Analgesic effects of combined transversus abdominis plane block and intramuscular electrical stimulation in patients undergoing cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy: a randomized controlled trial.

BACKGROUND: To evaluate the analgesic efficacy of a four-quadrant transversus abdominis plane (4QTAP) block and a combination of 4QTAP block with needle electrical twitch and intramuscular electrical stimulation (NETOIMS) in patients undergoing cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: Eighty-one patients who underwent CRS followed by HIPEC were included in this study. Patients were randomly assigned to one of three groups: group 1 (intravenous patient-controlled analgesia, control group), group 2 (preoperative 4QTAP block), and group 3 (preoperative 4QTAP block and postoperative NETOIMS). The primary study endpoint was the pain score assessed by the visual analog scale (VAS: 0, no pain; 10, worst imaginable pain) on postoperative day (POD) 1. RESULTS: The VAS pain score on POD 1 was significantly lower in group 2 than in group 1 (6.0±1.7 and 7.6±1.9, P =0.004), whereas that in group 3 was significantly lower than that in groups 1 and 2 ( P <0.001 and P =0.004, respectively). Opioid consumption and nausea and vomiting incidence during POD 7 were significantly lower in group 3 than in groups 1 and 2. Gait speed and peak cough flow on POD 4 and 7, as well as the quality of recovery (QoR)-40 score on POD 4, were significantly higher in group 3 than in groups 1 and 2. CONCLUSIONS: The combination of a 4QTAP block with NETOIMS provided more effective analgesia than a 4QTAP block alone after CRS, followed by HIPEC, and enhanced functional restoration and quality of recovery.

Comparison of pharmacologic therapies alone versus operative techniques in combination with pharmacologic therapies for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A randomized controlled trial.

BACKGROUND: Laparoscopic cholecystectomy (LC) causes moderate pain. Various operative analgesic techniques and pharmacologic treatments can reduce postoperative pain. This single-center, single-surgeon randomized controlled study aimed to assess the efficacy of combined operative analgesic techniques and pharmacologic analgesia in decreasing pain in patients undergoing LC. MATERIALS AND METHODS: Fifty-nine patients scheduled for LC were assigned into two groups. In the pharmacologic analgesia (P) group (n = 29), patients were treated with pharmacologic intervention, including preoperative celecoxib (200 mg), intraoperative acetaminophen (1 g), and dexamethasone (8 mg). In the operative analgesic treatments with pharmacologic analgesia (OP) group (n = 30), patients were treated with both operative analgesic techniques and pharmacologic analgesia, including low-pressure pneumoperitoneum, intraperitoneal normal saline irrigation, and aspiration of intraperitoneal carbon dioxide. The area under the curve (AUC) of pain score for postoperative 24 h was assessed at 0, 2, 6, and 24 h post-operation. The analgesic requirements and sleep quality at postoperative day 1 were assessed. RESULTS: The AUC/24 h of pain scores at rest and on cough were lower in the OP group (p < 0.001 and p = 0.001, respectively). The pain scores at rest were lower in the OP group at postoperative 2, 6, and 24 h (p = 0.001, p = 0.001, and p = 0.048, respectively). The pain scores on cough were lower in the OP group at postoperative 2 and 6 h (p = 0.004 and p = 0.008, respectively). Analgesic requirements were comparable. The sleep quality score at postoperative day 1 was higher in the OP group (56 ± 18 vs. 67 ± 15, absolute difference, 10; 95% confidence interval, 2 to 19; p = 0.017). CONCLUSIONS: Combined operative analgesic therapies and pharmacologic analgesia compared to pharmacologic analgesia alone decreased pain scores and increased sleep quality in patients undergoing LC.

Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study.

BACKGROUND: Remimazolam is a new rapid offset benzodiazepine used for procedural sedation and general anaesthesia. This study evaluated the efficacy and safety of i.v. bolus remimazolam during induction of anaesthesia. METHODS: A total of 120 patients undergoing general anaesthesia were randomly allocated into six dose groups (n=20) of i.v. bolus remimazolam (0.02-0.27 mg kg-1). Loss of consciousness, respiratory depression, patient state index (PSI), and haemodynamic variables were evaluated during anaesthetic induction. Parametric time-to-event models were used to identify the 50% effective dose (ED50)/95% effective dose (ED95) associated with loss of consciousness and respiratory depression. Non-linear mixed-effect models analysed the PSI and haemodynamic changes after i.v. bolus remimazolam. RESULTS: Loss of consciousness and respiratory depression onset showed steep dose-responses with ED50/ED95 of 0.11/0.19 and 0.14/0.27 mg kg-1 and Hill coefficients of 5.3 and 4.6, respectively. Older age was significantly associated with lower ED50/ED95 for both endpoints. ED50/ED95 and the Hill coefficient of PSI decline were 0.12/0.68 mg kg-1 and 1.7, respectively. We propose optimal doses of 0.25-0.33, 0.19-0.25, and 0.14-0.19 mg kg-1 in patients aged <40, 60-80, and >80 yr, respectively, based on the ED95 estimates for the corresponding age groups. The maximum percentage reduction of MAP was 27.8% and the ED50/ED95 were 0.14/2.60 mg kg-1. The effect of remimazolam on heart rate was insignificant. CONCLUSIONS: The ED50/ED95s of i.v. bolus remimazolam were successfully estimated from the time to loss of consciousness and respiratory depression. No serious adverse events occurred within the range of tested doses. CLINICAL TRIAL REGISTRATION: NCT04901871.

The effects of two-handed jaw thrust on i-gel™ placement in anesthetized non-paralyzed patients.

BACKGROUND: I-gelTM is a second-generation supraglottic airway device with a non-inflatable cuff. In this prospective randomized investigation, we evaluated the effects of two-handed jaw thrust technique on i-gel insertion in anesthetized non-paralyzed patients. METHODS: Seventy-four adult patients were allocated to two groups (N.=37 each). In the jaw thrust group, two-handed jaw thrust technique was applied to facilitate i-gel insertion. In the control group, conventional i-gel insertion was performed. The success rate at the first attempt, air leakage pressure, insertion time, and postoperative sore throat incidence were recorded. RESULTS: The success rate at the first attempt was higher in the jaw thrust group (37 [100%] vs. 31 [84%], difference of 16%, 95% confidence interval for the difference: 1 to 33%, P=0.03). The median air leakage pressure was higher in the jaw thrust group than in the control group (20 [interquartile range 13] vs. 17 [interquartile range 3] cmH2O, difference: 6, 95% confidence interval of the difference: 3 to 8, P<0.01). The mean insertion time was shorter in the jaw thrust group (27±14 vs. 41±29 seconds, difference: 14 seconds, 95% confidence interval of the difference: 3 to 24, P=0.01). The incidence of postoperative sore throat at the postoperative one hour was lower in the jaw thrust group (seven [20%] vs. 15 [41%], difference 22%, 95% confidence interval for the difference: -1 to 42%, P=0.04). CONCLUSIONS: The two-handed jaw thrust technique facilitated i-gel insertion compared to the conventional technique in anesthetized non-paralyzed patients.

Effect of chlorpheniramine administration on postoperative catheter-related bladder discomfort in patients undergoing transurethral excision of bladder tumor: a prospective randomized study.

PURPOSE: Catheter-related bladder discomfort (CRBD) is postoperative distress caused by a urinary catheter. CRBD is related to muscarinic receptor activation. Chlorpheniramine has antimuscarinic properties. Hence, this investigation was undertaken to evaluate the efficacy of chlorpheniramine in preventing CRBD in patients undergoing transurethral resection of bladder tumor (TURBT). METHODS: Seventy-six patients scheduled for TURBT under general anesthesia were assigned into two groups. In the chlorpheniramine group (n = 38), 100 ml normal saline containing 0.1 mg/kg chlorpheniramine was infused after general anesthesia induction. In the control group (n = 38), 100 ml normal saline alone was infused. The incidence and severity of CRBD were assessed at 1, 6, and 24 h postoperatively. RESULTS: The 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group based on the unadjusted analysis [16 (42%) vs. 28 (74%), risk difference 32%, 95% confidence interval 8-51, p = 0.005]. After adjusting the size of the urinary catheter, post hoc analysis showed that the 1-h postoperative incidence of CRBD was lower in the chlorpheniramine group (p = 0.004). The CRBD severity score was lower in the chlorpheniramine group at 1 and 6 h after operation based on the unadjusted analysis (p = 0.012 and p = 0.007, respectively). After adjusting the urinary catheter size, post hoc analysis showed that 1- and 6-h CRBD severity score was lower in the chlorpheniramine group (p = 0.012 and p = 0.008, respectively). The incidence of rescue medication was lower in the chlorpheniramine group [10 (26%) vs. 20 (53%), risk difference 26%, 95% confidence interval 3-47, p = 0.019]. The overall incidence of complications such as nausea, vomiting, dry mouth, flushing, dizziness, and blurred vision was comparable between the two groups. CONCLUSIONS: Chlorpheniramine administration significantly reduces the incidence and severity of CRBD in the patients undergoing TURBT. TRIAL REGISTRATION: KCT0004880 ( https://cris.nih.go.kr/ ).

Influence of two-handed jaw thrust during tracheal intubation on postoperative sore throat: a prospective randomised study.

OBJECTIVE: General anaesthesia with tracheal intubation results in sore throat. We evaluated the influence of the two-handed jaw thrust on postoperative sore throat in patients who require tracheal intubation. METHODS: In this prospective, double-blind, single-centre, parallel-arm, and randomised trial, 92 patients who were scheduled for general anaesthesia for total hip arthroplasty were allocated to one of two groups. In the jaw thrust group (n = 46), the two-handed jaw thrust manoeuvre was applied at intubation. In the control group (n = 46), conventional intubation with sham jaw thrust was performed. Incidences of airway morbidities including sore throat, hoarseness, and cough at 2, 4, and 24 hours postoperatively were compared. RESULTS: During the postoperative 24 hours, the incidence of sore throat (8 [17%] vs. 20 [44%]) and hoarseness were lower in the jaw thrust group (8 [17%] vs. 18 [39%]) compared with the control group. The incidence of cough during the postoperative 24 hours was similar between the groups. CONCLUSIONS: The jaw thrust manoeuvre significantly reduced sore throat and hoarseness in patients after general anaesthesia using tracheal intubation.Clinical trial registration: NCT03568279.

Evaluation of transmitted glow point at a priori chosen depth (1 cm below vocal cords) for lightwand intubation: a prospective observational study.

OBJECTIVE: When performing lightwand intubation, an improper transmitted glow position before tube advancement can cause intubation failure or laryngeal injury. This study was performed to explore the transmitted glow point corresponding to a priori chosen depth for lightwand intubation. METHODS: Before lightwand intubation, we marked the transmitted glow point from a bronchoscope on the neck when it reached 1 cm below the vocal cords. Lightwand intubation was then performed using this marking point. The distances from the mark to the upper border of the thyroid cartilage, upper border of the cricoid cartilage, and suprasternal notch were measured. RESULTS: In total, 107 patients were enrolled. The success rate of lightwand intubation using the mark was 93.5% (95% confidence interval, 88.7%-99.2%) at the first attempt. The marking point was placed 12.0 mm (95% confidence interval, 10.6-13.4 mm) below the upper border of the cricoid cartilage. CONCLUSION: Anaesthesiologists should be aware of the appropriate point of the transmitted glow on the patient's neck when performing lightwand intubation. We suggest that this point is approximately 1 cm below the upper border of the cricoid cartilage.Trial registration: ClinicalTrials.gov NCT03480035.

Two-handed jaw thrust decreases postoperative sore throat in patients undergoing double-lumen endobronchial intubation: A randomised study.

BACKGROUND: Tracheal intubation using a double-lumen endobronchial tube (DLT) causes postoperative sore throat. OBJECTIVE: To determine the effect of two-handed jaw thrust on postoperative sore throat in patients requiring insertion of a DLT. DESIGN: A randomised study. SETTING: A tertiary teaching hospital from December 2017 to May 2018. PATIENTS: One-hundred and six patients undergoing one-lung anaesthesia. INTERVENTIONS: Patients were allocated to one of two groups (n=53 each). In the jaw thrust group, the two-handed jaw thrust manoeuvre was applied at intubation and advancement of the DLT. In the control group, conventional intubation with a sham jaw thrust was performed. MAIN OUTCOME MEASURES: Incidence of sore throat at 1, 6 and 24 h postoperatively. RESULTS: The incidence of sore throat at 6 h postoperatively was higher in the control group than in the jaw thrust group [31 (59%) vs. 14 (26%), risk ratio (95% confidence interval) 0.45 (0.27 to 0.75), P < 0.01]. The overall incidence of sore throat was higher in the control group than in the jaw thrust group [35 (66%) vs. 18 (34%), risk ratio (95% confidence interval) 0.51 (0.34 to 0.78), P < 0.01]. CONCLUSION: The jaw thrust manoeuvre can reduce the incidence of sore throat in patients undergoing DLT insertion for one-lung ventilation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03331809.

2018 Korean Society of Hypertension Guidelines for the management of hypertension: part II-diagnosis and treatment of hypertension.

The standardized techniques of blood pressure (BP) measurement in the clinic are emphasized and it is recommended to replace the mercury sphygmomanometer by a non-mercury sphygmomanometer. Out-of-office BP measurement using home BP monitoring (HBPM) or ambulatory BP monitoring (ABPM) and even automated office BP (AOBP) are recommended to correctly measure the patient's genuine BP. Hypertension (HTN) treatment should be individualized based on cardiovascular (CV) risk and the level of BP. Based on the recent clinical study data proving benefits of intensive BP lowering in the high risk patients, the revised guideline recommends the more intensive BP lowering in high risk patients including the elderly population. Lifestyle modifications, mostly low salt diet and weight reduction, are strongly recommended in the population with elevated BP and prehypertension and all hypertensive patients. In patients with BP higher than 160/100 mmHg or more than 20/10 mmHg above the target BP, two drugs can be prescribed in combination to maximize the antihypertensive effect and to achieve rapid BP control. Especially, single pill combination drugs have multiple benefits, including maximizing reduction of BP, minimizing adverse effects, increasing adherence, and preventing cardiovascular disease (CVD) and target organ damage.

Influence of intraoperative sevoflurane or desflurane on postoperative sore throat: a prospective randomized study.

PURPOSE: Tracheal intubation for general anesthesia causes postoperative sore throat. The purpose of this study was to evaluate the effect of sevoflurane and desflurane on prevalence of postoperative sore throat in patients after general anesthesia. METHODS: Ninety-six patients scheduled for orthopedic lower extremity surgery under general anesthesia were assigned to sevoflurane group or desflurane group. In the sevoflurane group (n = 48), sevoflurane was used as a maintenance anesthetic agent. In the desflurane group (n = 48), desflurane was used. Prevalence of sore throat, number of patients with rescue analgesics, and analgesics requirements were evaluated. RESULTS: The overall prevalence of postoperative sore throat in the sevoflurane group was lower than that in the desflurane group [21 (44%) vs. 32 (67%), p = 0.024]. The prevalence of sore throat at postoperative 4 h in the sevoflurane group was lower than that in the desflurane group [6 (13%) vs. 18 (38%), p = 0.005]. The number of patients requiring rescue analgesics was lower in the sevoflurane group [25 (52%) vs. 36 (75%), p = 0.020]. The requirement of diclofenac was also lower in the sevoflurane group (30 ± 37 mg vs. 47 ± 40 mg, p = 0.031). CONCLUSIONS: We have shown that sevoflurane was associated with less frequent sore throat than desflurane in patients undergoing orthopedic lower extremity surgery.

The novel myokine irisin: clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women.

PURPOSE: To clarify the association of circulating irisin with muscle, liver and bone, and to evaluate irisin as a biomarker for sarcopenia in postmenopausal women. METHODS: Quadriceps cross-sectional area (QcCSA), bone mineral density (BMD), liver attenuation (measured in Hounsfield units (HU)) were assessed using quantitative computed tomography in 153 postmenopausal women, mean age of 72.20 ± 5.96 years. Muscle strength and physical performance were evaluated by handgrip test and short physical performance battery, respectively. Serum irisin was measured by an enzyme-linked immunosorbent assay kit. In addition, 147 young women were recruited as a reference group to define cut-off values for sarcopenia. RESULTS: Circulating irisin was positively correlated with QcCSA/body weight (BW) and liver HU even after adjusting for multiple covariates, and the serum level was significantly lower in the sarcopenia group (QcCSA/BW<-2SD of the mean values for young women) than in the presarcopenia (-2SD≤QcCSA/BW<-1SD) or control groups (1SD≤QcCSA/BW<2SD). Logistic regression models showed that the relationship between circulating irisin and prevalence of sarcopenia remained significant after adjusting for confounding factors (per 1.0 ng/mL decrease of irisin, odds-ratio = 1.95, 95% confidence interval 1.33-2.87, p-value = 0.001). CONCLUSIONS: In postmenopausal women, serum irisin may be used as a biomarker for sarcopenia, and we showed the potential for the development of irisin-based early screening and staging tool for sarcopenia.

The influence of high-dose intraoperative remifentanil on postoperative sore throat: a prospective randomized study: A CONSORT compliant article.

BACKGROUND: Endotracheal intubation for general anesthesia causes postoperative sore throat (POST). This study is designed to evaluate the effect of high-dose remifentanil on the incidence of POST in patients after general anesthesia. METHODS: Ninety-two patients scheduled for orthopedic lower extremity surgery under general anesthesia were randomly assigned into 1 of 2 groups. In the high-dose remifentanil (HR) group (n = 46), remifentanil was infused at a rate of 0.25 µg/kg/min and subsequently increased or decreased by 0.05 µg/kg/min per clinical demand. In the low-dose remifentanil (LR) group (n = 46), remifentanil was infused at a rate of 0.05 µg/kg/min. The incidence of POST was monitored at 0, 2, 4, and 24 hours postoperatively. Complications regarding opioids were compared between groups. RESULTS: The overall incidence of POST was higher in the HR group compared with that in the LR group [33 (72%) vs 18 (39%), P = .022]. The incidence of POST at 0, 2, and 24 hours after surgery was higher in the HR group compared with that in the LR group (P < .001, P = .001, and P = .001, respectively). The incidence of postoperative nausea, vomiting, drowsiness, and headache was similar between the groups. The incidence of postoperative shivering was higher in the HR group than in the LR group [10 (22%) vs 2 (4%), difference 17%, 95% CI 2%-33%, P = .027]. CONCLUSION: A relatively large dose of intraoperative remifentanil increased the incidence of POST in patients for orthopedic surgery under general anesthesia. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03173339.

Empirical design of slot-die having shallow reservoir for thin-film printed electronics.

Slot-die coating plays an important role in printed electronics, which are fabricated by stacking thin films and patterns. As electronic devices are being required to have higher performance, the importance of coating uniformity cannot be overestimated in the slot-die coating. The coating uniformity consists of two directions: nozzle direction, which is affected by the interior design of the head, and machine direction, which is majorly related to exterior operating conditions. In this research, the empirical design procedure of a slot-die head is proposed. The internal resistance values of the slot-die were calculated using the experimental parameter obtained through a coating experiment, and the acquired resistances were reflected in the modeling of the interior design of the slot-die head. The hanger type reservoir was adapted to minimize the consumption of ink. After fabricating the slot-die head, coating experiments were carried out using PEDOT:PSS ink. The resulting deviation of the coating thickness was within ±1.7%, thus proving that the proposed design predicted the uniformity of the actual thickness of the coating correctly. The significance of the slot-die design method presented in this paper is that it is based on the experimental equation that can be readily applied to the printed electronics industry.

Air-Water Interfacial Properties of Chloroform-Spread versus Water-Spread Poly((d,l-lactic acid- co-glycolic acid)- block-ethylene glycol) (PLGA-PEG) Polymers.

Polymers at fluid interfaces are used for a number of applications that include coatings, electronics, separation, energy, cosmetics, and medicines. Here, we present a study on an amphiphilic block copolymer, poly((d,l-lactic acid- co-glycolic acid)- block-ethylene glycol) (PLGA-PEG), at the air-water interface. PLGA-PEG at the air-water interface prepared by using an organic spreading solvent exhibits an extremely high surface pressure without the occurrence of desorption, making it an attractive candidate for a variety of uses in the areas mentioned above. The origin of this high surface pressure increase was shown to be due to the glass transition of the PLGA segments. The temperature at which this glass transition occurs for the PLGA segments of PLGA-PEG at the air-water interface was measured to be about 290 K by thermodynamic analysis based on the two-dimensional Maxwell relations. However, from an applications standpoint, spreading by an organic solvent greatly limits its scope of feasible uses. To explore the possibility of maintaining the excellent surface mechanical properties of the PLGA-PEG at the air-water interface while not using an organic solvent, we investigated the air-water interfacial properties of water-spread PLGA-PEG. When spread with water, it was shown that the initial micelles that form in the aqueous spreading solution remain intact even after being spread onto the air-water interface. Due to this different morphology, the surface pressure and monolayer stability were greatly reduced for the water-spread PLGA-PEG at the air-water interface. We used the Daoud and Cotton's blob scaling model to describe the desorption process of the water-spread PLGA-PEG at the air-water interface. From the scaling concept, it was shown that with higher PEG molecular weight and larger micelle size, the adsorption energy of the water-spread PLGA-PEG to the air-water interface was increased.

Clinical, technological, and economic issues associated with developing new lung surfactant therapeutics.

Discovery of lung surfactant deficiency as a main cause of neonatal respiratory distress syndrome (NRDS) has influenced a steep increase in lung surfactant research. Although this has yielded impactful scientific discoveries, much of the basic research on lung surfactants has failed to translate into clinical practices. This is attributed to insufficient information covering the entire lung surfactant ecosystem, from the basic science to economics surrounding the development and clinical practices. In this manuscript, developments related to improving therapeutic lung surfactant as well as the degree of unmet need are analyzed from both technical and economic perspectives. Two potential opportunities are emphasized: (1) aerosolized lung surfactants to treat NRDS infants, and (2) synthetic lung surfactants for acute respiratory distress syndrome (ARDS) patients. Each has a modestly projected US market size of $120 million and $4 billion, well enough to make up for the high development costs associated with investigational drug development. Both opportunities have been pursued in the past, but to date these attempts have met with no success mainly due to technical limitations. With the recent advancements in both fields, technology improvements have created opportunities to solve both decades-old problems.

Stylet angulation of 70 degrees reduces the time to intubation with the GlideScope®: A prospective randomised trial.

Objective The GlideScope® videolaryngoscope provides a good view of the glottis. However, directing and inserting an endotracheal tube is sometimes difficult during intubation with the GlideScope®. In this study, we compared two GlideScope® stylet angulations (90° vs. 70°) in terms of the time to intubation. Methods In total, 162 patients scheduled for elective surgery under general anaesthesia were randomly assigned to one of two groups. In the 90 group ( n = 79), a 90° stylet was used. In the 70 group ( n = 78), a 70° stylet was used. The time to intubation was recorded. The number of intubation attempts was assessed. Results The time to intubation was significantly shorter in the 70 than 90 group [26.0 (23.0-32.0) vs. 37.0 (30.0-43.0) s, respectively]. The first-time intubation success rate was significantly higher and the number of failed intubations was significantly lower in the 70 than 90 group (100% vs. 87% and 0% vs. 6%, respectively). Conclusions This investigation suggests that a 70° angle stylet is superior to a 90° angle stylet for GlideScope® intubation. Trial Registration Clinicaltrials.gov Identifier: NCT02547064.

Polymer Lung Surfactants.

Animal-derived lung surfactants annually save 40 000 infants with neonatal respiratory distress syndrome (NRDS) in the United States. Lung surfactants have further potential for treating about 190 000 adult patients with acute respiratory distress syndrome (ARDS) each year. To this end, the properties of current therapeutics need to be modified. Although the limitations of current therapeutics have been recognized since the 1990s, there has been little improvement. To address this gap, our laboratory has been exploring a radically different approach in which, instead of lipids, proteins, or peptides, synthetic polymers are used as the active ingredient. This endeavor has led to an identification of a promising polymer-based lung surfactant candidate, poly(styrene-b-ethylene glycol) (PS-PEG) polymer nanomicelles. PS-PEG micelles produce extremely low surface tension under high compression because PS-PEG micelles have a strong affinity to the air-water interface. NMR measurements support that PS-PEG micelles are less hydrated than ordinary polymer micelles. Studies using mouse models of acid aspiration confirm that PS-PEG lung surfactant is safe and efficacious.

Determining the effects of PEI adsorption on the permeability of 1,2-dipalmitoylphosphatidylcholine/bis(monoacylglycero)phosphate membranes under osmotic stress.

Polycations are used for a number of biological applications, including antibiotics and gene therapy. One aspect of the use of polycation gene carriers such as polyethylenemine (PEI) in gene therapy that is not well understood is their ability to escape from the vesicles they are internalized in. Here, in an attempt to gain a better understanding of PEI interaction with endosomal lipids under osmotic stress, we performed investigations using monolayers and vesicles derived from a mixture of neutral and negative lipids (1,2-dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate (BMP), respectively). X-ray reflectivity (XR) and Langmuir trough measurements confirmed PEI adsorption to the negatively charged membrane. Confocal microscopy imaging indicated that PEI adsorption actually increases the overall integrity of the DPPC/BMP vesicle against osmotic stresses while also causing overall deformation and permeabilization of the lipid membrane, thus leading to leakage of contents from the interior of the vesicle. These confocal microscopy observations were also supported by data gathered by dynamic light scattering (DLS). STATEMENT OF SIGNIFICANCE: In recent decades, researchers have investigated polyamine-based gene delivery systems as useful alternatives to viral gene carriers. One step that is crucial to the performance of polyamine gene carriers such as polyethylenemine (PEI) is escape from late endosomal vesicles during intracellular delivery. However, the ability of polyamine/DNA polyplexes to effectively escape from endosomes is a little-understood part of the gene therapy techniques that use these polyplexes. Here, we performed investigations using monolayers and vesicles derived from a mixture of neutral and negative lipids (1,2-dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate (BMP), respectively) as model systems for late endosomes in order to examine the interactions of PEI with the DPPC/BMP membranes and study the subsequent effects on the stability and permeability of these membranes.