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1.
Mol Biol (Mosk) ; 51(4): 677-682, 2017.
Artigo em Russo | MEDLINE | ID: mdl-28900087

RESUMO

During the process of spermatogenesis, the proliferation of spermatogonia (stem cell descendants) is replaced by their differentiation in growing spermatocytes responsible for the preparation to meiosis, which is accompanied by a cardinal change in transcriptional programs. We have demonstrated that, in drosophila, this process is accompanied by a splash of the expression of ß-subunit of nascent polypeptide-associated complex (NAC) associated by ribosomes. Nascent polypeptide-associated complex is known as a chaperone involved in co-translational protein folding. This is the first case of the detection of tissue-specific co-translational NAC cofactor in multicellular eukaryotes. It is proposed that spermatocyte specific NAC is involved in the modulation of the expression of the proteins that provide the functioning of subsequent stages of spermatogenesis.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Chaperonas Moleculares/genética , Espermatócitos/metabolismo , Testículo/metabolismo , Animais , Diferenciação Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Masculino , Meiose , Chaperonas Moleculares/metabolismo , Biossíntese de Proteínas , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Espermatócitos/crescimento & desenvolvimento , Espermatócitos/ultraestrutura , Espermatogênese/genética , Testículo/crescimento & desenvolvimento
2.
Mol Biol (Mosk) ; 48(2): 223-31, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25850291

RESUMO

The functions of the evolutionary conservative complex NAC (Nascent polypepetide Associated Complex) and its subunits are discussed. The heterodimeric NAC protein contains alpha- and beta-subunits and is found to be reversibly bounded to the ribosome in all eukaryotes, from yeast to humans. NAC contacts the nascent polypeptide and protects it from proteolysis. NAC participates in polypeptide chain folding and modulates protein secretion and transmembrane protein formation. Mutations and deletions of genes, encoding NAC subunits are lethal in early development of multicellular eukaryotes. NAC is involved in the ribosome biogenesis. The beta-subunit interacts with caspase-3 and may be involved in the regulation of the apoptotic pathway. The variants of NAC proteins can be considered as chaperone complexes, involved in the response of the cell and the organism to stress factors, as well as regulators of apoptosis. The genes encoding beta-subunits are rapidly evolved, their duplications cause the formation of tissue specific beta-subunit variants with a different number of putative caspase cleavage sites. The homodimer of alpha-subunits is shown to be the RNA/DNA binding protein and acts as a transcriptional cofactor. The diversity in the functioning of NAC is a prime example of a protein that performs a variety of biological functions (moonlighting protein).


Assuntos
Células Eucarióticas/metabolismo , Regulação da Expressão Gênica , Chaperonas Moleculares/genética , Biossíntese de Proteínas , Subunidades Proteicas/genética , Caspase 3/genética , Caspase 3/metabolismo , Células Eucarióticas/citologia , Evolução Molecular , Humanos , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Ligação Proteica , Dobramento de Proteína , Multimerização Proteica , Estabilidade Proteica , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais
3.
Mol Biol (Mosk) ; 43(3): 400-6, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19548525

RESUMO

Family of betaNACtes genes in the Drosophila melanogaster genome is a model to investigate the mechanisms of molecular evolution of recently evolved genes. The betaNACtes genes encode proteins, homologous to beta subunit of nascent polypeptide-associated complex (NAC), are expressed in testes and localized on the X chromosome as two two-gene clusters and one separate copy. We collected population polymorphism data for betaNACtes genes using several wild-type stocks of D. melanogaster and compared betaNACtes paralogs with each other. We have shown heterogeneous pattern of betaNACtes genes polymorphism: genes in 3' region of two-gene clusters are low polymorphic, whereas separate betaNACtesl gene is most variable. 5'betaNACtes copies in two-gene tandems are practically identical, whereas 3'betaNACtes copies are highly diverged. Thus, we propose local gene conversion providing selective homogenization of 5'genes. Comparison of betaNACtes paralogs has shown that majority of amino acid differences are in N-terminal part of proteins, containing betaNAC domain. McDonald-Kreitman test of betaNACtes paralog divergence shows the involvement of positive selection in the course of betaNACtes gene family evolution.


Assuntos
Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Genes de Insetos , Família Multigênica , Polimorfismo Genético , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Masculino , Testículo/metabolismo , Cromossomo X/metabolismo
4.
Neoplasma ; 55(5): 387-93, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18665748

RESUMO

Polysaccharides represent the major part of the yeast cell wall dry weight and build the skeletal carcass defining cell wall stability and cell morphology (beta-D-glucans) or constitute amorphous matrix and cell surface fibrous material (mannans and mannoproteins). It is known that yeast cell wall beta-D-glucans reveal immunomodulating properties, which allows for their application in anti-infective and antitumor therapy. Recent data also suggest that polysaccharides reveal antioxidant activity that can result in their protective function as antioxidants, antimutagens, and antigenotoxic agents. The paper provides a review of our continuing research involving water-soluble derivatives of beta-D-glucan isolated from the baker's yeast Saccharomyces serevisiae and of a glucomannan isolated from the industrial yeast Candida utilis. The results are confronted with the available literature data. The derivatives of beta-D-glucan demonstrated potent inhibitory effect on lipid peroxidation comparable to that of the known antioxidants and exerted DNA protection from oxidative damage. The free radical scavenging activity was confirmed by spin-trap electron paramagnetic resonance. Antimutagenic and antigenotoxic activity of the yeast polysaccharides was demonstrated using yeast, bacterial, and algal models. The derivatives of beta-D-glucan exerted potent enhancement of tumor necrosis factor alpha (TNF-alpha) released from murine macrophages and revealed synergistic effect with cyclophosphamide in the treatment of Lewis lung carcinoma and two types of lymphosarcoma in murine models. The results indicate significant protective antioxidant, antimutagenic, and antigenotoxic activities of the yeast polysaccharides and imply their potential application in anticancer prevention/therapy.


Assuntos
Anticarcinógenos/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Neoplasias/prevenção & controle , Polissacarídeos/farmacologia , Leveduras/química , beta-Glucanas/farmacologia , Animais , Candida/química , Parede Celular/química , Quimioprevenção , Proteínas Fúngicas/farmacologia , Humanos , Mananas/farmacologia , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/farmacologia
5.
Neoplasma ; 55(4): 280-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18505337

RESUMO

N-nitrosomorpholine (NMOR) belongs to the group of N-nitrosamines and represents a known hepatocarcinogen. Exposure to this compound is considered to be a potential health hazard to humans. There is, however, considerable evidence that the effect of many carcinogenic agents can be markedly influenced or altered by various natural substances. The objective of this study was to assess the DNA-protective and anticlastogenic effects of the derivative of a natural compound, carboxymethyl chitin-glucan (CM-CG), against genotoxicity of N-nitrosomorpholine (NMOR) in human hepatoma cells HepG2 and hamster lung cells V79 cultured in vitro. The exponentially growing cells were pre-treated during 24 h with three different concentrations of CM-CG (150, 750 and 1500 mg/ml) and then treated with different concentrations of NMOR. DNAprotective effects of CM-CG were evaluated by single-cell gel electrophoresis (SCGE, comet assay) and anticlastogenic effects by chromosomal aberration assay. At the SCGE assay a short-term (30 min) and at the chromosomal aberration assay a continuous treatment with NMOR was used. In both HepG2 and V79 cells pre-treated with CM-CG, a significant decrease of the percentage of DNA lesions induced by NMOR was observed along with a reduction of NMOR-induced chromosomal aberrations. We did not find any substantial differences between the genotoxic effects of NMOR on HepG2 and V79 cells, which have different histopathological origins and different levels of metabolizing enzymes. Three different concentrations of CM-CG exerted a similar protective effect against NMOR-induced DNA lesions and chromosomal aberrations in both HepG2 and V79 cells.


Assuntos
Antimutagênicos/farmacologia , Carcinoma Hepatocelular/genética , Quitina/análogos & derivados , Aberrações Cromossômicas , Glucanos/farmacologia , Neoplasias Hepáticas/genética , Nitrosaminas/toxicidade , Animais , Linhagem Celular , Quitina/farmacologia , Cricetinae , Dano ao DNA , Humanos , Pulmão , Mutagênicos/toxicidade , Células Tumorais Cultivadas
6.
Prostate ; 68(9): 994-1006, 2008 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-18386292

RESUMO

BACKGROUND: The correlation between Zinc concentration in the prostate's peripheral zone to the onset or presence of malignant process needs to be evaluated in detail. METHODS: Zinc concentration was measured in approximately 1-4 mm3 segments of fresh needle-biopsy cores, with X-ray fluorescence, and correlated with the histological findings of these tissue segments. RESULTS: Local Zinc concentration is correlated with the presence of cancer (PCa); the higher the Gleason score the greater the Local Zinc depletion. The Zinc value averaged over the entire extracted tissue is specific only to Gleason score 8-9 PCa. The results refer to patients avoiding Zinc-rich supplements since those show elevated prostatic Zinc concentration in identified cancer tissue. A computer simulation analysis of randomly located 0.03-3.3 cm3 lesions, with particular Gleason score and the measured Local Zinc concentration, revealed a potential diagnostic approach definitely superior to PSA, with sensitivity to the tumor grade and with excellent detection capability for Gleason score >6. Further clinical studies have been designed, both on full prostates after radical prostatectomy as well as on biopsy cores at higher resolution, to establish the accuracy of the method for Gleason score = 6. CONCLUSIONS: The PCa diagnostic potential of Local Zinc concentration is confirmed and there is indication that the amount of Zinc depletion could be used as a measure of the Gleason score of the tumor. Local Zinc concentration mapping has the potential to improve patient selection for biopsy, biopsy site selection and local therapy (e.g., Cryotherapy, Brachytherapy) site selection.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias da Próstata/metabolismo , Zinco/metabolismo , Adenocarcinoma/química , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Simulação por Computador , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Curva ROC , Espectrometria por Raios X , Zinco/análise
7.
J Helminthol ; 82(3): 211-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18394210

RESUMO

Mesocestoides vogae tetrathyridia infection in mice causes hepatocyte injury, hepatic granulomatous inflammmation, liver fibrosis and chronic peritonitis manifested with portal hypertension. To reduce the detrimental effect of parasites on the host liver, the effect of the anthelmintic drug praziquantel (PZQ) in combination with natural products silymarin (an antioxidant) and beta-glucan (an immunomodulator) was investigated. The therapeutic effect of drugs was assessed by means of aminotransferase (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) activities, content of albumin, total proteins and hyaluronic acid (HA) in sera of ICR mice infected with M. vogae larvae. Animals were treated with PZQ suspended in oil emulsion (Group 1), PZQ combined with silymarin incorporated into lipid microspheres (LMS) (Group 2), PZQ combined with beta-glucan incorporated into liposomes (LG) (Group 3), PZQ co-administered with LMS and LG (Group 4). Untreated animals (Group 5) served as the control. Treatment of animals started at the early chronic phase of infection (day 14 p.i.) and lasted 10 days; serum samples were collected on days 0, 7, 14, 25, 28, 31, 35 and 45 p.i. ALT and AST activities were significantly (P < 0.05) decreased in Groups 2, 3 and 4. HA content was significantly (P < 0.05 and 0.01) lower in Groups 2 and 4. Albumin levels were decreased in Groups 2 and 4, total protein concentration decreased in Groups 1 and 3 (P < 0.05 and 0.01). These results showed that combined treatment of PZQ with silymarin and/or beta-glucan was able to ameliorate or suppress fibrogenesis in the liver, protect liver cells from oxidative damage and, possibly, stimulate regeneration of the parenchyma.


Assuntos
Infecções por Cestoides , Hipertensão Portal/tratamento farmacológico , Hepatopatias Parasitárias/tratamento farmacológico , Fígado/lesões , Mesocestoides/isolamento & purificação , Camundongos Endogâmicos ICR/parasitologia , Alanina Transaminase/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Antioxidantes/administração & dosagem , Aspartato Aminotransferases/farmacologia , Quimioterapia Combinada , Fatores Imunológicos/administração & dosagem , Fígado/parasitologia , Masculino , Mesocestoides/efeitos dos fármacos , Camundongos , Cavidade Peritoneal/parasitologia , Praziquantel/administração & dosagem , Silimarina/administração & dosagem , beta-Glucanas/administração & dosagem
8.
Acta Trop ; 104(2-3): 122-32, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17915186

RESUMO

Anthelmintic activity of benzimidazole carbamate anthelmintics is low against dormant Toxocara canis larvae during late infections in paratenic hosts. The present study was conducted to examine the efficacy of pure fenbendazole, or drug incorporated into sterically stabilized liposomes (SL-FBZ) administered to T. canis-infected mice alone and after its co-administration with the immunomodulator (1-->3)-beta-D-glucan against larvae localized in muscles and brains. Therapy with either drug forms (in total 250 mg/kg in 10 doses) commenced on day 28 post-infection (p.i.) and the efficacy of treatment, examined on day 30 after the last dose of drug, was the highest in groups of mice treated with SL-FBZ in combination with glucan (89.5+/-5.8% in the muscles, 66.1+/-8.1% in brains). During 56 days of follow-up after termination of therapy, serum levels of anti-TES IgG antibodies, circulating IgG-TES immune complexes (CIC) as well as IgG antibodies to the most immunogenic part of recombinant myosin antigen of T. canis larvae were investigated. In contrast to anti-TES IgG antibodies, levels of CIC and anti-myosin antibodies were in the linear correlation with the efficacy of treatments beginning from day 38 post-therapy. We also showed that the serum levels of CIC as well as anti-myosin IgG antibodies seem to be the suitable serological markers for the monitoring of progress in larval destruction and TES resorption from the tissues.


Assuntos
Fenbendazol/uso terapêutico , Glucanos/uso terapêutico , Toxocara canis/imunologia , Toxocaríase/tratamento farmacológico , Animais , Anticorpos Anti-Helmínticos/sangue , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/parasitologia , Quimioterapia Combinada , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Fenbendazol/química , Glucanos/química , Proteínas de Helminto/imunologia , Imunoglobulina G/sangue , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Larva/efeitos dos fármacos , Larva/imunologia , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculos/efeitos dos fármacos , Músculos/parasitologia , Miosinas/imunologia , Toxocaríase/imunologia , Toxocaríase/parasitologia , Resultado do Tratamento
9.
Biomacromolecules ; 8(9): 2697-705, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17691842

RESUMO

A sample of high-molar mass hyaluronan was oxidized by seven oxidative systems involving hydrogen peroxide, cupric chloride, ascorbic acid, and sodium hypochlorite in different concentrations and combinations. The process of the oxidative degradation of hyaluronan was monitored by rotational viscometry, while the fragments produced were investigated by size-exclusion chromatography, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, and non-isothermal chemiluminometry. The results obtained imply that the degradation of hyaluronan by these oxidative systems, some of which resemble the chemical combinations present in vivo in the inflamed joint, proceeds predominantly via hydroxyl radicals. The hyaluronan fragmentation occurred randomly and produced species with rather narrow and unimodal distribution of molar mass. Oxidative degradation not only reduces the molecular size of hyaluronan but also modifies its component monosaccharides, generating polymer fragments that may have properties substantially different from those of the original macromolecule.


Assuntos
Ácido Hialurônico/química , Medições Luminescentes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Detecção de Spin , Viscosidade
10.
J Pharm Biomed Anal ; 44(5): 1056-63, 2007 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-17553647

RESUMO

Changes in dynamic viscosity of the solutions of a high-molar-mass hyaluronan (HA) were monitored using a rotational viscometer. The degradative conditions generated in the HA solutions by a system comprising ascorbate plus Cu(II) plus H(2)O(2) were studied either in the presence or absence of a drug--naproxen or acetylsalicylic acid. Continual decrease of the dynamic viscosity of HA solution was indicative of the polymer degradation. Addition of the drug retarded/inhibited the HA degradation in a concentration-dependent manner. The characteristics of the fragmented polymers were investigated by FT-IR spectroscopy and by two different liquid chromatographic techniques, namely by size-exclusion chromatography equipped with a multi-angle light scattering photometric detector and by high-performance liquid chromatography connected on-line to a spectrofluorometer.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/química , Ácido Ascórbico/química , Aspirina/farmacologia , Cobre/química , Ácido Hialurônico/antagonistas & inibidores , Ácido Hialurônico/química , Naproxeno/farmacologia , Anti-Inflamatórios não Esteroides/química , Aspirina/química , Cátions Bivalentes/química , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Peróxido de Hidrogênio/química , Estrutura Molecular , Peso Molecular , Naproxeno/química , Oxidantes/química , Oxirredução , Soluções/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Viscosidade/efeitos dos fármacos
11.
J Med Food ; 10(1): 189-93, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17472486

RESUMO

In this study we have analyzed antioxidant capabilities of the carboxymethylated (1 --> 3)-beta-D-glucan (M(w) = 5.88 x 10(5)) against lipid peroxidation induced by ultraviolet (UV) radiation--UVA (320-400 nm), which is known to produce mainly singlet oxygen, (1)O(2) . Lipid peroxidation was monitored by measuring the absorption spectra of the conjugated dienes and quantified by Klein oxidation index. The results imply that the (1 --> 3)-beta-D-glucan derivative studied is an antioxidant with the scavenging ability lying between alpha-tocopherol and hyaluronic acid. Thus, glucan as a potential safe and effective dietary supplement may be used for a prolonged time for a systemic photoprotection of humans.


Assuntos
Antioxidantes/farmacologia , Glucanos/farmacologia , Peroxidação de Lipídeos/efeitos da radiação , Lipossomos/química , Raios Ultravioleta , Suplementos Nutricionais , Radical Hidroxila/química , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos/química , Oxigênio Singlete/química
12.
Genetika ; 43(1): 18-26, 2007 Jan.
Artigo em Russo | MEDLINE | ID: mdl-17333934

RESUMO

Studies of the position effect resulting from chromosome rearrangements in Drosophila melanogaster have shown that replication distortions in polytene chromosomes correlate with heritable gene silencing in mitotic cells. Earlier studies mostly focused on the effects of euchromatin--heterochromatin rearrangements on replication and silencing of euchromatic regions adjacent to the heterochromatin breakpoint. This review is based on published original data and considers the effect of rearrangements on heterochromatin: heterochromatin blocks that are normally underrepresented or underreplicated in polytene chromosomes are restored. Euchromatin proved to affect heterochromatin, preventing its underreplication. The effect is opposite to the known inactivation effect, which extends from heterochromatin to euchromatin. The trans-action of heterochromatin blocks on replication of heterochromatin placed within euchromatin is discussed. Distortions of heterochromatin replication in polytene chromosomes are considered to be an important characteristic associated with the functional role of the corresponding genome regions.


Assuntos
Drosophila melanogaster/fisiologia , Eucromatina/fisiologia , Heterocromatina/fisiologia , Animais , Montagem e Desmontagem da Cromatina , Replicação do DNA , Drosophila melanogaster/genética , Eucromatina/genética , Rearranjo Gênico , Heterocromatina/genética , Cromossomo X/genética , Cromossomo X/fisiologia
13.
Bioorg Khim ; 33(1): 119-30, 2007.
Artigo em Russo | MEDLINE | ID: mdl-17375667

RESUMO

3-Aminopropyl glycosides of alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyra-nosyl-(1-->2)-alpha-D-mannopyranose, alpha-D-mannopyranosyl-(1-->3)-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(l -- 2)-alpha-D-mannopyranose, and alpha-D-mannopyranosyl-(1-->2)-[alpha-D-mannopyranosyl-(1-->3)]-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(1-->2)-alpha-D-mannopyranose were efficiently synthesized starting from ethyl 2-O-acetyl(benzoyl)-3,4,6-tri-O-benzyl-l-thio-alpha-D-mannopyranoside, ethyl 4,6-di-O-benzyl-2-O-benzoyl-1-thio-alpha-D-mannopyranoside, ethyl 4,6-di-O-benzyl-2,3-di-O-benzoyl-l-thio-alpha-D-mannopyranoside, and 2,3,4,6-tetra-O-benzoyl-alpha-D-mannopyranosyl bromide. The oligosaccharide chains synthesized correspond to the three structural types of side chains of mannan from Candida albicans cell wall. A conjugate of the third pentasaccharide with bovine serum albumin was prepared using the squarate method.


Assuntos
Candida albicans/química , Parede Celular/química , Mananas/química , Oligossacarídeos/química , Animais , Sequência de Carboidratos , Bovinos , Dados de Sequência Molecular , Oligossacarídeos/síntese química , Soroalbumina Bovina/química
14.
Neoplasma ; 53(6): 524-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17167723

RESUMO

Naturally occurring polysaccharides isolated from the yeasts are the substances with versatile intriguing biomodulatory activities. One of the novel derivatives prepared from the (1 --> 3)-beta-D-glucan isolated from the cell walls of baker's yeast Saccharomyces cerevisiae is sulfoethyl glucan (SEG). Its DNA-protective, antimutagenic, anticlastogenic and cytotoxic/cytostatic enhancing effect was evaluated using five eukaryotic systems. SEG showed bioprotective effect in recombination- repair-deficient strain of alga Chlamydomonas reinhardtii against methyl methanesulfonate-induced genotoxicity, antimutagenic effect against ofloxacin-induced genetic changes in yeast Saccharomyces cerevisiae assay and anticlastogenic activity in plants Vicia sativa and Vicia faba assays against maleic hydrazide-induced clastogenicity. In the combined application with cytostatic drug vumon, SEG exerted enhancement of the drug's cytotoxic/cytostatic effect in the cell revitalization assay using mouse leukemia cells. The study sheds light on the possible mechanisms of actions and utilization of this microbial polysaccharide derivative in the cancer prevention and therapy.


Assuntos
Anticarcinógenos/farmacologia , Antimutagênicos/farmacologia , Divisão Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Saccharomyces cerevisiae/química , beta-Glucanas/farmacologia , Animais , Antibacterianos/toxicidade , Parede Celular/química , Chlamydomonas reinhardtii/efeitos dos fármacos , Metanossulfonato de Metila/toxicidade , Mutagênicos/toxicidade , Ofloxacino/toxicidade , Proteoglicanas , Saccharomyces cerevisiae/efeitos dos fármacos , Teniposídeo/farmacologia , Vicia faba/química , Vicia sativa/química , beta-Glucanas/isolamento & purificação
15.
Neoplasma ; 53(5): 434-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17013539

RESUMO

The connection between dietary intake of carboxymethyl chitin-glucan (CM-CG, approximately 200 mg/kg body weight, during 21 days) and the response of freshly isolated rat cells to genotoxic treatment with a combination of photosensitizer Methylene Blue and visible light (MB+VL) was evaluated in presented study. Blood lymphocytes, testicular cells, and hepatocytes were isolated from rats fed by a standard or CM-CG enriched diet and in ex vivo conditions challenged with oxidative agent. Induced DNA damage was assessed using a modified comet assay. When added to the diet, CM-CG itself did not induce any negative effect on the health condition of animals or on level of DNA breaks in rat cells. Moreover, the cells isolated from CM-CG fed animals were more resistant to oxidative stress induced by visible light-excited Methylene Blue. In conclusion, we have demonstrated that carboxymethyl chitin-glucan represents a natural fungal polysaccharide that is able to exert antimutagenic properties upon application in diet.


Assuntos
Antimutagênicos/administração & dosagem , Quitina/análogos & derivados , Dano ao DNA/efeitos dos fármacos , Glucanos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Células Cultivadas , Quitina/administração & dosagem , Ensaio Cometa , Dieta , Masculino , Azul de Metileno/toxicidade , Oxidantes/toxicidade , Ratos , Ratos Sprague-Dawley
16.
Biomacromolecules ; 7(3): 659-68, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16529395

RESUMO

Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments.


Assuntos
Ácido Hialurônico/química , Substâncias Macromoleculares/química , Espécies Reativas de Oxigênio , Animais , Antioxidantes/química , Sequência de Carboidratos , Humanos , Inflamação , Modelos Biológicos , Modelos Químicos , Dados de Sequência Molecular , Polímeros/química , Xenobióticos/química
17.
Exp Oncol ; 28(4): 308-13, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17285116

RESUMO

AIM: One of the advanced methodologies of the tumor therapy is the application of the so-called biological response modifiers used for activation of the endogenous antitumor mechanisms and combined with classical cytotoxic agents. The aim of this work was the investigation of the effect of sulfoethylated (1-->3)-beta-D-glucan (SEG) in the treatment of experimental murine leukoses in combination with cyclophosphamide (CPA) and its ability to modulate the activity of lysosomal enzymes in tumor tissues. MATERIALS AND METHODS: The solid forms of inoculated murine leukoses P388 and L1210/1 were transplantated to male DBA/2 mice. The therapy was performed by treating animals with CPA (Biokhimik, Saransk, Russia) alone or in combination with SEG (Institute of Chemistry, Slovak Academy of Sciences, Slovakia). CPA was administered in saline as a single intraperitoneal (ip) injection on the 10th day after tumor transplantation; SEG was administered to mice ip 3 days after tumor transplantation with the intervals in 3 days. The therapy effect was estimated by measuring of solid tumor volume. Activity of the cysteine proteases--cathepsins B and L--was measured fluorometrically using fluorescent substrates Z-Arg-Arg-MCA and Z-Phe-Arg-MCA (Sigma, USA), respectively. The apoptosis was estimated evaluating the number of cells with fragmented nuclei using optical microscope. RESULTS: It has been demonstrated that application SEG leads to inhibition of tumor growth and potentiates therapeutic action of CPA, especially at repeated administrations during the whole treatment/observation At addition of SEG, therapeutic effect of a one-half reduced dose of CPA is equal or higher than that of the full dose. Therapeutic action of CPA and SEG on the studied tumors is realized predominantly through induction of apoptosis and is accompanied by a substantial increase of the activity of cysteine proteases cathepsins B and L in tumor tissues. The highest cathepsin B and cathepsin L activity in tumor tissue accompanied with the strongest inhibition of tumor growth. It is suggested that this phenomenon is due to the infiltration of the macrophages rich in the named enzymes into the tumor, where they phagocytize the apoptotic cells and tissue debris. CONCLUSION: Utilization of this polysaccharide BRM, sulfoethylated (1-->3)-beta-D-glucan, might potentially enhance efficiency of antitumor therapy with standard cytostatics without a need of substantial increase of their dosage and hence avoiding their toxic side-effects.


Assuntos
Antineoplásicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucemia/tratamento farmacológico , beta-Glucanas/uso terapêutico , Animais , Catepsina B/efeitos dos fármacos , Catepsina L , Catepsinas/efeitos dos fármacos , Cisteína Endopeptidases/efeitos dos fármacos , Sinergismo Farmacológico , Masculino , Camundongos , Camundongos Endogâmicos DBA , Transplante de Neoplasias
18.
Talanta ; 70(5): 914-21, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-18970860

RESUMO

We present our studies of prostatic Zn concentration measurements, carried out in the light of a novel prostate cancer (CAP) diagnosis method proposed by us. The method is based on in vivo prostatic Zn mapping by XRF trans-rectal probe. We report on the extensive clinical studies, intended to assess the validity of the novel proposed diagnostic method. Zn content was measured in vitro in needle-biopsy samples from several hundreds of patients, and was correlated with histological findings and other patient parameters. For this purpose, a technique of absolute Zn content determination in approximately 1mm(3) fresh tissue samples by XRF was developed. The experimental details and the main clinical-evaluation results are presented. We further outline the suggested design of the XRF trans-rectal probe for an efficient in vivo detection and mapping of the Zn fluorescence radiation from the prostate through the rectal wall. Laboratory phantom studies, a preliminary design concept and its expected performance are also reported.

19.
Chaos ; 15(1): 13104, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15836258

RESUMO

Motion of two gravitating spherical stellar shells around a massive central body is considered. Each shell consists of point particles with the same specific angular momenta and energies. In the case when one can neglect the influence of gravitation of one ("light") shell onto another ("heavy") shell ("restricted problem") the structure of the phase space is described. The scaling laws for the measure of the domain of chaotic motion and for the minimal energy of the light shell sufficient for its escape to infinity are obtained.


Assuntos
Dinâmica não Linear , Modelos Estatísticos , Modelos Teóricos , Oscilometria , Física/métodos
20.
Photomed Laser Surg ; 22(3): 249-53, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15315733

RESUMO

OBJECTIVE: We investigated the therapeutic efficiency of laser irradiation and Bio-Oss, both and separately, on the post-traumatic regeneration of bone tissue in rats using infrared spectroscopy as an informative and accurate measuring method. BACKGROUND DATA: The therapeutic effect of low-power laser irradiation on bone tissue regeneration processes in animal models has been studied using morphogenic, biochemical, roentgenographic and electron microscopic measurements. Natural bone minerals, such as Bio-Oss collagen, were recommended for the reconstruction of bone defects in the alveolar process. MATERIALS AND METHODS: 29 male Wistar rats, divided into four random groups in a blinded manner were operated on the right alveolar process. A bone defect was made by penetrating the right alveolar process of the mandible bone using a 3-mm drill. The rats were divided into four groups as follows: Group I, left side served as intact bone and right injured side as the control; Group II, right injured side was treated by organic bovine bone (Bio-Oss); Group III, right side bone defect was treated by HeNe laser (632.8 nm, 35 mW) applied transcutaneously for 20 min to the injured area daily for the following 14 consecutive days; and Group IV, Bio-Oss was placed loosely in the right side defect followed by laser treatment. After 2 weeks, the intact bone and bone replicas of the trauma area were removed and analyzed by infra-red spectroscopy technique. The composition and the structure of the bone tissue mineral substances were determined and compared among the four groups. For quantitative analysis of the regenerative bone process, the Mineralization index was used. An increase in this index indicates regenerative bone processes. RESULTS: The normal state analysis of the IR spectra of the normal alveolar bone tissue within the intervals of 400 to 4000 cm(-1) revealed characteristic absorption bands for the inorganic bone component in spectrum regions 450-1480 cm(-1), and the organic component at 1540-3340 cm(-1). In the case of trauma, the intensity of absorption of the inorganic component was decreased by 54%, and the absorption band became narrow, which can be interpreted as quantitative changes of the bone tissue mineral content. The wavelength characteristics of the inorganic component remained unchanged; that is, the induced trauma under these experimental conditions did not provoke alterations in the structure of the phosphate framework. The organic component showed decreased absorption by 10-15%, compared to the normal bone, and slight displacement of the wavelength, which can be interpreted as changes occurring in the quality of the organic content of the bone tissue. In the Bio-Oss-treated group, the intensity of absorption of the inorganic component increased by 43%, compared to the control injured area; however, there was a decrease of 22.6% in the normal bone. The wavelength characteristics of the inorganic component remained unchanged. The organic component showed similar absorption results in the injured non-treated group and absorption was 10-15% less than in the normal bone. Mineralization Index in the Bio-Oss-treated group was 0.93, compared to 0.63 in the control group and 2.04 in the normal bone. In the laser-treated group, the intensity of absorption of the inorganic component increased by 62, compared to the control injured area, and decreased only 11.4% in the normal bone. The wavelength characteristics of the organic component remained unchanged; that is, the organic component was similar to that of normal bone. Mineralization Index in the laser-treated group increased significantly to 1.86, compared to 0.63 in the control group and 2.04 in the normal bone. In the combined laser and Bio-Oss-treated groups, the intensity of absorption of the inorganic component and organic component was similar to that of normal bone. Mineralization Index in this group increased significantly to 1.98, compared to 0.63 in the control group and 2.04 in the normal bone. CONCLUSION: The results suggest that low-power laser irradiatults suggest that low-power laser irradiation alone and in combination with Bio-Oss enhances bone healing and increases bone repair.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos da radiação , Substitutos Ósseos/farmacologia , Terapia com Luz de Baixa Intensidade/métodos , Minerais/farmacologia , Animais , Substitutos Ósseos/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Osso e Ossos/efeitos da radiação , Masculino , Traumatismos Mandibulares/fisiopatologia , Traumatismos Mandibulares/terapia , Minerais/uso terapêutico , Modelos Animais , Ratos , Ratos Wistar , Método Simples-Cego , Espectrofotometria Infravermelho , Resultado do Tratamento
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