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1.
Exp Parasitol ; 241: 108354, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36027930

RESUMEN

Atovaquone (ATV) has a growth inhibitory effect against Babesia gibsoni. The target site is considered mitochondria, as in the case of Plasmodium spp.; ATV would collapse the mitochondrial membrane potential. B. gibsoni has also reported that single nucleotide polymorphisms in cytochrome b of mitochondria are involved in ATV susceptibility. However, the details are still unknown. The study aim was to measure the mitochondrial membrane potential of B. gibsoni and evaluate the effect of ATV alone and combined with proguanil (PG) on the mitochondrial membrane potential. As a result of exposure of wild-type B. gibsoni to ATV alone, the number of cells with decreased mitochondrial membrane potential increased. When wild-type B. gibsoni was exposed to the ATV + PG combination, the peak value of mitochondrial membrane potential was larger than that when exposed to ATV alone. It was suggested that ATV alone affects the mitochondrial membrane potential of B. gibsoni, and the effect is enhanced by the combination of ATV and PG. The effect of ATV was weakened for B. gibsoni having reduced sensitivity to ATV (B. gibsoni with M121I), and the effect was not enhanced by the combination of ATV and PG. Although we still need to elucidate the mechanism of ATV and PG for B. gibsoni, these results strongly suggests that the target of ATV for B. gibsoni is also cytochrome b of mitochondria.


Asunto(s)
Babesiosis , Enfermedades de los Perros , Animales , Atovacuona/farmacología , Citocromos b/genética , Perros , Potencial de la Membrana Mitocondrial
2.
Drug Metab Dispos ; 46(1): 46-52, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29101097

RESUMEN

The constitutive androstane receptor (CAR) is a nuclear receptor that acts as a transcription factor for a variety of genes, including genes encoding xenobiotic, steroid, and drug-metabolizing enzymes and transporters. Transactivation of a target gene by a transcription factor is generally mediated through the concerted and stepwise recruitment of various proteins termed coregulators, including coactivators and corepressors. In this study, TRIM24 (also known as transcriptional intermediary factor 1 alpha) was found to interact with the CAR. TRIM24 enhanced the CAR-dependent transactivation in reporter assays using the direct repeat-4 motif, a binding site of the CAR. This enhancement was synergistically augmented in the presence of steroid receptor coactivator (SRC) 1 or SRC2, both of which are coactivators of the CAR. In addition, TRIM24 was recruited to the CAR-binding element of the CYP2B6 promoter together with the CAR. We also noted that knockdown of TRIM24 suppressed CAR-induced CYP2B6 mRNA expression in HepTR/CAR and HepaRG cells and suppressed CAR-induced CYP3A4 mRNA expression in HepaRG cells but not HepTR/CAR cells. From these results, we suggest that TRIM24 is a novel coactivator of the CAR that is involved in cell- and/or promoter- selective transactivation.


Asunto(s)
Proteínas Portadoras/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Activación Transcripcional , Proteínas Portadoras/genética , Receptor de Androstano Constitutivo , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Coactivador 1 de Receptor Nuclear/genética , Coactivador 1 de Receptor Nuclear/metabolismo , Coactivador 2 del Receptor Nuclear/genética , Coactivador 2 del Receptor Nuclear/metabolismo , Regiones Promotoras Genéticas/genética , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Receptores Citoplasmáticos y Nucleares/genética
3.
J Clin Lab Anal ; 32(3)2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28737838

RESUMEN

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) contributes to rapid identification of pathogens in the clinic but has not yet performed especially well for Gram-positive cocci (GPC) causing complicated urinary tract infection (UTI). The goal of this study was to investigate the possible clinical use of MALDI-TOF MS as a rapid method for bacterial identification directly from urine in complicated UTI. METHODS: MALDI-TOF MS was applied to urine samples gathered from 142 suspected complicated UTI patients in 2015-2017. We modified the standard procedure (Method 1) for sample preparation by adding an initial 10 minutes of ultrasonication followed by centrifugation at 500 g for 1 minutes to remove debris such as epithelial cells and leukocytes from the urine (Method 2). RESULTS: In 133 urine culture-positive bacteria, the rate of corresponded with urine culture in GPC by MALDI-TOF MS in urine with standard sample preparation (Method 1) was 16.7%, but the modified sample preparation (Method 2) significantly improved that rate to 52.2% (P=.045). Method 2 also improved the identification accuracy for Gram-negative rods (GNR) from 77.1% to 94.2% (P=.022). The modified Method 2 significantly improved the average MALDI score from 1.408±0.153 to 2.166±0.045 (P=.000) for GPC and slightly improved the score from 2.107±0.061 to 2.164±0.037 for GNR. CONCLUSION: The modified sample preparation for MALDI-TOF MS can improve identification accuracy for complicated UTI causative bacteria. This simple modification offers a rapid and accurate routine diagnosis for UTI, and may possibly be a substitute for urine cultures.


Asunto(s)
Bacterias/química , Tipificación Molecular/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Carga Bacteriana , Humanos , Orina/microbiología
4.
Mol Vis ; 23: 52-59, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28331281

RESUMEN

PURPOSE: Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells. METHODS: The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h). The expression of the factors involved in the unfolded protein response pathway was examined using quantitative real-time reverse transcription (RT)-PCR and immunoblot analysis. The aggregation of short-wavelength opsin (S-opsin) in the murine photoreceptor cells was observed with immunostaining. The effect of S-opsin knockdown on ATF4 expression in the murine photoreceptor cell line was also investigated. RESULTS: Exposure to blue LED light increased the bip, atf4, and grp94 mRNA levels, induced the expression of ATF4 protein, and increased the levels of ubiquitinated proteins. Exposure to blue LED light in combination with ER stress inducers (tunicamycin and dithiothreitol) induced the aggregation of S-opsin. S-opsin mRNA knockdown prevented the induction of ATF4 expression in response to exposure to blue LED light. CONCLUSIONS: These findings indicate that the aggregation of S-opsin induced by exposure to blue LED light causes ER stress, and ATF4 activation in particular.


Asunto(s)
Factor de Transcripción Activador 4/metabolismo , Luz , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patología , Opsinas de Bastones/metabolismo , Animales , Línea Celular , Ditiotreitol/farmacología , Técnicas de Silenciamiento del Gen , Ratones Endogámicos C57BL , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/efectos de la radiación , Poliubiquitina/metabolismo , Agregado de Proteínas/efectos de los fármacos , Agregado de Proteínas/efectos de la radiación , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Tunicamicina/farmacología , Ubiquitinación/efectos de los fármacos , Ubiquitinación/efectos de la radiación , Respuesta de Proteína Desplegada/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de la radiación
5.
Brain Behav Evol ; 90(3): 224-231, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28850945

RESUMEN

The olfactory system of mammals comprises a main olfactory system that detects hundreds of odorants and a vomeronasal system that detects specific chemicals such as pheromones. The main (MOB) and accessory (AOB) olfactory bulbs are the respective primary centers of the main olfactory and vomeronasal systems. Most mammals including artiodactyls possess a large MOB and a comparatively small AOB, whereas most cetaceans lack olfactory bulbs. The common hippopotamus (Hippopotamus amphibius) is semiaquatic and belongs to the order Cetartiodactyla, family Hippopotamidae, which seems to be the closest extant family to cetaceans. The present study evaluates the significance of the olfactory system in the hippopotamus by histologically analyzing the MOB and AOB of a male common hippopotamus. The MOB comprised six layers (olfactory nerve, glomerular, external plexiform, mitral cell, internal plexiform, and granule cell), and the AOB comprised vomeronasal nerve, glomerular, plexiform, and granule cell layers. The MOB contained mitral cells and tufted cells, and the AOB possessed mitral/tufted cells. These histological features of the MOB and the AOB were similar to those in most artiodactyls. All glomeruli in the AOB were positive for anti-Gαi2, but weakly positive for anti-Gαo, suggesting that the hippopotamus vomeronasal system expresses vomeronasal type 1 receptors with a high affinity for volatile compounds. These findings suggest that the olfactory system of the hippopotamus is as well developed as that of other artiodactyl species and that the hippopotamus might depend on its olfactory system for terrestrial social communication.


Asunto(s)
Artiodáctilos/anatomía & histología , Bulbo Olfatorio/anatomía & histología , Bulbo Olfatorio/citología , Animales , Masculino , Neuronas , Nervio Olfatorio/fisiología , Vías Olfatorias/anatomía & histología , Vías Olfatorias/fisiología , Olfato/fisiología
6.
BMC Ophthalmol ; 17(1): 161, 2017 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-28851319

RESUMEN

BACKGROUND: Lutein and zeaxanthin are suggested micronutrient supplements to prevent the progression of age-related macular degeneration (AMD), a leading cause of blindness worldwide. To monitor the levels of lutein/zeaxanthin in the macula, macular pigment optical density (MPOD) is measured. A commercially available device (MPSII®, Elektron Technology, Switzerland), using technology based on heterochromatic flicker photometry, can measure both absolute and estimated values of MPOD. However, whether the estimated value is applicable to Asian individuals and/or AMD patients remains to be determined. METHODS: The absolute and estimated values of MPOD were measured using the MPSII® device in 77 participants with a best-corrected visual acuity (BCVA) > 0.099 (logMAR score). RESULTS: The studied eyes included 17 young (20-29 years) healthy, 26 aged (>50 years) healthy, 18 aged and AMD-fellow, and 16 aged AMD eyes. The mean BCVA among the groups were not significantly different. Both absolute and estimated values were measurable in all eyes of young healthy group. However, absolute values were measurable in only 57.7%, 66.7%, and 43.8%, of the aged healthy, AMD-fellow, and AMD groups, respectively, and 56.7% of the eyes included in the 3 aged groups. In contrast, the estimated value was measurable in 84.6%, 88.9% and 93.8% of the groups, respectively, and 88.3% of eyes in the pooled aged group. The estimated value was correlated with absolute value in individuals from all groups by Spearman's correlation coefficient analyses (young healthy: R2 = 0.885, P = 0.0001; aged healthy: R2 = 0.765, P = 0.001; AMD-fellow: R2 = 0.851, P = 0.0001; and AMD: R2 = 0.860, P = 0.013). Using the estimated value, significantly lower MPOD values were found in aged AMD-related eyes, which included both AMD-fellow and AMD eyes, compared with aged healthy eyes by Student's t-test (P = 0.02). CONCLUSIONS: Absolute, in contrast to estimated, value was measurable in a limited number of aged participants; however, it was correlated with estimated value both in young and aged Asian populations with or without AMD. These results may inform future clinical studies investigating the measurement of MPOD in understanding the role of macular pigments in the pathogenesis of AMD.


Asunto(s)
Pueblo Asiatico , Luteína/metabolismo , Degeneración Macular/metabolismo , Retina/fisiología , Zeaxantinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Kansenshogaku Zasshi ; 91(1): 14-9, 2017 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-30277682

RESUMEN

Carbapenem-resistant Enterobacteriaceae (CRE) are increasing globally. Particularly, carbapenemase-producing Enterobacteriaceae (CPE) are of concern. Rapid and accurate detection of these strains is critical for appropriate antimicrobial use and hospital infection control. In the present study, criteria for CPE screening were examined using a carbapenem susceptibility disk. Carbapenemase producers showed minimal inhibition zones for faropenem (5 µg): 6-12 mm (mean: 6.9 mm). Some strains with the IMP-6 genotype showed inhibition zones of >30 mm for imipenem (10 µg) and biapenem (10 µg). All strains that formed inhibition zones for FRPM had the IMP-6 genotype. The cut off values of carbapenemase-producers, determined by ROC analysis, were 12 mm for FRPM, 24 mm for meropenem (10 µg), 29 mm for BIPM, 25 mm for doripenem (10 µg), 26 mm for IPM, and 24 mm for panipenem (10 µg). Thus, the sensitivity was the highest (100%) for FRPM. Specificities were 93.44% for MEPM and DRPM and 85.25% for FRPM. Consequently, a drug sensitivity test using FRPM (5 µg) disks facilitates simple and accurate CPE screening.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Proteínas Bacterianas/biosíntesis , Enterobacteriaceae Resistentes a los Carbapenémicos/metabolismo , Difusión , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/biosíntesis
8.
BMC Infect Dis ; 16(1): 427, 2016 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-27538488

RESUMEN

BACKGROUND: ESBL (Extended spectrum beta-lactamase) producing enterobacteriaceae are challenging organisms with little treatment options. Carbapenems are frequently used, but the emergence of carbapenem resistant enterobacteriaceae is a concerning issue, which may hinder the use of carbapenems. Although cephamycins such as cefoxitin, cefmetazole or cefotetan are effective against ESBL-producers in vitro, there are few clinical data demonstrating effects against bacteremia caused by these organisms. METHODS: We performed a retrospective observational study on cases of bacteremia caused by ESBL-producers to investigate the efficacy of cefmetazole compared with carbapenems. We also evaluated whether the trend of antibiotic choice changed over years. RESULTS: Sixty-nine patients (male 34, age 69.2 ± 14.4), including two relapse cases, were reviewed for this analysis. The most common causative organisms were Escherichia coli (64, 93 %), followed by Klebsiella pneumoniae and K. oxytoca (2 each, 4 %). The group that received carbapenem therapy (43, 62 %) had increased severity in the Pittsburgh Bacteremic score than the group that received cefmetazole therapy, (1.5 ± 1.5 vs 2.5 ± 2.1, p = 0.048), while analysis of other factors didn't reveal any statistical differences. Five patients in the carbapenem group and one patient in the cefmetazole group died during the observation period (p = 0.24). CTX-M-9 were predominant in this series (59 %). Infectious disease physicians initially recommended carbapenems at the beginning of the current research period, which gradually changed over time favoring the use of cefmetazole instead (p = 0.002). CONCLUSION: Cefmetazole may be safely given to patients with bacteremia caused by ESBL-producers as a definitive therapy, if one can select out relatively stable patients.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Carbapenémicos/uso terapéutico , Cefmetazol/uso terapéutico , Enterobacteriaceae/enzimología , beta-Lactamasas/metabolismo , Anciano , Bacteriemia/microbiología , Farmacorresistencia Bacteriana , Escherichia coli/aislamiento & purificación , Femenino , Humanos , Klebsiella oxytoca/aislamiento & purificación , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología
9.
Nutr Neurosci ; 19(1): 32-42, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26304685

RESUMEN

OBJECTIVES: The pathogenesis of Alzheimer's disease (AD) is strongly correlated with the aggregation and deposition of the amyloid beta (Aß1-42) peptide in fibrillar form, and many studies have shown that plant-derived polyphenols are capable of attenuating AD progression in various disease models. In this study, we set out to correlate the effects of anthocyanoside extracts (Vaccinium myrtillus anthocyanoside (VMA)) obtained from bilberry on the in vitro progression of Aß fibril formation with the in vivo effects of this compound on AD pathogenesis. METHODS: Thioflavin T fluorescence assays and atomic force microscopy were used to monitor Aß amyloid formation in in vitro assays. Effects of Aß amyloids on cellular viability were assayed using cultured Neuro2a cells. Cognitive effects were probed using mice that simultaneously expressed mutant human Aß precursor and mutant presenilin-2. RESULTS: Addition of VMA inhibited the in vitro formation of Aß peptide fibrils and also reduced the toxicity of these aggregates toward Neuro2a cells. A diet containing 1% VMA prevented the cognitive degeneration in AD mice. Curiously, this diet-derived retention of cognitive ability was not accompanied by a reduction in aggregate deposition in brains; rather, an increase in insoluble deposits was observed compared with mice raised on a control diet. DISCUSSION: The paradoxical increase in insoluble deposits caused by VMA suggests that these polyphenols divert Aß aggregation to an alternate, non-toxic form. This finding underscores the complex effects that polyphenol compounds may exert on amyloid deposition in vivo.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Antocianinas/farmacología , Fragmentos de Péptidos/metabolismo , Extractos Vegetales/farmacología , Amiloide/antagonistas & inhibidores , Péptidos beta-Amiloides/genética , Animales , Benzotiazoles , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Línea Celular Tumoral , Cognición/efectos de los fármacos , Trastornos del Conocimiento/prevención & control , Femenino , Humanos , Masculino , Ratones , Microscopía de Fuerza Atómica , Fragmentos de Péptidos/genética , Polifenoles/farmacología , Tiazoles/metabolismo , Vaccinium myrtillus/química
10.
Histopathology ; 66(6): 816-23, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25066097

RESUMEN

AIMS: Pulmonary ground-glass nodules (GGNs) are frequently observed. Histopathologically, their presentation can indicate a wide range of disorders from an inflammatory process to malignancy. An accurate diagnosis based on GGNs can sometimes be challenging on small-sized biopsies. Mutations in the EGFR gene are detected in pulmonary adenocarcinomas (ADCs). Immunohistochemical analysis using antibodies that detect specific EGFR mutations has been shown to correlate with mutational status as determined by molecular methods. We hypothesized that these antibodies could be used to discriminate between ADCs and benign pneumocyte hyperplasias. METHODS AND RESULTS: Surgically resected, pre-invasive to invasive lung ADC (n = 32) and reactive pneumocyte hyperplasia (n = 40) tissue samples were probed with antibodies against EGFR mutations, p53, Mouse double minute 2 and 14-3-3 sigma. Of the 32 lung ADC specimens analysed, 12 (38%) were positive using the EGFR mutation-specific antibodies, while no immunoreactivity was observed in reactive pneumocyte hyperplasia specimens. Analyses of receiver operating characteristic curves showed that the highest area under the curve values were associated with the use of EGFR mutation-specific antibodies. In addition, a high concordance rate was observed between surgically resected and corresponding biopsy materials using these antibodies. CONCLUSIONS: EGFR mutation-specific antibodies can be used to discriminate between lung ADC and benign pneumocyte hyperplasia, even in small-sized biopsies.


Asunto(s)
Adenocarcinoma/diagnóstico , Anticuerpos Monoclonales/inmunología , Receptores ErbB/genética , Enfermedades Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico , Mutación , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Células Epiteliales Alveolares/patología , Área Bajo la Curva , Diagnóstico Diferencial , Humanos , Hiperplasia/diagnóstico , Inmunohistoquímica , Pulmón/patología , Neoplasias Pulmonares/genética , Curva ROC , Sensibilidad y Especificidad
11.
Retina ; 35(4): 820-6, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25473786

RESUMEN

PURPOSE: To analyze the association between macular pigment optical density (MPOD), which reflects lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) in the macula, and background characteristics. METHODS: Fifty-five healthy adult volunteers were analyzed. Macular pigment optical density was measured using a heterochromatic flicker photometry technique, and serum concentrations of carotenoids and lipoproteins were by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Dietary intake of nutrient was determined by a validated self-administered questionnaire on ingestion frequency. RESULTS: Macular pigment optical density was positively correlated with serum concentrations of L and Z and dietary L intake and inversely correlated with serum oxidized low-density lipoprotein (LDL). Although MPOD decreased with age (95% confidence interval, -0.011 to -0.002; correlation coefficient, -0.269; P = 0.007), serum L/Z and dietary L intake did not. In contrast, serum oxidized LDL was positively correlated with age (95% confidence interval, 0.69-2.34; correlation coefficient, 0.333; P = 0.0004). After adjusting for age, sex, and oxidized LDL, serum L was positively correlated with MPOD (95% confidence interval, 0.88-1.69; P = 0.000001). After adjusting for age, sex, and serum L, serum oxidized LDL was inversely correlated with MPOD (95% confidence interval, -0.002 to -0.0004; P = 0.006). CONCLUSION: Macular pigment optical density was inversely correlated with serum oxidized LDL. Further study to know the impact of oxidized LDL on MPOD may be warranted.


Asunto(s)
Lipoproteínas LDL/sangre , Luteína/análisis , Mácula Lútea/química , Pigmento Macular/análisis , Zeaxantinas/análisis , Adulto , Cromatografía Líquida de Alta Presión , Densitometría , Ensayo de Inmunoadsorción Enzimática , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Fotometría/métodos , Encuestas y Cuestionarios , Adulto Joven
12.
Biochem Biophys Res Commun ; 446(2): 535-40, 2014 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-24613837

RESUMEN

The mechanism by which lutein, a carotenoid, acts as an antioxidant in retinal cells is still not fully understood. Here, lutein treatment of a neuronal cell line (PC12D) immediately resulted in reduced intracellular ROS levels, implying that it has a direct role in ROS scavenging. Significantly, lutein treatment also induced phase II antioxidative enzyme expression, probably via a nuclear factor-like 2 (Nrf2) independent pathway. This latter mechanism could explain why lutein acts diversely to protect against oxidative/cytotoxic stress, and why it is physiologically involved in the human neural tissue, such as the retina.


Asunto(s)
Carotenoides/farmacología , Luteína/farmacología , Neuronas/enzimología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Humanos , Factor 2 Relacionado con NF-E2 , Neuronas/efectos de los fármacos , Células PC12 , Ratas
13.
Biosci Biotechnol Biochem ; 78(10): 1748-52, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25273141

RESUMEN

Practical application of flavonoid-poor menus was evaluated on the bioavailability of anthocyanins as model flavonoids. Detectable amounts of flavonoids were not found in plasma and urine collected from 13 participants, who took the menus. After ingesting bilberry anthocyanins (919 µmol), average plasma AUC0-6h, Cmax, Tmax values and urinary recovery were 386.0 nmol h/mL, 139.1 nM, 1.31 h and 0.21%, respectively.


Asunto(s)
Antocianinas/farmacocinética , Flavonoides/análisis , Comidas , Vaccinium myrtillus/química , Adulto , Antocianinas/sangre , Antocianinas/orina , Disponibilidad Biológica , Humanos , Masculino , Factores de Tiempo
14.
BMC Complement Altern Med ; 14: 120, 2014 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-24690313

RESUMEN

BACKGROUND: Blue light is a high-energy or short-wavelength visible light, which induces retinal diseases such as age-related macular degeneration and retinitis pigmentosa. Bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea) contain high amounts of polyphenols (anthocyanins, resveratrol, and proanthocyanidins) and thus confer health benefits. This study aimed to determine the protective effects and mechanism of action of bilberry extract (B-ext) and lingonberry extract (L-ext) and their active components against blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage. METHODS: Cultured murine photoreceptor (661 W) cells were exposed to blue LED light following treatment with B-ext, L-ext, or their constituents (cyanidin, delphinidin, malvidin, trans-resveratrol, and procyanidin B2). 661 W cell viability was assessed using a tetrazolium salt (WST-8) assay and Hoechst 33342 nuclear staining, and intracellular reactive oxygen species (ROS) production was determined using CM-H2DCFDA after blue LED light exposure. Activation of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor-kappa B (NF-κB), and LC3, an ubiquitin-like protein that is necessary for the formation of autophagosomes, were analyzed using Western blotting. Caspase-3/7 activation caused by blue LED light exposure in 661 W cells was determined using a caspase-3/7 assay kit. RESULTS: B-ext, L-ext, NAC, and their active components improved the viability of 661 W cells and inhibited the generation of intracellular ROS induced by blue LED light irradiation. Furthermore, B-ext and L-ext inhibited the activation of p38 MAPK and NF-κB induced by blue LED light exposure. Finally, B-ext, L-ext, and NAC inhibited caspase-3/7 activation and autophagy. CONCLUSIONS: These findings suggest that B-ext and L-ext containing high amounts of polyphenols exert protective effects against blue LED light-induced retinal photoreceptor cell damage mainly through inhibition of ROS production and activation of pro-apoptotic proteins.


Asunto(s)
Luz , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Fitoterapia , Polifenoles/farmacología , Enfermedades de la Retina/metabolismo , Vaccinium myrtillus/química , Vaccinium vitis-Idaea/química , Animales , Antocianinas/química , Antocianinas/farmacología , Antocianinas/uso terapéutico , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Técnicas In Vitro , Ratones , FN-kappa B/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/efectos de la radiación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Polifenoles/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Retina/efectos de los fármacos , Retina/metabolismo , Retina/efectos de la radiación , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/etiología , Estilbenos/farmacología , Estilbenos/uso terapéutico , Sales de Tetrazolio , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Can Vet J ; 55(4): 366-8, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24688137

RESUMEN

A 13-year-old castrated male miniature dachshund dog was presented with chronic vomiting and diarrhea. Contrast radiography and surgical exploration revealed an ileal cyst, which was excised. A diagnosis of epidermoid cyst was made from a combination of the clinical findings and histological examination of the surgical specimen.


Kyste épidermoïde de l'iléon chez un chien Dachsund miniature. Un chien Dachsund miniature mâle castré âgé de 13 ans a été présenté avec des vomissements et de la diarrhée chroniques. Une radiographie à contraste et une exploration chirurgicale ont révélé un kyste iléal, qui a été excisé. Un diagnostic de kyste épidermoïde a été posé à partir d'une combinaison de constatations cliniques et de l'examen histologique du spécimen chirurgical.(Traduit par Isabelle Vallières).


Asunto(s)
Enfermedades de los Perros/patología , Quiste Epidérmico/veterinaria , Enfermedades del Íleon/veterinaria , Animales , Enfermedades de los Perros/cirugía , Perros , Quiste Epidérmico/patología , Quiste Epidérmico/cirugía , Enfermedades del Íleon/patología , Enfermedades del Íleon/cirugía , Masculino
16.
Biochemistry ; 52(51): 9202-11, 2013 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-24308332

RESUMEN

The co-chaperonin GroES (Hsp10) works with chaperonin GroEL (Hsp60) to facilitate the folding reactions of various substrate proteins. Upon forming a specific disordered state in guanidine hydrochloride, GroES is able to self-assemble into amyloid fibrils similar to those observed in various neurodegenerative diseases. GroES therefore is a suitable model system to understand the mechanism of amyloid fibril formation. Here, we determined the cytotoxicity of intermediate GroES species formed during fibrillation. We found that neuronal cell death was provoked by soluble intermediate aggregates of GroES, rather than mature fibrils. The data suggest that amyloid fibril formation and its associated toxicity toward cell might be an inherent property of proteins irrespective of their correlation with specific diseases. Furthermore, with the presence of anthocyanins that are abundant in bilberry, we could inhibit both fibril formation and the toxicity of intermediates. Addition of bilberry anthocyanins dissolved the toxic intermediates and fibrils, and the toxicity of the intermediates was thus neutralized. Our results suggest that anthocyanins may display a general and potent inhibitory effect on the amyloid fibril formation of various conformational disease-causing proteins.


Asunto(s)
Amiloide/antagonistas & inhibidores , Antocianinas/farmacología , Proteínas de Escherichia coli/antagonistas & inhibidores , Frutas/química , Proteínas de Choque Térmico/antagonistas & inhibidores , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Vaccinium myrtillus/química , Amiloide/efectos adversos , Amiloide/metabolismo , Amiloide/ultraestructura , Animales , Antiparkinsonianos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Suplementos Dietéticos/análisis , Proteínas de Escherichia coli/efectos adversos , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/ultraestructura , Proteínas de Choque Térmico/efectos adversos , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/ultraestructura , Potenciales de la Membrana/efectos de los fármacos , Ratones , Microscopía Electrónica de Transmisión , Peso Molecular , Neuronas/metabolismo , Neuronas/ultraestructura , Nootrópicos/farmacología , Extractos Vegetales/química , Pliegue de Proteína/efectos de los fármacos , Solubilidad
17.
BMC Biochem ; 14: 1, 2013 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-23289756

RESUMEN

BACKGROUND: The ubiquitin ligase COP1, COnstitutively Photomorphogenic 1, functions in many biological responses in mammalian cells, but its downstream pathway remains unclear. RESULTS: Here, we identified FIP200, a key regulator of mammalian autophagy, as a novel COP1-interacting protein by yeast two-hybrid screening. The interaction was confirmed by a GST-pulldown assay. Split-GFP analysis revealed that interaction between COP1 and FIP200 predominantly occurred in the cytoplasm and was enhanced in cells treated with UV irradiation. Different forms of FIP200 protein were expressed in cultured mammalian cells, and ectopic expression of COP1 reduced one of such forms. CONCLUSIONS: These data suggest that COP1 modulates FIP200-associated activities, which may contribute to a variety of cellular functions that COP1 is involved in.


Asunto(s)
Autofagia/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Proteínas Relacionadas con la Autofagia , Línea Celular , Citoplasma/metabolismo , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Células 3T3 NIH , Proteínas Nucleares/genética , Unión Proteica , Transducción de Señal , Técnicas del Sistema de Dos Híbridos , Ubiquitina-Proteína Ligasas/genética , Rayos Ultravioleta
18.
Lab Invest ; 92(1): 102-9, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21894150

RESUMEN

Anthocyanin-rich bilberry extract, a plant-derived antioxidant, has been utilized as a popular supplement for ocular health worldwide. However, it is unclear whether this extract has any biological effect on visual function, and the mechanism for such an effect is completely unknown. In this study, we generated a mouse model of endotoxin-induced uveitis (EIU) that shows retinal inflammation, as well as uveitis, by injecting lipopolysaccharide. We pretreated the mice with anthocyanin-rich bilberry extract and analyzed the effect on the retina. Anthocyanin-rich bilberry extract prevented the impairment of photoreceptor cell function, as measured by electroretinogram. At the cellular level, we found that the EIU-associated rhodopsin decreased and the shortening of outer segments in photoreceptor cells were suppressed in the bilberry-extract-treated animals. Moreover, the extract prevented both STAT3 activation, which induces inflammation-related rhodopsin decrease, and the increase in interleukin-6 expression, which activates STAT3. In addition to its anti-inflammatory effect, the anthocyanin-rich bilberry extract ameliorated the intracellular elevation of reactive oxygen species and activated NF-κB, a redox-sensitive transcription factor, in the inflamed retina. Our findings indicate that anthocyanin-rich bilberry extract has a protective effect on visual function during retinal inflammation.


Asunto(s)
Antocianinas/farmacología , Retinitis/tratamiento farmacológico , Visión Ocular/efectos de los fármacos , Animales , Endotoxinas/toxicidad , Ratones , Ratones Endogámicos C57BL , FN-kappa B/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales , Retinitis/fisiopatología , Factor de Transcripción STAT3/metabolismo , Uveítis/tratamiento farmacológico , Vaccinium myrtillus
19.
No Shinkei Geka ; 40(12): 1087-93, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23180746

RESUMEN

Awake surgery for lesions in the non-dominant parietal lobe is rare. We report two cases of right parietal lobe glioma for which awake surgery was performed in order to avoid ataxie optique and hemispatial neglect due to injury in the superior and inferior parietal lobule, respectively. Among several tests to assess the dysfunction of spatial recognition, line bisection test was selected for the task during awake surgery because of its simplicity, easy repetition, and utility. The tumor was successfully removed without any neurological deficit in both the cases. The line bisection test is simple and useful for preserving spatial recognition during an awake surgery.


Asunto(s)
Neoplasias Encefálicas/cirugía , Glioma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Lóbulo Parietal/cirugía , Vigilia , Anciano , Mapeo Encefálico/métodos , Neoplasias Encefálicas/patología , Femenino , Lateralidad Funcional , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Parietal/patología , Percepción Espacial/fisiología , Resultado del Tratamiento
20.
J Feline Med Surg ; 24(12): e505-e512, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36383208

RESUMEN

OBJECTIVES: Lipids containing n-3 fatty acids have been reported to have protective effects on renal function, with docosahexaenoic acid (DHA) expected to be particularly effective. However, no reports have demonstrated the renoprotective effects of DHA-enriched lipids in cats with chronic kidney disease (CKD). Therefore, the aim of this pilot study was to examine the renoprotective effects of DHA-enriched fish oil in cats. METHODS: Five healthy cats and five cats with early non-azotaemic CKD due to autosomal dominant polycystic kidney disease (PKD) were orally administered DHA-enriched fish oil in liquid form (250 or 500 mg/kg body weight [BW] and 250 mg/kg BW of DHA, respectively) for 28 days. Inappropriately dilute urine and markedly increased urinary N-acetyl-d-glucosamine (NAG) index were detected in cats with PKD before DHA-enriched fish oil administration. Changes in the fatty acid composition ratio in the blood of all 10 cats were assessed after orally administering 250 mg/kg of DHA. RESULTS: Post-administration, no adverse clinical effects were observed, and blood and urine tests were within the reference intervals in healthy cats. Cats with PKD showed significantly decreased serum symmetric dimethylarginine (SDMA), urine protein:creatinine ratio (UPC) and urinary NAG index at post-administration. Furthermore, oral administration of DHA-enriched fish oils significantly decreased the blood concentration ratio of arachidonic acid (AA) in cats with PKD post-administration. Furthermore, the concentration ratio of DHA in the blood significantly increased in both healthy cats and cats with PKD, and the DHA:AA ratio also increased. CONCLUSIONS AND RELEVANCE: Oral administration of DHA-enriched fish oils for 28 days significantly decreased blood AA levels and significantly increased DHA concentration and DHA:AA ratios in cats with PKD, and improved the SDMA, UPC and urinary NAG index, suggesting its potential for renoprotective effects in cats with early non-azotaemic CKD due to PKD.


Asunto(s)
Enfermedades de los Gatos , Enfermedades Renales Poliquísticas , Insuficiencia Renal Crónica , Gatos , Animales , Ácidos Docosahexaenoicos/uso terapéutico , Proyectos Piloto , Estado de Salud , Enfermedades Renales Poliquísticas/veterinaria , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/veterinaria , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/prevención & control
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