Quantitative determination of ademetionine in tablets utilizing ATR-FTIR and partial least squares methods approaches.

In this study there were utilized a combination of Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and partial least squares (PLS) regression method to develop quantitative models for determining the concentration of ademetionine in commercial tablets. The established and validated models were specifically designed for a commercial product containing ademetionine 1,4-butandiesulfonate. The coefficient of determination for the developed model was 0.999. Relative standard deviation (RSD) does not exceed 1.6% for repeatability and intermediate accuracy, which meets the international ICH and AOAC requirements for the method performance. The validation results effectively confirmed that this method is suitable and meets the current requirements for analytical methods in drug quality control. Consequently, this approach can be used for routine ademetionine analysis in pharmaceutical products and has the potential to be applied to other active pharmaceutical ingredients (APIs) in drug quality control.

[Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies].

AIM: To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009. MATERIALS AND METHODS: The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients. RESULTS: The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30 10(9)(/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). CONCLUSION; The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.

[Review of conservative replacement methods of the included minor defects of dentitions].

The paper reports the review of replacement methods of one absent tooth. The study was an assessment of prosthetic work in 275 patients with similar diagnosis. The aim of the study was to compare the indications for different fixed appliances with adhesive bonding on the example of schematic clinical situations.

[Sequential degradation of p-cresol by photochemical and biological methods].

Sequential photo- and biodegradation of p-cresol was studied using a mercury lamp, as well as KrCl and XeCl excilamps. Preirradiation of p-cresol at a concentration of 10(-4) M did not affect the rate of its subsequent biodegradation. An increase in the concentration of p-cresol to 10(-3) M and in the duration preliminary UV irradiation inhibited subsequent biodegradation. Biodegradation of p-cresol was accompanied by the formation of a product with a fluorescence maximum at 365 nm (lambdaex 280 nm), and photodegradation yielded a compound fluorescing at 400 nm (lambdaex 330 nm). Sequential UV and biodegradation led to the appearance of bands in the fluorescence spectra that were ascribed to p-cresol and its photolysis products. It was shown that sequential use of biological and photochemical degradation results in degradation of not only the initial toxicant but also the metabolites formed during its biodegradation.

[The results of a multicenter randomized trial on the treatment of acute myeloid leukemia of adults].

AIM: Systematization of the results of 20-year multicenter randomized trial of the efficacy of treatment of acute myeloid leukemia (AML) of adults; presentation of the design of the study of the strategy of consolidation and maintenance therapy after high-dose consolidation initiated in 2007. MATERIAL AND METHODS: Treatment outcomes on the protocol AML-01.01 are presented for 354 AML patients from 29 hematological centers located in 22 towns of Russia and 2 towns of Ukraine. The patients were randomized into 3 groups by variant of therapy: 124 patients (62 males and 62 females; age median 42 years) received 4 courses of 7+3+VP-16 and 5 courses of maintenance therapy (7+3 with thioguanin); 130 patients (65 males and 65 females, age median 41 year) received 2 courses of 7+3+VP-16, 2 courses 7+3, maintenance--5 courses 7+3 with thioguanin; 126 patients (57 males and 68 females, age median 40 years) were given 2 courses of 7+3+VP-16, 2 HAD courses, treatment discontinuation. RESULTS: A complete remission after the first course of 7+3+VP-16 was achieved in 55% patients, after the second course--in 30% after the course 7+3+VP-16 or 7+3 with mitoxantron, in 70%--after NAM. Overall and recurrence-free survival were 18 and 35%; 30 and 20%; 36 and 30%, respectively. There was no significant difference in efficacy of the treatment scheme. CONCLUSION: The multivariate analysis has shown that a leading factor having impact on treatment results was the number of randomized patients: the less patients were randomized, the worse were the results.

[Estimation of local fraction of cardiac output in the view of the active diastole theory].

Is shown, that as against single-phase model of pulse hemodynamics (the theory of passive diastole), the expression of pulse component in formula of definition of stroke volume on chest rheography explains satisfactorily in the view of two-phase model (the theory of active diastole). The new original rheographic index of blood supply of a studied vascular zone--local fraction of cardiac output is offered. Calculation of the given parameter has much in common with calculation of quantitative definition with pulse component of stroke volume, but is calculated under more simple formula and can practically be used for any site of cardiovascular system.

Fluorescence analysis of photoinduced degradation of ecotoxicants in the presence of humic acids.

The photolysis of humic acids and phenols in water containing humic acids was investigated. Humic acids extracted from peat (Vasuygan Bog, Tomsk Region, Russian Federation) induce the phototransformation of 4-chlorophenol at 365 and 222 nm. Humic acids were characterized by UV-, fluorescence-, IR- and EPR-spectroscopy and laser-induced fluorescence. The influence of humic acids on the phototransformation of phenols in different irradiation conditions was investigated. Comparison of the data on mercury lamp irradiation showed that the most effective phenols degradation was observed under exposure to KrCl* exilamp light (lambda = 222 nm) in the presence of humic acids.

[Substantiated diagnostic properties of two-component analysis of rheogram].

The paper presents a conclusive basis applicable to the parameters of two-component analysis of biosignals of the pulse filling of the rheogram type conditioning the parameters' specific use. A new original rheographic parameter is suggested for the examined zone of vascular filling--local fraction of cardiac output. A verbal model of general hemodynamic pulse filling developed by the author previously and specified within the present cases study has been used for the purpose. The model was constructed as a specific description of the working cardiovascular system during cardiac cycles, which is based on the two-phase cardiac function, with respect to the active heart work both in the systolic and diastolic phases of the cardiac cycle.

[The phase electrocardiogram structure as viewed from the position of a refined model of the pulse hemodynamics]. / Fazovaia struktura élektrokardiogrammy s pozitsii utochnennoi modeli pul'sovoi gemodinamiki.

The EKG phase structure during the cardiac cycle is presented, in which a scheme of separating the trans-membrance action potential into the sodium, calcium and potassium constituents is used and which is based on a previously developed qualitatively novel model related with the functional regularity of the cardio-vascular system during the cardiac cycle. Not only the active systolic functioning of the myocardium but also the active (energy-dependent) diastolic activity is duly considered in it.

[A visual diagnostic evaluation of the cerebral hemodynamics by rheo-encephalogram]. / Vizual'naia diagnosticheskaia otsenka tserebral'noi gemodinamiki po reoéntsefalogramme.

A technology of a diagnostic evaluation of the cerebral-hemodynamic functional state made on the basis of rheoencephalogram end involving the two-component analysis method is described in the paper. The method consists in a quantitative representation of a qualitatively new regularity pertaining to the functioning of the cardiovascular system with a two-phase structure of cardiac output, i.e. the positive systolic one and the negative diastolic one, which is in line with the active functioning of the myocardium both in the systolic and diastolic cardiac-cycle phases. A partial separation of the arterial and venous components of rheoencephalogram, which reflect (during the cardiac cycle) the pulse fluctuations of voluminous blood filling in the arterial and venous sections of the examined bloodstream portion, is made use of. The method parameters provide for separate diagnostic evaluations of the tonus and blood filling of the arteries, veins and small peripheral vessels of the examined blood-stream portion. The computer-aided version of two-component analysis supports the rheoencephalogram processing in the sitting registration posture covering the full neurological examination range with respect to sex and age-related peculiarities of cerebral hemodynamics.

Alternative processing of the tryptophanyl-tRNA synthetase mRNA from interferon-treated human cells.

We have analysed the structure of mRNA isoforms of the human gene encoding tryptophanyl-tRNA synthetase (Trp-tRNA synthetase) expressed in the epithelial CaOv cells and MT-4 lymphocytes. The Trp-tRNA synthetase gene is induced by interferon-gamma in both lines and, in MT-4 lymphocytes, also by interferon-alpha. Four Trp-tRNA synthetase mRNA isoforms have different combinations of the first exons IA, IB and II. Two transcription initiation sites (P1 and P2) were detected 90 bp from each other. Processing of the primary transcript initiated from the P1 start site generates the mRNA isoform where exon IA joins to exon II. The other three isoforms are produced by alternative splicing of the primary transcript produced from the P2 start site. Isoform 2 has a 3'-end fragment of exon IA joined to exon II. Isoform 3 contains exons IA and IB. Isoform 4 contains exon IA and exon III and lacks exon II encoding the N-terminus of the Trp-tRNA synthetase. Therefore, the two primary transcripts of the Trp-tRNA synthetase gene differ only in the 5' flank sequence between P1 and P2, and this fragment regulates their processing. Both interferon-alpha and interferon-gamma induce exon IA-containing and exon IB-containing isoforms of the Trp-tRNA synthetase mRNA.

Cloning of a cDNA encoding a human protein which binds a sequence in the c-myc gene similar to the interferon-stimulated response element.

A human cDNA clone encoding a c-myc promoter-binding protein (IRLB) was selected by screening a human fibroblast lambda gt11 phage library with the hexamer oligodeoxyribonucleotide (oligo) 5'-GGCGGGAAAAAGAACGGA, corresponding to the protein-binding element of human c-myc similar to the interferon-stimulated response element (ISRE). The lambda gt11 phage clone, encoding a fusion protein which bound the probe oligo, was used to create an strain of Escherichia coli. The deduced amino-acid sequence of the cloned protein contains a putative alpha-helix which is expected to act as the DNA-binding domain. DNase footprinting analysis and oligo-binding specificity assays showed that the cloned factor recognizes the ISRE-like element of the P2 promoter region of human c-myc.

[Changes in the central and cerebral blood flows of patients with arteriosclerosis obliterans of the arteries of the lower extremities after different types of anesthesia]. / Izmeneniia tsentral'nogo i mozgovogo krovotoka u bol'nykh obliteriruiushchim aterosklerozom arterii nizhnikh konechnostei posle raznykh vidov anestezii.

A comparative analysis of changes in central hemodynamics and cerebral circulation depending on the technique of anesthesia used has been performed in 63 patients after reconstructive surgery on aorto-ileo-femoral segment. Signs of ischemic heart disease have been revealed preoperatively in 40 patients. The majority of them (88%) showed hypokinetic type of hemodynamics. Signs of cerebral atherosclerosis were found in 90% of patients. Rheoencephalographic index in them was lowered by 42%. A statistically significant deterioration in central hemodynamic and cerebral circulation parameters has been recorded immediately after the operation in patients with concomitant ischemic heart disease operated on under general endotracheal anesthesia. An improvement in central hemodynamic parameters after surgery has been observed in the group of patients operated on under epidural anesthesia.

[Dynamics of the development of disseminated intravascular coagulation syndrome in dystocia]. / Dinamika razvitiia sindroma disseminirovannogo vnutrisosudistogo svertyvaniia krovi pri diskoordinirovannoi rodovoi deiatel'nosti.

A comprehensive investigation of the hemostasis system permitted to follow the dynamics of disseminated intravascular hemocoagulation syndrome in patients with dystocia. In patients with spastic contractility and myometrial hypertonicity hypercoagulation stage of the aforementioned syndrome was preserved, in those with uterine inertia a transitory stage persisted, those with hypotonicity demonstrated hypocoagulation stage of the syndrome development. It was concluded that the prevention of acute syndrome stages depended on the rapid recovery of coordinated uterine contractility.