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Method for prediction of dysthyroidism

IPC classes for russian patent Method for prediction of dysthyroidism (RU 2446401):
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FIELD: biotechnology.

SUBSTANCE: methods for determination, purification and filtration of sugar chains containing GlcNAc synthesized by GnT-V using at least one type of GlcNAc-specific lectins with affinity to sugar chains with GlcNAc synthesized by GnT-V, that are chosen out of the group including GSL-II and PHA-L and at least one type of GlcNAc-specific lectins with no affinity to sugar chains with GlcNAc synthesized by GnT-V, that are chosen out of the group including BLL and ABA and are used in combination as a medium for determination of sugar chains with GlcNAc synthesized by GnT-V or in combination for contact with sugar chain sample. One of the group of the inventions is a set including two types of GlcNAc-specific lectins.

EFFECT: development of precise method for determination of sugar chains with GlcNAc synthesized by GnT-V.

4 cl, 1 ex, 1 tbl, 5 dwg

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FIELD: medicine.

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EFFECT: means provides the improvement of the accuracy of nonspecific serodiagnosis of syphilis seronegative forms due to the activation of the syphilis process as a result of inserted highly specific antibody of cultural pale treponemas which allows changing the course of seronegative syphilis that is characterized by no immune reply to the syphilis activator to the seropositive form that is characterized by the immune reply to the activator.

1 dwg

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In lacrimal liquid one should detect the content of interleukin 8 (IL-8) and that of interleukin 1 beta (IL-1β) to calculate prognostic coefficient (PC) due to dividing the first value by the second one by the following formula: At PC value being below 10.0 one should predict favorable disease flow, and at PC value being above 10.0 - unfavorable flow.

FIELD: medicine.

SUBSTANCE: method involves woman's pre-delivery blood serum examination for nitrogen oxide and relaxin that is followed by calculation of the NO/relaxin relation. If the relation is 3.6 and less, dysthyroidism is predicted.

EFFECT: use of the method provides high-accuracy preclinical prediction of dysthyroidism that enables well-timed optimisation of management and treatment in the patients suffering given pathology.

3 ex

 

The invention relates to medicine, namely to obstetrics, and can be used to predict discoordination labor.

Many aspects of early diagnosis and prediction of pathology in childbirth, and in particular, discoordination generic activities requires new approaches using technologies of molecular biology and medicine. Pathology contractile activity of the uterus leads to an increase in the duration of delivery, number of surgical interventions, the frequency of obstetric injury, pathologic hemorrhage, intrauterine asphyxia of the fetus. Dramatically increases perinatal mortality and mestorozhdenii.

It is known that for discoordination labor activity is characterized by the presence of abnormal contractions that differs from the physiological not the absolute voltage value of the myometrium during its decline as a violation of the procedure for changing the amounts of the various divisions of the uterus (Art. Active management of labour. // Special literature, St. Petersburg., 1999, 667 S.).

Direct inducer of contraction of the smooth muscle cells of the myometrium are calcium ions (CA2+quickly coming from the extracellular environment to the cytoplasm through the opening in plasmalemma CA2+-channels. The action of the muscles that are specific regulators contra is tilen activity of the uterus, by maintaining physiological levels of calcium ions in the cells of the myometrium. Violation of their products leads to an imbalance of the ratio of intra - and extracellular level of CA2+accompanied discoordinating reduction cells of the myometrium (Vierbuchen, Lierelease "Premature birth and new strategies for their correction: a literature review". Bulletin SB RAMS, №3 (131), 2008).

For the prevention of discoordination labor activity is important for timely detection of this pathology.

There are methods of diagnosing abnormalities of labor activity using hysterography: external and internal (Art. Active management of labour. // Special literature, St. Petersburg., 1999, S. 667). A common shortcoming of these methods is that they diagnose the abnormality of labor activity at the stages of its manifestation. While the disadvantages of internal hysterography should be considered at high risk of developing complications from the mother and the fetus (intrauterine infection, acute asphyxia, detachment of normally situated placenta, as well as the need in interpreting results involving complex, bulky programs using a computer).

There is a method of predicting pregnancy outcome in threatening childbirth (RF patent No. 2132069 published 20.06.1999)by defining p is referecnce blood content CD16 and CD3 and calculate their ratio, largest of which predict risk of premature birth.

The disadvantages of this method should include the fact that it can not predict the nature of labor, and the possibility of premature birth.

A known method for predicting anomalies labor before childbirth (RF patent No. 2134418 published 10.08.1999) forecasting anomalies of labor activity by ultrasonic method, examining the tissue of the uterus on the border with the lower segment and identifying hyperechoic line on the background hypoechoic myometrium predict this pathology.

The disadvantages of this method include the fact that this method does not allow us to predict discoordination labor activity, and therefore cannot carry out targeted therapy.

From the practice of medicine is known a method for predicting anomalies labor activity (patent RF №2229722 published 27.05.2004), including the determination of enzyme activity in peripheral blood in women at 38-39 weeks of gestation. The disadvantages of this method should include significant difficulties in obtaining the true value of the activity of Na, K-ATPase due to the complexity of the conditions during the implementation of this study, resulting in the observed high percentage of false-positive results. Being the major disadvantage of the method can be considered as the absence of a differential nature of the violation of labor.

There is a method of predicting discoordination labor in pregnant women risk group (patent RF №2235499 published 10.09.2004)by registering oscillations of heart rate in the low frequencies (LF)and high frequency (HF) and their values shall prognosis of this disease. This method is designed only for pregnant women at risk, which limits its use in other conditions.

A known method for predicting violations of labor activity (patent RF №2268465 published 20.01.2006) by microscopy obtained serum samples dried in the form of a drop on a glass slide at a temperature of 18-25°C for 18-24 hours. In the presence of extremely low levels of structureborne and the absence of a radially symmetric pattern of facies, predict a violation of the generic activities that require rapid completion of the delivery. A condition for the realization of the developed method of forecasting is the beginning of the run it for 3-5 days before giving birth. Moreover, in the case of development over this period of preterm birth, it cannot be used. Other disadvantages of this method include the fact that it is impossible to predict the type of violation of labor.

A known method for predicting anomalies labor, fixed (patent RF №2296993 published 10.04.207), which consists in determining osmoresistens erythrocytes in the presence of blocker-1 (1-isopropylamino)-3(1-naphthalenyl-oxy)-2-propanol hydrochloride and under certain its values predict anomalies of labor activity in the preliminary or first stage of labor. The disadvantage, of course, is that the data on which it is possible to predict anomalies labor activity obtained in the preliminary or first stage of labor, and this reduces the possibility of the timely appointment of therapy. In addition, this method cannot be differentiated to predict the weakness of the labour forces or their discoordination.

The prototype of the present invention is elected as a method for predicting discoordination generic activities described in the copyright certificate №16483446 (bull. 1991, No. 18, p.17). The essence of the prototype method is that in the blood of the cervix to determine the activity of adenozindezaminazy and increase the norm predict discoordination.

The disadvantages of this method include:

Forecasting discoordination generic activities carried out during the period of childbirth, which significantly reduces time opportunity for preventive measures.

These drawbacks are eliminated in the invention.

The objective of the claimed invention - development method is, allowing even at the preclinical stage to predict with high accuracy discoordination labor.

The problem is solved as follows: at the end of pregnancy at 38-40 weeks in serum by ELISA to determine the content of metabolites of nitric oxide (NO2-and NO3-)equivalent to the level of nitric oxide, and relaxin, when the ratio of the level of nitric oxide (NO) to the level of relaxin equal to 3.6 and below, predict discoordination labor.

The technical result obtained during use of the invention is to improve the prediction accuracy of discoordination labor activity in the antenatal assessment in the serum ratios of nitric oxide and relaxing, which enables it to form a high risk group.

Contractile activity of the myometrium is coordinated by the combined action of various bioactive substances, acting as its uterotonic and relaxants. In the processes of spontaneous labor activation are regulatory mechanisms, an important place among whom are the connections that provide the reaction to the relaxation of the myometrium during labor. The latter include nitric oxide and relaxing (Min G. et al. Eridence that endogenous relaxin promotes growth of the vagina and uterus during pregnancyin gifts. Endocrinology, 1997, 138, 560-565; Bgerman, Ividorami, Mguni. Structural and functional basis of coordination of the contractile activity of the myometrium (the vascular system of the uterus). Grew up with. lead, akush.-gin., 2003, 5, 21-22).

Nitric oxide (NO)as an endogenous inhibitor of the reduction of the myometrium, acts as a paracrine regulator, indicating its important role in labor activity. Thus relaxin by binding to receptors in the myometrium increases the level of camp, while the nitric oxide increases cGMP, which results in the opening of CA2+channels, due to the corresponding concentration of CA2+on the physiological background of its revenues in the cells of the myometrium (Vierbuchen, Lierelease "Premature birth and new strategies for their correction: a literature review". Bulletin SB RAMS, No. 3 (131), 2008: S. 38-44).

The imbalance of these regulatory processes causes the change of transport Sa2+through slotted contacts myocytes, which leads to disruption of coordinated contractions of the myometrium.

Changes during pregnancy products relaxin and absence of nitric oxide leads to the disorganization of the contractile function of the myometrium, which in turn is implemented in discoordination labor, because, obviously, at physiological for the generic act equally necessary soo the appropriate level of nitric oxide, and relaxing.

Detailed description of the method and examples of its clinical application. Pregnant women before labor activity in the period 38-40 weeks perform taking blood from the cubital vein with subsequent obtain serum, which determine the content of metabolites of nitric oxide (NO2-and NO3-and relaxin. Calculate the ratio and amount equal to 3.6 and below forecast in this patient, discoordination labor.

Endogenous levels of nitric oxide, equivalent to the level of metabolites of nitric oxide (NO2-and NO3-)specify in 0.1 ml of serum using the classical reaction Griss (L.Green et al., 1982) recruitment firm R&D (USA) in accordance with the Protocol of the manufacturer. The optical density of the color of the solution obtained after the reaction, register on the photocolorimeter "Victor multilabe counter - 1420 (Finland).

Determination of the level of relaxin in serum perform enzyme-linked immunosorbent assay using kits (R&D Systems, Inc., USA) on the device "Immunolite".

The performance of the claimed method the following examples.

Example 1.

Pregnant-VA NV, 31. Case history No. 5292/843 from 27.12. 2009

Diagnosis: a Birth I, the term 39-40 weeks. Age perforada.

28.12.200 year after informed consent taken blood from the cubital vein for determination of metabolites of nitric oxide (NO 2-, NO3-)equivalent to the level of nitric oxide (NO), and relaxin. The content of nitric oxide in the blood serum was 1811 PG/ml, and relaxin 488 PG/ml the Ratio of the nitric oxide/relaxin was reached 3.7. According to our method, is obtained allowed us to predict the optimal course of childbirth.

29.12.2009 year, the patient began labor activity. Data delivery was uneventful and ended through the birth canal alive full-term, healthy baby.

Example 2.

Pregnant To the Islands ETC., 29 years. Case history No. 5585/818 from 6.02.2009,

Diagnosis: a Birth I, the period of 40 weeks online. Dystocia cervix. Intrauterine hypoxia. Age perforada. Large fruit.

7.02.2009 year after informed consent taken blood from the cubital vein for determination of metabolites of nitric oxide (NO2-, NO3-)equivalent to the level of nitric oxide (N0), and relaxin. The content of nitric oxide in the blood serum was 1650 PG/ml, and relaxin 458 PG/ml the Ratio of the nitric oxide/relaxin was equal to 3.6. This ratio can predict discoordination labor.

8.02.2009 year women began labor activity. Childbirth has been accepted way; was carried out corticotropinby monitoring. Effective the guard force and frequency of contractions, as well as the disclosure of the cervix was assessed through monitoring. Data readings used diagnostic equipment and the nature of clinical symptoms (dystocia cervix, hypertonicity of the uterus) testified to discoordination labor. Childbirth is completed by an emergency caesarean section. He was born full-term, live baby.

This clinical example confirms the possibility of predicting discoordination labor.

Example 3.

Pregnant B-VA, I.I., 32 years. History of births No. 3421/616 from 16.09.2010.

Was admitted to hospital for birth 17.09.2010,

Diagnosis: a Birth I, the period of 40 weeks online. Dystocia cervical cancer, once the tight entanglement of the umbilical cord of the neck of the fetus. Late gestosis E, hypothyroidism Art. I, chronic autoimmune thyroiditis. Colpitis.

After informed consent was taken blood from the cubital vein for determination of metabolites of nitric oxide, equivalent to the level of nitric oxide (NO), and relaxin. The concentration of metabolites of nitric oxide (NO2-NO3-) in the serum was 1600 PG/ml, and relaxin 513 PG/ml Ratio NO/relaxin corresponded to 3.1. This ratio can predict discoordination labor.

18.09.2010 mothers at 39-40 weeks began labor activity. Childbirth led the under monitor cardiocentro. Power efficiency and regularity of contractions and cervical dilatation was assessed through monitoring. Was diagnosed discoordinated labor, and fetal - acute distress. Performed a caesarean section with a favorable outcome. Born live, full-term baby.

This clinical example confirms the possibility of early detection of discoordination generic activities and effective obstetric tactics.

Diagnostic specificity and accuracy of the method is equal to 100% (no false-positive and false-negative results).

By the present method were examined in 59 women, among whom 31 pregnant diagnosed physiological childbirth. The latter value NO/relaxin in serum was equal to 3.7 and above. With 28 women indicator was equal to 3.6 and below, combined with discoordinating labor.

The above confirms the prognostic value of the claimed method.

Thus, the inventive method is specific and accurate than known.

1. The method is specific, as it allows the ratio of substances (and NO relaxin), which is the specific muscles that control in smooth muscle cells of the myometrium level of calcium ions, providing the contractile activity of the uterus, prognozirovaniya labor.

2. It has high precision.

3. Clinical application of the method will allow the timely implementation of obstetric tactics.

In clinical practice, this will allow us to predict discoordination generic activities to optimize the management and treatment of patients with this pathology.

The inventive method of predicting discoordination labor activity tested at a sufficient volume of clinical material and can be recommended for use in obstetric hospitals.

A method for predicting discoordination labor activity by biochemical analysis of blood, characterized in that in the antenatal period in the serum of pregnant immunoassay method to determine the content of metabolites of nitric oxide and relaxing with subsequent calculation of their ratio and amount equal to 3.6 and below, predict discoordination labor.

 

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