Method of complex evaluation of indications for administration of cardiometabolic therapy in case of infectious diseases

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to paediatric cardiology and paediatric infectious diseases, and can be used for evaluation of indications for cardiometabolic therapy in case of infectious affection of myocardium in children. For this purpose quantitative evaluation of clinical, electrocardiographic, biochemical and echocardiographic indices is determined and realised. As clinical indices auscultative symptomatic: sonority of tones, presence of noises, parameters of arterial pressure are evaluated. As biochemical indices evaluated are: activity of cardiospeciphic enzymes: MB-fraction of creatine phosphokinase, α-hydroxybutyrate dehydrogenase, aspartic transaminase, alanine transaminase and cardiospecific troponin I protein. Echocardiographic examination is realised with application of Dopplerography for evaluation of diastolic ventricular function. Each of indices is evaluated by from 1 to 3 points. Points are summed up and obtained result is used to evaluate indications for cardiometabolic therapy. If the total sum is lower than 3 points, cardiometabolic therapy is not indicated. If the total sum is from 3 points to 7 point including, peroral introduction of cardiometabolic preparations is carried out. If the total sum is from 8 points and higher, parenteral introduction of cardiometabolic preparations is realised.

EFFECT: method provides possibility of determining presence of indications to administering cardiometabolic therapy objectively in minimal terms, including situations, when part of results of additional examination is absent because of some reasons, and of evaluating its efficiency in differential way.

1 tbl, 4 ex

 

The invention relates to medicine, namely to medical treatment of complications of infectious diseases, can be used for objective evaluation of the testimony to the appointment of metabolic therapy for myocarditis varying severity and secondary cardiomyopathies, emerging infectious diseases in children.

Currently, it is proved that lesions of the myocardium can develop in infectious diseases of various etiologies. It is believed that acute myocarditis is accompanied by about 2% of all cases of acute respiratory diseases (ARD), including influenza. Acute intestinal infections (AII) can also be accompanied by myocardial complications. Due to the high prevalence and yet with the complexity of the diagnosis, the unavailability of high-tech methods in everyday practice, the who expert Committee in 1997 it was proposed to use a work, the term "inflammatory cardiomyopathy". To it is recommended to include all cases of acute and chronic myocardial lesions developing on the background of infectious diseases, including myocarditis and dilated cardiomyopathy.

The main areas of treatment are considered to be the etiological (antibacterial, antiviral, antifungal and anti-inflammatory (non-steroidal PR is tivovospalitiona and corticosteroids). An important component of comprehensive treatment for the restoration of cardiomyocytes and limiting the affected area, is a metabolic therapy. Today in pediatric practice are applied inosine, drugs, potassium and magnesium, carnitine, ubiquinone, Neoton. Most of the drugs available in various forms - in the form of tablets, aqueous solutions for oral administration and intravenous administration.

Early appointment of this group of drugs leads to more rapid and complete recovery. However, since the appearance of the first symptoms to their destination often is held for a long period. Typically, this is due to the long time required for obtaining and interpreting specialists of the results of additional tests, especially in the outpatient setting. Quick timely diagnosis is hindered by the lack of criteria, allowing a high degree of accuracy to confirm or refute the diagnosis, because lesions of the myocardium can be accompanied by various clinical, ECG, ultrasound and laboratory manifestations. Each of these symptoms is not specific to infectious myocarditis or cardiomyopathy may be associated with other cardiovascular or other pathology that requires with testwuide therapy, and sometimes - only observations. High-tech equipment to diagnose complication (ultrasonic devices with densitometry plots infarction magnetic resonance imaging with contrast, endomyocardial biopsy) in most cases, inaccessible and often unjustified by economic criteria or safety issues for the child.

Now it is proved that a large number of myocarditis occurs in the lungs and deleted forms. However, even in these patients may rapidly growing pronounced deterioration associated generally with life threatening arrhythmias and acute heart failure in the absence of adequate treatment. On the other hand it is known that the portion of changes in the cardiovascular system, which can be interpreted as the possible symptoms of myocarditis are a natural reaction of the organism to infectious-inflammatory process and additional treatment is not required. These include, for example, transient systolic murmur in hyperthermia, bradycardia during convalescence, infectious hyperferritinemia on one or two cardiospecific indicators in the serum.

Thus, there is no doubt the need for a total assessment of the significance of detected clinically the fir, laboratory and instrumental parameters of the violations of the condition of the myocardium in a patient for the timely appointment of adequate therapy.

Apply today how to determine the indications for prescription of metabolic therapy based on the diagnosis of myocarditis or cardiomyopathy by one method or another. However, often the results of additional studies are equivocal or conflicting, and some of them are not available for some reason.

There is a method of early diagnostics of infectious-toxic cardiopathy in infants, the proposed Lebedeva, O. V. and N. Cherkasov.With. The method is based on the simultaneous determination of the activity of MB-CPK in serum of venous blood dehydrogenase (LDH) and glitserofosfatdegidrogenazy (GPDH) in lymphocytes of capillary blood. If the level of MB-CPK from 9.0 to 16 IU/l and the reduction SDG 7.6 to 5.2 g/limp., GFDG from 6.5 to 4.8 g/limp. diagnose infectious-toxic cardiopathy (RF Patent No. 2200322, IPC G01N 33/573, publ. 10.03.2003).

The disadvantages of the method are nespecificnomu lymphocytic reaction, the possibility of increasing the activity of MB-CPK in the natural infectious giperfermentemii, lack of improvement in the later stages of myocardial lesions, the need for special laboratory equipment.

closest to the claimed method is a method of determining the indications for antioxidant therapy in children with infectious diseases, proposed Ivanova centuries, Govorova L. C., and Vershinino E. N. (Patent RF №2282188, IPC G01N 33/49, publ. 20.08.2006). The method is based on determining the intensity of free radical oxidation by assessing the activity of superoxide dismutase in blood lymphocytes by chemiluminescence. The disadvantage of this method is the need for special laboratory equipment, the time to obtain results and initiation of therapy.

Thus, currently there is no way comprehensive assessment of a variety of symptoms of infarction for objective justification of metabolic therapy in the early stages, which is especially important for patients with mild forms on an outpatient basis.

The technical task to be solved by the invention is a method of assessment of clinical symptoms, biochemical parameters, results of electrocardiographic and echocardiographic examinations in children with presumed infectious lesions of the myocardium, providing an opportunity in the shortest time to objectively determine the presence of evidence to the appointment of metabolic therapy, including in situations where part of the results of the additional examination is not available for any reason.

The goal of the project resets the same time, according to the proposed invention, in the method of assessing the indication for metabolic therapy in infectious lesions of the myocardium in children, which consists in identifying and quantifying clinical, electrocardiographic, biochemical and echocardiographic indices, each of which is evaluated from 1 to 3 points, the points are added up and the results are assessing the indications for metabolic therapy, if the total amount is less than 3 points-metabolic therapy is not shown, when the total amount of from 3 to 7, inclusive, prescribe oral-metabolic drugs, with total of 8 points and above prescribed parenteral metabolic drugs.

In addition, the inventive method is characterized by the following essential features:

as clinical indicators auscultatory symptoms: a sonorous tones, the presence of noise; blood pressure;

as biochemical indicators activity cardiospecific enzymes: MB fraction of creatine phosphokinase, α-hydroxibutiratdehydogenase, aspartic transaminase, alanine transaminase) and cardiospecific protein troponin I;

echocardiographic study of the implementation is given with the use of Doppler for the assessment of diastolic function of the ventricles;

clinical, electrocardiographic, biochemical and echocardiographic indicators in points, namely

the muting or deafness tones - 1 point,

systolic and/or diastolic murmur - 1 point,

tachycardia or bradycardia, do not correspond to the phase of the disease, - 1 point,

arterial hypotension is 1 point,

signs of heart failure II - III degrees (congestive rales in the lungs, the pastos or edema, hepatomegaly) - 1 point,

arrythmia, conduction disturbance (newly diagnosed) - 1 point,

the reduction of voltage - 1 point,

violation of repolarization - 1 point,

the expansion chambers of the heart - 1 point,

a reduced ejection fraction - 2 points,

failure of diastolic function - 1 point,

increased activity at the same time, the MB-ck, α-HBDH, de Ritis coefficient (AST/ALT>1,5) - 3 points, increasing the activity of any two of cardiospecific indicators (MB-ck, α-HBDH, AST/ALT) - 1 point,

increased troponin 1-3 points,

severe forms of infectious lesions of the myocardium accompanied asistoliei and/or cardiogenic shock, on the basis of natural manifested by marked clinical, electrocardiographic, laboratory and echocardiographic violations, estimated at 8 points.

The technical result, which is provided to the realization what their inventive combination of essential features, is the reduction of time defining the indications for metabolic therapy and the choice of route of administration of the drug for patients with infectious myocardial lesions of varying severity in outpatient and residential settings.

The method is as follows.

During clinical examination of the patient appreciate the auscultatory symptoms: a sonorous tones, the presence of noise; measure blood pressure; then record the electrocardiogram (ECG) in 12 standard leads, conduct echocardiographic (ECHO KG) study using Doppler for the assessment of diastolic function of the ventricles. To determine the activity cardiospecific enzymes: MB fraction of creatine phosphokinase (MB-ck), α-hydroxibutiratdehydogenase (α-HBDH), aspartic transaminase (ACT), alanine transaminase (ALT) and cardiospecific protein troponin I in a patient taking blood from a vein on an empty stomach in the amount of 3 ml of Blood is centrifuged with a speed of 1500 rpm./min for 15 minutes, after which receive the serum, which analyze the levels of these indicators using biochemical semi-automatic photometer and a standard set of reagents for quantitative photometric analysis.

The detected violations are assigned points as follows:

muffled the th or deafness tones - 1 point,

systolic and/or diastolic murmur (up to the present disease absent) - 1 point,

tachycardia or bradycardia, do not correspond to the phase of the disease, - 1 point,

arterial hypotension is 1 point,

signs of heart failure II - III degrees (congestive rales in the lungs, the pastos or edema, hepatomegaly) - 1 point,

cardiogenic shock, asystole - 8 points,

arrythmia, conduction disturbance (newly diagnosed) - 1 point,

the reduction of voltage - 1 point,

violation of repolarization - 1 point,

the expansion chambers of the heart - 1 point,

a reduced ejection fraction - 2 points,

failure of diastolic function - 1 point,

increased activity at the same time, the MB-ck, α-HBDH, factor de

The Rytis (AST/ALT>1,5) - 3 points,

the increase in the activity of any two of cardiospecific indicators (MB-ck, α-HBDH, AST/ALT) - 1 point,

increased troponin 1-3 points.

The points are added up. When the total amount is less than 3 points-metabolic therapy is not shown, when the total amount of from 3 to 7, inclusive, prescribe oral-metabolic drugs, with total of 8 points and above prescribed parenteral metabolic drugs.

Examples of specific applications of the method.

Example 1. Patient C., 1 year and 4 months.hospitality the van by ambulance with complaints, according to his mother, vomiting 7 times a day, liquid stool greenish color 8 times per day, expressed lethargy, fever to 39.8°C.

From the anamnesis of the disease: pain in acute, 2 days ago, when there were such complaints. Homes treated by smectite, regidron, Linex, interiorism, antipyretic. Due to the ineffectiveness of therapy are hospitalized.

From the anamnesis of life: were regularly observed a district pediatrician at the place of residence, at the dispensary was not. Vaccinated according to their age.

When entering a state of moderate severity. Pronounced lethargy. The body temperature of 37.8°C. the pale Skin. No edema. Auscultation: the lungs breathing puerile, no wheezing, heart sounds sonorous, rhythmic, systolic murmur of medium intensity with a maximum at the top and V point auscultation, increases in vertical position. Heart rate is 130 beats per minute. Blood pressure is 90/60 mm RT. Art. the Abdomen is soft, swollen. The liver increased by 1.0 see Focal neurological and meningeal symptoms no.

The preliminary diagnosis: acute infectious gastroenteritis. In connection with newly diagnosed clinical symptoms of infarction (systolic murmur) the designated examination: blood MV-ck, α-HBDH, ACT, ALT; ECG and ECHO-KG surveys.

According to the results of anal is for blood: MV-UFC - 31,5 U/l; α-HBDH - 183,2 U/l; ACT - 31 U/l; ALT - 14 IU/L. de Ritis Coefficient (AST/ALT)=2,2.

According to the results of the ECG: sinus rhythm, 130 beats per min Normal position of the electrical axis of the heart. Violation of repolarization in the rear-diaphragmatic (inversion of teeth, T) and lateral (smoothness of splines T) departments.

According to the results of the ECHO-KG: the mitral valve of 1 degree, impaired diastolic function of the right ventricle.

Thus, the clinical diagnosis: acute infectious gastroenteritis, the intermediate form, infectious cardiomyopathy.

Evaluate the symptoms of infarction: for the first time revealed a systolic murmur - 1 point, exceeding normal values MV-ck, α-HBDH, de Ritis coefficient is 3 points, a violation of repolarization on the ECG - 1 point, impaired diastolic function of the right ventricle - 1 point. Total: 6 points. Shows metabolic therapy.

Conclusion: the total score of all symptoms can objectively in a timely manner to define indications for metabolic therapy. In this situation, medication may be prescribed by the attending physician, without waiting for the advice of a cardiologist, when only the results of biochemical analysis of blood on MV-ck, α-HBDH, ACT and ALT. ECG and ECHO-KG only confirm the diagnosis.

Example 2. Patient K., 2 years 4 months hospitalized by ambulance brigade the same time with complaints, according to his mother, cough, loose stools up to 4 times per day, expressed lethargy, fever to 39.9°C.

From the anamnesis of the disease: pain in acute, 5 days ago, when there were such complaints. The house received treatment: Augmentin, Lasolvan, berodual (inhalation), zyrtec, Linex, without visible effect.

From the anamnesis of life: were regularly observed a district pediatrician at the dispensary is not. Vaccinated according to their age.

During the inspection: a serious condition. The temperature of 38.3°C. the Frequency of respiratory movements - 40 minutes no Edema. In the lungs, breathing hard, weakened right, scattered dry and moist rales. Muffled heart sounds, systolic murmur of medium intensity with a maximum at V point auscultation, increases in vertical position. Heart rate is 130 beats per minute. Blood pressure is 90/50 mm RT. senior Abdomen soft, liver is not enlarged.

The preliminary diagnosis: acute respiratory disease, acute bronchitis, it is impossible to exclude right-sided pneumonia. In connection with the first detected signs of heart disease scheduled examination: biochemical analysis of blood on MV-ck, α-HBDH, ACT, ALT; ECG, ECHO-cardiography. In connection with changes in the lungs are shown radiography of the chest.

In the analysis of blood MV-UFC - 55,4 U/l; α-HBDH - 249,8 U/l; ACT - of 35.4 U/l; ALT - 11,5 E is/l, de Ritis coefficient (AST/ALT)=3,1. X-ray signs of upper - and srednedushevoj right-sided pneumonia, and the expansion of the shadow hearts (cardiothoracic index=60%). ECG: sinus tachycardia, the vertical position of the electrical axis of the heart, reducing the voltage of the QRS complex, impaired repolarization in the rear-diaphragmatic departments. According to the results of the ECHO-KG:

moderate expansion of both ventricles, diastolic dysfunction of the ventricles. Thus, the clinical diagnosis: acute respiratory disease, severe, right-sided upper and srednedushevoe pneumonia, acute infectious myocarditis.

Evaluated the symptoms of the pathology of the myocardium: muting tones of heart - 1 point, for the first time revealed a systolic murmur - 1 point, exceeding normal values MV-ck, α-HBDH, de Ritis coefficient - 3 points; violation of repolarization on the ECG - 1 point, reduction of the voltage of QRS complex - 1 point; failure of diastolic function of the ventricles - 1 point, the expansion chambers of the heart - 1 point. Total: 9 points. Shown parenteral metabolic therapy.

The main treatment regarding the right-sided pneumonia, added carnitine, Panangin intravenous drip.

After 4 days of lethargy decreased significantly. A state of moderate severity. The temperature was 37.4°C. the Frequency of respiratory movement is basic - 32 minutes In the lungs remain breathing hard, weakened right, scattered dry and moist rales. Muffled heart sounds, mild systolic murmur in the V point auscultation. Heart rate - 122 min. Blood pressure is 90/55 mm RT.article Abdomen soft, liver is not enlarged. In the analysis of blood MV-UFC - 48,7 U/l; α-HBDH - 213,3 U/l; ACT - 31,9 U/l; ALT to 11.2 IU/l, de Ritis coefficient (AST/ALT)=2,8. ECG - positive dynamics: the voltage of QRS complex in normal, impaired repolarization in the rear-diaphragmatic departments is maintained. The ECHO-KG - diastolic dysfunction of the ventricles, the sizes of the chambers of the heart is within normal limits.

Evaluated the symptoms of the pathology of the myocardium: muting tones of heart - 1 point, persistent systolic murmur - 1 point, exceeding normal values MV-ck, α-HBDH, de Ritis coefficient - 3 points; violation of repolarization on the ECG - 1 point, impaired diastolic function of the ventricles - 1 point. Total: 7 points. Shows oral-metabolic therapy.

Conclusion: the use of the method of complex assessment of the indications for the purpose of metabolic therapy in this patient allows the physician if there are only results of the clinical examination and rengenografii of the chest in the early stages to assign metabolic therapy, without waiting for the results of the ECG, ECHO-KG the consultation of the cardiologist. Additional studies confirm the diagnosis and allow you to give an objective justification for the parenteral administration of drugs with the subsequent transition, the improvement in oral intake.

Example 3. Patient T., 5 years, 10 months.hospitalized by ambulance with complaints, according to parents, runny nose, cough, diarrhea, up to 7 times a day, poor appetite, lethargy, fever up to 39.5°C.

From medical history: acutely ill, 4 days ago, when there were such complaints. Received treatment: Arbidol, hexanal, Lasolvan, smectite, regidron, without any significant effect.

From the anamnesis of life: ARD 4-5 times per year, is at the dispensary at otolaryngologist (adenoids 2 degrees) and the allergist (atopic dermatitis, pollinosis). Vaccinated according to their age.

At survey: the state of moderate severity. A body temperature of 38°C. pale Skin. No edema. Zev grainy, hyperemic. In the lungs the breath puerile, no wheezing. Heart sounds loud, 110 beats per minute, mild systolic murmur with a maximum at the top. Blood pressure 95/60 mm RT.article The abdomen is soft.

The preliminary diagnosis: acute respiratory infections, acute infectious gastroenteritis.

In connection with newly diagnosed symptoms of myocardial scheduled examination: blood MV-ck, α-HBDH, ACT, ALT; ECG; ECHO KG.

In anal is ze blood: MV-UFC - 37,8 U/l; α-HBDH - 172,4 U/l; ACT - of 38.5 U/l; ALT - 46,0 U/L., de Ritis coefficient (AST/ALT)=0,8.

ECG: sinus tachycardia, normal position of the electrical axis of the heart. The ECHO-KG - dimensions of the chambers of the heart, the ejection fraction, diastolic function of the ventricles within the age norm. Diagnosis clinical: acute respiratory disease, moderate to severe form, acute infectious gastroenteritis, the intermediate form.

Evaluate the symptoms of infarction: for the first time revealed a systolic murmur - 1 point, exceeding normal values MV-ck, α-HBDH - 1 point. Total: 2 points. Metabolic therapy is not shown.

Conclusion: the application of the method of complex assessment of the indications for metabolic therapy in this patient allowed us to objectively determine the absence of indications to additional treatment, although first identified by clinical examination systolic murmur. Changes are of a functional nature, which is confirmed by the results of ECG and ECHO-KG.

Example 4. Using a comprehensive evaluation of the testimony to the appointment of metabolic therapy in clinical studies.

In a study conducted to determine the effectiveness of metabolic means levocarnitine (drugs elcar 20% solution for oral administration and carnitene 1 g/5 ml for intravenous injection), included 122 children. All children would and hospitalized with acute respiratory infections and acute intestinal infections of various etiologies, accompanied on one or the other of hospitalization symptoms of infarction. In the main group, in which the metabolic correction was appointed levocarnitine, included 64 children. In the comparison group were 58 children, which to the basic therapy was added inosine. The study included only patients with symptoms of myocardial estimated according to the proposed scale of 3 points or more. The compared groups were fully comparable in terms of age groups, etiology and severity of the underlying disease, comorbidity, conducted basic therapy, duration of hospitalization. To adequately assess the effectiveness of the drugs in each group, patients were divided into subgroups with the corresponding number of points at the time of inclusion: subgroup A-3-4 points, subgroup B - 5-7 points, subgroup C - 8 or more points. In the subgroup C was performed parenteral therapy with transition to oral medication when the value of the index of integrated assessment less than 8 points. Effectiveness was evaluated in terms of normalization of clinical, laboratory, ECG and ultrasound results in the respective subgroups. The data obtained are shown in table 1.

Table 1
The number of patients with persistent symptoms of infectious lesions of the myocardium at different times on the background of metabolic therapy.
The time from the beginning of the development of complicationsPatients who received l-carnitine (study group, n=64)Patients treated with inosine (comparison group, n=58)
Subgroup A (3-4 points), n=28(100%)Subgroup (5-7 points), n=21 (100%)The subgroup With (8 or more points), n=15 (100%)Subgroup A (3-4 points), n=25 (100%)Subgroup (5-7 points), n=19 (100%)The subgroup With (8 or more points), n=14 (100%)
28-35 days4(14%)12(57%)15(100%)7 (28%)13 (68%)14(100%)
58-65 day05 (24%)*7 (47%)3(12%)10(53%)*10(71%)
88-95 day0(10%)* 3 (20%)07 (37%)*6 (43%)
*- the difference is significant, p<0,05.

As shown in the table, levocarnitine had significantly more effective than inosine, among patients Into sub-groups, having from 5 to 7 inclusive of the developed scale. A differentiated approach allowed us to identify groups of patients with different severity of symptoms and depending on this, with different prognosis.

Thus, the application of the method of complex assessment of symptoms of infarction, developing on the background of various infectious diseases, allowing you to quickly determine the indications for metabolic therapy and differentially to evaluate its effectiveness.

The method of assessing the indication for metabolic therapy in infectious lesions of the myocardium in children, which consists in identifying and quantifying clinical, electrocardiographic, biochemical and echocardiographic indices, at the same time as clinical indicators auscultatory symptoms: a sonorous tones, the presence of noise; blood pressure, as biochemical indicators activity cardiospecific Fe the cops: MB fraction of creatine phosphokinase, α-hydroxibutiratdehydogenase, aspartic transaminase, alanine transaminase) and cardiospecific protein troponin I, echocardiographic examination is performed with the use of Doppler for the assessment of diastolic function of the ventricles, each of the indicators from 1 to 3 points, namely
the muting or deafness tones - 1 point,
systolic and/or diastolic murmur - 1 point,
tachycardia or bradycardia, do not correspond to the phase of the disease, - 1 point,
arterial hypotension is 1 point,
signs of heart failure II-III degrees (congestive rales in the lungs, the pastos or edema, hepatomegaly) - 1 point,
arrythmia, conduction disturbance (newly diagnosed) - 1 point,
the reduction of voltage - 1 point,
violation of repolarization - 1 point,
the expansion chambers of the heart - 1 point,
a reduced ejection fraction - 2 points
failure of diastolic function - 1 point,
increased activity at the same time, the MB-ck, α-HBDH, de Ritis coefficient (AST/ALT>1,5) - 3 points
the increase in the activity of any two of cardiospecific indicators (MB-ck, α-HBDH, AST/ALT) - 1 point,
increased troponin I - 3 points
severe forms of infectious lesions of the myocardium accompanied asistoliei and/or cardiogenic shock, on the basis of natural manifested by marked clinical, ele is tlocateoptions, laboratory and echocardiographic violations, estimated at 8 points, the points are added up and the results are assessing the indications for metabolic therapy, when the total amount is less than 3 points-metabolic therapy is not shown, when the total amount of from 3 to 7, inclusive, prescribe oral-metabolic drugs, with total of 8 points and above prescribed parenteral metabolic drugs.



 

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7 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biology and toxicological chemistry and can be used in practice of sanitary and epidemiological stations, chemical-toxicological, forensic and veterinary laboratories. A biological material, containing substituted 2-methoxyhydroxybenzene, is two times (each time for 30 minutes) infused with ethylacetate with mixing, separate extracts are separated from solid particles of the biological material, combined, ethylacetate is evaporated in an air flow at 18-22°C, residue is repeatedly processed with acetone, acetone extracts are separated, combined, dehydrated, evaporated in an air flow at 18-22°C, and then in a nitrogen flow until a solvent is completely removed, residue is dissolved in hexane, extracted with a buffer solution with pH 12-13, a water-alkaline extraction is separated, acidified to pH 2-3, saturated with sodium sulphate, extracted with diethyl ether, the ether extract is separated, dehydrated, evaporated in an air flow at 18-22°C, and then - in a nitrogen flow until the solvent is completely removed, residue is dissolved in a mixture of solvents hexane-dioxane-propanol-2, taken in a ratio of 20:5:1 by volume, chromatographed in macrocolumn with silicagel KSS No 3 80/120 mcm with the application of a mobile phase hexane-dioxane-propanol-2 in a ratio of 20:5:1 by volume, eluate fractions, containing the analysed substance, are combined, the eluent is evaporated first in an air flow at a temperature of 18-22°C, and then in a nitrogen flow until the solvent is completely removed, residue is dissolved in dichloromethane, processed for 20 minutes with N-tert-butyl-dimethylsilyl-N-methyltrifluoroacetamide under conditions of heating at a temperature of 60°C with carrying out determination by a chromatography-mass spectrometry method with the application of a capillary column 25 m long with an internal diameter of 0.2 mm with an immobile phase (5%-phenyl)-methylpolysiloxane, with the application of a mass-selective detector, working in an electron impact mode, an initial temperature of the column thermostat constitutes 70°C, the said temperature is kept for 3 minutes, further the temperature is programmed from 70°C to 290°C at a rate of 20°C per minute, the final column temperature is kept for 10 minutes, the injector temperature constitutes 250°C, the quadrupole temperature is 150°C, the temperature of a ion source is 230°C, the temperature of the detector interface is 300°C, intensity of a signal, conditioned by charged particles, formed in the bombardment of the analysed substance, leaving the capillary column and getting into the ion source, with a ionising beam of electrons with the energy of 70 eV, is registered, the mass-spectrum by the complete ion flow is registered and an amount of substituted 2-methoxyhydroxybenzene is calculated by the area of a chromatographic peak of its trimethylsilyl derivative.

EFFECT: achievement of an increased analysis sensitivity.

4 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biology and toxicological chemistry and can be used in chemical-toxicology, expert forensic and clinical laboratories. The method includes: crushing a biological object containing N-(4-nitro-2-phenoxyphenyl)-methanesulphonamide, settling twice for 45 minutes with portions of an organic isolating agent which is methyl acetate, combining the obtained extracts, evaporating the solvent from the resultant extract, treating the residue with acetone, separating the acetone extract, evaporating the solvent from resultant extract, dissolving the residue in diethyl ether, extracting the ether solution with a buffer solution at pH 9-10, acidifying the aqueous alkaline extract with 24% hydrochloric acid to pH 2-3, saturating the obtained solution with sodium bromide, extracting with ethyl acetate, evaporating the obtained extract in an air current at 20-22°C until a dry residue is obtained, dissolving the residue in a mixture of hexane and acetone taken in volume ratio of 8:2, performing chromatography on a macrocolumn with silica gel L 40/100 mcm using a hexane-acetone mobile phase in volume ratio of 8:2, combining eluate fractions containing the analysed substance, evaporating the eluent in an air current at 20-22°C until complete removal of the solvent, dissolving the residue in methanol and performing determination via a combined physical-chemical method in the form of chromatography-mass spectrometry, using a DB-5 MS EVIDEX capillary column with a mobile phase which is 5% phenyl-95% methylpolysiloxane, using a mass-selective detector operating in electron impact mode, the initial thermostat temperature of the column is 70°C, maintaining said temperature for 3 minutes, further raising the temperature from 70°C to 290°C at a rate of 20°C per minute, maintaining the final temperature of the column for 16 minutes, the temperature of the injector is 250°C, the temperature of the quadrupole is 150°C, the temperature of the detector interface is 300°C, detecting strength of the signal resulting from charged particles formed when bombarding the analysed substance coming from the capillary column and falling into an ion source with an ionising electron beam with energy of 70 eV, recording the mass spectrum on the full ion current, while calculating the amount of N-(4-nitro-2-phenoxyphenyl)-methanesulphonamide from the area of the chromatographic peak.

EFFECT: high sensitivity of analysis.

2 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to clinical, laboratory diagnostics, microbiological methods of research, and is aimed at standardisation of saliva analysis by method of wedge dehydration/crystallography. Claimed is method of obtaining standard, quality sample of mixed saliva facia for crystallography with application of portable laboratory device with inbuilt levels on axes X and Y, legs, regulated by height and isolating cover. From 20 to 40 microscope slides are simultaneously placed on the surface of portable laboratory device after obtaining smooth horizontal without inclination angle surface. After that, one sample of mixed saliva in amount 0.02 ml, preliminarily centrifuged for 20 min at 3000 rev/min, is applied on each microscope slide by means of micropipette. As a result a round 1.0 mm high drop of mixed saliva with diameter from 4.0 to 5.0 mm, corresponding to standard parameters, is obtained. Then, standard in dimensions drop on microscope slide placed on the surface of portable laboratory device, adjusted by levels, is dried at room temperature +18…+25°C under isolating cover for 5 hours, with further performance of microscopy of standard quality sample of saliva facia.

EFFECT: obtained sample makes it possible to interpret indices of crystallography without distortions, as standard in volume, dimensions and shape drop of mixed saliva is obtained, and there is no displacement of crystallisation centre and impairment of figures of saliva facia (crystallography pattern) in drop, dried on ideal horizontal surface of the device, ratio of central and peripheral zones of facia exactly correspond to organism's condition, which reduces percentage of false results of crystallography.

3 ex, 1 tbl, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the chemical-pharmaceutical industry and represents a pharmaceutical composition used for treating or preventing a cardiovascular disease in an individual in need thereof and containing at least 95% ethyleicosapentaenoate (ethyl-EPA) encased in a capsule containing gelatine, glycerol, sorbitol, maltitol and purified water, wherein the composition has an initial peroxide number of no more than 5 mEq/kg and the second peroxide number of no more than 8 mEq/kg if stored at 25°C and relative humidity (RH) of 60% for 6 months.

EFFECT: invention refers to a method of treating or preventing the cardiovascular diseases involving administering a therapeutically effective amount of this composition into the individual in need thereof.

18 cl, 4 ex, 4 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: according to a known method of treating the liver disease accompanying type 2 diabetes mellitus involving the baseline therapy of diabetes mellitus and prescribed hepatoprotectors, the above hepatoprotector is presented by Mexicor in a daily therapeutically effective dose of not less than 16 weeks. The therapeutically effective dose of Mexicor makes 100 mg 4 times a day.

EFFECT: higher clinical effectiveness ensured by eliminating the liver disease more prominently, reducing the length of treatment, normalising the liver function test results over a short period of time, and avoiding any side effects.

2 cl, 2 tbl

Pcsk9 vaccine // 2538162

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to immunology and biotechnology. Presented is an immunogen for inducing an immune response to the PCSK9 protein, containing the PCSK9 antigen peptide specified in a group consisting of the disclosed SEQ ID NO: 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 314, 318 and 319, containing the amino acid sequence TRFHRQ, and SEQ ID NO: 182, 183, 184, 185, 186, 187, 188, 317, 401, 402 and 403, containing the amino acid sequence SIPWNLE, wherein the above PCSK9 peptide is conjugated with an immunogenic carrier specified in CRM197 or a Qbeta viral-like particle (VLP). Described is a composition for inducing the immune response to the PCSK9 protein containing at least two immunogens in immunologically effective amounts, wherein the first immunogen represents the above immunogen. Disclosed is a composition for inducing the immune response to the PCSK9 protein containing at least two immunogens in the immunologically effective amounts, wherein the first immunogen is specified in a group of immunogens containing the amino acid sequence SIPWNLE, and wherein the second immunogen is specified in a group of immunogens containing the amino acid sequence TRFHRQ; and wherein the composition can additionally contain at least one adjuvant. What is also presented is a pharmaceutical composition for preventing, treating or relieving PCSK9-related disorders containing: the above immunogen in a therapeutically effective amount, or one of the above compositions, and a pharmaceutically acceptable excipient.

EFFECT: invention enables preparing the effective vaccine for the disorders related to a reaction of the PCSK9 protein and its LDLR receptor.

24 cl, 19 dwg, 6 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyrazolopyridine derivatives of formula (I) , a based pharmaceutical composition, and using them for treating and/or preventing disorders or conditions related to nictonamide adenine dinucleotide phosphatoxidase (NADPH-oxidase), as well as to a method for preparing them and an intermediate of formula (VIII) . In general formula (I), G1 is specified in H; and optionally substituted heteroaryl-C1-C6-alkyl; G2 is specified in H; optionally substituted C1-C6-alkyl; optionally substituted C2-C6-alkenyl; optionally substituted C2-C6-alkinyl; optionally substituted aryl; optionally substituted C1-C6-alkylaryl; optionally substituted aryl-C1-C6-alkyl; optionally substituted heteroaryl; optionally substituted C1-C6-alkylheteroaryl; optionally substituted heteroaryl-C1-C6-alkyl; optionally substituted C2-C6-alkenylaryl; optionally substituted aryl-C2-C6-alkenyl; optionally substituted C2-C6-alkenylheteroaryl; optionally substituted heteroaryl-C2-C6-alkenyl; optionally substituted C3-C8-cycloalkyl; optionally substituted C3-C8-heterocycloalkyl; optionally substituted C1-C6-alkyl-C3-C8-cycloalkyl; optionally substituted C3-C8-cycloalkyl-C1-C6-alkyl; optionally substituted C1-C6-alkyl-C3-C8-heterocycloalkyl and optionally substituted C3-C8-heterocycloalkyl-C1-C6-alkyl; G3 is specified in H; optionally substituted amino; optionally substituted aminoalkyl; optionally substituted aminocarbonyl; optionally substituted alkoxy, optionally substituted alkoxy-C1-C6-alkyl; optionally substituted carbonyl; optionally substituted C1-C6-alkyl; optionally substituted C2-C6-alkenyl; optionally substituted C2-C6-alkinyl; optionally substituted aryl; optionally substituted aryl-C1-C6-alkyl; optionally substituted C1-C6-alkylaryl: optionally substituted heteroaryl; optionally substituted C1-C6-alkylheteroaryl; optionally substituted heteroaryl-C1-C6-alkyl; optionally substituted C2-C6-alkenylaryl; optionally substituted aryl-C2-C6-alkenyl; optionally substituted C2-C6-alkenylheteroaryl; optionally substituted heteroaryl-C2-C6-alkenyl; optionally substituted C3-C8-cycloalkyl; optionally substituted C3-C8-heterocycloalkyl; optionally substituted C1-C6-alkyl-C3-C8-cycloalkyl; optionally substituted C3-C8-cycloalkyl-C1-C6-alkyl; optionally substituted C1-C6-alkyl-C3-C8-hterocycloalkyl and optionally substituted C3-C8-heterocycloalkyl-C1-C6-alkyl; G4 is specified in -NR2-C(O)-R1 and -(CHR3)m-(CH2)n-R4, G5 represents H.

EFFECT: preparing the pharmaceutical composition for treating and/or preventing the disorders and conditions related to nictonamide adenine dinucleotide phosphatoxidase.

16 cl, 3 tbl, 87 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely to endocrinology, and can be used for treating non-alcoholic liver disease accompanying type 2 diabetes mellitus. The declared preparation Mexicor provides reducing manifestations of cytolysis and cholestasis, decreasing the steatosis index, enables improving metabolic lipid and glycaemic values and reducing insulin resistance. Mexicor is applied in a daily therapeutically effective dose of 100 mg 4 times a day for at least 16 weeks.

EFFECT: high pharmacological activity of Mexicor has been shown by achieving the pronounced and stable elimination of fatty liver disease that enables reducing the length of treatment with no side effects.

2 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: pharmaceutical composition contains aleglitezar or its sodium salt in a dose of 0.01 to 0.9 mg.

EFFECT: pharmaceutical composition of aleglitezar is used for treating or preventing type II diabetes mellitus or cardiovascular diseases.

32 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of biotechnology. Characterised is application of therapeutically efficient quantity of peptide GGF2, which contains domain, similar to epidermal growth factor (EGF-like), in treatment or prevention of heart failure in mammal by injection of said peptide every 48 hours in dose, which constitutes from approximately 0.001 mg/kg to approximately 10 mg/kg.

EFFECT: invention improves therapeutic effect with introduction of neuroregulin with minimisation of any potential side effects.

14 cl, 15 dwg, 11 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to phenol derivatives of formula (1), wherein R1 represents C1-C6 alkyl group, C1-C6 alkynyl group, C1-C6 halogen alkyl group, C1-C6 alkyl sulphanyl group or a halogen atom, R2 represents a cyano group or a halogen atom, R3 represents a hydrogen atom, and X represents -S(=O)2. Besides, the invention refers to a drug preparation containing a compound of formula (I) as an active ingredient.

EFFECT: phenol derivatives of formula (1) characterised by the high urine concentration of the permanent compound, and possess the uricosuric action.

11 cl, 1 dwg, 2 tbl, 42 ex

FIELD: biotechnologies.

SUBSTANCE: invention relates to compositions containing vasoactive intestinal peptide (VIP) or its fragments, and to application of such compositions in treatment of aorta fibrosis.

EFFECT: group of inventions is effective in treatment and prophylaxis of aorta fibrosis.

10 cl, 4 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to pharmaceutics and represents a pharmaceutical composition for parenteral administration containing sub-micron particles of dosocahexaenoic acid ester dispersed in a water phase with the use of mixture of at least two surfactants specified in a) at least one fatty acid polyoxyethylene ester and b) at least one phospholipide derivative, as well as a method for preparing the above pharmaceutical composition.

EFFECT: invention provides higher pharmacological activity.

14 cl, 3 dwg, 3 tbl, 2 ex

FIELD: veterinary medicine.

SUBSTANCE: ferroglyukin is administered to new-born calves with iron deficiency anaemia at a dose of 150 mg (2 ml) intramuscularly, twice with an interval of 4 days. Crezacyne 5 mg/kg per day is included in the watering scheme for 4 days, starting simultaneously with the first injection of ferroglyukin. Gamavit is administered intramuscularly once a day in the morning at a dose of 0.05 ml/kg for 4 days, starting simultaneously with ferroglyukin and crezacyne.

EFFECT: method enables to normalise consistently the platelet activity in new-born calves with iron deficiency anaemia during a short period of exposure, transferring it to the level typical of healthy calves, after 4 days of treatment, and to provide long-term maintenance of platelet haemostasis in the optimal mode of operation, eliminating the risk of thrombotic complications in animals and contributing to their normal growth and development.

1 ex

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