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The article analyzes past history, main milestones of making, research and improvement of anatoxins from works of Gaston Ramon who first proposed 100 years ago method of obtaining reliable vaccine preparation (anatoxin) on the basis of formalin neutralized diphtheria (and then tetanus) toxin (1922-1923) to nowadays scientific achievements in prevention and treatment of these infectious diseases.
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Toxinas de Cianobactérias , Formaldeído , TropanosRESUMO
OBJECTIVE: To reveal pathological lung changes in baclofen poisoning and to assess their dynamics. MATERIAL AND METHODS: The experiment included 20 mature (at age 20 weeks) male rats of Wistar line weighing 290-350 gr. The animals were divided into 3 study groups (5 rats in each) depending on experiment's duration after 85 mg/kg baclofen administration: 3, 4.5 and 24 h in the 1st, 2nd and 3rd groups, respectively. Control group consisted of 5 animals without baclofen administration. RESULTS: A number of pathological reactions, including circulatory disorder (venular and capillary congestion, hemorrhage in interalveolar septa, alveoli, sludge) and the appearance of emphysema loci (interalveolar septa at emphysema loci are thinned), alternating with atelectases and dystelectases. The area taken up by vessels after 4.5 h. baclofen administration was statistically significantly higher than in control group, and after 24 h. - statistically significantly higher than in 4.5 h. The area with white blood cells and WBC/IAP ratio after 4.5 h of baclofen administration were statistically significantly higher than in control group after 3 and 24 h of administration. The number of white blood cells, giving PAS positive reaction, increases during baclofen administration. The complex of pathological lung changes, revealed by ourselves, has a certain dynamics. CONCLUSION: The data on morphological lung changes combined with results of chemical examination can be used to diagnose baclofen poisoning and to determine the time elapsed since this medicine administration.
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Baclofeno , Enfisema , Ratos , Masculino , Animais , Ratos Wistar , Pulmão/patologia , Enfisema/patologiaRESUMO
INTRODUCTION: Previously, the placement of a nephrostomy tube was considered standard practice during percutaneous nephrolithotomy (PCNL) to ensure repeat access and kidney assessment. However, some publications have shown that in certain cases, a totally tubeless approach may be a viable alternative, provided that PCNL is performed properly and safely. AIM: To analyze the results and complications of totally tubeless PCNL. MATERIALS AND METHODS: A retrospective analysis of 40 patients with renal stones who underwent totally tubeless PCNL using a single percutaneous access of 16 Ch or 26 Ch at the urology department of NUZ KB "RJD-Medicine", Krasnoyarsk, Russia, from September 2021 to March 2023, was carried out. Factors that could affect the efficiency and safety of PCNL were analyzed. RESULTS: The mean duration of the procedure was 39.6 +/- 14.4 minutes. The average decrease in hemoglobin level was 5.9 +/- 5.5. Narcotic analgesics were used postoperatively in 17.5% (7) of patients. The mean length of stay was 4.7 +/- 1.1 days. Transient fever was observed in 4 (10%) cases. In one case, an exacerbation of chronic pyelonephritis developed. There were no cases of significant bleeding during the PCNL, and no patients required blood transfusion. CONCLUSIONS: Our results confirm that totally tubeless PNL is a safe alternative to standard procedure and is not associated with an increased risk of early postoperative complications. This technique is efficient and safe for kidney stones and may be recommended for a select group of patients.
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Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Nefrolitotomia Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Renais/cirurgia , Cálculos Renais/etiologia , Nefrostomia Percutânea/métodosRESUMO
The effect of the toxic dose of the muscle relaxant baclofen on the parameters of the cardiovascular and respiratory systems was studied in adult male Wistar rats (n=20). Systolic and diastolic BP, HR, and respiratory rate were measured; histological changes in the lungs 3, 4.5, and 24 h after drug administration. Baclofen was administered orally in a sublethal toxic dose of 85 mg/kg under anesthesia. Cardiac activity was analyzed using RSM physiological indicators monitoring system with MouseMonitor S (Indus Instruments) software. Histological examination was performed by light microscopy. Baclofen significantly decreased the respiratory rate and increased HR and BP. Histological examination of the lungs revealed a complex of general pathological processes, such as local circulatory disorders (venular and capillary fullness, sludge), leukocyte infiltration of the interalveolar septa and their thickening due to edema. These findings can be used to estimate the time elapsed after baclofen treatment.
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Baclofeno , Sistema Cardiovascular , Ratos , Animais , Masculino , Baclofeno/farmacologia , Ratos Wistar , Pressão Sanguínea , PulmãoRESUMO
In the history of science, there are great scientists who, without being physicians, wrote golden pages in the History of Medicine. Such was Louis Pasteur, founder of scientific microbiology and immunology. Such was his follower Gaston Ramon (1886-1963), French veterinarian and immunologist who created 100 years ago first anatoxin for active prevention of diphtheria and later tetanus and thus opened era of anatoxins (toxoids) - vaccines based on toxin molecule devoid of toxic properties, but preserving immunogenicity and antigenic specificity. For many centuries, diphtheria (originally known as 'croup') was incurable contagious disease, especially among children. In XIX century, it affected in France up to 30,000 people per year and killed every second infected child. In 1888, at the Pasteur Institute (Paris), Emile Roux (1853-1933) and Alexandre Yersin (1863-1943) demonstrated for first time that symptoms of diphtheria are caused not by bacteria themselves, but by deadly toxin released by them. The long-term search for method of treatment and prevention of diphtheria did not bring the desired result. It will take many years, before Gaston Ramon in 1923 will be able to neutralize diphtheria toxin by acting on it with formalin at certain temperature and thus will receive "anatoxin", mean of vaccination against diphtheria. The article analyzes stages of these studies, which proved high effectiveness of anatoxin and proceeded with widespread implementation of vaccination against diphtheria and later tetanus in short time in France and in Russia (with active participation of Pavel F. Zdrodovsky, 1890-1976). The separate section of the article is devoted to life story of Gaston Ramon and his activities in the Pasteur Institute. The scientist who opened the era of anatoxins did not become Nobel Prize winner, despite the fact that various organizations and scientists from many countries of the world have nominated him 155 times for the Nobel Prize in Physiology or Medicine in different years. He received recognition in France, his Motherland: Gaston Ramon is holder of the Grand Cross of the Order of the Legion of Honor and streets, colleges, lyceums, schools are named after him.
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Difteria , Tétano , Vacinas , Humanos , Criança , Difteria/prevenção & controle , Difteria/história , Vacinação , FrançaRESUMO
In this Letter, we consider optical bound states in the continuum (BICs) in the infrared range supported by an all-dielectric metasurface in the form of subwavelength dielectric grating. We apply the random forest machine learning method to predict the frequency of the BICs as dependent on the optical and geometric parameters of the metasurface. It is found that the machine learning approach outperforms the standard least square method at the size of the dataset of ≈4000 specimens. It is shown that the random forest approach can be applied for predicting the subband in the infrared spectrum into which the BIC falls. The important feature parameters that affect the BIC wavelength are identified.
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BACKGROUND: - This study intends to address the scarcity of data regarding the pathogenesis of Baclofen poisoning in humans, which has seen a recent increase, worldwide, especially amongst the young people. Another reason for the conduction of this study was lack of the substantial data about the histo-pathological findings of lungs, in synergistic toxicity of Baclofen with Ethanol, in-spite of it being very common in humans, and both being respiratory depressant with similar mechanism of action. PURPOSE: - The authors aimed to understand the pathogenesis of fatal poisonings in humans due to Baclofen in combination with Ethanol via an animal research model. The enhancement of the overall scientific literature by extending research along the lines of the handful studies available in this regard was another adjunct goal of the study. MATERIAL AND METHODS: Fifteen Wistar rats were divided into control and test group of five and ten subjects respectively. The test group was further divided into two sub-groups of five each, with Baclofen administered to one, and it in conjunction with Ethanol to the other, in lowest dosages adjusted for the humans. Rats in both the groups were euthanized by dislocation of the cervical vertebrae for the histopathology examination. RESULTS: Capillary and venous plethora, hemorrhages in the inter-alveolar septi, hemorrhages into the alveoli and sludging was seen in the 1st sub-group. The plethora of venules, capillaries and arterioles, with sludging by the WBC (white blood corpuscle) infiltrates was seen in the 2nd sub-group. Desquamation of the ciliated epithelium and edematous thickening of the intra-alveolar septi, along with features suggestive of the peri-vascular edema was seen in the 2nd sub-group. The morphometric analysis of the micro vessels showed a significantly higher value of the arteriolar diameter in the 2nd sub-group, in comparison to 1st, but the venular diameter in the two sub-groups did not differ to any extent.
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Baclofeno , Etanol , Adolescente , Animais , Baclofeno/farmacologia , Humanos , Alvéolos Pulmonares , Ratos , Ratos WistarRESUMO
AIM: to assess the possibility of using neural network algorithms in choosing a method for surgical treatment of urolithiasis. MATERIALS AND METHODS: treatment results of 625 patients with kidney stones were analyzed in the study. Information about each patient was presented in the form of a multidimensional vector characterized by following preoperative investigations: questionnaires, clinical examination, instrumental and laboratory studies. A register was created where information on more than 50 parameters for each patient was added. Each example has an output parameter representing a predefined treatment strategy (extracorporeal shock-wave lithotripsy [ESWL] - 1, percutaneous nephrolithotomy [PCNL] - 2, pyelolithotomy or nephrolithotomy - 3). The initial database served as the basis for training the neural network estimation technique. RESULTS: A prospective trial was conducted to assess the clinical efficiency of the recommendations of neural network. A cohort of 150 patients admitted to the urology department was divided into two groups of 75 people. In the group 1, patients received treatment according to the standard recommendations. In group 2, treatment strategy was chosen based on the results of neural network analysis. In the group 1, ESWL was performed in 40 (53.3%) patients. The average number of sessions was 1.8. At the discharge, residual fragments were diagnosed in 12 (30%) cases. In 4 patients, acute pyelonephritis developed, which required performing ureteral catheterization and subsequent treatment. In group 1, the efficiency of ESWL was 75%. In the group 2, where the neural network assessment technique was used, the average number of sessions was 1.4. At the discharge, 7 (15.6%) patients had residual fragments: 4 in the kidney, in 3 in the lower ureter ("steinstrasse"). In 4 cases, a conversion for PCNL was performed. ESWL efficiency was 91.1%. Stone-free rate for ESWL in the second group was significantly higher due to the greater number of stone fragmentation. In addition, number of shock waves was lower (the average number of sessions was 0.4 less). Improvement of treatment tactics through the use of neural network algorithms led to a decrease in hospitalization times, as well as to an improvement in the quality of treatment. The low efficiency of ESWL, as the first-line method, led to a change in treatment tactics in 25% of patients in group 1 and only in 8.9% of patients in group 2. Using these algorithms, it was possible to reduce hospitalization time, need for changing treatment strategy, number of auxiliary procedures, readmission rates, the incidence of inflammatory complications, and the number of residual fragments after ESWL. CONCLUSIONS: The possibility of using the neural network prediction technique at the preoperative stage in patients with kidney stones has been shown. This technique allows practicing urologist to make a decision on the choice of the optimal treatment method on an individual basis, thereby minimizing the risk of early postoperative complications.
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Cálculos Renais , Litotripsia , Urolitíase , Algoritmos , Humanos , Cálculos Renais/terapia , Estudos Prospectivos , Urolitíase/cirurgiaRESUMO
Pelvic organ prolapse (POP) is a common condition in menopausal and postmenopausal women. POP is a chronic, slowly progressive disease that leads to physical and psycho-emotional discomfort, brings physical and moral suffering to the patient and reduces the quality of life. Among the factors contributing to the development of this pathology, there is a history of obstetric trauma, obesity, heavy physical labor, as well as genetically determined connective tissue dysplasia. Conservative methods of treating POP are known, but the low frequency of their use is due to low efficiency and late diagnosis of this pathology. The main method of treatment is surgical. Currently, more than 500 methods of surgical correction of POP in women have been described. However, the relapse rate reaches 38%. The introduction of mesh implants also did not solve this problem due to the development of implant-associated complications. Thus, it is currently relevant to further study the causes of pelvic organ prolapse, taking into account the genetic, phenotypic and clinical-anamnestic risk factors of the patient, as well as to develop a personalized approach to choosing the optimal method of surgical treatment in each individual case.
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Epidemias , Prolapso de Órgão Pélvico , Feminino , Humanos , Prolapso de Órgão Pélvico/diagnóstico , Prolapso de Órgão Pélvico/epidemiologia , Prolapso de Órgão Pélvico/etiologia , Qualidade de Vida , Fatores de Risco , Telas Cirúrgicas , Resultado do TratamentoRESUMO
The interaction of non-monochromatic radiation with arrays comprising plasmonic and dielectric nanoparticles has been studied using the finite-difference time-domain electrodynamics method. It is shown that LiNbO3, TiO2, GaAs, Si, and Ge all-dielectric nanoparticle arrays can provide a complete selective reflection of an incident plane wave within a narrow spectral line of collective lattice resonance with a Q-factor of 103 or larger at various spectral ranges, while plasmonic refractory TiN and chemically stable Au nanoparticle arrays provide high-Q resonances with moderate reflectivity. Arrays with fixed dimensional parameters make it possible to fine-tune the position of a selected resonant spectral line by tilting the array relative to the direction of the incident radiation. These effects provide grounds for engineering novel selective tunable optical high-Q filters in a wide range of wavelengths, from visible to middle-IR.
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Antibodies specific to ß-Glucocerebrosidase were selected from phage displayed naïve scFv libraries. Biopannings were performed against recombinant human protein ß-Glucocerebrosidase immobilized on polystyrene surface, specific phages were eluted with 50% ethylene glycol in citrate buffer (pH 6.0). Several specific binders were discovered and converted to full-size hIgG1 antibodies leading to highly stable binders with dissociation constants (Kd) in the range 10-40 nM. The antibodies were used further as ligands for affinity chromatography, where efficient and selective recovery of biologically active ß-Glucocerebrosidase from cultured media of Chinese hamster ovary cells was demonstrated. ß-Glucocerebrosidase was purified to nearly homogeneous state and had specific activity comparable to the commercially available preparations (40-44 U/mg protein). The obtained immunoaffinity sorbents have high capacity and can be easily regenerated.
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Cromatografia de Afinidade/métodos , Enzimas Imobilizadas/isolamento & purificação , Glucosilceramidase/isolamento & purificação , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/isolamento & purificação , Animais , Especificidade de Anticorpos , Células CHO , Cricetulus , Ensaios Enzimáticos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/imunologia , Etilenoglicol/química , Glucosídeos/química , Glucosilceramidase/química , Glucosilceramidase/imunologia , Humanos , Cinética , Ligantes , Poliestirenos/química , Ligação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Anticorpos de Cadeia Única/biossíntese , Anticorpos de Cadeia Única/químicaRESUMO
Collective lattice resonances (CLRs) in finite-sized $ 2D $2D arrays of dielectric nanospheres have been studied via the coupled dipole approximation. We show that even for sufficiently large arrays, up to $ 100 \times 100 $100×100 nanoparticles (NPs), electric or magnetic dipole CLRs may differ significantly from the ones calculated for infinite arrays with the same NP sizes and interparticle distances. The discrepancy is explained by the existence of a sufficiently strong cross-interaction between electric and magnetic dipoles induced at NPs in finite-sized lattices, which is ignored for infinite arrays. We support this claim numerically and propose an analytic model to estimate a spectral width of CLRs for finite-sized arrays. Given that most of the current theoretical and numerical researches on collective effects in arrays of dielectric NPs rely on modeling infinite structures, the reported findings may contribute to thoughtful and optimal design of inherently finite-sized photonic devices.
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A new super resolution imaging technique which potentially enables sub-µm spatial resolution, using a detector of pixels much larger than the spatial resolution, is proposed. The method utilizes sample scanning through a large number of identical X-ray microprobes periodically spaced (the period corresponds to a multiple of the pixel size), which reduces drastically the scanning time. The information about the sample illuminated by the microprobes is stored by large detector pixels. Using these data and sample position information, a super-resolution image reconstruction is performed. With a one-dimensional (1D) high aspect ratio nickel single lens array designed for theoretically expected sub-µm microprobes at 17 keV and fabricated by deep X-ray lithography and electroforming technique, 2 µm X-ray microprobes with a period of 10 µm were achieved. We performed a first experiment at KARA synchrotron facility, and it was demonstrated that the smallest structure of a test pattern with a size of 1.5 µm could be easily resolved by using images generated from a detector having a pixel size of 10.4 µm. This new approach has a great potential for providing a new microscopic imaging modality with a large field of view and short scan time.
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Crystal structure of LaF3 single crystal is refined in tysonite-type trigonal unit cell P [Formula: see text] c1 using density functional theory calculations and Raman spectroscopy. It is shown that trigonal structure with P [Formula: see text] c1 space group is more energy-efficient than hexagonal structure with space group P63 cm. Simulated Raman spectra obtained using LDA approximation is in much better agreement with experimental data than that obtained with PBE and PBEsol functionals of GGA. The calculated frequency value of silent mode B 2 in case of hexagonal structure P63 cm was found to be imaginary (unstable mode), thus the energy surface obtains negative curvature with respect to the corresponding normal coordinates of the mode which leads to instability of the hexagonal structure in harmonic approximation. The A 1g line at 214 cm-1 in Raman spectra of LaF3 related to the translation of F2 ions along c axis can be connected with F2 ionic conductivity.
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Two ammonium oxofluorovanadates, (NH4)3VO2F4 and (NH4)3VOF5, have been investigated by temperature-dependent infrared and Raman spectroscopy methods to determine the nature of phase transitions (PT) in these compounds. Dynamics of quasioctahedral groups was simulated within the framework of semi-empirical approach, which justified the cis-conformation of VO2F43- (C2v) and the C4v geometry of VOF53-. The observed infrared and Raman spectra of both compounds at room temperature (RT) revealed the presence at least of two crystallographically independent octahedral groups. The first order PT at elevated temperatures is connected with a complete dynamic disordering of these groups with only single octahedral state. At lower temperatures, the octahedra are ordered and several octahedral states appear. This PT is the most pronounced in the case of (NH4)3VOF5, when at least seven independent VOF53- octahedra are present in the structure below 50K, in accordance with the Raman spectra. Ammonium groups do not take part in PTs at higher and room temperatures but their reorientational motion freezes at lower temperatures.
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Significant suppression of resonant properties of single gold nanoparticles at the surface plasmon frequency during heating and subsequent transition to the liquid state has been demonstrated experimentally and explained for the first time. The results for plasmonic absorption of the nanoparticles have been analyzed by means of Mie theory using experimental values of the optical constants for the liquid and solid metal. The good qualitative agreement between calculated and experimental spectra support the idea that the process of melting is accompanied by an abrupt increase of the relaxation constants, which depends, beside electron-phonon coupling, on electron scattering at a rising number of lattice defects in a particle upon growth of its temperature, and subsequent melting as a major cause for the observed plasmonic suppression. It is emphasized that observed effect is fully reversible and may underlie nonlinear optical responses of nanocolloids and composite materials containing plasmonic nanoparticles and their aggregates in conditions of local heating and in general, manifest itself in a wide range of plasmonics phenomena associated with strong heating of nanoparticles.
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The composition and technology of complex probiotic in hard gelatin capsules was developed in Perm Branch "Biomed" of "Microgen" State Company. The preparation contains three production strains: Lactobacillus plantarum 8P-A3, L. acidophilus K3W24 and Bifidobacterium bifidum 1. Laboratory and experimental (preclinical) study of the probiotic included investigation of the antagonistic activity, "acute" and "chronic" toxicity, the effect of the preparation on histology and hematology of laboratory animals. The result of these studies suggested of the probiotic had high inhibitory activity against pathogenic microflora when compared with probiotic monopreparations and had no toxic effects on laboratory animals.
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Antibiose , Descoberta de Drogas/métodos , Probióticos , Administração Oral , Animais , Cápsulas , Camundongos , Testes de Sensibilidade Microbiana , Probióticos/administração & dosagem , Probióticos/farmacologia , Probióticos/toxicidade , Ratos , Testes de Toxicidade Aguda , Testes de Toxicidade CrônicaRESUMO
AIM: Study safety, reactogenicity and immunologic effectiveness of a national combined vaccine against diphtheria, pertussis (acellular component), tetanus, hepatitis B and Hib-infection during immunization of volunteers aged 18-60 years. MATERIALS AND METHODS: The study was carried out in accordance with ethical standards and requirements, regulated by Helsinki declaration and Good clinical practice (ICHGCP). In a simple non-randomized clinical trial 20 adult volunteers took part, the mean age of those was 46.9 years. RESULTS: Registered: post-vaccination reactions (both local and systemic) were mild and of moderate degree of severity, stopped independently after 2-3 days without administration of drug treatment. Postvaccinal complications were not noted. Parameters of general and biochemical analysis of blood, urine, IgE content in dynamics of immunization were within normal limits. A single administration of aAPDT--HepB+Hib to individuals aged 18-60 years resulted in development of antibodies against all the components of the preparation. Seroconversion factor fluctuated from 6.9 to 53.5: CONCLUSION: The results obtained allow to recommend the vaccine for evaluation of its safety, reactogenicity, immunologic and prophylaxis effectiveness in randomized clinical observation trials in children.
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Anticorpos Antibacterianos/biossíntese , Anticorpos Antivirais/biossíntese , Difteria/prevenção & controle , Infecções por Haemophilus/prevenção & controle , Hepatite B/prevenção & controle , Tétano/prevenção & controle , Coqueluche/prevenção & controle , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Difteria/imunologia , Difteria/microbiologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/química , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/microbiologia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/química , Vacinas Anti-Haemophilus/imunologia , Hepatite B/imunologia , Hepatite B/virologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/química , Vacinas contra Hepatite B/imunologia , Humanos , Imunidade Humoral/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Tétano/imunologia , Tétano/microbiologia , Vacinação , Vacinas de Subunidades Antigênicas , Coqueluche/imunologia , Coqueluche/microbiologiaRESUMO
AIM: To study the results of deferoxamine (Deferal) administration in intensive therapy program of 63 patients with severe acute pancreatitis to decrease effect of oxidative stress and endotoxemia. MATERIAL AND METHODS: In deferoxamine group (31 patients) there were decrease of serum iron's level and inhibition of free radical oxidation that led to early relief of endotoxemia, reducing periods of organs' dysfunction. It was not observed in comparison group (32 patients). RESULTS: Deferoxamine decrease risk of pancreatic necrosis and pancreatogenic sepsis. It allows reducing ICU- and hospital-stay and number of extended surgical procedures.
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Two glioblastoma groups, which are distinguished from each other by expression level of 416 genes (P < 0.05), were determined using a mathematical model of linear Boolean programming on the basis of gene expression data, obtained by microarray analysis of the glioblastomas and available in Gene Expression Omnibus (GEO) data base. The expression level of 15 genes was more than two-fold higher in the first group of glioblastoma (80 samples) in comparison with the second group (144 samples) and 401 genes and--more than two-fold lower as compared to the second group. 10 of 15 genes, which expression level prevailed in the first group, encode the proteins involved in cell cycle regulation and cell proliferation. A significant percentage of 401 genes are the genes that encode proteins involved in the functioning of neural cells and participating in the processes such as synaptic transmission, neurogenesis, the formation of myelin sheath, axon formation. Kohonen map, built on the basis of the data of 15 genes with prevailed expression in the first group and 60 (of4 01) genes, whose expression level elevated in the second group, confirmed the existence of two glioblastoma groups with specific gene expression profiles. Distribution of the glioblastomas into two groups may reflect two pathways of astrocytic glioma development, one of which leads to the formation of tumors with higher levels of gene expression, which protein products are involved in cell cycle regulation and proliferation. On the other hand, the existence of two molecular variants may reflect different states of glioblastoma progression.