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Empagliflozin and metformin are oral antidiabetic drugs commonly used to treat type 2 diabetes mellitus as a combination therapy. This study aimed to compare the pharmacokinetics and safety of a newly developed fixed‐dose combination of 5‐mg empagliflozin L‐proline and 1000‐mg metformin with the reference drug. A randomized, open‐label, single‐dose, 2‐period, 2‐treatment, crossover study was conducted in healthy Korean subjects. The subjects received a single oral dose of reference drug or test drug at each period. The pharmacokinetic (PK) parameters were calculated using a noncompartmental method. The geometric mean ratios and 90% confidence intervals of the plasma maximum concentration (Cmax) and area under the concentration–time curve from time zero to the last quantifiable concentration (AUClast) were calculated. A total of 27 healthy subjects were included in the PK analysis. For empagliflozin, the geometric mean ratios (90% confidence intervals) of the test to reference drug for Cmax and AUClast were 1.03 (0.99–1.08) and 1.03 (1.00–1.06), respectively. For metformin, the corresponding values for Cmax and AUClast were 0.99 (0.92–1.06) and 1.00 (0.94–1.06), respectively. In conclusion, a fixed‐dose combination of empagliflozin L‐proline and metformin showed similar PK characteristics to the reference drug, and both drugs were safe in healthy subjects. [ABSTRACT FROM AUTHOR]

This study aimed to compare the pharmacokinetic profile of combined CKD‐395 0.5/1000 mg treatment with that of the coadministration of lobeglitazone sulfate 0.5 mg and metformin hydrochloride (HCl) extended‐release (XR) 1000 mg and assess the effect of food on the pharmacokinetics of CKD‐395 0.5/1000 mg. Two clinical trials were conducted as part of an open‐label, single‐dose, randomized, 2‐period, 2‐sequence crossover study. In study 1, a total of 26 subjects received either CKD‐395 0.5/1000 mg as a test drug or coadministration of lobeglitazone sulfate 0.5 mg and metformin HCl XR 1000 mg individually as a reference treatment under fed conditions. In study 2, a total of 16 subjects received CKD‐395 0.5/1000 mg treatment under either fasted or fed conditions. Blood samples were collected at intervals from 0 to 48 hours. In study 1, the geometric mean ratios and 90% confidence intervals of pharmacokinetic parameters for lobeglitazone and metformin were all within 80%–125% in the fed condition. In study 2, there were no high‐fat meal effects on the area under the curve extending up to the last sampling time (AUClast) of lobeglitazone, but there was a decrease in the maximum plasma concentration (Cmax) of lobeglitazone by approximately 32% in the fed condition. Although the AUClast of metformin increased by approximately 70% in the fed condition, there was no effect of food on the Cmax of metformin, which is consistent with the already‐established food effect on metformin HCl XR. No adverse drug reactions or serious adverse events were observed. This study suggests that CKD‐395 0.5/1000 mg exhibits similar exposure and absorption rates to coadministration of single agents and is well tolerated under both fasted and fed conditions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether, when subjects were living in a moderately warm environment: (1) the softness of clothing worn during the daytime could influence the subjects’ preference in the evening for the softness of clothing and a face towel; and (2) the softness of bedding materials could modulate their nocturnal body temperature, overnight urinary catecholamine excretion, and sleep quality. Six females were tested during the luteal phase of their menstrual cycles. The experiment was conducted over three consecutive days and nights in a climatic chamber controlled at 28 ± 0.2 °C and 50% RH during the evening (from 19:30 to 21:30 h) and at 29 ± 0.2 °C and 50% RH during the sleep period (from 22:30 to 07:00 h). The first night was for adaptation to the experimental chamber. Five different sets of clothing and bedding were used; these were identical except for the softness/hardness of the materials used (due to treatment with fabric softener or starch), and material softness decreased in the order: Type A (softest) > Type B > Type C > Type D > Type E (hardest). There were two phases to the experiment, conducted in random order. In one phase, subjects wore “soft type” (Type B) T-shirt and shorts in the daytime and, in the other phase, “hard type” (Type D/E) T-shirt and shorts. In both phases, subjects were asked at 21:30 h to select a T-shirt and a face towel which they felt would be most comfortable to use. At night, they slept on bedding (a mattress cover, a pillowcase and a covering blanket) which was of the same degree of softness as the T-shirt and shorts that had been worn in the daytime in that phase. Rectal temperature, skin temperatures at seven sites, and body movement were measured during sleep, an overnight urine sample was taken for measurement of urinary excretion of adrenaline and noradrenaline, and subjective sleep quality was assessed on being woken the following morning. The main results were as follows: (1) T-shirt preference in the evening showed large inter-individual variation but did not differ significantly between the two phases (when “hard type” or “soft type” clothing had been worn during the daytime). The preferred texture of the face towel was softer than that of the T-shirt, the difference in softness between the chosen face towel and T-shirt being significant (p < 0.05 andp < 0.10, respectively, when having worn “soft type” and “hard type” clothing in the daytime). (2) Rectal temperature and mean skin temperature were not significantly different when sleeping with “soft type” (Type B) and “hard type” (Type D/E) bedding materials. (3) Overnight secretions of urinary adrenaline and noradrenaline were significantly less with “soft type” than “hard type” (p < 0.01 andp < 0.05 for adrenaline and noradrenaline, respectively) bedding. (4) When sleeping with “soft type” bedding materials, five out of the six subjects showed less body movements during the sleep period and reported that they had slept better. These results suggest that, in a moderately warm environment, bedding materials with a softer texture might be more comfortable to the subject (due to less tactile stimulation of the skin, which results in neurophysiological relaxation) and provide them with better sleep quality. [ABSTRACT FROM PUBLISHER]

In human circadian rhythm research, rectal temperature is the traditional gold standard for estimating core temperature, but the measurement of rectal temperature is inconvenient and unacceptable to some subjects. This study examined whether the circadian rhythm of forehead skin temperature would be an alternative to that of rectal temperature in sedentary subjects living in a thermally neutral environment. Six healthy female volunteers participated as subjects for 37.5 h, from 21:30 h on day 0 to 06:30 h on day 2. They were tested twice while wearing two different types of clothing. One type of clothing covered the whole body except the head and hands (Type L); the other exposed the head and distal extremities (Type H). Subjects lived in a climatic chamber controlled at 23.8 ± 0.2 °C and 60 ± 5% RH with light intensity of 500 lux from 06:30 to 19:30 h, 100 lux from 19:30 to 22:30 h and 0 lux from 22:30 to 06:30 h. Rectal temperature and skin temperatures at seven sites were recorded continuously at 10 min intervals. The extent to which the circadian rhythms of forehead and hand skin temperature mirrored that of rectal temperature was determined by cross-correlation and cosinor analyses. Cross-correlation analysis of data from the group or individuals, and whether wearing Type L or Type H clothing, indicated that the profile of forehead skin temperature was similar to that of rectal temperature, with highly significant positive correlation coefficients (r = 0.9099–0.9744) and time lags of 0.17–0.33 h. By contrast, the profile of hand skin temperature was approximately in antiphase, with smaller correlation coefficients (though still highly significant:r = 0.6036–0.7526), and with time lags of 11.00–14.11 h. Cosinor analysis indicated that the acrophase of the circadian rhythm of forehead skin temperature for individuals was slightly, but not significantly, earlier than that of rectal temperature with both types of clothing (0.54 ± 0.68 and 0.35 ± 0.64 h with Type L and Type H clothing, respectively). The circadian rhythm of forehead skin temperature showed a significantly greater amplitude and lower mesor than rectal temperature, whether wearing Type L or Type H clothing. Individuals’ data gave 0.38 ± 0.09 and −2.92 ± 0.31 °C, respectively, with Type L clothing and 0.40 ± 0.26 and −2.86 ± 0.35 °C with Type H clothing; these differences were not significantly different between the two types of clothing. It is concluded that, in sedentary subjects living in a thermally neutral environment, forehead skin temperature gives information regarding phase and some aspects of amplitude that can act as substitutes for rectal temperature data. [ABSTRACT FROM AUTHOR]

Abstract: Nuclear magnetic resonance (NMR) techniques coupled with multivariate data analysis were used to conduct monitoring of biochemical changes of black raspberry fruits at different stages of maturation and under various extraction and NMR dissolution solvent conditions: extraction with 50% methanol and D2O as an NMR dissolution solvent, extraction with 50% methanol and 50% methanol-d 4 as an NMR dissolution solvent, and extraction with 100% ethyl acetate and 100% methanol-d 4 as an NMR dissolution solvent. Partial least-squares discriminant analysis reliably distinguished black raspberry fruits according to the maturation stage, whereby the relative levels of various compounds such as amino acids, organic acids, sugars and phenolic compounds were compared using analysis of variance. Sucrose and most of the amino acids, and organic acids decreased, whereas fructose, glucose, and cyanidins increased in relative concentration according to maturation of black raspberry fruits. The total number and kinds of assigned compounds of the three solvent systems were also compared. This research demonstrates that the metabolic profile of black raspberry fruits changes during maturation, and provides objective criteria for determining the stage of black raspberry fruit maturation via a 1H NMR-based metabolomics technique using multiple solvent systems. [Copyright &y& Elsevier]

Abstract: The effect of administration of Korean black raspberry (BR) to smokers was assessed by 1H nuclear magnetic resonance (NMR) coupled with multivariate statistical analysis. In this study, to investigate the effect of BR on the level of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), biomarker for DNA damage, 38 male smokers between 20 and 30years old were treated with BR or placebo for 4weeks. After 4weeks of administration, urinary level of 8-OHdG was measured, and the metabolic profiling of plasma samples of all volunteers were established using 1H NMR-based metabolomics techniques. The volunteers of BR administered group were divided into responder group (BR-R group) and nonresponder group (BR-NR group) based on the mean decrement of urinary 8-OHdG level of placebo group (12%). There was a clear separation among weeks 0 and 4 of seven volunteers at BR-R group in principal component analysis (PCA) derived score plots. The levels of 16 metabolites including amino acids, and organic acids changed significantly between weeks 0 and 4. Then the comparative metabolic profiling of the BR-R and BR-NR groups at week 0 was performed. There was also clear separation in PCA-derived score plot. The relative levels of glycine and trimethylamine N-oxide in plasma changed significantly between the two groups, indicating that these compounds could be used as screening biomarkers to predict the 8-OHdG modulating activity of BR in smokers. [Copyright &y& Elsevier]

The biological treatment of a tri-component mixed waste gas system in BRC1 and BRC2 biofilters packed with rock wool-compost media was studied. The model gases were NH3, H2S and toluene. The gases were fed initially at about 50–55ppm each. H2S was found to have the shortest start-up while toluene had the longest. Under two different NH3:H2S:toluene concentration ratios of 250:120:55 and 120:220:55 (in ppm) for BRC1 and BRC2, the removal efficiencies of NH3, H2S and toluene were found to be affected by their respective loading rate. On the other hand, toluene removal was observed to be inhibited at H2S concentration of 220ppm as well. Almost complete removal of NH3 and H2S was achieved when loading rate was applied up to 16.14g-NH3/(m3 bedh) and 36.09g-H2S/(m3 bedh), respectively. The maximum elimination capacity for NH3 was determined to be 23.67g-NH3/(m3 bedh) at 78.6% removal efficiency and for H2S, 38.50g-H2S/(m3 bedh) at 68.1% removal efficiency. The maximum toluene elimination capacity was 30.75g-toluene/(m3 bedh) at 87.9% removal efficiency when the concentration of NH3:H2S:toluene was 250:120:55 in BRC1, and was 16.60g-toluene/(m3 bedh) at 45.5% removal efficiency when the concentration of NH3:H2S:toluene was 120:220:55 in BRC2. The pressure drops along both columns were low and the ratio of bed compactions over biofilter height was observed to be less than 0.02. [Copyright &y& Elsevier]

Metabolic alterations of Cordyceps bassiana mycelium were investigated under the following culture medium and light conditions: dextrose agar supplemented with 0.5% yeast extract (SDAY) medium with light (SL), SDAY medium without light (SD), nut medium without light (ND), and iron-supplemented SDAY medium without light (FD). The levels of asparagine, aspartic acid, glutamic acid, glutamine, histidine, lysine, ornithine, and proline were significantly higher under SD and SL conditions. The levels of most of the alcohols, saturated fatty acids, unsaturated fatty acids, fatty acid esters, sterols, and terpenes were higher under the ND condition than in the other conditions, but beauvericin was not detectable under the ND condition. The FD condition was favorable for the enhanced production of aminomalonic acid, malic acid, mannonic acid, and erythritol. Thus, the metabolic characteristics of C. bassiana can be manipulated by varying the cultivation conditions, rendering this fungus potentially favorable as a nutraceutical and medicinal resource.

The quantitative performance of a simple home-built preparative gas chromatography (prep-GC) arrangement was tested, incorporating a micro-fluidic Deans switch, with collection of the target compound in a deactivated uncoated capillary tube. Repeat injections of a standard solution and peppermint sample were made into the prep-GC instrument. Individual compounds were eluted from the trapping capillary, and made up to constant volume. Chloronaphthalene internal standard was added in some cases. Recovered samples were quantitatively assayed by using GC-MS. Calibration linearity of GC-MS for menthol standard area response against number of injections (2-20 repeat injections) was excellent, giving R(2) of 0.996. For peppermint, menthol correlation over 2-20 repeated injections was 0.998 for menthol area ratio (versus IS) data. Menthone calibration for peppermint gave an R(2) of 0.972. (1) H NMR spectroscopy was conducted on both menthol and menthone. Good correspondence with reference spectra was obtained. About 80 μg of isolated menthol and menthone solute was collected over a sequence of 80 repeat injections from the peppermint sample, as assayed by 600 MHz (1) H NMR analysis (∼100% recovery for menthol from peppermint). A procedure is proposed for prediction of number of injections required to acquire sufficient material for NMR detection., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This study investigated how socks-wearing habit or habitual barefoot in the cold winter affected skin temperatures of distal lower extremities, the urinary excretion of adrenaline, noradrenaline and cortsisol in young children. In Experiment I for preschool children, the measurements of foot and leg skin temperatures were conducted for 30 min in the classroom controlled at 23+/-2 degres C and 50+/-5%RH, and the excretion of urinary catecholamines and cortisol during nocturnal sleep were analyzed. In Experiment II for elementary school children, nocturnal secretion of urinary catecholamines and cortisol was analyzed. While leg skin temperature tended to be lower in barefoot group than in socks group during Experiment I, foot skin temperature was not significantly different between the two groups. Fall of leg skin temperature during 30 min measurement tended to be smaller in barefoot group than in socks group. Urine volume and urinary excretion of cortisol tended to be greater in barefoot group than in socks group for preschool children. Urinary noradrenaline was significantly greater and cortisol tended to be greater in barefoot group than in socks group for elementary school children. Considering that most of the findings shown above were in the proximity of the established level of statistical significance, it was provisionally concluded that young children with barefoot habituation might show more effective cold adaptation of metabolic type than those without the habituation do, by keeping their skin temperatures higher even in the cold and enhancing the metabolic rate.