肺表面活性物质联合经鼻间歇正压通气治疗新生儿呼吸窘迫综合征

目的观察肺表面活性物质联合经鼻间歇正压通气治疗新生儿呼吸窘迫综合征(NRDS)的临床疗效。方法 66例NRDS患儿根据随机数字表法分为试验组36例和对照组30例,分别给予珂立苏、固尔舒配合经鼻间歇正压通气治疗。结果两组患儿治疗后肺功能指标a/APO2、PaO2/FiO2均明显提高,与治疗前比较差异有统计学意义(P<0.01),氧合功能好转;试验组和对照组治疗有效率分别为94.4%、96.7%,两组比较差异无统计学意义(P>0.05)。结论两种药物联合经鼻间歇正压通气治疗NRDS均有显著疗效,但进口PS制剂固尔舒价格相对国产PS制剂珂立苏昂贵,在临床可根据患者的情况选择使用。     

极低出生体重儿转归因素分析及肺表面活性剂的作用

目的:探讨影响极低出生体重儿(VLBWI)转归的相关因素及肺表面活性剂(PS)在其中的作用.方法:将305例VLBWI分别按出生体重和住院年份分组,对其临床资料进行回顾性分析.结果:所有住院惠儿均有一种及以上的并发症,最常见的为病理性黄疸(53.4%)、酸中毒(43.3%)、呼吸暂停(33.3%)、新生儿硬肿症(32.1%).本组总体院内病死率为3.0%,其中出生体重≤1 000 g组、～1 250 g组及～1 500 g组分别为12.0%、3.3%和1.6%,组间比较差异有统计学意义(P<0.05).前三年后四年两个时间段比较.病死率差异无统计学意义(P>0.05).导致VLBWI死亡的主要原因为新生儿呼吸窘迫综合征(66.6%):使用PS组治疗NRDS治愈率显著高于未使用PS组(61.5%比21.7%,P<0.05).结论:体重、严重新生儿并发症是影响VLBWI转归的重要因素;NRDS是致VLBWI死亡的最主要原因;应用PS可以明显提高临床NRDS的治愈率.     

肺表面活性物质治疗新生儿重症胎粪吸入综合征疗效观察

目的:探讨肺表面活性物质(PS)治疗新生儿重症胎粪吸入综合征(MAS)的临床疗效。方法:将新生儿MAS患儿52例随机分为治疗组和对照组各26例。两组均给予上呼吸机及常规治疗,治疗组在气道充分灌洗后应用肺表面活性物质(固尔苏)100～150 mg/kg气管内给药。观察两组患儿的氧合功能、病程及预后,并进行统计学分析。结果:治疗组患儿的氧合指数低于对照组(P<0.05),动脉/肺泡氧分压比值高于对照组(P<0.05),治疗组上机时间、住院时间、并发气胸和呼吸机相关性肺炎(VAP)均少于对照组(P<0.05)。结论:肺表面活性物质能有效改善MAS患儿的肺氧合功能,缩短机械通气时间、住院时间及病程,减少气胸及VAP的发生。     

肺泡表面活性物质联合经鼻持续气道正压通气治疗新生儿呼吸窘迫综合征临床观察

目的:探讨肺泡表面活性物质(PS)联合经鼻持续气道正压通气(n CPAP)治疗新生儿呼吸窘迫综合征(NRDS)的临床疗效及价值。方法:选取2012年5月至2013年11月我院治疗的NRDS患儿74例,随机分成对照组36例和观察组38例,两组均在早期采用PS(固尔舒)气管内注入治疗,观察组使用n CPAP,对照组使用机械通气。治疗1 h后,观察两组患儿心率、呼吸频率、氧合指数、血气指标改善情况及治疗效果。结果:观察组总有效率92.11%(35/38),高于对照组的72.22%(26/36)(P<0.05)。观察组患儿心率、呼吸、氧合指数等指标较对照组改善更明显(P<0.05)。结论:PS联合n CPAP治疗NRDS,疗效显著,能明显改善患儿的临床症状,对改善患儿预后及生活质量具有积极意义,值得临床推广应用。     

肺表面活性物质联合俯卧位机械通气治疗新生儿呼吸窘迫综合征的临床研究

目的:研究肺表面活性物质(PS)联合俯卧位机械通气(PPV)治疗新生儿呼吸窘迫综合征(NRDS)的临床疗效。方法:将收入我院行机械通气的NRDS患儿分成三组,治疗1组采用PS联合PPV,治疗2组仅采用PPV,对照组仅采用仰卧位机械通气,三组患儿其他治疗方法相同。采用多功能监护仪监护,分别在机械通气前、机械通气30 min、机械通气6 h、机械通气24 h监测患儿血气分析指标,了解患儿动脉血PaO2、PaCO2,以及各阶段呼吸机的平均气道压(MAP)、吸入氧浓度(FiO2)、氧合指数(OI),详细记录患儿用机时间、平均住院日、并发症呼吸机相关性肺炎(VAP)和呼吸机相关性肺损伤(VILI)以及预后情况。结果:三组患儿治疗前后各阶段血气分析、呼吸机指数比较差异有统计学意义(P<0.05);治疗1组与对照组治疗后各阶段血气分析、呼吸机指数比较差异均有用统计学意义(P<0.01);治疗2组与对照组治疗24 h后血气分析、呼吸机指数比较差异均有统计学意义(P<0.05),治疗24 h内差异无统计学意义(P>0.05);治疗2组和对照组用机时间、平均住院日、并发症VAP和VILI比较差异有统计学意义(P<0.05);治疗1组与对照组用机时间、平均住院日、并发症VAP和VILI比较差异有统计学意义(P<0.01)。结论:机械通气能有效治疗NRDS,PPV优于仰卧位机械通气,PS联合PPV治疗NRDS能有效缩短呼吸机使用时间,减少机械通气并发症,提高NRDS患儿的存活率,改善预后。     

肺泡表面活性物质联合经鼻气道持续正压通气治疗新生儿呼吸窘迫综合征的疗效观察

目的分析采用肺泡表面活性物质联合经鼻气道持续正压通气治疗新生儿呼吸窘迫综合征的疗效。方法通过把我院新生儿科2014年1月~2015年2月收治的诊断为新生儿呼吸窘迫综合症的45例患儿分为观察组与对照组,观察组采用肺泡表面活性物质联合经鼻气道持续正压通气(NCPAP)治疗,对照组采用经鼻气道持续正压通气治疗,观察两组患儿治疗前后临床症状、肺部X线、动脉血氧分压(Pa O2)等变化及预后情况。结果两组患儿在治疗12h后二氧化碳分压(Pa CO2)、氧合指数(OI)明显下降,Pa O2、动脉/肺胞氧分压比值(a/AO2)明显上升。与治疗前相比均有统计学意义(P0.05),治疗后12~24h复查胸部X线片观察组好转率达80.9%,而对照组好转率为50.0%,两组对比差异有统计学意义(P0.05),观察组治愈好转率85.7%明显高于对照组58.3%(P0.05),并发症发生率明显低于对照组(P0.05)差异均有统计学意义,平均住院天数观察组亦明显少于对照组,差异有统计学意义(P0.05)。结论两种方式治疗新生儿呼吸窘迫综合征均可以有效起到治疗作用,而PS联合NCPAP治疗NRDS能更好地改善氧合,降低NRDS病死率,减少并发症发生。     

PS治疗41例新生儿呼吸窘迫综合征的临床观察

目的 探讨肺表面活性物质(PS)对新生儿呼吸窘迫综合征(NRDS)的治疗效果.方法:将符合标准的41例患儿在常规治疗的基础上给予PS治疗,观察肺氧合功能、呼吸机机械通气参数变化及临床疗效.结果:PS治疗后2h、6h、12h患儿动脉血PaO2升高、pH值升高、PaCO2下降,与治疗前比较有显著性差异(P＜0.05):机械通气参数PIP、PEEP、RR在治疗后2h逐渐降低,12h显著下降.与治疗前比较有显著性差异(P＜0.05);临床总有效率100%.结论:PS能够显著提高NRDS疗效,无毒副作用,值得临床推广.     

珂立苏预防新生儿呼吸窘迫综合征的临床研究

目的 探讨珂立苏对预防新生儿呼吸窘迫综合征(NRDS)的有效性.方法 将小于30周早产儿及30～32周高危早产儿55例分为实验组和对照组,实验组在出生后尽早经气管内滴入肺表面活性物质,对照组不使用.比较两组患儿的NRDS发生率、严重程度、FiO2、血气分析、吸氧方式及转归.结果 实验组发生NRDS率为13.3%,对照组发生NRDS率为36.0%,两者相比,差异有统计学意义(P<0.05),且实验组患儿出现NRDS程度较对照组程度轻.实验组患儿治疗后6h血气分析显示PaO2明显高于对照组,差异有统计学意义(P<0.05),而PaCO2及FiO2明显低于对照组(P<0.05).实验组吸氧方式及转归好于对照组,但差异无统计学意义(P>0.05).结论 珂立苏可以有效预防早产儿NRDS发生,减轻NRDS程度,改善氧合及通气,降低病死率,是一种安全有效的生物制剂.     

低剂量牛肺表面活性物质防治新生儿呼吸窘迫综合征的临床研究

目的探讨早期应用低剂量牛肺表面活性物质防治新生儿呼吸窘迫综合征的疗效。方法 24例早产儿为观察组,生后6h内气管内滴注低剂量牛肺表面活性物质,24例同期住院未应用牛肺表面活性物质治疗的早产儿为对照组,进行临床对照研究,对两组病例不同时间段的血气分析、氧合指数进行比较,并记录两组早产儿NRDS的发生率、机械通气率、死亡率及住院时间。结果观察组12h、24h的PaO2和氧合指数高于对照组,观察组12h、24h的PaCO2低于对照组,差异均有统计学意义(P均0.05)。观察组NRDS的发生率和机械通气率明显低于对照组(P均0.05),两组死亡率差异无统计学意义(P0.05),观察组平均住院时间较对照组短,但差异无统计学意义(P0.05)。结论应用低剂量牛肺表面活性物质对预防早产儿发生新生儿呼吸窘迫综合征有效,可改善临床症状,减少NRDS发生,提高早产儿存活率。     

高频振荡通气治疗新生儿呼吸窘迫综合征的效果

目的探讨高频振荡通气治疗新生儿呼吸窘迫综合征(NRDS)的效果。方法回顾性分析我院收治的NRDS 50例,随机分为常频机械通气(CMV)组25例和高频振荡通气(HFOV)组25例,比较两组治疗后的血气分析、氧合指数及并发症的发生情况。结果 HFOV组患儿的血气分析值和氧合指数明显优于CMV组,差异有统计学意义(P<0.05),而发生气胸、肺气漏、慢性肺疾病等并发症低于CMV组(P<0.05)。结论高频振荡通气治疗新生儿呼吸窘迫综合征的疗效肯定,并降低患儿对机械通气的需要,是安全、可靠的新型机械通气方法。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.     

Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat

The rat whole embryo culture was compared to an in vivo experiment with regard to embryotoxicity as well as exposure characteristics, using phenytoin as a model compound. Intra-embryonic concentrations and their embryotoxic effects were determined on gestation day 11 after in vitro administration of 50-150 microg/ml or in vivo gavage of 500-1500 mg/kg body-weight on gestation day 10. In addition, exposure kinetics were studied in vivo after a single oral dose on gestation day 10, and developmental defects on gestation day 21 were scored. The embryotoxic effects observed on gestation day 11 were more pronounced after in vitro exposure in comparison to in vivo exposure at similar intra-embryonic concentrations. Exposure of phenytoin on gestation day 10 in vitro via the culture medium resulted in general embryotoxicity on gestation day 11, whereas in vivo effects as determined on gestation day 11 were minimal. Plasma concentrations of phenytoin increased and plateaued around 35 microg/ml during the 48 hr monitoring period. Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used. Although the developmental effects were minimal as observed in vivo on gestation day 11, specific malformations (defects encompassing the urogenital. craniofacial and skeletal systems) were observed on gestation day 21. These findings show that with similar intra-embryonic concentrations of phenytoin the embryotoxicity in rat whole embryo culture was not comparable with the in vivo embryotoxicity as determined on gestation day 11. This discrepancy may at least partly be explained by differences in exposure characteristics.     

Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin

The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied "in situ" in rats and "in vitro" in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in both absorption models. GRX permeability depends on the intestinal segment, reflecting the previously reported different expression level of the efflux transporters along the gut in rat. A first attempt to correlate the "in vitro" and the "in situ" data has been done. The mathematical model has been constructed using very simplistic assumptions and it will require further refinement but, nevertheless, the results are promising and demonstrate that a good modelling approach helps to identify the system critical parameters and how the system behaviour change when the parameters are modified as it happens when we move from the "in vitro" to the "in situ" level. Predicted versus experimental permeability values show a good correlation, demonstrating that the relevance of the secretion process "in situ" in rat can be predicted from the "in vitro" cell results.     

Comparison of pulmonary and hepatic glucuronidation and sulphation of ethanol in rat and rabbit in vitro

1. Pulmonary and hepatic UDP-glucuronyltransferase and sulphotransferase activities in subcellular fractions from rats and rabbits were determined, comparing ethanol with known substrates for these enzymes.

2. No ethyl glucuronide formation was detected with either hepatic or pulmonary microsomal incubations.

3. Chromatographic, autoradiographic and scintillation counting analysis indicated that ethanol is sulphated by rat and rabbit pulmonary cytosol, although this activity was approx. 2–6% of that in liver.

4. Rat hepatic and pulmonary sulphotransferase activities with β-naphthol were approx. 13 and 60 times higher than with ethanol, respectively.

5. Rabbit hepatic and pulmonary sulphotransferase activities with both substrates were higher than those in rat.