A Decrease in the Percentage of CD3+ Cells Is Correlated With Clinical Improvement During Plasmapheresis in Patients With Myasthenia Gravis

Plasmapheresis not only removes circulating antibodies but also modulates cellular immunity, including lymphocyte subsets. To investigate the effect of double‐filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in patients with myasthenia gravis (MG), we examined the percentages of B‐cells, T‐cells, T helper (Th) cells, T suppressor (Ts) cells, natural killer (NK) cells, NKT cells, and Th/Ts ratio before and after a single DFPP session and after a course of DFPP. A total of 26 patients were recruited; their peripheral blood lymphocyte subsets were assayed using flow cytometry. After a single session of DFPP treatment, the percentages of T‐cells (P = 0.0200), Th cells (P = 0.0178), and the Th/Ts ratio (P = 0.0309) decreased significantly, whereas the percentage of NK cells (P = 0.0007) increased significantly. More importantly, after one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T‐cells (r = 0.5005, P = 0.0092). Fourteen thymectomized MG patients had decreased percentages of T‐cells (P = 0.0304) and Th cells (P = 0.0444), whereas they had increased NK cells (P = 0.0197) after a single DFPP session. Here, transiently decreased percentages of T‐cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients.     

Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low‐dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose‐dependent inhibition of 4‐AP‐evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl ‐threo‐beta‐benzyl‐oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization‐induced increase in [Ca²⁺]_C but did not alter 4‐AP‐mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca_v2.2 (N‐type) and Ca_v2.1 (P/Q‐type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]_C caused by Ca²⁺ entry through presynaptic voltage‐dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades. Synapse 67:568–579, 2013 . © 2013 Wiley Periodicals, Inc.     

基于剪切波变换的医学图像融合算法

剪切波变换是一种新颖的多尺度几何分析工具,具有多分辨率、多方向性、效率较高等优点,比小波变换、曲波变换、轮廓波变换等图像表示方法有独特有的优势.基于剪切波变换提出一种医学图像融合算法,先将原始图像通过剪切波变换分解为低频子带图像和高频方向子带图像,然后采用非负矩阵分解方法融合低频子带系数,再通过深入研究人类视觉系统的特性提出最大视觉能量对比度方法,利用局部对比度和局部区域的能量和进行高频方向子带系数的融合,最后通过剪切波逆变换得到融合图像.两组实验均显示所提出的融合方法在与其余3种融合方法的比较中,采用的5项客观评价指标均有4项指标达到最优值,证明所提出的方法获取的融合图像效果最好.     

Effect of riluzole on cytosolic Ca2+ increase in human osteosarcoma cells

In human osteosarcoma MG63 cells, the effect of the neuroprotective drug riluzole on the intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. Riluzole (50-500 micromol/l) caused a rapid and sustained plateau increase in [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 150 micromol/l). The riluzole-induced rise in [Ca(2+)](i) was prevented by 58 and 20% by extracellular Ca(2+) removal and nifedipine, respectively, but was not changed by La(3+) and verapamil. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i), after which the increasing effect of riluzole on [Ca(2+)](i) was attenuated by 84%; also, pretreatment with riluzole abolished the thapsigargin-induced [Ca(2+)](i) increase. U73122, an inhibitor of phospholipase C, abrogated the ATP (but not riluzole)-induced rise in [Ca(2+)](i). A low concentration (6 micromol/l) of riluzole selectively potentiated the bradykinin (but not ATP and histamine)-induced increase in [Ca(2+)](i). These results suggest that riluzole rapidly increases [Ca(2+)](i) by stimulating both the extracellular Ca(2+) influx via a nifedipine-sensitive pathway and intracellular Ca(2+) release from the ER via an as yet unidentified mechanism(s).     

Rechallenge prior sildenafil nonresponders

To assess inappropriate use as a cause of sildenafil (Viagra ) failure and the feasibility of successfully rechallenging nonresponding patients, a total of 60 consecutive erectile dysfunction (ED) patients who first presented to our hospital and claimed poor response to sildenafil were enrolled into the study. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate their baseline ED status and a self-administered sildenafil-use questionnaire composed of nine questions (SUQ-9) to assess how they had used sildenafil. A total of 44 subjects consent to rechallenge with sildenafil and were given thorough instruction based on individual answers to SUQ-9 and four doses of sildenafil 100 mg. After a 4-week follow-up, end point efficacy of rechallenge was evaluated using the IIEF-5 and the global assessment question (GAQ), 'After the treatment, did you have successful sexual intercourse?' Of the 60 subjects, 44 (77.3%) had one or more areas of major suboptimal use of sildenafil: 18 (30.0%) did not know that sexual stimulation was necessary for sildenafil to work, 36 (60.0%) attempted to use sildenafil less than four times, and 27 (45.0%) took a maximal dose less than 100 mg. Of the 44 patients undergoing sildenafil rechallenge, 34 (77.3%) completed the follow-up, while seven (15.9%) received only GAQ assessment by telephone interview and three (6.8%) were lost to follow-up. The total follow-up rate was 93.2% (41/44). Based on answers to the GAQ, the response rate to rechallenge was 58.5% (24/41). The mean improvement in the IIEF-5 score was 8.4+/-5.5 in responders (P <0.05). With individualized thorough instruction based on answers to SUQ-9 and scheduled follow-up, a high success rate was achieved by rechallenge with sildenafil in prior failures. The efficacy of sildenafil could be improved to a great extent by adequate education of patients and continuing medical education given to primary-care physicians.     

Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells

In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured using fura-2. Maprotiline (>2.5 µM) caused a rapid rise of [Ca²⁺]_i in a concentration-dependent manner (EC₅₀ 200 µM). Maprotiline-induced [Ca²⁺]_i rise was reduced by removal of extracellular Ca²⁺ or by addition of La³⁺, but was not altered by voltage-gated Ca²⁺-channel blockers. Maprotiline-induced Mn²⁺ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca²⁺ influx. In Ca²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺]_i rise, after which the increasing effect of maprotiline on [Ca²⁺]_i was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca²⁺]_i rise. U73122, an inhibitor of phospholipase C, abolished [Ca²⁺]_i rise induced by ATP (but not by maprotiline). Overnight incubation with 1–10 µM maprotiline enhanced cell viability, but 20–50 µM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca²⁺]_i in renal tubular cells by stimulating both extracellular Ca²⁺ influx and intracellular Ca²⁺ release, and may modulate cell proliferation in a concentration-dependent manner.     

Triethyltin increases cytosolic Ca(2+) levels in human osteoblasts

In human osteosarcoma MG63 cells, effect of triethyltin, an environmental toxicant, on intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by using fura-2. Triethyltin (1-50 μM) caused a rapid and sustained plateau rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50)=10 μM). Triethyltin-induced [Ca(2+)](i) rise was prevented by 50% by removal of extracellular Ca(2+) but was not altered by voltage-gated Ca(2+) channel blockers. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of triethyltin on [Ca(2+)](i) was attenuated by 60%; also, pretreatment with triethyltin abolished thapsigargin-induced [Ca(2+)](i) increase. Depletion of mitochondrial Ca(2+) with carbonylcyanide m-chlorophenylhydrazone (CCCP; 2 μM) did not affect triethyltin-induced Ca(2+) release. U73122, an inhibitor of phoispholipase C, abolished ATP (but not triethyltin)-induced [Ca(2+)](i) rise. A low concentration (1 μM) of triethyltin failed to alter ATP and bradykinin-induced [Ca(2+)](i) rises. These findings suggest that triethyltin rapidly increases [Ca(2+)](i) in osteoblasts by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release via as yet unidentified mechanism(s).