FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

[The role of mycological culture studies in diagnostics of otomycoses]. / Znachenie mikologicheskogo kul'tural'nogo issledovaniia v diagnostike otomikozov.

The present work was designed to analyze the results of themycological culture study involving 350 patients at the age varying from 14 to 75 years with the diagnosis otomycosis. The pathogenic fungi known to induce the clinical picture of otomycosiswere identified in 227 (64.8%) patients. The majority of the pathogeneticall most significant species belonged to the genus Candida (45.4%). The mold fungi occurred in 30.8% of the patients. In 11.5% of the cases, they occurred together with bacterial microflora and in 6.7% of the cases in association with the yeast fungi. The species of the genus Aspergillus prevailed among the mold fungi. It is concluded that the complicated forms of otomycosisdevelop as a result of infection caused not only by mold fungi but also by yeast fungi and/or associations of the two groups. These findings suggestthe necessity of usingthe differential approach to the prescription of the adequate medications.

[Pathogenic properties of fungi Fusarium genus isolated from patients with atopic dermatitis].

AIM: Study of adhesive activity and growth speed of fungi Fusarium genus isolated from the surface of cutaneous covering in patients with atopic dermatitis (AD). MATERIALS AND METHODS: Clinical and museum F. oxysporum, F. solani strains were used in the study. Seeding was carried out into agarized Czapek and Sabouraud medium. The cultures were studied for9 days at 30 +/- 2 degrees C, adhesive properties of fungi were determined by using model based on nitrocellulose film (S.A. Lisovskaya et al., 2006). RESULTS: The studies carried out showed statistically significant differences in adhesive properties and intergrowth intensity of various Fusarium spp. Adhesion level of F. solani microconidia was almost 2.5 times higher compared with F. oxysporum. Formation of the first germ tube by F. solani microconidia was noted during the first 10 hours whereas by F. oxysporum--only at day 2. CONCLUSION: The data obtained confirm species differences of Fusarium spp. pathogenic properties that emphasize the importance of species identification of fungi.

[Determination of a Candida albicans antigen using an amperometric immunoenzyme sensor]. / Opredelenie antigena Candida albicans s pomoshch'iu amperometricheskogoimmunofermentnogo sensora.

Determination new variant enzyme immunoassay with amperometric enzyme immunosensor, including the immobilizing enzyme-choline esterase and antibodies against Candida albicans (CA) in biosensitivity part of sensor, for diagnose disease of CA. The method for determination of CA based on combination immunochemical reactions and voltammetric indication of analytical signal was developed. Amperometric enzyme immunosensor developed has been used as detector. Differences dilutions of antibody (Ab) against antigen (Ag) of CA immobilizing in common with choline esterase (CE). The method of immobilization developed allows to receive the sensor with including the immobilized CE and Ab in common. The method of determination of CA based on combination the reaction of forming immune complex tAb-AgI with enzyme immunosensor for its detection. The dynamic range of concentrations determined of Ag depends on degree of dilution of Ab used for manufactory biosensitivity part of sensor. The data indicate that the [Ab-Ag] immune complexes are stable. This is also confirmed by the values of [Ab-Ag] binding constants, obtained in Scatchard coordinates. This method of determination doesn't require special preparation of a sample. Selectivity, sensitivity, simplicity and quickness are characterize of this method which could be used for manufacturing test-sistem for determination CA in blood.

[Biochemical activity hyperbranched polyol Boltorn H20 and polycarboxyBoltorn H20 in relation to aspartic proteinase of Candida albicans].

Hyperbranched polyol Boltorn H20 and polycarboxyBoltorn H20 synthesized on its multifunctional nanoscaffold influence catalytic activity of aspartic proteinase Candida albicans (C. alb.). The results of study catalytic activity proteinase C. alb. in relation to hemoglobin at presence Boltorn H20 show, that the effect of activation is mainly observed. The inhibition effect much more poorly also has dot character. PolycarboxyBoltorn H20 render activating effect in area of high concentration (1 x 10(-3) - 5 x 10(-4) M), however this effect is stronger (140%). A kinetic parameters enzyme proteolysis of hemoglobin (the maximal speed (V(m)) and Mikhaelis constant (K(m))) are estimated, seeming types are certain and constants at presence Boltorn H20 and policarboxyBoltorn H20 are calculated.

Administration of vitamin D3 improves antimetastatic efficacy of cancer vaccine therapy of Lewis lung carcinoma.

AIM: To analyze antitumor efficacy of experimental cancer vaccine therapy combined with introduction of vitamin D3 (VD3) for treatment of Lewis lung carcinoma (3LL). MATERIALS AND METHODS: Cancer vaccines composed from recombinant murine beta-defensin-2 (mBD-2) and 3LL cell lysate, or DNA, coding for mBD-2-Muc1 fusion construct cloned in pcDNA3+ vector, were prepared and used for intradermal vaccination. Experimental cancer vaccines introduced i. d. at therapeutic and prophylactic regimens to 3LL-bearing C57Bl mice, were applied alone or in combination with VD3 (administered per os) and/or low-dose cyclophosphamide (CP, administered intraperitoneal). Efficacy of treatments was analyzed by primary tumor growth dynamics indexes and by metastasis rate in vaccinated animals. RESULTS: As it has been shown, administration of the protein-based vaccine composed from mBD-2 and 3LL cell lysate in combination with VD3 and CP, but not in VD3 free setting, led to significant suppression of primary tumor growth (p < 0.005) and had significant antimetastatic effect. Introduction of VD3 with or without CP in the scheme of treatment with mBD- 2-Muc1-DNA vaccine at therapeutic regimen has led to significant suppression of primary tumor (p < 0.05) and metastasis volumes (p < 0.005), while in the groups of animals treated with DNA-vaccine + VD3 with or without CP at prophylactic regimen, significant antimetastatic effect (p < 0.05) and elevation of average life-span (p < 0.05) have been registered. CONCLUSION: The results of this pilot study have shown promising clinical effects of VD3 administration in combination with cancer vaccinotherapy in vivo.

Expression patterns of murine beta-defensin-2 mRNA in Lewis lung carcinoma cells in vitro and in vivo.

AIM: To evaluate the anti-tumor activity of murine beta-defensin-2 (mBD-2) expression in vitro and in vivo. MATERIALS AND METHODS: Based on pcDNA3 vector, constructs containing mBD-2 cDNA coding mature defensin molecule (pcDNA3-mBD2), and Igk-mBD-2 insertion, coding secretory sequence plus mature defensin molecule (pcDNA3-Igk-mBD-2) were generated. Lewis lung carcinoma (3LL) cells were transfected in vitro with these plasmids and with blank pcDNA3 vector, and the proliferative rate and clonogenic ability of obtained cell lines cultivated in vitro were analyzed using (3)H-incorporation technique and colony formation in semi-soft medium, respectively. Expression of mBD-2 mRNA was studied by semiquantative RT-PCR analysis. Also, transfected cells were transplanted to C57B mice, and the patterns of tumor growth in vivo were analyzed by routine techniques. RESULTS: We have found out that in the 3LL cells transfected with pcDNA3-mBD-2 and pcDNA3-Igk-mBD-2, the expression of mBD-2 mRNA is significantly down regulated compared to wild-type cells and 3LL cells transfected with blank vector. The cells with suppressed mBD-2 expression differed from parental cells and cells transfected with blank vector by higher proliferation rate (p < 0.001) and higher clonogenic ability. The 3LL-mBD-2 and 3LL-Igk-mBD-2 cells that are transplanted to C57B mice gave rise to more aggressive tumors that possessed significantly higher growth rate (p < 0.01) than those that arise from wild-type 3LL cells. CONCLUSION: The obtained results indicate the relation between mBD-2 expession in 3LL cells and their proliferation rate and malignant phenotype, and also allow to hypothesize the possibility of regulation of mBD-2 mRNA expression in these cells by a feedback mechanism.

[Effect of Zn(II) and Mn(II) on catalytic activity of aspartic proteinases from Candida albicans].

The interaction of secreted aspartic proteinases Candida albicans (SAP C. albicans) with ZnCl2 and MnCl2 was studied. Logarithms of stability constant from the data of electronic spectroscopy were calculated: lgbeta = 4.73 +/- 0.20 for the complex [SAP C. albicans - Zn(II)] and lgbeta = 7.02 +/- 0.20 for the complex [SAP C. albicans - Mn(II)]. The composition and maximum accumulation of complexes in solution were calculated. The optimal conditions of hydrolysis of the substrate, HAS (human serum albumin) in the presence of proteinases were determined: [HSA] = 0.004 g/ml, [SAP] = 2.33 microM, pH = 4.5, the time of incubation of 25 min. The activity SAP C. albicans in the presence of ZnCl2 and MnCl2 in different concentrations in optimal conditions of enzymic hydrolysis was estimated. For the first time the activating action of ZnCl2 on catalytic activity of proteinase in concentration 5 x 10(-7) mol/l was discovered. The maximal rate of enzymic reaction (Vm), the Michaelis constant (Km) and constants of effects in presence and absence as the effector of ZnCl2 were calculated. The estimation of albuminatic activity of C. albicans infections family in different diseases localization in the presence and the absence as the effector of ZnCl2 was evaluated.

[Amperometric enzyme immunosensor for determination of Klebsiella pneumoniae antigen].

An amperometric enzyme immunosensor for detecting the bacterial antigen Klebsiella pneumoniae has been developed. The biosensing part of this analytical device consists of cholinesterase and antibodies to Klebsiella pneumoniae co-immobilized into the cellulose nitrate membrane. The conditions of immunosensor functioning (ratio of enzyme and antibodies, substrate concentration, pH of working buffer solution) were chosen. The sensor with antibodies in dilution 1:20 demonstrated the best analytical characteristics. Working concentrations were ranged from 1 x 10(-9) to 1 x 10(-3) mg/ml, the detection limit was 5 x 10(-10) mg/ml. The cross-reactivity of used antibodies to antigens of bacteria, causing similar diseases was evaluated. The conditions of immunosensor reuse by regeneration of its biosensing part were chosen. The developed immunosensor was probed on blood sera of patients suffering from urea tract diseases.