Targeted drug delivery

Chemist Dr. Doping tells about the "magic bullet", the effects of chemotherapy and the drug development process.What are the challenges faced by scientists working on the problem of targeted drug delivery? What are the prospects for the development of medicines? And what will the region develop targeted therapies?

The traditional approach in any chemotherapy, whether chronic or acute disease - is a drug which improves the state of the patient, because it acts on the ailing tissue or organ, or circulate in the bloodstream, is distributed on the human body both in healthy and in the affected tissue. Of course, most drugs have side effects because of the fact that they are in the systemic circulation, that is not much work selectively targeted, as desired.

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One of the trends, emerging today in biomedicine, very best including from chemistry, biology and medicine - is Targeted or targeted delivery of medications, drugs only in the affected organs and tissues. This idea is quite old and first appeared at the Paul Ehrlich, who called it "magic bullet" or "magic bullet" that would hit only those organisms or organs, which need to be cured.

Most pathological tissues in the body, those who are sick, for example, cancer cells differ from healthy cells by the receptors, that they have on the surface, by the way they behave metabolically, ie they are not exactly the same, even at the very beginning disease. If we, from a biological point of view, to know what these cells differ from healthy, and can be chemically synthesized compound, or a certain drug delivery systems are known only in these specific tissues, it would be very good.

FAQ: Targeted Therapies in Oncology

5 facts about the various targeted drugs, types of breast cancer and the future of targeted medicine.

The approach to the cure of such complex diseases like cancer, can now be based on the analysis of the interaction of various proteins and genes that are combined with each other in complex networks. Activation of various proteins belonging to such a network, causes the cell to divide uncontrollably and to metastasize, ie turn from normal to cancerous.

• 1.A variety of anticancer drugs

By the nature of the impact of anti-cancer drugs can be classified into four classes.
First is a monoclonal antibody (maby, monoclonal antibodies), i.e. protein molecules or complexes of protein molecules that are produced by the immune system in response to any antigen-oncogenes. Such monoclonal antibodies bind to and inhibit its oncogenic activity.
A variety of such monoclonal antibodies are the so-called killer monoclonal antibody or killermaby which are complexes of a cytostatic agent that kills the cell, and an antibody having high affinity (affinity) for the antigen.
If monoclonal antibodies are macromolecules, the other class of targeted anticancer drugs - niby or kinase inhibitors - are low molecular weight compounds. As a rule, these compounds reduce the activity of some specific oncogenes that affect the formation of a signal in the cell, causes cells to divide uncontrollably.
A fourth class of targeted therapy in oncology are, conversely, inhibitors and activators, but not tumorigenic and onco-suppressor (suppressor) signaling pathways that cause, for example, necrosis, apoptosis or cell differentiation. These drugs include various stimulants necrosis, apoptosis or differentiation.

• 2.Feature of targeted therapies

All of these drugs are called targeted or targeted because they act selectively on some of the properly expressed, increased expressed or improperly arranged, that is mutated oncogenes.

These drugs are usually prescribed in clinical practice by immunohistochemistry of tumor biopsy. In the immunohistochemical study tumor sample taken from the cancerous tissue and then determined by an appropriate antibody expression level of a key oncogene.

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• 3.Types of Breast Cancer

One of the first and the most expensive of targeted anticancer drugs - Herceptin or Trastuzumab - appeared at the end of the XX century, was produced by Roche and was intended for the treatment of a particular form of breast cancer.

Scientists in the last century have identified two types of hormone-dependent breast cancer: estrogen-dependent and progestero-dependent. The third type, the most malignant, doctors initially designated as "neither one nor the other." Then it turned out that the development of this third type of breast cancer called heregulic responsible or neuregulinic receptor his doctors called HER2 / neu, biologists it is known under the international name of ErbB-2. He is a relative of the receptor of epidermal cell growth factor, but normally it determines the growth of nerve tissue. In HER2-dependent breast cancer is pathologically-expressed, constant signals that causes the cell to divide.

• 4.How the first targeted medication was invented

The first drug Trastuzumab was very expensive and not easy in production is due to the fact that this drug elaborated mouse embryonic cells that had been engineered by genetic engineering so as not to contain antigens for extra person. It was as if artificially humanized, that is the most diverse in the human genes thereof have been removed and replaced by men. In the second week of embryonic development the embryo produced monoclonal antibodies against HER2-dependent breast cancer.

As a result, this technology was very expensive, the drug was worth about as an apartment in Moscow, and efficiency even in the appointment on the testimony, detectable in the immuno-histochemical study was very low, not more than 30%.

• 5.Prospects of Targeted Medicine

Of course, Herceptin, or Trastuzumab, - it is quite an old drug with more than 14 years of history; targeted for modern medicine, it is very solid experience. Today there are more than one hundred targeted agents registered and approved for medical use in different countries. At the stage of pre-clinical and clinical trials are hundreds of new mabs and cheaper than maby, nibs. How do doctors understand such an amount of drugs and to prescribe the most appropriate given the patient?

To help your doctor come to the fundamental biology and bioinformatics.

The system-biological platform was created for the purpose of targeted anticancer drugs by the results of microarray transcriptome studies of all human patient. This method uses the expression levels of the results of the survey of tens of thousands of genes, among which the majority is either onco-genes or onco-supressor. Now we can say that personalized medicine - it's not a dream of philosophers and strict medical, biological and mathematical technology.

Hemostatic system

Biophysicist Dr. Doping tells about mortality from hemorrhage, the role of platelets in the body and the blood coagulation system. How does the system of hemostasis? What are the main features of this system? What is the role played by platelets in the body? How are the main methods of treatment of disorders of the hemostatic system?

If we talk about the different systems of the human body, the hemostasis system, which is responsible to stop bleeding in wounds, hemorrhages and other types of violations of the integrity of the vascular system, is the most problematic in our body. People may have a variety of diseases, but they die more often from disorders of hemostasis.

Our body has several levels of protection against bleeding and haemorrhage. One level - is vascular hemostasis. Muscle contraction in certain situations can lead to a narrowing of blood vessels (vasoconstriction) and slow down or even halt some minor bleeding. The next layer - platelet hemostasis. Special cells are present in our blood - platelets, which stick together in case of damage to the plug and seat damage. Platelet bit them about 10 times smaller than red blood cells, and the size (assuming per volume) are an order of magnitude or two lower. So apparently it seems that platelets are not very many. Nevertheless, they are vital to stop the bleeding. The third level - the blood clotting system - artful cascade of reactions in the blood plasma, which is completed by the fact that a specialized protein fibrin begins to polymerize and make three-dimensional grid. Such a three-dimensional network at the micro level can hold within themselves the amount of water that is a thousand times superior to its weight.

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Given how difficult it is arranged hemostasis system, in a sense, it is not surprising that we have problems with the diagnosis of its disorders and their adequate treatment. What people do during the XX century, to a great extent it was the result of empiric selection of therapy methods or diagnostic methods of the invention.

Methods for diagnosing disorders of the hemostatic system

Biophysicist Dr. Doping told about innovations in medicine, there is a test on blood clotting and identifying thrombosis risk. Why are existing methods of diagnostics of blood clotting problems do not meet the researchers? As a developing understanding of the hemostatic system? And what are today developed diagnostic methods for hemostatic disorders?

In the field of medicine that deals with the state of human coagulation or hemostasis system, all complex systems involved in stopping the bleeding, now there is a huge dissatisfaction with the state of affairs in the first diagnosis. Doctors all over the world say directly that the current state of research methods clotting extremely unsatisfactory. The man at the fence blood can clot directly in a syringe needle, but diagnostic tests show that he's all right. A person may have severe bleeding, and diagnostic tests can not detect.

At the end of the 80s picture of the hemostatic system works more or less developed, and it became clear that the existing tests work very badly. On the one hand, people have tried to get around this by complicating the test, that is, they are gradually supplemented kakimi-to modifications, variants, other types of tests, has not yet appeared what is now called coagulogram - more or less well-established set of dozens of tests, which will allow very experienced doctor to give an idea of how the hemostatic system. Unfortunately, there are things that coagulation, in principle, does not see and can not see, such as an increased tendency to thrombosis. The risk of thrombosis, which is one of the deadly threats to human coagulation hardly sees.

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The fact that the process of hemostasis - essentially spatial process. If you have an injury, you will need to make a "cap" at the injury site, in any case, not more. If you do it on, break the blood supply to any organ. It is impossible to mimic in vitro, where there is complete mixing, you need a spatially inhomogeneous system. It has been developed - initially for basic research, and then to the application - such a system, in which the activation of the coagulation process occurs locally nano to tissue factor. It spreads out the coagulation process plasma in the space. After several years of searching for the people who would be able to support this system, we have managed to get support from the "Rosnano" and start a company "GemaKor", which was engaged in the commercialization of the system. Now this test is available at leading hematology and cardiovascular clinics in Russia.

Blood test

Cardiologist Dr. Doping says about of leukocyte types, variations in standards and functions of post-cellular elements. Along with cardiologist Dr. Doping we tell what elements is the blood and how to understand its analysis. Do not forget that the rules of almost all blood values are very dependent on age and sex.

Hemoglobin and red blood cells

Hemoglobin is a protein that carries oxygen. It is within the erythrocytes. The more hemoglobin, more oxygen may move the blood. The fall in hemoglobin or red blood cells is below a certain value, the order of 110-120 g / l, called anemia. The rate of red blood cells for men - 130,0-160,0 g / l, and for women - 120,0-140,0 g / l. Red blood cells - it is the red blood cells that are biconcave discs. They carry oxygen due to the presence of hemoglobin. Red blood cells lack nuclei, that is, they are from a scientific point of view, not cells, and so-called post-cellularelements. The lifetime of a red blood cell is about 3-4 months. Increasing the number of red blood cells seen in people who live in the mountains, as well as those who suffer from a specific type of blood disease, so-called erythrocytosis, and those who take a drug in the form of the hormone erythropoietin, which accelerates the formation of red blood cells. The rate of red blood cells in men - 4,0-5,0 × 1012 / L, and for women - 3,9-4,7 × 1012 / L.

The color indicator and the average content of hemoglobin

Indicators of hemoglobin inside the red blood cell, color index and the average concentration reflect how many of the key oxygen-carrying protein, is within the red blood cell. You have to understand that the key point, which reduces hemoglobin or drops of color indicator - is iron deficiency. The color indicator is calculated as 3 × Hb in g / l / three older red blood cell count category (in millions). Iron is a key part of the hemoglobin which carries oxygen inside the so-called heme. When a small shortage of erythrocytes iron produced at the same rate as before, but they contain less hemoglobin. First with a small iron deficiency begins to decrease just the volume of red blood cells and hemoglobin inside them. And only with an increase in iron deficiency, when it gets critical, already begins to decrease and the number of red blood cells. In other types of anemia, when a person lacking folic acid or vitamin B12, erythrocyte volume, in contrast, increases. The rate of color indicators - 0.85-1.05 and the average content of hemoglobin in a red blood cell - 30-35 m.

Hematocrit

Hematocrit is a total content of cellular elements in the blood volume unit. Basically hematocrit forms most of red blood cells. The percentage of cells other than erythrocytes with very little. And as hematocrit correlated with the number of red blood cells, it decreases in anemia and iron deficiency. The rate of hematocrit: men - 40-48%, women - 36-42%.

Reticulocytes

Reticulocytes are a form of immature red blood cells. They are not included in conventional analysis. Usually they say that if a person has anemia and needs to know what it is connected. That is, with anemia associated with iron deficiency reticulocyte levels may even be slightly increased. The same occurs when blood loss when you need to activate the formation of red blood cells. And with anemia associated with a deficiency of vitamin B12 and folic acid, the number of reticulocytes decreases, since due to the lack of these vitamins can not effectively share cells - red blood cell progenitors. The rate of reticulocytes - 5-12%.

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Platelets

Platelets are devoid post-cellular core elements that are involved in blood clotting. This is a very, very small plates, which closes up vessels when they are damaged. Decrease platelets observed in various serious diseases, including cancer. Drop them below 100 × 109 is fraught with heavy bleeding. In addition, at the wrong fence blood platelets form clots, it is their aggregation. Therefore, they can often be conditions such as pseudo-thrombocytopenia when an automatic blood analyzer shows a reduced number of platelets in their normal amount. And healthy people with a lack of platelets need to be sure to count the number of platelets "by hand". The increase in the number of platelets is also the companion of a variety of pathological conditions, and it should be interpreted only in terms of the overall clinical picture. The rate of platelet - 180,0-320,0 × 109 / L.

White blood cells

Leukocytes are white blood cells, are our main defense against infectious diseases caused by bacteria, as well as become the path of cancerous degeneration of the body's own cells. The number of leukocytes is increased by a variety of inflammatory diseases and infections, for exhaustion and decreased. Normal - 4-9 × 109 / L.

Leukocytes are divided into neutrophils, eosinophils, basophils, lymphocytes, depending on the color. Neutrophils - this is the largest part of the white blood cells, the cells that fight first of all bacterial infections. We can say that this kind of regular army. These include several groups of elements. Myelocytes - a form which is typically present in bone marrow. Their presence, and still less mature blast cells in the blood test could indicate a very serious blood disease - leukemia. Metamyelocytes - "young" form appear in the case of severe infections, and it is extremely rare, when you need to release more immature forms. Immature forms into the blood when the big defenders, segmented neutrophils, is not enough.

There is a division of neutrophils in the degree of maturity: a form of neutrophil nuclei depends on the age, and by evaluating the shape of the nucleus, we estimate the age of the neutrophil. Band neutrophils are present in normal healthy people. This form is characterized by a more youthful cells. The rate of band - 1-6%. Segmented - mature segmented neutrophils typically predominate in the blood test. The rate - 47-72%.

Eosinophils - are cells that are involved in a variety of allergic reactions. In addition, they help us to deal with parasites, such as roundworms, with worms. Increasing the number of eosinophils observed in the various allergies. The marked increase in the number of eosinophils, ie above 20%, may be indicative of a very serious rheumatological (inflammatory) disease. In the absence of eosinophils and basophils can suspect the presence of severe blood disorders. When the number of other forms of leukocyte can be suspected leukemia. For them, the rate - 0.5-5%. Basophils also participate in allergic reactions. The increase in their number is marked at different allergies and some rare diseases. Norm of basophils - 0-1%.

Lymphocytes are cells of the immune system. There are many subtypes of lymphocytes, each of which performs a specific function. These cells help recognize antigens, ie determine which specific type of pathogen causes inflammation to develop weapons is against this pathogen. Guns are antibodies - large molecules that bind to specific sites on the surface of the pathogen. They are produced by B-lymphocytes. A T-lymphocytes recognize the foreign agent help and are involved in various immune processes. In addition, T-cells protect us from cancer. Reducing the amount of exhaustion observed when lymphocytes and increase - in various infections. The slight increase in the number of lymphocytes is observed after a recent infection. The marked increase in the number of lymphocytes, particularly T-lymphocytes, may be indicative of lymphoma, that is, on hematological malignancies, which are often incorrectly referred to as cancer of the blood. Average number of lymphocytes - 19-37%.

Monocytes - is one leukocyte subtype. In contrast, lymphocytes which are dotted and are set to destroy specific pathogens, monocytes are able to fight directly against a very wide range of different pathogens. They are converted into the tissue and to larger cells (macrophages) with a large number of processes. Macrophage phagocytosis is performed, that is eaten by bacteria and other microorganisms. Then they were dissolved and destroy them using different intracellular enzyme systems. Furthermore, they are also separated into individual microorganisms present their types and their lymphocytes to recognize those portions of microorganisms against which antibodies could be synthesized. Increasing the number of monocytes it is most often noted for infections, including tuberculosis. But a small increase in their number is often associated with the error of the method: not all automatic analyzers correctly determine their number. Norm of monocytes - 3-11%.

Plasma cells - this is one of the subtypes of lymphocytes, which is formed in the presence of a bacterial infection. Most of these cells are involved in the synthesis of antibodies, however, they may occur in people with bacterial infections, increases sharply when the number of cells which synthesize antibody. While there is no infection, these cells do not need, so they are not.

Speed (reaction) erythrocyte sedimentation rate is estimated as follows: choose a thin capillaries and estimated that the rate at which red blood cells settle. erythrocyte sedimentation rate depends on the composition of the blood plasma protein. Increased ESR observed in various inflammatory diseases and cancer. Women may be more speed - most likely, this is due to the peculiarities of the protein composition of blood plasma and red blood cells. Norm: men - 2-10 mm / hour, women - 2-15 mm / hour.

The morphology of the red blood cells, ie, their shape changes when a large number of various anemias. Morphology of white blood cells varies in the presence of severe infections. Indicators morphology of leukocytes is important to evaluate manually. Not all analyzers successfully evaluate the presence of atypical pathological granularity of leukocytes.

FAQ: Molecular modeling for drugs

6 facts about cell mutations, targeted therapies and approaches to cancer treatment

Cancer is known to mankind for a long time. It is a disease in which the treatment throughout the history of mankind is practically unable to achieve any success. With the advent of antibiotics people almost forget the terrible infections from plague and ending with syphilis. However, as the world population ages, the probability for each of us to meet growing cancer in life. Unfortunately, despite the hundreds of billions of dollars that have been spent in the developed world since the late '80s, and decades of research, we do not see a significant breakthrough in the treatment of cancer. The increase in life expectancy of cancer patients was not due to the fact that there were revolutionary therapies for the last 20-30 years, but mainly because the cancer began to be diagnosed at an earlier stage. The problem is that the medicine can diagnose the disease at a phase where no treatment after a year in the number of cancer cells will be such that the weight or volume of the tumor will be measured already hundreds grams.

• 1.Genetic Background

The human body, like any animal organism comprises genes in its genome, which are used for cancer of the development. At first glance, this seems illogical. In order to grow from a single cell and become a human being, you must use the mechanisms that are at a mature age are dangerous or unnecessary. In particular, in order to prevent rejection of the fetus in the mother, the embryo cells learn to deceive her immune system, posing as "their own", and thus prevent the mother's immune system to destroy the embryo. This explains a lot of pathologies. This favorable evolution of the acquisition, but the same genes being activated in adulthood, can help a cancer cell to trick the immune system and prevent the destruction of cancer cells. To protect heart cells doctors use Meldonium for sale.

• 2.Age-related causes of cancer

In fact, the body of each adult healthy person - millions of cancer cells that are in balance with the body, and continuously determined cells of the immune system are destroyed. However, with age, the number of possible errors in the execution of the genetic program begins to grow, and at some point the amount of stress is greater than the possibility of damage control systems. At this point, the cancer cells are knocked loose. The danger lies in the fact that all signs are cells of the same organism. At first, they have almost the same genetic code as all other human cells, and it does not allow the protective systems to quickly identify them.

• 3.Mutation of cancer cells

Cancer cells begin to rapidly mutate, and new copies of the genome fight against the body's defense systems. New forms of these cells, which are absolutely not similar to the original cell or any other cells to the patient. Studies show that cancer swollen the same patient is not one type of cancer, and many species. In fact, it is not about how to deal with any one disease, but to fight with different, quite unlike forms of the disease. In this sense, there is no one disease - cancer. There are many different forms of cancer, and even in the case of each patient simultaneously realized very many different forms of cancer. It is for this reason that effective cancer control devices, except for surgery and very aggressive forms of chemotherapy or radiation therapy, has been invented.

• 4.Disadvantages of anti-cancer therapies

Another complicating factor is that the immune system is a major defense against human cancer. Cells of the immune system and tumor cells divide rapidly, and most of the therapies aimed at the destruction of rapidly dividing cells, at the same time lead to the destruction or suppression of immune functions. Thus, many treatment leads to the fact that the body gets strong toxicological damage and simultaneously suppressed immunity. We are talking about the fact that a lot of money in a very expensive hospital during the life of the patient increases less than a year.

• 5.Possibilities of targeted therapies

In this regard, the question arises: where to find a reason for the hope that cancer will ever be healed? Rapid progress can not be expected, but recent studies provide some hope. We must look for ways to distinguish between cancer cells and healthy people and come up with Targeted, specific therapies that allow the immune system to either recognize or specifically destroy those cells that are not strongly resemble the cells of healthy tissue.
In this way, in recent years there has been considerable progress. In particular, certain types of cancer could develop targeted agents, which allow to operate against a very specific genes activated only in cancer cells. Thus, in recent years has made significant strides in pediatric oncology, where the percentage of surviving patients was significantly increased. Also it managed to get a great response ( "response of patients") in some forms of cancer, such as breast cancer. specific markers have been developed, which allowed to identify the patient population for which certain specific tools would be useful, and get a very high percentage of cure in specific categories, even for small groups of patients.

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This approach has some advantages, but has some drawbacks. In order to apply a tablet or therapy genotyped individuals have first, and then determine that, for example, only 2% of the 100% of people will be able to respond to this therapy. It is extremely difficult clinical research in oncology. If only a percentage or a few percent of the entire population of patients respond to this drug, the pharmaceutical companies largely disappears the reason for which they are developing these drugs. After all, if the number of patients will be measured in tens or hundreds of thousands, this drug will receive the status of "Orphan Drug» (orphan drug), only work for a very small group of patients, which is unlikely to be able to create effective demand, in order to recoup the research.

Currently, biotechnology will likely move in the direction of the search universal mechanism that will effectively inhibit cancers using these or other unique arrangements. As the embryo is cheating mother's immune system in order to stay alive and cancer cells using this mechanism to control immunity. The destruction of this mechanism will not bring any damage to healthy cells, but is likely to help immunity or some means of immune therapy to cope with cancer. In 2013, in the second phase for the first time showed the success of GSK drug companies, which managed to get the immune-boosting drugs, raised its forecast for the survival of patients in combination with different forms of therapy or independently.

• 6.Glycolysis as an energy source

It is known that cancer cells use an entirely different way of breathing. When the immune system is trying to kill a particular cell of the organism, cell death occurs through the destruction of the mitochondria - a special organelle of the cell, which is responsible for energy production. Those cancer cells that were able to shut down the mitochondria, or get rid of it, obviously, can not be killed in this way, so after a few weeks or months after the onset of a cancerous disease in humans, almost all cancer cells breathe without mitochondria, using a completely different mechanism for energy It called "glycolysis". Glycolysis is ineffective, so it does not use the normal cells. Drugs that would cut out glycolysis, would be able to leave the cancer cells are starved and kill them either alone or in combination with other drugs. It is in this way recently in preclinical and early phase clinical trials, progress has been made with the drugs that control various forms of cancer metabolism.
So far there is no evidence other than animal testing, that this approach or an approach that is associated with immune therapy, will allow us to ever talk about the possibility of treatment of cancer patients. However, the fact that the attempts of the past dozen years to develop a drug to target a narrow group of people against specific markers the researchers once again start to move towards a universal anti-cancer drugs with a wide effect, allows us to hope that sooner or later the disease will be controlled.

FAQ: Molecular modeling for drugs

7 facts about the creation of drugs with the help of computer technology.

Drug development - is an expensive and risky process. Consulting companies estimate that for the successful development of the drug you need to spend a billion dollars, and it usually takes more than 10 years. The worst thing is that because of the increasing security requirements for more and more drugs that are already spent hundreds of millions of dollars and years of work, can not pass clinical trials. The number of failures in the registration of medicines. This means that if it goes on, then very soon You can not find people who agree to finance this process because of the high risks.

• 1.Moreover, diseases confronting medicine become complicated. Simple disease cured, increasingly difficult to find some one cause of the disease (such as a bacterium or virus). In this way, it is impossible, for example, still can not be cured Alzheimer's disease or diabetes. Often extremely expensive therapy is not able to defeat the deadly disease and only slightly prolong the patient's life (more than half of the cost of treatment can occur in the last year of life of the patient). Worse, all people are genetically different, and each person has cancer or diabetes, your. Per patient within one puncture liver cancer can provide four or more types of cancer cells. This means that while the number of diseases that we must learn to treat, is constantly growing, the price tag in the hundreds of millions of dollars and huge risks limit the desire of people to do it. If not there will be any breakthrough technologies that will significantly accelerate the development process and reduce the cost of an increasing number of more specific and safe drugs, possibly after 100 years, we will live as much as we live today. In principle, this is not such a big problem, because in the past hundred years, the maximum life span is practically not changed. We are lucky that we live in a time when the life of the average duration has increased rapidly in a short time, mainly due to the increase in sanitation standards and the emergence of effective antibiotics. But the breakthrough technologies appear, and the key here - the use of advanced computational tools, artificial intelligence.
• 2.Biology - a very capacious science of facts, most of which, unfortunately, are random. To the question "Why?" One answer: "It happened. Evolutionary. Because it's been such a very complex trajectory of the genes in the ancestor of man. " For successful treatment of diseases you want to associate a lot of facts, but these facts are many random connections that are extremely difficult to analyze. There is no logic, a single creator or a single scheme, for which all this would be organized. Therefore, for the analysis of genetic networks and signaling pathways that lead to the development of certain diseases simply necessary to use powerful computing resources.
• 3.Computers make it possible to analyze the signaling pathways and study how genes affect one other. Since nature based on the principle of maximum survival i.e. maximum stability, many genes delegated connection between a so-called master control genes that are simultaneously connected with a large number of genes. Identify the master controls, which are activated by diseases and are not active in a normal state, and there is the problem of determining targets for medical intervention. It uses a variety of methods. This is mainly genomics; Now there transcriptomics, ie followed by genome sequencing studies of gene expression and metabolite levels in cells.
  
  Thus, there is a way to study the tens and perhaps in the near future, and hundreds of thousands of parameters of each cell. Are revealed subtle differences of gene expression, and most importantly, it turns out, some of the genes being expressed at the wrong time, give rise to changes in healthy cells to the patient. They have a chance to become those targets for which the pharmaceutical industry is to develop medications that really will benefit from this or that disease. For example, Meldonium is very good for heart protect.
• 4.Until now, much of the drug was found, oddly enough, by trial and error, even if it was a question about the industry. The method of the so-called high-throughput screening tested dozens, hundreds, sometimes under a million substances in certain cellular models of various diseases from which tens and hundreds of advanced further as potential drugs. Unfortunately, in recent years, large companies have spent millions of dollars to screen hundreds of thousands of compounds against certain pathologies, where none of these agents has not produced a worthy candidate. Computer molecular modeling method allows you to simultaneously explore the tens of millions of molecules for their binding to a particular target. Since these molecules are generated against a particular target, which should not be a healthy person, it appears less likely that such a molecule would be toxic and will not pass the next stages of preclinical and clinical studies.
• 5.Thus, the creation of such technologies is not just faster and cheaper research and conception allows, in principle, to find anything from the most important diseases. In this way, for example, recently we have been obtained from a molecule of viral hepatitis. This summer they have been approved in the United States, and hence in the world. For the first time in human history, hepatitis C has become, if not curable, the disease controlled. For a certain type of breast cancer appeared very effective, so-called targeted therapies, which significantly increased the survival prognosis of patients.
  
  We are at the beginning of this process. Computers for the development of drugs have been used 15 years ago, but about the last 5 years, we finally see examples where it was really prepared.
• 6.Is it possible to apply molecular modeling in some other area? Of course you can. In addition to the search for new drugs, the people are the problem of creating new materials: polymers, materials for energy or photonics, etc. Everywhere, where you need to come up with a molecule which have not yet been in the nature, need good methods of molecular modeling. Biology is probably one of the polygons, where now these methods are practiced to the stage where we can first for any biological molecule found an artificial molecule which it regulates, and in the future will be able to create new crystals, semiconductors, materials with unique properties, which in nature it has never been. For example, quantum computers, which are believed by many to require the creation of fundamentally new materials whose properties can only now imagine. To improve brain functionality – buy Phenotropil.
• 7.Pharmaceuticals is one of the most advanced areas of business. This business will obviously use any opportunities that arise, including the possibility of molecular modeling. International pharmaceutical and biotechnology companies are very receptive to any new technology, they constantly try them. I am convinced that only thanks to the emergence of these technologies, we will see new medicines that would cost probably is not the money that is now to be a real help to patients, even if it will be necessary to make a drug that takes only a hundred patients planet. Now this question is not even worth it: because of the cost and risk of any one company will not make a drug that will require ten thousand people. But in the future personalized medicine will be able to diagnose, develop and apply therapies that would make sense for small groups in all, maybe even just for one patient!

Alternative antimicrobials

The biologist Dr. Doping talks about security levels of bacteria, E. coli and potential antibiotics. What is the role of microorganisms in environmental antibiotics? What do the microbes produced bacteriocins? And is it possible introduction of alternative antimicrobial agents in medical practice?

Antibiotics - it is a kind of "marking territory", that is, is that the microorganism produces (scientifically speaking - secreted) into the environment, and that not even such a killing, how much deters foreign body. Both concentrations of antibiotics that are commonly used in medicine, by orders of magnitude higher than that amount in which they exist in nature. This is precisely the root of the fact that when the microbes live permanently under this pressure, they naturally try to adapt quickly.

Over the last 20-25 years there has been a very serious breakthrough in biotechnology that can be produced in very large quantities of proteins of very different nature, with any changes that people want, that is, to introduce some mutations that allow this protein to acquire any necessary properties . Assume infra-red tag to the protein to sew that it will be possible to observe the motion of the protein molecule in the body, that is, under the infrared laser beam to a depth of up to a few centimeters inside the human body can be observed some fluorescence can be understood, where moving the molecule, then have thus control the pharmacokinetics - which moves the medication the way it exists in the human, for example, the bloodstream.

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The potential is there, and conventional antibiotics, again from that modern combinatorial organic chemistry is highly developed, that is, now it is possible to calculate the computer, computer to simulate what we want - this, however, is that more used to some medicines from the field of immunological or antiviral - I, frankly, have not heard about antibiotic developed in this way, but, nevertheless, it is possible. Antimicrobial peptides have certain common properties, ie, they can be again changed at the behest or on the calculation of scientists, respectively, in order to make them more stable, better able to penetrate into the enemy microbe specialized in relation to some one microbes, or, on the contrary, a common action - that is, there are very broad prospects.

FAQ: Antibiotics and colds among children

7 facts about the stability of bacterial flora

Antibiotics were discovered almost 80 years ago and has since been a great help mankind to fight bacterial diseases. But they only help against diseases caused by bacteria, which they inhibit. And other bacteria to use them is useless, useless, and especially their use in viral infections.

• 1.Antibiotics are threatening respiratory diseases, where a large part of humanity consumes a huge amount of antibiotics completely in vain. 93% - 95% of all colds are caused by viruses. Thus, cold - viral disease, particularly in children. Here are facing two trends. On the one hand, the creation of new antibiotics that act on bacteria still larger circle. And the massive use of antibiotics for colds, ie, viral diseases. It would seem that antibiotics are not very toxic substance: they cause, of course, side effects, but not much, and not what it is. The fact that by using antibiotics, we accustom microbial effect transfer antibiotic resistance we create bacterial flora which in us.
• 2.In humans, the bacterial cells are much more than human, so anyone who has a parasite, it is very difficult to say. These microbes perform certain useful function. For example, in the nose are found Streptococcus pneumoniae and Haemophilus influenzae, and while they're found, Staphylococcus aureus on the nostrils can not penetrate. You take away the antibiotic Streptococcus pneumoniae and Haemophilus influenzae, Staphylococcus and get to where they do not need to get and develop resistance. But pneumococci develop resistance, and Haemophilus influenzae develops resistance to a growing number of antibiotics - and in the end we have a man, stuffed resistant to this antibiotic or different microbes.
• 3.Resistant germs him until a certain time, do not harm, but when the OIG did not get where you want, for example, to the lungs, into the cavity of the middle ear, to fight will be very hard with them. But not only his own. Around him, people walk, they get it as a stable flora. For example, in Russia Streptococcus pneumoniae - the main respiratory pathogen that we do not like, acquired resistance to penicillin and other antibiotics about 10% of cases - it's not much, but every 10 patients with pneumonia we can not get a fast effect of the treatment. And in France, until recently, it was 40% resistant pneumococcus - apparently, there ate spoonfuls of antibiotics. Who resistant pneumococci was lower. Much higher resistance in infants two - four years: 20% -25%. What's the deal here? Just in children, very dense population of pneumococcus, children still do not have antibodies to it, and in that dense populations easier to form a clone resistant microbes. And if you go to kindergarten, there will be a 50% -60% of pneumococci resistant. And if you come to the orphanage in residential institutions - where up to 80% -90% is sustainable. And this is our handmade work. We are doing everything to ensure that antibiotics had no effect. And it's not just a theory, we constantly meet with antibiotic-resistant forms, and now they are observed more and more frequently.
• 4.Among the population, such as macrolides (it erythromycin, azithromycin), stability is not the greatest, 8%, and if we look at the clinic of children who are sick - they have 30%. And we get sick with pneumonia, which was treated early elementary macrolides, and now is not treated. Otitis media, which too had been treated with these drugs, it is not treated, it is necessary to appoint other drugs. What does it mean? This means we have a very high frequency of resistant flora. It would seem, let's let the other antibiotics that act on a stable and flora. Producing, creating new antibiotics, but in recent years began to create new antibiotics is very, very little. We have over 12 years of this century have received two or three new antibiotic is not very safe, deliciously expensive and with the recommendation to use them rarely, as little as possible, including not to create resistance to these drugs. Powerful new drugs used in hospitals, and we now have a huge amount is not pneumococci, and the more "serious" germs: stafilokkov, Klebsiella, Enterococcus, Pseudomonas aeruginosa, and others that are resistant to new antibiotics.. This is a very big problem, which starts with an innocent colds.
• 5.You ask. "Well, if not antibiotics, than to treat a cold?". There are very good people's observation that if treat a cold, it lasts for one week, and if not treated, seven days. This observation is very correct. Why do children often suffer from viral infections? Because they do not have antibodies to the virus. Vaccines against these viruses yet, except for influenza, but it secure and protected at 85%, for some reason, people really do not love and fear, although we still have not seen any flu vaccinated child. Do not vaccinated - much as you want and vaccinated does not happen, and if it happens, it is probably so light that we do not see it.
• 6.Viruses - activators of respiratory infections very much. So far they have not been ill child, he will not get the antibodies to these viruses. Therefore, whether we like or do not like a child from zero to school sick at least fifty times with viral infections. And if you count the smallest episodes, we get a hundred times. And nothing happens to children if they are not treated with antibiotics. Complex nasal spray IRS 19- helps recover 2 times faster , nasal spray IRS 19 reduces the risk of acute respiratory infections during epidemics. Buy IRS-19.
  Than to treat viral infection in a child? - First of all, it is necessary to drink enough, with an increase in body temperature it loses water through sweat. If it is sufficiently hydrated, he is not afraid of a viral infection symptoms - cough, runny nose - at all enough water in his body. Second - if the baby rolls over temperature of 39.0 - 39.5, should be given an antipyretic. If less, no need to make, because the temperature helps to combat viruses. Finally, pharmacies sold an infinite number of remedies for flu, cough, from everything. If you like, you can use them, and can not be used, too, nothing of that happens.
• 7.And to the question of why science is stalled with antibiotics - is that few new ideas in the development of antibiotics. Original antibiotics were created from the waste products of various fungal mold growth, new approaches to the development of antibiotics sold slowly. But it is also important to understand why people use antibiotics where it is not necessary? This question belongs to the science of psychology to mass psychology, the development of mass psychosis and habits. I wish that those scientists who are engaged in our consciousness, would find ways to influence this behavior in order to save antibiotics for future generations.

Antibiotics

The biologist Dr. Doping about the history of the discovery of substance, antibiotic resistance, and the end of medicine. What is the history of the discovery of antibiotics? Why antibiotics are no longer effective? And what are the different methods of combating microorganisms resistant to antibiotics?

In 1928, English scientist Alexander Fleming forgot cup inoculated culture is moldy, and found Penicillium mold fungi secrete a substance, destructive bacteria. On this basis and based search for antibiotics, which will operate the most detrimental to certain microorganisms, especially pathogens. Antibiotics in the modern sense - it is a small-molecule biological standards that distinguish different organisms. This was first discovered by the example of molds, later it revealed that antibiotics are selected and fungi and other bacteria, and plants and animals. It is semi-prophylactic measure that organisms use to conquer a niche in the environmental community, and scare off their opponents.

For prophylactic heart disease use Meldonium, and to improve brain work Noopept and Phenotropil, Cerebrolisine.

Concept antibiotics ruined no medical use, and the fact that synthesize them become cheap and they began to actively use in agriculture. Antibiotics are used for disease prevention, pollination stalls, chicken houses, it all fell into the water and soil, it turned out that to adapt to the constant presence of antibiotics are not only bacteria, against which they are used in medicine, but also completely harmless microbes that live in environment. They are opportunistic. Suppose for a healthy person these organisms do not pose any particular risk, but by interacting with the body, which has weakened the immune system in hospitals, maternity hospitals, nursing homes, burn centers, they grow with terrible force.

Features antibiotics are far from exhausted. Under the current system of certification of the drug, which takes many years and costs hundreds of millions of dollars, is on the shoulder only to large companies, and, of course, companies are counting on those medicines which will have stable sales. In recent decades, the pharmacological industry is increasingly focused on stabilization of chronic diseases. For example, drugs against blood pressure or nerve disorders, there are more than tuberculosis, but tuberculosis - a much more serious and widespread social phenomenon, but it is a disease of the poor.