The way to determine the level of nonspecific resistance of the organism

 

(57) Abstract:

The invention relates to the field of medicine, but can also be used in veterinary medicine to determine the level of nonspecific resistance of the organism (UNRO) both human and animal. Determine the content of thiol (-SH) and disulfide (-SS-) groups in the studied substrate of blood and thiol-disulfide ratio (TDS). As a test substrate used at the same time whole blood and cellular concentrate blood. Define TDS in whole blood and TDS in cell concentrate blood repeatedly for at least 24 hours of cultivation with an interval of 30-180 minutes. Build graphics dependency indicators TDS on the time of cultivation. UNRO determined by the ratio of the area under the graph of dependency RTD - time cultivation in whole blood to the area under the graph of dependency RTD - time cultivation” in cell concentrate blood. The method improves the accuracy of determining the level of nonspecific resistance of the organism.

The invention relates to medicine (but may be used in veterinary medicine) for systematic evaluation of the level of nonspecific resistance of a living organism of both man and animal with different the ptx2">The known method for integral evaluation of human health (see RF Patent №2119768, IPC 6 And 61 In 10/00 published 10.10.98, Bulletin No. 28) by examination of the person for each element of the system of “health”, and the number of elements of this system, in addition to health indicators reflecting human activity, include the factors of environment and society, affecting human health factors), an evaluation of each element of the system of “health”, including nonspecific resistance of the organism (NRA), produced on the basis of specific quantitative criteria in actual or contingent (point) units of measurement, system of “health” are quantitatively differentiated on the six levels of health, then determine the overall level of health, then prognostically evaluate the dynamics of the whole system of “health” and its separate elements; to assess the level of nonspecific resistance and immune protection carry out a quantitative assessment of the content in blood of various populations of lymphocytes (T-, B-, O-lymphocytes and immunoglobulins (G, M, A).

Also known quantitative method of complex assessment of human physical performance (I. C. Aulich. The definition of physical health h the IR major physiological systems of the body without consideration of environmental factors and society.

The disadvantages of these methods is the large number of ongoing qualitative and quantitative assessments not only psycho-physiological functions of the human body, but also environmental factors, the practical difficulty of their application in clinical medicine, insufficient assessment of factors related to non-specific resistance and the immune defense of the organism.

The closest medical fact to claimed is a method of assessing the NRA (centuries Sokolovsky. Thiol-disulfide ratio of blood as an indicator of the state of nonspecific resistance of the organism. The tutorial. St. Petersburg, 1996, 30 s), according to which determine the content of thiol and disulfide groups in the studied substrate of blood and calculate the measure of their quantitative ratio (thiol-disulfide ratio - TDS).

The main disadvantages of this method are significant fluctuations in TDS in a short period of time, a large variability in the performance of RTD using different laboratory methods of research that depends on the type used selective electrodes (platinum, silver, mercury, and others) using the method of amperometrical criteria correlation between the degree of change in TDS and severity of the pathological condition of the body. In addition, not installed, what is the constituent of blood cellular elements, serum, plasma; protein, protein-free part of the substrate, etc.,) or whole blood are the most appropriate substrate for an adequate assessment of TDS as a criterion of the level of the NRA (UNRA).

The basis of the invention is the task of such improved method of estimating the NRA, which due to use as a test substrate at the same time whole blood and blood cell concentrate, as well as multiple dynamic monitoring TDS allows the most accurate determination of specific UNRO and assess the extent of changes in various pathological conditions.

The task is achieved in that in the method of assessing the level of nonspecific resistance of the organism, including the determination of thiol and disulfide groups in the studied substrate of blood and their quantitative ratio (TDS), and then determine the state of the NRA, according to the invention as a test substrate used at the same time whole blood and cellular concentrate blood, determine TDS in whole blood and TDS in cell concentrate blood many times within n the Yeni cultivation, and UNRO determined by the ratio of the area under the graph of dependency RTD - time cultivation in whole blood to the area under the graph of dependency RTD - time cultivation” in cell concentrate of blood.

The causal link between the proposed set of features and achievable medical results is as follows.

Numerous experimental and clinical studies have shown that the reversible thiol-disulfide system is critical in the regulation of redox balance in cells and tissues of the human body; with her related biochemical mechanisms of virtually all physiological processes, including cell division and growth, the intensity of metabolism and enzyme activity, regulation of the permeability of biological membranes, muscle contraction, hormonal functioning and neuroreceptors, and operation of the various components of the immune system and nonspecific defense. In clinical and experimental studies in humans and animals fluctuations TDS had a clear connection with the development of physiological adaptation to unfavourable conditions (noise, vibration, laser and electron what I trauma and stem vagoinsulyarnogo paroxysm, ischemic heart disease and myocardial infarction, toxicosis of pregnancy and septic conditions). It is established that the definition of close binaries in the blood of people and animals can be used for detection of pre-pathological conditions, early diagnosis of diseases and monitoring of the in vivo state of nonspecific resistance of the organism and prognosis of the disease.

Laboratory methods of determining the content of thiol and disulfide groups include amperometric titration with silver nitrate, spectrophotometric method with reagent Allman, chromatography and other Substrate for the study can serve as blood and other body fluids and tissues, but most often the TDS is in the blood or its components (cellular fraction, plasma). However, due to the very high volatility (fluctuations) and the sensitivity of the indicator RTD to the effects of their own biorhythms of the body and environmental factors (temperature, natural background solar radiation, electromagnetic waves, radioactive rays and other) and consequently poor reproducibility metric TDS there is a need to develop a more stable and informative indicator for assessing the status is Ovi and cellular concentrate blood, again, within a certain period of time (i.e., dynamics). It is known that blood cells are largely reflect the state of the main biochemical processes and nonspecific resistance at the level of the microorganism. The extracellular part of blood comprises a system of functional humoral factors of nonspecific resistance. The proposed correlation dynamics TDS in whole blood compared to TDS in cell concentrate blood is able, in our opinion, more fully and accurately reflect adaptive capacity, level of homeostasis and nonspecific resistance of the organism taking into account this structural dvukhkomponentnoi blood system, the consequence of which is increased informativity assessment of the NRA.

The application of the proposed method includes the following sequence of actions implemented in the following specific examples of implementation of the proposed method.

The patient in the morning on an empty stomach made the blood from the cubital vein in a volume of 3.0 ml, mixed it with anticoagulant 5% solution of sodium citrate (0.3 ml). Then nitrate blood was divided into 2 tubes in equal parts, then Proboscidea of them was carefully removed the supernatant liquid part and the remainder of the cell concentrate was used for further studies (control sample). At the same time used whole blood from another tube, which served as the main sample of the study. Method amperometric titration with silver nitrate was determined at the same time the original TDS in whole blood lysate and cell lysate concentrate blood. Then both tubes were cultured in an incubator, and after 30 minutes, 1 hour, 3 hours and 24 hours of cultivation was re-defined RTD in the main and control samples. Then build 2 plot of TDS from the time of cultivation (main and control) and perform the calculation of the ratio of the areas under the graphs as TDS factor (CTDS):

CTDS=“TDS×time cultivation” inTDS×time cultivation in QC

where is the blood, QC - cell concentrate of blood.

This indicator has a high reproducibility and does not depend on the method of its determination (amperometric titration with silver nitrate, including various selective electrodes, or by spectrophotometric determination).

This study was conducted in 352 patients. The results obtained showed that the rate CTDS has a high correlation (r=0,91) with H individuals (blood donors) indicators CTDS ranged from 1.0 to 0.9 (conventional units), reflecting normal UNRO. Most patients with various degrees of violations of the health status indicators CTDS varied from 0.89 to 0.30 (.E.). The conventional division of the severity of the patient at 3 degrees (General condition of “good”, “moderate”, “severe”) correlated with the gradation reduce CTDS first degree (CTDS in the range of 0.89-0.70 to do.E.), Grade II (CTDS within 0,69-0,50.E.) and III (CTDS in the range of 0.40-0,30.E.) respectively. For a more detailed assessment of ORO used selection 2 subgroups (a and B) for each degree of changes in this indicator, which helped to highlight the 6 levels of the NRA, correspond to the following ranges of indicator CTDS: 0,89-0,80 consistent decrease in UNRO light (I) the extent of 0.79-0.70 to - moderate (I B degree) reduction, 0,69-0,60 - significant (II And extent) the decrease of 0.59-0.50 to - expressed (II degree) the decrease of 0.49-0.40 is pronounced (III And degree) reduction and 0.39-0.3 to critical (III B degree) decrease.

Thus, we propose a modification of the universally recognized indicator of the state of nonspecific resistance (RTD), qualitative (definition CTDS) and quantitative aspects (gradation degrees ISME, Kiev diagnosed with adenocarcinoma of the upper and middle lobes of the right lung with metastasis to the lymph nodes in the mediastinum and upper lobe of the left lung, metastatic exudative pleurisy on the right (with the presence of malignant cells in the exudate); IV stage IV clinical group. The patient's General condition was assessed as moderate, CTDS=0,78 (decrease I B degree, i.e. the reduction of moderate). Then the patient received chemoimmunotherapy (cycle of chemotherapy alternated with subsequent immunotherapy) monthly 4 of course, the effect of the treatment were assessed as “stabilization of disease; indicators CTDS (monthly) ranged approximately at the same level: 0,72 (decrease I B degree) - in November 2002, 0,70 - in December 2002, from 0.76 in January 2003, Then came deterioration with clinical and radiographic evidence of progression of the neoplastic process, CTDS=0,42 (February 2003, a decrease III And extent, i.e. the reduction pronounced). However, using ordinary course of chemoimmunotherapy conducted with individual selection of drugs on the method of pre-screening with blood in vitro) achieved partial regression of the tumor and metastases, metric CTDS again increased to 0,71 (March 2003), the reduction of the I B degree), and then in April 2003 CTDS=0,77 (there is further regression of the tumor). In may 2003, after the 6th course of chemoimmunotherapy state snizhenie significant in the face of moderate anemia, b=98 g/l). After haemostimulating therapy (iron preparations, recombinant erythropoietin, vitamin C, b group, folic acid) overall condition and performance of improved blood (b=122 g/l) figure CTDS (June 2003) was 0.73 (decrease I B degree, i.e., a moderate decrease). The patient achieved remission of neoplastic disease with partial regression of adenocarcinoma in both the lungs and the lymph nodes in the mediastinum, the complete elimination of metastatic pleural effusion; the General condition of the patient is assessed as satisfactory, the quality of life is good.

Example 2. Patient T., 70 years. In October 2002, KB No. 17, Kiev diagnosed with cancer of the middle lobe of the right lung with metastasis in the left lung, IV phase IV clinical group. The patient's General condition was assessed as moderate, CTDS=0,75 (decrease I B degree, i.e. the reduction of moderate). Then in October-December 2002, the patient received monthly rate (1st, 2nd, 3rd courses) individualized (based on the screening of drugs in blood in vitro) chemoimmunotherapy, the condition was stable, relatively satisfactory, were observed partial regression of the tumor in the lungs. Indicators CTDS was also on the same level: 0,87 (decreased I continued to receive individualized chemoimmunotherapy (4, 5-th, 6-th courses), under the influence of which neoplastic disease stabilized, the patient's General condition was satisfactory. Indicators CTDS during this time was also stable: 0,87 (decrease I And degree, January 2003), 0,81 (decrease I And degree, February 2003), 0,86 (decrease I And degree, March 2003). In April 2003, the patient was observed exacerbation of ischemic heart disease with ekstrasystolichniy fibrillation. The patient's General condition suffered slightly, remained relatively satisfactory, CTDS=0,78 (decrease I B extent, the decrease moderate, April 2003). The patient received a cardiac treatment with positive clinical and ECG dynamics. Currently, the patient is in satisfactory condition of the house, neoplastic disease stabilized, the quality of life is good.

The way to determine the level of nonspecific resistance of the organism (UNRA), including the determination of thiol (-SH) and disulfide (-SS-) groups in the studied substrate of blood and their thioldisulfide ratio (TDS), characterized in that as the test substrate used at the same time whole blood and cellular concentrate blood, determine TDS in whole kratom build dependency graphs of figures TDS on the time of cultivation, and UNRO determined by the ratio of the area under the graph of dependency RTD - time cultivation in whole blood to the area under the graph of dependency RTD - time cultivation” in cell concentrate of blood.



 

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