Mechanical Antiallodynic Effect of Intrathecal Nefopam in a Rat Neuropathic Pain Model.

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 µg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.

Usefulness of B-mode and doppler sonography for the diagnosis of severe acute viral hepatitis A.

BACKGROUND: To investigate B-mode and Doppler ultrasonography (US) features correlating with laboratory findings for the diagnosis of severe acute hepatitis (SAH) in patients with hepatitis A virus infection. METHODS: Thirty-nine consecutive serologically proven patients were enrolled. Decreased parenchymal echotexture, periportal tracking, gallbladder wall change, and splenomegaly were assessed on B-mode images. Blood flow velocities were measured in the main portal (V(PORTAL)) and in the hepatic veins, and the hepatic venous pulsatility index was calculated. SAH was defined as high model for end-stage liver disease (MELD) score ≥ 15 with or without coagulopathy. The relationship between US features and laboratory findings was assessed, and SAH diagnosis was evaluated. RESULTS: Serum alanine transaminase and prothrombin time were significantly different depending on the presence of gallbladder wall change and splenomegaly (p < 0.05). V(PORTAL) was inversely correlated with MELD score (r = -0.485) and several laboratory markers. The hepatic venous waveform and hepatic venous pulsatility index were significantly correlated with MELD score. For the diagnosis of SAH, the area under the receiver operating characteristic curve of V(PORTAL) was 0.798. It reached 0.869 in the patients with typical GB change. CONCLUSIONS: Both B-mode and Doppler US correlated well with several laboratory variables and may be helpful to diagnose SAH in patients with hepatitis A virus infection.

Effective analgesia with ultrasound-guided interscalene brachial plexus block for postoperative pain control after arthroscopic rotator cuff repair.

PURPOSE: Ultrasound (US)-guided continuous interscalene brachial plexus block (CBPB) is known to provide effective pain relief for arthroscopic rotator cuff repair. This study was conducted to compare analgesic efficacy and forearm muscle tone of the basal infusion rate and bolus dose of 0.2 % ropivacaine for US-guided CBPB with intravenous patient-controlled analgesia (IV-PCA). METHODS: In a prospective trial, 99 patients scheduled to undergo arthroscopic rotator cuff repair were divided into three groups. In groups A and B, an US-guided 17-gauge Tuohy needle was inserted into the interscalene brachial plexus. A loading dose of 10 ml 0.2 % ropivacaine was administered via the needle. A 19-gauge perineural catheter was then inserted through the needle and advanced to a depth of 1.5 cm beyond the needle tip between the C5 and C6 nerve trunks. After surgery, groups A and B received a continuous infusion of 0.2 % ropivacaine at 4 or 0 ml/h, a bolus of 0 or 4 ml, and a lockout time of 60 min through the catheter, respectively. Group C received IV-PCA. Pain scores and the forearm muscle tone of patients were compared using a numeric rating scale (NRS), rates of patients taking supplementary opioid analgesics, and manual muscle test (MMT) scoring. RESULTS: The NRS scores and rate of patients taking supplementary opioid analgesics in groups A and B were lower than those in group C after surgery. Groups A and B showed similar clinical efficacy. There were no significant differences in MMT scoring among the three groups. CONCLUSIONS: The bolus dose of 0.2 % ropivacaine using US-guided CBPB would provide equivalent analgesic efficacy comparable with the basal infusion and motor weakness comparable with IV-PCA after arthroscopic rotator cuff repair.

General anesthesia using propofol infusion for implantation of an implantable cardioverter defibrillator in a pediatric patient with Andersen-Tawil syndrome: a case report.

Andersen-Tawil syndrome (ATS) is a rare genetic disease characterized by a triad of episodic flaccid muscle weakness, ventricular arrhythmias, and physical anomalies. ATS patients have various cardiac arrhythmias that can cause sudden death. Implantation of an implantable cardioverter-defibrillator (ICD) is required when life-threatening cardiac arrhythmias do not respond to medical treatment. An 11-year-old girl underwent surgery for an ICD implantation. For general anesthesia in ATS patients, anesthesiologists should focus on the potentially difficult airway, serious cardiac arrhythmias, such as ventricular tachycardia (VT), and delayed recovery from neuromuscular blockade. We followed the difficult airway algorithm, avoided drugs that can precipitate QT prolongation and fatal cardiac arrhythmias, and tried to maintain normoxia, normocarbia, normothermia, normoglycemia, and pain control for prevention of sympathetic stimulation. We report the successful application of general anesthesia for ICD implantation in a pediatric patient with ATS and recurrent VT.

Effect of local warming for arterial catheterization in adult cardiac surgery: a randomized controlled trial.

Background: The increase in internal diameter (ID) and cross-sectional area (CSA) may facilitate better arterial catheterization. Since an increase in body temperature can cause peripheral vasodilation, we aimed to determine if local warming of the radial artery (RA) catheterization site could improve the success rate of catheterization. Methods: This randomized, controlled study enrolled 160 patients aged >18 years who were scheduled for heart surgery. They were randomized into non-warming palpation (NP), non-warming ultrasonography-guided (NU), warming palpation (WP), and warming ultrasonography-guided (WU) groups. After induction, the baseline RA ultrasonography images were collected. In the warming groups (WP, WU), local warming was applied on the catheterization site. Before catheterization, the RA ultrasonography images were collected. The primary outcome was the first-attempt success rate. The secondary outcomes included the ID and CSA of the RA and overall complications. Results: Totally 152 adults were included in the analysis. The first-attempt success rates in each of the four groups were not significantly different (P=0.985). The rates in the non-warming (NP + NU) and warming (WP + WU) groups were also not different (P=0.827). Unlike non-warming group, the warming group had increased ID (3.34±0.78 vs. 3.02±0.73 mm; P<0.001) and CSA (6.9±2.8 vs. 5.8±2.4 mm2; P<0.001) compared with baseline. Conclusions: Local warming for peripheral artery catheterization does not increase the first-attempt success rate in adults undergoing cardiac surgery; however, it can increase the ID and CSA of the RA and prevent vasospasm. Trial Registration: ClinicalTrials.gov NCT04969692.

Hypothermic cardiopulmonary bypass for minimally invasive mitral valve plasty in adult moyamoya disease.

A 43-year-old man underwent minimally invasive mitral valve plasty of a flail mitral valve. Four years previously, he had been diagnosed with moyamoya disease (MMD) by cerebral magnetic resonance imaging/angiography findings. In MMD, risk factors for cerebral stroke include changes in arterial carbon dioxide partial pressure, blood pressure, and body temperature. And during cardiopulmonary bypass (CPB), these hemodynamic changes can be challenging. However, hypothermia during CPB can decrease cerebral oxygen consumption and have a cerebral protective effect. We performed a minimally invasive mitral valve plasty, using hypothermic CPB, in a patient with MMD, without any neurological deficits.

Availability of a 5% lidocaine patch used prophylactically for venipuncture- or injection-related pain in children.

PURPOSE: Venipuncture- or injection-related pain is still major problem during anesthetic induction in children. This study was designed to determine the availability of a 5% lidocaine patch used prophylactically for venipuncture- or injection-related pain during the induction of anesthesia. METHODS: In a randomized, double-blind study, 72 pediatric patients were allocated to one of two groups: pretreatment with a 5% lidocaine patch (Lidoderm(®), Endo Pharmaceuticals, Chadds Ford, PA, USA) (group A) or pretreatment with a placebo patch (group B). Pain severity was evaluated on the Faces, Legs, Activity, Cry, and Consolability Scale (FLACC) during venipuncture, and a 4-point scale during the injection of rocuronium. RESULTS: The FLACC score during venipuncture was significantly lower for group A than group B (p < 0.001). There was no significant difference in the grades of the 4-point scale observed during the injection of rocuronium between groups A and B. No significant adverse effect was noted for the groups. CONCLUSION: Although pretreatment with a 5% lidocaine patch was found to be a safe, effective, and simple method of preventing venipuncture pain in children, this method did not reduce drug injection pain during the induction of anesthesia.

A Review of Anesthesia for Lung Transplantation.

Lung transplantation is the only treatment option for patients with end-stage lung disease. Although more than 4,000 lung transplants are performed every year worldwide, the standardized protocols contain no guidelines for monitoring during lung transplantation. Specific anesthetic concerns are associated with lung transplantation, especially during critical periods, including anesthesia induction, the initiation of positive pressure ventilation, the establishment and maintenance of one-lung ventilation, pulmonary artery clamping, pulmonary artery unclamping, and reperfusion of the transplanted lung. Anesthetic management according to the special risks associated with a patient's existing lung disease and surgical stage is the most important factor. Successful anesthesia in lung transplantation can improve hemodynamic stability, oxygenation, ventilation, and outcomes. Therefore, anesthesiologists must have expertise in transesophageal echocardiography, extracorporeal life support, and cardiopulmonary anesthesia and understand the pathophysiology of end-stage lung disease and the drugs administered. In addition, communication among anesthesiologists, surgeons, and perfusionists during surgery is important to achieve optimal patient results.

Comparison of the effect of electromyogram activity during emergence on anesthetic depth monitoring between phase lag entropy and bispectral index: a prospective observational study.

BACKGROUND: The bispectral index (BIS) is the most widely used algorithm for measuring anesthetic depth. The BIS has been demonstrated as inaccurate when neuromuscular blocking drugs (NMBDs) are used. Compared with BIS, phase lag entropy (PLE), which measures the anesthetic depth based on a 4-channel EEG signal, is less affected by EMG. The purpose of this study was to compare the effect of EMG activity during emergence on anesthetic depth monitoring between PLE and BIS. METHODS: Twenty five consecutive patients with physical status I-II of American Society of Anesthesiologists undergoing general anesthesia (age range, 20-60 years). The anesthesiologist attached the sensors of BIS and PLEM 100 on the patient's forehead. NMB reversal was performed by intravenously injecting sugammadex after confirmation of shallow NMB (TOF count 1-4) under neuromuscular monitoring. The BIS and PLE scores were recorded with neuromuscular monitoring at 1-min intervals for 5 min after administration of sugammadex. RESULTS: The BIS and BIS-EMG measured at 1 min after sugammadex injection were significantly higher at 1 min [51.650 (46.100, 62.225) (P<0.001); 28.500 (27.800, 31.075) (P=0.003)] than at 0 min. However, there was no between-time point difference in the PLE score and PLE-EMG (P=0.0843, P=0.329). CONCLUSIONS: In general anesthesia using propofol-remifentanil, the BIS at 1 min after sugammadex reversal during emergence appears to be more affected by EMG activity than the PLE score. Therefore, immediately after sugammadex administration (within 1 min), it may be clinically useful to evaluate the consciousness status through the PLE score.

Comparison of Continuous and Programmed Intermittent Bolus Infusion of 0.2% Ropivacaine after Ultrasound-Guided Continuous Interscalene Brachial Plexus Block in Arthroscopic Shoulder Surgery.

Background: Despite the clinical effectiveness of the programmed intermittent bolus (PIB) method for epidural analgesia, evidence for this method in continuous interscalene brachial plexus block (CIBPB) is unclear. This study aimed to investigate the pain relief effect after arthroscopic shoulder surgery according to the administration method by comparing the PIB and continuous infusion methods among the administration methods of local anesthetics. Methods: Sixty-four patients aged >19 years scheduled for elective arthroscopic shoulder surgery were enrolled and divided into two groups. Ultrasound-guided CIBPB was performed to control postoperative pain. The infusion pump was programmed so that 0.2% ropivacaine was continuously injected at 1.1 mL/h in group A, whereas in group B, 0.1 mL/h was continuously injected and 4 mL was periodically injected at 4 h intervals. In both groups, a further infusion of 4 mL of 0.2% ropivacaine was administered if the patient requested additional analgesia, and the lockout time was set at 30 min. Postoperative pain quality was assessed using a visual analog scale (VAS), and the incidence of patients requiring additional analgesics, motor blockade using a modified Bromage scale (MBS), and consumed doses of local anesthetic were assessed. Results: The VAS and incidence of rescue analgesics were performed when the patient could communicate voluntarily after admission to the post-anesthetic care unit, and at 24 and 48 h after surgery showed no significant difference between the two groups. The MBS at 24 h after surgery was significantly higher in group B (p = 0.038). In the comparison of consumed doses of local anesthetic, group B had a significantly higher bolus injection dose (p = 0.047) and frequency of bolus use in the 24 h after surgery (p = 0.034). Conclusion: The PIB method in CIBPB after arthroscopic shoulder surgery provided a similar analgesic effect, with a higher bolus injection dose of local anesthetic and increased motor blockade than the continuous infusion method.

Choice of the correct size of endotracheal tube in pediatric patients.

Selection and insertion of an endotracheal tube (ETT) of appropriate size for airway management during general anesthesia in pediatric patients is very important. A very small ETT increases the risk of inadequate ventilation, air leakage, and aspiration, whereas a very large ETT may cause serious complications including airway damage, post-intubation croup, and, in severe cases, subglottic stenosis. Although the pediatric larynx is conical, the narrowest part, the rima glottidis, is cylindrical in the anteroposterior dimension, regardless of development, and the cricoid ring is slightly elliptical. A cuffed ETT reduces the number of endotracheal intubation attempts, and if cuff pressure can be maintained within a safe range, the risk of airway damage may not be greater than that of an ETT without cuff. The age-based formula suggested by Cole (age/4 + 4) has long been used to select the appropriate ETT size in children. Because age-based formulas in children are not always accurate, various alternative methods for estimating the ETT size have been examined and suggested. Chest radiography, ultrasound, and a three-dimensional airway model can be used to determine the appropriate ETT size; however, there are several limitations.

Identifying the acute toxicity of contaminated sediments using machine learning models.

Ecological risk assessment of contaminated sediment has become a fundamental component of water quality management programs, supporting decision-making for management actions or prompting additional investigations. In this study, we proposed a machine learning (ML)-based approach to assess the ecological risk of contaminated sediment as an alternative to existing index-based methods and costly toxicity testing. The performance of three widely used index-based methods (the pollution load index, potential ecological risk index, and mean probable effect concentration) and three ML algorithms (random forest, support vector machine, and extreme gradient boosting [XGB]) were compared in their prediction of sediment toxicity using 327 nationwide data sets from Korea consisting of 14 sediment quality parameters and sediment toxicity testing data. We also compared the performances of classifiers and regressors in predicting the toxicity for each of RF, SVM, and XGB algorithms. For all algorithms, the classifiers poorly classified toxic and non-toxic samples due to limited information on the sediment composition and the small training dataset. The regressors with a given classification threshold provided better classification, with the XGB regressor outperforming the other models in the classification. A permutation feature importance analysis revealed that Cr, Cu, Pb, and Zn were major contributors to toxicity prediction. The ML-based approach has the potential to be even more useful in the future with the expected increase in available sediment data.

Accidental epidural injection of rocuronium.

Epidural administration of local anesthetics or opioid during general anesthesia is a widespread method for postoperative analgesia. Despite the availability of this technique, inadvertent administration of nonepidural medications into the epidural space can be associated with serious neurological complications. We report a case of accidental epidural rocuronium injection.

Comparison of the Oblique Interlaminar and Transforaminal Lumbar Epidural Steroid Injections for Treatment of Low Back and Lumbosacral Radicular Pain.

BACKGROUND: Transforaminal epidural steroid injections (TF-ESIs) effectively deliver small amounts of drugs to inflamed sites via the ventral epidural space. However, there is a high risk of nerve damage as the needle narrowly approaches the spinal nerve. Therefore, we devised an oblique interlaminar (OIL) approach as an alternative method. We compared the efficacy of fluoroscopic-guided OIL-ESIs with that of TF-ESIs in the management of lower back and unilateral lumbosacral radicular pain. MATERIALS AND METHODS: Sixty-six patients were randomized to receive a fluoroscopic-guided ESI either through the OIL (n = 33, group OIL) or TF (n = 33, group TF) approach. They were evaluated for effective pain relief using the visual analogue scale (VAS) and for functional improvement using the Oswestry Disability Index (ODI) and Roland Morris Disability Questionnaire (RMDQ). Other outcome measures were the presence of ventral and contralateral spread of contrast, patients' satisfaction, and adverse events. RESULTS: There were no significant differences between the groups in the VAS, ODI, and RMDQ scores during the 12-week period. The differences in the ODI and RMDQ scores before and after the treatment were higher in group TF than in group OIL. The contralateral spread of contrast was higher in group OIL than in group TF. There were no significant differences in the other outcomes between the groups. CONCLUSION: ESIs delivered through the OIL approach are equally effective in pain relief and functional improvement as those delivered via the TF approach in the management of low back and unilateral lumbosacral radicular pain.

Increased pulmonary venous resistance in morbidly obese patients without daytime hypoxia: clinical utility of the pulmonary artery catheter.

BACKGROUND: The pulmonary artery (PA) diastolic-pulmonary capillary wedge pressure (PAD-PCWP) gradient has been shown to be increased in morbidly obese patients without daytime hypoxia. In sepsis, the increased pulmonary venous resistance (PvR) contributes to increases in PAD-PCWP gradient. In addition, the obesity-related endotoxemia is known to be involved in the pathophysiology of metabolic syndrome in obesity. Therefore, it is possible that the increased PvR contributes to increases in PAD-PCWP gradient in morbid obesity. We examined this possibility. METHODS: Included were 25 obese patients without daytime hypoxia undergoing bariatric surgery under general anesthesia. PvR was calculated as the difference between mean PA output pressure and PCWP divided by cardiac index. Mean PA output pressure was computed from the harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA pressure and PCWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and PvR, the PvR/TPVR ratio was used. RESULTS: There was a good correlation between PvR/TPVR ratio and PAD-PCWP gradient (r2=0.785, P<0.0001). When patients were divided into two groups based on PAD-PCWP gradient, the PvR/TPVR ratio was 0.67+/-0.06 (mean+/-SD) in the group with a PAD-PCWP gradient of at least 6 mmHg and 0.48+/-0.05 in the other group (P<0.0001). CONCLUSIONS: A strong correlation between PvR/TPVR ratio and PAD-PCWP gradient suggests that the increased PvR contributes to increased PAD-PCWP gradient in obese patients without daytime hypoxia.

EC(50) of remifentanil to prevent withdrawal movement associated with injection of rocuronium.

PURPOSE: Various strategies have been studied to reduce the discomfort of rocuronium injection. This study was designed to determine the effect-site target concentration (Ce) of remifentanil at which there was a 50% probability of preventing movement from pain in response to the injection of rocuronium (EC(50)). METHODS: Anesthesia was induced with a propofol target-controlled infusion (TCI, Marsh model) and remifentanil TCI (Minto model). Effect-site target concentration of propofol was 3 microg/ml. Ce of remifentanil for the first patient started at 2.0 ng/ml. Ce of remifentanil for each subsequent patient was determined by the response of the previous patient by the Dixon up-and-down method with an interval of 0.5 ng/ml. After both drugs reached target concentration, rocuronium 0.8 mg/kg was administered, and the pain response was observed. RESULTS: The EC(50) of remifentanil was 1.5 +/- 0.45 ng/ml by Dixon's up-and-down method. From probit analysis, the EC(50) of remifentanil was 1.37 ng/ml (95% confidence limits, 0.69-2.15 ng/ml), and the EC(95) was 3.19 ng/ml (95% confidence limits, 2.31-11.24 ng/ml). CONCLUSION: The EC(50) of remifentanil to blunt the withdrawal responses to rocuronium injection was 1.37-1.5 ng/ml during 3 microg/ml propofol TCI anesthesia.

Takotsubo cardiomyopathy associated with nonepileptic seizure after percutaneous endoscopic lumbar discectomy under general anesthesia.

Nonepileptic seizures are rare complication after general anesthesia. Postoperative seizure-induced oxidative stress promotes acute catecholamine toxicity of the myocardium. Takotsubo cardiomyopathy may be more frequent in the perioperative setting than commonly appreciated. We report a case of nonepileptic seizure developed during emergence from general anesthesia. The patient subsequently developed takotsubo cardiomyopathy. We now clearly recognize that patients with seizure activities after general anesthesia may be a higher risk for takotsubo cardiomyopathy.

4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice.

Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer's disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2-trans-nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex's oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.

The Validity of the YMCA 3-Minute Step Test for Estimating Maximal Oxygen Uptake in Healthy Korean and Vietnamese Adults.

BACKGROUND: Cardiorespiratory fitness (CRF) is a fundamental component of physical fitness. While maximal oxygen uptake (VO2max) is the gold standard for quantifying CRF, standard maximal exercise tests using direct measurements VO2max are dependent on the availability of laboratory equipment, and thereby expensive and time consuming. Recently, an equation was formulated to indirectly estimate VO2max using the YMCA 3-minute step test. METHODS: The study included 15 Korean (KR) and 15 Vietnamese (VN) healthy adults aged 19-35 years. All subjects completed a YMCA 3-minute step test (YMCA 3MST) and a maximal exercise treadmill test to predict VO2max and VO2max measures, respectively. RESULTS: There was a significant relationship between VO2max predicted from the YMCA 3MST and actual VO2max measurements from the treadmill test (r = 0.80, p < 0.0001; KR group: r = 0.81, p < 0.0001; VN group: r = 0.93, p < 0.0001). Bland-Altman analysis revealed statistical agreement between tests, although there was a systematic overestimation of 3.36 mL/kg/min for the KR group. CONCLUSION: The equation for predicting VO2max from the YMCA 3MST was validated among the study subjects. However, future research should explore the validity and reliability of the YMCA 3MST equation for estimating VO2max in other populations.

Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial.

OBJECTIVE: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. METHODS: Subjects who met the inclusion criteria (3 × 103 ≤ peripheral blood leukocyte level ≥ 8 × 103 cells/µL) were recruited for this study. Enrolled subjects (n = 120) were randomly assigned to either the PTE group (n = 60) and were given 2.5 g/day of PTE (as PTE) in capsule form or the placebo group (n = 60) and were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed based on measuring natural killer (NK) cell activity, cytokines level, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. RESULTS: Compared with baseline, NK cell activity (%) increased for all effector cell-to-target cell ratios in the PTE group after 8 weeks; however, changes were not observed in the placebo group (p < 0.10). Subgroup analysis of 101 subjects without URI showed that NK cell activity in the PTE group tended to increase for all effector cell/target cell (E:T) ratios (E:T = 12.5:1 p = 0.068; E:T = 25:1 p = 0.036; E:T = 50:1 p = 0.081) compared with the placebo group. A significant difference between the two groups was observed for the E:T = 25:1 ratio, which increased from 20.3 ± 12.0% at baseline to 23.2 ± 12.4% after 8 weeks in the PTE group (p = 0.036). A significant difference was not observed in cytokine between the two groups. CONCLUSION: PTE supplementation appears to enhance immune function by improving NK cell activity without adverse effects in healthy adults.