Theoretical Study on the Structures and Properties of Phenobarbital Imprinted Polymers

Recently, the investigation of novel molecularly imprinted polymers（MIPs） has attracted a lot of interest and becomes a fascinating field. The phenobarbital（PHN） was taken as an imprinted molecule and the 2-vinyl-4,6-diamino-1,3,5-triazine（VDAT） was considered as a functional monomer in this study. The geometry optimization, natural bond orbital（NBO） charge, and molecular electrostatic potential（MEP） of PHN and VDAT were studied at the M062 X level belonging to one of the hybrid density functional theories. Furthermore, we discussed the bonding conditions of PHN molecular imprinted polymers（PHN-MIPs） via the hydrogen bond length and atoms in molecules（AIM） theory. The rebinding property of PHN-MIPs was also researched. The results of MEP and NBO charge analysis were coincident. The stability property was excellent when the ratio of PHN and VDAT was 1：4. Except the classic hydrogen bonds, non-classical hydrogen bonds also existed in the imprinted polymers. By simulating the rebinding energies between the pentobarbital（PNT）, barbital（BAR）, and PHN-MIPs after the elution of PHN, the rebinding property of PHN-MIPs to PHN was excellent when PNT and BAR existed all at once. This research can provide theoretical reference for the synthesis and characterization of novel PHN-MIPs.

Computer Simulation and Experimental Investigations of Phenobarbital Molecular Imprinting System

The interaction process between the phenobarbital（PHN） and acrylamide（AM） was studied using the M062X/6-31G（d,p） method. The PHN and AM were used as the template and functional monomer,respectively. The molecular electrostatic potential（MEP） was simulated for predicting the reactive sites. The atoms in molecules theory helped to reveal the imprinting mechanism and optimize the molar ratios for PHN and AM. The molecular imprinted polymers（MIPs） containing PHN were synthesized through the precipitation polymerization. The diameter range of the obtained MIPs was from 150 to 390 nm. According to the computational results,MIPs with the molar ratio of PHN and AM equal to 1：6 showed high selective adsorption for PHN. The apparent maximum adsorption quantity（Q_（max）） of MIPs toward PHN was 7.9 mg/g,and the Qmax of nonimprinted polymer microspheres（NIPs） was 3.2 mg/g. Herein,the studies can provide theoretical and experimental references for the controllable fabrication of MIPs.

Influence of Phenobarbital and Carbon tetrachloride on the Modulation of Tissue Retention Profile of Hexachlorocyclohexane in Rats

The study was designed to investigate the role of hepatic metabolic activity on body burden of HCH residue. Male albino rats were orally administered 0, 5, and 10 mg/kg HCH for 90 days, followed by either sodium phenobarbital or carbon tetrachloride treatment for 0, 15 and 30 days after withdrawal of their respective HCH administration. The liver weight was significantly increased at 30 days after the administration of phenobarbital and carbon tetrachloride in both 5 mg and 10 mg/kg HCH withdrawal groups when compared to control. HCH residue was maximun in fat followed by adrenal>thymus>liver>kidney>spleen>testes>brain>plasma. Carbon tetrachloride caused an accumul-ation of HCH residues in the liver 15 and 30 days after administration of both doses of HCH. Phenobarbital did not show significant variation in HCH residues in hepatic tissue. Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities. Significant decreases in activities were observed by carbon tetrachloride when compared to animals treated with HCH alone. The overall results clearly suggest the role of P450 protein on the body burden of HCH residues.

PHENOBARBITAL FOR THE PREVENTION OF IVH INCHINESE PREMATURE INFANTS

Objectivs To evaluate the effect of phenobarbital in preventing intraventricular hemorrhage inpremature infants. Methods A randomized controlled trial for the prevention of neonatal intraventricularhemorrhage (IVH) was carried out in 57 Chinese premature infants with gestation of 34 weeks. These prematureinfants were randomly assigned to prevented (23 cases) or control (34 cases) groups. Results No statisticallysignificant differences in general data between the two groups were found. It was noticed that the average Apgarscore in prevented group was lower than that in the control group. The average age at the time of the loading dosesof phenobarbital was 8.9± 8.3 (0.5～25)h (outborn babies usually delay to receive phenobarbital), and the averageduration of the maintenance dose was 5d. The mean value of serum phenobarbital level obtained on day 4 was 20.9±5.2mg/L. The results demonstrated that the incidence of IVH and severe IVH decreased significantly inprevented group (74% vs 97%, P<0.05 and 13% vs 62%, P<0.01 respectively). NO severe IVH and hydrocephaluswere develOPed in the infants with IVH grade Ⅱ in the prevented group. While 7 infants with grade Ⅱ developedgrade Ⅲ during very short period, and 2 infants had to shunt for hydrocephalus in the control group. Infants onphenobarbital had not observed any side - effects. The duration of clinical symptoms was markedly shortened in theprevented group. Conclusion The study supports the use of phenobarbital for the prevention of IVH and severeIVH in Chinese premature infants. It is suggested that phenobarbital prophylaxis should be routinely carried outin all preterm infants with gestational age 34 weeks within 6h alter birth.

PHENOBARBITAL FOR THE PREVENTION OF INTRACRANIAL DAMAGE IN CHINESE NEONATES WITH SEVERE ASPHYXIA

Objective TO evaluate the effect of phenobarbital on preventing intracranial damage and seizurein Chinese neonates with severe asphyxia. Methods A control trial was carried out in 60 Chinese neonates withsevere asphyxia. 30 neonates received loading dose of phenobarbital on an average of 5.6h of age. Results Themean value ol phenobarbital serum level obtained at the 4th day after birth was 21.9μg/ml. No significantdifference was observed in the two groups in terms of birth weight, gestational age, Apgar scores, sex, etc. Theimaging diagnosis within 3d of age in all subjects showed normal brain in 14, brain edema in 9 andintraventricular hemorrhage (IVH) in 7 in the treated group with a 53.3% of total complication rate, and normalbrain in 5, brain edema in 15, IVH in 9 and subarachnoid hemorrhage (SAH) in 1 in the untreated group with a83.3% of total complication rate. The incidence of intracranial damage in the untreated group was significantlyhigher than that in the treated group (83.3% vs 53.3%, P<0.05). In the treated group, 4 neonates with seizuresymptom were effectively controlled soon, and none of the other 26 developed seizure. The period of seizure in thetreated group was significantly shorter than that in the untreated group (P<0.05). Other clinical symptoms werealso sooner improved and no side effects were observed among the neonates treated with phenobarbital. Con-clusion The incidence of postasphyxiated intracranial damage was obviously decreased, and seizure could beprophylactically intervened by phenobarbital. It is recommended that early application of preventive phenobarbitalin severely asphyxiated neonates is reasonable in reducing the incidence of intracranial lesions and subsequentselzures.

Anesthetic effect of phenobarbital sodium on female BALB/c mice

Objective:Anesthetics are of great importance in avoiding severe pain and suffering in animals and ensuring experimental progress.This study was aimed at elucidating the anesthesia score of phenobarbital sodium as a general anesthetic at different concentrations and doses in BALB/c mice,and finding the suitable anesthesia strategies for experimental surgeries.Methods:Phenobarbital sodium was administrated intraperitoneally at the doses of 75,100,125,150,and 200 mg/kg and randomly in different concentrations(2%,5%,and 10%)to female BALB/c mice.The anesthesia score was evaluated based on the stimulus index including tail-pinch,front and hind limb withdrawal,and eyelid reflexes.The speed and duration of anesthesia in different groups were recorded per the occurrence and duration of the righting reflex.Results:The anesthetic effect of phenobarbital sodium on female BALB/c mice showed an obvious dose-dependency.Respiratory suppression caused by high-dose anesthesia may lead to mouse death.Based on the anesthesia score,when the phenobarbital sodium treatment was greater than or equal to five percent or 200 mg/kg,more than 80%mice meet the anesthesia depth that surgical operation needed.The rates of achieving surgical anesthesia depth(standard-reaching rate)in mice treated with 2%sodium phenobarbital were 0%in the 75 mg/kg group,0%in the 100 mg/kg group,50%in the 125 mg/kg group,66.7%in the 150 mg/kg group,and 100%in the 200 mg/kg group.The standard-reaching rate of mice treated with 5%concentration of phenobarbital sodium were:0%in the 75 mg/kg group,0%in the 100 mg/kg group,83.33%in the 125 mg/kg group,100%in the 150 mg/kg group,and 100%in the 200 mg/kg group.The standard-reaching rate of mice treated with 10%concentration of phenobarbital sodium were:50%in the 75 mg/kg group,66.7%in the 100 mg/kg group,100%in the 125 mg/kg group,100%in the 150mg/kg group,and 100%in the 200 mg/kg group.Sedation and hypnosis were induced in the low-concentration dose group,and anesthesia was induced in the high-concentration dose group.In the 5%and 125 mg/kg phenobarbital sodium groups,the mortality rate of mice was 0,the anesthesia induction time was(35.5±7.92)minutes,and the anesthesia duration was(106±39.59)minutes.In the 5%and 150 mg/kg phenobarbital sodium groups,the mortality rate of mice was 0,the anesthesia induction time was(34.83±5.27)minutes,and the anesthesia duration was(131.7±36.75)minutes.Conclusion:Phenobarbital sodium alone can provide appropriate general anesthesia in female BALB/c mice.Both the concentration and dose of phenobarbital sodium can affect the anesthetic effect.On the basis of our findings,we recommend the 5%and 125 mg/kg and 5%and 150 mg/kg concentration–dose combinations of phenobarbital sodium for anesthetizing mice according to the surgical requirement.

Short and Long Term Effects of Pomegranate （Punica Granatum） Extracts on Apoptosis in Rat Kidney Induced by Diethylnitrosamine and Phenobarbital

Pomegranate （Punica granatum L.） has strong anti-inflammatory, antioxidant, anti obesity, and anticancer effects. The effect of different pomegranate extracts, PE （peel extract）, SOE （seed oil extract）, and PJ （pomegranate juice） extract on levels of kidney caspase-3, DNAF （DNA fragmentation） and kidney function tests in rats treated and untreated with DEN （diethyl nitrosamine） and PB （Phenobarbital） during short （35 days） and long （154 days） period was studied. Injected of rats with DEN and PB caused an increased in the levels ofDNAF, caspase-3 and kidney function tests, compared to the control in both period of study. Treatment of rats with PE, SOE, PJ pre, during, and post DEN and PB administration improved kidney function and decreased the levels of DNAF, and caspase-3 activities compared to the DEN group in both period of study, indicates that PE, SOE, PJ reduced and treatment apoptosis induced by DEN and PB. Treatment of healthy rats with PE, SOE, and PJ only for 35 days not increased kidney function or induced apoptosis for kidney tissues. Treatment with PJ alone in healthy kidney induced apoptosis which was higher than that induced by SOE and PE in case of long period study, this mean that fresh fruit or pomegranate juice safe for healthy in general at harvesting season only.

Therapeutic effect of phenobarbital combined with mild hypothermia on neonatal asphyxia

Objective: To analyze the efficacy of phenobarbital combined with mild hypothermia in the treatment of neonatal asphyxia. Methods: Subjects selected 50 children with neonatal asphyxia treated in our hospital from February 2016 to August 2017. They were randomly divided into a control group and an observation group with 25 cases in each group. The two groups of children were given routine resuscitation treatment. The control group was given phenobarbital injection on the basis of this. The observation group was given phenobarbital combined with mild hypothermia treatment, the heart rate, respiration, blood pressure changes, liver and kidney function, coagulation function and blood gas analysis after treatment were analyzed and compared between the two groups. At the same time, the outcomes and NBNA scores of the two groups were compared. Results: During the course of treatment, the heart rate of the observation group at the same time period was significantly lower than that of the control group (P<0.05);After treatment, Respiratory, systolic and diastolic blood pressures in two groups of children, serum urea (BUN), serum creatinine (Scr), thromboplastin time (PT), plasma thrombin time (TT), arterial serum pH, blood, There was no significant difference in partial pressure of oxygen (PO2) and remaining alkali (BE) (all P>0.05), the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and NBNA scores in the observation group were significantly higher than those in the control group (all P<0.05), the length of hospitalization and feeding time were significantly lower than those in the control group (all P<0.05). Conclusion: Phenobarbital combined with mild hypothermia for neonatal asphyxia can significantly improve brain damage and liver and kidney function in children, reduce acidosis and respiratory depression, and have no negative effect on heart rate, blood pressure, coagulation function, etc. The efficacy is good and its safety is high.

Phenobarbital Use as Adjunct to Benzodiazepines in the Treatment of Severe Alcohol Withdrawal Syndrome

Severe AWS （alcohol withdrawal syndrome） and AWD （alcohol withdrawal associated delirium） are common indications for intensive care unit admissions. Approximately 25% of patients with severe alcohol withdrawal require prolonged critical care hospital courses, often complicated by respiratory failure, need for mechanical ventilation due to administration of sedative continuous infusions and development of nosocomial infections. Although benzodiazepines are the mainstay of therapy for alcohol withdrawal, some patients exhibit benzodiazepine-refractory alcohol withdrawal. The use of phenobarbital as adjunct to benzodiazepines has been shown in studies to be effective in enhancing therapeutic responsiveness to benzodiazepines and reducing the need for mechanical ventilation. The objective of this study is to evaluate whether severe alcohol withdrawal treatment based on combining symptom-triggered benzodiazepine therapy with adjunctive phenobarbital will result in decreased mechanical ventilation rates, decreased use of continuous sedative infusions, decreased time to withdrawal symptom resolution and decreased length of stay in the intensive care unit. Chart reviews were utilized to determine total amount of benzodiazepine and phenobarbital use, need for mechanical ventilation, requirement of continuous lorazepam, dexmedetomidine or propofol infusions, average intensive care unit length of stay and incidence of adverse effects.

Phenobarbital in the treatment of alcohol withdrawal syndrome

Alcohol withdrawal syndrome(AWS)is a serious disorder affecting alcohol-dependent patients who abruptly stop or reduce their drinking.Mild or moderate AWS usually appears within 6 to 24 h after the last drink,and symptoms may include increased blood pressure and rapid pulse,tremors,high fever,irritability,anxiety,headache,nausea,and vomiting.These symptoms may progress to a more severe AWS characterized by delirium tremens,seizures,coma,cardiac arrest,and death.This article will analyze the phenobarbital(PB)treatment of AWS and make a brief review'.

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time.

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the

苯巴比妥治疗新生儿惊厥的稳态谷浓度分布及影响因素分析

目的 对苯巴比妥治疗新生儿惊厥时稳态谷浓度(C_(0))的分布及其影响因素进行分析,为新生儿临床安全、合理使用苯巴比妥提供参考。方法 回顾性收集2020年1月至2023年12月郑州大学第二附属医院收治的使用苯巴比妥治疗新生儿惊厥并行血药浓度监测的患儿临床资料,分析C_(0)的分布情况,并采用多元线性回归方法分析C_(0)的影响因素。结果 共纳入86例患儿,苯巴比妥C_(0)为(28.94±12.86)mg/L。以15~40 mg/L为苯巴比妥C_(0)治疗靶值范围,64例(74.41%)患儿C_(0)达标。多元线性回归分析结果显示,患儿出生后日龄、苯巴比妥给药方式、白蛋白、直接胆红素对C_(0)有显著影响(P<0.05)。结论 临床使用苯巴比妥治疗新生儿惊厥时,有必要根据出生后日龄、苯巴比妥给药方式、白蛋白、直接胆红素优化苯巴比妥给药方案。

江苏省农村癫痫患者苯巴比妥治疗的疗效分析

目的:评价江苏省农村地区惊厥性癫痫患者接受苯巴比妥单药治疗的疗效。方法:对2005年1月—2020年12月符合入组条件的癫痫患者实行苯巴比妥单药治疗和随访管理,评价分析患者的临床特征、服药剂量、疗效以及不良反应等。结果:本研究共纳入4315例惊厥性癫痫患者,其中73.8%癫痫患者苯巴比妥最大服用剂量为30~90 mg/d。2715例患者随访满4年,治疗有效率为75.44%,约20%患者癫痫症状恶化。治疗1个月时,不良反应发生率为16.2%,随访满4年后降低至10.87%,其主要表现为困倦、头晕、头痛等症状。结论:苯巴比妥单药治疗惊厥性癫痫患者具有良好的临床效果,可以在农村地区继续推广实施。

ABCB1基因C3435T多态性对苯巴比妥透过癫痫患者血-脑屏障的影响

目的探讨ABCB1基因C3435T多态性对苯巴比妥(PB)透过癫痫患者血-脑屏障(BBB)及癫痫发作的影响。方法选择62例接受PB单药治疗的全身强直-阵挛发作癫痫患者,记录6个月治疗期间的癫痫发作次数。对患者进行ABCB1基因C3435T多态性基因分型,测定脑脊液(CSF)及血清(S)中PB的药物浓度,计算CSF/S-PB浓度比作为PB透过BBB的指标。结果62例患者经ABCB1基因C3435T基因测序分型,其中CC型17例,CT型32例和TT型13例;CC型、CT型和TT型患者CSF-PB分别为(44.71±10.95)μmol/L、(52.75±13.24)μmol/L、(65.64±14.34)μmol/L,CSF/S-PB分别为0.47±0.12、0.53±0.17、0.66±0.19,差异有统计学意义(P<0.05)。CC型发作9次2例,8次1例,7次3例,6次2例,发作超过5次CT型和TT型仅有1例,CC基因型和低CSF/S-PB与癫痫发作频率增加相关(P<0.05)。结论ABCB1基因C3435T多态性显著影响癫痫患者CSF/S-PB浓度比和癫痫发作频率,可能是癫痫耐药的机制之一。

亚低温配合苯巴比妥治疗新生儿窒息对患儿氧化应激指标、心肌损伤标志物水平的影响

目的探讨亚低温配合苯巴比妥治疗对新生儿窒息患儿的影响.方法选取2020年2月—2023年10月该院收治的80例新生儿窒息患儿为研究对象,按照随机数字表法将其分为对照组与观察组.对照组(n=40)采用苯巴比妥治疗,观察组(n=40)于对照组基础上采用亚低温治疗.对比两组相关临床指标、氧化应激指标、心肌损伤标志物水平、脑组织损伤相关指标.结果观察组意识恢复时间、反射恢复时间、住院时间、肌张力恢复时间分别为(3.77±0.31)d、(6.41±1.12)d、(13.02±2.74)d、(6.17±1.14)d,均短于对照组,组间差异有统计学意义(P<0.05).治疗后,观察组神经元特异性烯醇化酶、丙二醛、肌钙蛋白T、肌酸激酶同工酶、星形胶质源性蛋白水平分别为(9.31±1.58)U/mL、(2.12±0.67)μmol/L、(0.44±0.11)μg/L、(66.73±9.33)U/L、(3.02±1.04)ng/mL,均低于对照组,超氧化物歧化酶、谷胱甘肽水平分别为(98.55±10.57)U/L、(112.53±12.08)U/L,均高于对照组,组间差异有统计学意义(P<0.05).结论在新生儿窒息患儿中应用亚低温配合苯巴比妥治疗,能够促进临床相关指标改善,减轻机体氧化应激反应,缓解心肌损伤,降低脑组织受损程度.