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1.
BackgroundSeveral recent studies have focused on the utility of drug repurposing to expand clinical application of approved therapeutics. Here, we investigate the efficacy of midazolam (MDZ) and cytokines for regenerating calcified tissue, using immortalized porcine dental pulp (PPU7) and mouse skeletal muscle derived myoblast (C2C12) cells, with the goal of repurposing MDZ as a new treatment to facilitate calcified tissue regeneration.HighlightsWe noted that PPU7 and C2C12 cells cultured with various MDZ regimens displayed increased bone morphogenic protein (BMP-2), transforming growth factor beta (TGF-β), and alkaline phosphatase activity. These increases were highest in PPU7 cells cultured with MDZ alone, and in C2C12 cells cultured with MDZ and BMP-2. PPU7 cells cultured under these conditions demonstrated markedly elevated expression of odontoblastic gene markers, indicating their likely differentiation into odontoblasts. Expression levels of osteoblastic gene markers also increased in C2C12 cells, suggesting that MDZ potentiates the effect of BMP-2, inducing osteoblast differentiation in these cells. Newly formed calcified deposits in both PPU7 and C2C12 cells were identified as hydroxyapatite via crystallographic and crystal engineering analyses.ConclusionMDZ increases ALP activity, inducing expression of specific marker genes for both odontoblasts and osteoblasts while promoting hydroxyapatite production in both PPU7 and C2C12 cells. These responses were cell type specific. MDZ treatment alone could induce these changes in PPU7 cells, but C2C12 cell differentiation required BMP-2 addition.  相似文献   
2.
李昕  张晓宁  谢昕  高婷婷 《西部医学》2022,34(2):216-219
目的 探讨右旋氯胺酮分别联合右美托咪定(Dexmedetomidine)、咪达唑仑(Midazolam)应用于泌尿系内镜检查患者的镇静效果。 方法 收集中国医科大学肿瘤医院泌尿科行内镜检查患者68例的临床资料,镇静方案采用右旋氯胺酮联合右美托咪定者纳入D组(n=37),右旋氯胺酮联合咪达唑仑者纳入M组(n=31)。比较入室后(T1)、给药完毕时(T2)、检查15 min时(T3)、检查结束时(T4),两组患者生命体征[心率(HR)、平均动脉压(MAP)、血氧饱和度(SpO2)]水平变化,对比两组患者右旋氯胺酮用量、麻醉恢复时间及药物不良反应发生率。 结果 T2、T3、T4时,D组患者HR水平均较T1时有显著下降(P<0.05),与M组间同一时间比较差异均有统计学意义(P<0.05);D组患者MAP、SpO2水平均较T1时无明显变化(P>0.05),但MAP明显低于同期M组(P<0.05)。两组患者检查持续时间及恶心/呕吐、谵妄发生率比较差异无统计学意义(P>0.05),D组患者右旋氯胺酮用量、麻醉恢复时间、离室时间及呼吸抑制发生率均明显少于M组(P<0.05)。结论 右旋氯胺酮联合右美托咪定用于泌尿系内镜检查患者时,患者生命体征稳定性更高,可减少右旋氯胺酮用量,且患者恢复时间缩短。  相似文献   
3.
Introduction and objectivesThis study aimed to assess the safety and efficacy of midazolam and ketamine as adjuvants to the peribulbar block in vitreoretinal surgeries.Patients and methodsThis randomized controlled trial included 93 adult patients undergoing vitreoretinal surgeries performed with peribulbar anaesthesia. Patients were randomly allocated to 3 groups (31 participants each): control (standard anaesthetic mixture), midazolam (standard mixture + midazolam), and ketamine (standard mixture + ketamine). The primary outcomes were onset of globe akinesia and duration of analgesia. Secondary outcomes were duration of motor blockade, onset of corneal anaesthesia and lid akinesia, and changes in vital data (blood pressure, oxygen saturation, and pulse rate).ResultsThe ketamine group vs. the control and midazolam groups showed the most rapid onset of lid and globe akinesia (p < 0.001) and corneal anaesthesia (0.7 ± 0.2 vs. 1.5 ± 0.5 and 1.2 ± 0.4, respectively; p < 0.001) and the longest duration of both analgesia (3.7 ± 0.6 vs. 2.3 ± 0.4 and 3.1 ± 0.6, respectively; p < 0.001) and akinesia (3.8 ± 0.5 vs. 3.0 ± 0.4, and 3.7 ± 0.5, respectively; p < 0.001). The midazolam group showed better outcomes than controls, but the drug was less effective than ketamine. There were no significant differences in vital data among groups (p > 0.05).ConclusionsKetamine is an effective adjuvant for peribulbar blockade. It enhances both motor and sensory blockade by hastening onset and prolonging duration. These effects are desirable in lengthier ophthalmic procedures such as vitreoretinal surgeries. The effects of ketamine were superior to those of midazolam.  相似文献   
4.
5.
目的:探讨单用丙泊酚、单用咪达唑仑和2者联用在难治性癫痫持续状态治疗中的疗效、不良反应等,以寻找较好的抗癫痫治疗方案。方法回顾性分析难治性癫痫持续患者75例。使用丙泊酚治疗的患者25例,使用咪达唑仑的患者25例,2药联合使用的患者25例。记录用药前、控制癫痫发作后、停药时这3个时点的心率(HR)、自主呼吸频率(RR)、收缩压(SBP)、舒张压(DBP)、血氧饱和度(SpO 2)以及治疗后镇静评级分数,癫痫控制起效时间以及不良反应的发生情况。结果联合用药组总体有效率为92.0%,显著高于丙泊酚组和咪达唑仑组的80.0%和84.0%(P<0.05)。3组患者用药前HR、RR、SBP、DBP、SpO 2与控制癫痫发作后、停药时所测得值相比,差异有统计学意义(P<0.05);联合用药后,药物使用总量分别低于单独使用的组别,癫痫控制时间缩短,镇静分数提高(P<0.05)。结论丙泊酚及咪达唑仑2者联合抗癫痫的疗效优于单独使用。  相似文献   
6.
1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUCABT/AUCveh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment.  相似文献   
7.
目的: 探讨不同镇静药对口腔颌面外科术后留置经鼻腔气管导管患者的镇静作用及其可能的不良反应。方法: 将60例口腔颌面外科术后留置经鼻腔气管导管患者按随机数字表法为3组,每组20例。患者入ICU后,各组患者均采用氢吗啡酮镇痛,分别采用咪达唑仑、丙泊酚和右美托咪定镇静,分别记录入ICU镇静前(T0)和镇静开始后30 min(T1)、1 h(T2)、2 h(T3)、6 h(T4)、12 h(T5)和拔管后10 min(T6)各时间点Ramsay镇静评分和BPS镇痛评分以及生命体征;记录各组患者不良反应发生率。采用SPSS 19.0软件包对数据进行统计学分析。结果: 咪达唑仑、右美托咪定和丙泊酚Ramsay评分差异无统计学意义(P>0.05)。在T3、T4、T5时,右美托咪定组BPS评分均显著低于咪达唑仑组和丙泊酚组(P<0.05)。3组患者低血压发生率差别无统计学意义(P>0.05);心动过缓发生率右美托咪定组显著高于与丙泊酚和咪达唑仑组(P<0.05);右美托咪定组和丙泊酚组患者并发躁动的人数显著低于咪达唑仑组(P<0.05)。结论: 右美托咪定和咪达唑仑、丙泊酚均能满足ICU患者的镇静需要,且右美托咪定具有一定的镇痛作用,可减少ICU患者躁动发生率。  相似文献   
8.

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.  相似文献   
9.
摘 要目的:探讨咪达唑仑联合不同剂量盐酸纳布啡用于重度肥胖患者无痛胃镜检查的效果。 方法:选择南昌市 第五医院 2018 年 1 月至 2020 年 7 月期间接受无痛胃镜检查的 126 例重度肥胖患者,按随机数字表法分为对照组和观察 组,各 63 例。观察组应用 2.5 mg 纳布啡复合咪达唑仑;对照组应用 5 mg 纳布啡复合咪达唑仑。比较两组患者的镇痛与镇 静情况、苏醒时间、体动与并发症。 结果:两组患者在苏醒后 5 min 的视觉模拟评分法(VAS)评分、麻醉诱导后 2 min 的 Ramsay 镇静评分比较,差异无统计学意义(P > 0.05);在苏醒后 30 min 两组患者的 VAS 评分较苏醒后 5 min 下降,差 异具有统计学意义(P < 0.05);但苏醒后 30 min 两组患者的 VAS 评分比较,差异无统计学意义(P > 0.05)。内镜入喉时, 两组患者的的 Ramsay 镇静评分均较麻醉诱导后 2 min 升高,差异具有统计学意义(P < 0.05);但内镜入喉时两组患者的 Ramsay 镇静评分比较,差异无统计学意义(P > 0.05)。观察组患者的完全苏醒时间为(5.03 ± 1.04)min,短于对照组的 (5.50 ± 1.20)min,差异具有统计学意义(P < 0.05)。两组患者均无严重体动发生,且一般体动的发生率比较,差异无 统计学意义(P > 0.05);观察组患者的并发症发生率为 7.94 %,低于对照组的 20.63 %,差异具有统计学意义(P < 0.05)。 结论:重度肥胖患者行无痛胃镜检查应用 2.5 mg 或 5 mg 的盐酸纳布啡复合咪达唑仑均可有效镇静镇痛,体动发生情况少, 但低剂量的盐酸纳布啡可减少并发症的发生,且利于患者苏醒。  相似文献   
10.
目的比较右美托咪定或咪达唑仑复合羟考酮用于经支气管镜超声引导针吸活检术(EBUS-TBNA)的镇静镇痛效果,以及对循环和呼吸功能的影响。方法选择纵隔淋巴结肿大择期行EBUS-TBNA患者60例,男33例,女27例,年龄18~65岁,BMI 18~24 kg/m^2,ASAⅠ或Ⅱ级,随机分为右美托咪定组(D组)和咪达唑仑组(M组),每组30例。入组患者均接受利多卡因口、鼻、咽部和环甲膜穿刺表面麻醉,D组于10 min内静脉泵注右美托咪定,负荷剂量为0.8μg/kg,继而以0.6μg·kg^-1·h^-1的速率维持泵入;M组以2 mg/min的速度静脉注射咪达唑仑0.05mg/kg。随后两组均静脉注射羟考酮0.08mg/kg。记录给药前(T0)、手术开始时(T1)、手术开始后5 min(T2)、10 min(T3)、15 min(T4)和术毕(T5)时的HR、SBP、DBP、SpO2,记录T1时Ramsay镇静评分、咳嗽评分,术毕时医师满意度和术后2 h患者满意度等指标。结果 T1时M组SpO2低于D组,但两组差异无统计学意义。T5时D组SBP明显低于M组(P<0.05)。与M组比较,D组Ramsay镇静评分、咳嗽评分明显降低(P<0.05),患者满意度中术中不适种类个数明显减少(P<0.05),愿意接受复查评分明显降低(P<0.05)。结论右美托咪定复合羟考酮用于EBUS-TBNA手术,患者咳嗽少,镇静适度,呼吸和循环更稳定,咪达唑仑复合羟考酮术后患者愿意接受复查的程度更高。  相似文献   
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