Background: Exenatide (EXE), a prototypical GLP-1R agonist, is known as glucoregulator, antiobesogenic and antidyslipidemic in hyperlipidic and hyperglucidic diet-induced obesity in rats (DIO). Objective: To evaluate bone effects of DIO and DIO treatment with EXE (DIO-

). Methods: 72-75-day-old male rats had access only to (i) hyperlipidic food (.2 kcal/g) and 30% sucrose solution for drinking (1.2 kcal/mL), or (ii) received normocaloric diet (3 kcal/g) and were allowed to feed and to drink water

ad

libitum. 122-125-day-old rats with 20% overweight were selected from i as obese and those with normal weight were selected from ii as control (C) animals. Thus, obese animals remained untreated (DIO) or were treated with 10 μg EXE/kg sc (DIO-) daily, for 20 days. Plasma levels of insulin (INS), leptin (LEP), osteocalcin (OCN), carboxy-terminal telopeptide of type 1 collagen (CTX-1) (ng/mL), as well as calcitonin (CT) and procollagen type 1 amino-terminal propeptide (P1NP) (pg/mL) were measured by ELISA. Bone mineral density of femur (BMDF) (g/cm³) was measured by X-rays. Results: DIO exhibited similar INS (12.±1.83, n=4) and CT (2.80±1.05, n=4), higher LEP (.33±.04, n=) and lower CTX-1 (.48±., n=3) than C. The treatment of DIO with EXE restored LEP (.04±.02, n=), decreased CTX-1 (.50±., n=) and increased CT (6.87±.72, n=). The levels of OCN (1.58±.41, n=), P1NP (.64±16.89, n=) and BMDF (1.±.07, n=) of C and those of DIO and DIO- were similar. Conclusions: Despite of increased LEP, decreased CTX-1 and normal OCN, P1NP and BMDF reflect a relative normal balance in bone turnover in DIO. Mechanical overloading due to high body mass is known as a factor that promotes this normal condition. Given that EXE decreases 14% body mass of DIO, the present study suggests that normalization of LEP and increased CT and decreased CTX-1 are concomitant beneficial effects of EXE that contribute for maintaining bone turnover under decreased mechanical load in DIO.

Supported by FAPESP, CNPq and CAPES

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At low levels, enterohemorrhagic Escherichia coli should be selectively isolated by suppressing competing microflora in meat samples. In conventional methods, MacConkey II Agar with C-T Sorbitol (cefixime-tellurite, CT-SMAC) which utilizes the ability of

E

. coli O157 to ferment sorbitol, and media containing -specific chromogenic substrates, are used for detecting

E

. coli O157.
In this study, we compared two types of CHROMagar^TM O157 for the isolation of enterohemorrhagic

E

. coli O157 (improved CHROMagar^TM O157 and conventional CHROMagar^TM O157) with CT-SMAC by using the Miles-Misra method and evaluating the recovers from ground beef and human fecal samples. The results obtained are described below:
1. In the inoculation test with three media by the Miles-Misra method, improved CHROMagar^TM O157 inhibited the growth of all organisms except

E

. coli O157 better than the two other media and allowed easy differentiation from

E

. hermannii, which could not be distinguished on CT-SMAC.
2. In the

E

. coli O157 detection test for ground beef artificially inoculated with

E

. coliO157 at 1 cfu/g, the detection rate of improved CHROMagar ^TM O157 was 95%, CTSMAC 75% and conventional CHROMagar^TM O157 40%, respectively.
4. In the

E

. coli O157 detection test for

E

. coli O157 positive human fecal samples, the detection rate of improved CHROMagar^TM O157 was 54.%, CT-SMAC 50% and conventional CHROMagar^TM O157 .7%, respectively.

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In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90° static light scattering. An exothermic lipid/protein interaction energy of W_P=190 kJ•mol^-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca²⁺ on the lipid/protein interaction were studied. Following Ca²⁺ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca²⁺. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-7,-diene-3β,,6β-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,6β-triol (4), 7-dehydrocholesterol () and cholecalciferol (6) were tested. The enzyme activities of MC3T3-1 cells were increased 3.-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, 3, and 6 did not induce MC3T3-1 cell ALP activity at .1—10 μM. These results suggested that the OH groups at C- and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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Amyloid β (Aβ) plays a key role in the pathology of Alzheimer’s disease (

) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aβ has high aggregative ability and potent toxicity due to the “toxic turn” at positions and 23. Furthermore, APP knock-in mice producing P-Aβ with the toxic turn exhibited -related phenotypes such as cognitive impairment, Aβ plaque accumulation, and tau hyperphosphorylation. In these mice, it is suggested that the activation of neuroinflammation and dysregulation of hypoxia-inducible factor (HIF) expression in the hippocampus contribute to the pathogenesis of -related phenotype. However, it remains unclear which cells are responsible for the dysregulation of HIF expression and the neuroinflammation which was induced by P-Aβ with the toxic turn. Here, we investigated the effects of chronic treatment with P-Aβ42 and lipopolysaccharides (LPS) on the inflammatory response in BV-2 microglia. Chronic treatment with P-Aβ42 and LPS increased nitric oxide production and the expression of interleukin-6 (IL-6), whereas it reduced the expression of HIF-1α and HIF-3α in BV-2 microglia. The reduction of HIF-1α caused by P-Aβ42 and LPS was milder than that caused by LPS. Furthermore, chronic treatment with P-Aβ42 and LPS increased the nuclear translocation of nuclear factor-kappaB (NF-κB). P-Aβ42 could enhance the inflammatory response of microglia with abnormal HIF signaling and contribute to the progression of pathology.

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Approximately 99% of the fat in huma milk is secreted into the alveoli by the mammary secretory epithelial cell (lactocyte) in membrane bound milk fat globules (MFG). The MFG, unlike small molecules such as lactose, have little effect on the osmotic balance between milk and blood and therefore they can be stored in large amounts in the alveolar lumen.Approximately 98% of the fat in the MFG are tri-acylglycerols (TAG). Importantly, different species, . g. women, rabbits, cows and elephants, have distinctive combinations of fatty acids esterified as TAG in their milk.We have measured 24-h milk production, fat content and fatty acid composition at 1, 2, 4, 6, , and 12 months of lactation in women.Mean (±SD) milk production (375.-1: 153.mL/24-h/breast) differed between breasts, between women and with stage of lactation (p<.05). Whereas the fat content (35.±7.86g/L) and the percentage composition of 18: 1n (32.24±3.3), 18: 2n6 (.18±2.66), 18: 3n3 (.76±.21), 20: 4n6 (.37±.07), : n3 (.17±.04), and : 6n3 (.2±.07) differed only between women and with stage of lactation (p<.05).In contrast, the amount delivered to the infant differed (p<.05) between women only for 18: 3n3, : n3 and : 6n3 and no differences in amounts delivered were observed for any of these fatty acids from 1 to 12 months of lactation.Each child received a mean (±SD) of 8.27-2.84 g 18: 1n; 2.38±.98g 18: 2n6;194±73mg 18: 3n3;±31mg 20: 4n6;43±14 mg : n3 and 49±21 mg : 6n3 every 24-h from breastmilk over the first year of life.These results indicate that variation in percentage composition of individual fatty acids (.g.18: 2n6) does not always translate to variation in the amount delivered to the infant.
Milk fat not only accounts for approximately 50% of the infant's energy intake, but also is responsible for the supply of the essential and long-chain polyunsaturated fatty acids that are required for the optimal development of the infant.For example, arachidonic acid (20: 4n6) and eicosapentaenoic acid (20: n3) are essential precursors for the synthesis of prostaglandins and immunomodulatory eicosanoids.On the other hand, docosahexaenoic acid (: 6n3, DHA) is a major polyunsaturated fatty acid in the membranes of the cerebral cortex and retina and higher intakes of DHA have been associated with higher ratings in intelligence tests particularly in children born prematurely. Fatty acids and mono-acylglycerols released by hydrolysis of TAG in the infant's digestive tract have a detergent like lytic action and inactivate enveloped viruses, gram positive and gram negative bacteria, fungi and protozoa.The membrane surrounding the human MFG contains mucin filaments that may act as a decoy to pathogenic micro-organisms ( coli).Micro-organisms recognise mucin filaments as membrane docking sites from which to launch an invasive infection and are thereby lured away from the membrane docking sites on the epithelial cells lining the infant's digestive tract.
Despite the importance of milk fat to the infant, it is the most variable component of human milk.It varies, over the course of a feed, over the course of the day, with stage of lactation, from one lactation to the next, between breasts, and between women. The major predictors of the fat content of milk over the course of a day have been shown to be the length of the interval between breastfeeds, the fat content at the end of the previous breastfeed, the amount of milk removed at the previous breastfeed and the amount of milk removed at the current feed.However, we have found that the fat content of milk is determined primarily by the amount of milk (degree of fullness) in the breast.For example, if the baby sleeps overnight, the mother's breasts will be full of milk in the morning and the fat content of fore-milk (milk obtained before a breastfeed) will be very low.

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This study set out to assess the respirable mass, surface area, and number concentrations of the α-quartz content particles (C_r-m, C_r-s and C_r-n) to which workers were exposed in six different exposure groups, the raw material handling (n=10), crushing (n=12), mixing (n=12), forming (n=10), furnace (n=10), and packaging (n=10), in a refractory material manufacturing plant. For C_r-m, the exposure values in sequence were found as: mixing (68.1 μg/m³)>packaging (55. μg/m³)>raw material handling (53.3 μg/m³)>furnace (31. μg/m³)>crushing (29.8 μg/m³)>forming (.4 μg/m³). We also found that ~21.2-68.2% of the above Cr-m exceeded the current TLV-TWA for the α-quartz content (50 μg/m³) suggesting a need for initiating control strategies immediately. We further conducted particle size-segregating samplings in four workplaces: crushing (n=3), mixing (n=3), forming (n=3), and furnace (n=3). We found that all resultant particle size distributions shared a quite similar geometric standard deviation (σ_g; =2.24-2.), but the process area, associated with higher mechanical energy (i.., crushing process), contained finer α-quartz content particles (mass median aerodynamic diameter; MMAD=3. μm) than those areas associated with lower mechanical energy (i.., mixing, forming, and furnace; MMAD=6.17, .95, and 8. μm, respectively). These results gave a ratio of C_r-m in the above four exposure groups (i.., crushing: mixing: forming: furnace=1.00: 2.30: .753: 1.04) which was quite different from those of C_r-s (1.00: 1.74: .654: .530) and C_r-n (1.00: 1.27: .572: .202). Our results clearly indicate the importance of measuring particle size distributions for assessing workers' free silica exposures.

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BACKGROUND

Atopic dermatitis (

) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of T cell-derived IL- in their pathogenesis. Although prostaglandin 2 (PGE2) is known to promote inflammation, little is known about its role in processes related to and ACD development, including IL- upregulation.

OBJECTIVES

We set out to investigate whether PGE2 has a role in T cell-derived IL-

induction and development of ACD, which has augmented prevalence in patients with .

METHODS

T cell cultures and in vivo sensitization of mice with powerful haptens (oxazolone and dinitrofluorobenzene) were used to assess the role of PGE2 in IL-

production. The involvement of PGE2 receptors and their downstream signals was also examined. The specific effects of PGE2 during ACD pathogenesis were evaluated by using the oxazolone-induced ACD mouse model. Gene expression of PGE2 and IL- signaling pathways was also investigated by using genomic profiling in human lesional skin biopsies.

RESULTS

PGE2 promotes IL-

production from T cells through its receptors, prostanoid receptor 2 (EP2) and EP4. This is mediated by its downstream cAMP-PKA signaling and probably involves the transcription factor aryl hydrocarbon receptor (AHR). Selective deletion of EP4 in T cells prevents hapten-induced adaptive IL- production in vivo. Importantly, blockade of endogenous PGE2 production by a COX inhibitor indomethacin or deletion of EP4 in T cells limit atopic-like skin inflammation in the oxazolone-induced mouse ACD model. Moreover, both PGE2 and IL- pathway genes were coequally upregulated in human lesional skin but were down-regulated after treatment with betamethasone or ultraviolet B (UVB) radiation, both common therapies for .

CONCLUSIONS

Our results thus define a crucial role for PGE2 in promoting ACD by facilitating T cell-derived IL-

production.

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This paper outlines a mathematical description of the stress dilatancy behaviour of granular materials which accounts for stress level and void ratio dependencies. The consideration of these aspects has important implications in the modelling of granular material behaviour. In fact, granular material mechanical response is largely dominated by the evolution of dilatancy, fabric and void ratio histories. The starting point in this study is the well established Rowe's theory which is revisited and ultimately modified by introducing a factor linked to governing state parameters in order to describe the complete behaviour of granular materials during deformation. Numerical simulations of triaxial tests on granular materials at different void ratios and stress levels are herein presented to illustrate the model.

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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin D₃ has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, 4, 6-trien-3-one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, 4-triazoline-3, -dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The , 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin D₃ compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin D₃, while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin D₃ ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin D₃.

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The gamma-ray spectrum and the conversion-electron spectrum are measured in the decay of the ^116mIn activity. Directional correlations are also measured for 818–1293 and 1097–1293 keV cascades. The M1-2 mixing ratio δ, and the -2 mixing ratio μ_k are obtained for 818.7 keV +→2₁⁺ transition to be δ=1.52−

0.22

+

0.26

, and μ_k≤6.1×10⁻⁴ respectively. The

E

2 branching ratio B(

E

2;

2₂

+→

0_g

+): B(

E

2;

2₂

+→2₁⁺): B(

E

2;

2₂

+→0₁⁺) is determined to be

0

.0158:1.

0

:

5

.86.

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Background: Exenatide (EXE), a prototypical GLP-1R agonist, has been reported as beneficial to the balance of bone turnover in hyperlipidic and hyperglucidic diet-induced obesity in rats (DIO). Objective: To identify the mediation by GLP-1R of insulin (INS), leptin (LEP), osteocalcin (OCN), calcitonin (CT), carboxy-terminal telopeptide of type 1 collagen (CTX-1), procollagen type 1 amino-terminal propeptide (P1NP) and bone mineral density of femur (BMDF) in DIO. Methods: 72-75-day-old male rats had access only to (i) hyperlipidic food (

.2 kcal/g) and 30% sucrose solution for drinking (1.2 kcal/mL), or (ii) received normocaloric diet (3 kcal/g) and were allowed to feed and to drink water

ad

libitum. 122-125-day-old rats with 20% overweight were selected from i as obese and those with normal weight were selected from ii as control (C) animals. Thus, obese animals remained untreated (DIO) or were treated sc with 100μg of the competitive antagonist of GLP-1R, exendin (-39) () per kg (DIO-) daily, for 20 days. Plasma INS, LEP, OCN, CTX-1 (ng/mL), CT and P1NP (pg/mL) were measured by ELISA. BMDF (g/cm³) was measured by X-rays. Results: DIO exhibited similar INS (12.90±1.83, n=4) and CT (2.80±1.05, n=4), higher LEP (.33±.04, n=) and lower CTX-1 (.48±., n=3) than C. The treatment of DIO with decreased CTX-1 (4.44±.63, n=3) and increased P1NP (163.40±39.80, n=3). DIO- decreased INS (.75±1.50, n=3) in relation to DIO, at the same level than C (10.58±1.49, n=4). LEP level in DIO- (.23±.02, n=3) was intermediate in relation to DIO and C (.16±.05, n=). OCN, CT and BMDF were similar among C, DIO and DIO-. Conclusions: Decreased CTX-1 and normal OCN, P1NP and BMDF reflect a relative normal balance in bone turnover in DIO. Since decreases CTX-1, a known effect of EXE in DIO, this alteration on CTX-1 extrapolates the GLP-1R binding and/or EXE and act as selective modulators with different actions in different targets. Furthermore, increases P1NP (not affected by EXE) and does not affect CT (increased by EXE). effects in DIO imply in increased osteoblastic and decreased osteoclastic activities, which promote an imbalance of bone turnover.

Supported by FAPESP, CNPq and CAPES

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We compared three groups of pregnant women: placebo with normotensive women, group A which included preeclamptics, and group B which comprised preeclamptics who were supplemented their diets with vitamins C and . MDA increased from 6. ± 2.8 (placebo) to 8.48 ± 1.2 (A) and 8.02 ± 1.8 nmol/gHb (B). NO concentrations were enhanced from 19.3 ± 4.2 (P) to 23.8 ± 6.4 (A) and 24.1 ± .4 μmol/L (B). GSH contents were decreased from 10.42 ± 2.81 (P) to 8.02 ± 2. (A) and .39 ± 1.02 μmol/g Hb (B), whereas GSSG concentrations increased from .98 ± .28 (P) to 1.24 ± .29 (A) and 1.08 ± .12 μmol/g Hb (B). SOD activity decreased 23% in A and 14% in B; GRx decreased 27% in A and .% in B; GPx decreased 12% in A and .6% in B. Catalase activity, however, increased 27% in A and 29% in B as compared to control. Thus, we conclude that the use of vitamins C and should be considered for the control of certain important biochemical indices during the development of preeclampsia; however, further studies are needed to develop methods for the prevention of preeclampsia in women at high risk.

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Distribution of bacteria which produce enzyme capable of lysing Str. mutans 49 strain in human dental plaques was investigated on adults of age 20 to . The activity of the enzyme (MLE) produced by an isolated strain (FDC-63) was also investigated. The results obtained are summarized as follows. 1. MLE producing bacteria were detected in 43 samples (37.1%) out of 116 samples of dental plaques obtained from adults of age 20 to . 2. Twenty four samples had MLE producing bacteria at the rate of over % of total number of bacteria in each sample. 3. The 40 strains isolated were composed of .% of Gram positive cocci, 2.% of Gram negative cocci and % of Gram positive rods. 4. Most of the isolates (84.6%) showed lytic activity against living cells of 49 on GAM agar plates. . The MLE produced by FDC-63 had lytic activity against both living and heat killed cells of 49 under aerobic or anaerobic condition. 6. The activity of the MLE was rather weak against purified cell walls of 49. 7. Optimal pH in the activity of the MLE was 6. and optimal temperature 37℃. The activity of the MLE was lost by heating at 60℃ for 60 min. 8. FDC-63 was identified as Streptococcus milleri.

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