In vitro anti-biofilm activity of macelignan isolated from Myristica fragrans Houtt. against oral primary colonizer bacteria

In early dental plaque formation, oral primary colonizers such as Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus are initially attached to the pellicle-coated tooth surface to form a biofilm. The study aimed to determine the efficacy of macelignan, isolated from nutmeg (Myristica fragrans Houtt.), in removing each single oral primary biofilm in vitro on a polystyrene 96-well microtiter plate. Four biofilm growth phases (4, 12, 20 and 24 h) were evaluated in this study after treatment with macelignan at various concentrations (0.2, 2 and 10 microg/mL) and exposure times (5, 10 and 30 min). Anti-biofilm activity of macelignan was measured as the percentage of the remaining biofilm absorbance after macelignan treatment in comparison with the untreated control. At 24 h of biofilm growth, S. mutans, A. viscosus and S. sanguis biofilms were reduced by up to 30%, 30% and 38%, respectively, after treatment with 10 microg/mL macelignan for 5 min. Increasing the treatment time to 30 min resulted in a reduction of more than 50% of each of the single primary biofilms. The results indicate that macelignan is a potent natural anti-biofilm agent against oral primary colonizers.     

Do ventilated neonates require pain management?

Mechanical ventilation is a stressful experience in neonates resulting in changes in neuroendocrine parameters, pain scores, and physiologic responses. Assisted ventilation in neonates is presumed to be associated with chronic repetitive pain, which in turn is associated with adverse long-term sequelae. Reasons to routinely sedate ventilated neonates include improved ventilator synchrony, improved pulmonary function, and decreased neuroendocrine responses, including cortisol, beta-endorphine, and catecholamines. Reasons not to treat include the well-known adverse side effects of pain medication, especially the opiates, including hypotension from morphine, chest wall rigidity from fentanyl, and tolerance, dependence, and withdrawal from both opiates and benzodiazepines. Additionally, adverse effects such as death and IVH are not improved with preemptive treatment. Chronic pain assessment is poorly validated and difficult to assess in this population, and most studies have evaluated only acute pain scores. If patients are treated, opiates are the most common class of drugs, with morphine the most well studied. Fentanyl may be advantageous in hypotensive, younger neonates because it has fewer cardiovascular effects. The benzodiazepines, midazolam and lorazepam, have been used in ventilated neonates, but midazolam has been associated with adverse effects in one small study so concern remains regarding its use. Significant gaps in our knowledge exist, especially in regard to long-term effects of treatment, or lack thereof, and in the assessment of the chronic pain associated with assisted ventilation.     

CACNA1H基因敲除对小鼠孤独症样行为及海马神经元形态学的影响

目的研究CACNA1H基因敲除(knockout, KO)对小鼠孤独症样行为及海马神经元形态学的影响。方法25只3~4周龄C57BL/6背景的CACNA1H KO小鼠作为实验组, 26只同年龄同背景的野生型(wild type, WT)小鼠作为对照组。通过三箱实验和旷场实验观察小鼠社交、焦虑和重复刻板行为后测量其脑质量与脑体积, 用尼氏染色法(Nissl staining)观察海马神经元数目。将CACNA1H杂合子小鼠与Thy1-GFP-O小鼠杂交, 构建CACNA1H^-/--Thy1⁺(KO-GFP)及CACNA1H^+/+-Thy1⁺(WT-GFP)小鼠, 观察海马神经元树突棘密度及成熟度。结果三箱实验中, 社交测试阶段, KO小鼠在陌生鼠箱中的时间比空箱更长(F_{1, 14}=95.086, P < 0.05;Post-Hoc: P < 0.05), 探索的偏好指数与对照组相比差异无统计学意义(t=1.044, P>0.05);新社交对象识别测试阶段, KO小鼠在新陌生鼠箱与陌生鼠箱中的时间差异无统计学意义(F_{1, 14}=18.062, P < 0.05;Post-Hoc: P>0.05), 探索的偏好指数低于对照组(t=2.390, P < 0.05)。旷场实验中, KO小鼠在旷场中心活动时间明显少于对照组(t=2.503, P < 0.05), 自梳理时间明显多于对照组(t=-2.299, P < 0.05)。形态学结果显示, KO小鼠脑质量/体质量和脑体积与对照组相比差异均无统计学意义(t=0.356, P>0.05;t=-0.660, P>0.05), 但其海马齿状回区神经元数目较对照组减少(t=2.323, P < 0.05), 且KO-GFP小鼠海马齿状回区树突棘密度较对照组增加(t=-2.374, P < 0.05), 而成熟度差异无统计学意义(t=-1.935, P>0.05)。结论CACNA1H KO小鼠具有孤独症样行为, 可能与海马齿状回区神经元数目减少及树突棘密度增高有关。     

胆囊切除术与结肠癌的关系

胆囊结石是外科最常见的疾病之一,胆囊切除术一直被视为本病最有效的治疗方法.结肠癌是胃肠道中常见的恶性肿瘤,近年来的统计资料表明,在胃癌、食管癌发病率下降的同时,结肠癌的发病率却不断增高,但病因尚未十分明确.胆囊切除术与结肠癌发病是否有关目前尚有争论,本文就有关问题做一综述.     

Critical Amino Acid Residues for Nicotine 5＇ -Hydroxylation in Human CYP2A Enzymes

Objective： We have continued previous work in which we demonstrated that #117 and #372 amino acids contributed to the high activities of human CYP2A13 in catalyzing 4-methylnitrosamino-1-（3-pyridyl）-1-butanone（NNK） and aflatoxin BI（AFB1） carcinogenic activation. The present study was designed to identify other potential amino acid residues that contribute to the different catalytic characteristics of two CYP2A enzymes, CYP2A6 and CYP2A13, in nicotine metabolism and provide insights of the substrate and related amino acid residues interactions. Methods： A series of reciprocally substituted mutants of CYP2A6lle^300→ Phe, CYP2A6Gly^301aAla, CYP2A6Ser^369 → Gly, CYP2A13Phe^300→ Ile, CYP2A13Ala^301 → Gly and CYP2A13Gly^369 → Set were generated by site-directed mutagenesis/baculovirus-Sf9 insect cells expression. Comparative kinetic analysis of nicotine 5＇hydroxylatin by wild type and mutant CYP2A proteins was performed. Results：All amino acid residue substitutions at 300, 301 and 369 caused significant kinetic property changes in nicotine metabolism. While CYP2A6Ile^300→ Phe and CYP2A6Gly^301→Ala mutations had notable catalytic efficiency increases compared to that for the wild type CYP2A6, CYP2A13Phe^300→Ile and CYP2A13Ala^301→Gly replacement introduced remarkable catalytic efficiency decreases. In addition, all these catalytic efficiency alterations were caused by Vmax variations rather than Km changes. Substitution of #369 residue significantly affected both Km and Vmax values. CYP2A6Ser^369 → Gly increase the catalytic efficiency via a significant Km decrease versus Vmax enhancement, while the opposite effects were seen with CYP2A13Gly^369 → Ser. Conclusion：#300, #301 and #369 residues in human CYP2A6/13 play important roles in nicotine 5＇ -oxidation. Switching #300 or #301 residues did not affect the CYP2A protein affinities toward nicotine, although these amino acids are located in the active center. Set369 to Gly substitution indirectly affected nicotine binding by     

脑梗死患者颈动脉彩色多普勒超声研究

目的 探讨颈动脉粥样硬化及其危险因素与不同类型的脑梗死间的关系。方法：根据头颅ＣＴ或ＭＲＩ结果将１８８例脑梗死患者分成四个亚组：皮层梗死组（ＣＩ）,皮层下梗死组（ＳＣＩ）,椎－基底动脉支配区梗死组（ＶＢＡＩ）及心源性脑栓塞组（ＣＥＩ）,用彩色多勒超声（彩超）对各型脑梗死患者颅外颈动脉粥样硬化严重程度进行评估,并对可能危险因素进行探讨。结果 ３０％的ＣＩ组患者,１０％ＣＥＩ患者,６．９％ＶＢＡＩ患者     

孤独症儿童血浆5-羟色胺、出生季节和母孕期母亲情绪的初步探讨

目的比较孤独症儿童和正常儿童血浆5-羟色胺(5-HT)浓度、出生季节和孕期母亲情绪,从而探索孤独症5-HT增高的原因和可能的发病机制.方法对54名孤独症儿童和55名正常儿童进行了血浆5-HT检测、并调查出生季节、孕期母亲情绪.对孤独症儿童还进行了适应行为评定量表评定.结果孤独症儿童适应行为评定量表的得分为67.65±1.67.孤独症儿童5-HT浓度为0.78±0.32 μmol/L;正常儿童5-HT浓度为0.62±0.16μmol/L,两组经t检验有统计学差异显著性(t=3.17;P=0.002),5-HT增高的孤独症儿童有17人.与正常儿童比较,孤独症儿童冬春季出生居多,母孕期母亲情绪问题明显.结论在胎儿神经发育的关键时期母体可能存在5-HT系统功能增强,可能是导致孤独症5-HT增高的原因,也许是孤独症可能的发病机制之一.     

双标记流式细胞术定量分析5-FU诱导胃癌细胞早期凋亡

目的 以Annexin V-FTTC/PI双标记流式细胞术检测5－FU诱导胃癌细胞株SCG7901早期凋亡。方法 250、125、50以及25mg/L不同浓度5－FU处理SCG7901胃癌细胞0、6、12、18、24、30h,Annexin V-FTTC/PI双标记流式细胞术检测肿瘤细胞凋亡。结果 早期（0－24h)瘤细胞凋亡比例随5－FU作用剂量增加和时间延长而显著提高（P＜0.01)；后期（24-30h)瘤细胞以坏死增加为主（P＜0.01)而凋亡比例反而降低。结论 5－FU诱导细胞凋亡呈时间以及剂量依赖关系。Annexin V/PI双标记法可以清楚区分正常、坏死、机械损伤以及凋亡细胞群落，是定量分析早期细胞凋亡的准确方法。