RESUMEN
Aim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСРstage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000âpg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.
Asunto(s)
Microbioma Gastrointestinal , Insuficiencia Cardíaca , Biomarcadores , Enfermedad Crónica , Clostridioides difficile , Humanos , Inflamación , Péptido Natriurético Encefálico , Fragmentos de PéptidosRESUMEN
We studied the levels endotoxin and microbial markers in the blood of female rats with experimental heart failure and the effects of preliminary treatment with a prebiotic complex based on fermented wheat bran and inactivated Saccharomyces cerevisiae culture on these parameters. The concentrations of endotoxin, markers of lactobacilli, and opportunistic microorganisms were found to increase in rats with experimental heart failure and significantly decreased against the background of treatment with prebiotic complex. The dynamics of markers of bifidobacteria, eubacteria, and propionibacteria were reciprocal. The observed effect of the prebiotic complex effect on gut microbiota in rats with experimental heart failure suggests that this complex can be used for the correction of intestinal dysbiosis and endotoxemia in this clinical condition.
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Disbiosis/dietoterapia , Endotoxemia/dietoterapia , Insuficiencia Cardíaca/dietoterapia , Prebióticos/administración & dosificación , Animales , Animales no Consanguíneos , Bacterias/crecimiento & desarrollo , Bifidobacterium/crecimiento & desarrollo , Modelos Animales de Enfermedad , Disbiosis/microbiología , Disbiosis/fisiopatología , Endotoxemia/microbiología , Endotoxemia/fisiopatología , Endotoxinas/biosíntesis , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Insuficiencia Cardíaca/microbiología , Insuficiencia Cardíaca/fisiopatología , Fenilefrina/administración & dosificación , Esfuerzo Físico , Propionibacterium/crecimiento & desarrollo , RatasRESUMEN
Recent advances of cancer treatment resulted in the increase of patient survival rate. Treatment for Hodgkin's lymphoma (HL) may impair reproductive function, which leads to a decrease of the quality of life of cancer survival. Today different approaches have been developed for fertility preservation, one of which is the cryopreservation of ovarian tissue with subsequent orthotopic transplantation. We have described a recovery of reproductive function in patient of 28 years with acute ovarian failure, which was induced after cancer treatment. After the orthotopic transplantation cryopreserved ovarian tissue ongoing pregnancy was achieved in the natural cycle after IVF insemination. We have described the first live birth in Russia after the orthotopic transplantation cryopreserved ovarian tissue in cancer patient. This approach has resulted in the recovery of endocrine function without replacement hormonal therapy and possibility for a woman to have her own biological baby. It suggests that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.
Asunto(s)
Criopreservación , Enfermedad de Hodgkin/cirugía , Ovario/trasplante , Recuperación de la Función , Reproducción , Adulto , Femenino , Humanos , Trasplante AutólogoRESUMEN
We studied the effects of tactivin and splenic polypeptides on learning and memory of thymectomized animals. In 3-week rats, thymectomy blocked active avoidance conditioning. Injections of tactivin (0.5 mg/kg) during 1 month after surgery restored learning capacity; splenic polypeptides were ineffective.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Péptidos/farmacología , Timectomía , Extractos del Timo/farmacología , Timo/química , Animales , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Memoria/fisiología , Nootrópicos/aislamiento & purificación , Especificidad de Órganos , Péptidos/aislamiento & purificación , Ratas , Ratas Wistar , Bazo/química , Extractos del Timo/aislamiento & purificación , Timo/fisiología , Timo/cirugíaRESUMEN
The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The pres- ence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymuspeptides and/or cytokines, controlled by them, enter the brain and exert influence on neuro- nalfunction, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.
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Sistema Nervioso Central , Citocinas/metabolismo , Neuropéptidos/metabolismo , Sistemas Neurosecretores , Timo , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiopatología , Homeostasis , Humanos , Neuroinmunomodulación , Sistemas Neurosecretores/metabolismo , Sistemas Neurosecretores/fisiopatología , Transducción de Señal , Timo/metabolismo , Timo/fisiopatologíaRESUMEN
AIM: The objective of this project was to explore the influence of immunoactive drugs (tactivin, thymulin, and thymosin fraction 5) on the development of the passive avoidance conditioned reflex. MATERIALS AND METHODS: Two types of passive avoidance boxes were used--a regular two-chamber box and a modified three-chamber box, comprising a dark chamber in which rats were exposed to electrical shock, a safe dark chamber, and a light chamber in the center. RESULTS: The project has established that the memory trace persists longer under the influence of the immunoactive drugs in both models, which is consistent with the reference nootropic piracetam test results. Notably, the immunoactive drugs' mnemotropic effect was more pronounced in the modified three-chamber box than in the standard two-chamber box. Using the modified box helped to establish the influence of tactivin, thymulin, and thymosin fraction 5 on the spatial memory component. Immunotropic preparations from thymus caused the animals to select the safe chamber 24 hours later and in subsequent tests. CONCLUSION: The project's results indicate that the drugs tested do possess mnemotropic properties, so their range of clinical use can be broadened.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Reacción de Prevención , Condicionamiento Clásico , Memoria , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Reacción de Fuga/efectos de los fármacos , Reacción de Fuga/fisiología , Masculino , Memoria/efectos de los fármacos , Memoria/fisiología , Modelos Biológicos , Péptidos/farmacología , Ratas , Ratas Wistar , Factor Tímico Circulante/farmacología , Timosina/análogos & derivados , Timosina/farmacología , Extractos del Timo/farmacologíaRESUMEN
In silico analysis of available bacterial genomes revealed the phylogenetic proximity levels of enzymes responsible for biosynthesis of lipopolysaccharide (LPS) of Yersinia pestis, the cause of plague, to homologous proteins of closely related Yersinia spp. and some other bacteria (Serratia proteamaculans, Erwinia carotovora, Burkholderia dolosa, Photorhabdus luminescens and others). Isogenic Y. pestis mutants with single or double mutations in 14 genes of LPS biosynthetic pathways were constructed by site-directed mutagenesis on the base of the virulent strain 231 and its attenuated derivative. Using high-resolution electrospray ionization mass spectrometry, the full LPS structures were elucidated in each mutant, and the sequence of monosaccharide transfers in the assembly of the LPS core was inferred. Truncation of the core decreased significantly the resistance of bacteria to normal human serum and polymyxin B, the latter probably as a result of a less efficient incorporation of 4-amino-4-deoxyarabinose into lipid A. Impairing of LPS biosynthesis resulted also in reduction of LPS-dependent enzymatic activities of plasminogen activator and elevation of LD(50) and average survival time in mice and guinea pigs infected with experimental plague. Unraveling correlations between biological properties of bacteria and particular LPS structures may help a better understanding of pathogenesis of plague and implication of appropriate genes as potential molecular targets for treatment of plague.
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Genes Bacterianos/fisiología , Lipopolisacáridos/biosíntesis , Yersinia pestis/enzimología , Yersinia pestis/genética , Amino Azúcares/metabolismo , Animales , Actividad Bactericida de la Sangre , Farmacorresistencia Bacteriana , Femenino , Cobayas , Humanos , Lípido A/biosíntesis , Masculino , Ratones , Peste/microbiología , Activadores Plasminogénicos/metabolismo , Polimixina B/farmacología , Espectrometría de Masa por Ionización de Electrospray , Virulencia , Yersinia pestis/efectos de los fármacos , Yersinia pestis/patogenicidadRESUMEN
Deletion mutants in the lpxM gene in two Yersinia pestis strains, the live Russian vaccine strain EV NIIEG and a fully virulent strain, 231, synthesise a less toxic penta-acylated lipopolysaccharide (LPS). Analysis of these mutants revealed they possessed marked reductions in expression and immunoreactivity of numerous major proteins and carbohydrate antigens, including F1, Pla, Ymt, V antigen, LPS, and ECA. Moreover, both mutants demonstrated altered epitope specificities of the antigens as determined in immunodot-ELISAs and immunoblotting analyses using a panel of monoclonal antibodies. The strains also differed in their susceptibility to the diagnostic plague bacteriophage L-413C. These findings indicate that the effects of the lpxM mutation on reduced virulence and enhanced immunity of the Y. pestis EV DeltalpxM is also associated with these pleiotropic changes and not just to changes in the lipid A acylation.
Asunto(s)
Antígenos Bacterianos/biosíntesis , Vacuna contra la Peste/inmunología , Yersinia pestis/inmunología , Animales , Epítopos , Femenino , Inmunización , Lípido A/genética , Lipopolisacáridos/biosíntesis , Ratones , Mutación , Factor de Necrosis Tumoral alfa/biosíntesis , Vacunas Atenuadas/inmunología , Virulencia/genética , Yersinia pestis/genética , Yersinia pestis/patogenicidadRESUMEN
Twenty-eight males with psychogenic (emotiogenic) autonomic dystonia with paroxysmal course (panic attacks) have been studied. Serum serotonin (S) concentration has been measured using ELISA. The deficit (147,36+/-69,80 ng/ml) of humoral S has been found compared to a control group (295,18+/-152,38 ng/ml). After the 8-weeks treatment with a SSRIs antidepressant rexetin in dosage 20 mg/day, a distinct clinical effect has been observed. There was a decrease of the number and severity of paroxysms as well as severity of symptoms of psychoautonomic syndrome (the reduction of depression, anxiety and optimization of autonomic regulation). Despite the therapeutic effectiveness of rexetin, serum S concentration has decreased still more to 59,92+/-23,06 ng/ml. The paradoxical phenomenon of growing deficit in the humoral pattern of serotonergic system during the short-term course of SSRIs antidepressant treatment is reviewed as a result of the transfer of neuromediator from the blood to the cerebral structures with the following activation of serotonergic system that provides the therapeutic effect.
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Antidepresivos/uso terapéutico , Trastorno de Pánico/sangre , Serotonina/sangre , Adolescente , Adulto , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trastorno de Pánico/diagnóstico , Trastorno de Pánico/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
The endotoxic activity of the lipopolysaccharides (LPS) with defined chemical structure from Yersinia pestis strains of various subspecies differing in their epidemic potential was studied. The LPS of two strains of Y. pestis ssp. caucasica and ssp. altaica, whose structures have not been studied earlier, were analyzed by high-resolution mass spectrometry. In addition to reported structural changes, an increase in the degree of LPS phosphorylation was observed when strain I-2377 (ssp. altaica) was cultivated at an elevated temperature. A high tumor necrosis factor alpha(TNF-alpha)-inducing activity observed for LPS samples from Y. pestis cultures grown at 25 degrees C correlated with an increased degree of lipid A acylation, particularly, with the presence of the hexaacyl form of lipid A, which was absent from the LPS when bacteria were cultivated at 37 degrees C. No correlation was found between the lethal toxicity of the LPS in vivo and its ability to induce TNF-alpha production in vitro.
Asunto(s)
Lipopolisacáridos/química , Lipopolisacáridos/toxicidad , Yersinia pestis/química , Animales , Secuencia de Carbohidratos , Línea Celular , Femenino , Dosificación Letal Mediana , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Datos de Secuencia Molecular , Temperatura , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The lpxM mutant of the live vaccine Yersinia pestis EV NIIEG strain synthesising a less toxic penta-acylated lipopolysaccharide was found to be avirulent in mice and guinea pigs, notably showing no measurable virulence in Balb/c mice which do retain some susceptibility to the parental strain itself. Twenty-one days after a single injection of the lpxM-mutant, 85-100% protection was achieved in outbred mice and guinea pigs, whereas a 43% protection rate was achieved in Balb/c mice given single low doses (10(3) to 2.5 x 10(4) CFU) of this vaccine. A subcutaneous challenge with 2000 median lethal doses (equal to 20,000 CFU) of fully virulent Y. pestis 231 strain, is a 6-10-fold higher dose than that which the EV NIIEG itself can protect against.
Asunto(s)
Eliminación de Gen , Vacuna contra la Peste/inmunología , Peste/prevención & control , Yersinia pestis/inmunología , Animales , Femenino , Cobayas , Lípido A/genética , Ratones , Ratones Endogámicos BALB C , Vacunas Atenuadas/inmunología , Virulencia , Yersinia pestis/genética , Yersinia pestis/patogenicidadRESUMEN
The lipopolysaccharide (LPS) of the opportunistic human pathogen Pseudomonas aeruginosa immunotype 5 was delipidated by mild acid hydrolysis, and the products were separated by high-performance anion-exchange chromatography and analyzed by ESI MS and NMR spectroscopy. LPS species of three types were found, including those with an unsubstituted core and the core substituted with one O-polysaccharide repeating unit or with an O-polysaccharide of a variable number of repeating units. The core region is highly phosphorylated, the major species containing two monophosphate groups and one ethanolamine diphosphate group. Based on these and published data on the O-polysaccharide structure, the full structure of the LPS of P. aeruginosa immunotype 5 was established.
Asunto(s)
Antígenos Bacterianos/química , Lipopolisacáridos/química , Oligosacáridos/química , Pseudomonas aeruginosa/química , Antígenos Bacterianos/inmunología , Conformación de Carbohidratos , Secuencia de Carbohidratos , Lipopolisacáridos/inmunología , Espectroscopía de Resonancia Magnética , Pseudomonas aeruginosa/inmunologíaRESUMEN
The products of the strong alkaline degradation of the lipopolysaccharide (LPS) of Pseudomonas aeruginosa immunotype 5 were separated by anion-exchange HPLC and studied by electrospray ionization mass spectrometry and NMR spectroscopy. It was found that two major products have the same inner core region and lipid A carbohydrate backbone (A) but different outer core regions (B and C). The difference is in the position of a rhamnose residue, which is substituted with either an additional glucose residue (B) or a disaccharide remainder of the degraded O-polysaccharide (C). The site and the configuration of the linkage between the O-polysaccharide and the core were determined and, together with published data, the structure of the so-called biological repeating unit of the O-antigen was defined (D). The glycosidic linkage of the quinovosamine residue is beta when it links the O-polysaccharide to the core (C) and alpha when it connects the interior repeating units of the O-polysaccharide to each other (D) [Formula: see text]. In the structures shown Rha stands for rhamnose, Kdo for 3-deoxy-D-manno-oct-2-ulosonic acid, Hep for L-glycero-D-manno-heptose, GalNAcA for 2-acetamido-2-deoxygalacturonic acid, QuiN for 2-amino-2,6-dideoxyglucose (quinovosamine), DeltaHexNA for 2-amino-2-deoxy-D-threo-hex-4-enuronic acid; all monosaccharides are in the pyranose form and have the D configuration, except for Rha and GalNAcA that have the L configuration. In C, the remainder of the degraded O-polysaccharide is shown in bold type.
Asunto(s)
Acetilglucosamina/análogos & derivados , Lipopolisacáridos/química , Antígenos O/inmunología , Pseudomonas aeruginosa/química , Lípido A/química , Espectroscopía de Resonancia Magnética , Antígenos O/química , Pseudomonas aeruginosa/inmunología , Ramnosa/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Lipopolysaccharide (LPS) expressed by isolates of Pseudomonas aeruginosa from cystic fibrosis patients lacks the O-polysaccharide chain but the degree to which the rest of the molecule changes has not been determined. We analyzed, for the first time, the core structure of an LPS from a rough, cystic fibrosis isolate of P. aeruginosa. The products of mild acid hydrolysis and strong alkaline degradation of the LPS were studied by ESI MS, MALDI MS, and NMR spectroscopy. The following structure was determined for the highest-phosphorylated core-lipid A backbone oligosaccharide isolated after alkaline deacylation of the LPS: [structure: see text] where Kdo and Hep are 3-deoxy-D-manno-octulosonic acid and L-glycero-D-manno-heptose, respectively; all sugars are in the pyranose form and have the D configuration unless stated otherwise. The outer core region occurs as two isomeric glycoforms differing in the position of rhamnose (Rha). The inner core region carries four phosphorylation sites at two Hep residues, HepI being predominantly bisphosphorylated and HepII monophosphorylated. In the intact LPS, both Hep residues carry monophosphate and diphosphate groups in nonstoichiometric quantities, GalN is N-acylated by an L-alanyl group, HepII is 7-O-carbamoylated, and the outer core region is nonstoichiometrically O-acetylated at four sites. Therefore, the switch to the LPS-rough phenotype in cystic fibrosis isolates of P. aeruginosa is not accompanied by losses of core monosaccharide, phosphate or acyl components. The exact positions of the O-acetyl groups and the role of the previously undescribed O-acetylation in the LPS core of P. aeruginosa remain to be determined.
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Fibrosis Quística/microbiología , Lipopolisacáridos/química , Pseudomonas aeruginosa/química , Conformación de Carbohidratos , Secuencia de Carbohidratos , Humanos , Espectrometría de Masas , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
The following structure of the O-specific polysaccharide of Citrobacter braakii O7a,3b,1c was established using sugar and methylation analyses and NMR spectroscopy, including 2D COSY, TOCSY, NOESY, and 1H, 13C heteronuclear single-quantum coherence (HSQC) experiments: (struture: see text). The main D-mannan chain of the polysaccharide studied has the same structure as the O-specific polysaccharide of Escherichia coli O9, Klebsiella pneumoniae O3, and Hafnia alvei PCM 1223.
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Citrobacter/química , Antígenos O/química , Secuencia de Carbohidratos , Datos de Secuencia Molecular , Estructura Molecular , Monosacáridos/análisis , Resonancia Magnética Nuclear Biomolecular/métodosRESUMEN
An acidic O-specific polysaccharide was obtained by mild acid degradation of the lipopolysaccharide of the bacterium Providencia alcalifaciens O7 and purified by gel chromatography followed by anion-exchange chromatography. On the basis of full acid hydrolysis, methylation, carboxyl reduction, selective cleavage with anhydrous hydrogen fluoride, and 1H- and 13C-NMR spectroscopy, including two-dimensional 1H,1H homonuclear and H-detected 1H,13C heteronuclear correlation spectroscopy and nuclear Overhauser effect spectroscopy (NOESY), the following structure of the linear tetrasaccharide repeating unit of the polysaccharide was established: [figure], where Rhap2Ac is 2-O-acetylrhamnopyranose.
Asunto(s)
Antígenos O/química , Providencia/química , Conformación de Carbohidratos , Secuencia de Carbohidratos , Cromatografía de Gases , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Datos de Secuencia MolecularRESUMEN
A neutral polysaccharide containing D-galactose, 2-acetamido-2-deoxy-D-glucose, and 3-acetamido-3,6-dideoxy-D-glucose (Qui3NAc) in the ratios 2:1:1 was obtained by mild acid degradation of lipopolysaccharide of the bacterium Providencia alcalifaciens O5 followed by gel chromatography and ion-exchange chromatography or treatment with anhydrous hydrogen fluoride. On the basis of full acid hydrolysis, methylation, and 1H- and 13C-NMR spectroscopy, including two-dimensional correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY), H-detected heteronuclear 1H,13C single-quantum coherence (HSQC), and nuclear Overhauser effect spectroscopy (NOESY), the following structure of the linear tetrasaccharide repeating unit of the polysaccharide was established: