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AIMS: To evaluate the effect of IM administration of three sedative drugs, acepromazine, alfaxalone and dexmedetomidine, in combination with morphine, on the size of the feline spleen using ultrasonography. METHODS: Twenty-four client-owned cats undergoing elective de-sexing or minor procedures were recruited for a focused ultrasonographic examination of the spleen prior to and at 10, 20 and 30â minutes following administration of one of three randomly assigned IM sedation protocols: 0.05â mg/kg acepromazine (ACE group), 3â mg/kg alfaxalone (ALF group), or 10 µg/kg dexmedetomidine (DEX group), in combination with 0.5â mg/kg morphine. B-mode images of the spleen were collected and measured following a standardised protocol. Cardiorespiratory parameters and sedation score were also recorded. Mean thickness of the head, body and tail of the spleen for each group at 10, 20 and 30â minutes after drug administration was compared to baseline. RESULTS: Mean splenic thickness increased over time in the ACE group (thickness of body at T0 = 8.9 (SE 2.1) mm and at T30 = 10.5 (SE 2.0) mm; p = 0.001) and the ALF group (thickness of body at T0 = 8.8 (SE 1.0) mm and at T30 = 10.3 (SE 1.7) mm; p = 0.022) but not in the DEX group (thickness of body at T0 = 8.6â mm (1.2) and at T30 = 8.9â mm (0.6); p = 0.67). Mean arterial blood pressure in the DEX group was significantly higher than in the other groups (p = 0.002). Sedation scores in the DEX group were consistently high for the entire period. However, the sedation score in the ACE group increased over 30â minutes (p = 0.007). Sedation score in the ALF group was highest at 10â minutes but gradually decreased over the following 20â minutes (p = 0.003). CONCLUSIONS: Sedation with IM dexmedetomidine and morphine did not change splenic size, whereas acepromazine or alfaxalone and morphine increased it regardless of the degree of sedation. CLINICAL RELEVANCE: Where splenomegaly is identified in a cat sedated with acepromazine or alfaxalone, the effects of the sedation protocol could be considered as a possible cause.
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Dexmedetomidina , Gatos , Animales , Dexmedetomidina/farmacología , Acepromazina/farmacología , Bazo/diagnóstico por imagen , Hipnóticos y Sedantes/farmacología , Morfina , UltrasonografíaRESUMEN
BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.
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Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Esofagoscopía , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esofagectomía/efectos adversos , Esofagectomía/mortalidad , Esofagoscopía/efectos adversos , Esofagoscopía/mortalidad , Femenino , Hospitales Universitarios , Humanos , Japón , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Endosonografía , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Esofagoscopía , Imagen de Banda Estrecha , Anciano , Carcinoma de Células Escamosas/cirugía , Resección Endoscópica de la Mucosa , Endosonografía/métodos , Mucosa Esofágica/diagnóstico por imagen , Mucosa Esofágica/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago , Esofagoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha/métodos , Invasividad Neoplásica/diagnóstico por imagen , Periodo Preoperatorio , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity.
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Ácido Glutámico/metabolismo , Hipocampo/fisiopatología , Proteínas del Tejido Nervioso/genética , Corteza Prefrontal/fisiopatología , Tálamo/fisiopatología , Animales , Autorradiografía , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Hipocampo/metabolismo , Ketamina/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiopatología , Técnicas de Placa-Clamp , Corteza Prefrontal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transmisión Sináptica/fisiología , Tálamo/metabolismoRESUMEN
BACKGROUND: The first-line combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and platinum-based doublet chemotherapy has not been sufficiently evaluated for patients with EGFR-mutant non-small cell lung cancer (NSCLC). This randomized phase II study was designed to select a combination regimen for phase III evaluation. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced non-squamous, EGFR-mutant NSCLC were randomly assigned to receive either a concurrent or a sequential alternating regimen with gefitinib (250 mg) and carboplatin/pemetrexed [area under the curve (AUC) = 6 and 500 mg/m(2); 3-weekly]. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), response, and safety. RESULTS: All 80 patients enrolled were eligible and assessable for efficacy (41 and 39 patients in the concurrent and sequential alternating regimen groups, respectively). Median PFS was 18.3 months for the concurrent regimen and 15.3 months for the sequential alternating regimen [hazard ratio (HR) 0.71 (0.42-1.20), P = 0.20]. Although OS data are immature (16 and 24 death events), median survival times were 41.9 and 30.7 months in the concurrent and sequential alternating regimen groups, respectively [HR 0.51 (0.26-0.99); P = 0.042]. Response rates were similar in both groups (87.8% and 84.6%). Hematological and non-hematological adverse events were common and reversible; interstitial lung disease was neither frequent nor fatal (two cases in each group; 5% of all patients). CONCLUSION: This is the first randomized study to investigate the efficacy of combinational EGFR-TKI and chemotherapy in the EGFR-mutated setting. Both regimens had promising efficacy with predictable toxicities, although concurrent regimens might provide better OS. The concurrent regimen was chosen to compare with gefitinib monotherapy in our ongoing phase III study. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN C000002789).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Inhibidores de Proteínas Quinasas/administración & dosificación , Quinazolinas/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Gefitinib , Predisposición Genética a la Enfermedad , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pemetrexed/administración & dosificación , Fenotipo , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
We have revealed the fundamental mechanism of specific Cs(+) adsorption into Prussian blue (PB) in order to develop high-performance PB-based Cs(+) adsorbents in the wake of the Fukushima nuclear accident. We compared two types of PB nanoparticles with formulae of Fe(III)4[Fe(II)(CN)6]3·xH2O (x = 10-15) (PB-1) and (NH4)0.70Fe(III)1.10[Fe(II)(CN)6]·1.7H2O (PB-2) with respect to the Cs(+) adsorption ability. The synthesised PB-1, by a common stoichiometric aqueous reaction between 4Fe(3+) and 3[Fe(II)(CN)6](4-), showed much more efficient Cs(+) adsorption ability than did the commercially available PB-2. A high value of the number of waters of crystallization, x, of PB-1 was caused by a lot of defect sites (vacant sites) of [Fe(II)(CN)6](4-) moieties that were filled with coordination and crystallization water molecules. Hydrated Cs(+) ions were preferably adsorbed via the hydrophilic defect sites and accompanied by proton-elimination from the coordination water. The low number of hydrophilic sites of PB-2 was responsible for its insufficient Cs(+) adsorption ability.
RESUMEN
BACKGROUND: The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). METHODS: MIA2 role was examined by immunohistochemistry of human OSCCs and knockdown studies using human 3 OSCC cell lines with MIA2 expression. RESULTS: MIA2 expression was observed in 62 (66.7%) of 93 OSCCs and was associated with tumour expansion and nodal metastasis. Melanoma inhibitory activity 2 expression was inversely correlated with intratumoral infiltration of lymphocytes. Invasion and anti-apoptotic survival were reduced by MIA2 knockdown in HSC3 cells. MOLT-3 lymphocytes infiltrating the HSC3 cell layer was enhanced by MIA2 knockdown or MIA2 depletion with the antibody. In HSC3 cells, MIA2 knockdown decreased the expressions of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D. The downregulation of VEGF-C and -D was caused by inhibition of p38 and extracellular signal-regulated kinase (ERK)1/2, respectively. Melanoma inhibitory activity 2 was co-precipitated with integrin α4 andα5 in HSC3 cells. Integrin α4 knockdown decreased p38 phosphorylation and increased apoptosis, whereas integrin α5 knockdown decreased c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis. Inhibition of JNK decreased apoptosis in the HSC3 cells. CONCLUSION: These findings suggest that the roles of MIA2 might be based on the variety of the integrins and the subtypes of mitogen-activated protein kinase.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Anciano , Antígenos de Neoplasias , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Integrinas/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias de la Boca/inmunología , Neoplasias de la Boca/patología , Proteínas de Neoplasias , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/inmunología , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Factor D de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
BACKGROUND: MicroRNA (miRNA)-126 (miR-126) is an endothelial-specific miRNA located within intron 7 of epidermal growth factor-like domain 7 (EGFL7). However, the role of miR-126 in cancer is controversial. METHODS: We examined the function of miR-126 in oral squamous cell carcinoma (OSCC) cells. Furthermore, a series of 118 cases with OSCC were evaluated for the expression levels of miR-126. RESULTS: MicroRNA-126 (miR-126) was associated with cell growth and regulation of vascular endothelial growth factor-A activity, and demethylation treatment increased expression levels of miR-126 and EGFL7 in OSCC cells. A significant association was found between miR-126 expression and tumour progression, nodal metastasis, vessel density, or poor prognosis in OSCC cases. In the multivariate analysis, decreased miR-126 expression was strongly correlated with disease-free survival. CONCLUSION: The present results suggest that miR-126 might be a useful diagnostic and therapeutic target in OSCC.
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Carcinoma de Células Escamosas/genética , Linfangiogénesis/genética , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Neovascularización Patológica/genética , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Anciano de 80 o más Años , Proteínas de Unión al Calcio , Línea Celular Tumoral , Supervivencia sin Enfermedad , Regulación hacia Abajo , Familia de Proteínas EGF , Factores de Crecimiento Endotelial/genética , Femenino , Humanos , Masculino , MicroARNs/antagonistas & inhibidores , Persona de Mediana Edad , Activación TranscripcionalRESUMEN
Intractable pneumothorax with interstitial pneumonia (IP) is famous for the disease finally to lead to death in case of persistent air leakage. It is because severe infection, respiratory insufficiency and tissue healing insufficiency by treatments with steroid hormones and immune-suppressants on IP. Pleurodesis is generally performed although the effect of it is questionable. It is important to stop immune-suppressants and reduce steroid hormones before the treatments to succeed in thoracoscopic surgery and thoracographic fibrin glue sealing method (TGF) if possible. Less invasive interventional treatments like TGF are recommendable because intractable pneumothorax with IP is in the high risk group to need to avoid surgery. Hand suturing, looping, covering and putting TachoComb on the air leak point instead of end-stapling should be performed in order to stop air leakage when forced to choose thoracoscopic surgery.
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Enfermedades Pulmonares Intersticiales/complicaciones , Neumotórax/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Adhesivo de Tejido de Fibrina/administración & dosificación , Humanos , Persona de Mediana Edad , Neumotórax/complicaciones , ToracoscopíaRESUMEN
Reverse osmosis (RO) membrane is one of the most powerful tools for solving the global water crisis, and is used in a variety of water treatment scenes such as drinking water purification, waste-water treatment, boiler feed water production, ultra pure water production for semiconductor industry, etc. The desired performance of RO membrane varies according to quality of feed water being treated, and Toray has been developing RO membranes with suitable characteristic for each operating condition. RO membranes for seawater desalination and wastewater reclamation are especially regarded as most promising targets. Recently, high boron removal and energy saving RO membrane for seawater desalination and low fouling RO membrane for wastewater reclamation have been developed. In this paper, the prospect of attaining these renovative RO membrane, and furthermore, job references will be discussed.
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Membranas Artificiales , Ósmosis , Reciclaje , Agua de Mar/química , Cloruro de Sodio/química , Eliminación de Residuos Líquidos/métodos , Boro/química , Contaminantes Químicos del Agua/química , Purificación del Agua/instrumentación , Purificación del Agua/métodosRESUMEN
Six plant sources of hydrolyzable tannins (HT) or HT and condensed tannins (CT; designated as HT1, HT2, HT3, HT + CT1, HT + CT2, and HT + CT3) were evaluated to determine their effects in vitro on CH(4) production and on ruminal archaeal and protozoa populations, and to assess potential differences in biological activities between sources containing HT only or HT and CT. Samples HT1, HT2, and HT3 contained only HT, whereas samples HT + CT1, HT + CT2, and HT + CT3 contained HT and CT. In experiment 1, in vitro incubations with samples containing HT or HT + CT resulted in a decrease in CH(4) production of 0.6 and 5.5%, respectively, compared with that produced by incubations containing the added tannin binder polyethylene glycol-6000. Tannin also suppressed the population of methanogenic archaea in all incubations except those with HT2, with an average decrease of 11.6% in HT incubations (15.8, 7.09, and 12.0 in HT1, HT2, and HT3) and 28.6% in incubations containing HT + CT (35.0, 40.1, and 10.8 in HT + CT1, HT + CT2, and HT + CT3) when compared with incubations containing added polyethylene glycol-6000. The mean decrease in protozoal counts was 12.3% in HT and 36.2% in HT + CT incubations. Tannins increased in vitro pH, reduced total VFA concentrations, increased propionate concentrations, and decreased concentrations of iso-acids. In experiment 2, when a basal diet was incubated with graded levels of HT + CT1, HT + CT2, and HT + CT3, the total gas and CH4 production and archaeal and protozoal populations decreased as the concentration of tannins increased. Our results confirm that tannins suppress methanogenesis by reducing methanogenic populations in the rumen either directly or by reducing the protozoal population, thereby reducing methanogens symbiotically associated with the protozoal population. In addition, tannin sources containing both HT and CT were more potent in suppressing methanogenesis than those containing only HT.
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Archaea/fisiología , Bovinos , Cilióforos/fisiología , Ácidos Grasos Volátiles/metabolismo , Metano/metabolismo , Rumen , Taninos/metabolismo , Animales , Archaea/efectos de los fármacos , Archaea/genética , Cilióforos/efectos de los fármacos , Femenino , Polietilenglicoles/farmacología , ARN Ribosómico 16S/genética , Rumen/metabolismo , Rumen/microbiología , Rumen/parasitología , Tensoactivos/farmacologíaAsunto(s)
Vacunación/métodos , Niño , Recolección de Datos , Femenino , Guías como Asunto , Humanos , Japón , Masculino , Estudios Prospectivos , ConvulsionesRESUMEN
AIMS: To develop a suite of group-specific, rRNA-targeted oligonucleotide scissor probes for the quantitative detection of the predominant bacterial groups within the ruminal microbial community with the rRNA cleavage reaction-mediated microbial quantification method. METHODS AND RESULTS: Oligonucleotides that complement the conserved sites of the 16S rRNA of phylogenetically defined groups of bacteria that significantly contribute to the anaerobic fermentation of carbohydrates in ruminal ecosystems were selected from among published probes or were newly designed. For each probe, target-specific rRNA cleavage was achieved by optimizing the formamide concentration in the reaction mixture. The set of scissor probes was then used to analyse the bacterial community in the rumen fluids of four healthy dairy cows. In the rumen fluid samples, the genera Bacteroides/Prevotella and Fibrobacter and the Clostridium coccoides-Eubacterium rectale group were detected in abundance, accounting for 44-48%, 2.9-10%, and 9.1-10% of the total 16S rRNA, respectively. The coverage with the probe set was 71-78% of the total bacterial 16S rRNA. CONCLUSIONS: The probe set coupled with the sequence-specific small-subunit rRNA cleavage method can be used to analyse the structure of a ruminal bacterial community. SIGNIFICANCE AND IMPACT OF THE STUDY: The probe set developed in this study provides a tool for comprehensive rRNA-based monitoring of the community members that dominate ruminal ecosystems. As the ruminal microbial community can be perturbed, it is important to track its dynamics by analysing microbiological profiles under specific conditions. The method described here will provide a convenient approach for such tracking.
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Bacterias Anaerobias/aislamiento & purificación , Bovinos/microbiología , Genes Bacterianos , Sondas de Oligonucleótidos/genética , ARN Ribosómico 16S/genética , Rumen/microbiología , Animales , Bacterias Anaerobias/genética , Secuencia de Bases , Ingeniería Genética , Datos de Secuencia Molecular , RibotipificaciónRESUMEN
Antagonism of some amino acids (AA) to the inhibitory effects of other AA (Ile, Phe, and Thr) on the growth rate of mixed ruminal bacteria was investigated. In vitro growth rate of the mixed ruminal bacteria was inhibited when the 3 inhibitory AA (1 mM each) were each added to individual control treatments in which an ammonium salt was included as a sole N source. The inhibitory effect caused by Ile was relieved by addition of Leu or Val (equimolar to Ile), and no significant inhibition was shown when both Leu and Val were added together with Ile. The growth inhibition caused by Phe was also alleviated by supplementing with Trp, and was completely negated by adding Tyr. The inhibitory effect of Thr, on the other hand, was not affected by addition of Lys or Met (which are synthesized using a common pathway with Thr), but was mitigated by supplementation with Glu, Ser, Val, Ala, or Gln. Among the antagonistic AA, Leu, Val, Trp, Tyr, and Glu were indispensable for the maximum growth rate of the ruminal bacteria under the experimental condition of supplementation of amino-N, the removal of which from a mixture of 20 protein AA caused the growth rate to decline. Removals of Ile along with Leu or Val or both, of Phe along with Trp or Tyr, and of Thr along with Glu recovered the promotion of bacterial growth rate. It was concluded that inhibitions of the bacterial growth rate caused by Ile, Phe, or Thr could be antagonized by some other AA (Leu, Val, Tyr, Trp, or Glu), and the role of these latter AA as relievers of the inhibitory effects could explain why they are indispensable for maximum growth rate of ruminal bacteria.
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Aminoácidos/administración & dosificación , Aminoácidos/antagonistas & inhibidores , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Rumen/microbiología , Animales , Bacterias/metabolismo , Bovinos , Dieta , Retroalimentación Fisiológica , Femenino , Fermentación , Ácido Glutámico/administración & dosificación , Isoleucina/administración & dosificación , Leucina/administración & dosificación , Nitrógeno/metabolismo , Fenilalanina/administración & dosificación , Treonina/administración & dosificación , Triptófano/administración & dosificación , Tirosina/administración & dosificación , Valina/administración & dosificaciónRESUMEN
OBJECTIVES: To conduct a phase I/II study of irinotecan with cisplatin to establish a recommended dose, and assess the safety, efficacy and feasibility of this regimen in unresectable advanced or recurrent gastric cancer. PATIENTS AND METHODS: In the phase I portion of the study, patients received a fixed dose of cisplatin (30 mg/m2) with escalating doses of irinotecan, ranging from 30 mg/m2 to 70 mg/m2, on days 1 and 15. In the phase II portion of the study, 40 patients were evaluated for response and safety at the recommended dose. RESULTS: Eighteen patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and neutropenia) appeared at the irinotecan dose of 70 mg/m2. Therefore, the recommended irinotecan dose was 60 mg/m2. In the phase II study, 40 patients received cisplatin (30 mg/m2) plus irinotecan (60 mg/m2). Twenty-five out of 40 patients had received prior chemotherapy. The median number of cycles was 3.5. The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The median survival time was 288 days. Four patients (10%) developed grade 4 neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non-hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of the patients. CONCLUSION: Bi-weekly administration of irinotecan and cisplatin is safe and active for the management of unresectable advanced or recurrent gastric cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Camptotecina/efectos adversos , Cisplatino/efectos adversos , Diarrea/inducido químicamente , Esquema de Medicación , Estudios de Factibilidad , Femenino , Humanos , Irinotecán , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neoplasias Gástricas/mortalidad , Tasa de SupervivenciaRESUMEN
AIMS: The object of the present study is isolation of methyl coenzyme-M reductase (MCR) genes (mcrA) from the bovine rumen fluid and determination of phylogenetical placements of the genes to investigate mechanisms of methanogenesis in the rumen from a point of view of mcrA genes. METHODS: Genes for methanogen-specific MCR were isolated from the bovine rumen by PCR amplification. The deduced amino acid sequences were fitted to the alignments of mcrA gene products from the referred sequences. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the deduced amino acid sequences of mcrA genes, isolated from the bovine rumen in the present study, were close to that of Methanobrevibacter ruminantium, these amino acid sequences did not fall into known clusters of MCR. The findings suggest that methanogenesis in the rumen would be partially carried out by unknown methanogens.