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Presbyopia is caused by age-related lenticular hardening, resulting in near vision loss, and it occurs in almost every individual aged ≥50 years. The lens experiences mechanical pressure during for focal adjustment to change its thickness. As lenticular stiffening results in incomplete thickness changes, near vision is reduced, which is known as presbyopia. Piezo1 is a mechanosensitive channel that constantly senses pressure changes during the regulation of visual acuity, and changes in Piezo1 channel activity may contribute to presbyopia. However, no studies have reported on Piezo1 activation or the onset of presbyopia. To elucidate the relevance of Piezo1 activation and cross-linking in the development of presbyopia, we analysed the function of Piezo1 in the lens. The addition of Yoda1, a Piezo1 activator, induced an increase in transglutaminase 2 (TGM2) mRNA expression and activity through the extra-cellular signal-regulated kinase (ERK) 1/2 and c-Jun-NH2-terminal kinase1/2 pathways. In ex vivo lenses, Yoda1 treatment induced γ-crystallin cross-linking via TMG2 activation. Furthermore, Yoda1 eye-drops in mice led to lenticular hardening via TGM2 induction and activation in vivo, suggesting that Yoda1-treated animals could serve as a model for presbyopia. Our findings indicate that this presbyopia-animal model could be useful for screening drugs for lens-stiffening inhibition.
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Canales Iónicos , Presbiopía , Ratones , Animales , Canales Iónicos/metabolismo , Proteína Glutamina Gamma Glutamiltransferasa 2 , Esclerosis , Transporte BiológicoRESUMEN
Anxiety is a symptom of various mental disorders, including depression. Severe anxiety can significantly affect the quality of life. Hesperidin (Hes), a flavonoid found in the peel of citrus fruits, reportedly has various functional properties, one of which is its ability to relieve acute and chronic stress. However, Hes is insoluble in water, resulting in a low absorption rate in the body and low bioavailability. Glucosyl hesperidin (GHes) is produced by adding one glucose molecule to hesperidin. Its water solubility is significantly higher than that of Hes, which is expected to improve its absorption into the body and enhance its effects. However, its efficacy in alleviating anxiety has not yet been investigated. Therefore, in this study, the anxiolytic effects of GHes were examined in a zebrafish model of anxiety. Long-term administration of diets supplemented with GHes did not cause any toxicity in the zebrafish. In the novel tank test, zebrafish in the control condition exhibited an anxious behavior called freezing, which was significantly suppressed in GHes-fed zebrafish. In the black-white preference test, which also induces visual stress, GHes-fed zebrafish showed significantly increased swimming time in the white side area. Furthermore, in tactile (low water-level stress) and olfactory-mediated stress (alarm substance administration test) tests, GHes suppressed anxious behavior, and these effects were stronger than those of Hes. Increased noradrenaline levels in the brain generally cause freezing; however, in zebrafish treated with GHes, the amount of noradrenaline after stress was lower than that in the control group. Activation of c-fos/ERK/Th, which is upstream of the noradrenaline synthesis pathway, was also suppressed, while activation of the CREB/BDNF system, which is vital for neuroprotective effects, was significantly increased. These results indicate that GHes has a more potent anxiolytic effect than Hes in vivo, which may have potential applications in drug discovery and functional food development.
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Advanced glycation end products (AGEs) in lens proteins increase with aging, thus inducing cataracts and/or presbyopia. Hesperetin (Hst), which is an abundant plant flavanone largely derived from citrus species, and its derivatives attenuate cataracts and presbyopia in vivo and in vitro; however, no reports have described its effects on AGE formation in lens proteins. The present study demonstrated that AGEs in lens proteins increase with age in mice. Additionally, it showed that Hst can prevent AGEs and N(ε)carboxymethyllysine generation and modification of lens proteins using in vitro in human lens epithelial cell lines and ex vivo in mouse lens organ cultures. Furthermore, treatment with Hst prevented lens hardening and decreased chaperone activity in lens proteins. These results suggested that Hst and its derivatives are good candidates for the prevention of presbyopia and cataracts.
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Catarata , Cristalinas , Presbiopía , Humanos , Ratones , Animales , Productos Finales de Glicación Avanzada/metabolismo , Reacción de Maillard , Catarata/tratamiento farmacológico , Catarata/metabolismoRESUMEN
Recently, the use of ergogenic aids in sports by both athletes and fans has increased. Moreover, the overall demand for new ergogenic aids has increased. Hesperidin is a polyphenol that is useful for improving exercise performance by activating energy generation through ß-oxidation and oxidative phosphorylation in skeletal muscles. However, it is difficult to use this compound as an ergogenic aid because of its poor water solubility and low bioavailability. Glucosyl hesperidin is formed when one molecule of glucose is transferred to hesperidin via glycosyl-transferase. It is 10,000× more soluble and has 3.7× higher bioavailability than hesperidin. In this study, we assessed whether continuous (14 days) intake of glucosyl hesperidin improves the aerobic exercise capacity of rats during long-term acute exercise. Although glucosyl hesperidin intake did not improve the performance of high-intensity running (30 m/min), we did observe improvement in low-intensity running (15 m/min) (p < 0.05). We demonstrate that in sedentary rats, glucosyl hesperidin intake increased ß-oxidation and oxidative phosphorylation in the skeletal muscle (p < 0.05 and p < 0.01, respectively). Glucosyl hesperidin intake may have created a metabolic state useful for long-term exercise. In conclusion, the continuous intake of glucosyl hesperidin improved the aerobic exercise capacity of rats during long-term acute exercise.
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Hesperidina , Carrera , Ratas , Animales , Hesperidina/farmacología , Glucósidos , Fosforilación OxidativaRESUMEN
Recent discoveries suggest links between abnormalities in cell morphogenesis in the brain and the functional deficiency of molecules controlling signal transduction in glial cells such as oligodendroglia. Rnd2 is one such molecule and one of the Rho family monomeric GTP-binding proteins. Despite the currently known functions of Rnd2, its precise roles as it relates to cell morphogenesis and disease state remain to be elucidated. First, we showed that signaling through the loss of function of the rnd2 gene affected the regulation of oligodendroglial cell-like morphological differentiation using the FBD-102b cell line, which is often utilized as a differentiation model. The knockdown of Rnd2 using the clustered regularly interspaced palindromic repeats (CRISPR)/CasRx system or RNA interference was shown to slow morphological differentiation. Second, the knockdown of Prag1 or Fyn kinase, a signaling molecule acting downstream of Rnd2, slowed differentiation. Rnd2 or Prag1 knockdown also decreased Fyn phosphorylation, which is critical for its activation and for oligodendroglial cell differentiation and myelination. Of note, hesperetin, a citrus flavonoid with protective effects on oligodendroglial cells and neurons, can recover differentiation states induced by the knockdown of Rnd2/Prag1/Fyn. Here, we showed that signaling through Rnd2/Prag1/Fyn is involved in the regulation of oligodendroglial cell-like morphological differentiation. The effects of knocking down the signaling cascade molecule can be recovered by hesperetin, highlighting an important molecular structure involved in morphological differentiation.
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Cyclic nigerosylnigerose (CNN) is a cyclic tetrasaccharide with properties distinct from those of other conventional cyclodextrins. We investigated the relative available energy of CNN in healthy humans. CNN digestibility was determined using brush border membrane vesicles from the small intestines of rats. CNN was not hydrolyzed by rat intestinal enzymes. To investigate breath hydrogen excretion, 13 human subjects were included in a double-blind cross-over, randomized, placebo-controlled study. The effects of CNN on hydrogen excretion were compared with those of a typical nondigestible, fermentable fructooligosaccharide (FOS). In the study participants, hydrogen excretion hardly increased upon CNN and was remarkably lower than for FOS. The available energy value was determined using the fermentability based on breath hydrogen excretion and was evaluated as 0 kcal/g for CNN. CNN was hardly metabolized and hence may be used as a low-energy dietary fiber.
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Metabolismo Energético , Glucanos/metabolismo , Adulto , Pruebas Respiratorias , Método Doble Ciego , Femenino , Fermentación , Humanos , Hidrógeno/metabolismo , MasculinoAsunto(s)
Diabetes Mellitus , Síndrome Metabólico , Método Doble Ciego , Voluntarios Sanos , Homeostasis , Humanos , TrehalosaRESUMEN
Presbyopia is characterized by a decline in the ability to accommodate the lens. The most commonly accepted theory for the onset of presbyopia is an age-related increase in the stiffness of the lens. However, the cause of lens sclerosis remains unclear. With age, water microcirculation in the lens could change because of an increase in intracellular pressure. In the lens, the intracellular pressure is controlled by the Transient Receptor Potential Vanilloid (TRPV) 1 and TRPV4 feedback pathways. In this study, we tried to elucidate that administration of α-glucosyl-hesperidin (G-Hsd), previously reported to prevent nuclear cataract formation, affects lens elasticity and the distribution of TRPV channels and Aquaporin (AQP) channels to meet the requirement of intracellular pressure. As a result, the mouse control lens was significantly toughened compared to both the 1% and 2% G-Hsd mouse lens treatments. The anti-oxidant levels in the lens and plasma decreased with age; however, this decrease could be nullified with either 1% or 2% G-Hsd treatment in a concentration- and exposure time-dependent manner. Moreover, G-Hsd treatment affected the TRPV4 distribution, but not TRPV1, AQP0, and AQP5, in the peripheral area and could maintain intracellular pressure. These findings suggest that G-Hsd has great potential as a compound to prevent presbyopia and/or cataract formation.
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Membrana Celular/metabolismo , Glucósidos/metabolismo , Hesperidina/análogos & derivados , Cristalino/metabolismo , Presbiopía/metabolismo , Animales , Acuaporinas/metabolismo , Proteínas del Ojo/metabolismo , Hesperidina/metabolismo , RatonesRESUMEN
Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4+ cells were stimulated with IL2, antiCD3 and antiCD28 antibodies for 3 days, followed by further stimulation with IL2 for 7 days. Subsequently, cells were stimulated with IL2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 µg/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 µM gHesp. Following culture for 28 days, reverse transcriptionquantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase7 (MMP7), nicotinamide nucleotide transhydrogenase (NNT) and CXC motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotileexposure induced alterations in MMP7, NNT and IL17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposureinduced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with highrisk human populations exposed to asbestos, such as workers involved in asbestoshandling activities.
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Amianto/efectos adversos , Linfocitos T CD4-Positivos/inmunología , Suplementos Dietéticos , Hesperidina/farmacología , Mesotelioma Maligno/inmunología , Trehalosa/farmacología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Humanos , Interferón gamma/inmunología , Interleucina-17/inmunología , Masculino , Mesotelioma Maligno/inducido químicamente , Mesotelioma Maligno/prevención & control , Persona de Mediana Edad , Receptores CXCR3/inmunologíaRESUMEN
Presbyopia is one of the most well-known diseases of the eye, predominantly affecting the adult population after 50 years'. Due to hardening of the lens and failure of accommodative change, patients lose the ability to focus on near objects. This eye symptom is reported to be an early symptom of age-related nuclear cataract, and we have previously reported that hesperetin treatment could delay the onset of nuclear cataractogenesis induced by sodium selenite. In this study, we examined whether oral intake of α-glucosyl-hesperidin (G-Hsd), which has greater water solubility than hesperetin, could delay the onset of presbyopia. G-Hsd treatment protected lens elasticity, upregulated the mRNA expression of anti-oxidative enzymes like glutathione reductase and thioredoxin reductase 1 in the plasma and lens, and prevented premature cataract symptoms in selenite-induced cataract rat lens. Thus, the anti-presbyopic effects of G-Hsd were attributed, at least in part, to its antioxidant effects. G-Hsd represents the first oral treatment agent with anti-presbyopia and/or anti-cataract properties.
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BACKGROUND: Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. METHODS: This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days. Their body compositions were assessed following 0, 4, 8, and 12 weeks; and serum biochemical parameters were assayed and oral 75-g glucose tolerance tests were performed at baseline and after 12 weeks. RESULTS: There were similar changes in body composition and serum biochemistry consistent with established seasonal variations in both groups, but there were no differences in any of these parameters between the two groups. However, whereas after 12 weeks of sucrose consumption, the plasma glucose concentration 2 h after a 75-g glucose load was significantly higher than the fasting concentration, after 12 weeks of trehalose consumption the fasting and 2-h plasma glucose concentrations were similar. Furthermore, an analysis of the participants with relatively high postprandial blood glucose showed that the plasma glucose concentration 2 h after a 75-g glucose load was significantly lower in the trehalose group than in the sucrose group. CONCLUSIONS: Our findings suggest that trehalose helps lower postprandial blood glucose in healthy humans with higher postprandial glucose levels within the normal range, and may therefore contribute to the prevention of pathologies that are predisposed to by postprandial hyperglycemia,, even if the daily intake of trehalose is only 3.3 g, an amount that is easily incorporated into a meal. TRIAL REGISTRATION: UMIN, UMIN000033536 . Registered 27 July 2018.
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Insulina , Trehalosa , Glucemia , Estudios Cruzados , Método Doble Ciego , Glucosa , Voluntarios Sanos , Homeostasis , Humanos , Periodo PosprandialRESUMEN
BACKGROUND: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. METHODS: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. RESULTS: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce adipocyte hypertrophy. CONCLUSIONS: The suppression of adipocyte hypertrophy in the presence and absence of trehalase indicates that trehalose mediates effects prior to being hydrolyzed into glucose. In both trehalase KO and WT mice, trehalose treatment increased the rate of CLDs in jejunal epithelium, reduced chylomicron migration from the intestinal epithelium to the periphery, and suppressed adipocyte hypertrophy. Thus, trehalose ingestion could prevent metabolic syndrome by trapping fat droplets in the intestinal epithelium and suppressing rapid increases in chylomicrons.
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Hesperetin is a natural flavonoid with robust antioxidant properties. Our previous study reported that hesperetin can prevent cataract formation. However, an important consideration regarding hesperetin consumption is the limited bioavailability due to its poor solubility. The present study investigated the anticataract effects of αglucosyl hesperidin in vivo and in vitro using a seleniteinduced cataract model. SD rats (age, 13 days) were orally administered PBS (0.2 ml) or αglucosyl hesperidin (200 mg/kg) on days 0, 1 and 2. Sodium selenite was subcutaneously administered to the rats 4 h after the first oral administration on day 0. Antioxidant levels in the lens and blood were measured on day 6. In vitro, human lens epithelial cells were treated with sodium selenite (10 µM) and/or hesperetin (50 or 100 mM) for 24 h and analyzed for apoptosis markers using subG1 population and Annexin VFITC/propidium iodide staining and DNA ladder formation. αglucosyl hesperidin treatment significantly reduced the severity of seleniteinduced cataract. The level of antioxidants was significantly reduced in the selenitetreated rats compared with in the controls; however, they were normalized with αglucosyl hesperidin treatment. In vitro, hesperetin could significantly reduce the number of cells undergoing apoptosis induced by sodium selenite in human lens epithelial cell lines. Overall, oral consumption of αglucosyl hesperidin could delay the onset of seleniteinduced cataract, at least in part by modulating the seleniteinduced cell death in lens epithelial cells.
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Antioxidantes/administración & dosificación , Catarata/tratamiento farmacológico , Glucósidos/administración & dosificación , Hesperidina/análogos & derivados , Selenito de Sodio/efectos adversos , Administración Oral , Animales , Antioxidantes/química , Apoptosis/efectos de los fármacos , Catarata/inducido químicamente , Catarata/patología , Muerte Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Glucósidos/química , Hesperidina/administración & dosificación , Hesperidina/química , Humanos , Cristalino/efectos de los fármacos , Cristalino/patología , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. METHODS: Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. RESULTS: Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. CONCLUSIONS: Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.
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The patient, a 79-year-old man, experienced a Hunt & Kosnik grade IV subarachnoid hemorrhage, presenting with sudden-onset coma and severe left hemiplegia. We performed cranial clipping surgery for a ruptured aneurysm on the right middle cerebral artery the same day. Post-operative recovery proceeded smoothly, with gradual improvements in disturbed consciousness and left hemiplegia. Three weeks post-operation, CT revealed low-density areas in the right frontal and temporal lobe, believed to be due to subarachnoid hemorrhage, as well as hydrocephaly. We then performed a lumbo-peritoneal (L-P) shunt for the hydrocephaly. Two months later, the patient experienced shunt occlusion, and we performed a ventriculo-peritoneal (V-P) shunt revision (pressure: 6 cm H(2)O). Headaches, severe decline in cognitive function, and worsened left hemiplegia were observed seven weeks post-shunt revision. Cranial CT revealed widespread low-density areas in right posterior cerebral white matter. We suspected unilateral posterior reversible encephalopathy syndrome (PRES) after performing cranial MRI and cerebral angiography. Increasing the set pressure of the shunt improved the symptoms and radiographic findings. PRES is typically bilateral, and unilateral incidents are rare. This is the first report of unilateral PRES secondary to shunt operation. Its unilaterality appears to have been caused by unilateral brain damage or adhesions to the brain surface from the subarachnoid cerebral hemorrhage. Overdrainage post-shunt can also induce PRES. Diagnosis of PRES is more difficult in unilateral cases;practitioners must keep PRES in mind as a rare complication post-shunt operation.
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Hidrocéfalo Normotenso/cirugía , Síndrome de Leucoencefalopatía Posterior/etiología , Complicaciones Posoperatorias , Hemorragia Subaracnoidea/cirugía , Anciano , Angiografía Cerebral , Humanos , Hidrocéfalo Normotenso/complicaciones , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Imagen Multimodal , Procedimientos Neuroquirúrgicos , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Síndrome de Leucoencefalopatía Posterior/patología , Hemorragia Subaracnoidea/etiología , Tomografía Computarizada por Rayos XRESUMEN
Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation, and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH.
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Diabetes Mellitus Experimental/complicaciones , Modelos Animales de Enfermedad , Hierro/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/complicaciones , Bazo/metabolismo , Animales , Hígado/metabolismo , Hígado/patología , Ratones , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
We previously performed animal studies that suggested that trehalose potentially prevents the development of metabolic syndrome in humans. To evaluate this possibility, we examined whether trehalose suppressed the progression of insulin resistance in a placebo-controlled, double-blind trial in 34 subjects with a body mass index (BMI) ≥23. The subjects were divided into two groups and were assigned to ingest either 10 g/d of trehalose or sucrose with meals for 12 wk. During the study, body composition and blood biochemical parameters were measured at week 0, 8, and 12. These parameters were also measured 4 wk after the end of intake to confirm the washout of test substances. In the trehalose group, blood glucose concentrations after a 2-h oral glucose tolerance test significantly decreased following 12 wk of intake in comparison with baseline values (0 wk). When a stratified analysis was performed in the subjects whose percentage of truncal fat approached the high end of the normal range, the change in body weight, waist circumference, and systolic blood pressure were significantly lower in the trehalose group than in the sucrose group. Our data indicated that a daily intake of 10 g of trehalose improved glucose tolerance and progress to insulin resistance. Furthermore, these results suggested that trehalose can potentially reduce the development of metabolic syndrome and associated lifestyle-related diseases, such as type 2 diabetes.
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Diabetes Mellitus Tipo 2/prevención & control , Síndrome Metabólico/prevención & control , Trehalosa/administración & dosificación , Adulto , Glucemia/metabolismo , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Resistencia a la Insulina , Estilo de Vida , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Persona de Mediana Edad , Factores de Riesgo , Trehalosa/sangre , Circunferencia de la CinturaRESUMEN
We report a case of a suspected secondary central nervous system(CNS)primitive neuroectodermal tumor(PNET)that developed 25 years after radiation therapy for a medulloblastoma of the cerebellum. At 5 years of age, the patient underwent craniotomy and subsequent radiation therapy of the whole brain(39Gy), whole spinal cord(9Gy), and posterior fossa(49Gy)for the treatment of a medulloblastoma of the cerebellum;the patient did not receive chemotherapy. After radiation therapy, the medulloblastoma completely receded and did not recur. Twenty-five years later, at 30 years of age, the patient visited our institution experiencing right-sided hemiparesis and aphasia that had arisen approximately 1 month prior and had gradually worsened. The patient was subsequently hospitalized after experiencing disturbed consciousness and a generalized convulsion seizure. Gadolinium-enhanced magnetic resonance imaging(MRI)revealed a mass accompanied by a large cyst in the left frontal lobe. Complete tumor resection was achieved via macroscopic surgery, and the histopathological findings were indicative of CNS PNET. Considering the tumor occurred in the same site where radiation therapy had been previously administered to treat a medulloblastoma, additional radiotherapy was avoided in favor of combination chemotherapy with ifosfamide, cisplatin, and etoposide. Tumor recurrence was not observed in a follow-up MRI after 6 courses of ICE therapy, and the patient has resumed a normal life. The present case, a CNS PNET, is suspected as a secondary brain tumor induced by radiation therapy previously used to treat a medulloblastoma, and it represents a rare late-onset complication of radiation therapy. For the treatment of PNET, we believe that maximal safe surgical resection of the tumor and post-operative radiation therapy are typically necessary for long-term survival. However, taking into account the risks of repeated exposure to radiation, we did not perform post-operative radiation therapy for this patient. We have not observed recurrence to date;however, the patient will require a strict follow-up schedule hereafter.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/terapia , Meduloblastoma/terapia , Recurrencia Local de Neoplasia/terapia , Tumores Neuroectodérmicos Primitivos/terapia , Adulto , Neoplasias Encefálicas/patología , Quimioradioterapia , Cisplatino/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Imagen por Resonancia Magnética/métodos , Masculino , Meduloblastoma/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/patología , Tumores Neuroectodérmicos Primitivos/diagnóstico , Resultado del TratamientoRESUMEN
The aim of this study is to evaluate the effects of NK-4, a kind of cyanine dye, on cholinergic memory deficits in mice. We examined whether NK-4 could reverse scopolamine-induced amnesia in mice since NK-4 displays a potent and selective inhibitory effect on acetylcholinesterase (AChE) in vitro. Intraperitoneal administration of NK-4 significantly reversed scopolamine-induced cognitive impairments in mice in the Y maze and the passive avoidance tests, and NK-4 also improved spatial learning ability in the Morris water maze test. Despite NK-4 displaying remarkable AChE inhibitory activity in vitro, we could not detect a significant reduction of AChE activity in brain homogenates of NK-4-treated mice. Although the mechanism through which NK-4 reverses cognitive impairments in scopolamine-treated mice remains unclear, these data suggest that NK-4 may have potential as a therapeutic agent for the treatment of dementia.
Asunto(s)
Carbocianinas/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Acetilcolinesterasa/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Butirilcolinesterasa/metabolismo , Carbocianinas/farmacología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/enzimología , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/enzimología , Trastornos de la Memoria/fisiopatología , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Endogámicas F344 , EscopolaminaRESUMEN
Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4-CD8-, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.