カラマツ大径材生産を目的とした強度間伐の有効性

長野県はカラマツ林業の中心地域であり，民有林面積の約半分はカラマツ人工林からなる。近年，カラマツ林業は低迷状態に陥っており，間伐手遅れ林分や施業放棄林分の増加をもたらしてしまった。その現状を打開するために，間伐経費の削減や作業省力化を図ることができる間伐方法の開発が緊急課題である。本研究は手良沢山演習林において強度間伐による大径材生産を目指し，従来の標準間伐と比較して，強度間伐の有効性を林木成長・材質の両面から明らかにすることを目的とした。その結果，林齢50年の強度間伐区は林齢78年の標準間伐区の林分成長状況とほぼ同じ，胸高直径の分布は30年に近い林齢の差があるにもかかわらず標準間伐区と近い様相を示した。また，強度間伐区の胸高直径成長量および予測戒長量が標準間伐区より高く，30cm以上の大径材の構成割合が多く，その成長の良さが伺えた。また，有用広葉樹樹種の構成が多いことから,将来,上本のカラマツとの針広葉混交・複層林および広葉樹の育成天然林の形成が可能と考えられる6木材強度試験の結果,強度間伐区は標準間伐区に比較して明らかな組違がなく,強度間伐区では肥大成長における材質の低下は見られず，成熟材部を形成して以後の強度間伐による成長促進は優良材生産に効果的であるといえる。Article信州大学農学部AFC報告 1: 63-71(2003)departmental bulletin pape

Developing dual hemofiltration plus cardiopulmonary bypass in rodents

Background: Emerging therapies for prolonged cardiac arrest (CA) include advanced circulatory interventions like emergency cardiopulmonary bypass (ECPB) and continuous venovenous hemofiltration (CVVHF). However, preclinical studies are limited because of the absence of a practical method of using CVVHF along with ECPB in rodents. ;Methods: We modified a CA model with ECPB resuscitation to include the CVVHF circuit. Adult rats were cannulated via the femoral artery or vein and the jugular vein for the ECPB circuit. A new circuit for CVVHF was added to allow ECPB and CVVHF to be started simultaneously. CVVHF blood flow at 3 mL/min could be controlled with a screw clamp during ECPB. After cessation of ECPB, the CVVHF flow was maintained using a roller pump. The filtration rate was controlled at 40 mL/h/kg in the standard volume of CVVHF and 120 mL/h/kg in the high volume (HV) of CVVHF. The driving force of hemofiltration was evaluated by monitoring transmembrane pressure and filter clearance (FCL). ;Results: Transmembrane pressure in both groups was stable for 6 h throughout CVVHF. FCL of blood urea nitrogen and potassium in the standard volume group was significantly less than the HV group (P < 0.01). FCL of blood urea nitrogen and potassium was stable throughout the CVVHF operation in both groups. ;Conclusions: We developed a method of CVVHF along with ECPB in rodents after CA. We further demonstrated the ability to regulate both standard and HV filtration rates. (C) 2015 Elsevier Inc. All rights reserved

Venoarterial extracorporeal membrane oxygenation resuscitation in diabetic ketoacidosis with hypothermic cardiocirculatory instability

Diabetic ketoacidosis with hypothermia is underrecognized, and the mortality rate is high at between 30% and 60%. The cause of hypothermia in diabetic ketoacidosis patients is speculative and has multiple factors. Insulin deficit is the most important factor that leads to a lack of substrate for cellular heat production [4]. Water depletion and low environment temperature may also be contributing factors, especially in patients with a severe diabetic coma. Hypothermia may also aggravate uncontrolled diabetes mellitus and complicate treatment because insulin secretion is impaired and exogenous administered insulin is less effective at low temperatures. We present a case, the first in the literature, of severe diabetic ketoacidosis with marked hypothermia and cardiovascular instability that was successfully resuscitated by venoarterial extracorporeal membrane oxygenation support. Based on this report, we suggest that portable venoarterial extracorporeal membrane oxygenation should be considered to treat patients with severe diabetic ketoacidosis and hypothermic cardiocirculatory instability

Effects of Acetyl-L-Carnitine and Oxfenicine on the Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetic Rats

研究背景： 對於糖尿病所引起的左心室心肌功能病變的治療方式，改變心肌細胞能量來源的代謝方式是其中一種方法。由於脂質代謝佔心肌能量來源的大部分，在這個研究裡，我們以肉鹼 (carnitine) 的衍生物乙醯左旋肉鹼 (acetyl-L-carnitine，ALC) 及羥苯甘胺酸 (oxfenicine，OXF) (一種carnitine palmitoyltransferase-1抑制劑) 來影響脂質進入粒腺體的代謝途徑，治療以鏈佐黴素 (streptozotocin) 所引發的糖尿病Wistar-Kyoto鼠，並利用測量左心室壓力與主動脈血流量以得知心臟的收縮功能與內部阻力，比較兩種不同治療方式對於心臟泵浦功能的影響。 研究方法： 以鏈佐黴素 (55mg/kg) 注入兩個月大Wistar-kyoto大鼠尾靜脈誘發糖尿病，之後分別每天餵與乙醯左旋肉鹼 (1 g/L於飲用水) 或是羥苯甘胺酸 (150 mg/kg經口灌食)，治療八週後分別與年紀相同之正常組與糖尿病未治療組作比較。在麻醉開胸後測量左心室壓力與升主動脈之血流，以計算最大收縮彈性 (maximal systolic elastance, Emax) 與理論最大血流 (theoretical maximum flow, Qmax)。生理上，Emax可以反映一個完整心臟的心肌收縮功能 (contractility)，而Qmax則是與左心室內部阻力有反比關係。 研究結果： 相較于正常組之Wistar-kyoto大鼠，糖尿病鼠的Emax下降，但Qmax不變，顯示心臟的收縮功能下降。不論是以乙醯左旋肉鹼或是羥苯甘胺酸治療糖尿病鼠，Emax均可以增加，顯示兩者均可以改善因糖尿病所引起的心臟收縮力下降。然而，僅有乙醯左旋肉鹼可以降低心肌細胞的丙二醇(malondialdehyde, MDA) 含量，減少脂質的過氧化產物產生。另一方面，以羥苯甘胺酸治療糖尿病鼠會增加週邊血管總阻力，減少Qmax，顯示在以羥苯甘胺酸治療後，心室內部阻力反而增加。 研究結論： 相對於羥苯甘胺酸，乙醯左旋肉鹼對於因糖尿病所引起的心臟泵浦功能不良的治療結果更為適當。因為乙醯左旋肉鹼不但可以增加心肌的收縮功能 (Emax)，且不會增加週邊血管總阻力，不至於增加心臟的內部阻力。Introduction: In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV function. For this study, we compared the effects of acetyl-L-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship. Methods: Diabetes was induced by a single tail vein injection of 55 mg kg-1 streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L-1 in drinking water) or oxfenicine (150 mg kg-1 by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax). Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Results: When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in Emax associated with the unaltered Qmax. Acetyl-L-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-L-carnitine or oxfenicine resulted in an increase in Emax, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Qmax showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Qmax corresponded to an increase in total vascular resistance when treated with oxfenicine. Conclusions: Acetyl-L-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.誌謝.......................................................i 中文摘要...................................................ii Abstract..................................................iv 目錄......................................................vi 第一章 研究背景..............................................1 1 正常心肌細胞的能量來源是葡萄糖與脂肪酸..........................1 2 糖尿病與心血管疾病..........................................3 2-1 糖尿病的血管病變..........................................3 2-2 糖尿病的心肌病變..........................................4 3 肉鹼棕櫚醯轉移酶-1與肉鹼.....................................7 3-1 乙醯左旋肉鹼.............................................7 3-2 羥苯甘胺酸..............................................9 4 鏈佐黴素引發之第一型(胰島素缺乏)糖尿病模式.....................10 5 研究目的.................................................11 第二章 研究方法.............................................13 1 實驗動物製備..............................................13 2 實驗動物分組..............................................13 2-1 乙醯左旋肉鹼之投藥方式....................................14 2-2 羥苯甘胺酸之投藥方式.....................................15 3 實驗儀器介紹..............................................15 3-1 高傳真壓力感應器.........................................15 3-2 電磁感應血流計..........................................16 4 實驗動物手術流程...........................................17 5 左心室/體重比.............................................18 6 彈性-阻力模型與左心室壓力...................................19 7 左心室收縮末期平衡點.......................................21 8 心臟dP/dtmax、dP/dtmin及左心室等容壓力下降的時間常數τ.........22 9 以硫巴比妥鹽檢測法估計左心室中的丙二醇含量.....................22 10 統計方法................................................24 第三章 研究結果與討論........................................25 1 乙醯左旋肉鹼可以減緩因鏈佐黴素誘發之糖尿病大鼠左心室肥大..........25 2 羥苯甘胺酸會增加鏈佐黴素誘發之糖尿病大鼠之主動脈平均血壓..........27 3 乙醯左旋肉鹼與羥苯甘胺酸均可改善糖尿病鼠的dP/dtmax，但乙醯左旋肉鹼還可以改善dP/dtmin...........................................28 4 彈性-阻力模型的擬合優度.....................................29 5 乙醯左旋肉鹼與羥苯甘胺酸均可改善糖尿病鼠的最大收縮彈性............30 6 羥苯甘胺酸會增加糖尿病鼠週邊血管總阻力並降低理論最大血流量........31 7 週邊血管總阻力增加，理論最大血流量降低，兩者呈現負相關............32 8 乙醯左旋肉鹼可以降低糖尿病鼠心臟之MDA/TBARS含量................33 9 研究討論.................................................34 10 研究成果................................................38 第四章 研究結論.............................................39 第五章 研究特色.............................................40 第六章 研究限制.............................................43 圖次 圖1.......................................................44 圖2.......................................................45 圖3.......................................................46 圖4.......................................................47 圖5.......................................................48 表次 表1 ALC與OXF隊以STZ誘發糖尿病大鼠血糖、體重與左心室重量的影響......49 表2 ALC與OXF隊以STZ誘發糖尿病大鼠血液動力學參數的影響............50 表3 ALC與OXF隊以STZ誘發糖尿病大鼠的心臟功能的影響................51 參考文獻...................................................52 附錄......................................................6

The Impact on Biochemical Profiles and Allograft Function for Patients Converted from Cyclosporine to Tacrolimus after Clinical Heart Transplantation

Objective. Tacrolimus, a potent calcineurin inhibitor, is a widely used immunosuppressant. This study sought to determine whether conversion from cyclosporine to tacrolimus afforded benefits on biochemical profiles and graft function among Chinese heart transplantation recipients. Methods. Forty-nine patients (44 men and 5 women) among 252 heart transplantations performed from 1995 to 2005 were converted from cyclosporine to tacrolimus due to rejection ( 69%) or to cyclosporine intolerance (31%). The median age of these recipients at transplantation was 46.4 years (range , 5 months to 68 years). Their median body weight was 60 kg( range, 4-84 kg). The allograft median ischemic time was 145 minutes (range, 52-300 minutes) . We compared the biochemical markers, rejection episodes and allograft function. Results. The mean duration from heart transplantation to conversion was 419 days. After conversion , the serum bilirubin and alanine transaminase levels were significantly improved at 1 year. The lipid profiles, including triglycerides, total cholesterol, and low- density lipoprotein were nonsignificantly changed. The rejection episodes significantly decreased from 1.53 to 0.15 per patient per year (P < .001). The left ventricular ejection fraction significantly improved from 54.3 + /- 17.9% to 63.2+ /- 10.9%(P < .01). The right atrial pressure significantly decreased from 9.1 +/- 5.8 mmHg to 6.3 +/- 4.3 mm, Hg (P < . 01). The pulmonary capillary wedge pressure significantly decreased from 15.3 +/- 9.5 mm Hg to 10.8 +/- 5.3 mm Hg (P = .04). Conclusion. In heart transplantation, conversion to tacrolimus owing to rejection or cyclosporine intolerance showed better liver profiles with fewer rejection episodes and improved graft function

Therapeutic Drug Monitoring of Tacrolimus in Cardiac Transplant Recipients: A Comparison with Cyclosporine Neoral

This study compares the pharmacokinetics of tacrolimus (TAC) and cyclosporine Neoral (CsA) in cardiac transplant recipients. METHODS: Twenty-six de novo cardiac recipients were prospectively and randomly assigned to receive oral TAC - or CsA-based regimens after 5 to 6 days of rabbit antithymocyte globulin induction. Blood samples were collected at 0 (before the dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, as well as 12 hours after drug administration. The pharmacokinetics of the first dose (PK-1) and at steady state (PK-S, 1 month after transplantation) were analyzed. RESULTS: Comparing the AUC per milligram dose, there was no significant difference between PK-1 and PK-S among TAC (46.0 +/- 24.3 ng x h/mg x mL versus 69.0 +/- 43.9 ng x h/mg x mL, P = .15 by paired t-test), but a significant difference in CsA (25.2 +/- 11.4 ng x h/mg x mL versus 45.4 +/ - 12.9 ng x h/mg x mL, P = .0005 by paired t-test). This means better TAC absorption in the early post-heart transplant period. Using a single-point blood level to predict AUC, TAC showed a significantly higher correlation than CsA at all corresponding sampling times. Besides, C12 in both PK-1 and PK-S of TAC displayed good correlations to the AUC (r2 = . 895, P = . 00 in PK-1 and r2 = .81, P = .00 in PK-S). The TAC trough level was accurate enough to predict the AUC. CONCLUSION: The pharmacokinetic profile of TAC is more reliable than that of CsA in the early post-heart transplant period. A high correlation of trough blood levels with AUC omits the requirement for a multiple sampling strategy to more accurately measure AUC as is needed with Cs

Urinary pi-glutathione S-transferase Predicts Advanced Acute Kidney Injury Following Cardiovascular Surgery

Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(alpha-) and pi-(pi-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and all-cause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary p-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p &lt; 0.05 by generalized estimating equation). Urinary p-GST predicted advanced AKI at 3 hrs post-surgery (p = 0.033) and composite outcome (p = 0.009), while the corresponding ROC curve had AUC of 0.784 and 0.783. Using GAM, the cutoff value of 14.7 mu g/L for p-GST showed the best performance to predict composite outcome. The addition of p-GST to the SOFA score improved risk stratification (total net reclassification index = 0.47). Thus, urinary pi-GST levels predict advanced AKI or hospital mortality after cardiovascular surgery and improve in SOFA outcome assessment specific to AKI

Therapeutic Drug Monitoring of Cyclosporine Neoral in De Novo Chinese Cardiac Transplant Recipients Treated with an Everolimus-Cyclosporine Immunosuppressive Regimen

This study determined cyclosporine Neoral (CsA) pharmacokinetics and the accuracy of a limited sampling strategy to predict the 12-hour CsA area- under-the-curve ( AUC) to provide a practical method for more accurate therapeutic drug monitor of CsA among de novo Chinese heart transplant recipients treated with an everolimus-CsA immunosuppressive regimen. Methods. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after oral administration of CsA in six de novo heart recipients receiving a CsA, everolimus, and methylprenisolone immunosuppressive regimen after rabbit antithymoglobulin sequential immuno-induction. We analyzed the pharmacokinetics of the first dose (PK-1) and steady state dose (PK-2) at 1 month after transplantation. The accuracy of a single- point sampling method to predict the AUC was generated by linear regression analyses. dResults. The t(max) and dose-normalized C-max of PK- 1 and PK-2 were similar. The correlations in single-point blood levels of PK -1 to predict the AUC(0-infinity) were much lower than the corresponding sampling times in PK-2. In PK-2 study, C4 had the best correlation (r(2) = 0.913, P =.003) to predict AUC( 0-12). In addition, the trough concentrations, C-0 (r(2) = 0.875, P =.006) and C-12 (r(2) = 0. 783, P =.02) also showed good correlations. C2 had insufficient correlation to predict AUC(0-infinity) in PK-1 or AUC(0-12) in the PK-2 study. In conclusion, the absorption of CsA was similar during PK-1 and PK -2. At steady dose, C4 had the best single -point correlation to predict AUC(0-12). Trough blood levels may be more practical in clinical use to monitor CsA