Developmental changes in the expression of GABAA receptor subunits alpha1, alpha2, and alpha3 in brain stem nuclei of rats

Gamma-aminobutyric acid (GABA)(A) receptor subunit switching is a suggested postnatal mechanism for changes in GABA transmission from depolarization to hyperpolarization. Previously, we found an apparent switch between GABA(A) alpha3 and alpha1 subunit expression in the rat pre-B?tzinger complex (PBC) on postnatal day (P) 12, a presumed peak critical period of respiratory nuclei development. The present study aimed at determining if GABA(A) subunit switching occurred in another respiratory nucleus, the ventrolateral subnucleus of the solitary tract nucleus (NTS(VL)), and in a non-respiratory cuneate nucleus (CN) of P0 to P21 rats. In both nuclei: (1) the expression of GABA(A) alpha1 subunit was relatively low at birth but increased with development; (2) that of GABA(A) alpha3 was relatively high at birth but declined with age; and (3) GABA(A) alpha2 remained relatively low and constant throughout development. However, the specific patterns differed between the two nuclei, but were similar between the NTS(VL) and the PBC. In the NTS(VL), GABA(A) alpha1 expression gradually increased from birth and peaked at P12, whereas that in the CN sharply rose from P7 and peaked at P10. GABA(A) alpha3 expression had a prominent decrease from P11 to P12 in the NTS(VL), whereas that in the CN only gradually declined from P10 to P12. The developmental trends of alpha1 and alpha3 in the NTS(VL) intersected close to P12, whereas those in the CN intersected at P10. Despite differences in timing, GABA(A) alpha subunit switching may be a common theme in the brain stem that may mediate different functional properties of GABA transmission.     

Peptide amphiphile delivery of sonic hedgehog protein promotes neurite formation in penile projecting neurons

Erectile dysfunction (ED) critically impacts quality of life in prostatectomy, diabetic and aging patients. The underlying mechanism involves cavernous nerve (CN) damage, resulting in ED in 80% of prostatectomy patients. Peptide amphiphile (PA) nanofiber hydrogel delivery of sonic hedgehog (SHH) protein to the injured CN, improves erectile function by 60% at 6?weeks after injury, by an unknown mechanism. We hypothesize that SHH is a regulator of neurite formation. SHH treatment promoted extensive neurite formation in uninjured and crushed CNs, and SHH inhibition decreased neurites >80%. Most abundant neurites were observed with continuous SHH PA treatment of crushed CNs. Once induced with SHH, neurites continued to grow. SHH rescued neurite formation when not given immediately. SHH is a critical regulator of neurite formation in peripheral neurons under uninjured and regenerative conditions, and SHH PA treatment at the time of injury/prostatectomy provides an exploitable avenue for intervention to prevent ED.     

Synthesis of 2 C‐14 labeled cathepsin C inhibitors: The use of a cyanide to displace a Benzotriazole

In support of the development of a new treatment for COPD, 2 C‐14 labeled compounds were required for in vitro animal studies. The synthesis of nitrile [ ¹⁴ C]‐1 was completed in 3 steps from C‐14 labeled 4‐bromobenzonitrile in accord with the previously developed medicinal chemistry route. The second compound, 2 , did not possess an arylnitrile as did 1 , which made the synthetic design more complex. An advanced, unlabeled benzotriazole containing intermediate, 10 , was synthesized in low yield over 3 steps and was subsequently reacted with K¹⁴CN to give a mixture of diastereomers 12 . Separation of the diastereomers followed by deprotection afforded [ ¹⁴ C]‐2 in a 13% radiochemical yield.     

Magnesium-deficiency does not alter calcineurin inhibitors activity in mice

Introduction

Tacrolimus (TAC) and cyclosporin (CsA) are commonly responsible for hypomagnesemia that predisposes in turn for hypertension, renal impairment and encephalopathy.

Objective

The effects of TAC on Mg²⁺-homeostasis and of pre-existing Mg²⁺-deficiency on TAC immunosuppressive activity were compared to CsA in mice.

Methods

Mg²⁺ was quantified in plasma, erythrocytes, urine, feces, and femurs from mice treated with TAC 5 mg/kg/day. Immunosuppression was assessed in splenocytes by mixed lymphocyte reaction, IL-2 quantification and CN activity determination.

Results

Plasma and urine Mg²⁺ levels in TAC-treated mice were significantly lower from day 7 until day 21 (p < 0.05 versus control) and returned to control value at day 28. Mg²⁺ levels were unchanged in erythrocyte, feces and femur. Inhibition of allogeneic proliferation, IL-2 production and CN activity were 68, 56 and 30% lower (p < 0.01) after 7 days of TAC-treatment, and 72, 68 and 51% lower (p < 0.01) after 7 days of CsA-treatment with a dose of 50 mg/kg/day. Dietary-induced hypomagnesemia resulted in significant inhibition of CN activity (p < 0.01) without alteration of IL-2 production or allogeneic proliferation. However, it did not alter the effects observed with CsA- or TAC-treatment on allogeneic proliferation, IL-2 production and CN activity.

Conclusion

By contrast with CsA, long-course TAC-treatment induced an early, but transient, and moderate hypomagnesemia without alteration of bone or erythrocyte stocks, intestinal absorption or renal function. Therefore, in clinical use, TAC should be preferred to CsA in patients with pathological or pharmacological conditions which favor Mg²⁺-deficiency. However, dietary-induced hypomagnesemia did not alter the immunosuppressive effects of TAC and CsA.     

离子刀髓核成形术颈椎脊神经节细胞HSP70表达意义

目的通过观察不同能量颈椎间盘等离子刀髓核成形术（Coblation Nucleoplasty,CN）脊神经节细胞HSP70表达及椎间孔处温度变化,探讨HSP70（Heat shock protein70）的表达与温度关系及意义,为CN临床安全有效应用提供基础研究。方法分别通过相同时间1、2、3档不同能量等离子刀行羊颈椎间盘髓核成形术,切取CN椎间盘节段两侧颈椎脊神经节,并对脊神经节细胞行HSP70免疫组化染色,观察CN后羊颈椎脊神经节细胞HSP70的表达,记录CN前后椎间孔处温度变化,对结果进行统计学分析。结果3档组HSP70阳性表达,阳性率95%,1、2档组及对照组无表达,脊神经节细胞HSP70的表达4组比较有统计学意义（P〈0.01）;三实验组温度比较其中1、2、3档组与对照组比较有显著差异（P〈0.01）,温度与能量相关分析成正相关,r=0.958（P〈0.01）,脊神经节细胞HSP70的表达与温度升高有关。结论CN时椎间孔温度随着档位能量的升高而升高,颈椎CN脊神经节细胞HSP70的表达与温度升高有关,HSP70可作为CN热损伤的判定指标。     

超声诊断先天性肾盂积水最终发展趋势的相关性研究

目的观察产前超声诊断先天性肾盂积水肾盂前后径（anteroposterlor renal pelvic diameter,APD）等数值的变化规律,探讨APD等相关数据在判断生理性或病理性肾盂积水中的临床价值。方法随访观察2011年4月至2013年2月69例行产前超声检查诊断为胎儿先天性肾盂积水患儿的临床资料,根据发展趋势分为生理性肾盂积水和病理性肾盂积水,并对两组积水APD值等相关数据进行比较分析。结果69例（73只肾）中,生理性肾盂积水55例（57只肾）,积水多在产后1—6个月消失。病理性肾盂积水14例（16只肾）,其中肾盂输尿管部梗阻12例（14只肾）,膀胱输尿管部梗阻2例,未发现其它泌尿系统畸形。两组积水在胎儿性别、积水侧别、积水发生时间及孕30～33周前APD、肾皮质厚度（renal parenchyma thickness,RPT）、肾盏形态上比较,P〉0．05,差异无统计学意义。在孕30～33周及孕30～33周后APD、RPT、肾盏形态上比较,P〈0．05,差异有统计学意义。结论胎儿先天性肾盂积水最终发展趋势与胎儿性别、积水侧别、积水发生时间及孕30～33周前APD、RPT、肾盏形态无相关性;与孕30～33周及孕30—33周后APD、RPT、肾盏形态有相关性。在定期随访过程中,生理性肾盂积水多于产后1～6个月恢复正常,病理性肾盂积水的各项指标呈渐进性发展,需及时手术治疗。     

小婴儿心内直视术后撤离呼吸机失败相关因素分析

目的：分析小婴儿心内直视术后撤离呼吸机气管插管拔管失败的相关风险因素。方法回顾性分析2012年1月至2014年1月本院行先天性心脏病（先心病）纠治术后计划性气管插管拔管失败、再插管的271例小于3月龄患儿临床资料。结果271例患儿中,32例（11．81％）术后拔管失败,失败组术后膈肌麻痹、NO 吸入、术后肺炎、肺不张的发生率较对照组升高,差异均有统计学意义（P值均＜0.05）,Logistic 回归多因素分析显示术后肺炎、肺不张（Odds Ratio：11．2,95％ CI ＝1．36～98．26）的发生与拔管失败的发生显著相关（P 值均＜0．05）。结论术后肺部感染、肺不张是小婴儿心内直视术后撤离呼吸机失败的主要相关因素,小婴儿先心病纠治术后应注意呼吸道管理,加强胸部理疗,防治肺部感染,以提高拔管成功率,缩短监护室滞留时间。     

复方利多卡因乳膏在婴幼儿先天性马蹄内翻足经皮跟腱切断术中的应用效果

【目的】对比复方利多卡因软膏和利多卡因注射液用于婴幼儿先天性马蹄内翻足经皮跟腱切断术的镇痛效果,并评估两组的不良反应、手术时间和出血量的差异。【方法】将80例婴幼儿先天性马蹄内翻足需行经皮跟腱切断术的病例随机分为利多卡因注射液组（A组）和复方利多卡因软膏组（B组）,各40例。A组采用利多卡因注射液局部浸润麻醉。B组采用复方利多卡因乳膏外涂局部麻醉。记录两组手术时、术后30 min、1 h、2 h、4 h、8 h、12 h、24 h的 FLACC疼痛评分、手术时间、手术出血量和不良反应并做统计分析。【结果】手术后两组的FLACC疼痛评分逐渐下降。两组手术时、术后30 min、1 h、2 h的FLACC疼痛评分相比,差异有统计学意义（ P ＜0．05）。复方利多卡因软膏组的FLACC疼痛评分低于利多卡因注射液组。复方利多卡因软膏组的手术时间和出血量低于利多卡因注射液组（ P ＜0．05）。无一例出现皮肤局部红肿、水泡等药物不良反应。无一例出现血管神经损伤。【结论】对于先天性马蹄内翻足患儿,采用复方利多卡因乳膏局麻行经皮跟腱切断术,能达到良好的麻醉效果,减轻患儿疼痛,方便术者操作,减少手术时间和出血,无明显不良反应。     

婴幼儿先天性心脏病外科治疗268例分析

目的总结婴幼儿先天性心脏病的外科治疗经验。方法回顾性分析2006年7月至2009年8月本院外科收治的268例婴幼儿先天性心脏病患儿的临床资料。年龄1～36个月，平均年龄（17．21±9．41）个月，其中年龄≤6个月53例；7～12个月82例；13～36个月133例。体重3．2—15．0kg，平均体重（9．12±2．45）kg，其中体重≤10kg者172例。采取根治性手术260例，姑息性手术8例。结果全组治愈262例，治愈率为98％，均获随访，随访时间1—36个月，随访期间无一例死亡，患儿生长发育良好。死亡6例，死亡率为2．2％，其中1岁以内死亡4例，占1岁以内患儿的2．96％，死亡原因为心、肾功能衰竭。出现并发症14例（5．2％），包括急性呼吸窘迫综合症3例，低心排出量综合征4例，急性肾功能衰竭3例，严重心律失常4例（其中2例为Ⅲ°-AVB），室间隔残余分流3例。结论婴幼儿先天性心脏病采取手术治疗可以取得满意疗效，准确把握手术适应症以及符合婴幼儿生理特点的围术期处理是手术成功的关键。