Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings

コウノウド ブドウトウ エ ノ ゼンバクロ ニ ヨル ラット スイ ランゲルハンス シトウ カラ ノ インスリン キソ ブンピ ノ ゾウキョウ

京都大学0048新制・課程博士博士(医学)甲第8812号医博第2315号新制||医||759(附属図書館)UT51-2001-F142京都大学大学院医学研究科内科系専攻(主査)教授 中尾 一和, 教授 今村 正之, 教授 清野 裕学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Evaluation of weekly bathing in allergic dogs with methicillin-resistant Staphylococcal colonization

We evaluated the efficacy of weekly bathing in reducing methicillin-resistant Staphylococcus (MRS) colonization in canine allergic dermatitis in a pilot clinical trial. Six dogs with allergic dermatitis controlled by prescription medications were treated with weekly bathing for 1 month. The Canine Atopic Dermatitis Extent and Severity Index version 3 (CADESI-03) and pruritus scores and frequency of mecA-positive Staphylococcus spp. isolated from three body sites between weeks 0 and 4 were compared. There was no significant difference in CADESI-03 scores with bathing, whereas the pruritus scores were significantly reduced (p < 0.05). Furthermore, MRS frequency was decreased in four of the six dogs (p < 0.05). In conclusion, weekly bathing should be considered for reducing MRS colonization in canine allergic dermatitis

Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)

Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression