RESUMEN
BACKGROUND: Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel. CASE PRESENTATION: A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency. CONCLUSION: Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.
Asunto(s)
Epilepsias Mioclónicas , Hipertermia Inducida , Masculino , Humanos , Adulto Joven , Adulto , Zonisamida/uso terapéutico , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/genética , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Canal de Sodio Activado por Voltaje NAV1.1/genética , Ácido Valproico/uso terapéutico , Hipertermia/tratamiento farmacológico , Anticonvulsivantes/uso terapéuticoRESUMEN
Unloading stress enhances oxidative stress, which in turn induces disuse muscle atrophy. This study evaluated the suppressive effect of lemon peel extract containing eriocitrin on muscle atrophy. Both lemon peel extract and eriocitrin suppressed weight loss in the gastrocnemius muscle under denervation in C57BL/6 mice. The mRNA level of ubiquitin ligases and their transcription factor were downregulated by eriocitrin. Eriocitrin inhibited the increase in lipid peroxidation and the ratio of glutathione disulfide/glutathione. These data suggest that eriocitrin ameliorated disuse muscle atrophy by suppressing the expression of ubiquitin ligase genes by its antioxidative effect.
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Citrus/química , Flavanonas/farmacología , Proteínas Musculares/metabolismo , Atrofia Muscular/tratamiento farmacológico , Proteínas Ligasas SKP Cullina F-box/metabolismo , Animales , Frutas/química , Peroxidación de Lípido , Masculino , Ratones Endogámicos C57BL , Estructura Molecular , Desnervación Muscular , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo , Extractos Vegetales/químicaRESUMEN
A critical factor for preventing osteoporosis after menopause is attenuation of the accelerated turnover rate of bone metabolism. The present randomized controlled study was conducted to clarify the effects of a lemon beverage with calcium (Ca) supplementation that makes use of the chelating action of citric acid. Comprehensive evaluations of bone were performed by assessments of bone mineral density (BMD) and biomarkers related to bone turnover. Seventy-nine postmenopausal women were enrolled and asked to participate in an 11-month continuous intake of the test beverages. The subjects were divided into three groups: those who consumed a lemon beverage containing citric acid with Ca supplementation (LECA group), those who consumed a lemon beverage containing citric acid without Ca supplementation (LE group), and those who consumed no test beverage (control group). Using a double-blind protocol, subjects in the LECA and LE groups consumed one bottle containing 290 mL of the test beverage each day. The ratio of change in BMD after 11 months was significantly higher in the LECA group as compared to the control and LE groups. The LECA group also showed significant decreases in concentrations of tartrate-resistant acid phosphatase 5b (TRACP-5b), a bone resorption marker, and bone alkaline phosphatase (BAP) as compared to the other groups, as well as a significant decrease in concentration of osteocalcin (OC), a bone formation marker, as compared to the LE group. Based on our findings, we speculated that bone resorption and bone formation in postmenopausal women might be suppressed along with an increase in Ca resorption caused by chelation of citric acid in association with continuous ingestion of a Ca-supplemented lemon beverage containing citric acid, resulting in suppression of high bone metabolic turnover. In addition, the results provide information regarding BMD maintenance in the bones of the trunk, including the lumbar spine and proximal femur.
RESUMEN
BACKGROUND: Radiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life. The aim of this clinical trial is to determine the efficacy of oral 5-aminolevulinic acid (ALA) phosphate with sodium ferrous citrate (SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. METHODS: The AMBER study is a prospective, single-center trial in patients with localized prostate cancer undergoing LDR-BT. Patients who undergo supplementary extra-beam radiotherapy are excluded, whereas those who undergo pre-implantation short-term (4-6 months) androgen deprivation therapy to decrease the prostate volume and/or improve oncological outcomes are included. After the screening and registration, the patients will be instructed to take capsules of ALA-SFC twice a day (200 mg and 229.42 mg per day) for 6 months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data will be collected before the implantation; during oral ALA-SFC treatment; and 1, 3, 6, 9, and 12 month(s) after seed implantation. The primary endpoint of this trial is the urinary frequency 3 months after seed implantation. At each visit, the 24-h urinary frequency, total voided volume, and mean voided volume on a frequency volume chart and other patient-reported outcomes are recorded. The data of the trial cases will be compared with those of historical controls, who are consecutive patients undergoing LDR-BT without supplementary extra-beam radiotherapy between January 2016 and January 2019. The number of subjects has been set to be 50 for trial cases and 150 for the historical control cases. Pre- and post-treatment clinicopathologic factors are compared between two groups. DISCUSSION: The goal of this trial is to determine the potential benefit of ALA-SFC in patients who undergo LDR-BT. To the best of our knowledge, this is the first study investigating the potential clinical benefit of oral ALA-SFC after radiotherapy. More evidence from a further randomized controlled trial is needed to change the standard of care and lead to better post-radiotherapy management. TRIAL REGISTRATION: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 5 December 2019. The reference number is jRCTs051190077, nara0013 (Certified Review Board of Nara Medical University).
RESUMEN
Candida albicans, one of the main pathogens in the oral cavity, is involved in the development of oral candidiasis. Various components of tea, and especially polyphenols, are believed to be effective against the growth of yeast or bacteria. The purpose of this study was to investigate the effect of polyphenols in Mongolian herbal tea on growth of C. albicans. Tea extract was prepared from Mongolian herbal tea and diluted with distilled water (DW) at concentrations of 10, 20, 30, 40, or 50%. Distilled water was used as the control. Acidification of the medium was determined by measuring its pH; the presence of polyphenols by the Folin-Ciocalteau colorimetric method; and growth of C. albicans by absorbance at a wavelength of 630 nm at 0-, 6-, 12-, and 24-hr intervals. The pH of the medium was 5.2 to 5.27 in all experimental groups compared with 7.1 in the control group. Polyphenols were present in all experimental groups, and at significantly higher levels than in the control group. Growth of C. albicans showed a significant and time-dependent increase in the control and all experimental groups. Growth of C. albicans in all the experimental groups was higher than that in the control group. These results suggest that Mongolian herbal tea promotes the growth of C. albicans, despite the presence of polyphenols.
Asunto(s)
Candida albicans/efectos de los fármacos , Extractos Vegetales/farmacología , Tés de Hierbas , Candida albicans/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Concentración de Iones de Hidrógeno , Pruebas de Sensibilidad MicrobianaRESUMEN
The common marmoset (Callithrix jacchus) is a nonhuman primate that is used for preclinical research on stem cell transplantation therapies due to its similarity to human beings as well as its small size, enabling researchers to perform experiments without preparing a large number of cells. In this study, we developed a marmoset hepatic fibrosis model for regenerative medicine research. Six female marmosets aged 4-6 years were administered thioacetamide (TAA) at a dose of 2.5-40 mg/kg two or three times a week. Hepatic fibrosis was assessed by liver biopsy when blood chemistry indicated liver damage. Administration of TAA increased total bile acid, aspartate aminotransferase, and total bilirubin and decreased serum albumin levels. Following more than 11 weeks of continuous injection of TAA, histological analyses detected hepatic fibrosis in all animals. Type IV collagen 7S serum levels in animals with hepatic fibrosis were significantly higher than in normal animals as a possible marker of hepatic fibrosis in marmosets. Serial liver biopsies following the last administration of TAA revealed that induced fibrosis remained up to 11 weeks. The results suggest that continuous TAA administration induces persistent hepatic fibrosis in the common marmoset and this nonhuman primate hepatic fibrosis model have the possibility to evaluate the therapeutic effects of test samples to ameliorate hepatic fibrosis.
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Callithrix , Modelos Animales de Enfermedad , Cirrosis Hepática/inducido químicamente , Tioacetamida/efectos adversos , Animales , Biomarcadores/sangre , Colágeno Tipo IV/sangre , Evaluación Preclínica de Medicamentos , Femenino , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Medicina Regenerativa , Tioacetamida/administración & dosificaciónRESUMEN
Coffee consumption reduces the risk of type 2 diabetes in humans, but the mechanism remains unclear. In this study, we investigated the effect of coffee on pancreatic ß-cells in the induction of diabetes by streptozotocin (STZ) treatment in mice. We examined the effect of coffee, caffeine, or decaffeinated coffee ingestion on STZ-induced hyperglycemia. After STZ injection in Exp. 1 and 2, serum glucose concentration and water intake in coffee ingestion (Coffee group) tended to be lowered or was significantly lowered compared to those in water ingestion (Water group) instead of coffee. In Exp. 1, the values for water intake and serum glucose concentration in caffeine ingestion (Caffeine group) were similar to those in the Water group. In Exp. 2, serum glucose concentrations in the decaffeinated coffee ingestion (Decaf group) tended to be lower than those in the Water group. Pancreatic insulin contents tended to be higher in the Coffee and Decaf groups than in the Water group (Exp. 1 and 2). In Exp. 3, subsequently, we showed that coffee ingestion also suppressed the deterioration of hyperglycemia in diabetic mice which had been already injected with STZ. This study showed that coffee ingestion prevented the development of STZ-induced diabetes and suppressed hyperglycemia in STZ-diabetic mice. Caffeine or decaffeinated coffee ingestion did not significantly suppress STZ-induced hyperglycemia. These results suggest that the combination of caffeine and other components of decaffeinated coffee are needed for the preventive effect on pancreatic ß-cell destruction. Coffee ingestion may contribute to the maintenance of pancreatic insulin contents.
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Café , Diabetes Mellitus Experimental/prevención & control , Hiperglucemia/sangre , Animales , Glucemia/metabolismo , Cafeína/farmacología , Hiperglucemia/prevención & control , Insulina/sangre , Células Secretoras de Insulina/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacosRESUMEN
Common marmosets (Callithrix jacchus) are potentially primate models for preclinical drug metabolism studies because there are similarities in the molecular characteristics of cytochrome P450 enzymes between this species and humans. However, characterization of non-cytochrome P450 enzymes has not been clarified in marmosets. Here, we report characterization of flavin-containing monooxygenases FMO1-FMO5 identified in marmoset tissues. Marmoset FMO forms shared high amino acid sequence identities (93%-95%) and phylogenetic closeness with human homologous FMO forms. FMO1 and FMO3 mRNA were abundantly expressed in the liver and kidneys among five marmoset tissues examined, where FMO3 protein was detected by immunoblotting. FMO inhibition assays using preheated tissue microsomes indicated that benzydamine N-oxygenation and sulindac sulfide S-oxygenation in the marmoset liver was mainly catalyzed by FMO3, the major hepatic FMO. Marmoset FMO3 protein heterologously expressed in Escherichia coli effectively catalyzed benzydamine N-oxygenation and sulindac sulfide S-oxygenation comparable to marmoset liver microsomes. These results indicate that the FMO3 enzyme expressed in marmoset livers mainly metabolizes benzydamine and sulindac sulfide (typical human FMO substrates), suggesting its importance for FMO-dependent drug metabolism in marmosets.
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Bencidamina/farmacocinética , Callithrix , Hígado/enzimología , Oxigenasas/metabolismo , Sulindac/análogos & derivados , Secuencia de Aminoácidos , Animales , Callithrix/genética , Callithrix/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Escherichia coli/genética , Femenino , Calor , Humanos , Masculino , Microsomas Hepáticos/enzimología , Especificidad de Órganos , Oxigenasas/genética , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Sulindac/farmacocinéticaRESUMEN
This study followed three field-scale hybrid subsurface flow constructed wetland (CW) systems constructed in Hokkaido, northern Japan: piggery O (2009), dairy G (2011), and dairy S (2006). Treatment performance was monitored from the outset of operation for each CW. The ranges of overall purification efficiency for these systems were 70-86%, 40-85%, 71-90%, 91-96%, 94-98%, 84-97%, and 70-97% for total N (TN), NH4-N, total P, chemical oxygen demand (COD), biochemical oxygen demand, suspended solid, and total Coliform, respectively. The hybrid system's removal rates were highest when influent loads were high. COD removal rates were 46.4 ± 49.2, 94.1 ± 36.6, and 25.1 ± 15.5â g COD m-2 d-1 in piggery O, dairy G, and dairy S, with average influent loads of 50.5 ± 51.5, 98.9 ± 37.1, and 26.9 ± 16.0â g COD m-2 d-1, respectively. The systems had overall COD removal efficiencies of around 90%. TN removal efficiencies were 62 ± 19%, 82 ± 9%, and 82 ± 15% in piggery O, dairy G, and dairy S, respectively. NH4-N removal efficiency was adversely affected by the COD/TN ratio. Results from this study prove that these treatment systems have sustained and positive pollutant removal efficiencies, which were achieved even under extremely cold climate conditions and many years after initial construction.
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Crianza de Animales Domésticos , Industria Lechera , Eliminación de Residuos Líquidos/métodos , Humedales , Compuestos de Amonio/análisis , Animales , Análisis de la Demanda Biológica de Oxígeno , Clima Frío , Enterobacteriaceae/aislamiento & purificación , Nitratos/análisis , Nitritos/análisis , Nitrógeno/análisis , Fósforo/análisis , Poaceae , Porcinos , Aguas Residuales/análisis , Contaminantes del Agua/análisisRESUMEN
BACKGROUND: Common marmosets (Callithrix jacchus) and cynomolgus monkeys (Macaca fascicularis) are used as non-human primate models in preclinical studies for drug development. OBJECTIVE: The assessment of P450 induction in hepatocytes from marmosets and cynomolgus monkeys was performed using typical P450 inducers. METHODS: Induction of cytochrome P450 1-4 family enzymes was analyzed in two lots of cultured hepatocytes from common marmosets and cynomolgus monkeys after 24-h treatment with typical human P450 inducing agents by real-time reverse transcription-polymerase chain reaction. RESULTS: Marmoset P450 3A4 mRNA and P450 2C8/2C19 mRNA in hepatocytes were strongly (>10- fold) and weakly (>2) induced by rifampicin, respectively. Marmoset 1A1 and 1A2 mRNA were induced strongly (>200-fold) by ß-naphthoflavone and omeprazole. Marmoset P450 2B6 mRNA was induced (~5-fold) by a constitutive androstane receptor agonist, but not by phenobarbital. Cynomolgus monkey P450 3A4 mRNA and P450 1A1 mRNA in cultured hepatocytes were also induced by rifampicin and omeprazole, respectively, but P450 2B6 mRNA was not induced by phenobarbital. CONCLUSION: These results indicate that P450 1A/3A induction by typical human P450 inducers in hepatocytes from marmosets and/or cynomolgus monkeys are similar to those of humans (except for P450 2B induction by phenobarbital in humans), suggesting that marmosets and cynomolgus monkeys might be suitable models for evaluating the drug interactions in preclinical studies.
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Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP3A/metabolismo , Inductores de las Enzimas del Citocromo P-450/farmacología , Modelos Animales , Animales , Callithrix , Evaluación Preclínica de Medicamentos/métodos , Interacciones Farmacológicas , Estudios de Factibilidad , Hepatocitos , Humanos , Macaca fascicularis/metabolismo , Masculino , Omeprazol/farmacología , Fenobarbital/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rifampin/farmacologíaRESUMEN
In Hokkaido, northern Japan, there are 12 hybrid subsurface constructed wetlands (HSCWs) and most of them are treating high concentrated organic wastewater. One of these systems is an HSCW situated in Embetsu, northern Hokkaido, and it has been in operation since November of 2006 to treat dairy milking parlor wastewater. The system is composed of two vertical flow beds and a horizontal flow bed. The influent and the effluent flow rates and pollutant concentrations and loads were extremely variable. Throughout its 6 years of operation, most of the pollutant removals were decently high. Removal efficiencies for COD, BOD5, and SS were ranging in the 90 %. Removal efficiencies for TN, NH4-N, and BOD5 were improving because of the development of the soil ecosystem and the Phragmites australis community. However, the removal efficiencies of TP were decreasing, presumably because of the declining adsorption ability. The accumulation of TP in the first and the second vertical beds had reached its plateau. Vertical beds had high removal efficiencies for TN, COD, BOD5, and SS. These high removal efficiencies of the first vertical bed may be caused from the efficient removal of solid material that is deposited as an organic layer of the first vertical bed. High NH4-N removal efficiencies exerted by the second vertical bed may be due to the recycling of wastewater. In conclusion, the HSCW was working excellently for its 6 years of operation, and it could be concluded that it has not reached its life yet.
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Contaminantes Químicos del Agua/análisis , Purificación del Agua , Humedales , Adsorción , Compuestos de Amonio/análisis , Análisis de la Demanda Biológica de Oxígeno , Clima Frío , Japón , Fósforo/análisis , Contaminantes del Suelo/análisis , Aguas Residuales/análisisRESUMEN
Ammonium hexafluorosilicate (AHF) has been applied to arrest caries without discoloration. The purpose of this study was to observe structural and elemental changes of demineralized and AHF applied primary tooth enamel. Enamel from the labial surface of 20 primary canines was divided into an unground side and ground side at the center of the tooth, and demineralized with 35% phosphoric acid for 6 min. The teeth were divided into 4 groups according to a 3-min application of AHF and 1 week of soaking in artificial saliva, as follows: group A (neither AHF nor saliva), group B (only saliva), group C (only AHF), and group D (AHF and saliva), and then subdivided according to whether the enamel was ground or unground. Specimens were analyzed with scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The data were statistically analyzed using ANOVA and Fisher's PLSD test at α = 0.05. In groups A and B, prism structures were seen, however, in groups C and D, enamel surfaces were covered with spherical particles. Ca/P ratio was significantly higher in groups C and D than in groups A and B. There was no significant difference between ground and unground enamel in the content of any element. The values for F, Na, Mg and Si persents and Ca/P ratio were significantly higher for the enamel surface than for points 10-30 µm beneath the surface. Results of this study suggest the possibility that AHF treatment arrests caries, although further study will be required to confirm this result.
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Cariostáticos/uso terapéutico , Esmalte Dental/efectos de los fármacos , Fluoruros/uso terapéutico , Ácido Silícico/uso terapéutico , Desmineralización Dental/prevención & control , Remineralización Dental/métodos , Diente Primario/efectos de los fármacos , Calcio/análisis , Cariogénicos/efectos adversos , Diente Canino/efectos de los fármacos , Diente Canino/ultraestructura , Esmalte Dental/ultraestructura , Fluoruros/análisis , Humanos , Magnesio/análisis , Microscopía Electrónica de Rastreo , Ácidos Fosfóricos/efectos adversos , Fósforo/análisis , Saliva Artificial/farmacología , Silicio/análisis , Sodio/análisis , Espectrometría por Rayos X , Diente Primario/ultraestructuraRESUMEN
Coffee has an anti-diabetic effect, specifically the amelioration of both hyperglycemia and insulin resistance, in KK-A(y) mice, a type 2 diabetes animal model. To investigate coffee's effect on insulin signaling in liver, skeletal muscle, and adipose tissue (epididymal fat), we assayed the tyrosine phosphorylation of insulin receptor (IR) and serine phosphorylation of Akt. In Expt. 1, we assayed insulin signaling under nonfasting conditions in KK-A(y) mice that ingested water or coffee for 4 wk. Coffee ingestion ameliorated the development of hyperglycemia but did not affect insulin signaling in liver or skeletal muscle under such conditions. In Expt. 2, we assayed insulin signaling under basal and insulin-stimulated conditions in KK-A(y) mice that ingested water or coffee for 3 wk. The levels of tyrosine phosphorylation of insulin receptor in response to insulin injection in insulin-sensitive tissues were not different between mice that drank water and those that drank coffee. Coffee ingestion significantly increased the insulin-induced serine phosphorylation of Akt in liver and skeletal muscle, but not in epididymal fat, of KK-A(y) mice. Our results also indicated that coffee ingestion may contribute to the improvement of insulin resistance and hyperglycemia in KK-A(y) mice via the activation of Akt in insulin signaling in liver and skeletal muscle.
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Café/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Insulina/sangre , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Glucemia/análisis , Peso Corporal , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Hígado/metabolismo , Masculino , Ratones , Músculo Esquelético/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Receptor de Insulina/metabolismo , Serina/metabolismo , Transducción de Señal , Tirosina/metabolismoRESUMEN
We have previously demonstrated that coffee and caffeine ameliorated hyperglycemia in spontaneously diabetic KK-A(y) mice. This present study evaluates the antidiabetic effects of coffee and caffeine on high-fat-diet-induced impaired glucose tolerance in C57BL/6J mice. C57BL/6J mice fed a high-fat diet were given regular drinking water (control group), or a 2.5-fold-diluted coffee or caffeine solution (200 mg/L) for 17 weeks. The ingestion of coffee or caffeine improved glucose tolerance, insulin sensitivity, and hyperinsulinemia when compared with mice in the control group. The adipose tissue mRNA levels of inflammatory adipocytokines (MCP-1 and IL-6) and the liver mRNA levels of genes related to fatty acid synthesis were lower in the coffee and caffeine groups than those in the control group. These results suggest that coffee and caffeine exerted an ameliorative effect on high-fat-diet-induced impaired glucose tolerance by improving insulin sensitivity. This effect might be attributable in part to the reduction of inflammatory adipocytokine expression.
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Glucemia/metabolismo , Cafeína/farmacología , Café , Dieta Alta en Grasa/efectos adversos , Hipoglucemiantes/farmacología , Insulina/metabolismo , Adipoquinas/genética , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Ingestión de Alimentos , Ácidos Grasos/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Papilio maackii females prefer a rutaceous plant, Phellodendron amurense, for oviposition, whereas another semi-sympatric Rutaceae feeder, Papilio protenor, never exploits this plant as a host in nature. However, the larvae of both species perform well on this plant in the laboratory. Phellamurin, a flavonoid present in the organic fraction from P. amurense inhibits egg laying by P. protenor. We examined whether phellamurin is involved in the differential acceptance of P. amurense by the two butterflies. The ovipositing females of P. maackii readily accepted P. amurense and a methanolic extract of the foliage, while P. protenor rejected them entirely. However, the aqueous fraction derived from the extract elicited significant oviposition responses of similar levels from the two species. Phellamurin did not induce oviposition behavior in P. protenor females. In contrast, P. maackii was stimulated to oviposit by phellamurin at concentrations exceeding 0.2%. The response was dose-dependent and reached ca. 70% at 2% phellamurin, which is approximately equivalent to its natural abundance in young leaves of P. amurense. Since the aqueous fraction was very stimulatory to both species, the combined effect of phellamurin and the aqueous fraction on oviposition was tested. The addition of phellamurin to the aqueous fraction enhanced the ovipositional activity of P. maackii, but dramatically suppressed the oviposition response of P. protenor even at 0.1% concentration. These results, taken together with those obtained from electrophysiological recordings with foretarsal chemosensilla, indicate that phellamurin acts as an oviposition stimulant for P. maackii, and as a potent deterrent for P. protenor. The results suggest that host range expansion or host shifts may be made by ovipositing females that overcome phytochemical barriers.
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Mariposas Diurnas/efectos de los fármacos , Flavonoides/farmacología , Phellodendron/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Mariposas Diurnas/fisiología , Femenino , Flavonoides/aislamiento & purificación , Japón , Oviposición , Especificidad de la EspecieRESUMEN
Epidemiological surveys have demonstrated that habitual coffee consumption reduces the risk of type 2 diabetes. The aim of this work was to study the antidiabetic effect of coffee and caffeine in spontaneously diabetic KK-A(y) mice. KK-A(y) mice were given regular drinking water (controls) or 2-fold diluted coffee for 5 weeks. Coffee ingestion ameliorated the development of hyperglycemia and improved insulin sensitivity. White adipose tissue mRNA levels of inflammatory cytokines (MCP-1, IL-6, and TNFalpha), adipose tissue MCP-1 concentration, and serum IL-6 concentration in the coffee group were lower than the control group. Moreover, coffee ingestion improved the fatty liver. Caffeine ingestion as drinking water also caused an amelioration of hyperglycemia and an improvement of fatty liver. These results suggest that coffee exerts a suppressive effect on hyperglycemia by improving insulin sensitivity, partly due to reducing inflammatory cytokine expression and improving fatty liver. Moreover, caffeine may be one of the effective antidiabetic compounds in coffee.
Asunto(s)
Adipoquinas/metabolismo , Cafeína/farmacología , Café/química , Diabetes Mellitus Experimental/metabolismo , Hígado Graso/prevención & control , Hiperglucemia/prevención & control , Adipoquinas/genética , Animales , Glucemia/análisis , Ratones , ARN Mensajero/genéticaRESUMEN
We developed an LC method for the sensitive and selective fluorometric determination of polythiols. This method employs pre-column intramolecular excimer-forming fluorescence derivatization with N-(1-pyrene)iodoacetamide followed by LC separation. Polythiols were converted to the corresponding dipyrene-labeled derivatives, and the derivatives afforded intramolecular excimer fluorescence (440-540 nm). After the optimization using dithiothreitol and dimercaprol as model polythiols, alpha-lipoic acid (LA) and alpha-lipoamide were determined with high sensitivity and selectivity. The detection limits for polythiols were 0.6-3.5 fmol on column. Furthermore, this method could be successfully applied to the determination of LA in commercial dietary supplements and in human urine.
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Cromatografía Liquida/instrumentación , Cromatografía Liquida/métodos , Compuestos de Sulfhidrilo/análisis , Ácido Tióctico/análisis , Espectrometría de Masas , Modelos TeóricosRESUMEN
This study investigated the expression of core-binding factor alpha-1 (cbfa-1), osteocalcin, and vascular endothelial growth factor (VEGF) relative to new bone formation during guided bone regeneration; cbfa-1 is a prerequisite transcription factor for osteoblastic differentiation. Osteocalcin, a bone-specific extracellular matrix protein, is a marker of mature osteoblasts, whereas VEGF, a mitogen for endothelial cells, is a polypeptide thought to stimulate new blood vessel formation. Membranes (expanded polytetrafluoroethylene) were applied to defects created in the left tibiae of rats, while right tibial defects remained uncovered as a control group. Animals were killed 6, 8, or 10 days later. The cbfa-1 was detected by immunohistochemistry, and reverse transcriptase-polymerase chain reaction was used to detect osteocalcin and VEGF. The ratio of cbfa-1 positive cells in experimental bone defects was higher than in the control group. Osteocalcin mRNA expression increased gradually in the control group but significantly in the experimental group over time. The VEGF mRNA expression in the experimental group at 10 days was significantly lower than in the control group. These findings suggested that osteogenic cells differentiated into osteoblasts in the membrane-covered defects and that the bone healing process would be completed at an early stage.
Asunto(s)
Regeneración Ósea/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/análisis , Regeneración Tisular Guiada Periodontal/métodos , Osteocalcina/análisis , Factor A de Crecimiento Endotelial Vascular/análisis , Animales , Biomarcadores/análisis , ADN Complementario/análisis , Masculino , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Tibia/cirugíaRESUMEN
The bacteriostatic activities of monoacyl sugar alcohols with different acyl chains and hydrophilic heads were examined against some thermophilic sporeformers. Monomyristoyl erythritol and xylitol efficaciously suppressed their spore development. The number and orientation of the hydroxyl groups also played important roles in this activity, and monomyristoyl xylitol exhibited the highest activity among the monomyristoyl sugar alcohols.