Real-Time Analytical Solutions as Series Formulas and Heaviside off/on Switch Functions for Multiple Intermittent Intravenous Infusions in One- and Two-Compartment Models

Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.

Application of Patient Simulators Combined with Internet plus Scenario Simulation Teaching Models on Intravenous Infusion Nursing Education in China

Objective: To explore the effectiveness of applying patient simulators combined with Internet Plus scenario simulation teaching models on intravenous (IV) infusion nursing education, and to provide scientific evidence for the implementation of advanced teaching models in future nursing education. Methods: Enrolled 60 nurses who took the IV infusion therapy training program in our hospital from January 2022 to December 2023 for research. 30 nurses who were trained in traditional teaching models from January to December 2022 were selected as the control group, and 30 nurses who were trained with simulation-based teaching models with methods including simulated patients, internet, online meetings which can be replayed and scenario simulation, etc. from January to December 2023 were selected as the experimental group. Evaluated the learning outcomes based on the Competency Inventory for Nursing Students (CINS), Problem-Solving Inventory (PSI), comprehensive learning ability, scientific research ability, and proficiency in the theoretical knowledge and practical skills of IV infusion therapy. Nursing quality, the incidence of IV infusion therapy complications and nurse satisfaction with different teaching models were also measured. Results: The scientific research ability, PSI scores, CINS scores, and comprehensive learning ability of the experimental group were better than those of the control group (P 0.05), and their assessment results of practical skills, nursing quality of IV infusion therapy during training, and satisfaction with teaching models were all better than those of the control group with statistical significance (P < 0.05). The incidence of IV infusion therapy complications in the experimental group was lower than that in the control group, indicating statistical significance (P < 0.05). Conclusions: Teaching models based on patient simulators combined with Internet Plus scenario simulation enable nursing students to learn more directly and practice at any time and in any place, and can improve their proficiency in IV infusion theoretical knowledge and skills (e.g. PICC catheterization), core competencies, problem-solving ability, comprehensive learning ability, scientific research ability and the ability to deal with complicated cases. Also, it helps provide high-quality nursing education, improve the nursing quality of IV therapy, reduce the incidence of related complications, and ensure the safety of patients with IV therapy.

Early Application Study of Intravenous Pain Pump Combined with Parecoxib Injection in Relieving Pain in Patients after Thoracoscopy

Objective: To explore the clinical effectiveness of combined use of intravenous pain pump with Parecoxib injection in alleviating pain in patients during the early postoperative period after thoracoscopic surgery. Methods: Eighty patients who underwent thoracoscopic surgery in a tertiary hospital were selected as the study subjects and randomly divided into two groups, with 40 patients in each group. The control group received routine postoperative treatment with intravenous pain pump, while the experimental group received Parecoxib in addition to the standard postoperative pain pump treatment. Visual Analog Scale (VAS) pain scores were used to evaluate postoperative pain relief in both groups, along with adverse reactions, postoperative complications, and patient satisfaction with pain relief. Results: Patients who received Parecoxib injection in addition to the routine use of intravenous pain pump had VAS pain scores lower than 3 points at 6 h, 12 h, 24 h, and 36 h postoperatively compared to those in the control group. The incidence of postoperative lung collapse, pleural effusion, and pulmonary infections was also significantly lower in the experimental group. The differences between the two groups were statistically significant (P Conclusion: Early combined use of Parecoxib injection in the early postoperative period after thoracoscopic surgery has shown good clinical efficacy. It can reduce the level of pain in patients, promote effective coughing and expectoration, facilitate early mobilization of patients, improve patient compliance, reduce complications, shorten hospital stay, and expedite patient recovery. Therefore, it is worth promoting the widespread clinical application of Parecoxib injection in this setting.

Effectiveness and safety of rocuronium or nitroglycerin plus ropivacaine on pain during intravenous regional anesthesia:A double-blind randomized controlled trial

Objective:To compare the effects of adding rocuronium and nitroglycerin to ropivacaine in intravenous regional anesthesia(IVRA)on pain and hemodynamic parameters.Methods:This randomized controlled trial was done in 2023.Participants were 177 candidates for forearm operation surgery under IVRA selected from Valiasr Hospital,Arak,Iran.They were allocated by block randomization to three different groups,namely nitroglycerin group,rocuronium group and control group.Hemodynamic parameters were recorded before tourniquet application up to postoperative recovery time.Sensory block and motor block onset and duration and pain were also evaluated.The data analysis was carried out by IMB SPSS software 20.0.Results:177 Eligible patients were included in study,with 59 in each group.Time to sensory and motor block onset in the nitroglycerin group was significantly less than the other groups and the time of motor block in the rocuronium group was statistically higher than the control and the nitroglycerin groups(P<0.001).Seven participants in the nitroglycerin group experienced headache and three from the rocuronium group experienced dizziness.The side effects occurrence in the nitroglycerin group was more prevalent than in the control and rocuronium groups(P=0.009).Conclusions:Nitroglycerin significantly reduces the time to sensory and motor block onset,while rocuronium is more effective in prolonging the time of motor block.Although there is no difference between nitroglycerin and rocuronium respecting the pain score and opioid need administration,nitroglycerin is associated with a higher prevalence of medication side effects.Therefore,both nitroglycerin and rocuronium can be used as adjuvant for IVRA.The final choice relies on patients’conditions and anesthesiologists’judgment.

Pain and immune function in patients undergoing gastric cancer surgery following stellate ganglion block with total intravenous anesthesia

BACKGROUND Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity.AIM To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer(GC)surgery to provide a refe-rence basis for the formulation of anesthesia protocols for radical GC surgery.METHODS This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024.There was no restriction on sex.The patient grouping method used was a digital random table method,and the num-ber of cases in each group was 56.The control group was administered total intravenous anesthesia,and the observation group compounded the stellate gan-glion block according to the total intravenous anesthesia protocol.Postoperative hemodynamics,pain levels,and immune indices were compared between the groups.RESULTS The heart rate and mean arterial pressure in the observation group after in-tubation were lower than those in the control group(P<0.05).Pain levels were compared between the two groups at 2 hours,12 hours,24 hours,and 48 hours after surgery(P>0.05).The number of CD3+,CD4+,and CD4+/CD8+cells at the end of surgery was higher in the observation group than in the control group,and the number of CD8+cells was lower in the observation group than in the control group(P<0.05).There were no significant differences between the two groups in terms of propofol dosage,awakening time,extubation time,or postoperative adverse reactions(P>0.05).CONCLUSION The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery.However,it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.

Research on the Causes and Nursing Interventions of Extravasation During Intravenous Infusion

Intravenous infusion,a common clinical drug treatment method,is widely used in the treatment of various diseases.Due to the invasive nature of puncture during intravenous infusion,patients may inevitably experience resistance and tension when facing nursing staff performing infusion procedures.Additionally,the complexity of the nursing staff’s work and the impact of the infusion therapy environment can exacerbate the tension between nurses and patients,leading to risks such as drug leakage and needlestick injuries.This article focuses on the factors influencing extravasation during intravenous infusion and elaborates on how high-quality nursing interventions can reduce the incidence of adverse events during intravenous infusion.These interventions aim to improve patient satisfaction with intravenous infusion nursing care and ensure the safety of intravenous infusion procedures.

Amylase intrapancreatic infusion delays insulin release during an intravenous glucose tolerance test,proof of acini–islet–acinar interactions

BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ.METHODS The study was performed on six pigs under general anesthesia.An intravenous glucose tolerance test was performed,with a bolus infusion of 50%glucose to the jugular vein,while amylase(5000 U/kg)or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate.RESULTS The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion,for>1 h.The intrapancreatic infusion of the vehicle(saline)did not have any effect on the time frame of insulin release.Infusion of 1%bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion,far beyond the glucose peak.CONCLUSION Intrapancreatic arterial infusion of amylase interrupted the integrated glucose–insulin interactions.This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.

Oncolytic virus-based hepatocellular carcinoma treatment:Current status,intravenous delivery strategies,and emerging combination therapeutic solutions

Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.

Efficacy and safety of intravenous tranexamic acid in total shoulder arthroplasty:A meta-analysis

BACKGROUND Total shoulder arthroplasty(TSA)results in a large amount of perioperative blood loss due to severe trauma.AIM To investigate the safety and efficacy of intravenous tranexamic acid(TXA)in TSA.METHODS We searched the PubMed,Cochrane Library,Embase and Web of Science databases for randomized controlled trials(RCTs)on the use of TXA in TSA.And all the results were checked and assessed by Reference Citation Analysis(https://www.referencecitationanalysis.com/).A meta-analysis was performed with Review Manager 5.3 to calculate the odds ratio(OR)or weighted mean difference(WMD)of related outcome indicators.RESULTS A total of 5 RCTs with level 1 evidence were included.There were 369 cases,with 186 in the TXA group and 183 in the placebo group.The meta-analysis showed that TXA can significantly reduce total blood loss during the perioperative period[WMD=-249.56,95%confidence interval(CI):-347.6 to-151.52,P<0.0001],and the incidence of adverse reactions was low(OR=0.36,95%CI:0.16-0.83,P=0.02).Compared with the placebo group,the TXA group had significantly less total haemoglobin loss(WMD=-34.39,95%CI:-50.56 to-18.22),less haemoglobin fluctuation before and after the operation(WMD=-0.6,95%CI:-0.93 to-0.27)and less 24-h drain output(WMD=-136.87,95%CI:-165.87 to-106.49).There were no significant differences in the operation time(P=0.11)or hospital length of stay(P=0.30)between the two groups.CONCLUSION The application of intravenous TXA in the perioperative period of TSA can significantly reduce the total volume of perioperative blood loss and reduce the incidence of adverse reactions,so TXA is worthy of widespread clinical use.

Double pigtail catheter reduction for seriously displaced intravenous infusion port catheter:A case report

BACKGROUND Implanted intravenous infusion port(TIAP)is mainly used for patients who need central venous infusion and poor peripheral vascular conditions.With the advantages of easy to carry,long maintenance cycle,few complications and excellent quality of life,it has been widely used in the fields of malignant tumor chemotherapy,parenteral nutrition support and repeated blood collection.Implanted intravenous infusion port(IVAP)dislocation can have significant complications if not recognised and reinstated immediately.CASE SUMMARY A 24-year-old man was treated with adjuvant chemotherapy for osteosarcoma.Severe displacement of IVAP catheter was found by chest X-ray examination.The IVAP cannot be used normally.Therefore,we conducted an emergency procedure to reset the catheter through double pigtail catheters,the operation was successful and the infusion port was restored.CONCLUSION When IVAP catheter displacement cannot be reset by conventional techniques,two pigtail catheters can be successfully used instead.

Progress in oncolytic viruses modified with nanomaterials for intravenous application

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor cells.Simultaneously,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer cells.However,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely restricted.In recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection.The most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and effectiveness.The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

Training needs in intravenous infusion care for children in China:A cross-sectional study

Aim:This study aims to evaluate demands for general and pharmacological knowledge and training related to intravenous(IV)therapy among pediatric nurses.Materials and Methods:This multicentric cross‑sectional study involved 12,707 pediatric nurses from 100 hospitals in China.A questionnaire was used to assess information about IV drug administration training received,and the demands for pharmacology‑related knowledge,and corresponding methods of acquisition.A generalized linear model using Logit link function was employed to assess relationships between factors and multivariate analysis was conducted.Results:More than 99%of participants showed their training demands for IV therapy training.Pediatric nurses’demands and methods for acquiring IV therapy knowledge and the knowledge related to IV therapy pharmacology have significant differences in social demographic factors,previous knowledge,whether they have received training or not,and other factors(all P<0.05).Received a needlestick injury in the past month(P=0.007)and knowledge acquired through in‑hospital or out‑of‑hospital training(P=0.039)were factors that reduced the demands for methods to acquire further pharmacology‑related knowledge of IV therapy.Working in internal medicine(P=0.025)and not having experienced a needlestick injury in the past year(P=0.007)reduced the demands for IV therapy knowledge.Attended hospital(P=0.007)or departmental meetings(P=0.009),being pediatric primary nurses(P=0.044),and studied special IV guidelines(P=0.006)reduced the desire for methods to acquire IV therapy knowledge.Conclusion:There was a high demand for greater general and pharmacological knowledge related to IV therapy among pediatric nurses.Resources should be coordinated to provide ongoing training to nurses to improve the quality of IV care.

Oral Glucose Combined with Short-Term Intravenous Nutrition for the Prevention of Hypoglycemia after Endoscopic Colorectal Polypectomy

Objective: To investigate the effect of oral glucose combined with short-term intravenous nutrition on the prevention of hypoglycemia after endoscopic colorectal polypectomy and to provide guidance for better management of such patients. Methods: 860 patients who underwent endoscopic colorectal polypectomy for colorectal polyps in the Department of Gastroenterology of the First Affiliated Hospital of Yangtze University from January 2020 to December 2021 were selected for the study. The patients were divided into experimental and control groups according to the random number table method, with 430 patients in each group. In the control group, 3 L of polyethylene glycol electrolyte dispersion was used for preoperative intestinal preparation and postoperative fasting was performed routinely for 24 h. Short-term intravenous nutrition support was provided by rehydration, and finger blood glucose was monitored at 1, 4, and 8 h after intravenous infusion or when there were symptoms such as panic and cold sweat;in the experimental group, oral glucose intervention was implemented on the basis of the control group. The incidence of postoperative hypoglycemia, quality of bowel preparation, and tolerance of patients during bowel preparation were compared between the 2 groups. Results: The incidence of postoperative blood glucose Conclusion: Based on the present study population, oral glucose combined with short-term intravenous nutrition can effectively prevent the incidence of hypoglycemia in patients after endoscopic colorectal polypectomy;however, this was limited to a single-center study and the number of cases was small.

Oral Glucose Combined with Short-Term Intravenous Nutrition for the Prevention of Hypoglycemia after Painless Endoscopic Gastric Polypectomy

Objective: To explore the application effect of oral glucose combined with short-term intravenous nutrition in preventing postoperative hypoglycemia after painless endoscopic gastric polyp resection, and to provide guidance for better management of patients undergoing such procedures. Methods: A total of 886 patients who underwent painless endoscopic gastric polyp resection in the Department of Gastroenterology, the First Affiliated Hospital of Yangtze University, from January 2020 to December 2021, were selected as the study subjects. According to the random number table method, they were divided into an experimental group and a control group, with 443 cases in each group. Patients in the control group were subjected to routine fasting and water restriction for 8 hours before surgery, and routine fasting for 24 hours after surgery. Short-term intravenous nutrition support was provided through fluid supplementation, and finger blood glucose levels were monitored at 1 hour, 4 hours, and 8 hours after completion of intravenous infusion, or when symptoms such as palpitations and cold sweats occurred. The experimental group received oral administration of 5% glucose solution (500 ml) 2 hours before surgery based on the procedures of the control group. The incidence of preoperative discomfort (hunger, thirst, and fatigue), residual gastric fluid volume, and postoperative hypoglycemia were compared between the two groups. Results: The incidence of postoperative blood glucose Conclusion: Based on the study population, oral glucose combined with short-term intravenous nutrition can effectively prevent the incidence of hypoglycemia in patients undergoing painless endoscopic gastric polyp resection. However, due to the limitations of a single-center study and a small number of cases, its feasibility needs to be further validated with more data from multi-center and large-sample cases.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus

Background:The appropriate antibiotic treatment for severe scrub typhus,a neglected but widespread reemerging zoonotic infection,is unclear.Methods:In this multicenter,double-blind,randomized,controlled trial,we compared the efficacy of intravenous doxycycline,azithromycin,or a combination of both in treating severe scrub typhus.Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled.The patients were assigned to receive a 7-day course of intravenous doxycycline,azithromycin,or both(combination therapy).The primary outcome was a composite of death from any cause at day 28,persistent complications at day 7,and persistent fever at day 5.

Early intravenous administration of tirofiban is recommended in patients with acute ischemic stroke treated with alteplase:a meta-analysis

Background:The occurrence of early neurological deterioration following intravenous thrombolysis(IVT)is considered a particularly ominous clinical event and is strongly correlated with poor outcomes.Initiating tirofiban within 24 h after IVT has been suggested as a better treatment option to achieve long-term functional outcomes.However,the rationality of this remedy is a controversial.The purpose of the study was to evaluate the safety and efficacy of early intravenous tirofiban administration after IVT in patients with acute ischemic stroke(AIS).Methods:Databases including PubMed,EMBASE,Cochrane Library,and Web of Science were searched for clinical trials on early tirofiban implementation after IVT in patients with AIS from inception to September 2022.Odds ratios(ORs)were generated for dichotomous variants via meta-analysis using STATA 17.0 MP.Results:Five clinical trials with 725 patients were eligible.The study outcomes demonstrated that early tirofiban administration after IVT was not associated with symptomatic intracranial hemorrhage(OR,0.78;95%confidence interval(CI),0.22–2.74;P=0.70),asymptomatic intracranial hemorrhage(OR,1.11;95%CI,0.52–2.37;P=0.80),systemic bleeding(OR,0.97;95%CI,0.42–2.23;P=0.94),and death(OR,1.05;95%CI,0.47–2.31;P=0.91),but may reduce the incidence of early neurological deterioration(OR,0.09;95%CI,0.02–0.50;P=0.01),and was significantly associated with 90-day excellent(modified Rankin scale score 0–1)(OR,2.01;95%CI,1.35–3.02;P=0.00)and favorable(modified Rankin scale score 0–2)(OR,2.30;95%CI,1.63–3.23;P=0.00)functional outcomes.Conclusion:The early intravenous administration of tirofiban after IVT in patients with AIS may be a safe and effective treatment strategy that improves long-term neurological functional outcomes without increasing the risk of adverse events.

The Effect of the Early Application of Tirofiban on Acute Ischemic Stroke (AIS) after Intravenous Thrombolysis with Urokinase

Objective:Discussion and analysis of the effect of the early application of Tirofiban on acute ischemic stroke(AIS)after intravenous thrombolysis with urokinase.Method:The subjects of this study are 40 patients with AIS admitted at the Yibin Fourth People’s Hospital,of which were computer-randomized into a control group(20 cases,with regular urokinase intravenous thrombolysis therapy)and a research group(20 cases,combined with early Tirofiban treatment)from January 2018 to December 2022.The intervention outcomes between these two groups were compared and analyzed.Result:The blood platelet-related parameters before treatment had no statistical difference between the two groups(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).The Barthel index before treatment in both groups had no statistical difference(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).Conclusion:Early Tirofiban treatment for patients with AIS after intravenous thrombolysis with urokinase could effectively regulate the blood platelet-related parameters,hence improving treatment benefits and living capacity for patients,with definite clinical benefits.

Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.

Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation

AIM:To investigate the effects of intravenous administration of the antioxidant glutathione (GSH) on reperfusion injury following liver transplantation. METHODS:Livers of male Lewis rats were transplanted after 24 h of hypothermic preservation in University of Wisconsin solution in a syngeneic setting.During a 2-h reperfusion period either saline (controls,n=8) or GSH (50 or 100 μmol/(h·kg),n=5 each) was continuously administered via the jugular vein. RESULTS:Two hours after starting reperfusion plasma ALT increased to 1 457±281 U/L (mean±SE) in controls but to only 908±187 U/L (P<0.05) in animals treated with 100 μmol GSH/(h·kg).No protection was conveyed by 50μmol GSH/(h·kg).Cytoprotection was confirmed by morphological findings on electron microscopy:GSH treatment prevented detachment of sinusoidal endothelial cells (SECs) as well as loss of microvilli and mitochondrial swelling of hepatocytes.Accordingly,postischemic bile flow increased 2-fold.Intravital fluorescence microscopy revealed a nearly complete restoration of sinusoidal blood flow and a significant reduction of leukocyte adherence to sinusoids and postsinusoidal venules.Following infusion of 50μmol and 100 μmol GSH/(h·kg),plasma GSH increased to 65±7 mol/L and 97±18 mol/L,but to only 20±3 mol/L in untreated recipients. Furthermore,plasma glutathione disulfide (GSSG) increased to 7.5±1.0 mol/L in animals treated with 100μmol/(h·kg) GSH but infusion of 50μmol GSH/(h·kg) did not raise levels of untreated controls (1.8±0.5 mol/L vs 2.2±0.2 mol/L). CONCLUSION:Plasma GSH levels above a critical level may act as a “sink” for ROS produced in the hepatic vasculature during reperfusion of liver grafts.Therefore,GSH can be considered a candidate antioxidant for the Drevention of reperfusion injury after liver transplantation,in particular since it has a low toxicity in humans.

Successful Treatment of Severe Heparin-induced Thrombocytopenia with Intravenous Immunoglobulin, Platelet Transfusion and Rivaroxaban: A Case Report

Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.