RESUMEN
Saponins, prominent secondary plant metabolites, are recognized for their roles in plant defense and medicinal benefits. Soyasaponins, commonly derived from legumes, are a class of triterpenoid saponins that demonstrate significant potential for plant and human health applications. Previous research and reviews largely emphasize human health effects of soyasaponins. However, the biological effects of soyasaponins and their implications for plants in the context of human health have not been well-discussed. This review provides comprehensive discussions on the biological roles of soyasaponins in plant defense and rhizosphere microbial interactions; biosynthetic regulation and compound production; immunological effects and potential for therapeutics; and soyasaponin acquisition attributed to processing effects, bioavailability, and biotransformation processes based on recent soyasaponin research. Given the multifaceted biological effects elicited by soyasaponins, further research warrants an integrated approach to understand molecular mechanisms of regulations in their production as well as their applications in plant and human health.
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Fabaceae , Ácido Oleanólico , Saponinas , Disponibilidad Biológica , Humanos , Glycine maxRESUMEN
In order to screen the endophytic fungi that can enhance the host(Dendrobium catenatum) resistance to Sclerotium delphinii, the antagonism between each of the 43 endophytic fungi and the pathogen S. delphinii were tested. The results showed that 6 endophytic fungi(DCR2, DCR5, DCR21, DCR22, DCR42, DCR43) have strong activities against the pathogen, the inhibition rates were 49.2%, 49.2%, 47.2%, 56.2%, 53.2%, 48.0%, respectively. Then D. catenatum plantlets were inoculated with both S. delphinii and each of these six endophytic fungi. As a result, the incidence rates of leaves and stems of the D. catenatum plantlets inoculated with DCR2 and the pathogen were both significantly lower than those with other treatments, and the plantlet death rate was 0. It showed that DCR2 Trichoderma polysporum could effectively inhibit the southern blight disease of D. catenatum. Through the endophytic fungal re-isolation test, it was found that DCR2 can colonize in the roots, stems, and leaves of D. catenatum. The research will provide new ideas for the prevention and treatment of the southern blight disease of D. catenatum. It is also significant for reducing pesticide use, ensuring food safety, and promoting the sustainable development of D. catenatum industry. Furthermore, it will provide a basis for the disease control in other crops.
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Dendrobium , Basidiomycota , Endófitos , Hongos , Hypocreales , Raíces de PlantasRESUMEN
BACKGROUND The purpose of this study was to investigate whether DEX exerts protective mechanisms in rats with acute lung injury (ALI) induced by the endotoxin lipopolysaccharide (LPS). The mortality rate of ALI is extremely high. DEX, an a2 adrenergic receptor agonist, has potent anti-inï¬ammatory and organ-protective effects in addition to its sedative and analgesic properties. We sought to elucidate whether DEX can attenuate acute lung injury. MATERIAL AND METHODS Forty-eight Wister rats were randomly divided into 4 groups (n=12, per group): the normal saline control (NS) group, receiving tail-vein injection of 0.9% normal saline (5 mL/kg); the LPS (L) group, receiving tail-vein injection of LPS (8 mg/kg); the LPS+DEX (L+D) group, receiving tail-vein injection of LPS (8 mg/kg), 0.5h before treated with DEX (50 ug/kg); and the DEX+LPS (D+L) group, receiving tail-vein injection of LPS (8 mg/kg) 0.5 h after being treated with DEX (50 ug/kg). Then, we measured the wettodry weight ratio of lung tissue, the ALI pathology score, and HE staining of lung tissue, and assessed the Oxygen Tension index. RESULTS The present study revealed that LPSinduced rats exhibited significant lung injury, characterized by the deterioration of histopathology, ALI Pathology Score, wettodry weight ratio, and Oxygen Tension index (MBP, PaO2, PaCO2, PH, HCO3-, and Lac), which were attenuated by DEX treatment. CONCLUSIONS Collectively, the present results demonstrate elucidate the molecular mechanisms by which DEX ameliorates LPSinduced ALI.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Dexmedetomidina/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Animales , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Endotoxinas , Lipopolisacáridos/farmacología , Pulmón/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Once hypertension is established, increased mechanical stretch stress becomes a leading cause of vascular remodeling. Clinical antihypertension guidelines demonstrate that antihypertension drugs prevent vascular remodeling in hypertensive patients mainly by lowering blood pressure, suggesting an indirect way of reducing the effects of stretch stress (hypertension). Whether these drugs can directly block the effects of the stretch stress on vascular remodeling has not been reported to date. This study was designed to answer this question and explore the underlying mechanisms. METHODS: Cultured quiescent vascular smooth muscle cells (VSMCs) were stimulated by stretch stress after pretreatment with nifedipine and hydrochlorothiazide. The phosphorylation levels of extracellular signal-regulated kinases (ERKs), cJun NH2-terminal protein kinases (JNKs), and p38 mitogen-activated protein kinase (MAPK) in VSMCs were detected via Western blotting. The treated cells were stained using triple-labeled immunofluorescence with Ki67 antibody and a TUNEL kit in the presence of DAPI for the detection of proliferative, apoptotic, and resting cells. RESULTS: Compared with the negative control, both nifedipine and hydrochlorothiazide had no influence on the phosphorylation of MAPKs and on the proliferation and apoptosis of VSMCs in resting state. Stretch stress could significantly induce increased phosphorylation of MAPKs as well as proliferation and apoptosis of VSMCs. Nifedipine inhibited the effects of stretch stress in a dose-dependent manner. Contrary to the effects of nifedipine, hydrochlorothiazide synergistically amplified the effects induced by stretch stress. CONCLUSION: Nifedipine and hydrochlorothiazide have opposing functions in the increased phosphorylation of MAPK and in the proliferation and apoptosis of VSMCs induced by stretch stress. The former plays a role as an inhibitor, while the latter functions as a promoter.
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Apoptosis/efectos de los fármacos , Hidroclorotiazida/farmacología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Músculo Liso Vascular/efectos de los fármacos , Nifedipino/farmacología , Remodelación Vascular/efectos de los fármacos , Apoptosis/fisiología , Western Blotting , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Técnica del Anticuerpo Fluorescente , Etiquetado Corte-Fin in Situ , Técnicas In Vitro , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Músculo Liso Vascular/fisiopatología , Fosforilación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
China's prevention and control of parasitic diseases has made remarkable achievements. However, the prevalence and transmission of parasitic diseases is impacted by the complicated natural and social factors of environment, natural disasters, population movements, and so on. Therefore, there are still the risks of the outbreak of emergency parasitic diseases affairs, which may affect the control effectiveness of parasitic diseases and endanger the social stability seriously. In this article, we aim at the analysis of typical cases of emergency parasitic disease affairs and their impacts on public health security in China in recently years, and we also elaborate the disposal characteristics of emergency parasitic disease affairs, and propose the establishment of response system to emergency parasitic disease affairs in China, including the organizational structure and response flow path, and in addition, point out that, in the future, we should strengthen the system construction and measures of the response system to emergency parasitic disease affairs, so as to control the risk and harm of parasitic disease spread as much as possible and to realize the early intervention and proper disposal of emergency parasitic disease affairs.
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Brotes de Enfermedades , Enfermedades Parasitarias/prevención & control , Salud Pública , China , Desastres , HumanosRESUMEN
Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.
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Antimaláricos/síntesis química , Antimaláricos/farmacología , Azetidinas/uso terapéutico , Descubrimiento de Drogas , Estadios del Ciclo de Vida/efectos de los fármacos , Malaria Falciparum/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrollo , Animales , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Compuestos de Azabiciclo/administración & dosificación , Compuestos de Azabiciclo/síntesis química , Compuestos de Azabiciclo/farmacología , Compuestos de Azabiciclo/uso terapéutico , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Azetidinas/farmacología , Citosol/enzimología , Modelos Animales de Enfermedad , Femenino , Hígado/efectos de los fármacos , Hígado/parasitología , Macaca mulatta/parasitología , Malaria Falciparum/prevención & control , Malaria Falciparum/transmisión , Masculino , Ratones , Fenilalanina-ARNt Ligasa/antagonistas & inhibidores , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/síntesis química , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Plasmodium falciparum/citología , Plasmodium falciparum/enzimología , SeguridadRESUMEN
BACKGROUND: Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. METHODS: This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. RESULTS: Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. CONCLUSION: Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.
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Hospitales de Veteranos/tendencias , Hipertensión/mortalidad , Hipotensión/mortalidad , Monitoreo Intraoperatorio/mortalidad , Monitoreo Intraoperatorio/tendencias , Complicaciones Posoperatorias/mortalidad , Determinación de la Presión Sanguínea/mortalidad , Determinación de la Presión Sanguínea/tendencias , Estudios de Cohortes , Femenino , Humanos , Hipertensión/diagnóstico , Hipotensión/diagnóstico , Masculino , Mortalidad/tendencias , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
This study aimed to isolate and characterize a new arsenic (As)-tolerant bacterial strain (XJ-1) from the Halosol soil, to evaluate its As tolerance, and to examine the variation in composition and relative content of accumulated photosynthetic pigments in response to As. The experiments were performed with high-performance liquid chromatography (HPLC), inductively-coupled plasma mass spectrometry (ICP-MS), liquid chromatography/mass spectrometry (LC/MS), thin-layer chromatography (TLC) and grayscale intensity image analysis using Gel-Pro analyzer software. Strain XJ-1 was identified as Rhodobacter (R.) capsulatus based on 16S rRNA gene sequencing and physiological characteristics. Strain XJ-1 was able to grow when exposed to arsenite [As(III)] and arsenate [As(V)] under anaerobic-light conditions. The median effective concentrations (EC50) of As(III) and As(V) were 0.61 mM and 2.03 mM, respectively. Strain XJ-1 could reduce As(V) to As(III), but As(III) could not be transformed back to As(V) or other organic As compounds. Accumulation of bacteriochlorophylls and carotenoids in strain XJ-1 varied in the presence of 0.2-1.2 mM As(III) and 0-2.5 mM As(V). As exposure resulted in pronounced variation in compositions and contents of photosynthetic pigments, especially hydroxyspheroidene, bacteriophaeophytin, the ratio of tetrahydrogeranylgeranyl to phytylated BChl a, and the ratio of spheroidene to spheroidenone. This research highlights the adaptative response of R. capsulatus strain XJ-1 photosystems to environmental As, and demonstrates the potential of utilizing the sensitivity of its photosynthetic pigments to As(III) and As(V) for the biodetection of As in the environment.
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Arseniatos/toxicidad , Arsenitos/toxicidad , Carotenoides/metabolismo , Clorofila/metabolismo , Rhodobacter capsulatus/efectos de los fármacos , Arsénico/toxicidad , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Espectrometría de Masas/métodos , Fotosíntesis/fisiología , ARN Ribosómico 16S/genética , Rhodobacter capsulatus/genética , Rhodobacter capsulatus/crecimiento & desarrollo , Rhodobacter capsulatus/metabolismoRESUMEN
BACKGROUND: The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes. METHODS: We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries. RESULTS: Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above. CONCLUSION: The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Colorrectales/genética , Mutación de Línea Germinal , Canadá/epidemiología , Neoplasias Colorrectales/epidemiología , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Persona de Mediana Edad , Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation. METHODS: We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases. RESULTS: Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03-5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36-7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family. CONCLUSION: The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Genes BRCA1 , Genes BRCA2 , Mutación de Línea Germinal , Heterocigoto , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidadRESUMEN
BACKGROUND: Current drugs for induction and maintenance of sedation in mechanically ventilated patients in the intensive care unit have limitations. Fospropofol, a prodrug of propofol, has not been studied as a sedative in the ICU setting. METHODS: In this randomized, open-label pilot study, patients received 1 of 3 regimens with a goal of maintaining a Ramsay Sedation Score of 2 to 5: (1) fospropofol IV infusion with a bolus and increased infusion rate for agitation events (infusion/bolus); (2) fospropofol IV infusion with an increased infusion rate for agitation events (infusion only); or (3) propofol IV infusion with an increased infusion rate for agitation events. RESULTS: Sixty patients received study drug and were included in the safety and efficacy analyses. Because incidence rates for adverse events were similar between fospropofol groups, and because the study was not powered to determine significant differences between treatment groups for safety variables, adverse events for both fospropofol groups were combined. In the fospropofol groups, 28 out of 38 patients (74%) experienced treatment-emergent adverse events in comparison with 14 out of 22 patients (64%) in the propofol group. The most common treatment-emergent adverse events with fospropofol were procedural pain (21.1%) and nausea (13.2%). Two patients (1 each in the fospropofol infusion/bolus and the propofol groups) experienced hypotension during the study as a potential sedation-related adverse event. Mean plasma formate levels were not significantly different among groups. Patients in all 3 treatment groups maintained Ramsay Sedation Scores of 2 to 5 for >90% of the time they were sedated. CONCLUSION: This pilot study suggests that fospropofol, administered in either an infusion/bolus or infusion-only regimen, is tolerable and effective for short-term induction and maintenance of sedation in mechanically ventilated intensive care unit patients.
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Cuidados Críticos , Hipnóticos y Sedantes/administración & dosificación , Intubación Intratraqueal , Propofol/análogos & derivados , Respiración Artificial , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Infusiones Intravenosas , Inyecciones Intravenosas , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Propofol/administración & dosificación , Propofol/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
Cryopreservation of sperm from tree shrews, which are considered primitive primates, would enhance genetic management and breeding programs. Epididymal sperm were surgically harvested from male tree shrews, cryopreserved in two Tes-Tris-based cryodiluents, and used in four experiments. In Experiment 1, there were no significant differences in motility and acrosome integrity among five concentrations of egg yolk in TTE after cooling to 4 °C. However, sperm frozen in TTE containing 20% egg yolk at -172 °C/min had better (P < 0.05) post-thaw motility and acrosome integrity. In Experiment 2, sperm held for 10 min prior to storage in liquid nitrogen had greater motility than those held for 5 or 15 min (P < 0.05), but acrosome integrity was not different (P > 0.05) among treatments. In Experiment 3, sperm frozen in TTE diluent had higher (P < 0.05) motility and acrosome integrity than those in TEST diluent. In Experiment 4, there were no differences (P > 0.05) in the fertilization rate of oocytes and the proportion of tree shrews yielding fertilized oocytes, following AI with fresh versus frozen sperm. In conclusion, tree shrew epididymal sperm were successfully cryopreserved, as assessed by post-thaw motility, acrosome integrity, and fertilizing ability.
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Criopreservación/veterinaria , Epidídimo/citología , Espermatozoides , Tupaia , Acrosoma/fisiología , Animales , Técnicas de Cultivo de Célula/veterinaria , Criopreservación/métodos , Crioprotectores/farmacología , Masculino , Motilidad EspermáticaRESUMEN
BACKGROUND: Identification of critical autoantigenic T-cell epitopes is key to developing antigen-based therapies for autoimmune diseases, including psoriasis. Our previous work demonstrated that 3 peptides on keratin 17 are able to stimulate peripheral blood lymphocytes of HLA-DRB1*07-positive patients with psoriasis and to serve as immunodominant T-cell epitopes. OBJECTIVE: We sought to determine antagonistic altered peptide ligands to psoriatic T cells with a down-modulatory effect in inhibiting keratinocyte proliferation. METHODS: Psoriatic altered peptide ligands were generated by single alanine residue substitutions at a critical T-cell receptor contact residue position. Antagonistic altered peptide ligands were identified by suppression screening of psoriatic T-cell activation and keratinocyte proliferation. RESULTS: Altered peptide ligands 119R and 355L can inhibit psoriatic T-cell activation more effectively than other altered peptide ligands, especially 355L, with inhibition of T-cell proliferation and the secretion of interferon gamma and interleukin 2 in parallel with the up-regulation of interleukins 4 and 10 as well as transforming growth factor-beta. In coincubation assay, altered peptide ligands 119R and 355L can down-regulate the function of psoriatic T cells more effectively than wild-type epitopes solely, but less effectively than altered peptide ligands solely. In prepulse assay altered peptide ligand 119R can down-regulate the activation of psoriatic T cells more effectively than in coincubation but less effectively as compared with altered peptide ligand 119R only. Altered peptide ligand 355L was also shown to have a similar presentation. T-cell culture supernatants (1:100) from the concentrations (10 microg.mL(-1) and 100 microg.mL(-1) with 119R, 100 microg.mL(-1) with 355L) were more effective than the other ratios in inhibiting keratinocyte proliferation. LIMITATIONS: This study had a relatively small sample size (52 patients and 48 healthy controls). CONCLUSION: Our findings show that the altered peptide ligands 119R (VAALEEANTELEVKI) and 355L (ENRYCVQASQIQGLI) are capable of inhibiting proliferative responses of psoriatic T cells and keratinocyte proliferation in vitro, at least, with enhanced helper T cell type 2 polarization. Thus, to our knowledge, this article is the first report of the demonstration of therapeutic activity of altered peptide ligands derived from keratin 17.
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Queratinocitos/citología , Queratinas/fisiología , Psoriasis/patología , Linfocitos T/citología , Proliferación Celular , Células Cultivadas , Humanos , Ligandos , Péptidos , Receptores de Antígenos de Linfocitos T/fisiologíaRESUMEN
PURPOSE: To assess the need for gross tumor volume (GTV) delineation protocols in head-and-neck cancer (HNC) treatment planning by use of positron emission tomography (PET)/computed tomography (CT) fusion imaging. Assessment will consist of interobserver and intermodality variation analysis. METHODS AND MATERIALS: Sixteen HNC patients were accrued for the study. Four physicians (2 neuroradiologists and 2 radiation oncologists) contoured GTV on 16 patients. Physicians were asked to contour GTV on the basis of the CT alone, and then on PET/CT fusion. Statistical analysis included analysis of variance for interobserver variability and Student's paired sample t test for intermodality and interdisciplinary variability. A Boolean pairwise analysis was included to measure degree of overlap. RESULTS: Near-significant variation occurred across physicians' CT volumes (p = 0.09) and significant variation occurred across physicians' PET/CT volumes (p = 0.0002). The Boolean comparison correlates with statistical findings. One radiation oncologist's PET/CT fusion volumes were significantly larger than his CT volumes (p < 0.01). Conversely, the other radiation oncologist's CT volumes tended to be larger than his fusion volumes (p = 0.06). No significant interdisciplinary variation was seen. Significant disagreement occurred between radiation oncologists. CONCLUSION: Significant differences in GTV delineation were found between multiple observers contouring on PET/CT fusion. The need for delineation protocol has been confirmed.
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Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , RadiofármacosRESUMEN
Central administration of angiotensin IV (Ang IV) or its analogues enhance performance of rats in passive avoidance and spatial memory paradigms. The purpose of this study was to examine the effect of a single bolus injection of two distinct AT4 ligands, Nle1-Ang IV or LVV-haemorphin-7, on spatial learning in the Barnes circular maze. Mean number of days for rats treated with either Nle1-Ang IV or LVV-haemorphin-7 to achieve learner criterion is significantly reduced compared with controls (P < 0.001 and P < 0.05 respectively). This is due to enhanced ability of the peptide-treated rats to adopt a spatial strategy for finding the escape hatch. In all three measures of learning performance, (1) the number of errors made, (2) the distance travelled and (3) the latency in finding the escape hatch, rats treated with either 100 pmol or 1 nmol of Nle1-Ang IV or 100 pmol LVV-haemorphin-7 performed significantly better than the control groups. As early as the first day of testing, the rats treated with the lower dose of Nle1-Ang IV or LVV-haemorphin-7 made fewer errors (P < 0.01 and P < 0.05 respectively) and travelled shorter distances (P < 0.05 for both groups) than the control animals. The enhanced spatial learning induced by Nle1-Ang IV (100 pmol) was attenuated by the co-administration of the AT4 receptor antagonist, divalinal-Ang IV (10 nmol). Thus, administration of AT4 ligands results in an immediate potentiation of learning, which may be associated with facilitation of synaptic transmission and/or enhancement of acetylcholine release.
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Angiotensina II/análogos & derivados , Antagonistas de Receptores de Angiotensina , Hemoglobinas/farmacología , Aprendizaje/efectos de los fármacos , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Conducta Espacial/efectos de los fármacos , Angiotensina II/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal , Inyecciones Intraventriculares/métodos , Masculino , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Receptores de Angiotensina , Factores de TiempoRESUMEN
OBJECTIVE: To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU). DESIGN: Randomized, open label. SETTING: Twenty-five centers in the United States and Canada. PARTICIPANTS: Two hundred ninety-five adults undergoing CABG surgery. INTERVENTIONS: At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice. MEASUREMENTS AND MAIN RESULTS: Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001). CONCLUSION: Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics.
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Sedación Consciente , Puente de Arteria Coronaria , Dexmedetomidina , Hipnóticos y Sedantes , Unidades de Cuidados Intensivos , Cuidados Posoperatorios , Propofol , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Anciano , Analgésicos Opioides , Antiarrítmicos/uso terapéutico , Biomarcadores/sangre , Presión Sanguínea/fisiología , Nitrógeno de la Urea Sanguínea , Canadá/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/terapia , Diuréticos/uso terapéutico , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Incidencia , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Morfina , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/fisiopatología , Respiración Artificial , Sístole/fisiología , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Vasodilatadores/uso terapéutico , gamma-Glutamiltransferasa/sangreRESUMEN
STUDY OBJECTIVE: To determine whether tracheoscopy is an accurate and quick method for verifying correct placement of the tracheal tube after intubation. DESIGN: Prospective, randomized study. SETTING: Operating rooms of a teaching hospital. PATIENTS: 26 patients scheduled for surgery and general anesthesia. INTERVENTIONS: 8.0-mm tracheal tubes were inserted into both the trachea and the esophagus. Tracheoscopy was performed consecutively through both tracheal tubes by a variety of clinicians. MEASUREMENTS: The times taken to correctly identify the trachea and the esophagus were recorded. MAIN RESULTS: Correct identification of either the esophagus or the trachea occurred with a 100% sensitivity and a 96% specificity. The mean time to recognize either the trachea or the esophagus was 22.0 seconds. CONCLUSIONS: Tracheoscopy is a reliable method for quickly verifying proper endotracheal placement of a tracheal tube.
Asunto(s)
Broncoscopios , Broncoscopía/métodos , Intubación Intratraqueal , Tráquea/anatomía & histología , Anestesia General , Método Doble Ciego , Esófago/fisiología , HumanosRESUMEN
Dexmedetomidine was evaluated for sedation of 401 post-surgical patients in this double-blind, randomized, placebo-controlled, multicenter trial. Dexmedetomidine or saline was started on arrival in the intensive care unit (ICU) (1.0 mcg/kg for 10 minutes), then titrated at 0.2 to 0.7 mcg/kg/h to effect. Patients could be given propofol if necessary. Morphine was administered for pain. Sixty percent of the dexmedetomidine patients required no other sedative to maintain an RSS > or = 3; 21% required < 50 mg propofol. In contrast, 76% of the control group received propofol; 59% required > or = 50 mg. Dexmedetomidine patients required significantly less morphine for pain relief (P <.001). Continuously given throughout the ICU stay, dexmedetomidine had no effect on respiratory rate, oxygen saturation, duration of weaning, or times to extubation. Nurses judged the dexmedetomidine patients were easier to manage. Later, fewer dexmedetomidine patients remembered pain or discomfort. The majority of dexmedetomidine patients maintained blood pressures within normal range, without rebound. Hypertension, atelectasis, and rigors occurred more frequently in the control group, while hypotension and bradycardia occurred more frequently in the dexmedetomidine group. Preoperative cardiovascular conditions were not risk factors for dexmedetomidine patients.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/uso terapéutico , Sedación Consciente/métodos , Cuidados Críticos/métodos , Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Cuidados Posoperatorios/métodos , Adolescente , Agonistas alfa-Adrenérgicos/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Bradicardia/inducido químicamente , Dexmedetomidina/farmacología , Método Doble Ciego , Monitoreo de Drogas , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipnóticos y Sedantes/farmacología , Hipotensión/inducido químicamente , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Propofol/farmacología , Propofol/uso terapéutico , Respiración/efectos de los fármacos , Desconexión del VentiladorRESUMEN
AIMS: The objective of this work was to express a novel mel gene, responsible for melanin formation, in Bacillus thuringiensis. METHODS AND RESULTS: A novel mel gene from Pseudomonas maltophilia was sub-cloned into B. thuringiensis using a shuttle vector plasmid and electroporation. Results revealed that the mel gene was expressed under the control of the CryIIIA promoter in B. thuringiensis and conferred u.v. protection on the recipient strain. CONCLUSIONS: The novel mel gene from Ps. maltophilia expressed in B. thuringiensis conferred u.v. protection on the recipient strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Products containing B. thuringiensis for pest control are sensitive to u.v. degradation. As melanin has the ability to act as a u.v. absorber, a recombinant B. thuringiensis strain producing melanin provides a new stability for B. thuringiensis preparations.
Asunto(s)
Bacillus thuringiensis/genética , Proteínas Bacterianas/genética , Toxinas Bacterianas , Monofenol Monooxigenasa/genética , Pseudomonas/genética , Bacillus thuringiensis/metabolismo , Bacillus thuringiensis/efectos de la radiación , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/metabolismo , Endotoxinas/genética , Expresión Génica , Genes Bacterianos , Proteínas Hemolisinas , Levodopa/biosíntesis , Melaninas/análisis , Datos de Secuencia Molecular , Monofenol Monooxigenasa/aislamiento & purificación , Monofenol Monooxigenasa/metabolismo , Proteínas Recombinantes/metabolismoRESUMEN
We report a 65-year-old male who developed severe methemoglobinemia only on reexposure to benzocaine. The patient needed two awake fiberoptic intubations for emergency surgeries. On the second exposure, the patient was septic and malnourished, and he was taking acetaminophen. He developed a methemoglobin level of 55%. Possible reasons for the methoglobinemia on reexposure are discussed in this report.