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 (2b) 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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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t_1/2

3

.05時間とt_1/2 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t_1/2α 4.46時間とt_1/2β 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, 18:2 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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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 (2b) sites surrounded by six Ti atoms in the crystal structure of , space group P6₃/mcm. Local vibration spectrum of hydrogen in measured by neutron inelastic scattering supports 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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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.2.7%-.%, ca. .7 %-99.%, ca. 28.%-90.8% and ca. .00-. 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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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.±.8 vs. 62.±1.5kg; p=.007), 造影剤量/体重が多く (2.5±. vs. 1.8±.1mL/kg; p=.018), 低左室駆出率で (45.8±4.2 vs. 56.±1.8% ; p=.030), /’ が高値 (.±.8 vs. 17.2±.cm/sec; p=.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=.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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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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A Fabry-Perot resonance (.P.R.) type Faraday rotator which consists of a magneto-optic medium with mirror coating at the ends has been made. The Faraday rotation of the medium is enhanced (1+Re^-αl)/(1−Re^-αl) times (R: reflectivity of the mirror, -αl: optical loss of the medium) under .P.R. condition. As a theory predicts, the Faraday rotations of the rotators using Pyrex glass and GGG with silver coating of R=. and . were enhanced 10 and 20 times, respectively, while, when the rotator using LPE-garnet film with silver coating of R=.8 was used, the enhancement was limited to times. The difference comes from the effect of the optical absorption -αl.

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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, 2s, 2p, 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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The thermo-isomerization of l-cis-pinane (1), 2-pinene (2) and 2 (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 (2) 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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2014年LIA法を原理とする血清H. pylori抗体価測定キット「LZテスト」が上市された。LZテストは従来のELISA法によるプレートとは異なる測定系であり, プレートに関する知見が通用する保証はない。今回, LZテストの陰性高値(抗体価.～.U/ml)がプレートと同様の取扱いができるかを検証した。対象は両検査法で抗体価を同時測定し両抗体価の少なくとも一方が10U/ml未満であった230例であり, 陰性高値内のH. pylori感染状態の構成比および“新ABC分類”(カットオフ値＝.U/ml)による分類結果を比較した。プレートでは陰性高値となる未感染は存在せず, LZテストでは16例(.5%)であった。未感染98例に新ABC分類を適応するとプレートではA群97例(99.%)D群1例(1.%), LZテストではA群例(84.7%), BCD群合わせて15例(15.%)であった。LZテストの陰性高値には未感染が多く含まれ, 新ABC分類をLZテストで行うと未感染者を要精検とする割合が増えるため, 未感染者が多数を占める検診ではプレートを用いることが望ましい。

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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-2A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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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 (5.2 kcal/g) and 30% sucrose solution for drinking (1.2 kcal/mL), or (ii) received normocaloric diet (

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/) was measured by X-rays. Results: DIO exhibited similar INS (12.90±1., n=4) and CT (2.80±1.05, n=4), higher LEP (.33±.04, n=5) and lower CTX-1 (.48±., n=) than C. The treatment of DIO with decreased CTX-1 (4.44±.63, n=) and increased P1NP (163.40±39.80, n=). DIO- decreased INS (5.75±1.50, n=) in relation to DIO, at the same level than C (10.58±1.49, n=4). LEP level in DIO- (.23±.02, n=) was intermediate in relation to DIO and C (.16±.05, n=5). 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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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 well².

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 (2-20mg/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<.0001, elimination rate .001657 min^-1(CI:.00098;.002336),p<.0001 and absorption rate 2.7119(CI:-45.7083; 51.1321),p=.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=.79(p<.0001).

Conclusions.

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

2.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.

2.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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Mace- extract obtained from seed covering of nutmeg is expected to show an antiarteriosclerotic effect due to its potentiation with unsaturated fatty acid, various vitamins, etc. In this study an effect of Mace- was examined from serum lipid and six constituents of thoracic aorta.
A total of 16 male rabbits of 38 months, including 8 with the Mcce- (M group), 4 with cholesterol (C group) and 4 with Mace- plus cholesterol (MC group) were used. to produce arterosclerosis cholesterol was orally given at 1g to the C and MC group. To the M and MC groups Mace- was given at 500mg/day. Sixteen weeks later referring to all the rabbits, total cholesterol (T. CHO), triglyceride (TRIG), β-lipoprotein (β-LIPO), HDL-cholesterol (HDL), 4 in total of serum lipids, were measured. Furthermore, all the rabbits were killed and constituents media of thoracic aorta were stained and observed histochemically, i. ., SMC with Azocarmine G stain, EL with Weigert's stain, CL with Van Gieson's stain, AMPS with Alcian blue stain and GP with PAS stain. T. CHO was 90.5mg/dl in M group, 369.8mg/dl in C group and 81.mg/dl in MC group respectively. The MC group showed no difference with M group but the significantly lower value than that of C group (p<.01). TRIG was 108.5mg/dl in M group, .mg/dl in C group and 94.4mg/dl in MC group respectively. No significant difference was observed among these groups. Beta-LIPO was 184.mg/dl in M group, 995.mg/dl in C group and 151.5mg/dl in MC group respectively. Compared with C group, M and MC groups showed significantly low value (p<.001-p<.01). HDL was 18.mg/dl in M group, .mg/dl in C group and 26.5mg/dl in MC group respectively. There was no significant difference among those group, although it was highest in MC group. When histochemically observed, C group was strongly disturbed, while MC group showed slight swelling of SMC and cell nucleus that was not remarkable though, and damage of EL and CL was minimal. AMPS and GP remained unchanged. From changes of serum lipid and observation of arterial tissue, it was suggested that Mace- has an antisclerotic effect.

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Virus-like particles (VLPs) were collected from geothermal vent water samples in the drift-way at Toyoha Mine, Hokkaido, Japan (−500 m level, 63.5°C) whose VLP and bacterial abundance was (No/ml±SD, n: 500), VLP: .60±.29×10⁸ and bacteria: .61±.14×10⁶. VLPs ranged in diameter from 30 to 320 nm, and the major size distribution (ca 62%) was .33. nm (n: 843). Ultrafiltration followed by CsCl density equilibrium ultracentrifugation gave purified TY-VLPs: 6.64×10¹³. Regardless of UV treatment, TY-VLP reduced the efficiency of plating to 68.6-.4% at a multiplicity of infection of ca . on Escherichia coli AB1157. Generalised transduction was observed on

E

. coli AB1157 with a frequency between 10^-4 and 10^-5 cells/particle using TY-VLPs without UV-treatment. The growth of generated

E

. coli transductants (TY--trans) was compared to that of an

E

. coli transductant (ST--trans) generated by Aquificales originating VLP (Chiura, 2002). The extent of the maximum growth of both transductants was ca 40% of the parental

E

. coli used as a recipient. TY--trans acquired "budding-like" particle productivity, which has been demonstrated for ST--trans. ST--trans produced five different size particles, whose DNA content ranged between 291.6 and 382. kb, and TY--trans produced ten different size particles between 68.5 and 190.2 kb, respectively.

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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 .5N aqueous at room temperature for 30-90min or with Amberlite CG-400 (OH^-) in H₂O 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 H₂O at pH .84 and ionic strength .50 at 25°C. Cyclization of a with NaH in AcNMe₂ 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 D₂O or Me₂SO-d₆ at 25°C or in H₂O at pH .84 and ionic strength .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 H₂O 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 HCONMe₂ 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 2-deuterated species 26 was also synthesized from 24 via 25 and 27.

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