Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect

WSTĘP. Tiazolidinediony (TZD) to grupa leków zwiększających wrażliwość na insulinę, które stosuje się w leczeniu cukrzycy typu 2. Działają one także przeciwmiażdżycowo. Celem badania było wyjaśnienie zależności między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu, leku z grupy TZD, u chorych na cukrzycę typu 2. MATERIAŁ I METODY. W badaniu wzięło udział 136 chorych na cukrzycę typu 2 narodowości japońskiej. Uczestników podzielono na 2 grupy: chorych leczonych pioglitazonem w dawce 30 mg na dobę przez 3 miesiące (n = 70) oraz pacjentów niepoddanych leczeniu (grupę kontrolną, n = 66). Podczas badania kontrolowano zmiany metabolizmu glikolipidów, stężenia w osoczu białka C-reaktywnego (CRP, C-reactive protein), leptyny i adiponektyny oraz prędkość fali tętna (PWV, pulse-wave velocity), aby przeanalizować zależność między przeciwmiażdżycowym a przeciwcukrzycowym działaniem pioglitazonu. WYNIKI. U osób leczonych pioglitazonem stwierdzono istotne obniżenie hiperglikemii, hiperinsulinemii i stężenia HbA1c oraz wzrost stężenia adiponektyny w osoczu w porównaniu z grupą kontrolną (p < 0,01). Ponadto, odnotowano istotne obniżenie stężenia CRP i PWV (p < 0,01). Przeciwmiażdżycowe działanie pioglitazonu zaobserwowano zarówno u pacjentów, u których nie uzyskano poprawy wyrównania cukrzycy, a redukcja stężenia HbA1c wynosiła poniżej 1% (n = 30) (nonresponders, osoby niepodatne na leczenie), jak i u chorych z dobrą odpowiedzią na terapię (responders, osoby podatne na leczenie), u których redukcja stężenia HbA1c przekraczała 1% (n = 40). Stosując model ANCOVA wykazano, że leczenie pioglitazonem wiązało się z niskimi wartościami CRP i PWV, niezależnie od zmian parametrów związanych z metabolizmem glukozy. WNIOSKI. W omawianym badaniu po raz pierwszy przedstawiono przeciwmiażdżycowe działanie pioglitazonu zarówno u chorych podatnych, jak i niepodatnych na przeciwcukrzycowe działanie leku. Wyniki badania sugerują, że pioglitazon może wywierać efekt przeciwmiażdżycowy niezależnie od wpływu na glikemię.INTRODUCTION. Thiazolidinediones (TZD), a class of insulin-sensitizing agents used clinically to treat type 2 diabetes, are also antiatherogenic. This study was designed to elucidate the relationship between the antiatherogenic and antidiabetic effects of pioglitazone, a TZD, in type diabetic patients. MATERIAL AND METHODS. A total of 136 Japanese type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (30 mg daily 3 months) (n = 70) and the untreated control group (n = 66). The changes in glycolipid metabolism as well as plasma high-sensitivity C-reactive protein (CRP), leptin, adiponectin, and pulse wave velocity (PWV) were monitored to analyze the relationship between the antiatherogenic and antidiabetic effects of pioglitazone. RESULTS. The pioglitazone treatment significantly reduced hyperglycemia, hyperinsulinemia, and HbA1c levels and increased plasma adiponectin concentrations relative to the control group (P < 0.01). It also significantly decreased CRP and PWV (P < 0.01). The antiatherogenic effect was observed in both the nonresponders showing < 1% of reduction in HbA1c (n = 30) and responders showing > 1% of reduction (n = 40). ANCOVA revealed that treatment with pioglitazone was associated with a low CRP and PWV, independent of the changes in parameters related to glucose metabolism. CONCLUSIONS. This study represents the first demonstration of the antiatherogenic effect of pioglitazone in both nonresponders and responders with respect to its antidiabetic effect and suggests that pioglitazone can exert its antiatherogenic effect independently of its antidiabetic effect

茶樹の炭疽病類に関する研究 (III) : 炭疽病菌類分生胞子の形成及び発芽について

1957年10月に静岡県金谷町に於て採集した罹病茶葉から分離した茶炭疽病菌GloeosporiumTheae-sinensis MIYAKE及びさきに外観健全な茶葉から得た茶赤葉枯病菌類Glomerella cingulata (STONEM.) S. & v. S., Glomerella sp.並びにGuignardia Camelliae (COOKE) BUTLERの4種からなる茶炭疽病菌類の分生胞子の形成及び発芽について2,3の実験を行つた。茶炭疽病菌分生胞子の形成及び発芽 : 6種の天然煎汁寒天培地及び煮茶葉培地の中煮茶葉培地は胞子形成速度が最も早く且多量に形成され胞子を用いる実験に対しこの培地が有利である。茶葉煎汁を用いた場合の分生胞子の発芽は, 水100ml.に生茶葉4gを1時間湯煎した煎汁中に於て, 24℃及び28℃, 24時間で最高平均発芽率約95%を示し, 煎汁中の茶葉成分が濃厚又は稀薄に過ぎるものではその発芽率が低下する。又乾杏煎汁中の発芽は最高平均発芽率約55%であつた。本菌の胞子は発芽する前に膨大化する。発芽の適温は24°&acd;28℃であつて, 20°又は32℃に於ても50%以上の発芽を示すことがある。煮茶葉培地に形成させた本菌胞子の蒸溜水中での発芽は永田(1954)の示した実験結果に比較して極めて不良であつたので, 馬鈴薯及び燕麦粉煎汁寒天培地から得た胞子の蒸溜水中の発芽を検討したが, 何れも発芽不良を示した。蒸溜水中の発芽が極めてわるく, 永田の結果と異る原因は水質によるか或は菌の系統その他の原因によるものか今日のところ不明である。併し種々の条件に対する胞子の生活力等を調査する場合には, ここに報告した茶葉煎汁を用いるのが便利で而かも適当な方法と考えられる。熱を加えないで茶の全葉又は切断葉を蒸溜水中に浸漬して得た溶液は, この胞子の発芽をある程度促進したが, 茶葉煎汁と比較すると劣つている。又茶葉から抽出されたglutamic acid又はteaninを10ppm。及び100ppm。の濃度に含む水溶液中での発芽は蒸溜水中の発芽と差がなかつた。これらの結果から乾杏煎汁及茶葉煎汁中に共通して含まれているものでglutamic acid及びteanin以外の成分が発芽に関係があるように推定される。4°&acd;-2℃に於て煮茶葉上の胞子を保存するとき, 5日間でその発芽力を半減し, 20日目には標準区の85%に対し, 僅々1.3%の発芽率にまで低下し越冬する分生胞子は低温の影響を蒙ることが推定される。茶赤葉枯病菌類の分生胞子の形成及び発芽 : Glomerella cingulata (G. C.)及びGuignardia Camelliae (G. U.)は光線の照射の有無にかかわらず20°&acd;30℃で胞子を形成したが, Glomerella sp. (G. 2)は室温に於て室内日光の照射をうける条件下で盛夏期に於てのみ胞子を形成する。そしてG. C.及びG. U.は室内日光の照射をうけない方が照射をうけるよりも胞子形成が良好であり, 又玉蜀黍煎汁寒天培地は馬鈴薯煎汁寒天培地よりも胞子形成に適していた。分生胞子の形成能力はG. C., G. 2及びG. U.の順序であつたが, G. U.の胞子形成については培地から胞子を集める方法について検討されなければならない。赤葉枯病菌類分生胞子の茶葉煎汁及び蒸溜水中での発芽はG. C.が最も良好であつて, 24℃20時間以内で95%以上の発芽率を示したのに反し, G. 2及びG. U.は発芽不良で20%以下の発芽率を示した。この実験結果はそれぞれの菌の病原性の程度と関連があるかもしれない。発芽試験に用いる胞子はその胞子源である培養の培養期間によつて発芽力に著しい差異を示した。例えばG. C.に於て培養期間60日のものが最も発芽が良好で, 30日及び90日培養のものは発芽率が極めて不良であつた。胞子を供給する培地の種類によつてその胞子の発芽力に差異を生じ, 馬鈴薯培地の胞子は玉蜀黍培地の胞子よりも発芽力が旺盛な結果を示した。このようなことがあるから人工培養によつて得た分生胞子を用いて行う発芽試験に於ては, 種々の観点から充分に検討されなければならない。G. 2の胞子は発芽に際して多数の隔膜を生じ, G. C.及びG. U.とは特に異つた形態を示した。Sporulation and germination of conidia of four anthracnose fungi (Gloeosporium Theae-sinensis MIYAKE, Glomerella cingulata (STONEM.) S. & v. S., Glomerella sp. and Guignardia Camelliae (COOKE) BUTLER) isolated from tea leaves were investigated. A. Gloeosporium Theae-sinensis MIYAKE Seven media were investigated for the sporulation. A medium made from autoclave sterilized tea leaves, causes the fungus to sporulate most rapidly and produce comparatively numerous conidia. This medium is advantageous in experiments where large number of conidia are required. Maximum percentages of germination of the conidia on tea leaves extract (extracted for 1 hour, 4g tea leaves per 100ml water) and apricot extract (extracted for 1 hour, 2.5g dried apricot per 100ml water) were approximately 95% and 55% respectively. The expansion of conidia in volume prior to germination was observed. Optimal temperatures for the conidial germination was between 24°&acd;28℃; and even at 20℃ and 32℃ conidia showed above 50% germinaton. Notwithstanding the difference of medium (potato, oat extract agar and autoclaved tea leaves) all conidia showed only scantly germination in distilled water. The cause for still lower germination than NAGATA\u27S results is not definitely known, except for the possible difference in the quality of water or the fungus strain used. However, the germination method using tea leaves extract appears more suitable to examine the vital force of the conidia for various conditions. While exudate of tea leaves or cutting of tea leaves in distilled water fairly stimulated the conidial germination beyound that of distilled water, they were still lower than the tea leaves extract. Although glutamic acid and teanin isolated from tea leaves have no influence upon the germination at concentrations of 10 and 100ppm respectively, other stimulative substances associated with tea leaves extract are presumed to contain in both apricot and tea leaves. When the conidia on autoclaved tea leaves were incubated at 4℃&acd;-2℃ in an electric refrigater, germinability reduced to 39.9% and 1.3% within 5 days and 20 days respectively. The check treatment of the conidia showed about 75&acd;85%. From these results low temperatures appear to have harmful effect on the conidia and their germination. B. Glomerella cingulata (STONEM.) S. & v. S. : G. C., Glomerella sp. : G. 2,Guignardia Camelliae (COOKE) BUTLER : G. U. While G. C. and G. U. sporulated with or without the subdue to radiation of the sun-light in room at 20°&acd;30℃, G. 2 required it, but the sporulation occures in the room during the season of mid-summer. G. C. aod G. U. sporulate more easily in nonradiated than when exposed to sun-light, and on corn extract medium than on potato extract medium. Ability of sporulation was in the order of G. C., G. 2 and G. U. but the method of spore collection from the culture must be search regared to G. U. Germination of conidia in tea leaves extract and distilled water was above 95% in G. C., and below 20% in G. U. and G. 2,and it may be suggested that the degree of pathogenicity of these fungi is presumed to be related to the percentage of germination. Germinability of the conidia differed by the age of culture, e. g. germination percentage of culture 60 days old of G. C. was highest, and it was lower in culture of 30 and 90 days old respectively. Also, conidia of G. C. produced on potato extract agar medium germinated more vigorously than that on corn extract medium. From the results described above, in performing experimental tests using conidia obtained from artificial culture various aspects of the fungus must be considered. The conidia of G. 2 produced many septa in germination, which was recognized as a very special morphological change when compared with G. C. and G. U.

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Contemporary Tasks of Educational Administration in a Changing Society

The present article aims to consider the contemporary tasks which educational administration should fulfil to meet urbanization and educational innovation exerting marked influence upon it. Urbanization is a making it necessary for educational administration to fulfil the following tasks: (1) To make a readjustment of conditions in the light of the fact that urbanization tends to polarize schools in the form of educationally advantaged and disadvantaged ones. (2) To take a drastic measures to reduce the regional inequalities from the viewpoint of social justice. (3) To re-appraise the unit of educational administration to meet changes in demographic structure, the expanding living sphere of people and the improvement in the quality of education. (4) Individual schools should develop their own curriculum. To meet the educational innovation, it is necessary, in the light of the tendency of school systems to be retarded in adapting themselves to innovation, that the conventional practice and ideas of educational administration be changed in terms of its whole aspects ranging from school equipment and facilities to ti meschedule and in-service training of teachers. In conclusion, contemporary tasks educational administration are those of decision-making based on the results of the comprehensive examination of various problems facing education today

Linkage of Forest Policies and Programs with Land Coverand Land Use Changes in the Northern Mountain Region of Vietnam: A Village-level Case Study(<Special Issue>Land Use Changes in the Uplands of Southeast Asia: Proximate and Distant Causes)

This paper examines the land cover and land use changes in one village in the Vietnam's northern mountainregion. It overviews the changing forest policies in Vietnam from the country's independence in 1954to 2005 and relates these changes to the management of forest land at the village level. Findings show thatuntil the late-1980s/early-1990s Vietnam's policies encouraged the harvesting of timber for nation buildingactivities and the expansion of cultivated land, leading to the decreased forest area within the village.After this, as government policies changed to encourage forest protection and the planting of trees by localpeople, tree covered forest land area increased. The trigger for the change in land cover and land use atthe village level in both periods is a consistent political intention represented in a series of laws and decreesand consequent extension activities. These established a strong linkage between national and the villagelevel forest governance and led to the almost simultaneous occurrence of national policy change and forestrecovery. It is concluded that it is important to recognize the multiple channels that link the governmentagencies with people and the intensive learning process needed for local people to understand the politicalintentions behind laws and regulations promulgated at the central government level

Successful autologous stem cell transplantation for light chain proximal tubulopathy with severe kidney injury

Key Clinical Message Light chain proximal tubulopathy (LCPT) is a rare type of monoclonal gammopathy of renal significance. Clinicians should consider LCPT in the differential diagnosis of patients with renal or proximal tubular dysfunction with monoclonal gammopathy. They should confirm diagnosis by renal biopsy and initiate chemotherapy before disease progression