Method of correction of lipid peroxidation in patients with ischemic heart disease

 

(57) Abstract:

The invention relates to medicine, namely cardiology, and can be used for the correction of lipid peroxidation in patients with ischemic heart disease. Spend complex treatment with long-acting nitrates, calcium antagonists, and aspirin. Additionally impose a suspension of fetal liver tissue, heart, lung, and placenta of the fetus 16-20 weeks simultaneously separately subcutaneously in the anterior abdominal wall in the amount of 1 ml Method helps to normalize blood lipid profile and peroxidation processes. It slows the progression of coronary atherosclerosis and improves patient outcomes. 3 table.

The present invention relates to the field of medicine, namely cardiology, and can be used in treatment of coronary heart disease (CHD) due to coronary stenosis atherosclerosis.

The increase in the concentration of peroxide oxidation of lipids (Pol) over the stationary level is regarded as a universal mechanism of cellular damage in various pathological conditions, including coronary heart disease, due to coroner Rakitnoe oxidation of lipids. As the progression of the disease increases the content of lipoperoxides in serum and antioxidant activity decreases, indicating a decrease in the body content of antioxidants (2). Correction of cholesterol and blood lipids in patients with coronary artery disease stabilize during atherosclerosis and contribute to clinical remission (3).

The known correction method personage lipid oxidation in patients with coronary heart disease, including use as an antioxidant drug Preductal in the dose of 60 mg/day (20 mg 3 times a day), divertida at a dose of 0.08 g/day (0.02 g 4 times a day) for 3-4 weeks. If necessary, after 3 months, repeat the treatment. These drugs are prescribed for a comprehensive treatment of coronary heart disease (4,5).

The disadvantages of the known method for correcting processes of lipid peroxidation should include the fact that these drugs are prescribed for a long time and after a certain period of time is necessary to repeat the treatment. In addition, Preductal contraindicated in patients with hypersensitivity to this drug.

Closest to the proposed therapeutic effect of oxidant vitamin E (-tocopherol). Action-tocopherol in the cell is associated with its ability to act as an antioxidant and stabilizer of cell membranes (6).

When coronary stenocereus atherosclerosis drug-tocopherol administered 100 mg / day vitamin And 0.125 mg/day for 20-40 days. After 3-6 months of treatment with vitamin E repeat (7).

The disadvantages of this method include the pain and the appearance of infiltrates intramuscular injection, the possibility of allergic reactions. Also be careful when using vitamin E in patients with severe infarction and myocardial infarction, as large doses of this drug can have the opposite effect - the intensification of the processes of peroxide oxidation (8).

The task of the invention is to develop a method that allows you to adjust the processes of lipid peroxidation and the level of LPO products in the body.

The technical result of the present proposal is to restore the oxidative processes in the body and, as a consequence, clinical remission for coronary heart disease.

This problem is solved by the method lies in the via, calcium antagonists and aspirin advanced simultaneously and separately impose a suspension of fetal liver tissue, heart, lung, and placenta of the fetus 16-20 weeks at number 1 ml subcutaneously in the anterior abdominal wall.

Comparative analysis of the claimed and known solutions shows that you don't know the use of complex fetal tissues liver, lung, heart, human placenta for the correction of peroxidation processes in patients with coronary atherosclerosis.

From the comparative analysis shows that the proposed facility meets the criterion of "novelty."

The inventive method achieves perceived by the applicant of the technical result, namely the stabilization of the flow of coronary heart disease by restoring the oxidative processes in the body.

In the implementation of the proposed method is a significant reduction products of lipid peroxidation: malondialdehyde (MDA) and diene conjugates (DC) 29.1 and 22.9%, respectively; the increase in the concentration of antioxidant-tocopherol 37.1%; the decrease in the concentration of total cholesterol on average by 10.8%, low density lipoprotein by 9.3%, triglycerides by 26.4% (ceeres 3 months from start of treatment).

Clinical remission is expressed in significantly reducing the number of angina attacks per day, lower doses of antianginal drug therapy, to increase tolerance to exercise, strengthen sexual function.

From the above it follows that the claimed invention meets the condition of patentability "industrial applicability".

In the analysis of known methods revealed in them, the lack of information on the impact of the distinctive features of the method on the achievement of the technical result, therefore, the invention meets the criterion of "inventive step".

The essence of the invention consists in the introduction into the body of the suspension of fetal liver tissue, heart, lung, and placenta.

The basis for the use of fetal tissues is their high plastic and functional capacity, the absence of factor immunogenicity and the ability to stimulate and/or compensation functions similar bodies - target in the body of the recipient.

So the liver is the main organ that performs the functions of regulation and synthesis of cholesterol, lipoproteins, triglycerides in the body.

Sanzinia cell receives a "fresh" genetic information about the normal operation of the body.

The use of suspensions of fetal placental cells due to the overall positive reaction of the recipient, which consists in the activation of all metabolic processes.

Fetal tissue has no factor immunogenicity and after transplantation does not occur complications such as graft versus host. Transplanted fetal tissue donor stimulates all the functions similar to the body of the recipient.

Clinical research of the authors of the proposed method found that transplantation of the proposed complex suspensions of fetal human tissue has a mild corrective and at the same time prolonged effect on the FLOOR system of the body - the main blood lipids, i.e., is a beneficial effect on the clinical course of CHD, which is expressed in clinical remission in the reduction of medication, basic treatment, to increase opportunities for physical activity in significantly reducing the number of angina attacks per day (p <0.01), and in enhancing sexual function in men, and slow the progression of the pathological process of coronary atherosclerosis (10). Thus, the authors of the proposed method on the 6th month of nabludenii 16.6%, increasing the concentration of antiatherogenic high-density lipoproteins HDL 24.9%.

The inventive method is as follows.

For the implementation of the proposed method obtaining fetal liver tissue, lung, heart and placenta human conduct when conducting a medical abortion in specialized medical institutions. Received fetal liver tissue, heart, lung, and placenta process technology, Moscow Institute of biological medicine, homogenized and then cryopreserved. Thereafter, the resulting suspension fetal tissues are placed in a separate cryo boxes and stored in liquid nitrogen (at a temperature of -196oC).

Immediately before transplantation containers with fetal tissue is thawed in a water bath at a temperature of 40oC for 5 min.

Thawed suspensions of fetal tissues of liver, heart, placenta enter 1 ml suspension subcutaneously in different areas of the anterior abdominal wall.

The essence of the proposed method is illustrated with an example.

In a clinical study group included 30 patients who received transplantation of fetal tissue between ochestration atherosclerosis of the coronary arteries, confirmed coronary angiography data. The average age of patients was 59,610,6 years (from 49 to 72 years). Disease duration before inclusion in clinical study was 5,00,4 year. 90% of patients in this group was diagnosed hypercholesterolemia.

2 weeks before the beginning of studies of drug therapy in these patients was the most standardized and included long-acting nitrates (conicet at a dose of 40 mg / day) and calcium antagonists (corinfar 60 mg per day) combined with aspirin 1 time a day at a dose of 0.125 mg per day.

Limitations in usual diet was not conducted.

All patients received local injection in the region of the anterior abdominal wall suspensions of fetal tissues of liver, heart, lung, and placenta of the fetus 16-20 weeks at number 1 ml subcutaneously. Each suspension contained 1 g of fetal tissue in 5 ml of cryoconserved /nutrient medium 199/.

Determination of investigated parameters was performed before treatment and subsequent testing after 3 weeks, 1,5; 3 and 6 months. When the statistical processing of the results was carried out using the method of variation statistics with the calculation of the coefficient of t student.

Indicators of lipid peroxidation is different patients are presented in table 2.

The control group consisted of a group of patients in 20 people who have received medical treatment, including long-acting nitrates (conicet 20 mg 2 times a day), calcium antagonists (Corinth 20 mg 3 times a day) and aspirin (0.125 mg per day).

Table 3 presents the results of the control group after 6 months of starting treatment.

The data given in tables 1 and 2 demonstrate the positive impact on CHD transplantation suspensions of fetal tissue, which confirms the change process indicators of lipid peroxidation and lipid profile. A distinct increase in antioxidant activity 56.4% observed after 1.5 months from the start of treatment, the concentration of vitamin E (-tocopherol) increased by 37.1% and, consequently, decreased the concentration of peroxide oxidation: malondialdehyde and diene conjugates 29.1 and 22.9%, respectively. As a result of normalization processes of peroxidation of normal blood lipid spectrum, resulting in significantly lower concentrations of total cholesterol by 10.8%, cholesterol of low-density 9.3%, cholesterol very low density 27.8%, triglycerides by 26.4%, FOS is, the increased concentration of high density lipoprotein by 7.4% (after 3 months from start of treatment). The trend toward normalization of lipid levels and processes of lipid peroxidation was observed within 6 months of starting treatment.

In the above example, the stabilization of the lipid spectrum of blood within 6 months indicate clinical remission of the disease and slow down the progression of coronary atherosclerosis.

Determination of antioxidant activity of blood serum was performed according to the method Klebanov, I. (11) at a wavelength of equal to 532 nm ( = 532 nm), then measured and expected concentration of diene conjugates method Gavrilova at = 232 nm (12) and TBA-active products by the method of Yagi K. at = 532 and 580 nm (13). Fluorimetric method was determined by the content-tocopherol (14).

Biochemical studies were performed using a standard set of firm Boehringer Mannheim (Germany) on the biochemical analyzer "Corona" by LKB (Sweden).

Cholesterol was determined using reagents enzyme cholesterol esterase in the formation of an equivalent amount of hydrogen peroxide, determined spectrophotometrically (15).

Triglycerides were determined by the method of enzymatic hydrolysis by release of glycerides glycerin, which was determined coulometrically (17).

Phospholipids were determined using cholinesterase education equivalent amount of hydrogen peroxide, which was colorimetrically (18).

These blood parameters: total cholesterol, HDL cholesterol, triglycerides, phospholipids determine colorimetrically, the following indicators mathematically; VLDL was determined by the ratio TG/5; cholesterol LDL-OH-Helpit-Helpop= Hpnp; haemoglobin rate CA:

(OH-Helpit)/Hlpvip (19).

Thus, the inventive method allows to correct the processes of lipid peroxidation and the level of LPO products in the body and consequently to achieve a clinical remission for coronary heart disease.

Literature

1. Cholbi M. R. , Paya and Icaraz: Experimentia, 47 (2). - 1991. - R. 195-199.

2. Dmitriev L. F. Biochemical aspects of atherogenesis: ralentissement //Therapeutic archive, 1995. - 12. - M. : Medicine. - S. 73-77.

3. Vladimirov, Y. A. , Arch the s medicines. Radar - Doctor /Ed. Krylov Y. F. , 2nd edition. M. , 1999. - S. 770.

5. The remedy for the treatment of diseases "Decortin": production, standardization, pharmacological properties and clinical research /Tyukavkina N. A. , Rudenko I. A. Kolesnik Y. A. and others

6. Versalovic B. N. , Podgorny, I. L. , Podgorny L. M. and other Impact-tocopherol in water-soluble form on the membrane of human erythrocytes during their contact with oxygen //Biol. science. - 1990. - 11 - C. 35-42.

7. Mashkovsky M. D. Medicines. So 2. - M. : Medicine, 1987. - S. 26.

8. Mashkovsky M. D. Medicines. So 2. - M. : Medicine, 1987. - S. 34.

9. Gale R. P. Fetal liver transplantation. - N. V. 1985. -P. 73-83.

10. Transplantation of fetal tissue and human cells. - M. , 1996. - S. 86-91.

11. Klebanov, I. , Babenkov I. C. , teselkin Y. O. Evaluation of antioxidant activity of blood plasma with the use of yolk lipoproteins //lab. case. - 1988. - 5. - S. 59-62.

12. Gavrilov Century B. , Meskarune M. I. Definition of diene conjugates in serum. - Lab. case. - 1983. - 3. - S. 33-36.

13. Yagi, K. , Nishigaki I. , H. ohama [hot news] Measurement of serum TBA-value. //Vitamins. - 1968. - V. 37. - 1. - R. 105-112; modification Yagi Y. , Matsuda M. , Yagi K. Fomation of lipoproxide in isdated sciatic nerve by chinoform-terric cheel et al. Clin. Chem. 29 (1075) 1983.

16. Burstein M. Et al. J. Lipid. Res. 11. 583. 1970.

17. Kohlmeir M. Clin. Chem. 32, 63, 1986.

18. Takayama et al. Glin. Chim. Acta 79; 93. 1977.

19. Klimov A. N. , Nikulicheva, 1984. - 168 C.

Method of correction of lipid peroxidation in patients with ischemic heart disease, including the introduction of long-acting nitrates, calcium antagonists and aspirin, characterized in that it further simultaneously separately injected suspension of fetal liver tissue, heart, lung, and placenta of the fetus 16-20 weeks at number 1 ml subcutaneously in the anterior abdominal wall.

 

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FIELD: medicine, otorhinolaryngological surgery.

SUBSTANCE: one should apply thin layer of "Solcoseryl" gel onto osseous facial walls of frontal and maxillary sinuses at the border with trepanation opening after removing pathological content out of them and before applying a transplant out of flat bone of human fetal cranial arch that exceeds the diameter of trepanation opening by 3-4 mm. Then, one should additionally fix the transplant by affecting with distal edge part of a light guide of semi-conductor laser "ATKUS-15" with contact-type technique at output power of laser radiation being 8 W at constant mode. The method enables to increase fixation density of allobrefobone to osseous walls of sinus along its whole diameter.

EFFECT: higher efficiency of fixation.

1 ex

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