RU2465905C2 - Method of slowing premature aging in workers of gas-producing enterprise - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to gerontology, and can be applied for slowing premature aging in workers of gas producing enterprise. For this purpose crestor (rosuvastatin) in dose 5 mg/day daily, independently from food intake and time of day is administered to patient.

EFFECT: invention ensures reduction of aging rate and normalisation of lipid metabolism in said group of patients.

3 tbl, 2 ex

Description

The invention relates to medicine, namely to preventive medicine and gerontology, and can be used to prevent premature aging of persons engaged in gas production.

From the practice of medicine, there is a known method for the prevention of aging, which consists in the fact that the body is exposed to an electromagnetic field with a varying magnetic flux density depending on the mass of selected targets responsible for the aging of the body, in the range from 10 ^-6 to 10 ^-20 G for a given time with the subsequent repetition of effects until a result is achieved, which manifests itself in noticeable changes in the functioning of the body [application No. 96124379/14, 05.25.1995]. However, the known method has disadvantages, such as low efficiency and many contraindications for its implementation.

Also known is a method of using thymalin as an immunomodulator as a geroprotector [Anisimov V.N. Molecular and physiological mechanisms of aging. - St. Petersburg: Nauka, 2003. - 468 p.]. Its disadvantage is the fact that uncontrolled consumption of immunomodulators can lead to an imbalance in the delicate mechanisms of homeostatic control. The effectiveness of its geroprophylactic properties in humans has not been proven, which is explained by the predominantly experimental work on short-lived laboratory animals, a small number of volunteers and a short observation period.

Another way to prevent premature aging is to use trovan (atorvastatin) as a geroprotector, the intake of which for 6 months caused an unreliable decrease in biological age [Pristrom MS, Sushinsky V.E., Semenenkov II, Vorobyova E.P. . Physiological and premature aging. The place of statins in preventing premature aging. // Medical news. - 2009. - No. 6. - S.25-30]. However, this method has the following disadvantages: a small number of examined (35 people), unproven geroprophylactic effect (unreliable decrease in biological age from 54.2 ± 1.02 years to 53.8 ± 1.21 years).

The present invention is aimed at slowing premature aging in workers of a gas production enterprise.

The specified technical result is achieved by appointing a cross (rosuvastatin) at a dose of 5 mg / day daily, regardless of the meal and time of day, which causes a slowdown in premature aging.

Krestor (rosuvastatin) is the most effective among many lipid-lowering drugs in lowering LDL cholesterol, which also significantly increases HDL cholesterol and slows the progression of the atherosclerotic process, the main cause of cardiovascular disease. Possessing an immunotropic effect, it suppresses the increased activity of physiological activators of apoptosis - pro-inflammatory cytokines, initiated by the chronic exposure to hydrogen sulfide-containing gas. As a result, the start of the apoptosis inducer, p53 protein, is blocked and the activity of apoptosis, which plays a leading role in the development of the premature aging of the body, is reduced. In our study, we used a significantly lower dose of cross (5 mg / day) than the recommended 10 mg / day, due to many factors (better adherence to treatment, good tolerance to low doses, which allowed taking all the examined patients without exception, the economic aspect associated with the high cost of the drug). Given the pharmacokinetic and pharmacodynamic characteristics of the drug Krestor, a single dose per day is sufficient to achieve the result, regardless of the time of day or meal.

All examined had a study of biological age according to the method of Chebotarev D.F. Aging is considered premature if the aging rate is the difference between biological (BV) and proper biological age (DBV)> 0, physiological with BV-DBV = 0. Potential long-livers BV-DBV <0. Determination of the concentration of interleukin-8 and p53 protein was carried out by the method of enzyme-linked immunosorbent assay using reagents OOO "Cytokine" St. Petersburg, JSC "BioHimMak", Moscow.

Initially, gas production workers showed a significant increase in the rate of aging compared to the control group and the concentration of statistically significant predictors of premature aging - interleukin-8, protein p53, total cholesterol, low-density lipoproteins (LDL) (table 1).

Examination during therapy with a cross revealed a significant decrease in the rate of aging by 1.5 times (34%), the concentration of the apoptosis inducer - protein p53 by 1.6 times (38%), and the pro-inflammatory cytokine - IL-8 by 1.2 times (17 %), total cholesterol 1.3 times (22.5%), LDL 1.4 times (29%). The total cholesterol values obtained during the treatment with the cross did not exceed 4.4 mmol / l, LDL - 3.5 mmol / l, interleukin-8 - 31.25 pg / ml, p53 protein - 2.02 U / ml, which corresponds to the level control groups (tables 2, 3).

In individuals who did not take the cross (comparison group), after 18 months, an increase in the studied parameters was found compared with the initial ones. The level of total cholesterol was 28% higher, LDL was 33% higher than that of people taking the cross. The aging rate increased by 40%, the concentration of the apoptosis marker - p53 protein - by 43%, the proinflammatory cytokine - IL-8 - by 17% compared with people who received geroprotective therapy. Received after 18 months, increased lipid profile, interleukin-8, p53 protein and the aging rate in people who did not take the cross, indicate the activity of premature aging under the influence of a complex of production factors of the gas producing enterprise and necessitate geroprophylaxis (tables 2, 3).

The proposed method was tested on 100 employees of Gazprom dobycha Astrakhan LLC for 18 months, all males, average age 43.46 ± 9.23 years, average work experience in contact with hydrogen sulfide 12.25 ± 8.5 years. The study was carried out on the basis of the Non-governmental Healthcare Institution “Health Unit”. The control group included 30 employees of the construction organization "AGAT" of the main working specialties who have no contact with hydrogen sulfide, the average age is 40.14 ± 10.1 years, experience 10.32 ± 7.42 years. Groups by age and length of service did not significantly differ from each other (p> 0.05). Exclusion criteria for both groups were conditions that can cause pro-inflammatory hypercytokinemia and activation of apoptosis: the presence of IHD, arterial hypertension, diffuse nodular goiter, proliferative diseases (prostate adenoma, cysts of various organs), hematological diseases, chronic diseases in the acute stage, and acute disease in the next 3 months, contact with infectious patients for a month.

Below are the results of testing.

Example No. 1

Patient K., born in 1956, master at Gazprom Dobycha Astrakhan LLC, 17 years of experience. Of the diseases - SARS, chronic gastritis in remission. Bad habits: smoking for about 25 years at 20 cigarettes a day, alcohol abuse denies. There are no relatives of long-livers.

About: Condition is satisfactory. Proper physique, moderate nutrition. The skin of normal color, clean. No peripheral edema. The vesicular breathing, no wheezing. NPV 18 per minute. The boundaries of relative cardiac dullness are not expanded, heart sounds of moderate volume, the rhythm is correct, heart rate is 89 beats. per minute, blood pressure 130/80 mm Hg The abdomen is soft, painless. Liver on the edge of the costal arch. Physiological administration is normal.

On examination:

Complete blood count: red blood cells 5.35 * 10 ¹² / l, hemoglobin 160 g / l, white blood cells 6.2 * 10 ⁹ / l, platelets 208 * 10 ⁹ / l, ESR 5 mm / hour.

Biochemical analysis of blood: glucose 5.7 mmol / L, ACT 31 IU / L, ALT 36 IU / L, creatinine 92.2 mmol / L, urea 6.6 mmol / L, total cholesterol 5.98 mmol / L, V -lp 61 srvc units, triglycerides 2.36 mmol / L, HDL 0.93 mmol / L, LDL 4.5 mmol / L, IPT 99%, fibrinogen 3.54 g / L.

General analysis of urine: s / f, acidic, specific gravity 1.010, protein neg., Sugar neg., Squamous epithelium single in p / s, urate salts.

The serum concentration of IL-8 was 35.72 pg / ml, p53 protein 2.38 U / ml. Biological age (BV) 56.6 years, due biological age (DBV) 51.3 years, the rate of aging (BV-DBV) is 5.3 years.

A patient with an accelerated rate of aging is assigned a cross at a dose of 5 mg / day, regardless of food intake and time of day.

After 18 months:

About: Condition is satisfactory. Proper physique, moderate nutrition. The skin of normal color, clean. No peripheral edema. The vesicular breathing, no wheezing. NPV 18 per minute. The boundaries of relative cardiac dullness are not expanded, heart sounds of moderate volume, the rhythm is correct, heart rate is 70 beats. per minute, blood pressure 120/80 mm Hg The abdomen is soft, painless. Liver on the edge of the costal arch. Physiological administration is normal.

On examination:

Complete blood count: red blood cells 5.21 * 10 ¹² / l, hemoglobin 149 g / l, white blood cells 5.8 * 10 ⁹ / l, platelets 240 * 10 ⁹ / l, ESR 7 mm / hour.

Biochemical analysis of blood: glucose 5.1 mmol / L, ACT 28 IU / L, ALT 28 IU / L, creatinine 86 μmol / L, urea 5.4 mmol / L, cholesterol 4.3 mmol / L, V-LP 43 conv. units, triglycerides 1.33 mmol / L, HDL 1.41 mmol / L, LDL 2.95 mmol / L, IPI 84%, fibrinogen 3.24 g / L.

General analysis of urine: s / f, acidic, specific gravity 1.018, protein neg., Sugar neg., Squamous epithelium, single in n / a.

The serum concentration of IL-8 was 30.14 pg / ml, p53 protein 1.68 U / ml. Biological age (BV) 56.6 years, due biological age (DBV) 52.2 years, the rate of aging (BV-DBV) is 4.4 years.

Thus, while taking the cross for 18 months, the content of total serum cholesterol decreased by 28%, LDL decreased by 34%, the concentration of IL-8 decreased by 16%, protein p53 by 29%, the aging rate slowed by 0.9 years (17%). Given that the levels of atherogenic lipids, a pro-inflammatory cytokine, and apoptosis marker have reached the parameters of the control group, this clinical example demonstrates the effectiveness of prescribing a cross as a means of slowing premature aging in people engaged in gas production. Because contact with harmful production factors continues, the patient is recommended to continue taking the cross (rosuvastatin).

Example No. 2

Patient M., born in 1958, gas welder at Gazprom dobycha Astrakhan LLC, 14 years experience. Of the diseases - SARS, osteochondrosis of the cervicothoracic spine. Bad habits: smoking - 25 cigarettes per day for about 20 years, alcohol abuse. The presence of relatives of the centenarians denies.

About: Condition is satisfactory. Proper physique, moderate nutrition. The skin of normal color, clean. No peripheral edema. The vesicular breathing, no wheezing. NPV 18 per minute. The boundaries of relative cardiac dullness are not expanded, heart sounds of moderate volume, the rhythm is correct, heart rate is 89 beats. per minute, blood pressure 130/80 mm Hg The abdomen is soft, painless. Liver on the edge of the costal arch. Physiological administration is normal.

On examination:

Complete blood count: red blood cells 4.9 * 10 ¹² / L, hemoglobin 152 g / L, white blood cells 6.7 * 10 ⁹ / L, platelets 224 * 10 ⁹ / L, ESR 6 mm / hour.

Biochemical analysis of blood: glucose 4.7 mm / l, ACT 14 IU / l, ALT 24 IU / l, creatinine 94.5 mmol / l, urea 5.1 mmol / l, cholesterol 5.92 mmol / l, B- lp 60 srvc units, triglycerides 2.07 mmol / L, HDL 0.93 mmol / L, LDL 4.8 mmol / L, IPT 102%, fibrinogen 3.2 g / L.

General analysis of urine: s / f, acidic, specific gravity 1.021, protein neg., Sugar neg., Squamous epithelium, single in p / s, urate salts.

The serum concentration of IL-8 was 34.02 pg / ml, p53 protein 2.97 U / ml.

Biological age (BV) 55.86 years, due biological age (DBV) 50.01 years, the rate of aging (BV-DBV) is 5.85 years.

The patient showed an accelerated rate of aging, increased lipid profile, interleukin-8 and p53 protein. The patient refused the recommended reception of the cross.

After 18 months:

About: Condition is satisfactory. Proper physique, moderate nutrition. The skin of normal color, clean. No peripheral edema. The vesicular breathing, no wheezing. NPV 18 per minute. The boundaries of relative cardiac dullness are not expanded, heart sounds of moderate volume, the rhythm is correct, heart rate is 72 beats. per minute, blood pressure 135/80 mm Hg The abdomen is soft, painless. Liver on the edge of the costal arch. Physiological administration is normal.

Complete blood count: red blood cells 5.16 * 10 ¹² / l, hemoglobin 158 g / l, white blood cells 7.4 * 10 ⁹ / l, platelets 268 * 10 ⁹ / l, ESR 9 mm / hour.

Biochemical analysis of blood: glucose 5.7 mm / l, ACT 32 IU / l, ALT 44 IU / l, creatinine 116 mmol / l, urea 7.1 mmol / l, cholesterol 6.88 mmol / l, V-lp 69 conv. units, triglycerides 2.9 mmol / L, HDL 0.86 mmol / L, LDL 5.4 mmol / L, IPT 107%, fibrinogen 3.94 g / L.

General analysis of urine: s / f, acidic, specific gravity 1.016, protein neg., Sugar neg., Squamous epithelium, single in p / s, leukocytes 1-2-1 in p / s, salts of oxalate.

The serum concentration of IL-8 was 36.86 pg / ml, p53 protein 3.46 U / ml.

Biological age (BV) 58.21 years, due biological age (DBV) 50.95 years, the rate of aging (BV-DBV) is 7.26 years.

Thus, over the past 18 months, the content of total cholesterol in blood serum increased by 14%, LDL by 11%, the aging rate increased by 1.41 years (by 19%), the concentration of IL-8 increased by 8%, p53 protein by 14 % An increase in the level of atherogenic lipids, a pro-inflammatory cytokine, a marker of apoptosis, and the rate of aging indicate that contact with harmful production factors leads to the progression of premature aging, and demonstrates the need to prescribe anti-aging agents.

The proposed method is achieved:

- slowdown of premature aging of gas production workers by 1.5 times (by 34%);

- a decrease in pro-inflammatory hypercytokinemia - a 1.2-fold decrease in the concentration of interleukin-8 (by 17%);

- a decrease in the concentration of the marker of apoptosis - p53 protein by 1.6 times (by 38%);

- a decrease in the content of atherogenic LDL lipids by 1.4 times (by 29%) and total cholesterol by 1.3 times (by 22.5%);

- the method is simple, affordable, well tolerated, performed in outpatient practice, does not require special training.

The proposed method is recommended for use in medical institutions serving persons employed in the production of gas production.

Table 1 Comparative characteristics of the aging rate, lipid profile, p53 and interleukin-8 protein concentration in the studied groups Groups Aging rate / years Total cholesterol / mmol / l LDL / mmol / L p53 protein, U / ml IL-8, pg / ml Primary (n = 100) 5.38 ± 0.7 ** 5.42 ± 0.6 * 4.36 ± 0.5 * 2.9 ± 0.37 * 34.9 ± 1.7 * Control (n = 30) 0.97 ± 0.58 4.1 ± 0.3 3.19 ± 0.18 1.7 ± 0.28 28.52 ± 2.5 * - p <0.05 - significantly in comparison with the control group ** - p <0.01 - significantly in comparison with the control group

table 2 Comparative characteristics of lipid profile before and after treatment Total cholesterol / mmol / l V-lp / srvc units Triglycerides / mmol / L HDL / mmol / L LDL / mmol / L Before treatment (n = 100) 5.42 ± 0.6 * 50.8 ± 5.9 1.64 ± 0.2 1.4 ± 0.2 4.36 ± 0.5 * After treatment (n = 70) 4.2 ± 0.2 43 ± 3.9 1.35 ± 0.2 1.5 ± 0.2 3.1 ± 0.4 Comparison Group (n = 30) 5.86 ± 0.48 ** 52.2 ± 4.7 2.17 ± 0.36 * 1.23 ± 0.19 4.61 ± 0.3 ** * - p <0.05 - significantly in comparison with indicators after treatment ** - p <0.01 - significantly in comparison with indicators after treatment

Table 3 The dynamics of the rate of aging, the concentration of p53 and IL-8 protein during treatment with a cross Protein p53, U / ml IL-8, pg / ml Aging rate / years Before treatment (n = 100) 2.9 ± 0.37 ** 34.9 ± 1.7 * 5.38 ± 0.7 * After treatment (n = 70) 1.8 ± 0.22 29.15 ± 2.1 3.52 ± 0.51 Comparison Group (n = 30) 3.14 ± 0.29 ** 35.2 ± 2.16 * 5.82 ± 0.61 ** * - p <0.05 - significantly in comparison with indicators after treatment ** - p <0.01 - significantly in comparison with indicators after treatment

Claims (1)

A method of slowing premature aging in workers of a gas production company, including prescribing the drug Krestor (rosuvastatin) at a dose of 5 mg / day daily, regardless of food intake and time of day.