RESUMEN
Very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare and life-threatening disease characterized by an enzymatic defect in the fatty acid ß-oxidation pathway. A nulliparous woman with VLCADD showed improvements in serum levels of the long-chain acylcarnitine moiety (C14:1) during pregnancy and successfully delivered a healthy infant vaginally. Pregnancy and vaginal delivery can be successfully completed in patients with VLCADD with careful management.
Asunto(s)
Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Errores Innatos del Metabolismo Lipídico/terapia , Enfermedades Mitocondriales/terapia , Enfermedades Musculares/terapia , Complicaciones del Embarazo/terapia , Embarazo de Alto Riesgo , Acil-CoA Deshidrogenasa de Cadena Larga/sangre , Reposo en Cama , Niño , Terapia Combinada , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Diagnóstico Tardío , Ácidos Grasos Monoinsaturados/sangre , Femenino , Hospitalización , Humanos , Recién Nacido , Japón , Trabajo de Parto Inducido , Errores Innatos del Metabolismo Lipídico/sangre , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/fisiopatología , Enfermedades Mitocondriales/sangre , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/fisiopatología , Enfermedades Musculares/sangre , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/fisiopatología , Mialgia/etiología , Mialgia/prevención & control , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/fisiopatología , Embarazo de Alto Riesgo/sangre , Diagnóstico Prenatal , Nacimiento a TérminoRESUMEN
The main purpose of the current study was to investigate the effect of a combination of alogliptin [a dipeptydil peptidase (DPP)-4 inhibitor] and lansoprazole [a proton pump inhibitor (PPI)] compared with alogliptin mono-therapy on glycemic control in patients with type 2 diabetes. This study was a multicenter randomized open-label study. One hundred type 2 diabetic patients were randomly assigned to either the alogliptin with lansoprazole group or the alogliptin mono-therapy group. After 3 months of treatment, the changes in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), serum gastrin, homeostasis model assessment (HOMA)-ß, and HOMA-insulin resistance (IR) were evaluated. A significant decrease in HbA1c and FPG, and a significant increase in HOMA-ß were observed in both groups (all with P <0.0001). However, there were no significant differences in changes in HbA1c, FPG, or HOMA-ß before and after therapy between the combination and alogliptin mono-therapy group (P =0.2945, P =0.1901, P =0.3042, respectively). There was a significant elevation of serum gastrin in the combination group compared with the alogliptin mono-therapy group (P =0.0004). This study showed that, although combination therapy with alogliptin and lansoprazole more effectively elevated serum gastrin levels compared with alogliptin mono-therapy, the effect of the combination therapy on glycemic control was equal to that of alogliptin mono-therapy during a 3-month study period.
Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Lansoprazol/uso terapéutico , Piperidinas/uso terapéutico , Uracilo/análogos & derivados , Anciano , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Resistencia a la Insulina , Lansoprazol/administración & dosificación , Masculino , Persona de Mediana Edad , Piperidinas/administración & dosificación , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/uso terapéuticoRESUMEN
Salmonella enterica serovar Enteritidis (SE) has consistently been the most common serotype associated with the foodborne Salmonellosis worldwide. In this study, the effect of a dietary direct-fed microbial (DFM) and yeast cell walls (YCW) under a challenge of nalidixic acid resistant SE strain using layer chicks has been investigated. A total of 160 newly hatched Dekalb White female chicks were randomly assigned into 2 experimental groups (80 birds/treatment), control group (CON) and treatment group (DY). Chicks were fed ad libitum a non-medicated-corn-soy based diet and DY was supplemented with the combination of DFM and YCW. At 8 days of age, 2.1 × 109 CFU/bird of the SE was given to all chicks by oral administration. On 3 days postinoculation (dpi), 20 chicks/group were euthanized and all cecal contents were collected for analysis. On 6, 10, and 14 dpi, the cecal contents were sampled from 16 chicks per group. The number of SE in the cecal contents was counted using culture-based methods. A 16S rRNA-based microbiota analysis was performed for additional microbial profiling. The CON and DY showed difference (P ≤ 0.05) in ß diversity throughout the trial. Prevalence of SE in cecal contents was lower (P ≤ 0.05) in DY across all time-points. Lower abundance of Salmonella spp. was also shown in DY by liner discriminant analysis effect size (LEfSe). DY increased (P ≤ 0.05) diversity of bacterial species in the cecal contents in DY at 10 and 14 dpi. For the SE challenged birds, SE reduction in DY was observed at 3 dpi and until the end of the trial at 14 dpi confirming a numerically larger difference between groups as well as an increase in bacterial species diversity in DY. It could be hypothesized that the SE reduction shown immediately after the challenge and the greater SE reduction shown after 10 dpi may be the synergistic effect of the combined feed additives.
Asunto(s)
Microbiota , Enfermedades de las Aves de Corral , Salmonelosis Animal , Animales , Ciego , Pared Celular , Pollos , Dieta/veterinaria , Femenino , Ácido Nalidíxico , ARN Ribosómico 16S , Saccharomyces cerevisiae , Salmonella enteritidisRESUMEN
Housaku Monogatari (HM) is a plant activator prepared from a yeast cell wall extract. We examined the efficacy of HM application and observed that HM treatment increased the resistance of Arabidopsis thaliana and Brassica rapa leaves to bacterial and fungal infections. HM reduced the severity of bacterial leaf spot and anthracnose on A. thaliana and Brassica crop leaves with protective effects. In addition, gene expression analysis of A. thaliana plants after treatment with HM indicated increased expression of several plant defense-related genes. HM treatment appears to induce early activation of jasmonate/ethylene and late activation of salicylic acid (SA) pathways. Analysis using signaling mutants revealed that HM required SA accumulation and SA signaling to facilitate resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola and the fungal pathogen Colletotrichum higginsianum. In addition, HM-induced resistance conferred chitin-independent disease resistance to bacterial pathogens in A. thaliana. These results suggest that HM contains multiple microbe-associated molecular patterns that activate defense responses in plants. These findings suggest that the application of HM is a useful tool that may facilitate new disease control methods.
Asunto(s)
Arabidopsis/genética , Brassica/genética , Colletotrichum/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/farmacología , Pseudomonas syringae/efectos de los fármacos , Arabidopsis/metabolismo , Arabidopsis/microbiología , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brassica/metabolismo , Brassica/microbiología , Pared Celular/química , Pared Celular/metabolismo , Quitinasas/genética , Quitinasas/metabolismo , Colletotrichum/fisiología , Ciclopentanos/metabolismo , Resistencia a la Enfermedad/genética , Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Oxilipinas/metabolismo , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/química , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/microbiología , Pseudomonas syringae/fisiología , Ácido Salicílico/metabolismo , Transducción de Señal/efectos de los fármacos , Levaduras/química , Levaduras/metabolismoAsunto(s)
Polimorfismo Genético , Neoplasias de la Próstata/genética , Receptores de Calcitriol/genética , Anciano , Anciano de 80 o más Años , Desoxirribonucleasas de Localización Especificada Tipo II , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
Molecular epidemiologic studies have reported a relationship between 1alpha,25 dihydroxyvitamin D3 (1,25(OH)2D3) and the development and progression of malignant tumors. (1,25(OH)2D3) exerts its biological activity by binding the vitamin D receptor (VDR), while recent studies have demonstrated that VDR gene polymorphisms affect serum levels of (1,25(OH)2D3). Serum levels of (1,25(OH)2D3) are reported to be significantly lower in patients with renal cell carcinoma (RCC) compared to non-cancer control patients. The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese RCC patients and non-cancer controls in order to determine if an association exists between VDR genotype and the risk of developing RCC as well as clinical risk factors. A total of 102 RCC patients and 204 controls were genotyped for a previously described TaqI restriction fragment length polymorphism (RFLP) of the VDR gene. Products were digested into T allele or the t allele according to the absence or presence of a TaqI restriction site. Individuals were classified as TT, Tt or tt. The genotype TT was statistically more frequent among RCC patients (80.4%) compared to controls (61.8%) (OR = 2.54; 95% CI, 1.44-4.46; p = 0.0006). In addition, the occurrence of the genotype TT was significantly higher in patients with rapid-growth-type group (92.1%) compared to slow-growth-type group (73.4%) (OR = 4.22; 95% CI, 1.15-15.53; p = 0.0175). These data demonstrate that VDR genotype plays an important role in determining the risk of developing more aggressive RCC in Japanese.
Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Anciano , Alelos , Pueblo Asiatico/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Grupos Control , Femenino , Frecuencia de los Genes , Genotipo , Crecimiento , Humanos , Japón , Neoplasias Renales/patología , Neoplasias Renales/fisiopatología , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: The purpose of this study was to determine the frequency of a polymorphism of the candidate metabolic enzyme N-acetyltransferase-2 (NAT2) in Japanese prostate cancer patients and Japanese non-cancer controls, in order to determine if an association exists between NAT2 genotype and the occurrence, clinical stage and grade of prostate cancer. METHODS: In the present case-control study, 111 patients with prostate cancer and 152 controls were genotyped for the NAT2 polymorphism using the polymerase chain reaction-based restriction fragment length polymorphism method. The NAT2 genotypes (slow or rapid acetylator genotype) were determined by the combination of three known NAT2 mutant alleles (M1, M2, M3) and the wild-type allele. RESULTS: The NAT2 slow acetylator genotype was statistically higher among prostate cancer patients (17.1%) compared with controls (8.6%) (Odds ration (OR) = 2.21; 95% confidence interval (CI), 1.04-4.69; P = 0.0289). In addition, there was a statistically increased risk of prostate cancer among smokers with the NAT2 slow genotype (OR = 3.78: 95% CI, 1.48-9.66; P = 0.0041). Furthermore, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with locally advanced and metastatic disease (22.7%) compared with controls (8.6%) (OR = 3.14; 95% CI, 1.40-7.06; P = 0.0051). Lastly, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with high-grade tumors (31.4%) compared with controls (8.6%) (OR = 4.90; 95% CI, 1.97-12.20; P = 0.0010). CONCLUSION: These data demonstrate that the NAT2 slow acetylator genotype plays an important role in determining the risk of developing prostate cancer in Japanese men and is also associated with more clinically advanced and pathologically aggressive disease. Furthermore, a possible interaction between the NAT2 slow acetylator genotype and smoking status was suggested.
Asunto(s)
Arilamina N-Acetiltransferasa/genética , Biomarcadores de Tumor/genética , Polimorfismo Genético , Neoplasias de la Próstata/genética , Acetilación , Anciano , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Japón/epidemiología , Masculino , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Neoplasias de la Próstata/enzimología , Factores de RiesgoRESUMEN
The pathway from averufin (AVR) to versiconal hemiacetal acetate (VHA) in aflatoxin biosynthesis was investigated by using cell-free enzyme systems prepared from Aspergillus parasiticus. When (1'S,5'S)-AVR was incubated with a cell extract of this fungus in the presence of NADPH, versicolorin A and versicolorin B (VB), as well as other aflatoxin pathway intermediates, were formed. When the same substrate was incubated with the microsome fraction and NADPH, hydroxyversicolorone (HVN) and VHA were formed. However, (1'R,5'R)-AVR did not serve as the substrate. In cell-free experiments performed with the cytosol fraction and NADPH, VHA, versicolorone (VONE), and versiconol acetate (VOAc) were transiently produced from HVN in the early phase, and then VB and versiconol (VOH) accumulated later. Addition of dichlorvos (dimethyl 2,2-dichlorovinylphosphate) to the same reaction mixture caused transient formation of VHA and VONE, followed by accumulation of VOAc, but neither VB nor VOH was formed. When VONE was incubated with the cytosol fraction in the presence of NADPH, VOAc and VOH were newly formed, whereas the conversion of VOAc to VOH was inhibited by dichlorvos. The purified VHA reductase, which was previously reported to catalyze the reaction from VHA to VOAc, also catalyzed conversion of HVN to VONE. Separate feeding experiments performed with A. parasiticus NIAH-26 along with HVN, VONE, and versicolorol (VOROL) demonstrated that each of these substances could serve as a precursor of aflatoxins. Remarkably, we found that VONE and VOROL had ring-opened structures. Their molecular masses were 386 and 388 Da, respectively, which were 18 Da greater than the molecular masses previously reported. These data demonstrated that two kinds of reactions are involved in the pathway from AVR to VHA in aflatoxin biosynthesis: (i) a reaction from (1'S,5'S)-AVR to HVN, catalyzed by the microsomal enzyme, and (ii) a new metabolic grid, catalyzed by a new cytosol monooxygenase enzyme and the previously reported VHA reductase enzyme, composed of HVN, VONE, VOAc, and VHA. A novel hydrogenation-dehydrogenation reaction between VONE and VOROL was also discovered.
Asunto(s)
Aflatoxinas/biosíntesis , Antraquinonas/metabolismo , Aspergillus/metabolismo , Antraquinonas/química , Aspergillus/crecimiento & desarrollo , Extractos Celulares , Citosol/metabolismoRESUMEN
BACKGROUND: E-cadherin is an epithelial cell adhesion molecule, and decreased E-cadherin expression in human prostate cancer is associated with tumor grade and advanced clinical stage. A -160 C-->A polymorphism in the promoter region of E-cadherin has been shown to decrease gene transcription. This allelic variation may be a potential genetic marker that can help identify those individuals at higher risk for invasive/metastatic disease. MATERIALS AND METHODS: We studied the effect of E-cadherin gene polymorphism on prostate cancer susceptibility in a case control study of 219 prostate cancer patients and 219 male controls, to determine whether this polymorphism is a biomarker for the risk and how aggressive the disease is. RESULTS: The genotype frequencies in the prostate cancer group were C/C: 0.607, C/A: 0.352, A/A: 0.041, and in the control group C/C: 0.671, C/A: 0.301, A/A: 0.027. A significant difference between the two groups was not found (p = 0.34), and the adjusted OR for A/A genotype was not statistically significant (OR = 1.66, 95% CI 0.58-4.78). Subdividing prostate cancer according to tumor differentiation and stage, we found no association between E-cadherin polymorphism and poor differentiation and invasiveness of prostate cancer. CONCLUSIONS: These data do not support an association between the E-cadherin genotype and the occurrence or progression of prostate cancer in Japanese populations.