Intraperitoneal Administration of Muramyl Dipeptide ß-Heptylglycoside to Pregnant and Non-Pregnant Female Mice Modulates Production of Th1/Th2/Th17/Tr1 Cytokines by Splenocytes Ex Vivo.

Muramyl dipeptide ß-heptylglycoside (C7MDP) was administered to non-pregnant CBA female mice and pregnant mice after non-abortion-prone mating (CBA×BALB/c) and mating associated with a high rate of spontaneous abortion (CBA×DBA/2). In non-pregnant females, C7MDP increased the production of IL-2, IL-4, IL-5, IL-6, IL-17, IFNγ, TNFα, and GM-CSF at constant production of IL-1α and IL-10. C7MDP increased the production of IL-10 and IL-17 and suppressed the production of IFNγ on day 8 of gestation in non-abortion-prone mouse couples and stimulated the synthesis of IL-4 and IFNγ, reduced IL-5 production, and slightly increased IL-1α secretion after abortion-prone mating. On day 14 of gestation, C7MDP elevated the yield of IL-2, IL-4, IFNγ, TNFα, and GM-CSF in CBA×BALB/c and CBA×DBA/2 couples and IL-17 in the fi rst variant of mating.

[Effect of tacrolimus on the results of living related kidney donor transplantation].

AIM: To elucidate whether and how tacrolimus affects the cumulative survival of patients after living related kidney donor transplantation. SUBJECTS AND METHODS: The clinical materials of 246 related kidney transplant recipients, including 108 patients in whom tacrolimus (Prograf and Advagraf) Astellas Pharma US, Inc) was included in the immunodepression protocol (Group 1) and 138 patients who did not receive the agent (Group 2), were analyzed. Comparative analysis used the following tests: the Kaplan Meier test estimating the cumulative survival of recipients and transplants; the Cox test assessing the cumulative risk; and the log-rank test. Allorenal graft losses and mortality rates were also calculated. RESULTS: Mathematical analysis of the above indicators demonstrated that the allograft and survival rates were far higher (p < 0.05) and the cumulative risk was much less in Group 1 (p < 0.02). Graft losses and the recipients' deaths were higher in Group 2. CONCLUSION: The analysis suggests that the incorporation of tacrolimus into the immunodepression therapy protocol positively impacts the results of lung related kidney donor transplantation.

[The role of immune monitoring in major liver resections from the position of the operative trauma and anaesthesia protection level].

Recently, the number of liver resection has increased, which requires adequate and safe anesthesia provision in this surgery area. Cytokine plasma spectrum is the one of the most important indicators characterizing inflammatory reaction intensity during and after surgery and postoperative period flow prognosis. Immune monitoring gives a notion about operative rauma features, liver damage severity, anaesthesia adequacy. Interleukin dynamics evaluation during liver resections is a topical theoretical and practical problem. The aim of this research was to evaluate the interleukins intraoperative dynamics in liver resection patients. Anaesthesia protocols were analyzed in 51 patients, 26 (51%) of which was a Sevorane multi-component balanced anaesthesia, and 25 (49%) - Propofol multi-component balanced anaesthesia. Intraoperative haemodynamics, metabolism, General and biochemical blood tests, coagulogramm, C3 and C4 complement factors dynamics, cytokines data were evaluated The obtained data testified systemic inflammatory response with a marked pro - and anti-inflammatory cytokines imbalance formation development in patients underwent organ-conserving and major liver resection. Sevorane use leads to a more pronounced anti-inflammatory cytokines synthesis in comparison with TIVA-group, the imbalance of pro - and anti-inflammatory cytokines is also more pronounced in Sevorane-group.

[Immunoassay of nine serological tumor markers on hydrogel-based microchip].

A prototype of test-system for simultaneous quantitative assay of nine tumor markers in blood serum was developed. The main constituent of the test-system is OM-9 biochip containing immobilized antibodies against nine oncomarkers: α-fetoprotein (AFP), carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), cancer antigen 15-3 (CA 15-3), cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), prostate-specific antigen, total (PSAtot) and free (PSAfree) forms, neuron-specific enolase (NSE). The biochip-based assay procedure for carrying out simultaneous quantitative determination of nine tumor markers in patient's blood serum: two-steps sandwich-immunoassay, was proposed. The main analytical characteristics of the method were obtained. The results permit to consider the prototype of the test-system as a promising instrument for clinical application. The test-system prototype was tested using blood serum samples of oncological patients (252 samples) and healthy donors (185 samples). Increased concentrations of one or more tumor markers above the normal level were found in 76.6% cases of oncological patients and only in 6% cases of healthy donors. For colorectal cancer patients group, application of modern statistical methods of data-processing in medical researchers, i.e. ROC-analysis and logistic regression, indicted that the simultaneous assay of nine tumor markers on biochips showed much more diagnostic significance (area under the ROC-curve (AUC) reached 0.84) than traditional assay of 2 tumor markers, CEA and CA 19-9 (AUC = 0.59). The developed biochip-based test-system can be recommended both for the estimation of people's health, e.g., for standard medical examination, and for tracking of tumoral process in postsurgical period or after specific tumor treatment.

[Assessment of anaesthesia sufficiency and stress response during liver resections].

Recently number of patients undergoing a surgery for primary and secondary liver damages is increased. Thus an adequate and safe anaesthesiological care for the surgeries is a very actual problem. The article deals with a study of anaesthesiological care in 51 patients. 26 patients (51%) received multimodal balanced anaesthesia based on sevoflurane and 25 patients (49%) received multimodal balanced anaesthesia based on continuous propofol infusion. Monitoring of haemodynamics, acid-base balance, common liquid volume, intracellular and extracellular liquid, stress hormones (cortisol and prolactin) was carried out during the surgeries. Haemodynamics and infusion and transfusion therapy were adequate during both methods of anaesthesiological care for liver resections. Strongly marked tissue injury during surgery causes neuroendocrine stress. Cortisol activity during anaesthesia based on continuous propofol infusion was less than during anaesthesia based on sevoflurane. This fact shows that propofol provides stronger protection than sevoflurane. Adequate level of anaesthesia does not cause outoregulative mechanisms suppression which is important during strongly traumatic surgery. Anaesthesia based on sevoflurane both to anaesthesia based on continuous propofol infusion is a method of choice for liver resection.

[Effect of clarithromycin on the systemic inflammatory response syndrome severity in patients after myocardial revascularization surgery].

The aim is to investigate the effectiveness of SIRS pharmacological correction in patients after CABG when adding clarithromycin to the standard antibacterial therapy. Patients of the 1st group (n=25) received Klacid- CP ("Abbott") in perioperative period plus to standard antibacterial therapy (3rd generation cephalosporins), patients of 2nd group received standard therapy. At 1st screening stage, as well as on the 2-nd and 4-th day after operation were recorded data of an anamnesis, concomitant pathology, examination, were measured the level of white blood cells, LII, biochemical blood analysis (CRP), defined the concentration of interleukins (IL-1, 6, 8,10,12) and TNF - a. In all studied patients, laboratory' and physical data did not go beyond the reference values, intraoperation data, blood loss and ALV duration did not statistically differ. According to the results of research in patients of both groups there were manifestations of SIRS in the form of reliable significant increase in body temperature, as well as the level of Il-6, IL-8, CRP, LII, TNF - a, leukocytosis. While in the clarithromycin group body temperature was significantly lower in all time points. The level of CRP for the 4th day in 1.5 times, and TNF in 4 times less than in the control group, and the values of anti-inflammatory IL-10 to the 2nd day, on the contrary almost in 2 times higher than those in the control group. Thus, the obtained data confirmed that the CABG is accompanied by non-inflammatory SIRS development. At the same time clarithromycin gives an independent proven anti-inflammatory effect and can be recommended for application in the schemes of prophylactic antimicrobial therapy during perioperative period in this category of patients.

[Immunity and cytokine status after surgeries on the large intestine].

The aim of our study was to examine the effect of individual schemes of multimodal analgesia on indicators of immunity and inflammation markers after operations on the colon. Patients of group 1 (n=15) received paracetamol, lornoxicam and epidural ropivacaine, 2nd group of patients (n=15)-paracetamol, epidural ropivacaine and tramadol. Comparison group (n=10) patients underwent patient controlled analgesia by promedol. Before surgery, 1st and 3rd days after surgery we examined the contents of cytokines in plasma: interleukin 12p70, interleukin 10, interleukin 6, and TNF. Before surgery and at 5-7 days after surgery indicators of cellular, fagocytal and humoral immunity were monitored. Before surgery patients with colorectal cancer revealed changes in the indices of different components of immunity, as well as an increase in pro-and anti-inflammatory cytokines compared with healthy donors. Multimodal analgesia in patients after operations on the colon is not accompanied by changes in plasma concentrations of cytokines and parameters of immune status in comparison with monoanalgesia by promedol.

[Enzyme-linked immunosorbent assay for determination of cyclosporin A in whole blood].

A test-system based on enzyme-linked immunosorbent assay (ELISA) for quantitative determination of cyclosporin A (CSA) in human whole blood has been developed. The detection limit of the method was 25 ng/ml, the linearity of the method in the concentration range 60-1400 ng/ml varied from 94 to 105%, the variation coefficient did not exceed 8%. The novel method exhibited good correlation with radio-immunoassay and polarization fluoroimmunoassay methods; the linear regression coefficients were 0.965 and 0.983, respectively. The developed test system is stable for at least 9 months when stored at 4 degrees C and can be used in clinical practice.

[Current protease-antibody-based serodiagnostic tools and their use in the diagnosis of autoimmune thyroid diseases].

The purpose of the investigation was to comparatively study the possible clinicodiagnostic and clinicoprognostic value of thyroglobulin (TG) autoantibodies (anti-TG autoAB) and thyroid peroxidase (TPO) (anti-TPO autoAB) with proteolytic activity (protease-AB) and to develop additional clinicoimmunological criteria for working out a protease-AB-based laboratory serodiagnosis protocol. Sera from 240 patients with autoimmune thyroiditis (AIT), 124 with diffuse toxic goiter (DTG), and 172 with other thyroid diseases were studied. Serum from 40 clinically healthy donors served as a control. Sera were screened for anti-TG and anti-TPO autoAB by enzyme immunoassay and/or radioimmunoassay. Nonspecific proteolytic activity was determined, by incubating a highly purified AB IgG-isotype solution with nonspecific substrate (such as BSA-FITS or thyoredoxine/Trx), followed by the measurement of relative fluorescence shifts at a wavelength of 470 nm. The blood samples taken from patients with AIT or DTG and the highly purified anti-TG or anti-TRO autoAB of IgG isotype were incubated with appropriate human substrates to determine AG-specific proteolytic activity. Proteolysis products were detected by PAAG electrophoresis. An association was found between the rise in the frequency of protease AB, their catalytic activity, a tendency toward autoAB between themselves, and the degree of thyroid tissue degradation in AIT and DTG; some specific features of a serological pattern were noted in diferent dorms of AIT and DTG. For example, the prevailing autoABs have been shown to be TG-specific in AIT and TPO-specific proteases in DTG; also, the detectable catalytic activity of both autoAB in AIT is an order of magnitude higher than that in DTG. No protease ABs have been recorded in other forms of thyroid diseases in which antithyroid autoABs are also frequently detected. The screening procedure for protease AB may be considered as a highly sensitive and specific indicator test in the diagnosis and prediction of AIT and DTG, which allows one to diagnose not only within the framework of major thyroid nosological entities, but much broader, by covering a great variety of syndromal forms of pathology.

[Method of pharmacological myocardial preconditioning with halogen-containing anesthetics in cardiosurgical patients].

The purpose of the investigation was to study whether isoflurane and sevoflurane might be used for pharmacological myocardial preconditioning (PMP) in patients with coronary heart disease during myocardial revascularization on the working (Part I) and arrested (Part II) heart and to develop a possible procedure for PMP. Part I deals with the study of the effect of PMP with halogen-containing anesthetics during myocardial revascularization on the working heart. The study included 66 patients who were divided into 4 groups; 1) sevoflurane feeding was started just after anesthesia induction and it lasted until some coronary arteries were ligated; 2) sevoflurane was fed for 15 min; 3) isoflurane was used; 4) controls. The markers of myocardial lesion (troponin T, I) were measured and the incidence of perioperative myocardial ischemia and needs for inotropic support were also analyzed. Part II was dedicated to the study of the effect of PMP during myocardial revascularization under extracorporeal circulation (EC). The study covered 65 patients who were divided into 4 groups; 1) sevoflurane was administered throughout the anesthesia until the aorta was ligated; 2) it was used for 15 min before aortic ligation; 3) sevoflurane was employed only to induce anesthesia; 4) controls. The variables similar to those in Part I of the investigation were chosen to assess the results of this study. The use of sevoflurane and isoflurane reduces a risk for myocardial ischemic lesion during myocardial revascularization both under EC and on the working heart. Short-term (15-min) use of an agent before myocardial ischemia suffices for PMP to develop its effect. The effect of PMP has its duration that is 76 min, as shown by our findings.

[Phospholipase A2, group IIa, as an earlier unknown immunohistological marker of cardiac myxoma].

Phospholipase A2, group IIA, gene expression has been analyzed in primary heart tumors. High expression has been demonstrated through several ways: reverse-transcriptase chain polymerase chain, Northern blotting hybridization at the RNA level and immunoblotting, immunohistochemical assay at the protein level. Human cardiac myxoma exhibits highly positive phospholipase A2, group IIA, immunophenotype (100% positive cases). The immunophenotype is unique among human primary cardiac tumors. Phospholipase A2, group IIA, can be proposed as a tissue marker for pathological examination after heart tumor resection.

[Clinical, diagnostic and surgical aspects of heart space-occupying lesions at children and youths].

Clinical, diagnostic and surgical aspects of primary heart tumors, pseudotumor and morphologically unidentified heart space-occupying lesions were analyzed at 52 childhood and adolescence patients. Difficulty of early diagnosis, more aggressive clinical course in majority cases, and individual approach to the choice of surgical approach has been demonstrated. Principle of oncological determinant has been ensured the success in surgical treatment of patients with non-malignant intracavitary and intramuscular neoplasms, and also with pseudotumor space-occupying lesions. Postoperative lethality was low (2.2%), and there were no true recurrences of disease in long-term period after surgery.

[Short- and long-term results of balloon dilatation of aorta coarctation].

Balloon dilatation is an alternative method of aorta coarctation (AC) treatment, and it may be effective in 80 - 90% cases with appropriate indications. Arterial hypertension is one of the symptoms of AC and frequent complication of short- and long-term postoperative period. Surgical correction does not guarantee regress of pathological symptoms in all the cases, and method of surgery does not influence the rate of postoperative arterial hypertension. The study reviews CA balloon dilatation experience and analyses cases of late arterial hypertension rate in long-term period after balloon dilatation procedure.

[Safety and quality of myoplegia in different types of abdominal surgeries]. / Bezopasnost' i kachestvo mioplegii pri razlichnykh tipakh abdominal'nykh vmeshatel'stv.

The efficiency of new non-depolarized myorelaxants, i.e. of rocuronium and cisatracurium, in abdominal surgery with general anesthesia (combined or total intravenous anesthesia) of 114 patients was evaluated clinically and accelerometrically. The use of the above drugs at 2 x ED95 was confirmed to ensure a high-quality myorelaxation in different surgery variations (laparoscopy or laparotomy). A lack of effect on the hemodynamics (according to continuous non-invasive monitoring) and release of histamine (according to radioimmunology assay) make it possible to use the myorelaxants in patients with concurrent cardiovascular disease and with burdened allergic history. A bigger degree of prognosticated effect duration is typical of cisatracurium versus rocuronium, whereas the latter is a myorelaxant of choice in case a fast trachea intubation is needed.

[Immunocorrectors in the complex treatment of postoperative suppurative-inflammatory complications in surgical patients and monitoring of immunological parameters]. / Immunokorrektory v kompleksnom lechenii posleoperatsionnykh gnoino-vospalitel'nykh oslozhnenii u khirurgicheskikh bol'nykh i monitoring immunologicheskikh pokazatelei.

The results of monitoring of immune parameters in different categories of surgical patients with postoperative purulent-inflammatory complications are described in the paper. The combined type of secondary immunodeficiency and degree second immunodeficiency according to A.M. Zemskov were detected in all patients. Immunocorrecting drugs, like polyoxidonium, imunofan and likopid, were added to the complex treatment of patients with the above complications. Their administration normalized the dynamic clinical course of the purulent-inflammatory processes and restored the immunological parameters.

[PRKAR1A gene mutations in two patients with myxoma syndrome (Carney complex)]. / Mutatsii v gene reguliatornoi sub"edinitsy 1-alpha tsiklo-AMF-zavisimoi proteinkinazy A (PRKAR1A) u dvukh bol'nykh s miksomnym sindromom (kompleksom Carney).

Carney complex is an autosomic dominant disorder initially described as the association of cardiac myxomas, spotty skin pigmentation and endocrine overactivity and considered as a multiple neoplasia and lentiginosis syndrome. Mutations in the tumor suppressor gene PRKAR1A, coding for the type 1-alpha regulatory subunit of cAMP-depended protein kinase A have been previously identified in about half of the Carney complex kindreds. In this paper we report identification of the molecular defect in PRKARIA gene in two Carney complex patients. A new mutation (403delAC) located in a 3rd exon of PRKARIA gene has been observed in one case, and a previously described mutation in exon 7 (847delTC) in the second case.

[Regulation of the functional status of the lower esophageal sphincter with gastrointestinal hormones in cardiospasm and reflux esophagitis]. / Patofiziologicheskie aspekty reguliatsii funktsional'nogo sostoianiia nizhnego pishchevodnogo sfinktera gastrointestinal'nymi gormonami pri kardiospazme i refliuks-ézofagite.

A role of gastrointestinal hormones in the regulation of the lower esophageal sphincter was studied in 22 patients with cardiospasm and 21 with reflux esophagitis. The levels of gastrin, vasoactive intestinal polypeptide (VIP), glucagon, insulin, and c peptide were determined by radioactive assay before and after surgical treatment. In opposite abnormalities (cardiospasm and reflux esophagitis), there is a different degree of VIP secretion both at the beginning and after functional exercises. Before and after functional exercises, the level of VIP was higher than in those with cardiospasm. The value of VIP on fasting and after functional exercises may be an additional information to establish the diagnoses of cardiospasm and reflux esophagitis and to evaluate the efficiency of the treatment performed.

[Clinical, diagnostic and therapeutic features of tricuspid infectious endocarditis]. / Osobennosti kliniki, diagnostiki i lecheniia infektsionnogo éndokardita trikuspidal'nogo klapana.

From 1987 to 1998, examination and treatment were conducted of 12 patients with infectious endocarditis of the tricuspid valve (TIE). 11 of them were operated. TIE was clinically characterized by lesser circulation thromboembolism and marked right ventricular failure. TIE was successfully diagnosed by echo-CG (diagnostic sensitivity 83.3%). Serious disturbances of cellular immunity demanded immunocorrection. Indications for surgical treatment are listed.

[Correction of secondary immunodeficiency as a method of prevention of suppurative-septic complications after surgery with artificial blood circulation]. / Korrektsiia vtorichnoi immunnoi nedostatochnosti kak sposob profilaktiki gnoino-septicheskikh oslozhnenii posle operatsii s iskusstvennym krovoobrashcheniem.

Eighty-five patients with acquired heart diseases with and without infective endocarditis (IE) were examined. In one group of patients traditional therapy was supplemented by the Russian drug immunofan, a synthetic hexapeptide with immunomodulating, antiinflammatory, and detoxifying effects. A course consisted of 10 intramuscular injections every other day (1 ml of 0.005% solution). The drug was prescribed after immunological studies on a laser flow cytometer (Becton Dickinson, USA). Correction was carried out before and after the operation. The postoperative period was uneventful in patients treated with immunofan; the incidence of clinical manifestations of IE was decreased. The concentrations of cytokines (IL-1, IL-6, TNF-alpha) in the blood were increased in patients with IE. In patients treated with immunofan, the concentrations of cytokines were decreased and immune parameters were normalized. Changes in the cytokine status can be used as a laboratory test for evaluating the efficiency of treatment in cardiosurgical patients with IE.