Arteriole dilation to synaptic activation that is sub-threshold to astrocyte endfoot Ca2+ transients

Ca²⁺-dependent pathways in neurons and astrocyte endfeet initiate changes in arteriole diameter to regulate local brain blood flow. Whether there exists a threshold of synaptic activity in which arteriole diameter is controlled independent of astrocyte endfeet Ca²⁺ remains unclear. We used two-photon fluorescence microscopy to examine synaptically evoked synthetic or genetic Ca²⁺ indicator signals around penetrating arterioles in acute slices of the rat neocortex. We discovered a threshold below which vasodilation occurred in the absence of endfeet Ca²⁺ signals but with consistent neuronal Ca²⁺ transients, suggesting endfoot Ca²⁺ is not necessary for activity-dependent vasodilation under subtle degrees of brain activation.     

Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis

Hydrogen sulfide (H₂S), formed by multiple enzymes, including cystathionine‐γ‐lyase (CSE), targets Ca_v3.2 T‐type Ca²⁺ channels (T channels) and transient receptor potential ankyrin‐1 (TRPA1), facilitating somatic pain. Pancreatitis‐related pain also appears to involve activation of T channels by H₂S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca_v3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T‐channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H₂S donor. In the mice with cerulein‐induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55‐0396 (NNC), a selective T‐channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca_v3.2 selectively among three T‐channel isoforms; and knockdown of Ca_v3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein‐induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca_v3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein‐induced pancreatitis. The data indicate that TRPA1 and Ca_v3.2 mediate the exogenous H₂S‐induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca_v3.2 targeted by H₂S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. © 2014 Wiley Periodicals, Inc.     

45d-6°头低位卧床对尿Ca和P含量及其昼夜节律的影响

目的研究45 d-6°头低位卧床对尿液中Ca和P元素昼夜节律的影响,探讨卧床实验中骨丢失的可能规律与机制。方法收集卧床实验8名受试者尿样,每个时间段连续收集3 d。采用电感耦合等离子体发射光谱仪(ICP-OES)对尿样中的Ca,P和K三种元素的含量进行检测,并对Ca和P等元素的昼夜节律特征进行分析。结果尿Ca总含量在卧床前、中、后3个时间段无显著差异,但Ca元素的日间含量在卧床中的早期和晚期阶段都显著降低,在卧床后又恢复至接近卧床前水平。尿中P元素总含量在卧床中的早期显著升高,随后不断下降,到卧床晚期则显著低于卧床前水平,P元素在日间和夜间的变化趋势差异不大。反映骨质变化的Ca/P参数在卧床中和卧床后也有显著变化。此外,卧床实验也对尿液中Ca和P含量变化的昼夜节律具有影响。结论卧床实验对于尿中Ca和P含量及Ca/P参数产生显著影响,同时也影响了Ca和P含量的节律性,这些变化可能与卧床过程中骨代谢失衡有关。     

Connexins in neurons and glia：targets for intervention in disease and injury

Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Amo...     

Amlodipine reduces blood pressure during dynamic resistance exercise in hypertensive patients

This study investigated the effect of the dihydropyridine calcium channel antagonist, amlodipine, on blood pressure (BP) during resistance exercise performed at different intensities in hypertensives. Eleven hypertensives underwent 4 weeks of placebo and amlodipine (random double‐blinded crossover design). In each phase, they performed knee extension exercise until exhaustion following three protocols: one set at 100% of 1 RM (repetition maximum), three sets at 80% of 1 RM, and three sets at 40% of 1 RM. Intraarterial BP was measured before and during exercise. Amlodipine reduced maximal systolic/diastolic BP values achieved at all intensities (100% = 225 ± 6/141 ± 3 vs. 207 ± 6/130 ± 6 mmHg; 80% = 289 ± 8/178 ± 5 vs. 273 ± 10/169 ± 6 mmHg; 40% = 289 ± 10/176 ± 8 vs. 271 ± 11/154 ± 6 mmHg). Amlodipine blunted the increase in diastolic BP that occurred during the second and third sets of exercise at 40% of 1RM (+75 ± 6 vs. +61 ± 5 mmHg and +78 ± 7 vs. +64 ± 5 mmHg, respectively). Amlodipine was effective in reducing the absolute values of systolic and diastolic BP during resistance exercise and in preventing the progressive increase in diastolic BP that occurs over sets of low‐intensity exercise. These results suggest that systemic vascular resistance is involved in BP increase during resistance exercise, and imply that hypertensives receiving amlodipine are at lower risk of increased BP during resistance exercise than non‐medicated patients.     

钙改性NiO/ZnO-Al2O3-SiO2吸附剂反应吸附脱硫效果

通过浸渍沉淀法制备了钙改性NiO/ZnO-Al₂O₃-SiO₂汽油脱硫吸附剂,并与S-Zorb工业吸附剂进行比较。物理性质分析、X射线衍射和原位吡啶吸附红外光谱表征结果表明,钙改性NiO/ZnO-Al₂O₃-SiO₂吸附剂比表面积为137.7 m²/g,孔容为0.31 cm³/g,NiO及ZnO晶体分布均匀且L酸总量更多。在420℃、2.9 MPa、质量空速10.98 h^-1、氢油体积比48:1的条件下,催化裂化汽油中的硫含量从243.38 μg/g降至10 μg/g以下,汽油辛烷值仅降低0.3;新鲜和再生吸附剂穿透硫容分别可达57.12 mg/g及47.33 mg/g,经过长周期再生循环后脱硫性能保持优良。同时,物理性质分析、光电子能谱等表征结果表明失活吸附剂再生后效果明显改善,汽油中硫元素最终被ZnO吸附生成ZnS。     

NT-proBNP 指导中重度心力衰竭患者β1受体阻滞剂使用的临床研究

目的：探讨通过监测血浆 NT-proBNP 水平来指导中重度心力衰竭患者β1受体阻滞剂(琥珀酸美托洛尔)使用的可行性。方法选择住院治疗的195例中重度心力衰竭患者,分为临床观察组和 NT-proBNP 监测组。分别按心力衰竭临床表现和患者血浆 NT-proBNP 降低的幅度来指导琥珀酸美托洛尔的使用。比较两组患者琥珀酸美托洛尔用药时间,患者心力衰竭复发率和因此导致的病死率,琥珀酸美托洛尔的最大使用剂量。结果NT-proBNP 监测组启动琥珀酸美托洛尔治疗平均时间比临床观察组短[(5.89±1.76)d vs .(7.03±2.08)d,P <0.01],NT-proBNP 监测组琥珀酸美托洛尔平均每天使用剂量大于临床观察组[(47.65±13.09)mg/d vs .(35.08±11.08)mg/d,P <0.01]。两组在住院期内心力衰竭复发率和病死率差异无统计学意义(P >0.05)。结论监测血浆 NT-proBNP 水平有助于中重度心力衰竭患者更早使用琥珀酸美托洛尔,也有助于患者短期内耐受较大剂量的琥珀酸美托洛尔,并不增加临床不良事件。     

Identification of potential bioactive peptides generated by simulated gastrointestinal digestion of soybean seeds and soy milk proteins

In this work, the bioactive peptides produced during in vitro gastrointestinal digestion of soybean seeds and soy milk were investigated. The analysis was performed on extracted protein samples from soybean seeds and milk or directly on untreated soy milk. Proteins samples were subjected to simulated gastrointestinal digestion and then analyzed by nano-liquid chromatography coupled to tandem mass spectrometry for peptide sequencing. The identified peptides were 1173 in soybean seed samples, 1364 in untreated soy milk samples and 1422 in soy milk samples in which proteins were extracted by precipitation. The peptide identifications were then employed to search specific databases and look for the presence of bioactive peptides in the investigated samples, either with known biological activity or with potential antimicrobial activity. Results pointed out that soybean proteins underwent an extensive degradation process during gastrointestinal digestion and generated a large number of bioactive peptides, some with established activity, some with predicted antimicrobial activity. Finally, the supernatants collected after protein precipitation with acetone from both soybean seeds and soy milk were also analyzed to evaluate the presence of peptides produced by the action of endogenous proteases. Likely, peptides found in soy milk samples could be formed during food processing.     

大鼠体内大脏器创伤模型涂布康派特?医用胶后生物反应观测

目的：评价康派特?医用胶对大鼠内脏创面止血后的安全性及其体内降解情况。方法：大鼠随机分为空白对照组,手术对照组和手术涂胶组,给胶组分别给予8μL或40μL康派特?医用胶。术后动物进行临床症状观察,体重、摄食量测定,血常规、血清生化学、脏器重量和组织病理学检查。结果：各项指标均未见与康派特?医用胶相关毒性反应;6个月组织病理学检查可见胶体被纤维结缔组织逐渐分割,多核巨细胞和炎症细胞参与异物降解。结论本实验条件下,未见康派特?医用胶对大鼠机体有毒性作用,胶体在大鼠体内6个月开始降解。     

Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine‐binding site of N‐methyl‐D‐aspartate receptor

Sunifiram is a novel pyrrolidone nootropic drug structurally related to piracetam, which was developed for neurodegenerative disorder like Alzheimer's disease. Sunifiram is known to enhance cognitive function in some behavioral experiments such as Morris water maze task. To address question whether sunifiram affects N‐methyl‐D ‐aspartate receptor (NMDAR)‐dependent synaptic function in the hippocampal CA1 region, we assessed the effects of sunifiram on NMDAR‐dependent long‐term potentiation (LTP) by electrophysiology and on phosphorylation of synaptic proteins by immunoblotting analysis. In mouse hippocampal slices, sunifiram at 10–100 nM significantly enhanced LTP in a bell‐shaped dose‐response relationship which peaked at 10 nM. The enhancement of LTP by sunifiram treatment was inhibited by 7‐chloro‐kynurenic acid (7‐ClKN), an antagonist for glycine‐binding site of NMDAR, but not by ifenprodil, an inhibitor for polyamine site of NMDAR. The enhancement of LTP by sunifilam was associated with an increase in phosphorylation of α‐amino‐3‐hydroxy‐5‐methylisozazole‐4‐propionate receptor (AMPAR) through activation of calcium/calmodulin‐dependent protein kinase II (CaMKII) and an increase in phosphorylation of NMDAR through activation of protein kinase Cα (PKCα). Sunifiram treatments at 1–1000 nM increased the slope of field excitatory postsynaptic potentials (fEPSPs) in a dose‐dependent manner. The enhancement was associated with an increase in phosphorylation of AMPAR receptor through activation of CaMKII. Interestingly, under the basal condition, sunifiram treatments increased PKCα (Ser‐657) and Src family (Tyr‐416) activities with the same bell‐shaped dose‐response curve as that of LTP peaking at 10 nM. The increase in phosphorylation of PKCα (Ser‐657) and Src (Tyr‐416) induced by sunifiram was inhibited by 7‐ClKN treatment. The LTP enhancement by sunifiram was significantly inhibited by PP2, a Src family inhibitor. Finally, when pretreated with a high concentration of glycine (300 μM), sunifiram treatments failed to potentiate LTP in the CA1 region. Taken together, sunifiram stimulates the glycine‐binding site of NMDAR with concomitant PKCα activation through Src kinase. Enhancement of PKCα activity triggers to potentiate hippocampal LTP through CaMKII activation. © 2013 Wiley Periodicals, Inc.