Laboratory method of diagnosing bipolar affective disorder

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to a method of diagnosing bipolar affective disorder. The essence of the method consists in the fact that reliable differences in the spectrum of protein distribution in blood serum without proteins albumin, immunoglobulin G, immunoglobulin A, antitrypsin, transferin and haploglobin in patients with endogenic psychosis. If protein spots are detected on electrophoretic gel in areas with the molecular weight of 200, 84, 75, 49, 40 kDa in the patient with endogenic psychosis, bipolar affective disorder is diagnosed.

EFFECT: application of the claimed method makes it possible to increase accuracy in diagnostics being simple in realisation.

2 ex

 

The invention relates to medicine, specifically to psychiatry, and can be used for laboratory diagnosis of bipolar affective disorder.

Bipolar affective disorder (previously manic depression) is a disorder characterized by repeated episodes in which the mood and activity levels are significantly disturbed [1, 2]. In some cases there is a lift in mood, increased mental and physical activity (mania or hypomania), in others, depressed mood, decreased energy and activity (depression), as well as mixed States in which the person has symptoms of depression and hypomania/mania at the same time (for example, depression with overexcitement, anxiety, or euphoria with retardation), or rapid change of symptoms (Hypo)mania and (sub)depression[1, 3, 4,].

The etiology of bipolar affective disorder (BAR) till now is not clear. The first episode often occurs at a young age - 20-30 years, however, it is possible the occurrence of the disease at any age from childhood onwards. Its frequency of occurrence in the population of 0.5-1.0%. Manic episodes usually begin abruptly and last from 2 weeks to 4-5 months. Depression have a tendency towards a longer period (average duration of about 6 IU�acev), although notes and duration more than one year. Subsequent affective (depressive, hypomanic/maniakalny, mixed) episodes within the BAR can occur with a certain periodicity. Remission typically shorten with age, and depression become more frequent and longer after middle age[1, 5, 6, 7].

In clinical practice, bipolar affective disorder often has a similar clinical picture with other endogenous disorders such as, schizophrenia, acute polymorphic psychotic disorder, especially if the structure of the current affective episode is present psychotic symptoms. But the tactics of treatment of psychosis and outcome of various diseases. Therefore, timely and accurate diagnosis of bipolar affective disorder plays a significant role in the appointment of adequate treatment and the formation of a favorable prognosis of the disease[8, 9, 10, 11].

Currently there is no laboratory method for diagnosis of bipolar affective disorder. For diagnosis use only clinical-psychopathological and anamnestic data, based on clinical assessments of the prevalence of pathological symptoms, defined by the International classification of diseases 10th revision [12]. Therefore, relevant search parak�incesti criteria for the diagnosis of bipolar affective disorder. In addition, laboratory findings will help to correct individual therapy for the patient.

In the studied literature adequate prototype of the present invention is not found. A patent search revealed no patents devoted to laboratory diagnosis BAR.

The object of the invention is to develop a laboratory method for the diagnosis of bipolar affective disorder.

The problem is solved by evaluating differences in the distribution of serum proteins in different types of endogenous psychoses method for one-dimensional electrophoresis. The differences in protein regions 200, 84, 75, 49, 40 kDa only characterize bipolar disorder. In patients with other forms of endogenous psychoses proteins in these areas does not occur. In healthy individuals protein spots in these areas are also absent.

New in the proposed method is to use the results of one-dimensional electrophoresis of serum of patients with endogenous psychoses and in the presence of the gel protein bands in the regions corresponding to molecular masses of 200, 84, 75, 49, 40 kDa diagnosed with bipolar affective disorder in comparison with other forms of endogenous psychoses and healthy individuals.

The study of differences in the electrophoretic distribution of the protein spectrum of blood serum of persons � different forms of endogenous psychoses and bipolar affective disorder was chosen as the that according to the literature and our results in the pathogenesis of these disorders revealed significant changes of protein spectrum of patients. At the present stage actual research aimed at finding a specific protein markers of endogenous psychoses [10, 11]. By proteomic analysis of serum or plasma of patients with mental disorders studies are not numerous and are represented mainly by the works of schizophrenia. For proteomic research BAR there are a few works. Specific protein markers BAR does not exist yet.

Looking at the distribution of serum proteins in bipolar affective disorder the method of one-dimensional electrophoresis was carried out. Identification of specificity of the distribution of proteins of the blood serum of bipolar affective disorder will be the basis for laboratory diagnosis of this disorder. The identification of specific protein markers, or regulatory proteins involved in the pathogenesis of bipolar affective disorder, is available for use for diagnostic purposes the biomaterial - serum will significantly increase the accuracy of diagnosis of bipolar affective disorder.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived isurava technology in this area is not obvious to the specialist. Identical set of features not found in the patent and scientific and medical literature. This method can be used in health care to apply individual treatment.

Based on the above, should be considered the present invention with the relevant conditions of paternopoli: "Novelty", "Inventive step", "Industrial applicability".

The invention will be clear from the following description.

The proposed criteria (differences in electrophoretic distribution of proteins in blood serum of patients BAR) the BAR method of laboratory diagnosis and differential diagnosis from other forms of endogenous psychoses and healthy persons received as a result of clinical and biological examination of patients with established relevant diagnoses. All patients were treated in offices, clinics, research Institute of mental health, Russian Academy.

Analyzed the serum protein spectrum of blood 100. Surveyed 80 people undergoing inpatient treatment in the clinics of the fgbi "mhri" SB ramsci. Of them, 55 people had a diagnosis of schizophrenia various forms and 25 bipolar affective disorder.

The control group consisted of 20 mentally and somatically healthy individuals matched for sex and age with the study groups. In all groups was held�ANO following ratio: 44% were male, and 56% women. The age range was from 19 to 46 years, mean age of 29.1±8,65 years, Diagnoses have been exposed psychiatrists clinics fsbi "mhri" SB ramsci in accordance with the international classification ICD-10 [12]. Psychopathological symptoms were documented according to the guidance "Evaluation checklist and a Glossary for mental disorders for ICD-10.

Laboratory examination of examined persons was conducted at admission to the clinic to pharmacotherapy. Blood sampling was performed in the morning on an empty stomach using a tube type activator Vacuette clot formation for separation of serum. For separation of serum from formed elements of the tube of blood was centrifuged at 2000 g for 20 minutes in a centrifuge cooled to +4 C0 Orto Alresa Digicen 21R (Spain).

Analysis of the proteome is complicated by the presence of major proteins in very high concentrations. To remove 6 major proteins (albumin, immunoglobulin G, immunoglobulin A, antitrypsin, transferrin and haptoglobin) studied serum after 5-fold dilution with buffer, centrifugation and filtration through a standard filter with a diameter of 22 microns was used affinity chromatography on the chromatograph of the company "Agilent Technologies (USA). After affinity chromatography purified proteins were concentrated to 1 ml with �via ultrafiltration through filters Microcon - ultra (MILLIPORE, France) at 5 kDa. Then concentrated protein samples were subjected to separation by electrophoresis in 12% polyacrylamide gel by the method of Laemmli U. K. After analytical electrophoresis gels were stained with a dye Coomassi Brilliant Blue G250 for 12 hours. Then washed before rendering coloring pages. To facilitate identification of the molecular weight of the proteins under investigation on an empty track made protein markers. A set of protein markers is a blend of 12 highly purified recombinant proteins after polyacrylamide gel electrophoresis and fixing Coomassie Brilliant Blue R-250 form a discrete band in the range of 10-250 kDa. The set of markers is suitable to estimate the size of the protein studied relative to the standards of the marker. The intensity of the bands corresponding to proteins of 25 and 80 kDa, arranged for easy identification. We used the markers company Fermentas.

The resulting gels were photographed using gel system-documentation Alliance 2.7 Uvitec manufacture of Cambridge. System gel documentation has a software package by which is calculated the molecular weight of separated proteins. Stand out protein bars, and the program automatically calculates the molecular mass of each protein spot from the marker.

Statistics�ical analysis of the research results conducted on a personal computer using the software package statistical software STATISTICA 8.0. The significance of differences between groups was determined using Fisher's exact test with correction Yates. Statistically significant differences were considered at p<0,05 [13].

The evaluation of the number of differences in the electrophoretic distribution of the proteins of the blood serum of patients with bipolar affective disorder and healthy subjects obtained significant differences in 16 regions of the protein spectrum allocation.

When comparing the distribution of proteins in patients with bipolar disorder and patients with schizophrenia were found significant differences between these two pathologies in 13 regions of the protein spectrum. Analyzing and comparing all the obtained results, identified areas of protein spectrum, characteristic only for bipolar affective disorder: 200, 84, 75, 49, 40 kDa. The detected differences in the spectrum distribution of proteins of blood serum is supposed to be used for laboratory diagnosis of bipolar affective disorder.

Thus, using the detected characteristic only for patients with bipolar affective disorder, differences in the electrophoretic spectrum of the distribution of proteins of the blood serum, as an additional paraclinical diagnostic method BAR will increase the accuracy of diagnosis and, sootvetstvenno�, assignment of the most appropriate individual treatment of the patient.

As an illustration, here are clinical examples:

Example 1. The patient Peninsula, 1968 year of birth. Place of work: not working.

History: Heredity burdened with mood disorders, dementia, alcohol dependence, antisocial and homicide behavior. The mother of the patient born out of wedlock, against her father knows nothing, "has a very strange character: grim, constantly irritated and yells". Could not talk for several days, only to shout back insults. Worked at the winery for 20 years on the bottling line, after the closure of the brewery was on the Association of the virion working. Incomplete higher education, he quit teaching on fartface medical Institute after 3rd year "for the birth of the patient."

Sister of the grandmother on the mother died in a psychiatric hospital in 1984, before his death did not recognize anyone. Almost all blood relatives on the mother "had a problem with alcohol, the law and head", "the two reached the bums, second cousin killed his father, served and sells drugs".

Father to 8 years old, also grew up in a single-parent family (father not known), his mother died of tuberculosis when my father was 8 years old, then grew up in an orphanage. Other close relatives of father no. Father nature "more than JWP�ventiv, but too violent, especially when drunk." He is easily the opinions of others, your point stands rarely, mostly no stopping mother. Often tricks without even thinking, writes an unthinkable history". The father higher technical education; worked in construction as an engineer, then a commercial Director and a procurement officer.

Family relationships were very difficult parents "strongly argued, even fought, then reconciled, were drinking together". Father abused alcohol. In childhood the patient education have engaged in more than father, mother looked after kids. Brother 39 years, "a different kind of character: toward a patient "refers with obvious condescension, as to the loser, always gives good gifts and free tickets to football, nothing helps". Is a candidate of technical Sciences, head of Department at a large enterprise.

Sister 38 years, she was head of Department in a large Bank; the nature like her mother ("touchy and taciturn"). A close relationship between the sisters is not.

Patient by nature was a very timid, shy, even withdrawn. Kindergarten did not attend, together with his brother and sister were under supervision of the grandmother. Time spent mostly at home in the company of brother and sister, they were playing in the yard. In games in childhood with other children was basically a slave. In HQ�flax age was obsesively the tips pioneer tie, biting my nails, pens. Nature "decided to change itself" after grade 8: more to communicate, make friends, in grade 9 elected YCL class, then groups (at the University). So began to play "first role". Studied well, was distinguished by diligence. All the items was easy. Didn't like the classes. Eagerly studied at the art school. Friends were few. Participated in the initiative was a host of concerts, painting posters, in high school, was on the Committee of the Komsomol. Wanted to be a doctor, scientist, teacher of Mineralogy or art history, "wanted to communicate with wonderful, interesting people."

On the advice of his mother after school he entered the faculty of Economics of TSU. At the University he was fond of cross-country skiing, had the first rank. 18 years experienced warm feelings for the man, the beginning of sexual life. At the age of 19 became pregnant, but the young man was frightened of responsibility", and she had an abortion (at the insistence of the mother). Experienced happened about two years, "just all burnt inside has changed a lot, became more rigid, very thin and angry". Beginning to take revenge on men, "dizzy and throw", "put fans in the collection.

He graduated from the University with honors. Distribution came on CPP immediately to a responsible position, one hundred�PWM economist-financier. Relationships at work was difficult, there was a conflict with the direct supervisor, the patient "has found more cash and peaceful place (jewelry store) and went away."

Married since 1990, the first few years of the relationship was harmonious, "then started the conflict". The husband seemed infantile, untenable. Later husband graduated and began working, in parallel, have started a business (with the patient) and became "self-sufficient person." In 1997, the first pregnancy with threatened abortion 4 weeks, was carried out hormonal support up to 14 weeks, was in hospital for saving for 7 months, then underwent emergency surgical delivery. Was born a healthy daughter. The patient again fell in love with her husband, could not breathe": he was the father, a businessman, to decide all questions... Soon got pregnant again, the decision was made about the birth of her second child: pregnancy was hard (on keeping in the hospital the patient was 2 months in the later stages, there was a high pressure), ended prompt delivery. In 2000, the husband became interested in another woman and left the family. Money in the family was not enough, the patient began to work in a pawnshop, since 2002, began working in the store selling hats. Job liked, brought prosperity, the patient was "just happy �and work." In the spring of 2010 production was sold to the "effective Manager", which led to bankruptcy of the enterprise.

In 2005 addressed to the psychiatrist of the center of social support of the population with complaints of irritability, depressed mood, tearfulness, resentment, loss of appetite, insomnia. In six months took fluoxetine, noted improvement in mood and overall well being. Also conducted psychotherapy (individual or group), provided financial assistance.

The present deterioration in the winter of 2010, when after the change of leadership became strained relationships in the team, significantly decreased wages, increased requirements for staff. Felt a sense of inner tension, irritability, hopelessness of the situation, disturbed sleep and appetite, decreased weight. By the summer of 2010, the mood began to rise spontaneously, appeared self-confidence, activity, energy. The patient decided for a pittance to purchase the production. Nights developed plans to change the organization of work in the enterprise. Easily convinced many friends to join equity, prepared the documents for the transaction. One morning she woke up and found that the energy is over, the mood was unstable, there were doubts and insecurities. �was rotaliana to lose weight, because "forgetting to eat", in the morning woke up at 4-5 o'clock in the morning, thinking about the correctness of the decision. Abandoned their plans, quit my job. On the recommendation of the psychologist of the center of social support have applied for consultative psychiatric help and agreed to hospitalization. 17.11.10 G. was admitted to hospital 3 Department clinic fsbi "mhri" SB ramsci.

Mental status on admission: looks younger than his age. Medium height, of asthenic physique has a deficiency of weight. During the conversation often changes the pose, sit with a straight back, head held high, occasionally straightens his shoulders. Hair long, painted in red color, carelessly combed. Cosmetics does not use. Facial expression happy, smiling. In the conversation formal. Voice quiet, good modulation. It is correct. The accelerated pace of speech. Vocabulary rich. In conversation marked a sudden change in the topic of discussion. In the sayings sarcastic, irritable. Had expressed criticism of family and self-criticism. Complains of constant headaches in the frontal-temporal region, tearfulness, feelings of inner tension, reduced appetite, weight. Also concerned about difficulty falling asleep and early awakening in the morning. Notes fatigue, decreased sense of vitality, a stimulus�spine. But then reports that it feels good that have previously experienced such feelings burst of energy, vigor and vitality. Says stopped watching TV, reading the newspaper that he prefers to move, to communicate. Its state regards as painful. The mood is unstable, with fluctuations over hours and days. Libido is reduced. Criticism of our behavior and the saved state.

The presence of hallucinations or other unusual psychic experiences, a sense of exposure, openness or otherness of thought denies. Attention is diffused. Memory on current events a bit low. The high intelligence, matches the quality of the education, age and lifestyle.

Mental state qualifies mixed affective state.

As a result of treatment leveled off mood, stabilized appetite, night sleep, gained weight, decreased irritability and makes plans for the future, independently carries out the work.

At discharge recommended: observation of a psychiatrist, a therapist at the place of residence, to continue taking Depakine-Chrono 1000 mg/day for at least 12 months with a subsequent decision of a question on necessity of prolongation normotimicheskoe therapy.

Rationale diagnosis:

Hereditary aggravated in the discussed case is Paul�the polymorphic character: mood disorders dementia, alcohol dependence, antisocial and homicide behavior. In history there is evidence of at least three depressive episodes (19, 38 and 42 years), hypomanic state in the summer of 2010; In the last years there has been a rapid cyclic formation of the current BAR. Currently, the clinical picture of the affective phase meets the criteria for a mixed state (mood change over hours and days, increased activity, energy, insomnia in the presence of a decreased appetite, weight and libido). Affective disorders chronologically experienced earlier signs of organic brain syndrome.

Diagnosis: Bipolar affective disorder, current mixed episode (F 31.6)

Electrophoretic analysis of the distribution of proteins of blood serum by the method of vertical electrophoresis revealed the presence of protein bands in the regions corresponding to molecular masses of 200, 84, 75, 49, 40 kDa. In areas corresponding to molecular masses 128, 114, 21 kDa protein bands are absent.

Example 2. (sick paranoid form of schizophrenia). Case history No. 1129. Patient L., born in 1980, sick 8 years, lives in Tomsk, a student.

History: heredity psychopathologies burdened: great-aunt was observed by a psychiatrist with "voices". Our patient was born as the second child�m of three children in an intact family. Grew and developed with a slight lead. The character was unsociable, extremely slow, modest, timid, shy. Relatives considered her wayward, as demanded from others "to do the right thing"; Moody, T. K. could "throw a tantrum" if you didn't get what she wants. In the school years was a "homebody". Considered myself a "gray mouse", "the ugly duckling", worried about the figures, considering himself too full. The school went from 7 years, classes are not duplicated. Study liked, was easy. The classes were responsible, was considered the "right hand" of the teacher, was President of the class, supervised school activities. Among classmates was considered the "black sheep".

After 11 classes enrolled in the Siberian state medical University at the faculty of pharmacy. In the first year studied successfully. While studying on the second year (1998-1999) the conflict began with the girls (roommates in the Dorm) due to the fact that the patient worked at night, because it was extremely slow. Very worried about this, ceased to absorb new material, a clock could be "stuck" on one page, not understanding the meaning of what was read. Often crying, disturbed sleep. In the same period of time began to notice that slowly flowing thoughts, break, get lost; became alarming. Appeared UB�idenote in what all the "wrong" relate to it, on the street, "look askance" at her heels. Felt intense fear, anxiety, feeling of "something awful". To anyone about their experiences was not told to the doctors for help was not sought. Against this background appeared academic debts, applied for academic leave. Then repeatedly tried to work in low skilled jobs (maid, nurse), but with extreme slowness, growing weakness, lethargy, apathy, increased fears the work was done satisfactory. Sought help from a psychiatrist, but refused hospitalization, medical treatment is received.

In 2002 he entered the medico-pharmaceutical College. The studying was hard, it was hard to write, to absorb new information, could not write lectures, because remember how to write the letter, did not understand the words of the lecturer, conflict with classmates. In connection with the academic Dept was expelled. In the spring of 2002 at the insistence of relatives again went to a psychiatrist. Was given a referral for inpatient treatment in the clinic of Institute of PZ; hospitalized in 2 office. But from the hospital went AWOL, because I realized that I would be able to handle myself. In December 2002, the state has further deteriorated: hearing women's condemning voice inside �olovi. Felt the sound of his own thoughts, felt her thoughts could manage, put the "wrong" thoughts. Thought stalking her, watching her surrounding. It seemed that back about "someone" who was watching her. Cried often appeared suicidal thoughts, disturbed sleep. Became even more closed fenced off. No longer cope with responsibilities at home, because he "forgot" the sequence of executed actions. Accompanied by relatives, came to the clinic of Institute of PZ. Hospitalized voluntarily.

Mental state at admission: focused true. Looks unkempt. Kept wary of the stress. Hypomimia, monotonous. With barely comprehending asked questions. Believes that stalking her, watching her, others do not so relate to it, "see" her through; hearing voices inside the head, giving orders. In thinking amorphous slips, mantissa, sperrung, ambivalence.

In the course of psychotherapeutic work in a hospital demonstrates isolation, isolation. The patient focused on psychotic symptoms, worries that will not be able to leave the hospital and start a normal life." By the third week condition improved significantly against the reduction of hallucinatory-paranoid symptoms, the patient became more Uwe�internal, making plans for the future.

As a result of the treatment condition improved; degenerate affective painted hallucinatory-paranoid symptomatology, systemized thinking, behavior, Varanasi mood and normal sleep. It moved as criticism full. After discharge, were able to recover in a College.

During the psychotherapy outpatient, the patient made the request to reduce stigmatizing effects of the disease, removal of the threat of repeated exacerbations. Profile of quality of life decreased subjective views on the vector of mental state, intellectual productivity. For the eighth session behavior has changed, the patient became less isolated in their experiences, it is easier to converge with people. After returning to school, talked with fellow students.

The presence of disorder in the film leading hallucinatory-delusional syndrome (syndrome Kandinsky-Louis-Nicolas clérambault), duration of disease, thought disorder, emotional-volitional reduction allows us to set the diagnosis of schizophrenia, paranoid form.

Electrophoretic analysis of the distribution of proteins of blood serum by the method of vertical electrophoresis revealed the presence of protein bands in the regions corresponding to the molecular mass of 128, 114, 21 kDa. In areas corresponding mole�usrnam masses 200, 84, 75, 49 and 40 kDa protein bands are absent, indicating the absence of a BAR.

The method is quite easy to implement, you only need a camera for the production of vertical electrophoresis in polyacrylamide gel of any firm. Typically the electrophoretic separation of proteins in polyacrylamide gels using all biochemical laboratories. All used reagents are very cheap, for determining the presence of proteins with the desired molecular weight is required only markers of molecular weights. The method allows to analyze simultaneously from 12 to 24 patients, the time period for this amount with regard to the preparation chamber for electrophoresis for about two hours.

Literature

1. Mosolov S. N. Bipolar affective disorder (diagnosis and treatment): monograph / S. N. Mosolov. - M.: Publishing house of Medpress, 2008. - 383 p

2. Martinez-Aran A, Vieta E, Colom F, Torrent C, Sanchez-Moreno J, et al. Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome // A. Martinez-Aran, E. Vieta, F. Colom, C. Torrent, and J. Sanchez-Moreno // Bipolar Disord. - 2004, No. 6. - 224 S.-32.

3. Martinez-Aran A, Vieta E, Sanchez-Moreno J, Goikolea JM, Salamero M, et al. Functional outcome in bipolar disorder: the role of clinical and cognitive factors // A. Martinez-Aran, E. Vieta, J. Sanchez-Moreno, JM. Goikolea, M. Salamero // Bipolar Disord. - 2006, No. 8. - S. 1-11.

4. Zubieta JK, Huguelet P, O'neil RL, Giordani BJ (2001) Cognitive function in euthymic bipolar I disorder // JK. Zubieta, P. Huguelet, RL. O'neil, BJ. Giordani // Psychiatry Res. - 2001, No. 102. - S. 9-20.

5. Bonnín CM, Martínez-Arán A, Torrent C, Pacchiarotti I, Rosa AR, et al. Clincal and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term, follow-up study. // CM. Bonnin, A. Martinez-Aran, C. Torrent, I. Pacchiarotti, AR. Rosa // Journal of Affective Disorders. - 2010, No. 121. - S. 156-160.

6. Kauer-Sant'anna M, Bond DJ, Lam RW, Yatham LN (2009) Functional outcomes in first-episode patients with bipolar disorder: a prospective study from the Systematic Treatment Optimization Program for Early Mania project // M. Kauer-Sant'anna, DJ. Bond, RW. Lam, LN. Yatham // Compr Psychiatry. - 2009, №50 (1) - S. 1-8.

7 Kauer-Sant'anna M, Yatham LN, Tramontina J, Weyne F, Cereser KM, et al. (2008) Emotional memory in bipolar disorder // M. Kauer-Sant'anna, LN. Yatham, J. Tramontina, F. Weyne, KM. Cereser // Br J Psychiatry. - 2008, №192 (6). - S. 458-63.

8 Samame, Martino DJ, Strejilevich SA (2012) Social cognition in euthymic bipolar disorder: systematic review and meta-analytic approach // C. Samame, DJ. Martino, SA. Strejilevich // Acta Psychiatr Scand. - 2012, №125(4). - S. 266-80.

9 Domenici, E. Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections // E. Domenici // PLoS. - 2010, №5. - S. 30-32.

10 Prabakaran, S. 2-D DIGE analysis of liver and red blood cells provides further evidence for oxidative stress in schizophrenia // S. Prabakaran, M. Wengenroth, H. Lokstone // Journal of Proteome Research. - 2007, №6. - S. 141-149.

11 Baez S, Herrera E, Villarin L, Theil D, Gonzalez-Gadea ML, et al. Contextual Social Cognition Impairments in Schizophrenia and Bipolar Disorder // S. Baez, E. Herrera, L. Villarin, D. Theil, ML. Gonzalez-Gadea // PLoS ONE- 2013, №8(3). - S. 564-74.

12. Churkin A. a Brief guide to using ICD-10 in psychiatry and addiction / A. A. Churkin, A. N. Martyusgov. - M.: publishing house of the Triad-X, 1999. - 232 p.

13. Glants S. Mediko-biological statistics / S. Glants. - M.: publishing house of the Practice, 1999. - 459 p.

Laboratory method for the diagnosis of bipolar affective disorder, characterized by the fact that they take blood from patients with endogenous psychoses, separate the serum to�AVI, removing proteins: albumin, immunoglobulin G, immunoglobulin a, antitrypsin, transferrin and haplogroup, spend one-dimensional electrophoresis and in the presence of the gel protein bands in the regions corresponding to molecular masses of 200, 84, 75, 49, 40 kDa, diagnosed with bipolar affective disorder.



 

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9 cl, 4 tbl, 4 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to a method of predicting a probability of reduction of the glomerular filtration rate (GFR) after 3 months of observation after aortocoronary bypass surgery without artificial blood circulation (ACBS without ABC). The essence of the method consists in the fact that the concentration of a kidney injury molecule of type 1 (KIM-1) is determined in blood serum, the ratio of the biomarker KIM-1 concentrations in two time points after 48 hours and 7 days after the operation is calculated and if its value is higher than 1.5, a conclusion about the probability of (GFR) reduction in the remote period after ACBS without ABC is made.

EFFECT: application of the claimed method makes it possible to predict the probability of the glomerular filtration rate (GFR) reduction after 3 months of observation after aortocoronary bypass surgery without artificial blood circulation in an efficient and accurate way.

1 tbl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: early diagnostic technique for pulmonary thromboembolism consists in the fact that if the patient shows any clinical signs indicative of the probability of pulmonary thromboembolism, blood serum fibrin D-dimer is supposed to be measured; if the fibrin D-dimer is less than 0.5 mg/l, a suspected case of pulmonary thromboembolism is cleared of, whereat blood serum fibrin D-dimer of 0.5 mg/l and more requires measuring blood serum interleukin-8 additionally by enzyme immunoassay, and if the measured concentration is 21.3 pg/ml and more, pulmonary thromboembolism is diagnosed.

EFFECT: more accurate and informative diagnostics.

2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of biotechnology, namely to obtaining oligopeptide compounds, containing a motive, interacting with a proliferating cell nuclear antigen (PCNA) and can be used in medicine. The oligopeptide compound consists of 14-70 amino acids and contains. a PCNA-interacting motive, representing [K/R]-[F/Y/W]-[L/I/V/A]-[L/I/V/A]-[K/R], at least one signal sequence of nuclear localisation and at least one signal sequence of penetration into a cell, with the PCNA-interacting motive being located towards an N-end relative to the signal sequence.

EFFECT: invention makes it possible to carry out the efficient treatment of hyperproliferative disorders by the application of the oligopeptide compound in cyctostatic therapy or in radiotherapy as a sensitising substance.

34 cl, 6 dwg, 4 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: method involves determining female serum cytotoxicity to male lymphocytes, including a combined culture with reference male and analysed female serum in a 96-well tray in the presence of the nutrient medium RPMI 1640 in a CO2 incubator. One day later, lymphocytes are counted in the well in a Goryaev's chamber with the male (reference) and female (analysed) serum. That is followed by determining a cytotoxic index (CI), which represents a quotient of the analysed cell count and the reference cell count. The normal cytotoxic index makes approximately 0.7 and less.

EFFECT: invention enables studying the responses of female humoral immune factors to male antigens and evaluating a risk of miscarriage, early spontaneous abortions and missed miscarriages.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a high-sensitivity method for measuring the amount of individual's blood plasma glycyrrhizin, glycyrrhetinic acid and their pharmaceutically acceptable salts. The high-sensitivity method for measuring the amount of glycyrrhizin, glycyrrhetinic acid and their pharmaceutically acceptable salts is characterised by the fact that a mixture of individual's blood plasma with methanol or ammonia water in the specific concentration is introduced into a solid phase having the reverse-phase distribution function and the anion exchange function; the solid phase is then washed with a cleaning fluid that is a single-component fluid or a mixed fluid of at least two components specified in a group containing water, alkali, alcohol and acetonitrile. That is followed by elution from the solid phase in acid alcohol specified in formic acid - methanol or formic acid - ethanol; that is followed by the stage of measuring glycyrrhizin, glycyrrhetinic acid and their pharmaceutically acceptable salts by liquid chromatography - mass spectrometry or liquid chromatography - mass spectrometry/mass spectrometry.

EFFECT: high-sensitivity method enables detecting and measuring the amounts of individual's blood plasma glycyrrhizin, glycyrrhetinic acid and their pharmaceutically acceptable salts.

4 dwg, 17 tbl, 7 ex

FIELD: veterinary medicine.

SUBSTANCE: method comprises selection of only living, mature females of Trichuris vulpis from colon, blind gut of wild and/or domestic carnivorous animals infected spontaneously with whipworms in the study with helminthological methods when autopsy, into separate tubes with officinal isotonic solution (0.9%) of sodium chloride (solutio Natrii chlorati isotonica) and the exposure of the tubes with the females of Trichuris vulpis at t = 37.5-39°C for 5 hours under conditions of a thermostat.

EFFECT: method enables to select a large amount of fertilised eggs of T vulpis, not contaminated with particles of undigested feed, the particles of destroyed tissue of genitals of female of T vulpis and secondary bacterial microflora.

2 ex

FIELD: medicine.

SUBSTANCE: patient's peripheral venous blood is recovered to analyse genetic polymorphisms of coagulation factors VII 10976G/A FVII. A birth weight of a newborn of a woman delivering not for the first time in the stage of 37 and more weeks of pregnancy is determined by equation: y=6123.431-25.579x1+0.267x2+205.739x3, wherein y is an anticipated newborn's weight, x1 is a female's height in centimetres; x2 is an infant's weight at the previous delivery in grams, x3 is a genetic version of 10976G/A FVII locus with x3=1 for 10976 GG FVII genetic type, x3=2 for 10976 GA and 10976 AA FVII genetic types. A birth weight of a newborn of a woman delivering for the first time in the stage of 37 and more weeks of pregnancy is determined by equation: y=6278.037-21.739x1+232.170x2, wherein x1 is a female's height in centimetres; x2 is a genetic version of 10976G/A FVII locus with x2=1 for 10976 GG FVII locus, x2=2 for 10976 GA and 10976 AA FVII genetic types.

EFFECT: invention enables improving the prevention and treatment of the pregnancy complications.

2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: pre-operative fasting venous blood 1 ml is sampled at room temperature 20-24°C into an anticoagulant-free vacuum system (test tube). The test tubes are delivered in a sealed container at temperature 2-8°C for 2 hours to a laboratory for immunoenzyme assay and analysed to determine anti-thyroid stimulating hormone receptor antibodies. If the antibody level is 1.5 units/l or more, a thyroidectomy is performed, whereas the antibody level of less than 1.5 units/l requires performing a subtotal thyroid resection according to standard techniques.

EFFECT: invention enables reducing a probability of recurrent thyrotoxicosis in the patients after subtotal thyroid resection.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to a method for the prediction of a risk of early microvascular complications in the children suffering from type 1 diabetes mellitus. The substance of the method consists in defining a duration of the diseases in years, the patient's age in years, a desquamated endothelial cell count, high-density lipoprotein cholesterol, total cholesterol, triglycerides, atherogenic index, glycohaemoglobin, average daily glycaemic level; making a linear regression analysis and calculating a risk ratio (R) of early microvascular complications in the children suffering from type 1 diabetes mellitus by formula. If the risk ratio is ≥1, the high risk of early microvascular complications during one year is predicted; the ratio < 1 shows the low risk of microvascular complications during one year.

EFFECT: using the declared method enables increasing the prediction accuracy of microvascular complications in the children with type 1 diabetes mellitus.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and can be used for patient's status monitoring. A method for setting a time-varying physiological parameter warning signal involves patient's controlled parameter monitoring, comparing the controlled parameter to an initial cut-off criterion, varying the cut-off criterion temporarily by a cut-off criterion of deterioration after the therapy, and then after a certain period of time, by the cut-off criterion after the administration. The time allowed involves comparing the controlled parameter to the cut-off criterion of deterioration, and after the time allowed - to the cut-off criterion after the administration. The warning signal is initiated in response to the controlled parameter of one or more initial cut-off criteria, the cut-off criterion of deterioration and the cut-off criterion after the administration. The group of inventions also refers to a machine-readable carrier with software for implementing the method and to a system for user warning on the controlled parameter variation.

EFFECT: group of inventions provides higher accuracy and rate of assessing the patient's status according to the conducted therapy.

15 cl, 6 dwg

FIELD: medicine.

SUBSTANCE: invention can be used for the purpose of the early prediction of cystic periventricular leukomalacia (PVL) in the newborns with very low (VLBW) or extremely low body weight (ELBW). Substance of the method: the newborns with VLBW and ELBW on the 3rd-7th day of life are examined to assess the perinatal medical history, namely the presence of chorioamnionitis and amniotic fluid nature, 5th minute Apgar score, the absence of prolonged artificial pulmonary ventilation, a severity of respiratory distress syndrome, the presence of pneumonia, sepsis, convulsive disorder, anaemia, laboratory signs of the systemic inflammatory reaction, average values of carbon dioxide, anionic bicarbonate and base deficiency in capillary blood, interleukine-6 and receptor interleukine-1 antagonist in venous blood serum. Each sign is assigned with a prognostic coefficient (PC). That is followed by determining total PC, and it is expected cystic PVL that is decided for if total PC is at least (+)9.5, whereas no cystic PVL is expected if total PC is (-)9.5 or less.

EFFECT: invention provides the early (for the first 7 days of life) prediction of cystic periventricular leukomalacia in the most susceptible category of patients that are children with very low and extremely low birth weight.

6 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: interferon is measured in plasmocytoid dendrite cells at week 12 of the treatment. Its gain in adults and children twenty times as much as compared to the pre-treatment initial level, or 2.6×102 times as much in adults, and 1.2×102 as much as compared to the normal values, the stable positive antiviral treatment response is predicted.

EFFECT: method enables providing the more accurate prediction for selecting the optimum therapeutic approach in each patient.

4 ex

FIELD: medicine.

SUBSTANCE: invention represents a method for assessing the mucosal immunity state of open cavities accompanying the prediction of the clinical course of infectious-inflammatory processes, characterised by the fact that having a pathogenetic factor established, degrees of microbiocoenosis disturbances of a specific biotope are recorded with the use of a complex of methods for estimating colonisation resistance factors, namely normal microflora, opportunistic microflora, immunoglobulins G, M, A, secretory immunoglobulin A and sc component; the mucosal immunity state is assessed according to the degree of microbiocoenosis disturbance, and the favourable outcome implying agent eradication or chronisation with agent persistence is predicted. The invention also refers to a method for correcting the infectious-inflammatory processes with the Kipferon® immunomodulator added.

EFFECT: increasing the prediction accuracy of the clinical course of the disease, extending the range of the method for correcting the infectious-inflammatory processes.

2 cl, 3 ex, 6 tbl, 1 dwg

FIELD: medicine, psychiatry.

SUBSTANCE: one should isolate DNA out of lymphocytes of peripheral venous blood, then due to the method of polymerase chain reaction of DNA synthesis one should amplify the fragments of hSERT locus of serotonin carrier gene and at detecting genotype 12/10 one should predict the risk for the development of hallucino-delirious forms of psychoses of cerebro-atherosclerotic genesis.

EFFECT: more objective prediction of disease development.

3 ex

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