RESUMO
We present complex spectroscopic data of the synthetic brunogeierite (Fe2+)2Ge4+O4 with space group Fd3¯m of spinel structure: a = 8.3783 (6) Å, V = 588.12 (13) Å3. Brunogeierite crystals up to 200 µm in size were crystallized by the interaction of a boric acid solution on a metal iron wire in the presence of germanium oxide (GeO2) at 600/650 °C and 100 MPa. Mössbauer spectrum of synthetic brunogeierite consists of the symmetric doublet with the parameters IS = 1.104(1) mm/s and QS = 2.845(1) mm/s, that corresponds to the octahedral position of iron ions ([VI]Fe2+). The Raman spectra of Fe2GeO4 crystal consist of an intense main band at 756 cm-1 and four less intense bands at â¼644, 472, 302, and â¼205 cm-1 at ambient conditions. All five bands inherent in the spectrum of cubic spinel are present and gradual change in high pressure spectra up to 30 GPa. The color of the crystal changes from brown-orange to reddish at the center at 22.7 GPa and became opaque black up to 30.2 GPa. Herewith, in the high pressure spectra, we observed the splitting of some bands and the appearance of additional bands in a wide pressure range (from 1.6 to 30 GPa). The factor group analysis with the lattice dynamics calculation of potential crystal structure distortions shows the decreasing of the structure symmetry to tetragonal or rhombohedral in this pressure range.
RESUMO
Selective anxiolytic fabomotizole (Afobazol®) has affinity for the Sigma-1 chaperone receptor site, quinone reductase 2 (NQO2) and MAO-A regulatory sites, and melatonin receptor type 1 (MT1 receptor). The analysis of the effect of fabomotizole on the gene expression profile in the brain of MR (Maudsley Reactive) rats was carried out when modeling emotional stress in the open field test. A change in the expression of 14 genes was found, the results of the functional annotation of which showed that the mechanisms of action of fabomotizole may be associated with the regulation of translation of proteins (Rpl5, Rpl15, Ncl, and Ybx1), synaptic functions (Cplx2, Dlg4, Syngap1, Add1, Rab8b, Klc1, and Chn1), and cellular metabolism (Akr1d1, Bcat1, and Pkm).
Assuntos
Ansiolíticos , Comportamento Animal/efeitos dos fármacos , Benzimidazóis/farmacologia , Encéfalo , Regulação da Expressão Gênica/efeitos dos fármacos , Morfolinas/farmacologia , Proteínas do Tecido Nervoso/biossíntese , Estresse Psicológico , Animais , Ansiolíticos/química , Ansiolíticos/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Cinesinas , Proteínas Associadas aos Microtúbulos , Ratos , Receptores de Melatonina , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologiaRESUMO
Using the streptozotocin model of type 2 diabetes mellitus in Wistar rats, we compared antidiabetic activity of anxiolytic Afobazole with that of metformin. Afobazole in a dose of 10 mg/kg reduced streptozotocin-induced hyperglycemia and polyphagia and prevented accumulation of malonic dialdehyde, being not inferior to metformin in a dose of 300 mg/kg, and was even more effective than metformin in body weight recovery, elimination of polydipsia, and preservation of these effects after treatment withdrawal.
Assuntos
Benzimidazóis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hiperfagia/prevenção & controle , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Morfolinas/farmacologia , Animais , Ansiolíticos/farmacologia , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Reposicionamento de Medicamentos , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Masculino , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Cell damage depending on activity of quinone reductase 2 (MT3 receptor) was simulated in experiments on bone marrow cell suspension and assessed by menadione-induced DNA breaks measured by comet assay. We analyzed the protective effect of afobazole interacting with MT1, MT3, σ1 receptors, and monoamine oxidase A and its main metabolite M11 that specifi cally binds to MT3 receptors. Both compounds reduced the level of menadione-induced DNA damage (afobazole was effective in lower concentrations in comparison with M-11). Conclusion was made on the contribution of MT3 receptors to the protective effect of afobazole, but the observed concentration differences indicate possible contribution of other targets of anxiolytic drug to the protective mechanisms.
Assuntos
Ansiolíticos/farmacologia , Benzimidazóis/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Quebras de DNA/efeitos dos fármacos , Morfolinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Quinona Redutases/antagonistas & inibidores , Receptores de Melatonina/efeitos dos fármacos , Animais , Ansiolíticos/metabolismo , Benzimidazóis/metabolismo , Biotransformação , Células Cultivadas , Ensaio Cometa , Dicumarol/farmacologia , Avaliação Pré-Clínica de Medicamentos , Metalotioneína 3 , Camundongos , Monoaminoxidase , Inibidores da Monoaminoxidase , Morfolinas/metabolismo , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , Fármacos Neuroprotetores/metabolismo , Quinona Redutases/metabolismo , Receptor MT1 de Melatonina/efeitos dos fármacos , Receptores sigma/efeitos dos fármacos , Vitamina K 3/toxicidadeRESUMO
Antimutagenic effects of polypeptides isolated from Triticum kiharae wheat plantule extracts have been studied on human cells exposed to cadmium chloride. The most effective polypeptide Tk-AMP-BP ß -purothionin exhibited higher antimutagenic activity than wheat water extract and another peptide isolated from the same wheat species, Tk-AMP-γ 2 defensin; it also produced a pronounced antioxidant effect. This polypeptide can be used as a preventive agent for reducing the mutagenic potential of some environmental pollutants and for correction of human diseases associated with the defense system defects.
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Triticum/química , Cloreto de Cádmio/efeitos adversos , Células Cultivadas , Defensinas/farmacologia , Humanos , Medições Luminescentes , Linfócitos/efeitos dos fármacosRESUMO
The structure of a parasite system is formed and its functioning takes place in qualitatively different environments. The aquatic environment serves as a source of new elements and modules, energy, and information for parasite systems. And the parasite systems, for their part, affect the physical and biological parameters of the environment. Many intestinal infections caused by pathogenic microorganisms generally characterized by an acute disease course are related to a water factor. Such are typhus, typhoids, dysentery, cholera, salmonellosis, virus hepatitis, and others. Many parasitic diseases caused by pathogenic intestinal protistae (lambliasis, amebiasis, balantidiasis), blood parasite protistae (malaria), helminthes (opisthorchiasis, fascioliasis, diphyllobothriasis, cercariosis, pseudoamphistomosis) are also closely related to a water factor. Ascaridiasis, hymenolepiasis, trichocephalosis, and echinococcosis have a less close but still self-evident relationship to a water factor. The clbse relationships of many parasitic diseases to a water factor are also determined by the fact that the life cycles of many parasites necessarily include various intermediate hosts and parasite vectors, such as fishes, mollusks, crustaceans, and insects, which are aquatic organisms at some stages of their life. The results of continuous exposure of people to parasitic diseases are quite similar to the suppressive effects of the environment in the ecologically troublesome regions. The most prognostically useful information is formed while mapping by medical and ecological regions, by employing a combination of current mathematical and cartographical methods. The former include cluster analysis, quartering method, informational logical analysis, which are all described in this article and others. Regional mapping using the parasitological criteria should achieve at least two goals: 1) a scientific one that aids in finding causative connections and to prognosticate a situation; 2) a practical one that assists in developing regional programs for disease control and prevention. It is necessary to use the recommendations described in detail in the article in order to have the maximum results during medical and ecological mapping by the regions with a future goal of obtaining useful prognostic information.
Assuntos
Organismos Aquáticos/fisiologia , Ecologia/organização & administração , Parasitos/fisiologia , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/prevenção & controle , Animais , Organismos Aquáticos/microbiologia , Organismos Aquáticos/parasitologia , Organismos Aquáticos/virologia , Análise por Conglomerados , Ecossistema , Interações Hospedeiro-Parasita , Humanos , Teoria da Informação , Parasitos/microbiologia , Parasitos/parasitologia , Parasitos/virologia , Doenças Parasitárias/microbiologia , Doenças Parasitárias/parasitologia , Doenças Parasitárias/virologia , Projetos de Pesquisa , Federação Russa , Água/fisiologiaRESUMO
Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia restores impaired balance of excitatory and inhibitory amino acids in the striatum of mongrel rats, normalizes their content to control levels, and activates endogenous taurine-dependent system of neuroprotection.
Assuntos
Benzimidazóis/farmacologia , Doenças das Artérias Carótidas/metabolismo , Ataque Isquêmico Transitório/metabolismo , Morfolinas/farmacologia , Neostriado/metabolismo , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Animais , Pressão Sanguínea , Doenças das Artérias Carótidas/tratamento farmacológico , Artéria Carótida Primitiva/patologia , Avaliação Pré-Clínica de Medicamentos , Aminoácidos Excitatórios/metabolismo , Glicina/metabolismo , Ataque Isquêmico Transitório/tratamento farmacológico , Masculino , Neostriado/irrigação sanguínea , Ratos , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
Polymorphism of a 8 10-bp mitochondrial cox1 gene region was studied in 16 cercaria isolates of bird schistosomes (family Schistosomatidae), which were collected in water bodies of Moscow and Moscow oblast and represented three species: Trichobilharzia szidati, T. franki, and T. regenti. A substantial predominance of AT (65.4%) was characteristic of the cox1 sequences in all three species. Rare single nucleotide substitutions determined low (0.2-0.9%) intraspecific nucleotide and amino acid sequence diversity. Haplotype diversity h was high (80-100%) in all three species, suggesting a unique character for almost all cox1 sequences in the sample. Phylogenetic trees based on the nucleotide and amino acid sequence variations were constructed to study the relationships of the three schistosome species. A high support was observed for the main branching node that reflects differentiation of the monophyletic group Trichobilharzia and species of the genera Bilharziella (B. polonica), Dendritobilharzia (D. pulverulenta), and Gigantobilharzia (G. huronensis). Based on the nucleotide substitutions and amino acid polymorphisms, two groups of isolates, which infect Lymnaea stagnalis (T. szidati) and snails of the group Radix (T. franki and T. regenti) respectively, were isolated in the genus Trichobilharzia. The time of divergence between the two schistosome groups infecting snails of the genera Radix and Lymnaea was calculated from the cox1 nucleotide substitution rate, which is known for Asian and Indian blood flukes from the genus Schistosoma and is 2-3% per million years on average. Divergence of the three bird schistosome species under study and divergence of the Asian species of mammalian schistosome were almost concurrent, dating back to 2.5-3.8 Myr ago. Factors responsible for the lack of intraspecific subdivision with respect to the cox1 gene in bird schistosomes and the lack of separation between two species (T. franki and T. regenti) are discussed.
Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/genética , Proteínas de Helminto/genética , Proteínas Mitocondriais/genética , Filogenia , Polimorfismo Genético , Schistosoma/genética , Animais , Aves/parasitologia , MoscouRESUMO
According updates on molecular genetics, the development of human schistosomes in Asia with subsequent migration to the African continent is considered to be the most probable course of events. Generally, there are 2 hypotheses of the genus Schistoma. A hypothesis of Gondvana origin was based on snail host phylogeny and paleonthology and considered first schistosomes to originate on this continent to and appear in Asia from the Indian subcontinent platform 70-150 million years ago and in South America before Gondvana's split 60-120 million years ago. The recent data of molecular genetics show a high similarity between ITS2 sequences of S.bovis and S.intercalatum, with slightly lesser one between S.bovis and S.matthei. The similar pattern with slightly fewer differences can be seen in variability of cytochrome C subunit 1. Webster et al. 2006 noted a generally high similarity among species of the African group of schistosomes and considered it to originate from interspecies hybridization inside this group. Such hydridization occurring in both nature and a laboratory can make uncertain the determination of schistosome species based on a certain single gene marker.
Assuntos
Schistosomatidae/classificação , Infecções por Trematódeos/parasitologia , África/epidemiologia , América/epidemiologia , Animais , Ásia/epidemiologia , Citocromos c1/genética , DNA de Helmintos/genética , DNA Espaçador Ribossômico/genética , Evolução Molecular , Humanos , Filogenia , Schistosomatidae/genética , Análise de Sequência de DNA , Infecções por Trematódeos/epidemiologiaRESUMO
Selective anxiolytic afobazole (1 mM) inhibits monoamine oxidase A activity in mitochondria from rat brain and liver (IC(50) 0.36 and 0.43, respectively). Effect of the compound does not depend on the time of preincubation with mitochondria. Triple washout of mitochondria is followed by complete recovery of initial enzyme activity.
Assuntos
Ansiolíticos/farmacologia , Benzimidazóis/farmacologia , Encéfalo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Monoaminoxidase/efeitos dos fármacos , Morfolinas/farmacologia , Animais , Encéfalo/enzimologia , Fígado/enzimologia , Mitocôndrias/enzimologia , RatosRESUMO
In vitro radioligand assay revealed interaction of afobazole with sigma(1)-receptors (Ki=5.9x10(-6) M). Translocation of sigma(1)-receptors from the endoplasmic reticulum to the outer membrane was demonstrated by confocal microscopy. Experiments were performed on the model of HT-22 immortalized hippocampal cells after incubation with afobazole in a concentration of 10(-8) M.
Assuntos
Ansiolíticos/farmacologia , Benzimidazóis/farmacologia , Morfolinas/farmacologia , Fármacos Neuroprotetores/farmacologia , Receptores sigma/efeitos dos fármacos , Animais , Linhagem Celular Transformada , Imunofluorescência , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Células Jurkat , Camundongos , Ensaio Radioligante , Receptor Sigma-1RESUMO
The interaction of afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) and its main metabolite M-11 (2-[2-(3-oxomorpholine-4-yl)-ethylthio]-5-ethoxy benzimidazole hydrochloride) with neuroreceptors was studied using the method of radioligand analysis. The binding of afobazole with s1 (Ki =5.9 x 10(-6) M), MTI (Ki =1.6 x 10(-5) M), and MT3 (Ki =9.7 x 10(-7) M) receptors, as well as with a regulatory site of MAO-A (Ki = 3.6 x 10(-6) M) was revealed. The binding of M-11 with MT3 receptors (Ki = 3.9 x 10(-7) M) was demonstrated. The translocation of s1 receptor from endoplasmatic reticulum to the external membrane was revealed by the confocal microscopy technique on the immmortalized hippocampal HT-22 cells under the condition of 30- and 60-min-long afobazole (10(-8) M) application. Afobazole was shown to inhibit MAO-A reversibly. These properties of afobazole are consistent with our previous findings of the anxiolytic and neuroprotective effects of this drug.
Assuntos
Ansiolíticos/farmacologia , Benzimidazóis/farmacologia , Monoaminoxidase/metabolismo , Morfolinas/farmacologia , Receptor MT1 de Melatonina/metabolismo , Receptores de Melatonina/metabolismo , Receptores sigma/metabolismo , Animais , Ansiolíticos/metabolismo , Benzimidazóis/metabolismo , Ligação Competitiva , Encéfalo/citologia , Encéfalo/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Retículo Endoplasmático/metabolismo , Imunofluorescência , Metalotioneína 3 , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Morfolinas/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Transporte Proteico/efeitos dos fármacos , Ensaio Radioligante , Ratos , Ratos Sprague-DawleyRESUMO
Experiments on mice showed that a single intraperitoneal administration of anxiolytic afobazole (10 mg/kg) increases the effect of haloperidol in the apomorphine-induced climbing test and does not influence the catalepsy caused by the neuroleptic agent. The daily dose of afobazole 10 mg/kg during a five-day preliminary test reduced the extrapyramidal effects of haloperidole on rats and mice without significant change of the apomorphine-induced climbing test results. The ability of afobazole to reduce extrapyramidal disturbances caused by haloperidol can be related to the agonist effect of afobazole with respect to sigma 1 receptors.
Assuntos
Antipsicóticos/efeitos adversos , Benzimidazóis/farmacologia , Haloperidol/efeitos adversos , Morfolinas/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalepsia/tratamento farmacológico , Masculino , Camundongos , Ratos , Receptores sigma/metabolismoRESUMO
Anxiolytic afobazole was shown in the experiments on outbred rats to decrease the immobility in the Porsolt and Nomura swim tests. The degree of afobazole effect in a dose of 5 mg/kg (i.p.) is similar to that of the standard antidepressant amitriptyline administered in doses of 10 mg/kg. Data obtained are testifying to the antidepressant activity of afobazole.
Assuntos
Antidepressivos/farmacologia , Benzimidazóis/farmacologia , Morfolinas/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Masculino , RatosRESUMO
The involvement of paraoxonase family in antiathrogenesis has recently attracted attention of many researchers to these enzymes. Type 1 paraoxonase (PON 1) is a Ca-dependent hydrolase with a broad spectrum of substrate specificity. It is tightly bound to plasma high density lipoproteins (HDLP) and exhibits antioxidative and antiatherogenic activities. This review analyses publications concerning the structure, biological activity, and clinical significance ofparaoxonases, in the first place PON 1. Consideration of genetic and regulatory aspects of PON 1 is important for better understanding clinical and prognostic implications of this enzyme. These data are supplemented by the results of original observations of 60 patients with systemic lupus erythematosus and 20 with rheumatoid arthritis admitted to the Institute of Rheumatology. They confirm the published reports indicating reduced activity of this enzyme in patients compared with healthy donors.
Assuntos
Artrite/enzimologia , Arildialquilfosfatase/metabolismo , Animais , Biomarcadores/metabolismo , Progressão da Doença , HumanosRESUMO
Changes in the BDNF content in brain structures--hippocampus, hypothalamus, striatum, and frontal cortex--were determined in mice of different emotional-stress reaction phenotypes, which were subjected to emotional stress and treated by the selective anxiolytic afobazole. The changes were different in BALB/c and C57BL/6 mice. Afobazole exhibited a significant protector action against a decrease in the brain BDNF level caused by emotional stress in BALB/c mice.
Assuntos
Comportamento Animal/efeitos dos fármacos , Benzimidazóis/farmacologia , Química Encefálica/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Morfolinas/farmacologia , Estresse Psicológico/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , FenótipoRESUMO
The effect of N-(2-adamantyl)-N-(p-bromophenyl)amine (ladasten) on the behavior of MR and MNRA inbred rats with different emotional-stress reaction (ESR) phenotypes was studied in the conventional open-field test. Ladasten (30 mg/kg, i.p.) produced anxiolytic effect in MR rates, while not influencing MNRA animals. At the same time, a model stress induced disorder in the regulation of 3 H-diazepam binding to the benzodiazepine site of GABA(A) receptor in MR (but not in MNRA) rats. Ladasten administered in the anxiolytic dose prevented stress-induced changes in reception at this site.
Assuntos
Adamantano/análogos & derivados , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Estresse Psicológico/fisiopatologia , Adamantano/administração & dosagem , Adamantano/farmacologia , Animais , Ansiolíticos/administração & dosagem , Astenia/fisiopatologia , Encéfalo/efeitos dos fármacos , Diazepam/farmacologia , Masculino , Ratos , Ratos EndogâmicosRESUMO
The polymerase chain reaction with arbitrary (RAPD-PCR) or specific primers was used to study the population variation and to identify the species in cercariae of schistosomes of the Trichobilharzia ocellata species group (Trematoda, Schistosomatidae). In total, 28 cercariae were obtained from two spontaneously invaded mollusks Lymnaea stagnalis (LS) and L. ovata (LO), which were collected in different water bodies of Moscow. RAPD-PCR was carried out with two arbitrary primers, OPA9 and OPB11, which each detected different levels of individual and among-group variation and revealed considerable genetic differentiation of cercariae from different host mollusks. To check whether the cercariae of the two samples belong to one species, sequencing was performed with a region corresponding to intergenic transcribed spacer 2 (ITS2), which was earlier proposed for cercaria identification in three European species of bird schistosomes of the genus Trichobilharzia (T. franki, T. regenti, and T. szidati). The ITS2 sequences of two LO cercariae were identical, each consisted of 319 bp, and showed 100% homology to the T. franki ITS2 sequence. The ITS2 sequences of two LS cercariae were identical, each consisted of 323 bp, and showed 99.4% homology to the T. szidati counterpart. The causes of genetic variation in cercariae and prospects of using RAPD markers to study different stages of the life cycle in trematodes are discussed.
Assuntos
Variação Genética , Reação em Cadeia da Polimerase/métodos , Schistosomatidae/genética , Animais , Sequência de Bases , Southern Blotting , Primers do DNA , Dados de Sequência Molecular , Moluscos/parasitologia , Fases de Leitura AbertaRESUMO
The total antioxidant capacity (TEAC assay) of blood plasma from healthy donors was studied before and after 2- and 4-week consumption of the vitamin and mineral complex containing the major antioxidant vitamins and cofactors of antioxidant enzymes. Before the treatment the donors were divided into 2 subgroups with initially high and low total antioxidant capacity. After 2-week course of vitamin and mineral complex the total antioxidant capacity considerably decreased in group 1 donors, but increased in group 2 donors. After 4-week course this index increased in donors of both subgroups and slightly surpassed the baseline level typical of individuals with high total antioxidant capacity.