ラットに

3H

-CU-

83

(S)を25μg/kgで静脈内あるいは経口投与し，血液中濃度および尿糞中排泄を検討した．
静脈内投与後の血液中濃度推移は投与後5分より上昇し，投与後45分に25.74ng eq./mlのC_maxを示し，それ以後t1/

2

3

.05時間とt1/

2

33.09時間の二相で減少した．投与後72時間までのAUCは135.42ng eq.·hr/mlであった．
経口投与では，投与後

3

時間でC_max 4.10ng eq./mlに達し，以後t1/

2α

4.46時間とt1/

2β

26.

83

時間の二相で減少した．投与後72時間までのAUCは48.62ng eq.·hr/mlであった．
静脈内投与と経口投与のいずれの場合も，尿および糞中への放射能の排泄は，投与後48時間でほぼ終了した．静脈内投与では，投与後72時間までに投与量の30.52%が尿中に，60.42%が糞中に排泄された．経口投与では，同じく72時間までに40.34%が尿中に，69.24%が糞中に排泄された．

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The acetone extracts from three samples of the hepatopancreas of the poisonous scallops obtained on the Okhotsk Coast of Hokkaido Island were fractionated into two parts, hexane soluble fraction (fraction H) and 85% aqueous ethanol soluble fraction (fraction ) by partition to two layers. The majortoxic components in the mouse assay of “diarrheic shellfish toxin” by intra-peritoneal injection were found to be free unsaturated fatty acids showed the following toxicity in MU per g, 18:1 n- 35, 18: n-6 , 18: n- 167, 18:4 n- , 20:5 n- 167, and :6 n- , respectively. Toxicity of the fraction Hin MUper g was much lower than that of the fraction . However, the toxicity of the fraction H per 1 g of the hepatopancreas was about twice that of the fraction , since the fraction Hwas much more abundant than the fraction in the hepatopancreas. The method for the assay of the diarrhetic shellfish toxin must be reexamined by considering the toxic effect of the free unsaturated fatty acids.

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The percentages of germination of seeds, dyad cells, good pollen grains and the fcrtility of piants obtained by crossing between 8 varieties of Abel. esculerdu's and I variety of Abel. Manihot wcre different with the varieties of the mother plant, ranging ca..7%-.%, ca. .7 %-99.%, ca. 28.%-90.8% and ca. 0.00-0. per pod respectively. The strains showing the good percentage in the gerrnination of seeds were also superior in the other characters, while those tnat werepoor in the germination were also inferior in the other characters.

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The numerical values of the intervals betrween optieal levels are competed for the configurations *⁹4s, 5s, 6s and 7s of Cu⁺, according to the general expression of energy-levels derived in the previous paper The self-consistent field radial functions computed by Hartree adn Hartree are used for1s, s, p, s, p and d. Those of 4s, 5s, .s and are ealenlated from Hartree Hartree's core-functions by the numerical integrations. The calculated results are shown in Table I.The agreement with experiment is satisfactory

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-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-,5α,6β-triol (1). 1 induced ALP activities of MCT-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 MCT-1 cells by 1, ergosterol (), ergocalciferol (), cholesta-,5α,6β-triol (4), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and .4-fold by 10 μM 4. However, , , 5 and 6 did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C-5 and/or C-6 of 1 and 4 played an important role in their differentiation-inducing activities on MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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A full account is given of the chemical behavior observed for 7, -dialkyladeninium salts (16). On treatment with boiling 1N aqueous NaOH for 60min, 16a, b, d, (X=I), 16c (X=Br), and 16 (X=ClO₄) rearranged to isomeric N⁶, 7-dialkyladenines (21a-) in 50-91% yields. Treatment of the salts with 0.5N aqueous at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in at room temperature gave the ring-opened derivatives a- (in the trans-formamide form) in 56-% yields, and rate constants for the ring-opening reactions of 16a, b, d-g (X=ClO₄) and 16c (X=Br) leading to a-g were determined in at pH .84 and ionic strength 0.50 at 25°C. Cyclization of a with NaH in at room temperature or with boiling 1N aqueous NaOH produced 21a in 84% or 72% yield, respectively.In solution, the trans-formamides seemed to transform slowly into the cis-formamides 23, attaining equilibria. The existence of such an equilibrium in or -d₆ at 25°C or in at pH .84 and ionic strength 0.50 at 25°C was kinetically confirmed in the case of a, and the mechanism of the rearrangement of 16 to 21 through is discussed on the basis of the above kinetic results and Deslongchamps' theory of stereoelectronic control. On treatment with NaBH₄ in MeOH at room temperature, 16a (X=I) furnished the 7, 8-dihydro derivative 28 (84% yield), which slowly decomposed in at 60°C to give a in 49% yield.The 7, -dialkyladeninium salts (16) were found to be obtainable from N'-alkoxy-1-alkyl-5-formamidoimidazole-4-carboxamidines () through an alternative synthetic route : Alkylations of with alkyl halides in in the absence of base, followed by hydrogenolysis of the N'-alkoxy group and cyclizatio (or vice versa) produced 16 in acceptable yields. In order to interpret the proton nuclear magnetic resonance spectrum of a, the -deuterated species 26 was also synthesized from 24 via 25 and 27.

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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin 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, -epoxide generated by epoxidation of the 1, 4, 6-trien--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, , 4-triazoline-, 5-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 5, 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 compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin .

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The thermo-isomerization of l-cis-pinane (1), -pinene () and (10)-pinene () in the presence of synthetic zeolites (A-, A-4, A-5, - and TSZ-642) was investigated. Whith TSZ-642 zeolite, dihydromyrcene (5) was obtained with high selec-tivity (high 85%) in all converted products from (1). 4 /6 Z-Alloocimene (10) and 4 /6 -alloo-cimene (11) were obtained from () as the main products, amounting to 86% (77:) of the isom-erization product. Myrcene (12) was obtained from () as the main product, amounting to % of the isomerization product under the best conditions.

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In this study, the chemical composition and anti-inflammatory activities of hydrodistilled essential oil from Farfugium japonicum were investigated for the first time. The chemical constituents of the essential oil were further analyzed by GC-MS and included 1-undecene (.43%), 1-nonene (19.%), β-caryophyllene (12.26%), α-copaene (.70%), γ-curcumene (.86%), germacrene D (.69%), and 1-decene (.08%). The effects of the essential oil on nitric oxide (NO) and prostaglandin () production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages were also examined. The results indicate that the . japonicum essential oil is an effective inhibitor of LPS-induced NO and production in RAW 264.7 cells. These inhibitory effects of the . japonicum essential oil were accompanied by dose-dependent decreases in the iNOS and COX- mRNA expression. In order to determine whether . japonicum essential oil can safely be applied to human skin, the cytotoxic effects of . japonicum essential oil were determined by colorimetric MTT assays in human dermal fibroblast and keratinocyte HaCaT cells. . japonicum essential oil exhibited low cytotoxicity at 100 μg/mL. Based on these results, we suggest that . japonicum essential oil may be considered a potential anti-inflammatory candidate for topical application.

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本検討は, 経皮的冠動脈形成術 (PCI) 後の翌日血液透析 (HD) 時における透析中低血圧 (IDH) の発生因子について検討した. 対象は待機的PCI後, 翌日HDを施行した慢性HD患者連続

名 (年齢70±7歳, 男性64名). IDHの定義は, 収縮期血圧20mmHg以上の低下で, 症状を伴いかつHD中断を要したものとした. また, HD記録よりIDHを後方視的に調査し, Logistic回帰分析にてIDHの予測因子を検討した. IDH群 (12名) は非IDH群 (71名) に比して, 有意に低体重 (52.0±.8 vs. 62.±1.5kg; p=0.007), 造影剤量/体重が多く (.5±0. vs. 1.8±0.1mL/kg; p=0.018), 低左室駆出率で (45.8±4. vs. 56.0±1.8% ; p=0.030), /’ が高値 (.±.8 vs. 17.±0.cm/sec; p=0.038) であった. また, 冠動脈病変や侵襲的な治療について有意差は認めなかった. Logistic回帰分析では, 造影剤量/体重 (OR, 6.87; 95%CI, 1.-25.8; p=0.004) がIDHの有意な予測因子であった. 造影剤使用量が多い症例は, IDHを生じる危険性が高いことが示唆された.

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A new glucuronide, (R)-, 16β, , 26-tetrahydroxycholest-5-ene -O-α-L-rhamnopyranosyl-(1→)-β-D-gluc-uronopyranoside (1), was isolated from the aerial parts of Chinese Solanum lyratum THUNB. The structure of this new steroidal glucuronide was deduced by spectroscopic means and the identity of its aglycone was substantiated by comparison with an authentic sample derived from diosgenin acetate.

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性周期における牛の末梢血中遊離estrogen測定にITTRICH螢光法を応用して次の成績を得た。
Ittrich colorの最大波長をspectrofluorometer Hitachi MPF-AおよびType203で測定した結果,励起光538nm,螢光552.5nmであった。この螢光特性は, およびにそれぞれ共通であった。実際の測定では最大波長が接近しているので感度は若干低下するが510~520nmで励起し•螢光側552•5±•5nmを読み,ALLENの補正を行なった。この条件において,および-methyletherの最少検出量は1ngであった。回収率補正の目的で加えた6,7-

3H

-

E₂

-17βの全過程における回収率は平均60.

3

±11.7%であった。正常性周期を示す黒毛和種

2

頭の頸静脈血についてestrogenを分画測定した。その結果,両牛共

E₁

,

E₂

の各消長型は性周期の全期間を通じてほぼ同じ傾向を示したが,

E₂

は

E₁

にくらべ全般に高値であった。また

E₃

は検出されなかった。これらの牛のtotalestrogenは発情前期に増加し,排卵前に鋭いピーク(35.

3

および99.8ng/l;

E₁5.9

および16.0ng/l,

E₂29.4

および

83.8ng

/l)を形成し,排卵後は急激に減少して最低値(

3

.8~

5.3ng

/l;

E₁1.6

および

1.9ng

/l,

E₂2.2

および

3.4ng

/l)を示した。黄体期の最高値(10.1および27.0ng/l;

E₁2.4

および

3.4ng

/l,

E₂7.7

および23.6ng/l)は排卵後6~8日に認めた。すなわちestrogenの血中濃度は性周期の間に

2

つのピークを形成することを認めた。

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A structure analysis of has been carried out to determine the deuterium trap sites by neutron powder diffraction with the Rietveld profile analysis. It is revealed that the deuterium atoms are located at octahedral () sites surrounded by six Ti atoms in the crystal structure of , space group P6₃/mcm. Local vibration spectra of hydrogen in measured by neutron inelastic scattering support this result; the energy eigenvalue of the primary vibration mode is found at 7.53 kJ/mol (78 meV). The hole radius and the spring constant of the Ti-H(D) bond are discussed.

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Ferri-ghoseite（フェリゴース閃石）が和歌山県飯盛鉱山より見出された．X線実験に使用された部分はEPMAにより分析され，その化学式は，^A(Na_0.16K_0.02)_Σ0.18^B(+_1.08)

Σ2.00^C

(

Mg_3.78Mn²

+

0.52Fe³

+
_0.66Al_0.04)_Σ5.00^T(Si_7.95Al_0.05)

Σ8.00O₂₂^W

[(OH)

1.90F_0.10

]

Σ2.00

である．単結晶X線回折実験により得られた格子定数は， a =

9

.6389(7), b = 18.0534(10), c = 5.3138(

3

) angstrorm and beta = 102.896(

2

) degreeである．

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The EISCAT Svalbard Radar (ESR) has been used to obtain ion velocities in the lower thermosphere. By using beam swinging and assuming homogeneity and stationarity of the plasma, first approximations to the electric field have been deduced, and thus the thermospheric neutral wind has been estimated. From these derived parameters, we have estimated the gradient Richardson Number. Although many assumptions must be made, there is an indication that electrodynamics is able to contribute to enhancement or even production of neutral-air turbulence in the lower thermosphere. Finally, we outline a proposal for an analogy to the Reynolds Number, but reflecting the relative importance's of the contribution of ion-drag to the neutral dynamics and the kinematic viscosity.

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Immunosuppressive drugs exhibit high variability in metabolism and pharmacokinetics, that may result in drug toxicity or lack of efficacy. Low immunosuppressant drug exposure increases the risk of transplant rejection in the acute post-transplant period, while supratherapeutic drug concentration entails higher risk of adverse drug reactions¹. These issues may be resolved by population pharmacokinetic modeling.

Population pharmacokinetic modeling might be performed and researched by clinical pharmacologists, recently established clinical pharmacology residency in Lithuania may play a role in this area as

.

Aims:to broaden the competence of Lithuanian clinical pharmacologists by developing one-compartment model with first-order absorption of tacrolimus.

Methods.Anonymized medical records of kidney recipients receiving immunosuppressant tacrolimus and hospitalized at Limoges University Hospital(France) were included in the study. Tacrolimus analyses were performed using a liquid chromatography-tandem mass spectrometry method. A one-compartment model with first-order absorption was used as implemented in the NLMIXED

, which fits nonlinear mixed models. Data analysis was performed by using SAS University Edition software. Model parameter estimated are provided with p-values and confidence limits computed by NLMIXED procedure. The p-values and confidence limits were computed from approximate standard errors (using the delta method) for the estimates.

Results.Anonymized medical records of 189 patients receiving immunosuppressant tacrolimus (

-20mg/d BID regimen) were analyzed and a one-compartment model with first-order absorption was constructed. The population estimates in the final population model of tacrolimus were: clearance 14.64L/h(CI .66; 19.62),p<0.0001, elimination rate 0.001657 min^-1(CI:0.00098;0.002336),p<0.0001 and absorption rate .7119(CI:-45.7083; 51.1321),p=0.912. Mean value of concentration was 13.62(SD:7.5)µg/L, predicted concentration 10.(SD:10.)µg/L. Pearson correlation between measured and predicted concentrations was r=0.79(p<0.0001).

Conclusions.

1.Population pharmacokinetic models should be developed in-house.

.Clinical pharmacologists should participate in pharmacokinetic modeling process.

This research was funded by a grant (No.P-MIP-17-445) from the Research Council of Lithuania. This research was performed in cooperation with the Limoges University Hospital,France.

References

1.Noreikaite,A; Saint-Marcoux,

; Marquet,P; Kadusevicius,; Stankevicius,. Influence of cyclosporine and everolimus on the main mycophenolate mofetil pharmacokinetic parameters: Cross-sectional study. Medicine(Baltimore). 2017;96(13):6469. doi:10.1097/MD.0000000000006469.

.Maciulaitis,R. Pharmacology in Estonia,Latvia and Lithuania: From historical roots to nowadays achievements. Pharmacol Res.2016;113:723-730. doi:10.1016/J.PHRS.2016.04.024.

.PROC NLMIXED:Introduction: SAS/STAT(R) . User's Guide. https://support.sas.com/documentation/cdl/en/statug/63347/HTML/default/viewer.htm#statug_nlmixed_sect002.htm. Accessed January,2018.

Figure.Predicted vs. observed concentration (µg/L)

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