Spot-On Skin Lipid Complex as an Adjunct Therapy in Dogs with Atopic Dermatitis: An Open Pilot Study

The purpose of this paper was to evaluate the efficacy of topical skin lipid complex (SLC) in canine atopic dermatitis (AD). Eight dogs with chronic AD and no improvement of main therapy in symptoms, erythema, lichenification, excoriation, and alopecia in the previous month were treated with SLC topically as adjunct therapy at lesion sites twice weekly for 12 weeks. A statistically significant reduction (26.0%, P < 0.05) in the third version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03) modification from baseline was recorded 6 weeks after treatment, with marked reduction in the erythema subscore (36.2%, P < 0.005). A significant reduction in excoriation and alopecia subscores was observed 6 weeks after treatment (39.9%, P < 0.05 and 19.9%, P < 0.05, resp.). However, the lichenification subscore was not reduced significantly at 6 or 12 weeks. These findings suggest that topical SLC may have therapeutic and clinical benefits in dogs with AD

Differential remodelling of peroxisome function underpins the environmental and metabolic adaptability of diplonemids and kinetoplastids

The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialized peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens. The sister group of kinetoplastids are the diplonemids, which are among the most abundant eukaryotes in marine plankton. Here we demonstrate the compartmentalization of gluconeogenesis, or glycolysis in reverse, in the peroxisomes of the free-living marine diplonemid, Diplonema papillatum. Our results suggest that peroxisome modification was already under way in the common ancestor of kinetoplastids and diplonemids, and raise the possibility that the central importance of gluconeogenesis to carbon metabolism in the heterotrophic free-living ancestor may have been an important selective driver. Our data indicate that peroxisome modification is not confined to the kinetoplastid lineage, but has also been a factor in the success of their free-living euglenozoan relatives

Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period

金沢大学医学部附属病院胃腸外科Objective. The attainment of proficiency in thoracoscopic radical esophagectomy for thoracic esophageal cancer requires much experience. We aimed to master this procedure safely with our regular surgical team members under the direction of an experienced surgeon. We evaluated the efficacy of instruction during the induction period and the significance of our results. Methods. We compared the results of 12 thoracic esophageal cancer patients who underwent thoracoscopic radical esophagectomy in our institution (group A) to those of the initial 17 patients who underwent the same operation at the director\u27s institution (group B). Results. We were able to perform complete thoracoscopic radical esophagectomies without any direction after experiencing 10 cases that were performed under adequate direction. The number of dissected lymph nodes and the duration of the procedure were similar in the two groups: 34 (22-53) vs. 26 (9-55) nodes, P = 0.23; and 327.5 (230-455) vs. 315 (190-515) min, P = 0.947, respectively. The amount of thoracic blood loss was significantly less in group A than in group B: 185 (110-380) g vs. 440 (110-2360) g, P = 0.0035. Postoperative pneumonia and atelectasis were observed in 25.0% of group A patients and in 17.6% of group B patients. The incidence of recurrent nerve palsy was 30.7% in group A and 11.7% in group B, but there was no statistically significant difference (P = 0.19). The morbidity rates in group A and group B were 41.6% and 29.4%, respectively (P = 0.694). Conclusion. Thoracoscopic radical esophagectomy can be mastered relatively quickly and safely under the direction of an experienced surgeon and a regular surgical team. © 2008 The Japanese Association for Thoracic Surgery

Learning of thoracoscopic radical esophagectomy: How can the learning curve be made short and flat?

金沢大学附属病院胃腸外科Attainment of proficiency in video-assisted thoracoscopic radical esophagectomy (VATS) for thoracic esophageal cancer requires much experience. We have mastered this procedure safely under the direction of an experienced surgeon. After adoption of the procedure, the educated surgeon directed induction of this surgical procedure at another institution. We evaluated the efficacy of instruction during the induction period by comparing the results at the two institutions in which VATS had been newly induced. We defined the induction period as the time from the beginning of VATS to the time when the last instruction was carried out. From January 2003 to December 2007, 53 patients were candidates for VATS at Kanazawa University (institution 1). Of these, 46 patients underwent curative VATS by a single operator. We divided this period into three parts: the induction period of VATS, post-induction period, and proficient period when the educated surgeon of institution 1 directed the procedure at Maebashi Red Cross Hospital (institution 2). At institution 1, 12 VATS were scheduled, and nine procedures (75%) (group A) including eight instructions were completed during the induction period (from January 2003 to August 2004). Thereafter, VATS was performed without instruction. In the post-induction period, nine VATS were scheduled, and eight procedures (88.8%) (group B) were completed from September 2004 to August 2005. Subsequently, 32 VATS were scheduled, and 29 procedures (90.6%) (group C) were completed during the proficient period (from September 2005 to December 2007). The surgeon at Maebashi Red Cross Hospital (institution 2) started to perform VATS under the direction of the surgeon who had been educated at institution 1 from September 2005. VATS was completed in 13 (76.4%) (group D) of 17 cases by a single surgeon including seven instructions during the induction period at institution 2 from September 2005 to December 2007. No lethal complication occurred during the induction period at both institutions. We compared the results of VATS among four groups from the two institutions. There were no differences in the background and clinicopathological features among the four groups. The number of dissected lymph nodes and amount of thoracic blood loss were similar in the four groups (35 [22-52] vs 41 [26-53] vs 32 [17-69] vs 29 [17-42] nodes, P = 0.139, and 170 [90-380] vs 275 [130-550] vs 220 [10-660] vs 210 [75-543] g, P = 0.373, respectively). There was no difference in the duration of the thoracic procedure during the induction period at the two institutions. However, the duration of the procedure was significantly shorter in the proficient period of institution 1 (group C: 266 [195-555] minutes) than in the induction period of both institutions (group A: 350 [280-448] minutes [P = 0.005] and group D: 345 [270-420] mL [P = 0.002]). There were no surgery-related deaths in any of the groups. The incidence of postoperative complications did not differ among the four groups. Thoracoscopic radical esophagectomy can be mastered quickly and safely with a flat learning curve under the direction of an experienced surgeon. The educated surgeon can instruct surgeons at another institution on how to perform thoracoscopic esophagectomy. The operation time of thoracoscopic surgery is shortened by experience. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

赤色蛍光強発現遺伝子導入マウスにおける蛍光発現部位の形態学的検討

赤色蛍光強発現遺伝子導入マウス(tdTomatoマウス)は再生医療研究のバイオイメージングにおいて有望視されている実験動物である.特に,このマウスから採取した組織再生性細胞や組織片をヌードマウスなどの重症複合免疫不全マウスに移植してその組織再生能力を評価する実験系においては,移植後の細胞や組織片の体内動態をその赤色強蛍光を追跡することによりリアルタイムに観察できると期待されている.しかし,このマウスと既存の緑色蛍光強発現遺伝子導入マウス(EGFPマウス)とのバイオイメージングに関する有用性を比較した例はない.今回,我々はtdTomatoマウスの成体においてIVIS^ Lumina Imaging Systemを用いて蛍光シグナル強度を測定し, EGFPマウスと比較検討した.さらに同一試料における各蛍光タンパクのmRNA発現量を計測し,蛍光イメージングの結果と比較した.またtdTomatoマウスについては,生後7日齢を用いて全身の凍結連続切片を作製し,各臓器における組織レベルでの蛍光発現の詳細な検索を行い,蛍光イメージングならびにmRNA発現量との比較を行った.その結果, tdTomatoマウスより摘出されたほぼ全ての臓器において, IVIS^ Lumina Imaging Systemによる高い蛍光シグナル強度が認められたが, EGFPマウスでは肝臓,脾臓,腎臓において顕著な蛍光発現が認められず, EGFPの発現に臓器特異性が存在する可能性が示唆された.また各臓器のtdTomato mRNA発現量もIVIS^ Lumina Imaging Systemにより観察された蛍光シグナル強度と同様の傾向を示した.加えて, tdTomatoマウスの組織切片による観察では,ほとんどの臓器の細胞で蛍光発現を確認できた.しかしながら,蛍光イメージング, mRNA発現量,組織切片による観察結果において,同様の傾向を示さない臓器も認められたことから,今後,このような研究や検証には切片法を含めた複数の手法を用いる必要が示唆された.以上の結果から総合して判断すると, tdTomatoマウスは,既存のEGFPマウスと比較して,その移植実験への応用性の点で有用性が高いことが示唆された.The red fluorescent transgenic mouse has given us a promising insight into regenerative medicine. Each organ of this animal has already been investigated by the method of using a fluorescent imaging system, but not by histological methods. First of all, we compared all the organs of the red fluorescent transgenic mouse with previous studies using enhanced green fluorescent protein (EGFP) mice by the IVIS Luminal Imaging. Next the expression levels of each organs mRNA was measured by RT-PCR. Further, the histological sections of the red fluorescent transgenic mice (7 days after-birth) were taken by light microscope. The results of the three methods were compared and the following findings were made ; We found a discrepancy between the fluorescent imaging method which was used in past reports and the expression levels of mRNA and multiple discrepancies between these and the histological observations. Explaining the discrepancies was beyond the scope of this experiment. We thought that two or more methods including the histological examination were reguired by future research and verification. The red fluorescent transgenic mouse was more useful than the EGFP mouse in the fluorescent expression of the hepar, spleen and ren. All of the organs in the red fluorescent transgenic mouse have a strong fluorescent expression. We hope that these red fluorescent transgenic mice are used in the research of regenerative medicine and the metastic route of the tumor stem cell

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

富山県立中央病院金沢大学医薬保健研究域医学系金沢大学附属病院胃腸外科Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis

Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer

<p>Abstract</p> <p>Background</p> <p>We investigated the presence and distribution of the sentinel and the non-sentinel node micrometastases using complete serial sectioning and immunohistochemical staining (IHC), to inspect whether lymph node micrometastases spread to the sentinel lymph nodes first.</p> <p>Methods</p> <p>A total of 35 patients, who underwent gastrectomy with a sentinel lymph node biopsy for gastric cancer, were enrolled in this study. Total of 1028 lymph nodes of 35 patients having gastric cancer without metastasis of lymph node by permanent section with hematoxylin and eosin staining (H&E) were selected. There were 252 sentinel nodes and the other 776 were non-sentinel nodes. All nodes were sectioned serially and stained alternately with H&E and IHC. Lymph node micrometastases was defined as proving to be positive first either the IHC or the complete serial sectioning.</p> <p>Results</p> <p>Micrometastases were detected in 4 (11%) of the 35 patients, 6 (0.58%) of 1028 nodes. Of these 4 patients, 3 had micrometastases exclusively in sentinel nodes, and the other had micrometastasis in both sentinel and non-sentinel nodes. There was no patient who had the micrometasitases only in non-sentinel nodes.</p> <p>Conclusion</p> <p>These results support the concept that lymph node micrometastasis of gastric cancer spreads first to sentinel nodes.</p