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SCOPE: This study examines whether coingestion of γ-aminobutyric acid (GABA) and malic acid (MA) before meals enhances glucagon-like peptide-1 (GLP-1) secretion, and which affects subsequent insulin and glycemic responses in humans. METHODS AND RESULTS: Initially, a murine enteroendocrine STC-1 cell line is used to verify coadministration of GABA and MA synergistically induces GLP-1 secretion. Next, 22 healthy adults are given water (50 mL) containing 400 mg GABA and 400 mg MA (Test), or only 400 mg citric acid (CA) (Placebo) 20 min before meal tolerance test (MTT). Interval blood samples are taken postprandially over 180 min to determine GLP-1, insulin, and glucose responses. By comparison to preload of Placebo, preload of Test significantly increases plasma GLP-1 (total/active) levels (incremental area under the curve by 1.2- and 1.6-fold), respectively. However, there are no significant differences in postprandial blood glucose and insulin. CONCLUSION: Coingestion of GABA and MA before meals enhances postprandial GLP-1 secretion. Future studies should explore optimal dosage regimens to find the efficacy of the mixture on insulin and glycemic response.
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Insulina , Malatos , Adulto , Humanos , Glucemia/metabolismo , Estudios Cruzados , Péptido 1 Similar al Glucagón , Glucosa/farmacología , Periodo Posprandial/fisiologíaRESUMEN
This study investigated the glucagon-like peptide-1 (GLP-1)-releasing activity of an aqueous extract (ZeinS) from corn zein protein and aimed to identify the active compounds responsible for this activity. Glucagon-like peptide-1-releasing activity was evaluated using a murine enteroendocrine cell line (GLUTag). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on purified fractions of ZeinS to identify active molecules. ZeinS stimulated more GLP-1 secretion from GLUTag cells compared to zein hydrolysate. Fractions displaying biological activity were determined by solid-phase extraction and high-performance liquid chromatography (HPLC) fractionation. Subsequent LC-MS/MS analysis identified several amino acids in the active fractions of ZeinS. In particular, γ-aminobutyric acid (GABA) exhibited significant GLP-1-releasing activity both alone and synergistically with L-phenylalanine (Phe). Moreover, ZeinS-induced GLP-1 secretion was attenuated by antagonists for the GABA receptor and calcium sensing receptor. These results demonstrate that GABA and Phe identified in ZeinS synergistically stimulate GLP-1 secretion in enteroendocrine cells.
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Células Enteroendocrinas , Péptido 1 Similar al Glucagón , Zeína , Animales , Ratones , Cromatografía Liquida , Células Enteroendocrinas/efectos de los fármacos , Células Enteroendocrinas/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Fenilalanina/metabolismo , Proteínas/metabolismo , Espectrometría de Masas en Tándem , Zea mays/química , Zeína/metabolismoRESUMEN
Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.
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Infecciones por Escherichia coli , Infecciones Urinarias , Humanos , Cefmetazol/uso terapéutico , Cefmetazol/farmacología , Meropenem/uso terapéutico , Meropenem/farmacología , beta-Lactamasas/farmacología , Escherichia coli/genética , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacologíaRESUMEN
Isomaltomegalosaccharides with α-(1 â 4) and α-(1 â 6)-segments solubilize water-insoluble ligands since the former complexes with the ligand and the latter solubilizes the complex. Previously, we enzymatically synthesized isomaltomegalosaccharide with a single α-(1 â 4)-segment at the reducing end (S-IMS) by dextran dextrinase (DDase), but the chain length [average degree of polymerization (DP) ≤ 9] was insufficient for strong encapsulation. We hypothesized that the conjugation of longer α-(1 â 4)-segment afforded the promising function although DDase is incapable to do so. In this study, the cyclodextrin glucanotransferase-catalyzed coupling reaction of α-cyclodextrin to S-IMS synthesized a new α-(1 â 4)-segment at the nonreducing end (N-4S) of S-IMS to form D-IMS [IMS harboring double α-(1 â 4)-segments]. The length of N-4S was modulated by the ratio between α-cyclodextrin and S-IMS, generating N-4Ss with DPs of 7-50. Based on phase-solubility analysis, D-IMS-28.3/13/3 bearing amylose-like helical N-4S with DP of 28.3 displayed a water-soluble complex with aromatic drugs and curcumin. Small-angle X-ray scattering revealed the chain adapted to rigid in solution in which the radius of gyration was estimated to 2.4 nm. Furthermore, D-IMS with short N-4S solubilized flavonoids of less-soluble multifunctional substances. In our research, enzyme-generated functional biomaterials from DDase were developed to maximize the hydrophobic binding efficacy towards water-insoluble bioactive compounds.
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The dissolved silicate (DSi) concentration in coastal waters has decreased due to anthropogenic activities. Many studies have indicated that dam construction is a main reason for this reduction. However, recently, dam construction alone has not been sufficient to explain the DSi reduction in some coastal waters. In this study, we focused on silica removal at sewage treatment plants (STPs). DSi and particulate silica (PSi) concentrations were measured in STP influent and effluent waters from September 2020 to September 2021. Dissolution experiments on PSi were also conducted to estimate the fraction of soluble PSi in the STP influent. DSi and PSi were removed by 29.5% and 96.9%, respectively, at the STP. In addition, the soluble PSi in the STP influent accounted for 20.3% of the PSi removed. Therefore, in addition to the DSi removal in STPs, removal of soluble PSi can also cause potential DSi depletion in downstream and coastal waters. In addition to the effect of dams, the silica supply delivered to coastal waters may be further reduced in the future due to the progress of sewage treatment development in coastal areas.
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Aguas del Alcantarillado , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Aguas del Alcantarillado/análisis , Dióxido de Silicio , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisisRESUMEN
Quercetin and methylquercetin are present in a variety of sulfate and glucuronide conjugates in the plasma of quercetin-fed rats and humans. Quercetin conjugates exhibit various physiological activities, depending on the type and position of conjugation. However, little is known regarding the type and position of isomers of quercetin conjugates in the plasma, their accumulation in the liver and kidneys, and their excretion via urine. Using authentic standards of quercetin conjugates and liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis, we identified and quantified various quercetin conjugates in blood plasma, urine, liver, and kidney tissues 1, 4, and 10 h after orally administering 33.1 µmol kg-1 quercetin glucosides to rats. The profiles of quercetin conjugates were largely different among plasma, urine, liver, and kidneys. Very limited heteroconjugates (7-O-glucuronide-4'-O-sulfate) of quercetin and methylquercetin dominated in the plasma, but these heteroconjugates were much less excreted via urine and did not largely accumulate in the liver and kidneys. Heteroconjugates constituting sulfates other than 4' position sulfate, 7-O-glucuronide-3'-O-sulfate, 4'-O-glucuronide-7-O-sulfate, and 3'-O-glucuronide-7-O-sulfate were major metabolites in urine, but were minimally detected in the plasma. We also found that mono-sulfate conjugates were abundant in the liver and renal tissues. These results suggest that excretion of quercetin conjugates, especially heteroconjugates, into urine is highly selective. The heteroconjugates with 4'-O-sulfate may be scarcely excreted via urine, and thus accumulate in the blood plasma. Further research is necessary to evaluate the physiological effects of heteroconjugates accumulated in the plasma.
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Antioxidantes/farmacocinética , Quercetina/farmacocinética , Administración Oral , Animales , Antioxidantes/administración & dosificación , Cromatografía Liquida , Masculino , Plasma/metabolismo , Quercetina/administración & dosificación , Quercetina/sangre , Quercetina/orina , Ratas , Ratas Wistar , Espectrometría de Masas en TándemRESUMEN
In a Bacillus subtilis ugtP mutant lacking glucolipids, SigI was activated in the log phase, and the activation of SigI in the mutant was suppressed by the expression of native ugtP. By contrast, SigI was inhibited in a yfnI mutant lacking one of the lipoteichoic acid (LTA) synthase genes, and the inhibition was suppressed by the expression of yfnI. A series of mutation analyses of the sigI promoter revealed that the two WalR binding sites were involved in the increase of PsigI -lacZ activity in the ugtP mutant and decrease of the lacZ activity in the yfnI mutant. Transcription from the SigI recognition sequence was enhanced in the ugtP mutant, whereas yfnI disruption inhibited the transcription from the SigA recognition sequence in the sigI promoter. We found that not only SigI but also WalKR, the essential two-component system, was activated in the ugtP mutant and inhibited in the yfnI mutant. The walK mutants with activated WalR exhibited abnormal morphology, but this phenotype was suppressed by the addition of MgSO4 . We conclude that glucolipids and LTA are key compounds in the maintenance of normal cell surface structure in B. subtilis.
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Bacillus subtilis , Proteínas Bacterianas , Factor sigma , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Lipopolisacáridos , Mutación , Factor sigma/genética , Factor sigma/metabolismo , Ácidos TeicoicosRESUMEN
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released from enteroendocrine L cells in response to meal ingestion. GLP-1 receptor agonists and GLP-1 enhancers have been clinically employed to treat diabetes owing to their glucose-dependent insulin-releasing activity. The release of GLP-1 is primarily stimulated by macronutrients such as glucose and fatty acids, which are nutritionally indispensable; however, excessive intake of sugar and fat is responsible for the development of obesity and diabetes. Therefore, GLP-1 releasing food factors, such as dietary peptides and non-nutrients, are deemed desirable for improving glucose tolerance. Human and animal studies have revealed that dietary proteins/peptides have a potent effect on stimulating GLP-1 secretion. Studies in enteroendocrine cell models have shown that dietary peptides, amino acids, and phytochemicals, such as quercetin, can directly stimulate GLP-1 secretion. In our animal experiments, these food factors improved glucose metabolism and increased GLP-1 secretion. Furthermore, some dietary peptides not only stimulated GLP-1 secretion but also reduced plasma peptidase activity, which is responsible for GLP-1 inactivation. Herein, we review the relationship between GLP-1 and food factors, especially dietary peptides and flavonoids. Accordingly, utilization of food factors with GLP-1-releasing/enhancing activity is a promising strategy for preventing and treating obesity and diabetes.
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Proteínas en la Dieta/farmacología , Células Enteroendocrinas/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Intolerancia a la Glucosa/dietoterapia , Fitoquímicos/farmacología , Animales , HumanosRESUMEN
The present study was conducted to examine region-dependent glucagon-like peptide-1 (GLP-1) responses to "meal ingestion" under physiological (conscious and unrestrained) conditions using rats with a catheter inserted into either the portal vein (PV) or the ileal mesenteric vein (ILMV). After recovery from the cannulation surgery, blood samples were collected from either PV or ILMV catheter before and after the voluntary ingestion of test diets. After an AIN-93G standard diet ingestion, GLP-1 concentration was higher in ILMV than in PV, and postprandial responses of peptide-YY (PYY) had similar trend, while that of glucose dependent-insulinotropic polypeptide showed an opposite trend to GLP-1/PYY responses. In a separated experiment, a protein-enriched diet containing casein at 25% wt/wt transiently increased GLP-1 concentration only in ILMV; however, a protein-free diet did not increase GLP-1 concentrations in PV or ILMV. These results indicate that postprandial GLP-1 is immediately released from the distal intestine under physiological conditions, and that dietary protein has a critical role in the enhancement of postprandial GLP-1 response.
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Proteínas en la Dieta/metabolismo , Péptido 1 Similar al Glucagón/sangre , Venas Mesentéricas/metabolismo , Animales , Glucemia , Recolección de Muestras de Sangre , Polipéptido Inhibidor Gástrico/sangre , Masculino , Péptido YY/sangre , Vena Porta/metabolismo , Periodo Posprandial/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
This study examined the effects of a combination of soybean fiber and α-glycosyl-isoquercitrin (AGIQ) on improving quercetin bioavailability and glucose metabolism in rats fed an obesogenic diet. For 9 weeks, rats were individually fed a control diet, a high-fat high-sucrose (H) diet, H with soybean fiber (HS), or with AGIQ (HQ), or with both (HSQ). Quercetin derivatives in plasma, feces, urine, and cecal content were quantified by high-performance liquid chromatography to assess the bioavailability of quercetin, and meal tolerance tests were performed to assess postprandial glycemia and glucagon-like peptide-1 (GLP-1) responses. The HSQ group had higher plasma quercetin levels than HQ. The postprandial glycemia was attenuated in the HSQ group when compared to the H group. The basal plasma GLP-1 concentrations positively correlated with plasma quercetin derivative concentrations. Hence, the combination of soybean fiber and AGIQ could be beneficial for reducing the risk of glucose intolerance, possibly involving enhanced quercetin bioavailability and GLP-1 secretion.
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Péptido 1 Similar al Glucagón , Quercetina , Animales , Disponibilidad Biológica , Glucemia , Dieta Alta en Grasa/efectos adversos , Homeostasis , Insulina , Quercetina/análogos & derivados , Ratas , Glycine max , SacarosaRESUMEN
BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, â¼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (â¼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.
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Regulación del Apetito , Calcio de la Dieta/farmacología , Calcio/farmacología , Ingestión de Alimentos/efectos de los fármacos , Péptido YY/sangre , Receptores Sensibles al Calcio/sangre , Respuesta de Saciedad/efectos de los fármacos , Administración Oral , Animales , Calcio/administración & dosificación , Cloruro de Calcio/farmacología , Calcio de la Dieta/administración & dosificación , Ingestión de Energía/efectos de los fármacos , Ayuno , Masculino , Periodo Posprandial , Ratas Sprague-Dawley , Receptores de la Hormona Gastrointestinal/metabolismo , SaciedadRESUMEN
Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2-4 g/kg), but not by that of dextrin (2-4 g/kg), in control rats (untreated Sprague-Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague-Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response.
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Dextrinas/farmacología , Dipeptidil Peptidasa 4/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Lípidos/farmacología , Proteína de Suero de Leche/farmacología , Alimentación Animal , Animales , Animales Modificados Genéticamente , Caseínas/administración & dosificación , Caseínas/farmacología , Dieta , Proteínas en la Dieta/administración & dosificación , Dipeptidil Peptidasa 4/genética , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Péptido 1 Similar al Glucagón/genética , Lípidos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Fosfato de Sitagliptina/farmacologíaRESUMEN
Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62·76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0·053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Péptido 1 Similar al Glucagón/metabolismo , Obesidad , Animales , Glucemia , Dieta Alta en Grasa , Insulina/metabolismo , Masculino , Obesidad/etiología , Obesidad/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: Uncomfortable care and histamine H2 antagonist (H2A) are implicated in precipitating delirium. In acute stroke, however, the need for them depends on stroke severity, an established risk factor for delirium. So, it is unclear whether care or H2A itself is responsible for delirium. We aimed to evaluate their causal effects on delirium in acute stroke patients. METHODS: This is a prospective cohort study on acute stroke patients admitted to a stroke care unit. Patients without stupor, coma, sedation, or delirium upon admission were enrolled. The treatment was H2A and five care modalities given during the first 24 h: restraint use, prohibited self-transfer, no oral feeding, indwelling catheters, and frequent nighttime care. The outcome was delirium within 5 days defined as Intensive Care Delirium Screening Checklist ≥4 points. We estimated the relative risk (RR) for delirium with regression models weighted by overlap weights using propensity scores estimated through logistic models incorporating known and potential confounders, including stroke severity. RESULTS: Of the 387 participants, 188 were given at least one care modality and 130 were given H2A. A total of 42 developed delirium. Delirium was significantly associated with prohibited self-transfer (RR 1.7, 95% CI 1.0-3.0), frequent nighttime care (RR 2.1, 95% CI 1.2-3.7), and multiple care modalities (RR 2.4, 95% CI 1.3-4.4), while other care modalities and H2A were not. CONCLUSIONS: This study showed possible causal effects of uncomfortable care on delirium and suggests that minimizing it could prevent delirium in acute stroke.
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Delirio , Accidente Cerebrovascular , Delirio/epidemiología , Delirio/etiología , Histamina , Antagonistas de los Receptores H2 de la Histamina , Humanos , Unidades de Cuidados Intensivos , Puntaje de Propensión , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
BACKGROUND AND PURPOSE: Delirium frequently complicates acute stroke and worsens outcomes. Because delirium is potentially preventable, predicting its occurrence is essential. Although several prediction scores have been proposed, nurses need to quickly predict delirium in stroke care units (SCUs). We aimed to develop a simple tool for this purpose by examining a comprehensive set of potential predictors. METHODS: This is a prospective cohort study on acute stroke patients admitted to an SCU. Patients without stupor, coma, or delirium upon admission were eligible. Participants were followed for 5 days from admission. Delirium was defined as Intensive Care Delirium Screening Checklist ≥4 points. We examined 27 potential predictors, of which 13 predictors were used to developed a least absolute shrinkage and selection operator-penalized logistic regression model. Five variables with the largest coefficients were assigned one point each in the prediction score. The internal validation was performed by bootstrapping. RESULTS: Delirium occurred in 42 of the 387 participants. The score consisted of prior delirium, alcohol, NIHSS ≥5, dementia, and auditory/visual impairment (PANDA). The apparent AUC was 0.84 (95% confidence interval [CI], 0.78-0.89), and the optimism-corrected AUC was 0.81 (95% CI, 0.73-0.88). With a cutoff of ≥2 points, sensitivity was 0.78 (95% CI, 0.65-0.90), and specificity was 0.74 (95% CI, 0.70-0.79). CONCLUSIONS: PANDA score is simple and predicts delirium in an SCU satisfactorily.
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Delirio , Accidente Cerebrovascular , Cuidados Críticos , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Humanos , Unidades de Cuidados Intensivos , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnósticoRESUMEN
Here we firstly report the pressure-induced superconductivity in phase change materials SnSb2Te4. Single crystals of SnSb2Te4 were grown using a conventional melting-down method. The resistance under pressure was measured using an originally designed diamond anvil cell with boron-doped diamond electrodes. The temperature dependence of the resistance under different pressures has been measured up to 32.6 GPa. The superconducting transition of SnSb2Te4 appeared at 2.1 K ([Formula: see text]) under 8.1 GPa, which was further increased with applied pressure to a maximum onset transition temperature 7.4 K under 32.6 GPa.
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A high-throughput first-principles calculation-assisted data-driven approach based on an inorganic materials database named AtomWork was performed to explore new superconducting materials. Specific band structures of a small band gap and flat band at band edges were used in a screening procedure. Among the candidates studied, we focused on AgIn5Se8, which shows a high density of state at the Fermi level. Single crystals of AgIn5Se8 were successfully obtained via a melt and slow cooling method. The valence states in AgIn5Se8 were estimated to be Ag1+, In3+, and Se2- using X-ray photoelectron spectroscopy. An electrical transport property of resistance was measured under high pressure using an electrodes-inserted diamond anvil cell. The sample exhibited an insulator-to-metal transition with a drastic decrease of the resistance by increasing the pressure up to 24.8 GPa. A possibility of a pressure-driven phase transition below this pressure was indicated by an enthalpy calculation. At a higher pressure region of 52.5 GPa, a pressure-induced superconducting transition was observed at 3.4 K. The maximum transition temperature was increased up to 3.7 K under the pressure of 74.0 GPa.
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Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released in response to meal ingestion and enhances insulin secretion from pancreatic ß cells. In several human studies, GLP-1 secretory responses to oral glucose load or a meal were decreased in subjects with obesity, glucose intolerance, or diabetes compared with those in healthy subjects. However, the results of meta-analysis and cohort studies do not necessarily support this concept. Results from animal studies are also inconsistent; in multiple studies, GLP-1 secretory responses to a meal were repeatedly higher in diet-induced obese rats than in control rats. Thus, the postprandial GLP-1 response is not necessarily decreased but rather enhanced during obesity development, which is likely to play a protective role against glucose intolerance.
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Péptido 1 Similar al Glucagón/metabolismo , Trastornos del Metabolismo de la Glucosa/metabolismo , Obesidad/metabolismo , Periodo Posprandial , Animales , HumanosRESUMEN
PURPOSE: To investigate the effects of water-soluble dietary fibers (pectin, soybean fiber, and guar gum) on the bioavailability of quercetin glucoside mixture (Q3GM) comprising quercetin-3-O-glucoside (Q3G, 31.8%) and its glucose adducts. METHODS: Male Wistar/ST rats were fed test diet containing 0.7% Q3GM with or without 5% of each dietary fiber for 8 weeks. Total quercetin derivatives were evaluated with liquid chromatograph tandem mass spectrometry (LC-MS/MS) as total quercetin derivatives after enzymatic deconjugation in plasma, urine, and fecal samples on week 2, 4, 6 and 8. Quercetin glucuronides excreted in feces were also measured. RESULTS: Fiber feeding elevated cecal weight and reduced cecal pH, indicative of cecal fermentation promotion. Changes in plasma and urinary quercetin levels revealed three phases of quercetin metabolism, including cumulative, transient, and stable phases. On week 2, total quercetin derivatives were higher in plasma samples from three fiber-fed groups than those control groups; however, urinary excretion increased in fiber-fed groups on week 4. Soybean fiber upregulated plasma and urinary quercetin levels on week 6 and 8. Intestinal degradation of quercetin by bacteria, calculated from differences between aglycone ingestion and sum of urinary and fecal excretion, was suppressed after dietary fiber supplementation especially in pectin fiber, which may partly contribute to the increase in quercetin bioavailability. Fecal quercetin glucuronide excretion was high in soybean fiber-fed rats, suggestive of the reduction of ß-glucuronidase in colon. CONCLUSION: Water-soluble dietary fibers, especially soybean fiber, enhanced quercetin bioavailability after chronic feeding and may promote beneficial effects of quercetin on disease prevention.
Asunto(s)
Dieta/métodos , Fibras de la Dieta/farmacología , Glycine max/metabolismo , Quercetina/metabolismo , Animales , Disponibilidad Biológica , Masculino , Ratas , Ratas Wistar , TiempoRESUMEN
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague-Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9-39) (Ex9, 100 µg/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0·9665 and P = 0·3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0·0457) and of insulin (after 2 and 4 weeks, P = 0·0486 and P = 0·0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0·0297 and P = 0·0486) was higher along with a lower insulin response compared with the HFS group (P = 0·0564 and P = 0·0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance.