Method for preventing placental deficiency under conditions of urogenital infecting with chlamydiosis

FIELD: medicine, obstetrics.

SUBSTANCE: one should conduct antibacterial therapy 3 mo before planned pregnancy consisting of preparations of tetracyclinic group or macrolides in combination with nystatin and metronidasol to continue it since the first day of menstrual cycle and, also, it is necessary to perform correction of vaginal biocenosis, and about 3-4 wk after therapy carried out for 2 next mo before planned pregnancy starting, also, since the first day of menstrual cycle - metabolic therapy; At the onset of pregnancy one should conduct courses for preventing placental deficiency dealing with introduction of preparations that improve uterine-placental circulation, and preparations that improve rheological properties of blood and vitamin-metabolic therapy or the same preparations, and additionally - introduction of macrolides ad viferon rectally in case of activation of chlamydial infection. The present innovation enables to sanitize uterine cavity, improve uterine-placental circulation, restoration of placental tissue structure that, in its turn favors the birth of healthy generation.

EFFECT: higher efficiency of prophylaxis.

1 cl, 9 tbl

 

The invention relates to medicine, in particular to obstetrics, and can be used for prevention of placental insufficiency, congenital malformations and stillbirths in women with urogenital chlamydiosis.

Many obstetric and extragenital pathology changes in the placenta. They are connected with nature, time and duration of adverse effects of the factors on the formation and development of the placenta, as well as the level of the lesion. Important role, for example, violation of uteroplacental blood flow in the pathogenesis of placental insufficiency have various acute and chronic infection.

The known method of prevention of placental insufficiency in terms of infection, which is to assign complex membranotubular (vitamin E and Essentiale) (Mikaelyan AV Violation of the condition of the fetus and energy metabolism in pregnant women with chronic nonspecific lung diseases//abstract. Diss. CMN, M., 1993). The disadvantage of this known method is its limitation (the method is only effective for chronic non-specific lung disease).

Closest to the claimed method is prevention of placental insufficiency in terms of viral-bacterial therapy, including when urogenital the Ohm infection with chlamydia (RF patent No. 2164417, A 61 K 38/43, a 61 P 43/00) by the use of antimicrobial therapy, immunomodulatory therapy during pregnancy, as well as the inclusion in the complex treatment of Wobenzym in standard dosages in terms of gestation 12-14, 22-24, 34-36 weeks.

However, the known method is not effective enough, as it implies the prevention and treatment during pregnancy, when antibacterial therapy, which is conducted in longer periods of time and large doses of antimicrobials are not always shown, and may in addition lead to a number of undesirable consequences. Meanwhile, for a favorable course of pregnancy and birth and the birth of healthy offspring, it is important to prevent changes in the placental tissue.

The invention solves the problem of creating effective method of prevention of placental insufficiency in terms of perinatal viral and bacterial infection chlamydia.

The technical result of the invention is to improve placental blood flow by preventing changes in the placental tissue.

This technical result is achieved by the fact that for the prevention of placental insufficiency in terms of urogenital infection with chlamydia by conducting antimicrobial, immunomodulatory and metabolic therapy, three months before planned pregnancy spend antibacterial therapy, which consists of drugs tetracycline or macrolide combined with nystatin and metronidazole and conducted from the first day of the menstrual cycle, as well as correction of vaginal biocenosis, and 3-4 weeks after treatment for 2 months before the planned pregnancy, starting also from the first day of the menstrual cycle, conduct metabolic therapy during pregnancy courses of prevention of placental insufficiency, which includes the introduction of tools that improves uteroplacental blood flow, drugs, improves blood rheology and vitamin metabolic therapy or these funds, in addition to the introduction of macrolides and rectal Viferon in case of activation of chlamydial infection.

The normalization of vaginal biocenosis can be done by vaginal administration of probiotics.

The method is as follows. If the women in pregravid period of urogenital chlamydiosis three months before the planned pregnancy have:

antibiotic therapy is individually tailored drugs tetracycline (tetracycline, doxycycline), or antibiotics-macrolides (erythromyc is h, rovamycin, Sumamed, ruled, klacid); metronidazol in therapeutic doses 1 through day 7 to day 9 of the menstrual cycle;

for prophylaxis of a dysbacteriosis - nystatin and metronidazole (0.5 g 4 times a day);

for the correction of vaginal biocenosis - probiotics: Bifidumbacterin, Lactobacterin, Azilect (vaginally 1 candle 10 days).

3-4 weeks for two months conducting metabolic therapy from the first days of the menstrual cycle: folic acid to 0.0001 g 3-4 times a day, 20-30 days; from 15 to 25 days cycle: vitamin E 100 mg (1 capsule.) 3 times a day, fish oil 1 capsule. (500 mg) 1-2 times per day, immunol 20 drops 3 times a day.

When the pregnancy courses of prevention of placental insufficiency, which includes the introduction of tools that improves uteroplacental blood flow, drugs: antispasmodics (papaverine, no-Spa), beta-agonists (General, partusisten), magnesium sulfate, or the same means, and in addition the introduction of macrolides and rectal Viferon in case of activation of chlamydial infection.

The inventive method solves the problem of placental insufficiency in women with urogenital chlamydiosis and therefore solves the problems that arise due to placental insufficiency, such as congenital malformations and stillbirths.

Examples of the implementation of the proposed method. P is d observation were 153 pregnant women with gestation from 5-6 to 41 weeks of pregnancy.

For the study of factors affecting placental insufficiency all pregnant women were divided into three groups:

Group I (basic) amounted to 61 women with urogenital chlamydiosis (ugh), which passed the full range of clinical laboratory tests and pregravidarnoy training (three months prior to pregnancy) with the proposed measures;

II group (comparison group) amounted to 62 pregnant with yrx surveyed during pregnancy, preparations, and received treatment ugh and the clinical manifestations;

The third group (control group) included 30 women with physiological pregnancy, which in the laboratory study were not selected pathogens infections.

Pregnant women of all groups studied in detail obstetric history. During the gestational period has been generally accepted clinical and laboratory tests (complete blood count, urinalysis, analysis of the vaginal smear on flora and others), consultations of medical specialists (physician, endocrinologist, dentist, ophthalmologist, otolaryngologist). A dynamic assessment of weight gain during pregnancy, growth of the uterus and the fetal status.

In utero the fetus and placenta were evaluated at the same time ultrasonic scanning machine, doplerometry and histological examination of the placenta.

The analysis was performed on generic activities were taken into account: the length and nature of labor, time using amniotic fluid, their character, estimation of blood loss in childbirth, the presence and treatment of complications, the use of operational manuals in childbirth, the characteristic injuries.

Also, an analysis was conducted of the condition of the newborn: physical condition of the children was assessed on a scale of Apgar scores at 1st and 5th minutes after birth, were taken into account mass-growth parameters. The structure of perinatal outcomes and complications in patients of all groups.

In the first group, all women were held for three months before planned pregnancy pregravidarnaya training. When there is ugh in the scheme of preparing women for pregnancy included:

1) antibacterial treatment is individually selected drugs tetracycline (tetracycline, doxycycline), or antibiotics-macrolides (erythromycin, rapamycin, Sumamed, ruled, klacid); metronidazol in therapeutic doses 1 through day 7 to day 9 of the menstrual cycle;

2) for prophylaxis of a dysbacteriosis - nystatin (0.5 g 4 times a day);

3) for the correction of vaginal biocenosis - Bifidumbacterin, Lactobacterin, Azilect (vaginally 1 candle 10 days).

Dispensary observed the e was carried out within 3 months. With the aim of establishing criteria of cure chlamydia study of clinical material (blood, swabs-scrapings and the biomaterial of the cervical canal) was performed 3-4 weeks after antibiotic treatment within 2 months.

The pregnancy was allowed women with clinical recovery in combination with etiological cure (disappearance of the pathogen) and the normalization biocenose vagina, which was conducted smear test, which included the following indicators: color Gram, the definition of leukocytes (1-2 in sight - norm), the presence of mucus (in small quantities - norm), epithelium (in small quantities - norm), flora (g/positive bacilli in small quantities - norm). In addition, he carried out the microbiological analysis, in which the presence of lactobacilli and bifidobakterii was regarded as the norm, and the presence of others, such as stafilokokom, a deviation from the norm. Within two months before the planned pregnancy women received metabolic therapy: from the first days of the menstrual cycle folic acid to 0.0001 g 3-4 times a day, 20-30 days; from 15 to 25 days cycle: vitamin E 100 mg (1 capsule.) 3 times a day, fish oil 1 capsule. (500 mg) 1-2 times per day, immunol 20 drops 3 times a day.

When the pregnancy was obligatory held the escarpment prevention and treatment of placental insufficiency (PI):

1) was used tools that improve uteroplacental blood - antispasmodics (papaverine, no-Spa), beta-adrenoceptor agonist (ginipral, partusisten), magnesium sulfate;

2) drugs that improve blood rheology drugs nicotinic acid (nicotinamide, ksantinola nicotinate), chimes, Actovegin, aspirin;

3) vitamin-metabolic therapy - vitamin E, folic acid, ascorbic acid, complex vitamins (hendevit, Complivit, obscene, Vitrum, prenatal Forte etc).

From the first months of pregnancy were controlled by the condition of the vaginal flora. When the manifestation of infection with the development of vaginal dysbiosis obligatorily carried out by local treatment with drugs depending on the type of pathogenic flora and pregnancy with subsequent correction of vaginal biocenosis. Upon activation of chlamydial infection was conducted antibacterial macrolide therapy (rovamycin or erythromycin for 5-7 days) followed by a reception nystatin. In these cases, was administered the drug Viferon - rectal candles from 28 to 34 weeks Viferon, containing 150 thousand IU of interferon Alfa-2B, during pregnancy, with 35 to 40 weeks Viferon 2 containing 500 thousand ME, 2 candles per day through the day, the course of treatment is 5 days.

In the comparison group chlamydial infection was first identified PR is this pregnancy. The treatment was carried out as in the prototype. Used traditional methods of diagnosis, treatment and prevention of complications during the entire gestational period. In cases of infection and arising in connection with these complications were antibiotic therapy with macrolides - erythromycin, rapamycin and, if necessary, local treatment and correction of vaginal biocenosis. Since the establishment of ugh in the plan pregnancy was introduced courses on the prevention of placental insufficiency. The treatment was carried out in stationary conditions.

Age of women surveyed ranged from 16 to 43 years (average of 25.7±3,37 year).

The average age of the first main group amounted to $ 24.8±2,4 years, in the II - 26,9±4,1, III, control, - 25,4±3.4 years. Thus, groups hardly differed among themselves by age.

When analyzing historical data about previous diseases of women surveyed noted that as a group of infectious and extragenital diseases in the two groups had no significant differences.

The survey revealed that when the ELISA blood test in the comparison group (II) IgG was detected in 100% (62 women) cases, with increasing titers 2-3 times recorded at three - 4,84%, IgM two women - 3,23%, IgA 5 times - 8,06%, i.e. we recorded 10 cases (16,13%) zabolevaniya genitourinary system detected chlamydia in 100% of subjects.

In women, prepared for pregnancy (group I), while the ELISA blood test in the first half were found to have low titers of IgG, which did not change during pregnancy, but did not disappear. Acute infection in 4 patients (6,56%), and among them were women, who prior to pregnancy as a result of treatment IgG was absent. Local chlamydia more prevalent in the second half of pregnancy, because before pregnancy the patient underwent a course of treatment, had normal vaginal biocenosis.

According to the results of clinical and laboratory studies (complete blood count, biochemical analysis and triglycerides blood, urinalysis), consultations of medical specialists (physician, endocrinologist, dentist, ophthalmologist, otolaryngologist) failed to reveal significant differences that would help to predict the development of changes in fetoplacental complex.

The frequency and nature of obstetric complications and diseases of this pregnancy in women examined groups are presented in table 1.

-
Table 1
Obstetric complications and diseasesI group

(n=61)
II group

(n=62)
Group III

(n=30)
Abs.% Abs.%Abs.1%
The threat of miscarriageOnly1524,593353,231240
From the first floor. Taken.426,672678,79975
II sexes. taken.973,33721,21325
Infection of the genital tractOnly1727,8729of 46.771136,66
From the first floor. taken.741,181758,62654,55
II sexes. taken.1058,821241,38545,45
Infection of the urinary organsOnly2744,262337,09826,67
From the first floor. taken.5holds 18.52 626,09225
II sexes. taken.2281,481773,91675
AnemiaOnly2236,073251,611963,33
From the first floor. taken.2a 9.091031,25421,05
II sexes take.2090,911268.75 kilopascals578,95
ARIOnly711,481117,74723,33
From the first floor. take557,14218,18685,71
II sexes. taken.242,86981,82114,29
PolyhydramniosOnly58,269,68310
From the first floor. taken.-350,0266,67
II sexes. taken.5100350,0133,33
OligohydramniosOnly46,5669,68620
Of these floors I take--233,33--
II sexes. taken.4100466,676100
HfpnOnly2134,433962,901343,33
From the first floor. taken.--410,26215,38
II sexes. taken.211003589,741184,62
PreeclampsiaOnly2337,703048,391136,67
Of n is x in the second trimester --930,0218,18
in the third trimester231002170,0981,82
Malnutrition of the fetusOnly34,921422,582to 6.67
In the second trimester--535,71150
In the third trimester3100964,29150

The data presented indicate more favorable for gestational process in women of the first group (I)who received prophylaxis in accordance with the claimed method to improve placental blood flow, compared with pregnancy in women group of the second group, whose pregnancy was carried out in accordance with the method of the prototype without preparation, and the diagnosis of urogenital chlamydia trachomatis was first installed during this pregnancy.

Pregnant the second and third group with signs of placental insufficiency conductivity is the n treatments, aimed at improving blood flow to the placental complex.

You must pay attention to the high frequency of threat of miscarriage in women in the studied groups: in group I 2 times less - 24,59% (15)than in group II - 53,23% (33). In group III (healthy women) - 40% (12). Women who have never held a preparation for pregnancy (II and group III), this complication is frequently observed in the early stages (respectively 78,79% and 75%), and in I, the principal, the group only 24,59%.

Pregnant group I developed anemia in 36,07% (22), and in the first half of pregnancy was recorded only 9.09% of cases, and in women of group II and III respectively of 31.25 and 21,05%.

Infection generic ways in the main group was noted in 27,87% (17 women), in the group of healthy 36,66% (11), and in the comparison group in of 46.77% (29).

On the development of pregnancy, particularly in the placenta, had a negative impact of viral infection. Such diseases as SARS in group III (control) women had in 23,33% (7), in the II - 17,74% (11) and I (main) - 11,48% (7).

The diagnosis of polyhydramnion and low was set on the basis of ultrasound data, and conducted courses of treatment.

Women of the first group almost 2 times less than in group II was diagnosed hfpn, respectively 34,43% (21) and 62.9% (39), although the clinical manifestations of preeclampsia in percentage (in group 1 - 37,7% (13), in group II - 48,39% (30)) was distinguished by the slightly camping. Pregnant women with yrx by ultrasound scanning revealed pronounced structural changes in the placental tissue, and in 10,26% appeared already in the first half of pregnancy, which was not observed in group I, where hfpn detected only in the second half of pregnancy. In group III phenomena hfpn were installed in 43,33%, and in 15,38% in the first half of pregnancy, and clinically preeclampsia appeared in 36,67% of cases. Clinically manifested preeclampsia in the II and III groups from the second trimester, respectively 30% (9) and 18.8% (2) observed. In the group of women who were pregravidarnoy training, preeclampsia was observed in the third trimester - 100% (23).

Accordingly, changes were observed from the fruit, is also largely confirmed by ultrasound examination. The hypotrophy of the fetus was performed in group II were studied in 22,58% (14) cases of them are already in the second trimester in 35,71% (5), in group III only 6.67 per cent (2) and half of the cases in the second trimester and in the first group, all cases of fetal malnutrition to 4.92% (3) and all in the third trimester. With regard to complications and diseases, clinical manifestations of infection, conclusions additional research methods and laboratory data during the pregnancy of the surveyed women were trained therapy (table 6). Antibacterial and local treatment of the women in the comparison group (II) in pain the om percentage of cases - to 75.8% (47) and 58,6 (36), respectively, in the main (I) group - 47,54% (29) and 50,82% (31).

Table 2.
TreatmentsI group n=61Group II n=62Group III (N=30
abs.%abs.%abs.%
Antibacterial therapy2947,544775,81136,67
Prevention and treatment of NEF6098,364674,191550
Local treatment3150,823658,06826,67

However, in group II treatment was carried out at a later time, because chlamydial infection was detected immediately, often before specific courses of antibiotic treatment (macrolides) was conducted courses of antibiotics penicillin, broad-spectrum antibiotics, nitrofurans.

In the group of healthy women, the use of drug therapy was the least. Despite pregravidarnoy the preparation of the surveyed women before pregnancy (group I) breakdown of an InterMedia is optimum therapy and local treatment received almost half, because episodes of symptoms of chlamydia met in II and III trimesters of pregnancy. This process was controlled, was conducted courses on the prevention of NEF (98,36%), and the clinical manifestations of infection were timely administered and conducted specific treatment. Prevention in accordance with the inventive method, carried out before pregnancy, reduced the number of complications during pregnancy and to reduce the number of cases on the use of antibiotic therapy.

Results data delivery (see table 3) showed that a higher percentage of premature births observed among women from the second group of 8.06% (5), and in most genera resolved with surgery on the testimony from the fetus. The same indication was the reason for the rapid delivery and at term pregnancy that was 10,71%. The total percentage of caesarean sections for the groups were: group I - 6,56% (4), group II - 19,35% (12), group III - to 3.33% (1).

Table 3.
Results deliveryI group n=61Group II n=62Group III (n=30
abs.%abs.%abs. %
Delivery date5895,085791,942996,67
- operational23,45610,7126,9
Premature birth34,925of 8.0613,33
- operational266,675100--
All operational delivery46,561219,3513,3

In the first and third groups of preterm birth was observed in a small number of, respectively, 3 (4,92%) and 1 (3,33%). Complications arising during childbirth shown in table 4.

Table 4.
Obstetric complicationsI group n=61Group II n=62Group III (n=30
abs.%abs.%abs.%
Premature rupture of amniotic fluid711,4769,84/td> 723,33
The weakness of labor activity1016,3923,22620
The chorioamnionitis11,6423,22--
Hypotonic bleeding46,565of 8.06--
The defect of the placenta813,11711,29516,67

As can be seen from table 4, complications such as premature rupture of water, the weakness of labor activity is not typical for women with urogenital chlamydiosis.

The condition of the newborn after birth was assessed by the Apgar scale:

in group I at 8-9 estimated 90,16% (55), at 7-8 points - 9,84% (6), 6-7 points - no;

in group II at 8-9 estimated 75,81% (47), at 7-8 points - 14,52% (9), 6-7 points - 9,68% (6);

in group III, 8-9 estimated 70% (21), at 7-8 points - 26,67% (8), 6-7 points to 3.33% (1).

The General condition of the newborn at birth in women of group I was significantly better below 7-8 points on the Apgar scale children has not been evaluated. In group III the status of the newborns were assessed somewhat worse, maybe it's due to more frequent use of diagrams Rodopi is to be placed, well, in the comparison group for almost 10% of newborns born at 6-7 points, where there were more premature birth.

During observations of newborns in the hospital neonatologists were identified following diseases (see table 5):

Table 5.
Pathological condition in newbornsI group n=61Group II n=62Group III (n=30
abs.%abs.%abs.%
Chronic hypoxia1219,672743,55723,33
Malnutrition, IUGR46,561320,97413,33
The conjugation jaundice813,111422,58413,33
Prematurity34,92510,313,3

Almost half of children among women with chlamydial infection (II) were born with signs of chronic hypoxia (43,55%)and every fifth (20,97%) with symptoms of malnutrition, IUGR, which is podtverjdaet poor circulation in utero-placental complex. In neonates, the comparison group were more frequently observed conjugational jaundice (22,58%), three children were born with a diagnosis of congenital intrauterine infection (IUI) (including one child died from sepsis), and two with edematous syndrome, dysbiosis and two with congenital malformations. In the main group no cases of IUI, in one case there was hydrocephalic syndrome. In the group of healthy women on one occasion: congenital pneumonia, kefalogematoma, fracture of clavicle congenital clubfoot.

The reasons for complications and diseases of the second group of women surveyed was late diagnosis ugh, the result is a lack of preventive courses of treatment, untimely specific treatment, lack of ultrasound screening.

Morphometric characteristics of newborns are presented in table 6. It should be noted that the average length and weight of newborn babies are no different. A few less than average weight of the placenta in the second group, which accounts for the slightly more fetal-placental ratio. The weight of the placenta, possibly increased by compensatory abilities.

Table 6.
GROUPThe newborn length (cm)the newborn weight (g)the weight of the placenta (d) fruit of the placentas. factor
I52,17±0,373354±73.02555,0±32,86,04±2,22
II51,93±0,353307±65,88581,1±124,95,69±0,53
III52,03±0,343364±71,91596,9±126,45,64±0,57

Retrospectively (age of child 6-12 months), it was found that the health status of the 24 children of women of the first group, among which 8 (33,3%) relatively healthy and had not received any treatment, and with 16 (66.7%) were identified: conjugational jaundice, respiratory infection, bronchitis, intestinal dysbiosis. In the second group surveyed women from 21 children born on Zdorovie was only 3 (14%). In 19 (86%) children were observed conjugational jaundice, respiratory infection, bronchitis, intestinal dysbiosis, also in this group of children were identified cases of hip dysplasia (1), hepatolienal syndrome (2), convulsive States (1).

Thus, it is obvious that the women of the first group receiving specific and preventive treatment before pregnancy prevention insufficiency fetoplacental complex, was observed more favorable course of pregnancy, childbirth and the birth of a healthy sweat is mstv compared with a group of women, held prophylaxis in accordance with the method of the prototype.

Ultrasound is the primary diagnostic criterion prenatal diagnosis of intrauterine fetal status and uterine-placentero complex. Ultrasonic planetography allows to determine the localization of the placenta, its size, structure, to detect the presence of pathological lesions. Timely identify the symptoms of premature maturation of the placenta are the signs of chronic placental insufficiency. In order to further consider the extent of the lesion placental tissue and comorbidity each study group was divided into two subgroups: 1 - placenta without symptoms NEF and accompanying pathological changes, 2 - placenta symptoms NEF and its associated pathological changes. Observed manifestations of changes in the placenta on the results of ULTRASONIC findings throughout pregnancy. Table 7 presents an ultrasound of the fetus and the placenta of women in the comparison groups up to 20 weeks.

td align="left"> oligohydramnios
Table 7
The data of ultrasound scanThe pregnancy 21-29 weeks
I group n=61 Group III (n=30
abs.%abs.%abs.%
Placenta without symptoms NEF5285,253759,682790
including additional changes
low placentation--410,8113,7
the threat of termination35,76--27,41
hypoplasia of the placenta------
hyperplasia of the placenta35,7625,41--
placenta------
polyhydramnios23,85--13.70
oligohydramnios----3 11.11
malnutrition of the fetus----13,70
ICN------
Placenta symptoms NEF914,752540,32310,0
including additional changes
low placentation--416,0--
the threat of termination333,33--133,33
hypoplasia of the placenta--3to 12.0--
hyperplasia of the placenta------
placenta266,6728,0133,33
polyhydramnios1to 11.1128,0266,67
--416,0--
chorioamnionitis--624,0--
malnutrition of the fetus--28,0--
The IUGR fetus--28,0--

In women with yrx (group II) during the ULTRASONIC examination of the placenta in the first half of pregnancy (before 20 weeks) diagnosed phenomena NEF (21,57% of subjects), which was attended by the changes characteristic of the inflammatory process. 8 (72,73%) women phenomena Placentia, 4 (36,36%) - polyhydramnios, Hypo - and hyperplasia in 3. In I and III groups surveyed in the first half of pregnancy was observed in placentas with symptoms NEF, they appeared only in the second half of pregnancy and in a much smaller amount than in group II. In the second trimester of pregnancy picture of NEF was observed in group II - 40,32%, I - 14,75%, III - 10% of subjects. In the third trimester phenomena NEF was observed in group II - 56,45%, I - 24,59%, III - 20%.

In women with yrx diagnosed during pregnancy, was the primary lesion of the placenta from the first months of pregnancy, and the percentage of porage the Oia will be doubled in the next trimester.

In the group of healthy pregnant women and in the group of pregnant women with yrx, past pregravidarnoy training NEF increased from the second trimester to the end of pregnancy by 10%.

Signs of inflammatory changes of the ovum in the comparison group (group II) women can be traced throughout pregnancy, and begin with the symptoms - Placentia, polyhydramnion, and in the next trimester oligohydramnios, fetal hypotrophy, IUGR, with increasing percentage NEF.

In women with yrx the possibility of activation of infection exists in the entire pregnancy. In placental tissue affected chlamydial infection since the beginning of or during pregnancy to happen all the specific stages of the inflammatory process, despite courses of treatment. The result is mandatory rough defeat placental tissue is easily diagnosed by ultrasonography, with pronounced symptoms NEF, subsequently confirmed by histological examination. In these cases, the earlier diagnosed pathology and timely delivered courses specific treatment, the better the result, as in this case, the compensatory potential of the placental tissue is high (see results fruit-placental ratio of our patients). The results, especially the health of babies, when HEE was diagnosed in the third trimester the treatment was carried out closer to the date of delivery.

According to the ULTRASONIC study revealed that in the first half of pregnancy signs threats of termination had not been the main factor for the development of the NEF, as in the subgroup of subjects with NEF this symptom has been observed. The threat of miscarriage is much less than was observed in pregnant women, past pregravid training as MRI and clinical data.

Cardiotocography fetal conducted at a gestational age 32-34 - 38-40 on the grounds (clinically identified hypoxia diagnosed with ultrasound NEF etc). Results of the study are shown in table 8.

Table 8
Assessment of fetal statusI group n=28Group II (n=36Group III (n=14
abs.%abs.%abs.%
8-9 (normal fetus)2589,2921with 58.331285,71
5-7 points (initial symptoms of cardiac activity of the fetus)310,711233,332of 14.28
4 or less points (expressed changes of fetal status)--38,33--

Changes of cardiac activity of the fruit was mainly observed in the group of women whose treatment was conducted on the prototype method, that is, during pregnancy, i.e. where hfpn evolved from the first months.

In addition, morphological studies of placentas (table 9) and were identified qualitative changes in placental tissue during pregnancy. Chronic placental insufficiency say identified the following changes: the delay in the formation of membranes, calcium during early pregnancy (including pregnancy, fetal status, clinical status of women), heart attacks, hypoplasia of the placenta.

About the defeat of placental infection, and when the uplink transmission - chorioamnionitis, choriodecidua, i.e. the defeat of the parietal (parent) membranes, and when hematogenous transmission - phlebitis, Takayasu, willeit, basal decidua. In acute NEF have the following conclusions: bleeding in majorino space (characteristic intraplantarly loss), angiomatosis vessels (as a compensatory reaction), thrombosis of the umbilical cord (which is possible and sooner cut the umbilical cord). Such treason is Oia, how hyperplasia (thickening of the placenta), the abundance of fibrinoid, villus epithelium characterized by a compensatory reaction of the placenta. The rim on the periphery (excess fibrinoid) is regarded as a defect of development, is not considered as NEF did not affect the migration. These histological studies of placentas are presented in table 9.

Table 9
Conclusions histological examination of placentasI group n=61Group II n=62Group III (n=30
abs.%abs.%abs.%
Phenomena NEF none of them are infected4065,572438,711870,0
1435,01354,17527,7
Phenomena NEF has " infected2134,433861,29930,0
1152,382052,63444,44
All infected placentae2540,98 3353,23930

The presence of infected placentas in women treated before pregnancy 40,98% (25), although significantly lower than in the group treated by the method prototype indicates that it is possible, despite the negative test results prior to a planned pregnancy, we did not achieve full cure, and the infection continued to exist in the form of latent or persistent, and perhaps it was a reinfection. These data indicate that when the history of CHI, pregnancy should discuss with infectious wariness. The results of histological research data confirms that the infection does not always develop NEF, but the presence of CHI leads to a large number of lesions placental tissue - 61,29% (in group II). When pregravidarnoy training (group I) this number is reduced to 21 (61) - 34,43%. In the group of women not infected with chlamydia (III), and by many indications of pregnancy complications in excess of the first two (anemia, SARS, the threat of termination, genital tract infection, polyhydramnios and oligohydramnios), NEF has developed in 30% (9) of cases, with signs of inflammation 44,44% (4).

According to the ultrasound and histological findings was revealed that patients with yrx to infections placental tissue to normalize the process now is tenderly, pass all stages of the inflammatory process with the formation of sclerotic changes and deposition of calcium, but there are good compensatory potential of placental tissue after the treatment throughout pregnancy.

Data on the development of NEF in conclusion, histological studies in 61,29% (38) patients and by ultrasound in the third trimester - 56,45% (35) almost coincide, which could indicate a pronounced structural changes in the placental tissue, well diagnosed by ultrasonography. In the group of women without HEE (group III) percentage differences are slightly higher: if histology NEF was detected in 30% (9) cases, and ultrasound in the third trimester - 20% (6), which suggests that the cause of NEF in women without ugh, do not cause visible on ultrasound changes in placental tissue and, possibly, inflammatory changes (44,44% of infected placentas) began in the later stages of pregnancy. The last assumption is supported by data obtained in the first group, where the activation HEE, despite treatment, was shown at the end of the second and third trimester. These histological and ULTRASOUND conclusions differ by almost 10%, respectively - 34,43% (21) and 24,59% (15).

Despite treatment before pregnancy and monitoring during pregnancy, the possibility of activation HEE there is always that accompanied the fast development of the NEF: in the main group - in 34,43% of cases compared with patients of group III (without CHI) - 30%. However, we can assume that the treatment and preparation for pregnancy gives positive results, as in the second group of pregnant women, in whom the treatment yrx was conducted only during pregnancy, NEF has developed into 61,29% of cases and this is despite the fact that patients in this group were actively treated during pregnancy immediately upon diagnosis and the manifestation of the infection and later both of them were conducted courses on the prevention of NEF.

As mentioned above, prevention by the present method has allowed to reduce the number of complications during pregnancy and to reduce the number of cases on the use of antibiotic therapy, specific treatment from the moment of infection.

1. Method of prevention of placental insufficiency in terms of urogenital infection with chlamydia by conducting antimicrobial, immunomodulatory and metabolic therapy, characterized in that 3 months prior to planned pregnancy spend antibacterial therapy, which consists of drugs tetracycline or macrolide combined with nystatin and metronidazole and conducted from the first day of the menstrual cycle, as well as correction of vaginal biocenosis, 3-4 weeks after treatment within 2 days the blowing of months before the planned pregnancy, starting with the first day of the menstrual cycle, conduct metabolic therapy; pregnancy courses of prevention of placental insufficiency, which includes the introduction of tools that improves uteroplacental blood flow, drugs, improves blood rheology and vitamin metabolic therapy or these funds, in addition to the introduction of macrolides and rectal Viferon in case of activation of chlamydial infection.

2. The method according to claim 1, characterized in that the normalization of vaginal biocenosis performed by vaginal administration of probiotics.



 

Same patents:

FIELD: medicine, pharmacy.

SUBSTANCE: medicinal formulation possessing the bacteristatic effect consists of a core comprising the following components, wt.-%: clarithromycin, 40.0-80.0; polyvinylpyrrolidone, 3.0-10.0; sodium lauryl sulfate, 2.0-5.0; sodium croscarmelose, 4.0-10.0; aerosil, 0.5-2.0; magnesium stearate, 0.5-2.0, and microcrystalline cellulose, 10.0-31.0. Also, the medicinal formulation consists of envelope comprising the following components, wt.-%: hydroxypropylmethylcellulose, 30.0-70.0; polyethylene glycol, 12.0-22.0; titanium dioxide, 11.0-20.0, hydroxypropylcellulose, 2.0-10.0, dye yellow quinoline, 1.0-4.0, and vanillin, 1.0-4.0. Also, invention describes a method for preparing the medicinal formulation by wet granulation followed by tableting and applying the envelope from an aqueous suspension. Prepared tablets show the necessary mechanical strength, insignificant scattering index by mass (± 3.5%) and dissolving 88-91% for 30 min.

EFFECT: improved and valuable properties of medicinal formulation.

3 cl, 2 tbl

FIELD: medicine, gynecology, surgery.

SUBSTANCE: one should introduce 3.5%-chitosan ascorbate gel into fistulous channel that contains metronidasol at the dosage of 2 mg/ml, at the volume up to 20 ml once/2 d till complete fistula's closing. The present innovation enables to activate reparative processes and fistulous epithelization that favors for closing fistulous channel in earlier terms.

EFFECT: higher efficiency of therapy conducted.

2 ex

FIELD: medicine, surgery.

SUBSTANCE: one should apply a polycompositional film onto donor's wounds after autodermoplasty performed. This film contains the following components in weight proportions: chitosan 78.3-89.4; polyvinyl alcohol 9.8-19.8; antibiotic of aminoglycoside group 0.5-2.0; anesthetic 0.1-0.2. It is perforated at tension coefficient being 1:4. The innovation enables to decrease wound's traumatization, improves prophylaxis of suppuration and increases cosmetic effect even at a single application of the film suggested.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with application of pleuromutilin derivatives, that is valnemulin and thiamulin, for transdermal treatment of bacterial diseases, in particular those induced by Dichelobacter nodosus, Fusobacterium necrophorum, Bacteriodes nodosus and Bacteriodes melamnogenicus, for manufacturing medicinal preparation or as an active ingredient of medicinal preparation of the same indication and corresponding method for transdermal treatment of diseases, for example foot rot. It has been detected the capacity of antibiotics to penetrate skin and enter either plasma or blood at concentrations being efficient against systemic bacterial infections, so, medicinal preparation could be designed in the form of ointment, cream, solution, shampoo, powder and spray.

EFFECT: higher efficiency of application.

9 cl, 1 tbl

FIELD: biotechnology, immunology.

SUBSTANCE: invention proposes preparation that comprises the immunoelectrophoretically pure secretory immunoglobulin A isolated from whey milk and/or colostrum of immunized ungulate animals and pharmaceutically acceptable vehicles. The base preparation (substance) comprises 6-12% of secretory immunoglobulin A at pH 4-8, an anti-complementary activity at least 10 mg of protein, not activating 2 CH50, protects in >70% against corresponding infections (in infection macroorganism in doses ≥10 ID50), shows areactogenic property in intravenous administration, can comprise stabilizing additives in the total concentration 4%, not above. The preparation possesses high purity, low anti-complementary activity, stable in storage, useful for oral, parenteral and topical using and possesses therapeutic activity with respect to microorganisms and viruses against which humans and animals immunization have been carried out. Invention can be used in treatment and prophylaxis of immunodeficiency states, bacterial and viral infections in humans and animals.

EFFECT: valuable medicinal and veterinary properties of preparation.

9 cl, 1 tbl, 10 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel heterocyclic compounds comprising 2-aminopyridin-3-sulfonic fragment of the general formula (1) or their pharmaceutically acceptable salts, N-oxides or hydrates possessing properties of antagonists of glutamate-induced calcium ions transport, in particular, neuroprotective effect. Also, invention relates to the focused library for the search of biologically active leader-compounds comprising at least one heterocyclic compound of the general formula (1) and to pharmaceutical composition if form of tablets, capsules or injections placed into pharmaceutically acceptable package containing compounds of invention as an active substance. In compound of the general formula (1) R1 represents hydrogen atom; R2 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; or R1 and R2 in common with nitrogen and sulfur atoms to which they are bound form optionally substituted and optionally condensed with other cycles 1,1-dioxo-4H-pyrido[2,3-e][1,2,4]thiadiazine or optionally substituted and optionally condensed with other cycles 5,5-dioxo-5,6,7,9-tetrahydro-5-thia-1,6,9-triazabenzocyclohepten-8-one. Also, invention discloses methods for preparing different compounds of the general formula (1).

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

10 cl, 4 sch, 4 tbl, 9 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new heterocyclylsulfonyl alkylcarboxylic acids and their derivatives of the general formula (1): or their pharmaceutically acceptable salts, N-oxides or hydrates possessing the inhibitory effect on kinase activity and to the focused library for search of active leader-compounds comprising at least abovementioned compound. In the general formula 91) W represents optionally substituted heterocyclic radical, among them: pyrrole-3-yl, thiophene-2-yl, isooxazole-4-yl, pyrazole-4-yl, imidazole-4-yl, pyridine-3-yl, 1H-2,4-dioxopyrimidine-5-yl, 2,3-dihydro-1H-indole-5-yl, 2,3-dihydro-1H-indole-7-yl, 1,3-dihydro-2-oxoindole-5-yl, 2,3-dioxo-1H-indole-5-yl, 2-oxo-3H-benzoxazole-6-yl, benzothiazole-6-yl, 1H-benzimidazole-5-yl, benzo[1,2,5]oxadiazole-4-yl, benzo[1,2,5]thiadiazole-4-yl, 1,2,3,4-tetrahydroquinoline-6-yl, 3,4-dihydro-2-oxo-1H-quinoline-6-yl, quinoline-8-yl, 1,4-dihydro-2,3-dioxoquinoxaline-6-yl, 3-oxo-4H-benzo[1,4]oxazine-7-yl, 3-oxo-4H-benzo[1,4]thiazine-7-yl, 2,4-dioxo-1H-quinazoline-6-yl, 2,4-dioxo-1,5-dihydrobenzo[b][1,4]diazepine-7-yl or 2,5-dioxo-3,4-dihydrobenzo[b][1,4]diazepine-7-yl; Y represents optionally substituted methylene group; R1 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; n = 1, 2 or 3; or Yn represents carbon atom of optionally substituted (C3-C7)-cycloalkyl or optionally substituted (C4-C7)-heterocyclyl. Also, invention relates to a pharmaceutical composition in form of tablets, capsules or injections placed into pharmaceutically acceptable package.

EFFECT: valuable properties of compounds.

5 cl, 3 sch, 5 tbl, 6 ex

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: derivative of 9-deoxo-9a-aza-9a-homoerythromycin A of the formula (3) wherein R4 represents hydroxyl protecting group is prepared by protection of 2'-hydroxy-group of compound of the formula (5) to form compound of the formula (4)

and by oxidation of C-4''-hydroxy-group of compound of the formula (4) that is carried out by addition of dimethylsulfoxide to solution containing compound of the formula (4) and a solvent followed by cooling the mixture up to about -70°C, activation of dimethylsulfoxide in situ and defoaming the reaction mixture. Compound of the formula (4) is converted to the oxidation stage directly without its isolation. Also, invention proposes additive salt of trifluoroacetic acid of compound of the formula (3) and a method for its preparing by treatment of compound of the formula (3) with trifluoroacetic acid. Invention provides increasing yield and improving purity of the end product.

EFFECT: improved preparing method.

11 cl, 6 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with infecting macrophages and cells of macrophagous cell lines with pathogenic microorganisms, their treatment with medicinal remedies followed by gamma-irradiation, immunization of disease-resistant and disease-sensitive animal lines and infecting vaccinated animals with alive pathogenic microorganisms that leads to improved immunity to pathogenic microorganisms.

EFFECT: higher efficiency.

4 cl, 1 dwg, 3 ex

FIELD: medicine, gynecology.

SUBSTANCE: one should perform laparoscopy, drain purulent foci, remove destructive tissues and wash abdominal cavity with great amount of "Baliz-2" introduced into abdominal cavity by fractional portions per 1-1.5 l at exposure up to 3 min either once or up to three times. The method provides complex impact as antibacterial, antioxidant and immunocorrecting actions of the preparation in area of lesion and, thus, quick interruption of acute stage by preventing the development of adhesions and saving reproductive function in this category of patients.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: veterinary pharmacology.

SUBSTANCE: The suggested method deals with interaction of valerianic acid anhydride with steroid alcohol - 17α-acetoxy-3β-hydroxy-6-methylpregna-4.6-dien-20-on at molar ratio being 1.1-1.5:1 to steroid, which should be implemented in pyridine medium in volume-weight ratio of 1.5-2.0:1 pyridine to steroid at 22-25°C, excess of anhydride should be hydrolyzed with water at the quantity of 15-20% against the volume of reaction mass, as for developed valerianic acid, it should be dissolved in 1-1.5%-ammonia aqueous solution and a target product should be filtered, washed with water up to neutral reaction to be washed with methanol. The innovation provides obtaining new target product of higher purification degree.

EFFECT: higher efficiency.

7 ex, 7 tbl

FIELD: medicine, obstetrics, gynecology.

SUBSTANCE: one should intravenously inject Reamberin 1.5% up to 400 ml solution daily, percutaneously affect with magneto-infrared laser, wave length being 0.89 mcm, impulse power of infrared radiation corresponds to 4 W. One should affect uterine and adnexal area alternatively, at exposure being about 2-3 min for every region, radiation frequency being 5 Hz and 50 Hz altered every other day. Since the second day of therapy one should additionally supply laser light flow directly towards uterine area through vaginal arch for 1 min at frequency of 1000 Hz. Total course of therapy corresponds to about 5-7 d. The innovation enables to increase immunological body strength, decrease relapse frequency and decrease side effects of curative preparations applied.

EFFECT: higher efficiency of therapy.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves introducing 0.06% sodium hypochlorite solution from intravaginally arranged cathode during 10-15 min every session in 5-7 days long course.

EFFECT: reduced risk of abdominal pregnancy relapses; retained reproductive function.

1 tbl

FIELD: medicine, obstetrics.

SUBSTANCE: the present innovation deals with introducing the complex of medicinal preparations directed for treating different complications during pregnancy. Moreover, along with applying the above-mentioned complex it is necessary to introduce actovegin as uterotonic remedy per 2 tablets thrice daily. The innovation enables to normalize myometrium state and that of uterine-placental circulation at efficiency being 93%.

EFFECT: higher efficiency.

2 ex

FIELD: medicine, gynecology, surgery.

SUBSTANCE: one should introduce 3.5%-chitosan ascorbate gel into fistulous channel that contains metronidasol at the dosage of 2 mg/ml, at the volume up to 20 ml once/2 d till complete fistula's closing. The present innovation enables to activate reparative processes and fistulous epithelization that favors for closing fistulous channel in earlier terms.

EFFECT: higher efficiency of therapy conducted.

2 ex

FIELD: medicine, gynecology.

SUBSTANCE: the present innovation deals with treating vaginal dryness and reproductive dysfunction in women either during or after menopause. For this purpose, it is necessary to introduce (deaminohydroxy)thoremifen or its salts or ethers at dosage ranged 25-100 mg daily either perorally or transdermally. The innovation provides efficient therapy at resistance to other types of hormonal therapy, due to multi-component impact upon disease pathogenesis.

EFFECT: higher efficiency of therapy.

8 cl, 2 dwg, 1 tbl

FIELD: veterinary science.

SUBSTANCE: one should intravenously inject for a cow 150 ml 40%-glucose solution simultaneously with 100 ml 10%-calcium chloride solution 1 h after fetal birth, and oxytocin intramuscularly at the dosage of 6 U/100 kg body weight and magestrophan intramuscularly at the dosage of 2 ml, in 3 h one should introduce oxytocin intramuscularly at the same dosage. The suggested method is efficient in preventing puerperal uterine subinvolution in cows that enables to shorten sterility duration and coefficient of insemination.

EFFECT: higher efficiency of prophylaxis.

2 ex, 2 tbl

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes a compound of the general formula (I) or (II) wherein R1 represents hydrogen atom; R2 is taken among the group consisting of aryl and heteroaryl; R3 is taken among the group consisting of halogen atom, nitro-, cyano-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, trifluoromethyl, trifluoromethoxy-group, -NH2, -NH-(C1-C6)-alkyl and -N-(C1-C6)-alkyl)2; b is a whole number from 0 to 4; R4 is taken independently among the group consisting of halogen atom, hydroxy-, carboxy-, oxo-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C1-C6)-alkoxycarbonyl, phenyl (wherein phenyl group can be substituted optionally with one-three substitutes taken independently among RD), phenylsulfonyl, heteroaryl (wherein heteroaryl can be substituted optionally with one-three substitutes taken independently among RD), heterocycloalkyl, -NH2, -NHRA, -N-(RA)2,

wherein each RD is taken independently among halogen atom, hydroxy-, carboxy-, oxo-group, (C1-C4)-alkyl, (C1-C4)-alkylthio, hydroxy-(C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, (C1-C4)-alkylcarbonyl, trifluoromethyl, trifluoromethoxy-group, -NH2. -NHRA, -N-(RA)2, -C(O)N(RA)2, -SO2N(RA)2, acetylamino-, nitro-, cyano-group, formyl, (C1-C6)-alkylsulfonyl, carboxy-(C1-C6)-alkyl and aralkyl; c = 0; a means a whole number from 0 to 1; Y is taken among the group consisting of a residue -(C1-C)-alkyl, -C(O)-, -(C2-C6)-alkenyl)-carbonyl, -carbonyl-(C1-C6)-alkyl)-, -C(S)-, -C(O)NH-(C1-C6)_alkyl), -C(O)-(C3-C7)-cycloalkyl)- and (C3-C7)-cycloalkyl)-C(O)-; represents phenyl;

is taken among the group consisting of phenyl, heteroaryl and cycloalkyl under condition that when R1 represents hydrogen atom, R3 represents hydrogen atom, b = 0, c = 1, Y represents -CH2-, represents phenyl and represents phenyl then R2 is not trimethoxyphenyl, and its pharmaceutically acceptable salts. Also, invention describes a pharmaceutical composition designated for inhibition of activity of phosphodiesterase comprising a pharmaceutically acceptable vehicle and compound by cl. 1, method for preparing pharmaceutical composition, methods for treatment of sexual dysfunction by using compound by cl. 1 or pharmaceutical composition, method for increasing the concentration of cGMP in penis tissue and method for treatment of state when inhibition of activity of phosphodiesterase shows the favorable effect. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: valuable medicinal and biochemical properties of compounds and composition.

17 cl, 7 tbl, 98 ex

FIELD: veterinary science.

SUBSTANCE: the suggested stimulant of porcine reproductive function contains the germs of barley grain and lipoic acid at the following ratio of components, g: the germs of barley grains 100, lipoic acid 0.2. The innovation provides increased rate of estrus onset and conception rate in sows.

EFFECT: higher efficiency of reproductive stimulation.

1 ex, 1 tbl

FIELD: veterinary science.

SUBSTANCE: the present innovation deals with applying 7%-ichthyol against 0.85% sodium chloride solution and denatured emulsified placenta (DEP), the latter to be introduced subcutaneously at the dosage of 20 ml on the 1st, 5th, and 9th d of therapeutic course. Sterile 7%-ichthyol should be injected thrice subcutaneously being heated up to animal's body temperature on the 1st, 3d and 5th d at the dosages of 25, 30 and 35 ml.

EFFECT: higher efficiency of therapy.

4 ex, 4 tbl

FIELD: biotechnology, microbiology.

SUBSTANCE: invention proposes the strain Escherichia coli S5/98 producing microcine B 5/98 showing the broad spectrum of antagonistic activity against microorganisms of genus Escherichia, Salmonella and Klebsiella that is isolated from adult pig feces. The strain inhibits 69-99% of escherichia and 42.6-80% of salmonella of wild type and shows activity against colicinogenic strains of intestinal bacillus and 10 different species of salmonella. The strain has no pathogenicity and doesn't elicit toxic, toxigenic and allergic properties. The strain is deposited in All-Russian collection of industrial microorganisms at № B-8564. The strain is used in preparing probiotic microcicol B 5/98 in liquid and dry formulation. Using the invention shows regulatory effect on intestine microflora and enhances nonspecific resistance of animals.

EFFECT: valuable properties of strain and probiotic.

1 ex

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