Pharmacotherapeutic targeting of cation‐chloride cotransporters in neonatal seizures

Seizures are a common manifestation of acute neurologic insults in neonates and are often resistant to the standard antiepileptic drugs that are efficacious in children and adults. The paucity of evidence‐based treatment guidelines, coupled with a rudimentary understanding of disease pathogenesis, has made the current treatment of neonatal seizures empiric and often ineffective, highlighting the need for novel therapies. Key developmental differences in γ‐aminobutyric acid (GABA)ergic neurotransmission between the immature and mature brain, and trauma‐induced alterations in the function of the cation‐chloride cotransporters (CCCs) NKCC1 and KCC2, probably contribute to the poor efficacy of standard antiepileptic drugs used in the treatment of neonatal seizures. Although CCCs are attractive drug targets, bumetanide and other existing CCC inhibitors are suboptimal because of pharmacokinetic constraints and lack of target specificity. Newer approaches including isoform‐specific NKCC1 inhibitors with increased central nervous system penetration, and direct and indirect strategies to enhance KCC2‐mediated neuronal chloride extrusion, might allow therapeutic modulation of the GABAergic system for neonatal seizure treatment. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Spatio-temporal variations in cell-free layer formation near bifurcations of small arterioles

Blood flow partitioning at an arteriolar bifurcation could lead to spatio-temporal variations in cell-free layer formation in the upstream and downstream vessels of the bifurcation. To investigate this effect, we quantitatively analyzed characteristics of the cell-free layer in the vicinity of an arteriolar bifurcation in the rat cremaster muscle in normal physiological flow conditions. To simulate hemorheological relevance to humans, red blood cell aggregation was elevated by infusion of Dextran 500 to levels seen in humans in normal states. Spatial variations of the layer width were observed in both the parent and larger daughter vessels. A more pronounced attenuation of the layer width was generally observed in the parent vessel at its wall adjacent to the side branch than at its opposite wall. A thicker layer width was consistently found at the opposite than adjacent wall of the larger daughter vessel. Accordingly, large asymmetries of the layer widths could be developed on opposite sides of the larger daughter vessel, which were significantly greater (P<0.01) than those observed in the parent vessel. A positive correlation was generally observed between mean layer widths in the downstream vessel and on the side of the parent vessel from which bulk of the flow enters the downstream vessel. The fraction of the downstream layer formation constituted by the side branch decreased with increasing flow fraction in this vessel. These findings confirmed the modulation of the cell-free layer formation near an arteriolar bifurcation, implicated by flow separation at the bifurcation.     

口腔健康影响程度量表在口腔扁平苔藓诊疗中的初步应用

目的:通过观察口腔扁平苔藓患者治疗前后的口腔健康相关生活质量状况,分析口腔健康影响程度量表(OHIP-14)中文版应用于口腔扁平苔藓临床诊疗的反应度。方法:采用OHIP-14中文版对口腔扁平苔藓患者在治疗前后进行问卷调查,并结合效应大小、标准化反应均数等指标进行反应度分析。结果:治疗后患者的OHIP-14分值较治疗前明显降低(P0.01)。7个维度中除心理不适外,其余维度分值差异均有统计学意义(P0.01),其效应大小在0.24～0.55之间,标准化反应均数在0.33～0.72之间。结论:OHIP-14中文版具有一定的反应度,通过评测口腔扁平苔藓患者的口腔健康相关生活质量可以为疗效评估提供参考。     

小型猪Barx1基因的克隆及其在牙胚中的定量表达

目的 观察小型猪牙齿发育相关基因Barx1片段在胚胎发育40 d(E40)不同牙胚中的定量表达,探讨Barx1基因空间表达量与牙齿形态的关系.方法 应用基因克隆技术克隆小型猪Barx1基因片段;应用激光捕获显微切割技术精确分离胚胎40 d小型猪第一乳切牙、乳尖牙、第三乳前磨牙、乳磨牙牙胚;提取微量RNA,以甘油醛-3-磷酸脱氢酶为对照,通过实时定量聚合酶链反应检测Barx1的相对表达量.结果 得到小型猪Barx1基因698个碱基的片段,Barx1在第一乳切牙、乳尖牙、第三乳前磨牙、乳磨牙中的相对表达量为0.000 249、0.000 715、0.026 096、0.1 12 656,在牙弓中由前向后呈递增趋势.结论 Barx1基因表达量与牙齿形态发育存在一定关系,推测小型猪Barx1基因可能与牙尖的分化或牙尖数目相关.