The use of fecal calprotectin in monitoring activity of inflammatory bowel diseases.

AIM: To compare fecal calprotectin (FC) concentration with laboratory and diagnostic methods in patients with inflammatory bowel diseases (IBD). MATERIALS AND METHODS: The level of FC was measured in 110 patients with established IBD. Crohn diseases (CD) was diagnosed in 50 patients, ileocolitis - in 38 and terminal ileitis in 12 individuals. Ulcerative colitis (UC) was diagnosed in 60 patients, total colitis in 35, left-side colitis in 21 and 4 patients have proctitis. Laboratory data include measurement of FC, leukocytes, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), fecal occult blood. All patients underwent colonoileoscopy (CIS) at the start of disease flare and after 12 weeks of treatment. RESULTS: We found linear correlation between level of FCP and endoscopic activity of CD, analyzing FCP level and endoscopic activity of CD before (during disease flare) and after 12 weeks treatment (r=0.66, p<0.001). Linear correlation between FCP and SES-CD sustained after 12 weeks of treatment (r=0.77, p<0.001). We revealed correlation between FCP concentration. And CRP level (r=0.59, p<0.05). The linear correlation was detected between FCP and endoscopic activity of UC (r=0.88, p<0.001) before the treatment. After 12 weeks of treatment linear correlation was shown between FCP and Meyo scale (r=0.73, p<0.001). IBD patients with FCP more than 200 mcg/g have high risk of disease reccurence in short-term period of time (HR - 8.33; 95% CI 2.05-33.8; χ2 - 11.85; p<0.001) and (HR - 2.7; 95% CI 1.1-6.6; χ2 - 5.3; p<0.05), accordingly. CONCLUSION: Increased FCP level indicates poor effectiveness of treatment and high risk of reccurence. The level of FCP correlates strongly with recent laboratory and diagnostic indices of activity and enables to determine patients with high risk of reccurence. Thus, thorough monitoring, including additional procedures, contributes to just-in-time treatment modification.

[Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation].

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. AIM: To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. MATERIALS AND METHODS: Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. RESULTS AND DISCUSSION: Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. CONCLUSION: IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

Clostridium difficile in inflammatory bowel disease.

AIM: To study epidemiology and risk factors for Clostridium infection (CDI) associated with Clostridium difficile in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 1179 medical records were analyzed in a retrospective study of patients with IBD, of which 764 patients met the inclusion criteria. Patients were divided into 2 groups based on the presence of a preliminary diagnosis of CDI. Statistical analysis was carried out using Pearson Chi-square and two-sample t-test. RESULTS: The incidence of CDI in patients with IBD was 17.3%, with the same prevalence in patients with Crohn's disease (CD) (n=53/40.1%) and ulcerative colitis (UC) (n=79/59.9%). The mean age of occurrence of CDI in patients with IBD was 37.8±12.9, 84.8% of infections were community-acquired and only 4.5% occurred in medical institutions. Only 21.2% of all patients with CDI had a history of antibiotic use, and 24.2% had previously used steroids. Long-term immunosuppressive therapy in patients with IBD has an impact on the development of CDI: among patients with CDI 45.5% long-term received azathioprine/6-mercaptopurine, in patients without IBD - 17.7% (p<0.001). 18% of patients with CDI had control of the disease with salicylate therapy, while 62% of patients without CDI achieved remission by taking salicylates (p<0.05). CONCLUSION: The prevalence of CDI in UC and CD is comparable (p=0.16). The study shows that patients with IBD are more sensitive to the development of CDI at a young age, while not having such traditional risk factors as recent hospitalization or antibiotic use. Patients with IBD with CDI in history often noted the ineffectiveness of therapy with salicylates, often require the assignment of biological therapy. IBD patients with CDI have a lower average albumin, and a higher activity of the inflammatory process.

Biomarkers of inflammatory bowel disease activity.

The review presents data on calprotectin, lactoferrin, leukocytes labeled with isotope indium 111In, calgranulin C and pyruvate kinase type M2 - highly sensitive biomarkers to assess the severity of intestinal inflammation. Their importance in diagnostics, determination of treatment efficiency, including as predictors of recurrence of ulcerative colitis and Crohn's disease is shown.

Transcription profile analysis of the endometrium revealed molecular markers of the personalized 'window of implantation' during in vitro fertilization.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR). Differences in the level of mRNA expression of all the studied genes in the receptive endometrium were found in comparison to the prereceptive one, which allowed us to classify two functional states of the endometrium. The results of histological examination responded to the stage of maturation of the endometrium in 78.7% of cases. Receptive endometrial status can be determined based on the integral evaluation of mRNA expression level of 4 PAEP, DPP4, MSX1, and HLA-DOB genes. The model for determining a personalized `window implantation' is offered for practical application in ART.

Profiles of mRNA expression for genes involved in implantation, early and middle phases of secretion stage in human endometrium.

The expression of mRNA of 36 genes involved in implantation was studied by reverse transcription and real-time PCR. Significant differences in mRNA expression during the early and middle stages of the secretion phase were detected for genes mmp7, vegf, il2m, il1ß, il8, il18, tnfα, il10, tgfß, igfbp2, etc.

[Effect of short term graded physical exercise on the level of glycemia in children and adolescents with type 1 diabetes mellitus: data of long term ECG monitoring and registration of motor activity].

Study aim was to elucidate effect of graded physical exercise on glycemia level and interval QT duration in children and adolescents with type 1 diabetes mellitus. We carried out 25-hours parallel monitoring of glycemia, ECG and physical activity in 15 children and adolescents aged 9-17 years. During monitoring these patients performed an exercise test (PWC170). We found that there were two periods of significant and prolonged lowering of glycemia: in 120-420 min and 19-21 hours after exercise. Lowering of glycemia after physical exercise was associated with prolongation of QT interval. Registration of motor activity allowed to exclude changes of glycemia due to physical activity unrelated to graded exercise.

[Ovarian overstimulation syndrome: problem of intensive care].

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication, the basis for which is a hyperergic uncontrolled ovarian response to gonadotropins in the ovulation stimulation cycles and assisted procreation programs. The clinical picture of OHSS is characterized by a broad spectrum of clinical and laboratory manifestations: increased vascular permeability resulting in the excess release of liquid into the third space and its storage with the development of hypovolemia, hemoconcentration, oliguria, hypoproteinemia, electrolyte imbalance, polyserositis; in severe cases, acute renal failure, thromboembolic events, and adult respiratory distress syndrome develop. The goal of treatment is to prevent the development of multiply organ dysfunctions. Its leading methods are infusion therapy with colloid-crystalloid solutions and anticoagulant therapy. Whether diuretics and other drugs are administered is under consideration. Indications for laparocentesis and peritoneal transudate evacuation are discussed. Complications requiring surgery are identified.

Serum antibodies to the 27-kd heat shock protein in women with gynecologic cancers.

OBJECTIVES: Among women the association between heat shock protein immunity and cancer has been examined primarily for breast cancer. Autoantibodies to the 27-kd heat shock protein were detected in some patients with breast cancer but not in control subjects, and the presence of these antibodies was correlated with improved survival. We examined the relationship between autoimmunity to heat shock proteins and the diagnosis of malignancies of the female genital tract. STUDY DESIGN: Serum samples from women seen for possible gynecologic malignancies or returning for evaluation after surgery, radiation, chemotherapy, or a combination for gynecologic cancers were tested for immunoglobulin G antibodies to the 27-kd, 60-kd, 70-kd, and 90-kd heat shock proteins by enzyme-linked immunosorbent assay with the purified recombinant proteins bound to wells of a microtiter plate. Serum samples from women with no history of malignancies served as control preparations. RESULTS: Antibodies to the 27-kd heat shock protein were detected in only 1 of 29 healthy control subjects (3.4%) and 1 of 23 women whose lesions were benign (4.3%). In marked contrast, 39 of 96 women with gynecologic cancers (40.6%) had positive antibody detection (P =.0004 vs benign). The percentages of positive results seen for ovarian (17/34, 50%), endometrial (13/34, 38.2%), cervical and uterine (3/10, 30%), vaginal and vulvar (3/5, 60%), and other (3/13, 23.1%) cancers were not significantly different from each other. Similar prevalences of antibodies to the 27-kd heat shock protein were seen among patients with cancer who had untreated active disease and after treatment. Unlike the results with antibodies to the 27-kd heat shock protein there was no relationship between antibodies to the other heat shock proteins and any gynecologic cancer. CONCLUSION: Circulating autoantibodies to the 27-kd heat shock protein were found to be associated with malignancies of the female genital tract.

IgA antibodies to the 27-kDa heat-shock protein in the genital tracts of women with gynecologic cancers.

Heat-shock proteins promote cell survival under adverse environmental conditions. Synthesis of the 27-kDa (HSP27), 70-kDa (HSP70), and 90-kDa (HSP90) heat-shock proteins is increased in malignantly transformed cells and has been associated with tumor proliferation, metastasis, and resistance to chemotherapeutic agents. The increased expression of heat-shock proteins and their association with tumor-specific antigens may result in local immunity to the heat-shock proteins. We examined the occurrence of IgA antibodies to HSP27, HSP70, and HSP90 in the lower genital tracts of women with possible gynecologic cancers. Cervical samples were obtained from 119 consecutive women being evaluated for a gynecologic malignancy or returning for a follow-up examination following cancer treatment. Aliquots were tested for IgA anti-heat-shock protein antibodies by ELISA. Aliquots were also tested for IgG antibodies to HSP27 as well as for human papillomavirus. Anti-HSP27 IgA was detected in 85.7% of 21 women with endometrial cancer tested prior to diagnosis and in 41.1% of 17 women tested after treatment. In women with ovarian cancer, 77.8% of 9 women tested prior to diagnosis and 75.0% of 24 women evaluated after treatment were anti-HSP27 IgA-positive. Of 6 women with cervical cancer tested prior to diagnosis, 5 were positive for this antibody. None of 25 women with benign diagnoses or 46 healthy women were cervical IgA anti-HSP27-positive (P < 0.0001). In contrast, anti-HSP27 IgG was not associated with a gynecologic malignancy. HSP27 cervical antibodies were not associated with the presence of human papillomavirus. Cervical IgA antibodies to HSP90 were associated with ovarian cancer; antibodies to HSP70 were not cancer-associated. We conclude that cervical IgA antibodies to HSP27 may be indicators of a gynecologic malignancy.

Heat shock protein expression during gametogenesis and embryogenesis.

When cells are subjected to various stress factors, they increase the production of a group of proteins called heat shock proteins (hsp). Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. Heat shock proteins enable cells to survive adverse environmental conditions by preventing protein denaturation. Thus the physiological and pathological potential of hsps is enormous and has been studied widely over the past two decades. The presence or absence of hsps influences almost every aspect of reproduction. They are among the first proteins produced during mammalian embryo development. In this report, the production of hsps in gametogenesis and early embryo development is described. It has been suggested that prolonged and asymptomatic infections trigger immunity to microbial hsp epitopes that are also expressed in man. This may be relevant for human reproduction, since many couples with fertility problems have had a previous genital tract infection. Antibodies to bacterial and human hsps are present at high titers in sera of many patients undergoing in vitro fertilization. In a mouse embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. The gross morphology of these embryos resembled cells undergoing apoptosis. The TUNEL (terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling) staining pattern, which is a common marker of apoptosis, revealed that embryos cultured in the presence of hsp antibodies stained TUNEL-positive more often than unexposed embryos. These data extend preexisting findings showing the detrimental effect of immune sensitization to hsps on embryo development.

Vaginal heat shock protein expression in symptom-free women with a history of recurrent vulvovaginitis.

OBJECTIVES: The cause of recurrent vulvovaginitis remains unexplained in most cases. Heat shock protein synthesis is induced under conditions of stress; its presence in vaginal samples from women who were between episodes of recurrent vulvovaginitis thus might reflect a persistent perturbation in the local milieu. STUDY DESIGN: We undertook an evaluation by means of enzyme-linked immunosorbent assay of 60-kd heat shock protein and inducible 70-kd heat shock protein expressions in vaginal wash samples from 24 symptom-free women with a history of recurrent vulvovaginitis and 19 matched control subjects. The samples were also tested for Candida albicans, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, and human papillomavirus by polymerase chain reaction; for bacterial vaginosis by clinical and microbiologic evaluation; and for interleukin 10, interleukin 1, interleukin 8, RANTES, and eotaxin by enzyme-linked immunosorbent assay. RESULTS: The presence of 60-kd heat shock protein was detected in 11 women with recurrent vulvovaginitis (45.8%) and 1 control subject (5.3%, P =.005). Similarly, 70-kd heat shock protein was present in 8 patients with recurrent vulvovaginitis (33.3%) and no control subjects (P =.005). The presence of 60-kd heat shock protein and the presence of 70-kd heat shock protein were correlated with each other (P =.02), as were both 60-kd heat shock protein (P =.006) and 70-kd heat shock protein (P =.01) correlated with IL-10. There was no relation between the presence of 60-kd heat shock protein or 70-kd heat shock protein and detection of IL-1, IL-8, or any microorganism. CONCLUSION: The expression of heat shock proteins and IL-10 in the vaginas of women with a history of recurrent vulvovaginitis but not in the vaginas of control subjects suggests the existence of differences in the vaginal milieu between the 2 groups, even when both are without vaginal symptoms.

Chlamydia trachomatis Infection, Immunity, and Pregnancy Outcome.

Chlamydia trachomatis can ascend from the cervix to the fallopian tubes and survive for long periods of time without causing symptoms. The immune response to infection clears the extracellular organisms but leads to development of a persistent intracellular infection. Repeated cycles of productive infection and persistence eventually induce tubal occlusion and infertility. Persistently infected cells continue to synthesize the chlamydial 60 kD heat shock protein (hsp60). Immunity to conserved regions of hsp60 may result in autoimmunity to human hsp60. Expression of hsp60 by the embryo and decidua during early pregnancy may reactivate hsp60-sensitized lymphocytes, disturb pregnancy-induced immune regulatory mechanisms, and lead to immune rejection of the embryo. Due to this mechanism women with tubal infertility who are sensitized to the human hsp60 may have a decreased probability of successful outcome after undergoing in vitro fertilization and embryo transfer.

[The effect of lysenyl, an ergot alkaloid, on menstrual-reproductive functions]. / Osobennosti vliianiia na menstrualno-reproduktivnuiu funkciiu proizvodnogo alkaloidov sporyny--lisenila.

The usage of 0.6-0.8 mg of lysenile in the course of 6 months gives a possibility to stimulate pregnancy in 70% of patients and gain pregnancy in 20% of patients. In order to exceed the percentage of impregnantion, the course of medicine can be enlarged up to 15 months.

[Use of metergoline in the treatment of infertility associated with hyperprolactinemia]. / Opyt primeneniia metergolina v lechenii besplodiia, obuslovlennogo giperprolaktinemiei.

The usage of metergoline in patients with infertility and different forms (hinds) of hyperprolactinaemia was studied for 90 days at a dose of 12 mg. It gives a possibility to stimulate ovulation in 64% of patients and gain pregnancy in 8% of patients. In order to exceed the percentage of inpregnantion the course of medicine can be enlarged up to 6 months.

[Clinico-diagnostic indicators and late results of the treatment of infertility in hyperprolactinemia]. / Kliniko-diagnosticheskie pokazateli i otdalennye rezu'ltaty lecheniia besplodiia pri giperprolaktinemii.

Clinical manifestations of various hyperprolactinemia-associated conditions were studied in infertile females. The results of hormone therapy were evaluated with regard to various preparations employed, pregnancy outcomes in those females were followed up.

[Use of function tests in the diagnosis of hyperprolactinemia in women treated for sterility]. / Pouzití funkcních testu v diagnostice hyperprolaktinémie u zen lécených pro sterilitu.

28 women with hyperprolactinaemia were examined (prolactin levels varied from 720 to 66000mlU/l). These patients were subjected to the functional tests with GnRH, TRH and metoclopramid. In all groups of the patients, who were devided acording Prolactin levels, the sensitivity of lactotrophs was decreased. There is reserve correlation between levels of the prolactin and gonadotrophins (r = -0.64). The test with metoclopromid is more informative in the diagnosis of tumoral and functional hyperprolactinaemia.

[Insulin-induced structural transformations in the plasma membranes of liver and fat cells]. / Indutsirovannye insulinom strukturnye perestroiki v plazmaticheskikh membranakh pechenochnykh i zhirovykh kletok.

Two classes of SH-groups have been revealed with Ellman's reagent in isolated plasma membranes of epididimal fat cells from rats. Preincubation with 2 x 10(-9) M insulin (25 degrees C, 30 min) results in a 15% decrease of content of the fast reacting groups. The effect was absent in preparations solubilized with 0,06% Triton X-100 or 0,1% SDS. In the presence of insulin the rates of solubilization of liver plasma membranes by these two detergents have been found to increase. It is suggested that binding of insulin to receptor initiates the generalized structural rearrangement in both types of membranes.