIV infection

All HIV-infected people with HLA-B35 developed AIDS no earlier than 8 years after infection.


Question: How is HIV deciphered?

HIV infection

Sex partners who are incompatible with HLA class I have a lower risk of contracting HIV through heterosexual contact [39].


Question: How is HIV deciphered?

HIV infection

Changes in the immune system


Question: How is HIV deciphered?

HIV infection

In the acute phase of HIV infection, in the viremia stage, there is a sharp decrease in CD4+ T-lymphocytes due to the direct lysing effect of the virus and an increase in the number of copies of viral RNA in the blood.


Question: How is HIV deciphered?

HIV infection

After that, the process stabilizes with a slight increase in the number of CD4 cells, which, however, does not reach normal values [40].


Question: How is HIV deciphered?

HIV infection

The positive dynamics is due to an increase in the number of cytotoxic CD8+ T-lymphocytes.


Question: How is HIV deciphered?

HIV infection

These lymphocytes are able to destroy HIV-infected cells directly by cytolysis without restriction on the human leukocyte antigen class I (English: Human leukocyte Antigen-HLA) [41] [42].


Question: How is HIV deciphered?

HIV infection

In addition, they secrete suppressive factors (chemokines), such as RANTES, MIP-1alpha, MIP-1beta [43], MDC, which prevent the virus from multiplying by blocking coreceptors [44] [45] [46] [47].


Question: How is HIV deciphered?

HIV infection

HIV-specific CD8+ lymphocytes play a major role in controlling the acute phase of HIV infection [23], but in the chronic course of infection it does not correlate with viremia [48], as proliferation and activation CD8+ lymphocytes depend on antigen-specific CD4 T-helpers, while HIV also infects CD8+ lymphocytes, which can lead to a decrease in their number [49].


Question: How is HIV deciphered?

HIV infection

Acquired immunodeficiency syndrome is the terminal stage of HIV infection and develops in most patients with a drop in the number of CD4+ T-lymphocytes, blood below 200 cells/ml (CD4+ T-lymphocyte norm 1200 cells/ml) [50].


Question: How is HIV deciphered?

HIV infection

CD4+ cell depression is explained by the following theories [51]:


Question: How is HIV deciphered?

HIV infection

CD4+ T-lymphocyte death as a result of direct cytopathic action of HIV [52]


Question: How is HIV deciphered?

HIV infection

HIV primarily affects activated CD4 lymphocytes, and since HIV-specific lymphocytes are among the first cells activated during HIV infection, they are among the first to suffer [53].


Question: How is HIV deciphered?

HIV infection

The virus changes the CD4+ cell membrane of T-lymphocytes, which leads them to merge with each other to form giant syncytia, which is regulated by LFA-1 [54] [55]


Question: How is HIV deciphered?

HIV infection

Antibody damage to CD4 cells as a result of antibody-dependent cytotoxic action (English: ADCC-Antibody-dependent cellular cytotoxicity) [56] [57].


Question: How is HIV deciphered?

HIV infection

Activation of natural killer cells [58] [59].


Question: How is HIV deciphered?

HIV infection

Autoimmune damage [60] [61]


Question: How is HIV deciphered?

HIV infection

Binding of the gp120 virus protein to the CD4 receptor (masking the CD4 receptor) and, as a result, the impossibility of identifying the antigen, the inability of CD4 to interact with HLA class II [62].


Question: How is HIV deciphered?

HIV infection

Programmed cell death [63] [64].


Question: How is HIV deciphered?

HIV infection

Absence of an immune response (anergy) [65].


Question: How is HIV deciphered?

HIV infection

B-lymphocytes in HIV infection undergo polyclonal activation and release a large number of immunoglobulins, TNFα, interleukin-6 [66] and lectin DC-SIGN, which contributes to the penetration of HIV into T- lymphocytes [67].


Question: How is HIV deciphered?

HIV infection

In addition, there is a significant decrease in interleukin-2 produced by type 1 CD4 helpers and is critical in the activation of cytotoxic T-lymphocytes (CD8+, CTL) [68] [69] and suppression by macrophage secretion virus of interleukin-12, a key cytokine in the formation and activation of type 1 T-helpers and NK lymphocytes (English: Natural killer cells) [70].


Question: How is HIV deciphered?

HIV infection

One of the main factors in the pathogenesis of HIV is the hyperactivation of the immune system in response to infection [71] [72].


Question: How is HIV deciphered?

HIV infection

One of the features of pathogenesis is the death of CD4+ T helpers, the concentration of which is slowly but steadily decreasing.


Question: How is HIV deciphered?

HIV infection

Particularly significant negative consequences are the death of HIV-infected CD4+ T-lymphocytes of central memory and dendritic cells.


Question: How is HIV deciphered?

HIV infection

The main cause of T cell death in HIV infection is programmed cell death (apoptosis).


Question: How is HIV deciphered?

HIV infection

Even at the AIDS stage, the CD4+ infection rate of peripheral blood cells is 1:1000, which means that the virus itself is not able to kill the number of cells that die in HIV -infections.


Question: How is HIV deciphered?

HIV infection

It is also impossible to explain such a massive death of T cells and the cytotoxic effect of other cells.


Question: How is HIV deciphered?

HIV infection

At the same time, the main place where HIV replication occurs at all stages of HIV infection is secondary lymphoid tissue [73].


Question: How is HIV deciphered?

HIV infection

The most intensive replication of HIV occurs in lymphoid tissue associated with the intestine (en:gut-associated lymphoid tissue).


Question: How is HIV deciphered?

HIV infection

Infected memory T cells in this tissue are found 10-100, and sometimes almost 1000 times more often than in peripheral blood.


Question: How is HIV deciphered?

HIV infection

This is primarily due to the high content of CD4+CCR5+ T cells in this tissue, which are good targets for HIV infection.


Question: How is HIV deciphered?

HIV infection

For comparison, in the peripheral blood of such cells only 11.7%, tissue of lymph nodes 7.9%, while in lymphoid tissue associated with the intestine it is 69.4% [74].


Question: How is HIV deciphered?

HIV infection

Severe depletion of CD4+ cells due to HIV replication in intestinal lymphoid tissue occurs several weeks after infection and persists at all stages of HIV infection [75].


Question: How is HIV deciphered?

HIV infection

HIV infection disrupts the permeability of the mucosa to substances of microbial origin, such as lipopolysaccharides of gram-negative bacteria.


Question: How is HIV deciphered?

HIV infection

These substances, when entering the bloodstream, cause chronic nonspecific hyperactivation of innate and adaptive immunity [76].


Question: How is HIV deciphered?

HIV infection

Thus, HIV infection is mainly a disease of the intestinal mucosa, and the gastrointestinal tract is the main place for HIV replication [77].


Question: How is HIV deciphered?

HIV infection

A fundamentally important role in reducing the number of naive lymphocytes is the change in the structure of the lymphoid tissue of the lymph nodes caused by chronic immune activation.


Question: How is HIV deciphered?

HIV infection

After emigration from the thymus, naive T-lymphocytes form a stock of long-lived cells that circulate between tissues and secondary lymphoid organs.


Question: How is HIV deciphered?

HIV infection

Some of them die due to apoptosis, and some divide from time to time, replenishing the supply of dead cells.


Question: How is HIV deciphered?

HIV infection

At all periods of life, the number of cells that appear as a result of division exceeds exports from the thymus [78].


Question: How is HIV deciphered?

HIV infection

To prevent apoptosis of these cells at each stage of their development, they need specific survival signals.


Question: How is HIV deciphered?

HIV infection

Such a signal is realized when, during contact of the T-cell receptor (TCR) with the complex, its own antigen, MHC I, the naive lymphocyte receives stimulation with interleukin-7.


Question: How is HIV deciphered?

HIV infection

The entry of naive T cells into lymphoid tissue and interaction with microenvironment cells that synthesize IL-7 (for example, lymph node stromal cells, dendritic cells [79]) is a critical factor for preserving the naive T cell population.


Question: How is HIV deciphered?

HIV infection

The highly organized structure of secondary lymphoid tissue is extremely important for the survival of T cells and ensuring an immune response through the interaction of T-lymphocytes and antigen-presenting cells.


Question: How is HIV deciphered?

HIV infection

Chronic immune activation and replication of HIV in lymphoid tissue leads to the destruction of this structure and excessive accumulation of collagen, and ultimately to fibrosis of the lymph nodes.


Question: How is HIV deciphered?

HIV infection

Excess collagen production is a side effect of trying to counteract regulatory T cells (Treg) against the negative effects of immune activation.


Question: How is HIV deciphered?

HIV infection

Fibroblasts stimulated by cytokines (such as TGF-β1) of regulatory T cells produce collagen, the accumulation of which destroys the structure of lymphoid tissue and deprives naive T cells of access to the source IL-7.


Question: How is HIV deciphered?

HIV infection

This leads to the depletion of their supply, as well as to the limitation of its recovery when suppressing HIV replication to HAART [80].


Question: How is HIV deciphered?

HIV infection

Disorders in the functioning of the immune system increase over time to the complete inability to perform its main function - protecting the body from pathogens.


Question: How is HIV deciphered?

HIV infection

Against the background of hyperactivation, leukemia often occurs, which together leads to the fact that facultative parasites that coexist in a healthy body under the control of the immune system come out from control, becoming fatal to the body [81].


Question: How is HIV deciphered?

HIV infection

The main reservoir of HIV in the body is macrophages and monocytes.


Question: How is HIV deciphered?

HIV infection

There is no explosive reproduction in these cells, the release of virions is carried out through the Golgi complex.


Question: How is HIV deciphered?

HIV infection

It should also be noted that the innate immune system is not able to effectively recognize the virus during acute HIV infection and stimulate a timely adequate specific T-cell response [82 ].


Question: How is HIV deciphered?

HIV infection

The immune system can not recognize HIV well, as up to 45% of the human genome consists of endogenous retroviruses and retrotransposons.


Question: How is HIV deciphered?

HIV infection

Antibodies that occur as a result of the reaction to the gp-120 protein only contribute to an increase in the “infection”, but not to suppress it.


Question: How is HIV deciphered?

HIV infection

Thus, the human immune system only contributes to the multiplication of the virus by its response, so the creation of an HIV vaccine similar to the vaccine against the smallpox virus is impossible [83].


Question: How is HIV deciphered?

HIV infection

It should be noted that this view is not supported by many HIV researchers.


Question: How is HIV deciphered?

HIV infection

In addition, it contradicts the fact that the fundamental possibility of creating an HIV vaccine has been proven.


Question: How is HIV deciphered?

HIV infection

In 2009, a trial of the RV144 vaccine in Thailand showed effectiveness in preventing infections [84] [85].


Question: How is HIV deciphered?

HIV infection

epidemiology


Question: How is HIV deciphered?

HIV infection

As of 2011, 60 million people worldwide have become infected with HIV since then, of which 25 million have died and 35 million are living with HIV [86].


Question: How is HIV deciphered?

HIV infection

On a global scale, the epidemic situation is stabilizing, and the number of new HIV infections fell from 3.5 million in 1997 to 2.7 million in 2007 [87].


Question: How is HIV deciphered?

HIV infection

As of the end of 2013, 645,000 people in Russia lived with HIV infection, and 153,000 HIV-infected Russian citizens died from various causes between 1986 and 2013 [88].


Question: How is HIV deciphered?

HIV infection

In December 2016, at a meeting of the Presidium of the Russian Academy of Sciences, Vadim Pokrovsky, head of the Federal Scientific and Methodological Center for the Control and Prevention of HIV Infection approximately 1.5 million Russians, and 240,000 people died of AIDS [89].


Question: How is HIV deciphered?

HIV infection

“In Russia, due to the mixing of the previously dominant strain A1 in the Russian Federation and the new AG agent imported from Central Asia, a new virus A63 has appeared, which is much more dangerous than parents,” he said during the meeting of the Presidium of the Russian Academy of Sciences Head of the Laboratory of Immunochemistry


Question: How is HIV deciphered?

HIV infection

D. AND. Ivanovsky Eduard Karamov [90].


Question: How is HIV deciphered?

HIV infection

In 2016, 5.3% more new HIV infections were registered in Russia than in 2015 — 103.4 thousand [91].


Question: How is HIV deciphered?

HIV infection

According to Michel Sedibé, Deputy Secretary General of the United Nations, Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), Russia ranked third in the world after South Africa and Nigeria [92].


Question: How is HIV deciphered?

HIV infection

Clinical classification


Question: How is HIV deciphered?

HIV infection

The classification of HIV infection and AIDS has been repeatedly clarified and changed.


Question: How is HIV deciphered?

HIV infection

In the first WHO classification of 1988, 4 stages were distinguished.


Question: How is HIV deciphered?

HIV infection

This classification has become the basis for others who clarify and detail the stages of the disease [93]:


Question: How is HIV deciphered?

HIV infection

Stage I - initial (acute) HIV infection;


Question: How is HIV deciphered?

HIV infection

Stage II - persistent generalized lymphadenopathy;


Question: How is HIV deciphered?

HIV infection

Stage III — AIDS-associated complex (Pre-AIDS);


Question: How is HIV deciphered?

HIV infection

Stage IV — expanded AIDS.


Question: How is HIV deciphered?

HIV infection

CDC Classification


Question: How is HIV deciphered?

HIV infection

In 1993 [94], the US Centers for Disease Control and Prevention (English: CDC) developed a classification [95] that evaluates both clinical and laboratory parameters (the number of CD4+-T lymphocytes in 1 μl of blood).


Question: How is HIV deciphered?

HIV infection

According to the CDC classification, a patient is diagnosed with HIV infection or terminal stage AIDS, persons who fall under the criteria of categories A3, B3, C1, C2 and C3 are subject to registration as AIDS patients.


Question: How is HIV deciphered?

HIV infection

The number (%) of CD4+ T-lymphocytes in 1 μL Clinical categoryIA — asymptomatic acute (primary) or PGLP (persistent generalized lymphadenopathy) B — manifest C — AIDS-indicator diseases1.


Question: How is HIV deciphered?

HIV infection

> 500 (> 29%) A1B1S12.


Question: How is HIV deciphered?

HIV infection

200—499 (> 14—28%) A2B2S23.


Question: How is HIV deciphered?

HIV infection

< 200 (< 14%) A3V3S3


Question: How is HIV deciphered?

HIV infection

Symptoms of clinical categories according to the CDC classification:


Question: How is HIV deciphered?

HIV infection

A: acute retroviral syndrome: generalized lymphadenopathy (GLAP), asymptomatic course;


Question: How is HIV deciphered?

HIV infection

C: syndromes of the AIDS-associated complex: oral candidiasis, cervical dysplasia, organic lesions, herpes zoster, idiopathic thrombocytopenia, listeriosis, leukoplakia, peripheral neuropathy;


Question: How is HIV deciphered?

HIV infection

C: AIDS proper: candidiasis of the lungs or esophagus, cervical cancer, coccidioidosis, cryptosporidiosis, cytomegalovirus infection, herpetic esophagitis, HIV encephalopathy, histoplasmosis, isosporosis, sarcoma Kaposi, lymphoma, mycobacteriosis, pneumocystosis, bacterial pneumonia, progressive multifocal leukoencephalopathy, salmonellosis.


Question: How is HIV deciphered?

HIV infection

WHO clinical stages


Question: How is HIV deciphered?

HIV infection

The World Health Organization (WHO) developed a clinical classification of HIV/AIDS in 1990, which was last significantly expanded and updated in 2006 and published for countries Europe, December 1, 2006 in the WHO Protocols on the Treatment and Prevention of HIV/AIDS [96].


Question: How is HIV deciphered?

HIV infection

WHO clinical stages for adults and adolescents over 15 years of age [97]:


Question: How is HIV deciphered?

HIV infection

Acute HIV infection: asymptomatic, acute retroviral syndrome


Question: How is HIV deciphered?

HIV infection

Clinical stage 1: asymptomatic, persistent generalized lymphadenopathy (PGL)


Question: How is HIV deciphered?

HIV infection

Clinical stage 2: seborrheic dermatitis, angular cheilitis, recurrent oral ulcers (two or more episodes in 6 months), shingles (common lichen), recurrent respiratory infections — sinusitis, otitis media, pharyngitis, bronchitis, tracheitis (two or more episodes in 6 months), fungal nail infections, papular itchy dermatitis


Question: How is HIV deciphered?

HIV infection

Clinical stage 3: oral hairy leukoplakia, unexplained chronic diarrhea lasting more than 1 month, recurrent oral candidiasis (two or more episodes in 6 months), severe bacterial infection (pneumonia, empyema, purulent myositis, bone or joint infections, meningitis, bacteremia), acute ulcerative necrotizing stomatitis, gingivitis or periodontitis


Question: How is HIV deciphered?

HIV infection

Clinical stage 4*: pulmonary tuberculosis, extrapulmonary tuberculosis (excluding lymphadenopathy), unexplained weight loss (more than 10% within 6 months), HIV-debilitating syndrome [98], pneumocystis pneumonia, severe or radiographically confirmed pneumonia (two or more episodes in 6 months), cytomegalovirus retinitis (with or without colitis), herpes simplex virus (English: HSV) (chronic or persistent for more than 1 month), encephalopathy, progressive multifocal leukoencephalopathy, Kaposi's sarcoma and other HIV-related malignancies, toxoplasmosis, disseminated fungal infection (candidiasis, histoplasmosis, coccidioidomycosis), cryptosporidiosis, cryptococcal meningitis, nontuberculous mycobacteria infection, disseminated mycobacterimia (English: MOTT) )


Question: How is HIV deciphered?

HIV infection

* If supported by sufficient evidence, may include: anus carcinoma and lymphoma (T-cell Hodgkin lymphoma)


Question: How is HIV deciphered?

HIV infection

Clinical classification in the Russian Federation


Question: How is HIV deciphered?

HIV infection

In Russia and the CIS countries, the classification proposed by V. AND. Pokrovsky in 1989 [99] [94]:


Question: How is HIV deciphered?

HIV infection

I — incubation stage


Question: How is HIV deciphered?

HIV infection

II — stage of primary manifestations:


Question: How is HIV deciphered?

HIV infection

A is an acute febrile phase


Question: How is HIV deciphered?

HIV infection

B — asymptomatic phase


Question: How is HIV deciphered?

HIV infection

B — persistent generalized lymphadenopathy


Question: How is HIV deciphered?

HIV infection

III - stage of secondary manifestations:


Question: How is HIV deciphered?

HIV infection

A - weight loss of less than 10%, superficial fungal, bacterial, viral lesions of the skin and mucous membranes, herpes zoster, repeated pharyngitis, sinusitis;


Question: How is HIV deciphered?

HIV infection

B — progressive weight loss of more than 10%, unexplained diarrhea or fever for more than 1 month, repeated and/or persistent bacterial and protozoal lesions of internal organs (without dissemination) or deep lesions of the skin and mucous membranes: repeated or disseminated shingles, localized Kaposi's sarcoma;


Question: How is HIV deciphered?

HIV infection

B — generalized bacterial, fungal, viral, protozoal and parasitic diseases, pneumocystis pneumonia, esophageal candidiasis, atypical mycobacteriosis, extrapulmonary tuberculosis, cachexia, disseminated Kaposi's sarcoma, CNS lesions of various etiologies


Question: How is HIV deciphered?

HIV infection

IV — terminal stage


Question: How is HIV deciphered?

HIV infection

Appendix to the Instruction for Completing the Annual Form of State Federal Statistical Observation No. 61 “Information on Contingents of Patients with HIV Infection”, [100] approved by Order The Ministry of Health and Social Development of Russia dated March 17, 2006 No. 166 proposes the following classification of stages of HIV infection [101]:


Question: How is HIV deciphered?

HIV infection

The incubation stage;


Question: How is HIV deciphered?

HIV infection

The stage of primary manifestations.


Question: How is HIV deciphered?

HIV infection

Variants of the course: asymptomatic, acute infection without secondary diseases, acute infection with secondary diseases;


Question: How is HIV deciphered?

HIV infection

Subclinical stage.


Question: How is HIV deciphered?

HIV infection

The stage of secondary diseases.


Question: How is HIV deciphered?

HIV infection

Flow options:


Question: How is HIV deciphered?

HIV infection

weight loss less than 10%, fungal, viral, bacterial lesions of the skin and mucous membranes, repeated pharyngitis, sinusitis, shingles.


Question: How is HIV deciphered?

HIV infection

Phases: progression in the absence of antiretroviral therapy, against the background of antiretroviral therapy; remission (spontaneous, after antiretroviral therapy, against antiretroviral therapy);


Question: How is HIV deciphered?

HIV infection

weight loss of more than 10%, unexplained diarrhea or fever for more than a month, repeated persistent viral, bacterial, fungal, protozoal lesions of internal organs, localized Kaposi's sarcoma, repeated or disseminated shingles.


Question: How is HIV deciphered?

HIV infection


Question: How is HIV deciphered?

HIV infection

cachexia, generalized viral, bacterial, mycobacterial, fungal, protozoal, parasitic diseases, including: candidiasis of the esophagus, bronchi, trachea, lungs; pneumocystis pneumonia; malignant tumors; lesions of the central nervous system.


Question: How is HIV deciphered?

HIV infection


Question: How is HIV deciphered?

HIV infection

Terminal stage.


Question: How is HIV deciphered?

HIV infection

Stages of the infectious process


Question: How is HIV deciphered?

HIV infection

The total duration of HIV infection in patients who do not receive HAART is on average 10 years.


Question: How is HIV deciphered?

HIV infection

Throughout this time, there is a constant decrease in the number of lymphocytes in the patient's blood, which ultimately causes death from secondary (opportunistic) diseases [19].


Question: How is HIV deciphered?

HIV infection

Window period


Question: How is HIV deciphered?

HIV infection

The period of seroconversion — from infection to the appearance of detectable antibodies to HIV — ranges from two to 12 weeks (in immunocompromised people from twelve weeks to 6 months [103]) [19].


Question: How is HIV deciphered?

HIV infection

Acute phase


Question: How is HIV deciphered?

HIV infection

The acute phase lasts up to 1 month from the moment of infection.


Question: How is HIV deciphered?

HIV infection

Clinical manifestations of this stage: low-grade fever, urticaria, stomatitis, inflammation of the lymph nodes, which become enlarged, soft and painful (symptoms go under the mask infectious mononucleosis).


Question: How is HIV deciphered?

HIV infection

The maximum concentration of the virus and antibodies appears only at the very end of the prodromal period.


Question: How is HIV deciphered?

HIV infection

After HIV-1 infection and an incubation period, which can last from several days to several weeks [104], in most cases, acute flu-like syndrome develops, a manifestation of acute viremia, some patients describe it as the “worst flu” in their lives [19].


Question: How is HIV deciphered?

HIV infection

For the first time, flu-like syndrome was described [105] as a mononucleosis-like syndrome with fever, patchy-papular rash, ulcers on the oral mucosa, lymphadenopathy, arthralgia, pharyngitis, malaise, weight loss, aseptic meningitis and myalgia [106].


Question: How is HIV deciphered?

HIV infection

It is noted that the more severe the symptoms of the acute phase and the longer they persist, the faster AIDS develops [107] [108].


Question: How is HIV deciphered?

HIV infection

Fever (80%) and malaise (68%) were recognized as the most sensitive clinical criteria for the acute phase of HIV infection, while weight loss (86%) and oral ulcers (85%) were recognized as the most specific [19] [ 109] [110].


Question: How is HIV deciphered?

HIV infection

During the acute phase, the virus actively replicates and the viral load can reach 100 million copies of viral RNA per μl, and the number of CD4+ lymphocytes drops, sometimes to a level at which they can develop opportunistic infections [19].


Question: How is HIV deciphered?

HIV infection

This number of CD4+ cells then rises, but usually does not reach the original level (normal 1200 per μl).


Question: How is HIV deciphered?

HIV infection

The number of CD8+ lymphocytes is increasing, and the CD4/CD8 ratio may become less than 1 [111].


Question: How is HIV deciphered?

HIV infection

It has been shown that the higher the viral load, the more contagious the patient is, especially during the acute phase of HIV infection [112] [113].


Question: How is HIV deciphered?

HIV infection

The acute phase of HIV infection usually lasts 7 to 10 days, rarely more than 14 days.


Question: How is HIV deciphered?

HIV infection

Diagnosis of this stage of HIV infection is difficult due to the non-specificity of the symptoms and can be confirmed when viral RNA is detected in the absence of antibodies to HIV.


Question: How is HIV deciphered?

HIV infection

One of the best methods for diagnosing this phase is the detection of HIV-1 RNA in plasma (HIV RNA >10,000 copies/ml [114]) with sensitivity and specificity reaching 100% [109].


Question: How is HIV deciphered?

HIV infection

The sensitivity of the determination of the p24 protein is 79%, and the specificity is 99.5—99.96%.


Question: How is HIV deciphered?

HIV infection

The diagnosis of the acute phase of HIV infection must be confirmed after a few weeks by the detection of antibodies to HIV.


Question: How is HIV deciphered?

HIV infection

In some cases, the initiation of combination therapy at this stage may be beneficial for the health of the infected person [19].


Question: How is HIV deciphered?

HIV infection

Clinical symptoms of acute HIV infection [115]: Fever (96%), lymphadenopathy (74%), pharyngitis (70%), rash (70%) [116], myalgia (54%), diarrhea (32%), headache (32%), nausea and vomiting (27%), hepatosplenomegaly (14%), weight loss (13%), thrush (12%), neurological symptoms (12%) [117].


Question: How is HIV deciphered?

HIV infection

Latent period


Question: How is HIV deciphered?

HIV infection

After the end of the acute phase, a “balance” is established between the rate of reproduction of the virus and the immune response, and then for many months and years (up to 8-10 years), the infection is asymptomatic or form of persistent generalized lymphadenopathy (stage 1 according to WHO classification).


Question: How is HIV deciphered?

HIV infection

During this period, the virus multiplies actively and CD4 cells are constantly destroyed.


Question: How is HIV deciphered?

HIV infection

At the end of the asymptomatic phase, various symptoms and diseases may appear, which, however, are not AIDS criteria (WHO stage 2).


Question: How is HIV deciphered?

HIV infection

With a CD4+ lymphocyte count of more than 200 cells per μl, diseases characteristic of the AIDS stage rarely develop [118].


Question: How is HIV deciphered?

HIV infection

The latent period lasts 5-10 years, the characteristic symptoms of this stage are lymphadenopathy (enlarged lymph nodes).


Question: How is HIV deciphered?

HIV infection

The use of HAART makes it possible to extend this stage for decades [19].


Question: How is HIV deciphered?

HIV infection

HIV-infected patients in the latent stage of HIV infection can infect others, even if they use HAART, although treatment significantly reduces the likelihood of infection [19].


Question: How is HIV deciphered?

HIV infection

preAIDS


Question: How is HIV deciphered?

HIV infection

The duration of the stage is 1-2 years, the suppression of cellular immunity begins.


Question: How is HIV deciphered?

HIV infection

Typical diseases are: recurrent herpes (long-term non-healing ulcerations of the oral mucosa, genitals, stomatitis), leukoplakia of the tongue (growth of the papillary layer), mucosal candidiasis mouth and genitals.


Question: How is HIV deciphered?

HIV infection

AIDS


Question: How is HIV deciphered?

HIV infection

AIDS is the terminal (dying) stage of HIV infection.


Question: How is HIV deciphered?

HIV infection

In the absence of treatment, it lasts up to three years, on average 1-2 years.


Question: How is HIV deciphered?

HIV infection

At the AIDS stage, opportunistic infections and tumors are generalized, and in the case of dangerous secondary diseases, life expectancy in the absence of HAART is less than 1 year [19].


Question: How is HIV deciphered?

HIV infection

Typical diseases for this stage are: tuberculosis, salmonellosis and its transition to a generalized form, encephalitis, meningitis, Legionella pneumophila infection, influenza, herpes, cryptosporidiosis, toxoplasmosis, meningoencephalitis, candidiasis, histoplasmosis, cryptococcosis, malignant tumors (Kaposi's sarcoma, lymphomas), pneumocystis pneumonia.