According to a clinical study published in "Journal of the American Medical Association", drugs that are not inhibitors of a tumor necrosis factor (FNF) are more effective tool For the treatment of patients with rheumatoid arthritis, which do not react to anti-FNF drugs.

Anti-FNF drugs are used worldwide for treatment rheumatoid arthritis. They deactivate FNO - molecules produced by the immune system and causing inflammation. However, about a third of patients do not respond to this type of therapy.

The study was attended by 300 patients with rheumatoid arthritis, which had an insufficient response to anti-FNF drugs.

All participants were divided into two groups. In the first group, patients for 52 weeks have taken such anti-FNF drugs such as adalemab, etanecept, churnellizumab and infliximab. In the second group, patients accepted such non-FNF drugs as Tocilizumab, Rituximab and Abatasept.

The results of the study showed that 54% of patients who took anti-FNF drugs, and 69% of the participants who took non-FNF drugs were observed a moderate reaction to treatment.

In addition, more patients who have taken non-FLN drugs were recorded low level The activity of the disease on the 24th and 52 weeks of the study.

Researchers came to the conclusion that patients with rheumatoid arthritis, which did not respond to anti-FNF drugs, can benefit from non-FNF drugs.

• Medtorque released a new Tri-Gear rattling for spinal surgery
• Peripheral nerves can be restored by protein
• The new type of disease can seriously limit the mobility of the back.
• Probiotics help to recover after a spinal cord injury
• How do traditional rods affect the risk of complications in patients with early scoliosis?

head medical Center Dr. Zinchuk

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Preparations for the treatment of polyarthritis: drug overview

Polyarthritis is a type of arthritis, in which not one amazed, but at once a few joints. With this state, the diagnosis is extremely difficult, no less problematic and the treatment of an already diagnosed disease.

This is due to the fact that symptoms typical for polyarthritis, inherent in many other articular diseases. Therefore, often doctors are mistaken when diagnosing.

Symptoms characteristic of polyarthritis

For arthritis of any origin, a large number of common symptoms are characterized. The main are:

• Holy feelings in articulations.
• Deformation of the joints.
• Violation of their mobility.
• Temperature jumps.
• Punching at the place of defeat.
• Changing the color of the okolossertic skin.

The pain in arthritis can be of different intensity and character. It can almost disappear, then suddenly becomes unbearable. The strongest painfulness Patients usually experience at night and in the morning.

The limitation of mobility in the joints may be a consequence of painful pains (the patient is once again afraid to move the limb or fingers) or degeneration changes in the articular tissues.

With minor lesions of the cartilage, the patient remains able-bodied, mobility is limited only slightly. With severe polyarthritis forms, the functionality of the affected limb may be completely lost, and the person becomes disabled.

Acute inflammatory processes (reactive arthritis) are treatable. Chronic diseases (rheumatoid polyarthritis) remain with the patient until the end of life.

Causes of polyarthritis

The main causes of the polyarthritis are several:

1. violation exchange processes in organism;
2. infectious diseases, such as viral hepatitis, dysentery, gonorrhea;
3. various injuries of the joints;
4. the presence in the organism of autoimmune and allergic processes.

The structure of the synovial shell includes many blood vessels and the nerve endings that are internal and on the outer stimuli are instantly reacting with inflammation.

If infection is penetrated into the joint through blood, the patient may develop heavy purulent inflammation of the joints - pathology provoked by waste of vital activity of various microorganisms.

Some forms of polyarthritis arise as a result of deposits in the tissues of the joints of the salts traumuating the articular shell. The crystallization of salts is a consequence of the adverse effects of the environment, a failure in the immune system of the body, genetic predisposition. A vivid example of such a disease is a gap on the legs, especially its severe form when not one joint is affected, but several.

Diagnosis and treatment of this disease is difficult by its nature. Gout may be provoked by several factors, and its symptoms may be evidence of the development of other, no less serious diseases in the body of the patient's body.

Unfortunately, people suffer from polyarthritis, regardless of age and gender.

Treatment of polyarthritis

The treatment of polyarthritis is based on the appointment of medicines of symptomatic impact. In this regard, non-steroidal anti-inflammatory drugs are ideal. Such a medicine from polyarthritis exists in different forms (Tablets, solutions for injection, linimens, powders).

Non-steroidal anti-inflammatory drugs directly affect the focus of inflammation. This effect is due to the inhibiting prostaglandins (substances provoking inflammation). No less efficient NSAIDs are removed and painful syndrome.

The advantage of NSAIDs is that they act quickly and gently. Nonteroid group preparations cause fewer side manifestationsrather than other stronger, but very toxic medicines, which are also prescribed at a polyarthritis.

Here is a small list of these medicines:

• ROXICS.
• Brufen.
• Ortofen.
• Flugalin.

However, the NSAIDs have significant side effects that need to be taken into account when appointing treatment. The drugs of the nesteroid group are contraindicated in numerous diseases of the gastrointestinal tract, for example, with a stomach or duodenal ulcer.

The treatment of polyarthritis involves the appointment of corticosteroid drugs, which by suppressing the body's immune response, the inflammatory process is removed. Such an action makes corticosteroids are indispensable in the treatment of arthritis of autoimmune nature caused by, for example, systemic lupus. If this diagnosis is confirmed, the drugs of the corticosteroid group are discharged first.

To prevent the development of steroid-induced osteoporosis, doctors recommend that their patients take bisphosphonates. These drugs are excellent prevention with loss of bone mass.

In addition to corticosteroids and NSAIDs, the BPRP is prescribed at a polyarthritis (basic anthermatic drugs). With the help of these medicines it is possible to define the course of many pathologies provoking the occurrence of polyarthritis.

As a rule, the BPRP is prescribed in a complex with NSAIDs and corticosteroids. This is due to the fact that the action of the BPRP begins to be felt only two months after the treatment has begun, although the therapeutic mechanism of these drugs is also based on the suppression of the body's immune response, as in the case of corticosteroids.

The treatment of polyarthritis does not do without medicine methotrexate. This drug has found widespread use in conducting chemotherapeutic procedures in patients with cancer. However, for the treatment of articular diseases, a significantly lower dose is required.

Unfortunately, the methotrexate has a serious side effect in the form of a liver disorder, so patients need to regularly donate blood for analysis.

Patients suffering from polyarthritis are prescribed other BPRP: sulfasalazine and hydroxychlorookhin. Both of these drugs are antimalarial means, but effective in arthritis. Medicines can cause side effects from the authorities of vision, although such a phenomenon is extremely rare.

Dead fabrics with polyarthritis provoke the development of different inflammation. In such situations, the doctors appoint their anti-FNF patients. These are medicines that destroy the tumor necrosis factor.

Here is a small list of the most sought-after anti-FLN:

1. Infliximab.
2. Adalimumab.
3. Etnenercept.

Anti-FNF drugs are introduced subcutaneously or intravenously.

Anti-FNF is also not completely harmless. Weather treatment can provoke chills, heat, dizziness and headache, pain in muscles and joints, increased susceptibility to infections.

Non-media therapy

Treatment of polyarthritis folk remedies permissible, but it must be coordinated with a rheumatologist. Such precaution is due to the fact that many folk recipes Cause a number of side manifestations that are capable of rooting the situation.

Further, physiotherapy plays a latter role in the treatment of multiple joint disease. With the help of physiotherapy patient procedures, you can get rid of pain, swelling and tumor. These activities include:

• Paraffin treatment.
• Ultrasonic waves.
• Ozokeritotherapy.
• Cryotherapy.
• Magnetotherapy.

All listed types of physiotherapy helps to normalize the metabolism, contribute to the restoration of blood flow to the patients with joints, the process of reduction of bone tissue is inhibited.

Since it is impossible to completely defeat the polyarthritis, its treatment becomes continuous. Only due to constant maintenance therapy, the patient may remain natural activity, high quality of life and good health as a whole, which can be found in the video in this article.

- This is an extracellular protein that is practically absent in the blood of a healthy person. This substance begins to be actively produced in pathology - inflammation, autoimmunization, tumors.

In modern literature, you can meet its designation as FNF and TNF alpha. Last name It is considered obsolete, but still consumed by some authors. In addition to Alfa Fall, there is another form - beta, which is formed by lymphocytes, but much slower first - for several days.

FNF is produced by blood cells - macrophages, monocytes, lymphocytes, as well as endothelial vessels. If you get into the body of an alien protein-antigen (microorganism, its toxin, tumor growth products) for the first 2-3 hours of TNF reaches maximum concentration.

The tumor necrosis factor does not damage healthy cells, but at the same time it has a strong antitumor effect. For the first time, such an effect of this protein was proven in experiments on mice, who observed the regression of tumors. In this regard, the protein and got its name. Later, studies have shown that the role of FNF is not limited to the lysis of tumor cells, the effect of it is multifaceted, it takes part not only in the reactions in pathology, but also requires a healthy body. At the same time, all the functions of this protein and its true essence still cause a lot of issues.

The main role of FNF is participation in inflammatory and immune reactions. These two processes are closely related to each other, they cannot be distinguished. At all stages of forming an immune response and inflammation, the tumor necrosis factor acts as one of the main regulatory proteins. In tumors, both inflammatory and immune processes, "controlled by" cytokines, are also actively occurring.

The main biological effects of FNF is:

• Participation in immune reactions;
• Regulation of inflammation;
• Influence on the process of blood formation;
• Cyto toxic action;
• Intersystem effect.

If microbes, viruses, immunity are activated in the body of microbes, viruses, alien proteins. FNF contributes to an increase in the number of T- and B-lymphocytes, the movement of neutrophils into the focus of inflammation, the "sticking" of neutrophils, lymphocytes, macrophages to the inner sheath of the vessels at the place of inflammation. An increase in vascular permeability in the zone of development of an inflammatory response is also the result of the FLN.

Tumor necrosis factor (TNF) on body cells

Tumor necrosis factor affects hemopois. It slows down the reproduction of red blood cells, lymphocytes and cells of the white sprout of blood formation, but if the blood formation is suppressed for any reason, then the FNF will stimulate it. Many active proteins, cytokines, have a protective effect against radiation. This effects also possesses FNF.

The tumor necrosis factor can be detected not only in the blood, urine, but also a liquor, which indicates its intersystem effect. This protein regulates nervous and endocrine Systems. Beta-species FNF provides mainly local influence, and systemic manifestations of immunity, inflammation and regulation of metabolism, the body is obliged to alpha-form cytokine.

One of the most important effects of TNF is recognized by cytotoxic, that is, the destruction of the cells, Which fully manifests itself when developing tumors. TNF acts on the cells of the tumor, causing their death due to the release of free radicals, active forms of oxygen and nitrogen oxide. Since single cancer cells are formed in any body throughout the life, the FLF is necessary and healthy people For timely and rapid neutralization.

The transplantation of organs and tissues is accompanied by placing in the body of alien antigens, even if the organ is the most suitable for the set of specific individual antigens. Transplantation is often accompanied by activation of local inflammatory reactions, which also underlies the action of the FNF. Anyone else's protein stimulates the immune response, and transplanted fabrics are no exception.

After transplantation, it is possible to find an increase in the content of cytokine in the serum, which indirectly can speak about the start of the reaction reaction. This fact underlies research on the use of drugs - antibodies to FNF, capable of slowing down the rejection of transplanted tissues.

The negative effect of high TNF concentrations is traced when heavy shock Against the background of septic conditions. Especially expressed products of this cytokine when infected with bacteria, when the sharp depression of immunity is combined with cardiac, renal, hepatic insufficiency, leading to the death of patients.

FLF is able to split fat and deactivate the enzyme involved in the accumulation of lipids. Large cytokine concentrations lead to exhaustion (cached), so it was also called cachectin. These processes determine cancer cachexia and exhaustion in patients with long-term infectious diseases.

In addition to the properties described, FNF plays and reparative function. Following the damage in the focus of inflammation and the active immune response, healing processes are increasing. FLF activates the rolling system of blood, due to which the inflammation zone is separated by the microcirculatory bed. The microtrombus prevents further dissemination of infection. Activation of fibroblast cells and synthesis by collagen fibers contributes to the healing of the focus of damage.

Determination of the level of the FNF and its value

The Laboratory Study of the FNO level does not apply to frequently used analyzes, but this indicator is very important in individual types of pathology. The definition of TNF is shown at:

1. Frequent and long-term infectious and inflammatory processes;
2. Autoimmune diseases;
3. Malignant tumors;
4. Burn disease;
5. Injuries;
6. Collaplanzes, rheumatoid arthritis.

Increasing the level of cytokines can serve not only with diagnostic, but also prognostic criterion. So, when sepsis, a sharp increase in TNF plays a fatal role, leading to heavy shock and death.

For the study in the patient take venous bloodThe analysis is not allowed to drink tea or coffee, only ordinary water is allowed. Not less than 8 hours should exclude receiving any food.

The increase in TNF in the blood is observed at:

• Infectious pathology;
• Sepsis;
• Burns;
• Allergic reactions;
• Autoimmune processes;
• Scarmed sclerosis;
• Meningitis and encephalitis of bacterial or viral nature;
• DVS syndrome;
• Reactions "transplant against host";
• Psoriasis;
• Diabetes of the first type;
• Myeloma and other blood system tumors;
• Shock.

In addition to raising, perhaps and reduced FLNAfter all, it should be present, albeit in meager quantities, to maintain health and immunity. Reducing the concentration of FNF is characteristic of:

1. Immunodeficiency syndromes;
2. Indoor cancer;
3. Applications of some drugs - cytostatics, immunosuppressants, hormones.

Fly in Pharmacology

The variety of biological reactions mediated by FNF, ran across research in the field clinical application Preparations of tumor necrosis factor and its inhibitors. The most promising is antibodies that reduce the amount of FNF with severe diseases and warning deadly complications, as well as recombinant synthetic cytokine, assigned to oncological patients.

Preparations analogs are actively used. human factor Tumor necrosis in oncology. For example, such treatment along with standard chemotherapy shows high efficiency With regard to breast cancer and some other tumors.

TNF alpha inhibitors have anti-inflammatory effect. In the development of inflammation, there is no need to immediately appoint medicines of this group, because for recovery the body should have to go through all stages inflammatory process, form immunity and ensure healing.

Early suppression of natural protection mechanisms is fraught with complications, therefore FNE inhibitors are shown only at an excessive, inadequate reaction when the body is not able to control the infectious process.

Preparations inhibitors FLN - Remicade, Enbrel - prescribed with rheumatoid arthritis, crown disease in adults and children, ulcerative colitis, spondyloarthritis, psoriasis. As a rule, these funds apply not to the ineffectiveness of standard therapy hormones, cytostatics, antitumor agents, with its intolerance or presence of contraindications to the preparations of other groups.

Antibodies to FLN(infliximab, rituximab) suppress excessive products FNF and shown in sepsis, especially with the risk of shock development, with a developing shock they reduce mortality. Antibodies to cytokines can be assigned in the case of long-term infectious diseases With cachexia.

Thymbosin alpha. (Timaktid) refer to immunomodulatory funds. It is prescribed for diseases with impairment impairment, infectious pathology, sepsis, for the normalization of hematopois after irradiation, with HIV infection, severe postoperative infectious complications.

Cytokinotherapy - A separate direction in the treatment of oncopathology, which is developing from the end of the last century. Preparations of cytokines show high efficiency, but their independent use is not justified. The best result is possible only with an integrated approach and joint use of cytokines, chemotherapy and irradiation.

TNF drugs are destroyed by a tumor, prevent the spread of metastases, warn recurrences after removing the neoplasms. With simultaneous use with cytostatics, cytokines reduce their toxic effects and the likelihood of side reactions. In addition, thanks to a favorable impact on immunity, cytokines prevent possible infectious complications against the background of chemotherapy.

Among the preparations of FNF with antitumor activity, Refnotes and Ingaron are applied, registered in Russia. These are funds with proven efficacy against cancer cells, but their toxicity is an order of magnitude lower than cytokine generated in the human body.

Refnot It has a direct destructive effect on cancer cells, inhibits their division, causes hemorrhagic tumor necrosis. The viability of the neoplasm is closely related to its blood supply, and the refrigeration reduces the formation of new vessels in the tumor and activates the coagulation system.

An important property of the refunction is its ability to strengthen the cytotoxic effect of drugs based on interferon and other antitumor agents. So, it increases the effectiveness of cytarabine, doxorubicin and others, due to which high antitumor activity is achieved shared application Cytokines and chemotherapeutic drugs.

Refnot can be appointed not only when breast cancer, as indicated in official recommendations For use, but also with other neoplasms - lung cancer, melanoma, tumors of the female reproductive system

Side effects when using cytokines are small, it is usually a short-term increase in temperature, skin itch. Preparations are contraindicated in individual intolerance, pregnant women and nursing mothers.

Cytokinotherapy is prescribed exclusively by a specialist, about self-treatment in this case there can be no speech, And drugs can be purchased only by the prescription of the doctor. For each patient, an individual treatment scheme and a combination with other antitumor means is being developed.

Video: Lecture on the use of tumor necrosis factor

Video: TNF in the treatment of melanoma, lecture

The author selectively responds to adequate readers as part of their competence and only within the resource of Oncolib.Ru. Full-time consultations and help in organizing treatment are not at the moment.

A particular importance in the pathogenesis of the RA has a tumor necrosis factor (FNO-A), which is the most studied anti-inflammatory cytokine and is considered as a key mediator of the systemic inflammation and the immunocipal process with many rheumatic diseases. This cytokine is actively involved not only in the development of inflammation, but also fever, cachexia, synthesis of proteins of the acute phase, regulation of cascade of cytokines (IL-1, IL-6, IL-12, IL-15) and adhesion molecules.

Recognition of an important role of FNO-A in the pathogenesis of immunocal diseases led to the development of monoclonal antibodies aimed at inhibiting this cytokine. They are characterized by high specificity, which provides selective action At certain parts of the pathogenesis of immunocipal diseases and minimally affects the physiological mechanisms for the functioning of the immune system. These properties make it possible to significantly reduce the risk of unwanted reactions when applying immunoactive drugs.

Etanesept and infliximab were obtained from the FNO inhibitors of the highest distribution. Etanesept (embrel) is a synthetic protein consisting of an extracellular part of the TNF P75 receptor cell surface and the FC fragment of the IgG molecule. When it is introduced into the body (the drug is administered subcutaneously 25 mg 2 times a week or 50 mg 1 time per week) it binds to free TNF-A and lymphotoxin-A, blocking the activation of FN-A receptors. As for the infliximab (remixide), it is IgGL chimeric monoclonal antibodies, which are 75% consisting of human protein and 25% of the mouse. These antibodies obtained by genetically engineering, with high affinity, avidity and specificity are associated with the FNO-A and this most inactivate its pro-inflammatory activity. To increase the effectiveness of therapy with infliximab and neutralization of antibodies to the injected alien protein, the treatment of this GPI in RA is carried out in combination with MT or LEF.

Currently in clinical practice A number of other inhibitors of this pro-inflammatory cytokine are used - ada-mumab, containing fully humanized monoclonal antibodies to FNF, as well as sternalized pegol (Fab fragments of a humanized antibody to FNF connected to a polyethylene glycol (PEG)), GolimumAB (fully humanized monoclonal antibodies to FNF ) other.

FNO-A is synthesized by monocytes, macrophages and T-cells and has wide spectrum Biological effects. It increases the expression of the cellular and vascular molecules of adhesion-1, which participate in the migration of lymphocytes in the inflammation zone, activates lymphocytes and proliferation of fibroblasts, stimulates the synthesis of prostaglandins, leukotrienes, nitrogen oxide and matrix metalloproteinases, in particular collagenase, strromelysis and gelatinases. This cytokine by activating transcription factors (primarily a nuclear factor of kV) regulates the activity of several genes encoding the synthesis of cross-duty cytokines, such as IL-1,IL-6, a granulocytaric-macrophageal colonistimulating factor, interferon-y, and pro-inflammatory chemki-new (IL-8 or Rantes), as well as other inflammation mediators. In addition, affecting hepatocytes, it regulates a sharp phase response, increasing the content of C-reactive and other acute proteins. FNO-A induces the synthesis of free oxygen radicals and inhibits apoptosis of inflammatory cells.

Immunotherapeutic means Currently represented by four groups of drugs. Immununopressants. Anti-FNF drugs. Immunoglobulins for intravenous administration (IGVB). IFN

Immununopressants

The choice of the immunosuppression protocol (dose, the combination of drugs, the duration of therapy) depends on the disease, the type of transplantation and the degree of histocompatibility of the donor and the recipient.

Indicationsto the use of immunosuppressants :. treatment autoimmune diseases. Prevention and treatment of the reaction "Transplant against host" after transplantation bone marrow. Prevention and treatment of transplant rejection.

GK.they have systemic anti-inflammatory and immunosuppressive activity.

The mechanism of impact and change in the immune system .. After passive diffusion through the cytoplasmic membrane, they are associated with an intracellular receptor. When translocating the resulting complex in the cell core, it interacts with specific DNA sequences ( Gres., from. English glucocorticoid Responsive Elements) and transcription factors of genes ... for example, the GC activate the gene I Cappa B Alpha Factor that negatively regulates NF- K B (from English. nuclear Factor K b - nuclear factor K B). NF- K B - the transcription factor of the genes of the granulocyte monocytic colonystimulating factor (GM-CSF from the English. ), IL-2, IL-6, IL-8. Thus, the steroid-induced suppression of NF- K B causes a decrease in the secretion of these cytokines ... In addition, the GC inhibit the expression of IL-1 genes, IL-3, IL-4, FNF and neutrophil secretion products: collagenase, elastase and plasminogen activator .. GC reduce the number of all circulating leukocytes with the exception of neutrophils. However, due to the decrease in adhesion to the cells of the endothelium neutrophils lose the ability to leave the bloodstream and penetrate into infected and damaged areas. The bactericidal activity of neutrophils and monocytes is also suppressed. The immunosuppressive effect depends on the dose of GK. At low or medium doses (<2 мг/кг/сут эквивалентной дозы преднизона для детей и <40 мг/сут для взрослых) наблюдают кожную анергию. Умеренно снижается количество циркулирующих Т-лимфоцитов, причём CD4 + -клеток в большей степени, чем CD8+-клеток. Дозы преднизона >2 mg / kg / day for children and\u003e 40 mg / day for adults suppress the activation of lymphocytes and production at.

The risk of infectious complications of glucocorticoid therapy was significantly increased at a dose of prednisone\u003e 10 mg / day. The relative risk of opportunistic infections (pneumatic pneumonia) is significantly higher than typical viral (herpesviruses), bacterial ( Staphylococcus aureus. et al.) and fungi ( Candida.) infections. Propy infections and helminthoses are atypical, with the exception of endemic pathogens (for example, Plasmodium Falciparum.).

Some properties of frequently used GK .. Betamethasone: half-life 5.6 h, relative glucocorticoid activity 25, relative mineralocorticoid activity 0 .. Dexamethasone: half-life of 3.3 h, relative glucocorticoid activity 30, relative mineralocorticoid activity 0 .. Hydrocortisone: period half-life 1-2 h, relative glucocorticoid activity 1, relative mineralocorticoid activity 2 .. methylprednisolone: \u200b\u200bhalf-life 2-3 h, relative glucocorticoid activity 5, relative mineralocorticoid activity 0 .. prednisone: half-life 2,6-3 hours, relative glucocorticoid Activity 4, relative mineralocorticoid activity 1 .. Presenice: half-life of 1.7-3 h, relative glucocorticoid activity 3.5, relative mineralocorticoid activity 1 .. Triamcinolone: \u200b\u200bhalf-life 2-3 h, relative glucocorticoid activity 5, relative minocortic Inen activity 0.

Methotrexatinhibits dihydrofolate reductase, braking the synthesis of thymidine and some amino acids, and slows the cell division. In a dose of\u003e 20 mg / kg used for therapy of oncological diseases, the drug suppresses the primary and secondary cellular and humoral immune response and can cause the depression of bone marrow, hemorrhage and sepsis. With basic therapy of rheumatoid arthritis and other rheumtoid diseases (1 / 5-1 / 10 from an immunosuppressive dose - 7.5-15 mg / week once, the methotrexate has an anti-inflammatory effect, inhibiting the expression of adhesion molecules and cytokines. In a dose of 10-25 mg / week, methotrexate is used to treat psoriasis.

Mikophenolate Mofetila - A new effective immunosuppressant for the prevention of renewing renal grafts. The drug is in the clinical trial phase in the treatment of rheumatoid arthritis and SLE.

After receiving the inside, mycophenolate mofetyl is subjected to hydrolysis with education active component - Micofenolic acid, excreted mainly with urine. The half-life is 6 hours.

Mycofenolic acid reversibly inhibits the Inozine monophosphate dehydrogenase, thereby suppressing de Novo. Biosynthesis of purines. Lymphocytes substantially depend on the synthesis of purines de Novo. And to a lesser extent from the hypoxanthine guanine phosphoribosis of the transferase-mediated path of the Byros biosynthesis. Therefore, the drug acts mainly on lymphocytes, in which the concentration of guanine nucleotides is significantly reduced, which limits the synthesis of DNA and RNA and suppresses proliferation.

Mycofenolic acid suppresses: .. AT products cytotoxic T-lymphocytes.. Activity of NK cells .. Products of cytokines Il-1 A, IL-1 B, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-G, IFN- a, FLN-B, GM-CSF .. Expression of selectins lymphocytes and monocytes .. Recruitment of neutrophils, lymphocytes and monocytes.

Dosing: 1 g 2 r / day inside.

Side Effects: Fever, headache, infection, arterial hypertension, skin rash, insomnia, anemia, thrombocytopenia, leukopenia, dyslipidemia, hyperglycemia, electrolytic violations.

Leflunomide- Isoxazole derivative with antiproliferative effect.

The drug is used to prevent transplant rejection. Leflomide is also approved for rheumatoid arthritis therapy in the form of monotherapy or combination with methotrexate.

Mechanism of action .. Active metabolite of the leflomide - A77 1726 - has a half-life of more than 2 weeks and excreted with urine and fell .. Antiproliferative effect A77 1726 in lymphocytes is implemented in two mechanisms: ... in low concentrations the drug inhibits de Novo. Pyrimidine biosynthesis in phase G 1 cell cycle ... in high concentrations A77 1726 Suppresses the IL-2-induced phosphorylation JAK1 and JAK3 kinases and B-Title receptor to IL-2 .. Leflomoid also inhibits a humoral response, because Suppresses the proliferation of B-lymphocytes in the S-phase of the cell cycle, as well as the adhesion of mononuclear of peripheral blood and synovial fluid.

Dosing: In 1-3, 100 mg inwards in one, then 10-20 mg inside into one reception.

Side effects: gastrointestinal disorders, infections of respiratory and urinary systems, arterial hypertension, headache, baldness, skin rash, hypokalemia, diabetes, dyslipidemia, anemia, leukopenia, thrombocytopenia.

Cyclosporin- a cyclic peptide consisting of 11 amino acid residues produced by a mushroom TOLYPOCLADIUM INFLATUM..

The drug is used in transplantation of organs and autoimmune diseases.

The mechanism of action .. Cyclosporine is binding to the cytoplasmic receptor protein cyclochillin. The resulting complex inhibits calcium-dependent phosphatase calcinearine, responsible for activating the NF-AT transcription factor (from the English. nuclear Factor of Activated T Cells - nuclear factor of activated T-cells). This molecule is necessary for transcription of the genes of a series of cytokines (GM-CSF, IL-2, IL-3, IL-4, IL-5, IL-8, IL-13, FNF, FNF G) and CD40L membrane molecule (CD40 ligand) .. In addition, cyclosporine inhibits the activation of TCR-dependent (TCR - T-lymphocyte receptor, from English. T Cell Receptor) Alarm pathway in T-lymphocytes and an ag-representing function of monocytes / macrophages. Thus, the drug mainly suppresses cellular immunity; In this case, its effect is not associated with essential lymphopenia or leukopenia.

Dosing: Support the therapeutic concentration in serum 100-300 μg / l; The dynamic control of the serum level of cyclosporine is shown.

Side effects: nephrotoxicity, arterial hypertension, electrolyte disorders, hepatotoxicity, hirsutism, acne, viral, bacterial pneumonia, fungal sepsis.

Sirolimus- Macrolid of fungal origin, forms a complex with FK-binding proteins from a family of cyclophilines other than cyclosporine-binding cycloofillins. The drug is used to prevent transplant rejection. Sirolimus does not inhibit calcinearine. Mechanism of action .. Sirolimus is associated with a specific cytosolic protein - immunophiline (FK-binding protein-12), the FKPB-12-Sirolimus complex suppresses the activation of the kinase "targets of rapamycin mammals" (from English MTOR - mAMMALIAN TARGET OF RAPAMYCIN) Performing a basic role in the cell cycle .. Inhibition of MTOR leads to a blockade of several specific signal conversion pathways and, ultimately, to suppress the activation of lymphocytes and a decrease in immune forces. Dosing: initial dose of 6 mg, then 2 mg inside 1 p / day or under the control of serum concentration (therapeutic concentration of 4-12 ng / ml in combination with cyclosporin first 2-3 months, after cancellation of cyclosporin -12 -20 ng / ml).

Anti-Fly Preparations

Tumor necrosis factor A (TNF A) - pro-inflammatory cytokinewhich plays an important role in the pathogenesis of rheumatic and inflammatory diseases. New data on the value of FNF A in the pathophysiology of rheumatoid arthritis and Crohn's disease led to the development of a new class anti-FNF A preparations.

Inflicksimab (Humanized monoclonal AT against FNF A) - approved for the treatment of rheumatoid arthritis and crown disease in the active phase. Dosing: 5 mg / kg for 2 hours in / c. Side Effects: Viral infections, bronchitis, pneumonia, sinusitis, urinary system infections, vomiting, diarrhea, headache, dizziness, arterial hypertension. Contraindications: sepsis, manifest infection, abscess, pregnancy, age younger than 17 years old.

Immunoglobulins for intravenous administration

Immunoglobulins for intravenous administration (IGMB) - standard of therapy of humoral and combined immunodeficiency, as well as a number of autoimmune diseases.

Method of manufacture. All Igvv is prepared by the method of cold precipitation with ethanol. Serums of several thousand donors after screening on infectious pathogens are mixed for the production of single series drug. IGWH contains AT against the most common native viral and bacterial ag, as well as ag-vaccine. To reduce the risk of transmission of pathogens, pasteurization or processing by detergents are used. The final product usually contains more than 99% IgG in terms of protein. Up to 10% IgG molecules form polymer complexes. The half-life in the serum range ranks from 15 to 30 days. The content of IGA and complement components varies depending on the manufacturer.

IVVV Action Mechanisms: .. blockade and modulation of expression FC G -receptors .. Suppression of the proliferative response of lymphocytes .. Modulation of products and secretion of cytokines (IL-1, IL-1RA [receptor antagonist to IL-1], FNF A, TGF- B 1 [from English. transformating Growth Factor B - transforming growth factor B], IL-2, IL-10) .. Inhibition of the damaging effects of the complement .. Suppression of the proliferation of endothelium cells .. Stimulation of catabolism Catabolism of the IgG class autoantoler .. Suppression of FAS-mediated apoptosis (FAS is one of the cell membrane glycoproteins ) .. Regulation of idiocy antiydiotypic interactions.

Indications for the purpose .. Indications approved by the FDA: ... Coupled with X-chromosome Agamaglobulinemia ... hyper-IgM syndrome ... Transient hypogamaglobulinemia of newborns ... deficiency of IgG subclass deficit ... SURE SURE COMBINED Immunodeficiency ... Common variable immunodeficiency ... DJORI SYNDROM ... Syndrome Viscott-Oldrich ... Ataxia Teleangectasia ... Chediaiac Higashi Syndrome ... Captured with X-chromosome Limphoproliferative Syndrome ... hyper-IgE syndrome .. . Chronic lympholecosis with hypogammaglobulinemia ... Immunoprophylaxis ( varicella) ... Cavasaki disease ... recurrent infections when transplanting bone marrow ... idiopathic thrombocytopenic purple ... HIV infection in children .. readings based on the results of controlled clinical studies: ... Prevention of RSV and CMV infections ... Hyien-Barre syndrome ... Chronic inflammatory demyelinizing polyneuropathy.

States in which the effectiveness of the IGVB is studied: .. autoimmune neutropenia .. autoimmune hemolytic anemia.. bronchial asthma.. atopic dermatitis.. chronic urticaria .. lupus jade .. granulomatosis of veneman .. autimmune thyroiditis.. Glomerulonephritis .. Layella Syndrome .. Secondary immunodeficiency.

Dosing. The concentration of serum IgG in patients with hypogammaglobulinemia should be higher than 500 mg%. The AVIV dose required to achieve and maintain this level depends on the initial concentration of IgG, the frequency of administration of the drug and the intensity of catabolism of immunoglobulins in a separate patient. For most patients, a dose of 300 mg / kg is sufficient 1 time in 3 weeks or 400 mg / kg 1 time in 4 weeks.

Side Effects .. from 5 to 15% of patients experience adverse reactions IVVV: Facial redness, back pain, nausea, chills. Symptoms can disappear with a decrease in the rate of infusion. The first dose of the drug must be administered at a rate of 30 ml / h in adults and 10-15 ml / h in children. With good tolerability, subsequent infusions begin at a speed of 40 ml / h and increase the speed by 25% every 30 minutes .. from others side Effects OPON, thrombosis, migraine, aseptic meningitis, hemolytic anemia are possible.

Interferons

Pharmacological effects: antiviral, antiproliferative, immunomodulating.

Indications: Chronic viral hepatitis, various sharp viral infections, multiple sclerosis, chronic granulomatosis.

Side effects: fever, sweating, fatigue, arthralgia, Malgia, arrhythmia, depression, tremor, parrestzia, gastrointestinal disorders, hair loss, examine, itching.

Contraindications: heart disease, CNS disease, renal failure, liver failure, bone marrow oppression.

Reduction.NF- K B - K B nuclear factor (from English. nuclear Factor k b), GM-CSF - a granulocytic monocytarian colonistimulating factor (from the English. granulocyte-macrophage colony-stimulating factor), IGVB is immunoglobulins for intravenous administration.

Note.FDA - US Federal Service, Controlling Production, Storage and Food Implementation, medicinal preparations and cosmetics ( THE FOOD AND DRUG ADMINISTRATION).

Tumor necrosis factor (TNF) is a specific protein of a group of cytokines - hormone-like substances produced by the immune system. It is of great interest in medicine due to its properties - the ability to cause death of cells (necrosis) of intra-tumor tissue. This is a real breakthrough in medicine that allows us to apply drugs with TNN for treatment cancer disease.

History opening

By the beginning of the 20th century, regularity was discovered in medical practice: some patients had a decrease and / or disappearance of tumor formations after transferring any infection. After that, the American researcher William Kolya began to intentionally introduce a cancer infectious start (bacteria and their toxins).

The method was not recognized as effective, since he had a strong poisoning effect on the body of patients. But it was planned to begin a whole number of studies that led to the detection of a protein that called the necrosis factor of tumors. The substance was caused by the rapid death of malignant cells implanted under the skin experimental mice. A little later was allocated pure FNF, which made it possible to use it for research purposes.

This discovery contributed to the present breakthrough in cancer therapy. Previously, with the help of protein-cytokines, it was possible to successfully treat only some oncological formations - melanoma skin, kidney cancer. But to significantly advance in this direction allowed the study of the properties that the tumor necrosis factor has. Preparations based on it are included in the chemotherapy procedure.

Mechanism of action

The tumor necrosis factor acts on a certain cell - the target. There are several mechanisms of action:

• Through special FPN receptors, the multistage mechanism is launched - the programmable death is called cytotoxic. At the same time, there is either the complete disappearance of the neoplasm, or a decrease in its size.
• Through violation or complete cessation of the cell cycle. The cancer cell becomes incapable of division and tumor growth stops. Such an action is called cytostatic. Usually the tumor or ceases to grow, or decreases in size.
• By blocking the process of formation of new vessels of tumor tissue and damage to already existing capillaries. The tumor, devoid of food, necrotizes, decreases and disappears.

There are situations where cancer cells may be insensitive to the injected drugs due to mutations. Then the above-described mechanisms do not occur.

Use in medicine

The necrosis factor of tumors is used in the so-called cytokinotherapy - treatment with specific proteins generated by blood cells that are responsible for immunity. The procedure is possible at any stage and is not contraindicated to people with concomitant pathologies - cardiovascular, kidney, hepatic. To reduce toxicity, the recombination is used factor of tumor necrosis.

Treatment with cytokines is a new and progressively developing direction in oncology. At the same time, the use of FNF is considered the most efficient. Since this substance is highly toxic, it is used by the so-called regional perfusion. The method is that an infected tumor organ or part of the body with a special equipment is replenished from the overall blood flow. Then, artificially launch blood circulation with the introduced FNF.

Dangerous consequences

In medical practice, the tumor necrosis factor is used with caution. A number of studies prove that the TNF is the key component in the development of sepsis, toxic shock. The presence of this protein intensified pathogenicity of bacterial and viral infectionsthat is especially dangerous if HIV has a patient. It has been proven that TNF participates in the emergence of autoimmune diseases (for example, rheumatoid arthritis) in which the immune system erroneously takes fabrics and cells of its body for alien bodies and damages them.

The following measures are followed to minimize high toxic effects:

• use only locally at the site of the tumor;
• combined with other drugs;
• work with mutant less toxic TNF proteins;
• neutralizing antibodies are injected.

These circumstances are forced to limitably apply the tumor necrosis factor. Treatment to them should be competently organized.

Diagnostic indicator

Blood analysis does not register FNF in a healthy body. But its level increases sharply in infectious diseases, when the toxins of the causative agent arrive in the blood. Then it can be contained in the urine. The tumor necrosis factor in the articular fluid indicates rheumatoid arthritis.

Also, the increase in this indicator says allergic reactions, oncological diseases and is a sign of rejection of transplanted donor bodies. There is information that an increase in this indicator may indicate noncommunicable diseases, such as heart failure, bronchial asthma.

With different immunodeficiencies (including AIDS) and severely flowing viral diseasesAs well as injuries and burns are created conditions that reduce the tumor necrosis factor. A medicine possessing an immunosuppressive action will give a similar effect.

Preparations

FLN-based preparations are called targeted - capable acting to a specific cancer cell molecule, causing the death of the latter. At the same time, the influence on other organs remains minimal, which reduces the toxicity, which has a tumor necrosis factor. FLF-based preparations are used both independently (monotherapy) and combining with other means.

Today there are several funds based on FNF, namely:

• NGR-TNF - Foreign Preparation, active substance which derivative FNF. It is able to damage the vessels of the tumor, depriving it.
• "Alilin" - Russian development. Highly efficient in combination with interferons.

"Refnot" - a new Russian drug, contains thymosin-alpha 1. Its toxicity is extremely low, but effectiveness is equal to natural FNF and even exceeds it by immunostimulating action. The drug was created in 1990. He successfully passed all the necessary clinical trials and only in 2009 was registered, which gave the official permission to treat them malignant neoplasms.

Independent reception of any drugs based on tumor necrosis factor is categorically prohibited. Treatment of oncological diseases is a challenged process that proceeds solely under the supervision of a specialist.