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1.
Ter Arkh ; 96(3): 253-259, 2024 Apr 16.
Artigo em Russo | MEDLINE | ID: mdl-38713040

RESUMO

AIM: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval. RESULTS: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p=0.03; OR CMVO 0.65 (0.35-1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p=0.04; OR CMVO 0.61 (0.31-1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p=0.004; OR CMVO 0.63 (0.30-1.33); p=0.22. CONCLUSION: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/estatística & dados numéricos , Feminino , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/terapia , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Federação Russa/epidemiologia , Mortalidade Hospitalar , Resultado do Tratamento
2.
Biophysics (Oxf) ; 66(4): 589-595, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667331

RESUMO

In recent years, members of the Coronaviridae family have caused outbreaks of respiratory diseases (MERS, SARS, and COVID-19). At the same time, the potential of radiation-induced inactivation of this group of viruses have been little studied, although radiation technologies can be widely used both in the processing of personal protective equipment and in the sterilization of vaccines. In the present work, the effect of 10 MeV electron beams and 7.6 MeV bremsstrahlung on the coronavirus infection pathogen (transmissible gastroenteritis virus) has been studied in vitro. In the given experimental conditions, irradiation with photons turned out to be more effective. The virus-containing suspension frozen at -86°C was the most resistant to radiation: the dose required for complete inactivation of the virus in this case was from 15 kGy, while for the liquid suspension and lyophilized form the sterilizing dose was from 10 kGy. At lower radiation doses for all samples during passaging in cell culture, residual infectious activity of the virus was observed. These differences in the efficiency of inactivation of liquid and frozen virus-containing samples indicate a significant contribution of the direct effect of radiation.

3.
Phys Rev Lett ; 124(12): 127202, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32281858

RESUMO

The research field of magnetic frustration is dominated by triangle-based lattices but exotic phenomena can also be observed in pentagonal networks. A peculiar noncollinear magnetic order is indeed known to be stabilized in Bi_{2}Fe_{4}O_{9} materializing a Cairo pentagonal lattice. We present the spin wave excitations in the magnetically ordered state, obtained by inelastic neutron scattering. They reveal an unconventional excited state related to local precession of pairs of spins. The magnetic excitations are then modeled to determine the superexchange interactions for which the frustration is indeed at the origin of the spin arrangement. This analysis unveils a hierarchy in the interactions, leading to a paramagnetic state (close to the Néel temperature) constituted of strongly coupled dimers separated by much less correlated spins. This produces two types of response to an applied magnetic field associated with the two nonequivalent Fe sites, as observed in the magnetization distributions obtained using polarized neutrons.

4.
Phys Rev Lett ; 120(2): 027203, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29376713

RESUMO

Electric manipulation of magnetic properties is a key problem of materials research. To fulfill the requirements of modern electronics, these processes must be shifted to high frequencies. In multiferroic materials, this may be achieved by electric and magnetic control of their fundamental excitations. Here we identify magnetic vibrations in multiferroic iron borates that are simultaneously sensitive to external electric and magnetic fields. Nearly 100% modulation of the terahertz radiation in an external field is demonstrated for SmFe_{3}(BO_{3})_{4}. High sensitivity can be explained by a modification of the spin orientation that controls the excitation conditions in multiferroic borates. These experiments demonstrate the possibility to alter terahertz magnetic properties of materials independently by external electric and magnetic fields.

5.
Angiol Sosud Khir ; 20(1): 117-20, 2014.
Artigo em Russo | MEDLINE | ID: mdl-24722029

RESUMO

Quality of treatment for acute venous thrombosis is determined by adequacy of conservative treatment and optimization of the operative procedure. We analysed the outcomes of management of 1,768 patients presenting with various forms of lower-limb phlebothrombosis. Deep veins were affected in 1,158 (65.5%) cases. Of these, thrombosis of crural veins was revealed in 672 (58%) patients, iliofemoral phlebothrombosis in 486 (42%) subjects. A total of 47 (9.7%) patients were operated on for iliofemoral thrombosis with floating thrombus confirmed by ultrasonic angioscanning. Criteria for floatation were determined. A total of 610 (43.5%) patients were diagnosed as having ascending subcutaneous thrombophlebitis of the femur. Of these, a total of 592 (97%) patients were operated on within 1-48 hours following admission. We propose a methodology of comprehensive conservative treatment with the use of Antistax in a double dose and alternating pneumocompression with elevated pressure in the cuffs.


Assuntos
Dispositivos de Compressão Pneumática Intermitente , Quercetina/análogos & derivados , Procedimentos Cirúrgicos Vasculares/métodos , Veias , Trombose Venosa , Doença Aguda , Adulto , Antioxidantes/administração & dosagem , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Embolia Pulmonar/prevenção & controle , Quercetina/administração & dosagem , Ultrassonografia Doppler Dupla/métodos , Veias/diagnóstico por imagem , Veias/cirurgia , Trombose Venosa/diagnóstico , Trombose Venosa/fisiopatologia , Trombose Venosa/terapia
6.
Phys Rev Lett ; 111(22): 227201, 2013 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-24329467

RESUMO

All-electrical control of a dynamic magnetoelectric effect is demonstrated in a classical multiferroic manganite DyMnO3, a material containing coupled antiferromagnetic and ferroelectric orders. Because of intrinsic magnetoelectric coupling with electromagnons a linearly polarized terahertz light rotates upon passing through the sample. The amplitude and the direction of the polarization rotation are defined by the orientation of ferroelectric domains and can be switched by static voltage. These experiments allow the terahertz polarization to be tuned using the dynamic magnetoelectric effect.

7.
Vavilovskii Zhurnal Genet Selektsii ; 27(7): 898-905, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38213703

RESUMO

Modern investigations in biology often require the efforts of one or more groups of researchers. Often these are groups of specialists from various scientific fields who generate and share data of different formats and sizes. Without modern approaches to work automation and data versioning (where data from different collaborators are stored at different points in time), teamwork quickly devolves into unmanageable confusion. In this review, we present a number of information systems designed to solve these problems. Their application to the organization of scientific activity helps to manage the flow of actions and data, allowing all participants to work with relevant information and solving the issue of reproducibility of both experimental and computational results. The article describes methods for organizing data flows within a team, principles for organizing metadata and ontologies. The information systems Trello, Git, Redmine, SEEK, OpenBIS and Galaxy are considered. Their functionality and scope of use are described. Before using any tools, it is important to understand the purpose of implementation, to define the set of tasks they should solve, and, based on this, to formulate requirements and finally to monitor the application of recommendations in the field. The tasks of creating a framework of ontologies, metadata, data warehousing schemas and software systems are key for a team that has decided to undertake work to automate data circulation. It is not always possible to implement such systems in their entirety, but one should still strive to do so through a step-by-step introduction of principles for organizing data and tasks with the mastery of individual software tools. It is worth noting that Trello, Git, and Redmine are easier to use, customize, and support for small research groups. At the same time, SEEK, OpenBIS, and Galaxy are more specific and their use is advisable if the capabilities of simple systems are no longer sufficient.

8.
Vopr Virusol ; 68(2): 132-141, 2023 05 18.
Artigo em Russo | MEDLINE | ID: mdl-37264848

RESUMO

INTRODUCTION: Rabbit hemorrhagic disease is an acute highly contagious infection associated with two genotypes of pathogenic Lagovirus. Antibodies to major capsid protein (Vp60) are protective. The aim of the work ‒ is an evaluation of antigenic and immunogenic activity of virus-like particles (VLPs) based on recombinant major capsid proteins of both genotypes of rabbit hemorrhagic disease virus (RHDV) (recVP60-GI1 and recVP60-GI2). MATERIALS AND METHODS: Baculovirus-expressed VLPs were evaluated using electron microscopy and administered to clinically healthy 1.53 month old rabbits in a dose of 50 g. Rabbits were challenged with 103 LD50 of virulent strains Voronezhsky-87 and Tula 21 days post immunization. Serum samples were tested for the presence of RHDV-specific antibodies. RESULTS: VLPs with hemagglutination activity forming VLP 3040 nm in size were obtained in Hi-5 cell culture. Specific antibody titers in rabbits measured by ELISA were 1 : 200 to 1 : 800 on 21th day post immunization with VLPs. Immunogenic activity of recVP60-GI1 VLPs was 90 and 40%, while it was 30 and 100% for recVP60-GI2 VLPs after the challenge with RHDV genotypes 1 and 2 respectively. The immunogenicity of two VLPs in mixture reached 100%. DISCUSSION: VLPs possess hemagglutinating, antigenic and immunogenic activity, suggesting their use as components in substances designed for RHDV specific prophylaxis in rabbits. Results of the control challenge experiment demonstrated the need to include the antigens from both RHDV genotypes in the vaccine. CONCLUSION: Recombinant proteins recVP60-GI1 and recVP60-GI2 form VLPs that possess hemagglutinating an antigenic activity, and provide 90100% level of protection for animals challenged with RHDV GI1 and GI2 virulent strains.


Assuntos
Caliciviridae , Vírus da Doença Hemorrágica de Coelhos , Lagovirus , Animais , Coelhos , Vírus da Doença Hemorrágica de Coelhos/genética , Proteínas do Capsídeo/genética , Proteínas Recombinantes/genética
9.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(6. Vyp. 2): 84-90, 2022.
Artigo em Russo | MEDLINE | ID: mdl-35797201

RESUMO

The opinion article is devoted to the analysis of a large-scale comprehensive systematic review of relevant and practically oriented studies of vortioxetine use in depression for the period to 2020. The mechanisms of multimodal action, issues of efficacy and safety of the drug, including direct procognitive effects, effects on anhedonia, anxiety, sleep disorders, analgesic and anti-inflammatory effects are highlighted. An increase in the efficacy of vortioxetine when the dose is increased to 20 mg/day is emphasized. Prospective directions for antidepressant research are outlined.


Assuntos
Transtorno Depressivo Maior , Vortioxetina , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Estudos Prospectivos , Revisões Sistemáticas como Assunto , Vortioxetina/farmacologia , Vortioxetina/uso terapêutico
10.
Voen Med Zh ; 332(6): 25-31, 2011 Jun.
Artigo em Russo | MEDLINE | ID: mdl-21899075

RESUMO

The article reflects the results of the first laparoscopic appendectomy experiment which was conducted on the base of 30 person department of the military hospital for 150 patients. The researcher made the statistical analysis of the results of acute appendicitis diagnostic and cure among young men. For the group of patients whit catarrhal form of acute appendicitis separate analysis was committed. It was found out that in the half of cases the clinic and laboratory scheme of acute appendicitis does not differ from the destructive one. These results made the researcher comprehend the necessity of additional ways of diagnostic in the acute appendicitis shady cases. It is also necessary to develop a medicinal and diagnostic algorithm for shady appendicitis in accordance with diagnostic conditions of military hospital for 150 patients.


Assuntos
Apendicectomia , Apendicite/cirurgia , Hospitais Militares , Laparoscopia , Adulto , Apendicite/sangue , Apendicite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Federação Russa
11.
Sovrem Tekhnologii Med ; 13(6): 6-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35265354

RESUMO

The aim of the study was to develop, evaluate, and validate an artificial neural network to predict coronary microvascular obstruction (CMVO) during percutaneous coronary interventions (PCI) in patients with myocardial infarctions (MI) based on the parameters, which are routinely available in an operating room when choosing a surgical approach. Materials and Methods: 5621 patients with MI and emergency PCI were retrospectively selected from the database of the City Clinical Hospital No.13 (Nizhny Novgorod, Russia); among them, there were 3935 men (70%) and 1686 women (30%), their mean age was 61.5±10.8 years. CMVO was recorded in 201 (4%) patients (the blood flow in the infarction-related artery after PCI was less than 3 points according to TIMI flow grade). The following input parameters were assessed: age, gender, past history of coronary artery disease, previous revascularization, presence of ST-segment elevation, a class of acute heart failure, a fact of systemic thrombolytic therapy administration and its effectiveness, symptom-to-balloon time, severity of coronary thrombosis and atherosclerosis, the number of stents and the number of operated coronary arteries. The sampling was divided into a training group (n=4060), a testing group (n=717), and an independent validation group (n=844). Results: We developed an artificial neural network by a fully connected multilayer perception with forward signal propagation and two hidden layers (the area under the ROC curve - 0.69) to predict CMVO based on the subsampling for training and testing. The network model was tested on an independent subsampling (the area under the ROC curve - 0.64, negative predictive value - 97.4%, positive predictive value - 14.6%). Conclusion: The developed artificial neural network enables to use the parameters routinely available in an operating room when choosing a surgical approach and predict CMVO development during PCI in MI patients with accuracy sufficient for practical use.


Assuntos
Infarto do Miocárdio , Fenômeno de não Refluxo , Intervenção Coronária Percutânea , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Redes Neurais de Computação , Fenômeno de não Refluxo/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos
12.
Phys Rev Lett ; 104(9): 097202, 2010 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-20367008

RESUMO

Terahertz electromagnetic excitations in the multiferroic TbMnO3 single crystals are investigated across the magnetic field induced rotation of the magnetic spin cycloid. In addition to the electromagnon along the a axis, the detailed polarization analysis of the experimental spectra suggests the existence of an electroactive excitation for ac electric fields of the electromagnetic wave along the crystallographic c axis. This excitation is possibly the electroactive eigenmode of the spin-cycloid in TbMnO3, which has been predicted within the inverse Dzyaloshinskii-Moriya mechanism of magnetoelectric coupling.

13.
Sovrem Tekhnologii Med ; 12(1): 126-136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34513046

RESUMO

Controlling infection is crucial in treating patients with acute pancreatitis (AP). The infectious process in AP often predisposes to subsequent sepsis by damaging not only the pancreas, but retroperitoneal tissues as well. Among other AP-associated factors, are the rapidly developing immune imbalance, the poor penetration of antimicrobial agents into necrotic tissue, and the impossibility of a single surgical debridement. Antibacterial and antifungal therapy for patients with infected necrosis and AP-associated extra-pancreatic infections remains a complex and largely unresolved problem, partially due to the high occurrence of multiresistant pathogens. The preventive use of antimicrobial agents has been discussed in the literature; however, the lack of consistent results makes it difficult to develop a unified strategy and clinical guidelines on this specific issue. Recent meta-analyses provide no conclusive evidence that antibacterial prophylaxis reduces the infection rate, mortality, or the need for surgical treatment in patients with necrotizing pancreatitis. We found only two studies indicating the benefits of using carbapenems for prophylactic purposes and one meta-analysis indicating a reduction in mortality under antibiotic treatment started no later than 72 h after the onset of the attack. Selective bowel decontamination is considered as one of the preventive anti-infection measures, although the available data may not be fully reliable. The main indications for antibacterial therapy in patients with AP are confirmed infected necrosis or extra-pancreatic infection, as well as clinical symptoms of suspected infection. Intra-arterial administration or local treatment with antibiotics can increase the efficacy of antibacterial therapy. No randomized studies on antifungal prophylaxis in AP are available; some reports though recommend using such therapy among patients at high risk of invasive candidiasis.

14.
Bull Exp Biol Med ; 148(2): 305-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20027354

RESUMO

The use of afala in patients with benign prostatic hyperplasia and moderate urination disturbances reduced the symptoms of the disease, improved urodynamic parameters, and increased quality of life. Clinical efficiency of afala was comparable with the efficiency of Serenoa repens extract (reference preparation).


Assuntos
Anticorpos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Adulto , Idoso , Anticorpos/efeitos adversos , Anticorpos/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Qualidade de Vida , Resultado do Tratamento , Urodinâmica/efeitos dos fármacos
16.
Vopr Virusol ; 64(1): 16-22, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30893525

RESUMO

BACKGROUND: Rоtaviruses are amоng the leading causes of severe diarrhea in children all over the Wоrld. Vaccination is considered to be the mоst effective way to cоntrоl the disease. Currently available vaccines for prevention of rоtavirus infection are based on live attenuated rotavirus strains human оr animal origin. OBJECTIVES: The aim of this investigation was to study the biological and genetic properties of an actual epidemic human rotavirus A (RVA) strain Wa G1P[8] genotype. METHODS: RVA Wa reproduction in a monolayer continuous cell lines, purification and concentration of RVA antigen, PAAG electrophoresis and Western-Blot, electrophoresis of viral genomic RNA segments, sequencing. RESULTS: Human RVA G1P[8] Wa strain biological and molecular genetic properties were assessed in the process of the adaptation to MARC145 continuous cell line. Cell cultured RVA antigen was purified, concentrated and then characterized by the method of PAAG electrophoresis and immunoblot. To verify RVA Wa genome identity, electrophoresis of viral genomic RNA segments was performed. The lack of accumulation of changes in the RVA Wa genome during adaptation to various cell cultures and during serial passages was demonstrated by sequencing fragments of the viral genome. CONCLUSIONS: RVA Wa strain is stable, it possesses high biological activity: it has been successfully adapted to the MARC145 cell line and RVA Wa virus titer after the adaptation reached 7,5-7,7 lg TCID50/ml. The identity of the cultivated RVA to the original strain Wa G1P[8] was confirmed.


Assuntos
Antígenos Virais , Genoma Viral , Filogenia , RNA Viral , Infecções por Rotavirus , Rotavirus , Animais , Antígenos Virais/biossíntese , Antígenos Virais/genética , Linhagem Celular , Chlorocebus aethiops , Genótipo , Humanos , RNA Viral/biossíntese , RNA Viral/genética , Rotavirus/genética , Rotavirus/crescimento & desenvolvimento , Rotavirus/isolamento & purificação , Infecções por Rotavirus/genética , Infecções por Rotavirus/metabolismo , Suínos
17.
J Phys Condens Matter ; 30(17): 175602, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29437151

RESUMO

The Tb3+ (4f 8) crystal-field (CF) excitations and the infrared phonons in TbMnO3 are studied as a function of temperature and under an applied magnetic field. The phonon energy shifts reflect local displacement of the oxygen ions that contribute to the CF energy level shifts below 120 K and under magnetic field. The CF polarized transmission spectra provide interesting information about the debated nature of the excitations at 41, 65, 130 cm-1. We also evaluate the contribution of the charge transfer mechanism to the magnetoelectric process in TbMnO3 under magnetic field.

18.
Neurobiol Aging ; 18(3): 329-33, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9263199

RESUMO

Potential age differences in N-methyl-D-aspartate (NMDA) receptor binding were evaluated in rat brain using [3H]dizocilpine and [3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentanoic acid (CGP 39653) as the radioligands. Neither [3H]dizocilpine nor [3H]CGP 39653 binding in hippocampus revealed any age difference (7 vs. 23-25 months) in Bmax or Kd. High-affinity [3H]dizocilpine binding showed a developmental increase (8 vs. 2 months) in hippocampus but not in frontal cortex. No senescence-related change (25 vs. 8 months) was observed in either region. The lack of senescence-related differences in these biochemical markers does not preclude the possibility of functional changes in the NMDA receptor with aging.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , 2-Amino-5-fosfonovalerato/análogos & derivados , 2-Amino-5-fosfonovalerato/farmacologia , Animais , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Ensaio Radioligante , Ratos , Ratos Endogâmicos F344
19.
J Med Chem ; 41(19): 3690-8, 1998 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-9733494

RESUMO

3-(2(S)-Azetidinylmethoxy)pyridine (A-85380) has been identified recently as a ligand with high affinity for nicotinic acetylcholine receptors (nAChRs). Here we report the synthesis and in vitro nAChR binding of a series of 10 pyridine-modified analogues of A-85380. The novel compounds feature a halogen substituent at position 2, 5, or 6 of the 3-pyridyl fragment. Those with the substituents at position 5 or 6, as well as the 2-fluoro analogue, possess subnanomolar affinity for nAChRs in membranes from rat brain. For these ligands, Ki values range from 11 to 210 pM, as measured by competition with (+/-)-[3H]epibatidine. In contrast, 2-chloro, 2-bromo, and 2-iodo analogues exhibit substantially lower affinity. AM1 quantum chemical calculations demonstrate that the bulky substituents at position 2 cause notable changes in the molecular geometry. The high-affinity members of the series and (+)-epibatidine display a tight fit superposition of low-energy stable conformers. The new ligands with high affinity for nAChRs may be of interest as pharmacological probes, potential medications, and candidates for developing radiohalogenated tracers to study nAChRs.


Assuntos
Azetidinas , Piridinas , Receptores Nicotínicos/metabolismo , Animais , Azetidinas/síntese química , Azetidinas/química , Azetidinas/metabolismo , Ligação Competitiva , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Ligantes , Masculino , Modelos Moleculares , Agonistas Nicotínicos/metabolismo , Prosencéfalo/metabolismo , Piridinas/síntese química , Piridinas/química , Piridinas/metabolismo , Ratos , Ratos Endogâmicos F344 , Relação Estrutura-Atividade
20.
Biochem Pharmacol ; 40(5): 983-9, 1990 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-2167683

RESUMO

To examine the relationship between PKBS, a 17-kD protein covalently photolabeled by [3H]PK 14105, and its association with peripheral-type benzodiazepine binding sites, rat adrenal mitochondrial fractions were photolabeled with [3H]PK 14105, solubilized in digitonin, and subjected to anion-exchange chromatography over Q-Sepharose. The chromatographic behavior of PKBS was evident as principally two major fractions, signified as Q-I and Q-II. Specific binding sites for [3H]Ro5-4864 and [3H]PK 11195 were also assayed and found to cofractionate with each other and in a manner which coincided with the photolabeled PKBS profile. The Q-I and Q-II fractions were further distinguished based on their different molecular sizes observed by gel filtration, yet both fractions were characterized as containing peripheral-type benzodiazepine recognition sites according to the following criteria. Scatchard analysis of both subpopulations revealed a single class of binding sites for [3H]Ro5-4864 with an apparent KD of 14 nM for Q-I and 22 nM for Q-II; these affinities were slightly lower than those found in mitochondrial membrane preparations used as the starting material for solubilization. The rank order of potency to inhibit [3H]Ro5-4864 binding in both subpopulations was PK 11195 greater than Ro5-4864 greater than diazepam greater than clonazepam, in connection with the pharmacological specificity of membrane-associated peripheral-type benzodiazepine binding sites. These studies provide direct biochemical evidence that the recognition sites for benzodiazepines and isoquinoline carboxamides cofractionate in unison with the 17-kD PKBS protein, demonstrating an intimate relationship between this protein and the binding domains for peripheral-type benzodiazepine ligands.


Assuntos
Glândulas Suprarrenais/metabolismo , Benzodiazepinonas/metabolismo , Isoquinolinas/metabolismo , Receptores de GABA-A/metabolismo , Glândulas Suprarrenais/efeitos dos fármacos , Marcadores de Afinidade , Animais , Sítios de Ligação , Ligação Competitiva , Células Cultivadas , Fracionamento Químico , Convulsivantes/metabolismo , Mitocôndrias/metabolismo , Ensaio Radioligante , Ratos , Ratos Endogâmicos
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