RESUMO
Simultaneous poisoning by carbon monoxide (CO) and hydrogen cyanide is the major cause of mortality in fire gas accidents. Here, we report on the invention of an injectable antidote against CO and cyanide (CN-) mixed poisoning. The solution contains four compounds: iron(III)porphyrin (FeIIITPPS, F), two methyl-ß-cyclodextrin (CD) dimers linked by pyridine (Py3CD, P) and imidazole (Im3CD, I), and a reducing agent (Na2S2O4, S). When these compounds are dissolved in saline, the solution contains two synthetic heme models including a complex of F with P (hemoCD-P) and another one of F with I (hemoCD-I), both in their iron(II) state. hemoCD-P is stable in its iron(II) state and captures CO more strongly than native hemoproteins, while hemoCD-I is readily autoxidized to its iron(III) state to scavenge CN- once injected into blood circulation. The mixed solution (hemoCD-Twins) exhibited remarkable protective effects against acute CO and CN- mixed poisoning in mice (~85% survival vs. 0% controls). In a model using rats, exposure to CO and CN- resulted in a significant decrease in heart rate and blood pressure, which were restored by hemoCD-Twins in association with decreased CO and CN- levels in blood. Pharmacokinetic data revealed a fast urinary excretion of hemoCD-Twins with an elimination half-life of 47 min. Finally, to simulate a fire accident and translate our findings to a real-life scenario, we confirmed that combustion gas from acrylic cloth caused severe toxicity to mice and that injection of hemoCD-Twins significantly improved the survival rate, leading to a rapid recovery from the physical incapacitation.
Assuntos
Monóxido de Carbono , Porfirinas , Ratos , Camundongos , Animais , Antídotos/farmacologia , Oxigênio , Compostos Férricos , Cianetos/toxicidade , Ferro , Compostos FerrososRESUMO
Crown gall disease in grapevine is caused by pathogenic strains of Rhizobium vitis with a tumor-inducing (Ti) plasmids. A nonpathogenic strain, VAR03-1 of R. vitis, has been isolated from the grapevine root of nursery stock and it was shown to act as a biological control agent to crown gall disease. Its disease-suppressive effect was observed even when it was coinoculated with the pathogen in a 1:1 ratio. Here, we present the complete genome data of R. vitis VAR03-1, assembled by sequencing reads obtained by both PacBio and Illumina technologies with annotation. This genome sequence could contribute to investigations of the molecular basis underlying the biocontrol activity as well as the root-colonization ability of this bacterial strain.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Assuntos
Agrobacterium , Genoma Bacteriano , Agrobacterium/genética , Agentes de Controle Biológico , Genoma Bacteriano/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Vitis/microbiologiaRESUMO
Rhizobium (Agrobacterium) is one genus in the family Rhizobiaceae. Most of the species are epi- or endophytic bacteria which include tumorigenic or rhizogenic pathogens, root nodule bacteria, and commensal endosymbionts. Rhizobium vitis strain VAR06-30 is a commensal bacterium without pathogenicity which was isolated from a rootstock of grapevine in Japan. It also does not have antagonistic activity to the pathogenic strain of R. vitis. Here, we show the complete genome sequence data with annotation of R. vitis VAR06-30 which was analyzed by sequence reads obtained from both PacBio and Illumina platforms. This genome sequence would contribute to the understanding of evolutionary lineage and characteristics of Rhizobium commensal bacteria.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Assuntos
Genoma Bacteriano , Tumores de Planta/microbiologia , Rhizobium , Vitis/microbiologia , Filogenia , Rhizobium/genética , RizosferaRESUMO
Rhizobium vitis strain VAT03-9 (MAFF 211676) is a causal agent of crown gall disease in grapevine. It is one of the pathogenic strains of R. vitis isolated from graft unions of grapevine in Okayama Prefecture, Japan. Inoculation tests verified its virulence for gall formation on grapevine, tomato, and sunflower. It harbors tumor-inducing plasmid. Here, we present the complete genome sequence with annotation of R. vitis VAR03-9 obtained by assembling reads from PacBio and Illumina-sequencers. This genome sequence should be useful for the analyses of pathogenicity and evolutionary lineage of the pathogens of crown gall disease.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Assuntos
Genoma Bacteriano , Tumores de Planta/microbiologia , Rhizobium , Vitis/microbiologia , Rhizobium/genética , VirulênciaRESUMO
The effects of liposome-encapsulated hemoglobin with high O2 affinity (h-LEH), an artificial O2 carrier in skeletal muscle, were studied by in situ fatigue resistance test in fast-type plantaris (PLT) and slow-type soleus (SOL) muscles with or without ischemia in the rat. The distal tendons of PLT and SOL muscles were isolated in situ and individually attached to the force transducers to record the developed tension in response to stimuli (80 Hz tetanus train, 1.5 minutes) to the ipsilateral sciatic nerve. The fatigue resistance test (five sets separated by 2-minute rests) was evaluated in terms of tension attenuation (fatigue) from the initial to the last tension (A) during each set, attenuation of the initial (B) or last tension (C) in each set, as compared to the first set in the presence or absence of ischemia or h-LEH (10 mL/kg). While ischemia significantly enhanced fatigue only in PLT, h-LEH showed no effect regardless of the perfusion pattern (normal/ischemia) or muscle-type (PLT/SOL) during each set (A). In parameter (B), set-by-set fatigue development was observed in PLT, whereas h-LEH-SOL showed a trend of advanced fatigue resistance. Such trends became clear in the parameter C (last tension), because h-LEH-SOL exerted, rather than decreased, the tension enhancement regardless of the presence or absence of ischemia, whereas there were no h-LEH effects in PLT. In addition, faster recovery of the nicotinamide adenine dinucleotide content in the muscle after 10 minutes of all fatigue tests was observed in h-LEH-SOL, while saline-SOL still showed a significantly higher value than that of control. These results suggested that additional O2 supply by h-LEH may accelerate the tricarboxylic acid cycle/electron transport chain in slow-type aerobic SOL muscle containing abundant mitochondria and contribute to the faster removal of muscle fatigue substances such as lactate.
Assuntos
Substitutos Sanguíneos/farmacologia , Hemoglobinas/farmacologia , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Animais , Humanos , Masculino , Mitocôndrias Musculares/efeitos dos fármacos , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
The fibroblast growth factor receptor 1 (FGFR1) gene plays an important role in craniofacial morphogenesis. In our previous study, an association between FGFR1 single nucleotide polymorphisms (SNPs) and craniofacial morphology was demonstrated in Japanese and Korean subjects. The present study aimed to evaluate the relationship between a common FGFR1 SNP (rs13317) with craniofacial morphology, increasing the number of measurements and examining Egyptian subjects (n = 191) in addition to the Japanese (n = 211) and Korean (n = 226) subjects. Genotyping for rs13317 was performed using the TaqMan assay, and its associations with 81 craniofacial measurements derived from lateral and posteroanterior cephalograms were analyzed by multiple regression analysis controlling sex and facial size. The results from each of the populations were then statistically combined. In the Egyptian subjects, rs13317 was significantly associated with the nasion-orbitale depth (P = 0.00040), and a suggestive association was also observed in the Japanese (P = 0.037) and Korean subjects (P = 0.045). The combined analysis revealed that only the nasion-orbitale depth showed a significant association (P = 0.000062) and that several measurements showed a suggestive association. Our results strongly indicate that rs13317 is associated with a smaller depth between the nasion and orbitale, representing a relative protrusion of the cheekbones and retrusion of the nasal root. A similar characteristic is also observed in individuals with Pfeiffer syndrome, which is caused by a dysfunctional FGFR1 mutation.
Assuntos
Cefalometria , Face/anatomia & histologia , Estudos de Associação Genética , Processamento de Imagem Assistida por Computador , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Crânio/anatomia & histologia , Adolescente , Adulto , Pontos de Referência Anatômicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto JovemRESUMO
Artificial oxygen (O2 ) carriers were reported to be protective in ischemia/reperfusion (I/R) in various organs including the heart. In the current study, 20 rats underwent ligation (MI) of the left anterior descending artery, were treated with 10 mL/kg of PEGylated carboxyhemoglobin bovine (SANGUINATE, S+, n = 10) or saline (S-, n = 10) 10 minutes after MI and daily thereafter for 3 days, and were followed by weekly echocardiography for 4 weeks, when they had left ventricular pressure volume relationship (PVR) analyses followed by necropsy. Echocardiography showed an increase in end-systolic dimension rather than end-diastolic dimension, preserved fractional shortening (36 vs. 26%, P < .01), and milder mitral regurgitation in S+ compared with S- rats. PVR revealed a milder increase in end-systolic volume, larger stroke volume (101 vs. 74 µL, P < .005) and cardiac output (33.4 vs. 23.8 mL/min, P = .004) in S+ rats in actual determination and under a wide range of standardized loading conditions 4 weeks after MI. Excised heart showed significantly limited area of MI (8.9 vs. 13.3%, P = .028). The results suggest that SANGUINATE in short-term repeated doses may accelerate weight recovery, preserving the myocardium, mitral competence, and cardiac function after MI. The mechanism of action and optimal treatment for MI remain to be studied.
Assuntos
Substitutos Sanguíneos/uso terapêutico , Carboxihemoglobina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos , Ecocardiografia , Infarto do Miocárdio/diagnóstico por imagem , Ratos Endogâmicos LewRESUMO
Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract.
Assuntos
Imunoglobulina A Secretora/imunologia , Orthomyxoviridae/imunologia , Humanos , Imunoglobulina A Secretora/química , Testes de Neutralização , Estrutura Quaternária de ProteínaRESUMO
West Nile virus (WNV) particles assemble at and bud into the endoplasmic reticulum (ER) and are secreted from infected cells through the secretory pathway. However, the host factor related to these steps is not fully understood. Rab proteins, belonging to the Ras superfamily, play essential roles in regulating many aspects of vesicular trafficking. In this study, we sought to determine which Rab proteins are involved in intracellular trafficking of nascent WNV particles. RNAi analysis revealed that Rab8b plays a role in WNV particle release. We found that Rab8 and WNV antigen were colocalized in WNV-infected human neuroblastoma cells, and that WNV infection enhanced Rab8 expression in the cells. In addition, the amount of WNV particles in the supernatant of Rab8b-deficient cells was significantly decreased compared with that of wild-type cells. We also demonstrated that WNV particles accumulated in the recycling endosomes in WNV-infected cells. In summary, these results suggest that Rab8b is involved in trafficking of WNV particles from recycling endosomes to the plasma membrane.
Assuntos
Endossomos/enzimologia , Vírus do Nilo Ocidental/fisiologia , Proteínas rab de Ligação ao GTP/fisiologia , Animais , Transporte Biológico , Chlorocebus aethiops , Endossomos/virologia , Fibroblastos/enzimologia , Fibroblastos/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Camundongos Knockout , Transporte Proteico , Vesículas Transportadoras/virologia , Células Vero , Proteínas Virais , Liberação de Vírus , Replicação ViralRESUMO
Myoglobin reconstitution with various synthetic heme analogues was reviewed to follow the consequences of modified heme-globin interactions. Utility of dimethyl sulfoxide as the solvent for water-insoluble hemes was emphasized. Proton NMR spectroscopy revealed that loose heme-globin contacts in the heme pocket eventually caused the dynamic heme rotation around the iron-histidine bond. The full rotational rate was estimated to be about 1400 s(-1) at room temperature for 1,4,5,8-tetramethylhemin. The X-ray analysis of the myoglobin containing iron porphine, the smallest heme without any side chains, showed that the original globin fold was well conserved despite the serious disruption of native heme-globin contacts. Comparison between the two myoglobins with static and rotatory prosthetic groups indicated that the oxygen and carbon monoxide binding profiles were almost unaffected by the heme motion. On the other hand, altered tetrapyrrole array of porphyrin dramatically changed the dissociation constant of oxygen from 0.0005 mm Hg of porphycene-myoglobin to ∞ in oxypyriporphyrin-myoglobin. Heme-globin interactions in myoglobin were also monitored with circular dichroism spectroscopy. The observation on several reconstituted protein revealed an unrecognized role of the propionate groups in protoheme. Shortening of heme 6,7-propionates to carboxylates resulted in almost complete disappearance of the positive circular dichroism band in the Soret region. The theoretical analysis suggested that the disappeared circular dichroism band reflected the cancellation effects between different conformers of the carboxyl groups directly attached to heme periphery. The above techniques were proposed to be applicable to other hemoproteins to create new biocatalysts. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson.
Assuntos
Globinas/metabolismo , Heme/análogos & derivados , Heme/metabolismo , Mioglobina/metabolismo , Mapeamento de Interação de Proteínas/métodos , Animais , Transporte de Elétrons , Globinas/química , Heme/química , Histidina/química , Histidina/metabolismo , Humanos , Ferro/química , Ferro/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Mioglobina/química , Ligação ProteicaRESUMO
Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated non-metric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared from the subjects and genotyped for the hair morphology-associated SNPs. We observed a significant association of crown size with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans. Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages.
Assuntos
Estudos de Associação Genética , Cabelo/anatomia & histologia , Polimorfismo Genético , Dente/anatomia & histologia , Proteínas Wnt/genética , Alelos , Receptor Edar/genética , Frequência do Gene , Geografia , Humanos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Característica Quantitativa HerdávelRESUMO
To investigate the diversity of simian immunodeficiency virus (SIV) among nonhuman primates (NHPs) in Zambia, next-generation sequencing was performed to determine the complete genome sequence of a novel SIV recovered by co-culturing African green monkey (AGM) peripheral blood lymphocytes with human CD4+ T-cell lines. We report the first described SIV (SIVagmMAL-ZMB) from a malbrouck (Chlorocebus cynosuros). SIVagmMAL-ZMB was detected by real-time PCR analysis of splenic RNA in 3.2% (3/94) of AGMs and was undetectable in baboons (0/105). SIVagmMAL-ZMB possessed <80% nucleotide sequence identity to known SIV isolates and was located basally to vervet monkey SIV strains in all phylogenies.
Assuntos
Cercopithecinae/virologia , Filogenia , RNA Viral/genética , Síndrome de Imunodeficiência Adquirida dos Símios/epidemiologia , Vírus da Imunodeficiência Símia/classificação , Animais , Linfócitos T CD4-Positivos/virologia , Técnicas de Cocultura , Humanos , Papio , Reação em Cadeia da Polimerase em Tempo Real , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificação , Baço/virologia , Zâmbia/epidemiologiaRESUMO
Liposome-encapsulated hemoglobin (LEH) with high (h-LEH, P50 O2 = 10 mm Hg) or low O2 affinity (l-LEH, P50 O2 = 40 mm Hg) may improve O2 delivery to sensitize tumor tissues for radiotherapy. A total of 10 mL/kg of h-LEH, l-LEH, red blood cells (RBCs), or saline was infused in mice transplanted with murine colon carcinoma with near-infrared spectroscopy (NIRS) detectors set at the tumor (right leg) and intact muscle (left leg). NIRS recorded changes in the amount of oxyhemoglobin (oxyHb), deoxyhemoglobin (deoxyHb), and their sum (tHb) with the animals spontaneously breathing room air (10 min), pure O2 (5 min), and then back to room air. The tumor was finally excised for histological examination. In mice treated with h-LEH, tHb significantly increased compared to mice receiving other solutions. The magnitude was significantly attenuated in the tumor compared to the intact muscle under room air. Reciprocal changes in oxyHb and deoxyHb between intact muscle and tumor in response to infused solutions allowed assumption of average tissue PO2 between 30 and 40 mm Hg in muscle and at around 10 mm Hg in tumor. While O2 respiration increased oxyHb and decreased deoxyHb both in muscle and tumor, their sum or tHb consistently decreased in muscle and increased in tumor regardless of preceding infusion. Such responses were totally reversed when mice were placed under hypoxia (10% O2 ), suggesting that a lack of physiological circulatory regulation in tumor may account for heavier immunohistochemical staining for human hemoglobin in tumors of mice treated with h-LEH than with l-LEH. The results suggest that h-LEH may cause significant tumor oxygenation compared to RBC, l-LEH, or saline probably due to its nanometer size (vs. RBC) and high O2 affinity (vs. l-LEH) without increasing O2 content in the intact tissue (vs. O2 respiration) probably due to a lack of physiological circulatory regulation.
Assuntos
Substitutos Sanguíneos/farmacologia , Carcinoma/metabolismo , Neoplasias do Colo/metabolismo , Hemoglobinas/farmacologia , Neoplasias Experimentais/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Animais , Substitutos Sanguíneos/administração & dosagem , Carcinoma/patologia , Neoplasias do Colo/patologia , Hemoglobinas/administração & dosagem , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/patologia , Tamanho da Partícula , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Since liposome-encapsulated hemoglobin with high O2 affinity (h-LEH, P50 O2 = 10 mm Hg) has been reported to accelerate skin wound healing in normal mice, it was tested in dB/dB mice with retarded wound healing, as seen in human diabetics. Two full-thickness dorsal wounds 6 mm in diameter encompassed by silicone stents were created in dB/dB mice. Two days later (day 2), the animals were randomly assigned to receive intravenous h-LEH (2 mL/kg, n = 7) or saline (2 mL/kg, n = 7). The same treatment was repeated 4 days after wounding (day 4), and the size of the skin lesions was analyzed by photography, surface perfusion was detected by Laser-Doppler imager, and plasma cytokines and chemokines were determined on days 0, 2, 4, and 7, when all animals were euthanized for morphological studies. The size of the ulcer compared to the skin defect or silicone stent became significantly reduced on days 4 and 7 in mice treated with h-LEH (47 ± 8% of original size), similar to the level in wild-type mice, compared to saline-treated dB/dB mice (68 ± 18%, P < 0.01). Mice treated with h-LEH had significantly attenuated inflammatory cytokines, increased surface perfusion, and increased Ki67 expression on day 7 in accordance with the ulcer size reduction, while there was no significant difference in chemokines, histological granulation, epithelial thickness, and granulocyte infiltration detected by immunohistochemical staining in the ulcer between the treatment groups. The results suggest that h-LEH (2 mL/kg) early after wounding may accelerate skin wound healing in dB/dB mice to levels equivalent to wild-type mice probably via mechanism(s) involving reduced hypoxia, increased surface perfusion, suppressed inflammation, accelerated in situ cell proliferation and protein synthesis.
Assuntos
Substitutos Sanguíneos/farmacologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hemoglobinas/farmacologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Aerobiose/efeitos dos fármacos , Animais , Substitutos Sanguíneos/administração & dosagem , Modelos Animais de Doenças , Hemoglobinas/administração & dosagem , Humanos , Hipóxia/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia , Lipossomos , Masculino , Camundongos , Microcirculação/efeitos dos fármacos , Distribuição AleatóriaRESUMO
We tested a hypothesis that liposome-encapsulated hemoglobin (LEH) with high oxygen (O2 ) affinity (h-LEH, P50 O2 = 10 mm Hg) may work better than LEH with low O2 affinity (l-LEH, P50 O2 = 40 mm Hg) in cerebral ischemia and reperfusion injury using positron emission tomography (PET) in primates undergoing middle cerebral artery (MCA) occlusion and reperfusion. Cerebral blood flow (CBF), O2 extract fraction (OEF), and cerebral metabolic rate of O2 (CMRO2 ) were successively determined by PET before ischemia, at 2 h of ischemia, immediately after reperfusion, and 3 h after reperfusion. Five minutes after MCA occlusion, 10 mL/kg of h-LEH (n = 6) was intravenously infused and compared with the results from previous data of monkeys treated with l-LEH (n = 6), empty liposome (n = 4), or saline (n = 8) as control. After the series of PET studies, the integrated area of cerebral infarction was determined histologically in 12 coronal brain slices. There was no significant difference in CBF, OEF, or CMRO2 up to 2 h of ischemia. A high CBF with a low OEF tended to be suppressed after reperfusion in LEH-treated monkeys. Three hours after reperfusion, the area of mild CMRO2 reduction (down to -30%) decreased (P < 0.05) and the area of mild CMRO2 increase (up to 30%) expanded in LEH-treated monkeys (P < 0.05) regardless of O2 affinity with no difference in the area of moderate-to-severe reduction (<-30%) or increase (<+30%) in CMRO2 compared to animals treated with empty liposome or saline. Distribution of CMRO2 reduction and histological damages showed that LEH mainly protected the cerebral cortex rather than basal ganglia where neuronal dendritic processes were severely lost. There was little difference between the animals treated with l-LEH or h-LEH both at 10 mL/kg or between treatment with empty liposome or saline. In conclusion, LEH was effective regardless of O2 affinity in preserving CMRO2 and in reducing the area of histological damage in the cerebral cortex, but not in basal ganglia, shortly after occlusion/reperfusion of MCA in monkey.
Assuntos
Substitutos Sanguíneos/uso terapêutico , Encéfalo/metabolismo , Infarto Cerebral/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Hemoglobinas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Substitutos Sanguíneos/administração & dosagem , Substitutos Sanguíneos/química , Encéfalo/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Modelos Animais de Doenças , Hemoglobinas/administração & dosagem , Hemoglobinas/química , Humanos , Lipossomos , Macaca fascicularis , Oxigênio/química , Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , ReperfusãoRESUMO
Although transcatheter aortic valve implantation (TAVI) has been indicated for patients with high surgical risk, indications for or against the procedure become more difficult as vascular access becomes more proximal and/or invasive in order to accommodate patients with even higher risks. We compared preoperative factors including the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score with postoperative survival in 195 patients undergoing TAVI during 2.5 years (January 2010 to June 2012), when vascular access routes were developed from iliofemoral (IL/Fm access, n = 149), axillo-clavicular, apical, and direct aortic approaches (alternative access, n = 46). Logistic regression analyses showed that alternative access was associated with reduced 30-day survival (P = 0.024), while high surgical risk (>15% in both EuroSCORE and STS score) was associated with reduced 1-year survival (P = 0.046). Thus, patients treated via IL/Fm access had acceptable outcome regardless of preoperative risk levels while patients with low surgical risk (<15%) had favorable outcome irrespective of access route. Since the remaining patients with combined risk factors, high preoperative risk level (>15%) requiring alternative access, had a prohibitive risk in our experience, they might have been considered untreatable or not amenable even to TAVI and offered medical or alternative managements.
Assuntos
Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Período Pré-Operatório , Fatores de Risco , Análise de Sobrevida , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
Crown gall of grapevine, which is caused by tumorigenic Rhizobium vitis, is the most important bacterial disease of grapevine throughout the world. Screening tests of biological control agents resulted in the discovery of a nonpathogenic R. vitis strain ARK-1. By soaking grapevine roots with a cell suspension of strain ARK-1 prior to planting in the field, ARK-1 treatment significantly reduced the number of plants with crown gall symptoms. Several field trials result indicated that ARK-1 was very useful in the field, not only for grapevine but also for various other plant species. In experiments where a mixture of ARK-1 and a tumorigenic strain at a 1 : 1 cell ratio was examined in vitro and in planta, expression levels of the virulence genes virD2 and virE2 of the tumorigenic strain were significantly lower. The suppression of virulence genes, which can result in a reduction of gall formation and the pathogen population, seems to be a unique mechanism of ARK-1. These results indicated that ARK-1 is a promising new agent to control grapevine crown gall.
Assuntos
Tumores de Planta/microbiologia , Rhizobium/fisiologia , Vitis/fisiologia , Genes Bacterianos , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Virulência , Vitis/microbiologiaRESUMO
The Ryukyu Islands are located to the southwest of the Japanese archipelago. Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama. To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide single nucleotide polymorphism typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands. Principal component and cluster analyses revealed genetic differentiation among the island groups, especially between Okinawa and Miyako. No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations. The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions. Based on the observed genetic differences, the divergence time between the inhabitants of Okinawa and Miyako islands was dated to the Holocene. These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands.
Assuntos
Povo Asiático , Deriva Genética , Genoma Humano , Polimorfismo de Nucleotídeo Único , Análise por Conglomerados , Feminino , Genética Populacional , Humanos , Ilhas , Japão , Masculino , Paleontologia , Análise de Componente Principal , Isolamento ReprodutivoRESUMO
Patients with aortic stenosis tend to develop ventricular conduction problems, which are known adverse events following transcatheter aortic valve implantation (TAVI). Changes in ventricular conduction status after TAVI were analyzed in 195 consecutive patients from a single institute registered in FRANCE2 between February 2010 and June 2012. Among the 195 patients, 29 had a prior pacemaker implantation (+PM) and 6 had acute catastrophic hemodynamics that made a full electrocardiogram (ECG) unavailable. Among the remaining 160, PM was newly required in 28 (17.5%, PM+) but not in 132 (PM-), which included 21 (13.1%) who developed new left bundle branch block (BBB), 12 (7.5%) had right BBB, and 99 (61.9%) had no change. While PM requirement had no correlation with preoperative factors, there was significant association with the development of right BBB with Edwards Sapien/XT (P = 0.003), and new left BBB (P = 0.012) and complete heart block requiring PM with CoreValve (22.6% vs. Edwards Sapien/XT, 7.4%, P = 0.016). Whereas postoperative survival regarding PM status (+PM, PM+, PM-), vascular access, valve size or type showed no difference, delayed heart block (n = 12, Day 2 or later) was associated with poor survival (P = 0.038) compared with the remaining PM+ patients with earlier onset (n = 16, Day 0 or 1). As a result, PM+ patients (n = 28) had significantly longer intensive care unit (ICU) stay and hospitalization than PM- or +PM patients. The results suggest that ventricular conduction problems requiring PM occurred more frequently after TAVI (17.5%) than with usual surgical replacement. Nonetheless, conduction problems failed to influence postoperative survival for up to 3 years on average with use of PM, but therefore did increase medical costs.
Assuntos
Estenose da Valva Aórtica/cirurgia , Bloqueio de Ramo/etiologia , Ventrículos do Coração/fisiopatologia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/fisiopatologia , Bloqueio de Ramo/fisiopatologia , Eletrocardiografia , Feminino , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Masculino , Análise de SobrevidaRESUMO
The nonpathogenic strain of Agrobacterium (=Rhizobium) vitis ARK-1 is a biological agent able to effectively control grapevine crown gall. In this study, treating apple, Japanese pear, peach, rose, and tomato by soaking the roots in a cell suspension of ARK-1 before planting into soil infected with tumorigenic Agrobacterium spp. reduced the number of plants developing crown gall tumors. Meta-analyses of the results from six field trials of apple, four field trials of Japanese pear, and four field trials of peach, from 2010 to 2013, showed integrated risk ratio (IRR) after treatment with ARK-1 to be 0.38 for apple crown gall, 0.16 for Japanese pear crown gall, and 0.20 for peach crown gall, indicating that the disease incidence was significantly reduced by ARK-1 treatment. Meta-analyses of the results from three greenhouse trials of rose and three greenhouse trials of tomato showed IRR after treatment with ARK-1 to be 0.29 for rose crown gall and 0.16 for tomato crown gall, indicating that the disease incidence was significantly reduced by ARK-1 treatment. These results indicated that control by ARK-1 covers five different species of host plants and tumorigenic (Ti) strains of Agrobacterium species.