氯胺酮对大鼠海马锥体神经元电压门控型钠通道的影响

目的研究氯胺酮对大鼠海马锥体神经元电压门控型钠通道的影响。方法急性分离 Wistar 大鼠(鼠龄两周)的海马锥体神经元,应用全细胞膜片钳技术记录电压门控型钠通道电流(INa), 加用不同浓度(50、100、200、500、1000、2000μmol/L)氯胺酮后,计算INa抑制率及半数抑制浓度(IC50); 选择100μmol/L氯胺酮作INa稳态激活及失活曲线。结果50、100、200、500、1000、2000μmol/L氯胺酮对INa的抑制呈浓度依赖性,IC50为(794±21)μmol/L;100μmol/L氯胺酮使INa稳态激活、失活曲线均向超极化方向移动,激活曲线的半数最大激活电位从(-51．6±O．9)．mV移至(-58．5±0．8)mV(P< 0．05),斜率因子(κ)分别为2．0±1．0、(3．2±0．9)mV(P<0．05);失活曲线的半数最大失活电位从 (-66．8±0．8)mV移至(-79．9±0．5)mV(P<0．05),κ分别为-6．6±0．7、(-7．0±0．4)mV(P> 0．05)。结论氯胺酮对电压门控型钠通道有抑制作用,与其全身麻醉作用有关。     

异丙酚对海马锥体神经元钠通道电流的抑制作用

目的 研究异丙酚对海马锥体神经元钠通道电流的影响,探讨脑钠通道在异丙酚麻醉中的作用。方法 酶消化法急性分离SD大鼠(10～14 d)海马锥体神经元,全细胞膜片钳技术记录异丙酚和脂肪乳剂对其钠通道电流的影响。结果 在钳制电位-100 mV时,4组浓度(10、30、50、100μmol/L)的异丙酚分别抑制峰钠电流为:14.4％±8.7％、42.9％±8.8％、67.2％±18.1％和85.1％±14.9％,抑制程度与浓度呈正相关(r=0.993,P<0.01),IC50为32.5 μmol/L。与本研究中较高浓度异丙酚组(50和100μmol/L)对应浓度的脂肪乳剂(ILP50组和ILP100组)对峰钠电流无明显影响。结论异丙酚对脑钠通道电流有明显的抑制作用,且呈剂量依赖性,提示脑钠通道的抑制在异丙酚的麻醉中可能起一定作用。     

氟哌利多对大鼠背根神经节细胞钠电流的影响

目的 研究氟哌利多对大鼠背根神经节细胞钠通道电流的影响。方法 在急性分离的大鼠背根神经节细胞标本上,应用全细胞膜片钳技术记录氟哌利多对钠通道电流的影响。结果3～300μmol·L-1的氟哌利多对钠电流的抑制率为14.12％～78.46％（P<0.01,n=7）,该抑制作用具有浓度依赖性。钳制电位不同,氟哌利多对钠电流的抑制作用亦不同,在Vh分别为-80mV与-60mV时,其IC50值分别为（48.72±10.67）μmol·L-1和（35.37±10.51）μmol·L-1（P<0.05,0=7）。30μmol. L-1的氟哌利多使电流-电压曲线峰值平均降低53.18％（P<0.01,n=7）,对激活曲线无明显影响（P>0.05,n=7）,但可使稳态失活曲线向超极化方向移动7.95mV,用药前、后的V1/2分别为-28.58mV和-36.06mV（P<0.01,n=7）。结论 氟哌利多对背根神经节细胞钠通道电流有明显的抑制作用,且呈浓度依赖性,提示硬膜外镇痛时应用临床浓度的氟哌利多具有增强硬膜外镇痛效果的作用。     

异丙酚对大鼠海马神经元钾离子通道的影响

目的 采用大鼠海马神经元作为研究对象,研究异丙酚对神经元的瞬间外向钾通道、延迟整流钾通道的影响,以探讨静脉麻醉药作用的可能机制。方法 在急性分离的大鼠海马锥体神经元上,利用全细胞膜片钳技术,记录瞬间外向、延迟整流两种钾离子通道的电流。研究异丙酚对这些通道电流幅度和通道动力学的作用。结果 异丙酚对上述通道电流均具有抑制作用,呈可逆性和浓度依赖性,并对离子通道的激活和失活曲线有一定的影响。异丙酚对瞬间外向钾通道和延迟整流钾通道作用的EC50分别为(71±18)和(37±18)μmol·-1,最大抑制率分别为52％±3％和32％±5％。结论 异丙酚对海马神经元上的瞬间外向钾电流、延迟整流钾电流有不同程度抑制作用。异丙酚对锥体神经元兴奋性的影响,可能与影响记忆功能有关。     

氯胺酮对豚鼠心室肌细胞L-型钙电流的影响

目的观察氯胺酮对豚鼠心室肌细胞膜L-型钙电流(ICa-L)的影响。方法酶解法分离单个心室肌细胞,采用全细胞膜片钳技术,观察100μmol/L氯胺酮在不同钳制电压下以及不同浓度 (50-5 000μmol/L)氯胺酮在+10mV钳制电压下豚鼠心室肌细胞膜ICa-L的变化,并研究100μmol/L氯胺酮对ICa-L稳态激活曲线、稳态失活曲线和稳态失活后恢复曲线的影响。结果 100μmol/L氯胺酮抑制ICa-L,使电流密度-电压曲线上移,但不改变激活电压、峰值电压、翻转电压以及曲线形态;细胞外液冲洗后,ICa-L部分恢复。保持电压-40 mV、钳制电压+10 mV条件下,100-5 000 μmol/L氯胺酮呈浓度依赖性抑制ICa-L,其半数抑制浓度为926．6 μmol/L。100μmol/L氯胺酮对ICa-L激活曲线没有明显影响, 给药前后半数激活电压分别为-2．9±0．6、(-1．4±1．1)mV(P>0．05),斜率因子(k)分别为7．4±0． 5、(8．0±0．3)mV(P>0．05);100μmol/l氯胺酮使ICa-L的稳态失活曲线明显左移,给药前后半数失活电压分别为-14．8±0．8、(-19．6±0．7)mV(P<0．05),k分别为6．2±0．4、(5．9±0．3)mV(P>0．05); 100μmol/l氯胺酮使ICa-L的稳态失活后恢复曲线明显下移。结论氯胺酮可通过作用于L-钙通道的失活态,浓度依赖性地抑制豚鼠心室肌细胞ICa-L,产生负性肌力作用。     

氟哌利多复合丙泊酚对大鼠海马锥体细胞钠通道电流的影响

目的研究氟哌利多复合丙泊酚对大鼠海马锥体细胞钠通道电流的影响。方法酶消化法急性分离SD大鼠(10~14d)海马锥体细胞,全细胞膜片钳技术记录氟哌利多复合丙泊酚对钠通道电流的影响。结果在钳制电压(Vh)-80mV,刺激电压(Vt)0mV条件下,氟哌利多单独使用对钠电流抑制作用的半数抑制浓度(IC50)为(26·01±5·08)μmol/L(n=7),丙泊酚单独应用时对钠电流抑制作用的IC50为(44·53±3·89)μmol/L(n=6)。1/4和3/4IC50的氟哌利多与丙泊酚合用,对钠电流抑制作用的IC50值分别为(32·34±9·56)μmol/L(n=6)和(30·73±5·77)μmol/L(n=6)。等效线图分析结果显示1/4IC50的氟哌利多与丙泊酚合用时表现为相加作用;3/4IC50的氟哌利多与丙泊酚合用时表现为拮抗作用。结论氟哌利多和丙泊酚对海马锥体细胞钠通道电流均有明显的抑制作用,并呈浓度依赖性;较低浓度的氟哌利多与丙泊酚复合时,对钠通道电流的抑制作用表现为相加作用;而较高浓度的氟哌利多与丙泊酚复合时,表现为拮抗作用。     

异丙酚对大鼠海马CA1缺血神经元持续钠电流的影响

目的 探讨异丙酚对大鼠海马CA1缺血神经元持续钠电流的影响。方法 酶消化法急性分离SD大鼠海马CA1锥体细胞,通过低氧和无糖法制备神经元缺血模型,全细胞膜片钳技术记录异丙酚对缺血神经元持续钠电流的影响。结果 神经元缺血5 min后持续钠电流显著增强。异丙酚10μmol/L和100μmol/L均能明显抑制缺血引起的持续钠电流增强(与0μmmol/L组比,P<0.01),此作用为异丙酚100μmol/L较10μmol/L儿更强(P<0.05)。结论 异丙酚能够抑制体外脑缺血时海马神经元持续钠电流,这可能是其产生脑保护作用的机制之一。     

氟哌利多对大鼠海马锥体细胞钠通道电流的影响

目的　研究氟哌利多对大鼠海马锥体细胞钠通道电流的影响。方法　用酶消化法急性分离SD大鼠 (1 0～ 1 4d)海马锥体细胞 ,全细胞膜片钳技术记录氟哌利多对钠通道电流的影响。结果　在钳制电压 (Vh) 80mV、刺激电压 (Vt) 0mV条件下 ,0 3～ 30 0 μmol/L氟哌利多对钠电流抑制率为 1 3 1 2 %～ 82 2 5 % (P <0 0 5 ,n =7) ,IC50 为 2 6 0 1 μmol/L。 30 μmol/L的氟哌利多使电流 电压曲线峰值电流平均降低 4 1 93% (P <0 0 1 ) ,但不影响其形状 ,对激活曲线无明显的影响 (P >0 0 5 )。用药前、后 5 0 %通道激活时的去极化电压 (V1 / 2 )分别为 6 6 89mV和 6 5 35mV ;使稳态失活曲线向超极化方向移动 ,用药前、后 5 0 %的通道灭活时的条件脉冲电压 (V1 / 2 )分别为 5 8 75mV和 6 8 81mV。结论　氟哌利多对海马锥体细胞钠通道电流有明显浓度依赖性的抑制作用 ,其抑制作用主要与优先结合钠通道的失活状态而影响钠通道的失活有关     

异丙酚对大鼠脊髓背角神经元河豚毒素敏感型电压门控钠电流的影响

目的 探讨异丙酚对大鼠脊髓背角神经元河豚毒素敏感型电压门控钠电流的影响.方法 出生后1周的SD雄性大鼠,体重12～20 g,断头处死,取腰膨大段脊髓(L3-6),急性分离背角神经元,随机分为6组,对照组背角神经元施加细胞外液,不同浓度异丙酚组于距离神经元100 μm处施加0.3、1、3、10、30 μmol/L异丙酚,应用全细胞膜片钳记录模式,记录单刺激诱发的钠电流幅度,每组记录14个神经元.计算异丙酚的半数抑制浓度.向神经元施加半数抑制浓度的异丙酚,给予刺激电压-40～30 mV,梯度为10 mV的连续刺激,记录给药前后不同刺激电压下电流到达峰值的时间,共记录16个神经元.结果 与对照组比较,不同浓度异丙酚组钠电流峰值降低(P＜0.05),异丙酚的半数抑制浓度为(5.35±0.23)μmol/L.施加5.35 μmol/L异丙酚后,-30～10 mV刺激电压对应电流到达峰值时间较给药前延长(P＜0.05).结论 0.3～30 μmol/L异丙酚可抑制大鼠脊髓背角神经元河豚毒素敏感型电压门控钠通道电流,可能与延长钠通道电流到达峰值时间有关.     

氯胺酮对大鼠海马锥体神经元延迟整流钾电流的影响

目的观察氯胺酮对大鼠海马锥体神经元延迟整流钾电流(IK)的影响。方法酶消化法急性分离Wistar大鼠海马锥体神经元,采用全细胞膜片钳技术测定IK。加用不同浓度(10、30、100、300、1000μmol/L)氯胺酮后,计算IK抑制率,建立氯胺酮的浓度-效应曲线,选择30 μmol/L氯胺酮作IK 稳态激活(及失活)曲线。结果10、30、100、300、1 000μmol/L氯胺酮对IK的抑制率分别为(10±4)%、(19±4)%、(31±5)%、(50±7)%、(54±8)%。IC50为(100±18)μmol/L,Hill系数为1.33±0.48。激活曲线的半数最大激活膜电位(V1/2)(1.82±0.20)mV上升到(9.30±1.03)mV(n=8,P<0.05),K从(20.4±2.3)mV移动到(16.6±4.2)mV(P>0.05);失活曲线的V1/2从(-29±4)mV下降到(-73±6) mV(P<0.01),K从(26±6)mV上升到(53±11)mV(P<0.01)。30 μmol/L氯胺酮使IK的稳态激活曲线向去极化方向明显移动;使IK的稳态失活曲线向超极化方向明显移动。结论氯胺酮对IK通道有抑制作用,氯胺酮的对中枢神经系统的作用可能与IK抑制有关。     

2015年乳腺癌辅助化疗进展

【摘要】〓乳腺癌是危害我国女性健康的头号杀手,尽管近年来辅助化疗的研究进展突飞猛进,但临床中仍有不少问题未能明确,如辅助化疗的合适人群、化疗的开始时间、蒽环及紫杉类的地位和用法、强化维持治疗的作用、疗效及预后的生物标志物等。本文结合乳腺癌辅助化疗在临床上的常见问题和2015年各大乳腺癌会议阐述乳腺癌辅助化疗的最新进展。     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

β-半乳糖苷酶在体内外成骨细胞中的表达

目的 研究β—半乳糖苷酶(β—gal)在成骨细胞中的表达状况，为阐明MorquioB综合征的发病机制提供依据。方法 裸鼠各器官和骨组织标本行X-gal染色检测。抽取羊和人骨髓行骨髓基质细胞(BMSCs)培养，分为4组：I：Adv-hBMP-2转染组；Ⅱ：Adv—β—gal转染组；Ⅲ：未转染组；Ⅳ：地塞米松诱导组。分别行X-gal染色和RT-PCR检测β—gal的表达。结果 裸鼠骺板两侧、骨膜内面及松质骨的成骨细胞和破骨细胞可见多量β—gal的表达。未转染BMSCs组有少量β—gal的表达，其他3组细胞的β—gal表达增高。结论成骨细胞和破骨细胞可表达多量β—gal，该两种细胞的β—gal缺乏可能是MorquioB综合征骨骼异常的直接原因。     

西宁地区烧伤病人动脉血气分析观察

对高海拔地区的27例烧伤病人动脉血气变化进行了分析和观察。结果证明:无论是存活病人还是死亡病人伤后均存在有低氧血症问题。并且在死亡病人和烧伤合并吸入性损伤病人其低氧血症的发生早于单纯烧伤病人。提示:吸入性损伤病人应立即行气管切开术以保障氧气供给,单纯烧伤病人可常规吸氧以维持正常血 PaO_2,ARDS 均发生在合并吸入性损伤的病人,高频喷射通气技术对纠正低氧血症有一定效果。     

Controversies in Fistula in Ano

Managing a complex fistula in ano can be a daunting task for most surgeons; largely due to the two major dreaded complications—recurrence & fecal incontinence. It is important to understand the anatomy of the anal sphincters & the aetiopathological process of the disease to provide better patient care. There are quite a few controversies associated with fistula in ano & its management, which compound the difficulty in treating fistula in ano. This article attempts to clear some of those major controversies.     

Smoking-Attributable mortality in Spain in 2016

IntroductionSmoking-attributable mortality (SAM) is a valuable indicator that can be used to characterize the course and health burden of the smoking epidemic. The aim of this paper was to estimate SAM in Spain in 2016 in the population aged 35 and over, using the best available evidence.MethodsA smoking prevalence-dependent analysis based on the estimation of population-attributable fractions was performed. Smoking prevalence (never, former, and current smokers) was calculated from a combination of the Spanish Health Survey (2016) and the European Health Survey (2014); the relative risk of death among current and former smokers was taken from the follow-up of various cohorts; and mortality rates were obtained from National Center for Statistics data. SAM estimates are presented globally, and by sex, age groups, and major disease categories: cancer, cardiometabolic diseases and respiratory diseases.ResultsIn 2016, 56,124 deaths were attributed to tobacco consumption, 84% in men (47,000), and 50% in the population aged over 74 (27,795). Overall, 50% of SAM was due to cancer (28,281), 65% of which was lung cancer. One in 4 attributable deaths (13,849) occurred before the age of 65.ConclusionsOne in 7 deaths in Spain in 2016 were attributable to smoking. This estimation of SAM clearly highlights the great impact of smoking on mortality in Spain, mainly due to lung cancer and chronic obstructive pulmonary disease.     

MicroRNAs in hepatic pathophysiology in diabetes

MicroRNAs(miRNAs or miRs) are small approximately 22 nucleotide RNA species that are believed to regulate diverse metabolic and physiological processes.In the recent past,several reports have surfaced that demonstrate the role of miRNAs in various biological processes and numerous disease states.For a disease as complex as diabetes,the emergence of miRNAs as key regulators leading to the disease phenotype has added a novel dimension to the area of diabetes research.On the other hand,the liver,a metabolic hub,contributes in a major way towards maintaining normal glucose levels in the body as it can both stimulate and inhibit hepatic glucose output.This equilibrium is frequently disturbed in diabetes and hence,the liver assumes special significance considering the correlation between altered hepatic physiology and diabetes.While the understanding of the mechanisms behind this altered hepatic behavior is not yet completely understood,recent reports on the status and role of miRNAs in the diabetic liver have further added to the complexities of the knowledge of hepatic pathophysiology in diabetes.Here,we bring together the various miRNAs that play a role in the altered hepatic behavior during diabetes.     

Single center experience in single-incision laparoscopic surgery in children in Turkey

Purpose

Minimally invasive surgery has evolved into single-incision laparoscopic surgery (SILS) in the recent years. Few reports have addressed the practicality of SILS in children. Our current experience with regard to feasibility and effectiveness of SILS in children is presented.

Methods

A retrospective review of the operative database for patients operated on using SILS in our department from March 2009 to July 2010 was performed. Data regarding the type of the procedure, age, sex, operative performance, hospital stay, and complications were collected.

Main Results

Among 43 patients, cholecystectomy was performed in 11; appendectomy, in 10; unroofing for ovarian cysts, in 5; unroofing for splenic cysts, in 4; oophorectomy, in 6 (ovarian torsion, 2; teratoma, 4); ovary-preserving teratoma excision, in 1; splenectomy, in 1; gonadectomy, in 3; and varicocelectomy, in 2. There were no conversions to standard laparoscopic or open techniques. The only postoperative complication was a wound infection that occurred after an appendectomy.

Conclusion

Although currently more expensive, SILS can be performed in children in almost every pediatric surgical procedure that can be accomplished with conventional laparoscopic techniques. The most significant contribution of SILS procedure is cosmesis. Postoperative pain and length of hospital stay were not improved.