Clinical implication of detecting sensitization to iodinated radiocontrast media in the basophil activation test by flow cytometry.

The use of iodinated radiocontrast media is necessary for visualization. A number of patients have adverse effects of various nature and severity when these drugs are administered. Routine allergy tests do not provide adequate diagnosis of reactions to drugs in this group. The aim of this work is to assess the capabilities of the basophil activation test to confirm sensitization to non-ionic iodinated radiocontrast media, as well as to select a safe alternative drug in patients with a burdened history. Basophil activation test by flow cytometry was performed in 184 patients The Nikiforov Russian Centre of Emergency and Radiation Medicine¼ EMERCOM of Russia and 32 volunteers using ultravist, omnipack, and optiray. The presence of sensitization was assessed based on the basophil activation index, as well as spontaneous and anti-IgE antibody-induced activation of basophils and the population of T-lymphocytes type 2 immune response. The volunteers showed no sensitization to iodinated radiocontrast media. In patients with a medium degree of hypersensitivity reaction in vivo, in vitro sensitization to drugs was detected 4 times more often than in patients with a mild degree (51% versus 13.5%). In patients with systemic reactions to the administration of a known drug, in vitro sensitization was confirmed in 86% of cases, while the frequency of detection of sensitization to drugs did not differ. Spontaneous activation of basophils in patients and type 2 T-lymphocytes were 2 times higher than in volunteers. Patients were more likely to have low (less than 30%) activation of basophils for anti-IgE antibodies. The specificity of the basophil activation test with iodinated radiocontrast media was 100% with a sensitivity of 94.1%. Most patients were able to select a non-sensitizing contrast. Inclusion in the algorithm of spontaneous and anti-IgE antibody-induced activation of basophils and a population of T-lymphocytes type 2 immune response will allow the doctor to carry out a personalized approach to the management of patients with a burdened history.

[Multiple sclerosis vaccine: possibilities of the use of dendritic cells immunomodulatory potential].

For the first time we carried out a clinical assessment of the safety, tolerability and clinical efficacy course of repeated administration of experimental modified autologous vaccine interleykin (IL-10) dendritic cells in two patients with secondary-progressive multiple sclerosis patient and one with relapsing-remitting multiple sclerosis. In the course of treatment, we carried out clinical and immunological monitoring. It was found out that intradermal dose of 3 x 106 cells applied to spinal area 6-12. times did not cause any serious side effects. After the treatment with dendritic cells, the following results were observed: 1) a significant positive clinical effect in patients with secondary-progressive multiple sclerosis exacerbations; 2) moderate positive clinical effect in patients with relapsing-remitting multiple sclerosis, in a state of remission; 3) a complete absence of any clinical results in patients with secondary-progressive multiple sclerosis without exacerbations. The immune response was characterized by a significant absolute and relative increase of serum T-regulatory cells. Discovered distinct anti-inflammatory properties of dendritic cell therapy allow us to consider it as a promising area of personalized treatment based on an individual vaccination against multiple sclerosis.

[Evaluation of Efficacy and Safety of Longterm Feeding with Amino Acid-Based Formula in Infants with Cow's Milk Protein Allergy: Results of the Open-Label Prospective Controlled Post-Registration Trial].

Background: The cow's milk allergy (CMA) prevalence is 2−3% in children under one year. Approximately in 5% of cases transferring to extensively hydrolysed formula (eHF) doesn't lead to disappearance of CMA symptoms. Aims: Evaluation of efficacy and safety of amino-acid formula (AAF) longterm feeding in children under one year and development of predictors of successful transfer from AAF to eHF. Materials and Methods: In open-label prospective post-registration trial duration of 365 days were included 43 children aged from 3 to 12 months with CMA. CMA was based on Russian and international guidelines. When a patient was included in the trial, child received eHF for 4 weeks with the evaluation of the effect of elimination diet (ED): in case of absence of effect, for diagnostic purposes child feed with AAF for 2 weeks and upon receiving the effect, child continued to receive it for at least 6 months. Diet was considered effective if there were observed disappearance of clinical manifestations of CMA during of formula using. Results: Children fed with AAF gain weight and increased height statistically higher during the first 6 months, compared with children receiving eHF, but without subsequent difference in a year. After 4 weeks' of AAF feeding, there was a significant decrease in SCORAD index from 46.84 (SD 4.164) to 2.52 (SD 2.204) (p=0.005); disappearance of gastrointestinal manifestations of CMA from 3 to 14 day. After 4 weeks, the 100% normalization of previously elevated faecal calprotectin (p<0.05) was observed; and after 6months. ED, in 60% of children normalization of the index of activation of basophils with milk was observed. 38.7% of children were transferred to eHF in 6 months, 12.9% and 25.8% in 9 and 12 months respectively. Conclusions: Use of AAF for children with CMA is an effective and safe treatment without lengthening the period of elimination, which is necessary for the formation of tolerance to cow's milk protein and has a positive impact on weight and height. Normalization of specific activation of basophils with milk could be considered as a predictor of successful transfer from AAF to eHF in children with CMA.

[Biodistribution of the recombinant heat shock protein rhHsp70 in intracranial C6 glioma models in Wistar rats and subcutaneos B16/F10 melanoma in C57BL/6 mice].

For the first time, the biodistribution of recombinant heat shock protein in rhHsp70 rats with grafted intracranial C6 glioma was evaluated. It was assessed using the fluorescent antibody accumulation chaperone rhHsp70 conjugated with fluorochrome Alexa Fluor 555 in tumor cells by intratumoral or intravenous administration. Assessment of the distribution and accumulation of labeled protein was carried out on the model of subcutaneous B16/F10 melanoma in C57BL/6 mice with the use of single-photon emission computer tomography. After 60 minutes after intravenous administration rhHsp70-I123 (20 MBq, 5 mg chaperone) accumulation of the drug mainly in the liver and tumor tissue was showed. The coefficient of the differential accumulation of the labeled protein KDN(tumor/background) was 3.14. It was turned out that comparing the level of fixation of rhHsp70-I123 in the liver and the tumor KDN(tumor/ liver) = 0.76. After 24 hours from the time of injection of rhHsp70-I123 it was observed increase the level of fixation of the labeled protein in the liver and melanoma: KDN(tumor/background) = 3.43; KDN(tumor/liver = 0.78.

[The efficacy of polychromatic visible and infrared radiation used for the postoperative immunological rehabilitation of patients with breast cancer].

The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent significant elevation of their blood concentrations (IL-6 within 1 day) and IFN-gamma (within 7 days after mastectomy). The course of PT resulted in the decrease of their levels to the initial values. The follow-up of the treated patients during 4 years revealed neither recurrence of the disease nor the appearance of metastases.

[Investigation of the association of mammographic breast tissue density with glucose effects and circulating stem cells].

Our study involving healthy postmenopausal females established that mammographic breast tissue density was lower in cases of more intensive stimulation by glucose of reactive insulinemia and glucose-induced glyoxalase I activity in bood mononuclears as well as in women with higher concentrations of circulating CD90+stem cells. Conversely, the density tended to increase in those with higher ratio of glucose-induced generation of reactive oxygen species in mononuclears. Our data point to possible mechanisms of increased density as a breast cancer factor when concomitant with relative predominance of progenotoxic effect of glucose and lower CD90+stem cells levels which are believed by some authors to be capable of suppressing the growth of certain tumors.

[Successful combined surgical treatment double giant ureterocele complicated by double ureterohydronephrosis, cascade lithiasis and uterine myomatosis].

A case is reported of a 58 year old patient with a diagnosis: double giant ureterocele, secondary multiple calculi of the right ureterocele, calculus of the inferior calyx of the right kidney, calculus of the terminal part of the left ureter, double ureterohydronephrosis, chronic pyelonephritis, multiple calcifying myoma of the uterus. A combined single-stage operation (panhysterectomy, deletion of multiple calculi of the right ureterocele, deletion of the calculus of the left ureterocele, crosscut right ureterectomy with excision of ureterocele, right ureterocystoneostomy by Leadbetter-Politano, installation of the double J-stent into the right kidney, crosscut and longitudinal left ureterectomy with excision of ureterocele, left ureterocystoneostomy by Leadbetter-Politano, installation of intubating drainage into the left ureter, cystostomy) followed by extracorporeal shock-wave lithotripsy were performed in this adult patient with combined pathology of the urinary system.

[Evidence based medicine as background for development of stomatological patient report conducting].

Urgent need in methodology of information estimation for true clinical decision taking gave powerful impulse for evidence based medicine concept development that appeared at the end of 80th years. Proved efficacy and safety, optimal correlation of the indices were the stages of the methods and means selection for rationing. In our country such approach found its reflection in developing clinical protocol conducting (standards for doctors), in vitaly important medicines listing and lists of medicines that could be refunded in the system of additional medicine provision.

[An open randomized comparative trial of efficacy and safety of selective alpha-adrenoblocker setegis (terazosin) in therapy of patients with chronic bacterial prostatitis].

An open randomized comparative trial of setegis (terazosine) has shown good subjective and objective results in patients with chronic bacterial prostatitis. The drug is well tolerated and produces insignificant side effects. It is also demonstrated that combined therapy with alpha-adrenoblockers is more effective that monotherapy with antibacterial drugs in patients with bacterial prostatitis.

[Clinical efficacy and safety of terazosine (setegis) in patients with benign prostatic hyperplasia with concomitant cardiovascular diseases].

The aim of the study was assessment of clinical efficacy and safety of terazosine (setegis) in patients with benign prostatic hyperplasia (BPH) and concomitant cardiovascular disease. A total of 62 BPH patients with cardiovascular disease (ischemic heart disease, hypertension) having indications for alpha-adrenoblockers (mean age 74 +/- 11 years, 58-85) received terazosine in a dose 1-5 mg for 2 months. Clinical efficacy of terazosine was assessed by IPSS scale, residual urine, maximal voiding velocity. Safety of the drug was controlled by monitoring of arterial pressure, ECG, echo-CG. All the tests were made before therapy, on the treatment week 2, 4 and 8. The response was 90.3%. Overall symptoms score decreased by 37.0%, quality of life score rose by 23.8%. Amount of residual urine fell by 64.8%, maximal voiding velocity increased by 36.6%. Moderate effects of the drug (vertigo, weakness) occurred in 11.3% patients for 1 or 2 days after start of the therapy and were due to a moderate fall of arterial pressure in normotensive patients. Later artertial pressure stabilized, ECG registered no exacerbations of ischemic heart disease, no anginal attacks, no change in cardiac rhythm. Thus, terazosine (setegis) is effective and safe in BPH patients with cardiovascular disease. Pretreatment consultation of the cardiologist is desirable for correction of basic antianginal therapy.

[The TVT operation in injury of the pelvic ring]. / Operatsiia TVT pri travmaticheskom narushenii tazovogo koltsa.

The authors report a case of a woman with combination of stress urinary incontinence (SUI) with posttraumatic rupture and divergence of the pubic joint. The latter led to relaxation of the pelvic base and urethral ligaments resultant in SUI. The patient was treated surgically (a modified TVT operation). This rare case demonstrates possibility of SUI development consequently to trauma of the pelvic ring and a TVT operation efficacy made in non-standard setting.

[Metastases from renal tumor to adrenals]. / Metastazy opukholi pochki v nadpochechnikakh.

The aim of the study was assessment of diagnosis and surgical treatment of adrenal metastases (AM) of renal carcinoma (RC). 10 cases of RC AM have been analysed. Bilateral metastases were diagnosed in 2 patients, ipsilateral in 5 patients, contralateral in 3. Three patients had synchronous metastases, seven had metachronous ones. AM were detected 8 months to 14 years after after operation on the kidney. Non-invasive dynamic control over the retroperitoneal space after nephrectomy for RC using advanced visual methods (ultrasonography, x-ray and resonance magnetic CT) not only detects AM but also determines metastatic genesis of the tumor. Thus, significant verification of RC AM, especially of metachronous origin, requires the study of the findings obtained at clinical, laboratory, ultrasonic, radiation examinations as well as comparison of histological structure of the removed kidney tumor and the adrenal. Early diagnosis and removal of a solitary adrenal metastasis of RC provides prolongation of the patient's life and survival of patients with RC late stages.

Induction of the estrogen effect-switching phenomenon by ethanol and its correction.

Female rats (aged three months at the start of the study) were kept for four months on drinking water (group 1) or 5% ethanol. Rats drinking ethanol were additionally divided into six groups (groups 2-7). During the next two months of the experiment, animals of group 2 continued to drink only ethanol, while rats of group 3 additionally received N-acetylcysteine, those of group 4 received ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), those of group 5 received melatonin, those of group 6 received carnosine, and those of group 7 swam in the so-called training regime for five days a week. All animals underwent bilateral ovariectomy 2.5 weeks before experiments ended, and were given daily i.m. estradiol (2 microg) during the 11 days before the last experimental day. After treatments, blood estradiol and cholesterol levels were measured, along with progesterone receptor levels, peroxidase activity, the index of proliferation, the proportions of cells in the S and G2/M phases, the thickness of the endometrium, and the extent of DNA damage (using the "comet" technique) in uterine tissue. Liver estradiol 2-hydroxylase activity was also measured. The results led to the conclusion that drinking of 5% ethanol in combination with administration of estrogens was accompanied by induction of genotoxic (G) changes in the uterus and that this was prevented by administration of N-acetylcysteine and melatonin. The combination of vitamins C and E increased some of the manifestations of the hormonal (H) effect of estrogens (uterine weight and induction of progesterone receptors), but weakened others (the index of proliferation). As a result, the combination of N-acetylcysteine and optimum doses of ascorbic acid and alpha-tocopherol can be recommended for preventing the estrogen effect-switching phenomenon (increases in the G component on the background of weakening of the H component), which is seen particularly in patients consuming excessive amounts of alcohol, increasing the risk that the genotoxic version of hormonal cancerogenesis will develop.

[Induction by ethanol of 'phenomenon of switching estrogen effect' and its correction]. / Induktsiia étanolom "fenomena perekliucheniia éffekta éstrogenov" i ego korrektsiia.

Drinking of 5% ethanol in combination with estradiol induced genotoxic (G) changes in the rat uterine tissue. The changes could be prevented by N-acetylcysteine or melatonin. The data obtained suggest that ascorbic acid and alpha-tocopherol may be recommended in combination with N-acetylcysteine for repair of estrogen effect switching phenomenon.

[Metabolic effect of tobacco smoke and "switching" the estrogen effect: mechanism of increased genotoxicity]. / Vliianie tabachnogo dyma na metabolism i "perekliuchenie" éffektov éstrogenov: mekhanizmy povysheniia genotoksichnosti.

Earlier studies demonstrated dynamic changes in the hormonal and genotoxic effects of estrogens and a decrease in estradiol concentrations and/or aromatase (estrogen synthetase) activity in the uterine tissue in rats exposed to tobacco smoke (TS) and in endometrial and breast tumor tissues of female smokers. This study was the first to reveal an elevation in the excretion of 2- and 4-hydroxyestrogens in smoking postmenopausal women receiving estrogen-replacement therapy, an increase in estrogen-2-hydroxylase activity in the breast and endometrial tumors of the smokers, and no signs of higher aneuploidy frequency in the cervicovaginal epithelium of mice exposed to TS + estrogens. Thus, it can be concluded that there are different stages of endocrine and genotoxic effects of a TS + estrogen combination which may be related to the specific mechanisms and types of hormonal carcinogenesis. A combination of estrogens and smoking induces such variants of DNA damage, which are mediated mainly through the metabolism of catecholestrogens/free radical formation and not through increased or incorrect (aneuploidy) proliferation.

Effect of ethanol on uterotropic action of estrogens.

Female rats aging 3 months at the beginning of experiments received 5 or 15% ethanol and then were subjected to bilateral ovariectomy 2 weeks before end of the experiment. During the last 11 days they were daily injected intramuscularly with 2 microg estradiol. Drinking of 5% ethanol combined with injections of estrogens induced DNA damage in the uterus detected by comet assay and abolished induction of progesterone receptors, changes in peroxidase activity, proliferation index, endometrium thickness, and other indices reflecting the hormonal effect of estradiol on the uterus. Drinking of 15% ethanol was accompanied by an increase in DNA-damaging effects of estrogens and a decrease in their hormonal uterotropic effects. It is concluded that unlike tobacco smoking, drinking of moderate ethanol concentrations modifies primarily genotoxic, but not the hormonal effect of estrogens.

Study of tobacco smoke influence on content of estrogens and DNA flow cytometry data in uterine tissue of rats of different age.

Female rats aged 2.5-3 months ("young") and 6 months ("adult") were or were not exposed to the influence of tobacco smoke (mainstream cigarette smoke, 2 hrs/day during 3 weeks or 3 months). Treatment with tobacco smoke did not induce any changes in uterine weight or estrous cycle but led to the decrease of estradiol (E2) concentration in uterine tissue (especially in adult rats or in young rats after 3 months of experiment). No signs of aneuploidy were found in uteruses of animals-"smokers" though proliferation index and percentage of cells in S-phase were increased (according to flow cytometry data) by 3 weeks and decreased by 3 months of experiment. The data obtained support previously made assumption pointing to phasic character of changes in reproductive system under the influence of tobacco smoke and may be used for further confirmation of the concept explaining the role of smoking in the shift of hormonal (estrogen-induced) carcinogenesis type from promotional to genotoxic one.