The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Practical guide for safe sedation.

This practical guide has been developed to ensure safe and effective sedation performed in adult patients outside of the operating room, for instance in intensive care units and dental treatment rooms and in the field of palliative care. Sedation levels are classified based on level of consciousness, airway reflex, spontaneous ventilation, and cardiovascular function. Deep sedation induces loss of consciousness and protective reflexes, and can cause respiratory depression and pulmonary aspiration. Invasive medical procedures necessitating deep sedation include cardiac ablation, endoscopic submucosal dissection, and internal radiation therapy. Appropriate analgesia is necessary for procedures that require deep sedation. The sedationist should evaluate the risks of the planned procedure, explain the sedation process to the patient, and obtain the patient's informed consent. Major parameters to be evaluated preoperatively are the patient's airway and general condition. Equipment, instruments, and drugs necessary for emergency situations should be defined and routinely maintained. To prevent aspiration, patients scheduled for moderate or deep sedation should fast preoperatively. In both inpatients and outpatients, biological monitoring should be continued until the discharge criteria are met. Anesthesiologists should be involved in management systems that ensure safe and effective sedation even if they do not personally perform all sedation procedures.

Successful treatment of diabetic ketoacidosis secondary to fulminant type 1 diabetes mellitus using a closed-loop artificial pancreas in a pediatric patient.

Diabetic ketoacidosis (DKA) is a life-threatening complication of pediatric diabetes mellitus (DM). A bedside closed-loop artificial pancreas (AP) (STG-55; NIKKISO, Tokyo, Japan) maintains the blood glucose (BG) levels within the target range via automatic infusion of insulin and glucose. We report the application of the closed-loop AP to safely control the BG levels of a pediatric patient with DKA. A 12-year-old child with an unremarkable medical history presented with fever and restlessness. The patient was diagnosed with DKA secondary to fulminant type 1 DM and was treated with insulin infusion. He presented with Glasgow Coma Scale of E2V3M4. Arterial blood gas analysis revealed metabolic acidosis and BG levels of 489 mg/dL. His urine test was positive for ketones. Along with infusion therapy, automatic BG control using a closed-loop AP was initiated after ICU admission. This was adjusted to maintain BG levels within 100 mg/dL/6 h or less. After 24 h in the ICU, the patient regained consciousness and recovered from the metabolic acidosis. His general condition improved, and he was prescribed a diet treatment. The treatment was shifted to continuous insulin infusion, and he was transferred to the general ward, and was discharged on the 33rd day of hospitalization. The closed-loop AP prevented repetitive blood extractions, achieved prompt glycemic control, and prevented cerebral edema in a pediatric patient with DKA. This is the first report of successful treatment of DKA using a bedside closed-loop AP.

Maternal pain during pregnancy dose-dependently predicts postpartum depression: The Japan Environment and Children's Study.

BACKGROUND: Postpartum depression (PPD) affects women during the first year after delivery. This study investigated the association between prenatal pain (maternal pain during pregnancy) and PPD. METHODS: Data were analyzed from the Japan Environment and Children's Study (JECS), a nationwide prospective birth cohort study. Information on prenatal pain was collected twice during pregnancy through self-administered questionnaires. PPD symptoms were assessed using the Edinburgh Postnatal Depression Scale at one month postpartum. Poisson regression analyses were performed to investigate the association between prenatal pain and PPD, with other putative risk factors adjusted in the model. RESULTS: Among 84,801 study subjects, 11,535 (13.6%) were screened as positive for PPD. In the present study, the occurrence of prenatal pain was 69.6 and 84.0% at the first trimester and the second/third trimester, respectively. A positive relationship between any degree of pain and PPD in both the first and the second/third trimester was observed. A significant linear dose-dependent association was also found (Ptrend < 0.001) when the subjects were divided by the severity of pain. Using participants without any pain at either point as a reference, those with persistent pain both at the first and the second/third trimesters showed the highest risk for PPD: aRR = 1.95 (95%CI: 1.76-2.15; p < 0.001). LIMITATIONS: No detailed information regarding the type or site of prenatal pain was available in the JECS questionnaires, neither did data concerning delivery and postpartum pain. CONCLUSIONS: The study results suggest that prenatal pain is a dose-dependent risk factor for the development of PPD.

Impact of the First Wave of COVID-19 on the Number of General Anesthesia Cases in 34 Tertiary Hospitals in Japan: A Multicenter Retrospective Study.

Since the first case of coronavirus disease 2019 (COVID-19) was reported in Japan in January 2020, the COVID-19 pandemic has brought about a significant change in people's lives. Although the COVID-19 pandemic is expected to have had an impact on the work of anesthesiologists, the specific impact has been largely unreported. We hypothesized that the number of general anesthesia (GA) cases has decreased due to the COVID-19 pandemic. To test this hypothesis, we conducted a retrospective survey at 34 facilities in Japan as a part of the Japanese Epidemiologic Study for Perioperative Anaphylaxis. The results showed that the number of GA cases had significantly decreased, particularly in May 2020, under the government's declaration of a state of emergency. The decline in GA caseload had not fully recovered by July 2020. Furthermore, there were regional differences in the decline in the number of GA cases. The impact of the COVID-19 pandemic on the work of anesthesiologists was greater in prefectures where there were more COVID-19 patients and where the state of emergency was declared earlier. Our study suggested a region-dependent decrease in the number of GA cases due to the COVID-19 pandemic.

Reductions in Muscle Strength and Range of Motion Cause Locomotion Disability via Locomotion-Related Functional Limitation in Japanese Older Adults: A Cross-Sectional Study.

BACKGROUND: Functional issues (impairments, functional limitations, and disabilities) gradually occur with age. Nonetheless, maintaining physical capability may help prevent locomotion disabilities at an older age. The present study aimed to determine whether reductions in muscle strength and range of motion (ROM) cause locomotion disability via locomotion-related functional limitations among healthy older adults. METHODS: Data from a total of 144 participants (61 men, 83 women) were analyzed. To assess locomotion disability, the locomotor domain of the activities of daily living (ADLs) survey from the Ministry of Education, Culture, Sports, Science, and Technology of Japan was used. Muscle strength (grip strength) and two ROMs (hip flexion and knee flexion) were measured. To measure locomotion-related functional limitations, participants underwent a 10 m hurdle walking test and side-step test. Thereafter, path analysis was conducted for testing the hypothetical model. The goodness of fit in the model was assessed using statistical parameters, such as the chi-square value, goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA). RESULTS: The analysis revealed a nonsignificant chi-square value (chi-square = 41.885; p=0.113), as well as high values of GFI (0.944), AGFI (0.904), CFI (0.970), and RMSEA (0.046), indicating that locomotion disability was caused by locomotion-related functional limitations, which were influenced by muscle strength and ROM. CONCLUSIONS: The present study demonstrated that decreased muscle strength and ROM caused locomotion disability via locomotion-related functional limitations. Older adults should participate in physical exercise programs that focus on strengthening muscles and improving ROM to counteract age-related locomotion disability.

Current status of variations in in-hospital cardiac arrest call numbers in Japan: a nationwide survey.

The use of standardized internal hospital phone numbers for cardiac arrest is advocated in Europe. We evaluated the current status of variations in medical emergency call numbers for in-hospital patients in Japan and whether anesthesiologists would approve a standardized number. From June 2018 to August 2018, a questionnaire survey was mailed to anesthesiologists in 1373 Japanese Society of Anesthesiologists (JSA)-accredited hospitals. The basis for opinions on using a standardized cardiac arrest call number in all Japanese hospitals was evaluated. Of 1373 facilities (response rate, 58%, n = 800), 741/776 (96%) reported a response system for in-hospital cardiac arrest; 638/710 (90%) responded to cardiac arrest through loudspeaker broadcast, audible to both patients and staff; 346/777 (48%) used a number between one and five digits long, four-digit numbers being the most common. Across Japan, 370 different numbers were reported. Only 385/688 (56%) of respondents had the emergency number memorized. Finally, 423/776 (55%) respondents approved standardizing a hospital telephone number for summoning help. Multivariate analysis showed that facilities where the anesthesiologists already memorized the call number were the only reason identified for opposition to the standardization. Although 96% of JSA-accredited hospitals had a response system for in-hospital cardiac arrests, discussions for standardization of a unified number need to be encouraged for improved emergency response.

Body Composition and Physical Fitness Profiles of Elite Female Japanese Wrestlers Aged <12 Years until >20 Years.

Studies evaluating the physical fitness levels of elite wrestlers during junior high school are limited. This study aimed to examine the body composition and physical fitness profiles of elite Japanese female wrestlers aged <12 years until >20 years. There were 114 elite female wrestlers enrolled. Measurements were conducted in the following age categories: <12 years (U-12), <15 years (U-15), <17 years (U-17: cadet), <20 years (U-20: junior), and >20 years (senior). Body composition variables consisted of body mass index (BMI), percent body fat, fat free mass, and fat free mass index (FFMI). Fitness measurements included grip strength, back strength, sit-up, rope-climbing, and endurance running tests. The wrestlers in this study demonstrated comparable or greater FFMI values (e.g., FFMI: 17.9 ± 0.4 kg/m2 for light and 19.8 ± 0.9 kg/m2 for heavy weight categories in U-20), when compared with young female wrestlers in previous studies, whereas stature, body mass, and BMI of the wrestlers in our study were unremarkable. Regarding the fitness assessment, a remarkable increase in back strength was observed after late puberty. An outstanding enhancement of muscle strength after late puberty, which is unlikely to occur in ordinary women, would be an important requirement to become the world's top female wrestler.

Influence of hyperuricemia treatment on postoperative acute kidney injury among hyperuricemia patients: a single-center retrospective database analysis.

OBJECTIVE: Hyperuricemia has been reported to be associated with the development of postoperative acute kidney injury (pAKI). However, it remains underdetermined whether hyperuricemia treatment could decrease the potential risk of pAKI. Here, we investigated this hypothesis among hyperuricemia patients with previously normal renal function by performing a retrospective database analysis. RESULTS: The study screened 18,169 patients, and were examined preoperative serum creatinine, uric acid, and postoperative serum creatinine. Eight hundred thirty-six patients were finally analyzed for the study, of whom 232 were in the treatment group and 604 were in the non-treatment control group. After adjustment for multi-covariates including baseline (pre-treatment) serum uric acid (SUA) levels, the incidence of pAKI in the treatment group (9.05%; 95% CI 6.04-12.1%) was significantly lower than that in the control group (14.2%; 95% CI 11.2-17.2%). On the other hand, further adjusting for preoperative SUA levels, there was no significant difference in the expected incidence of pAKI between the groups.

Acute and long-term effects of haloperidol on surgery-induced neuroinflammation and cognitive deficits in aged rats.

PURPOSE: Neuroinflammation may contribute to the pathogenesis of the cognitive symptoms of postoperative delirium (POD) and its subsequent long-term cognitive impairment. Haloperidol (HAL), a dopamine receptor antagonist, is widely used to treat POD, whereas the effects of HAL on postoperative neuroinflammation and related cognitive deficits have been underdetermined. METHODS: Aged rats underwent sham or abdominal surgery and were subcutaneously treated with either vehicle, low-dose (0.5 mg/kg bolus, then 0.5 mg/kg/day infusion), or high-dose (2.0 mg/kg bolus, then 2.0 mg/kg/day infusion) HAL. All treatments were initiated immediately after surgery and continued for 48 h. On either postoperative day 2 (early) or 7 (late), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Following the cognitive testing, the levels of pro-inflammatory cytokines, as well as dopamine and its metabolite, in hippocampus and medial prefrontal cortex (mPFC) were measured. RESULTS: In the early postoperative period, surgery induced acute neuroinflammation along with related trace and context memory dysfunction. Dopamine turnover was increased in both hippocampus and mPFC, whereas no relationship with memory functions was observed. However, HAL even at high-dose failed to restore the surgery-induced neuroinflammation and related cognitive deficits. In the late postoperative period, chronic neuroinflammation was detected only in hippocampus, which was associated with context, but not trace memory dysfunction. Neither low- nor high-dose HAL could prevent the development of these late-phase neurocognitive deficits. CONCLUSION: Our findings indicate that perioperative administration with HAL may have no effects on postoperative neuroinflammation and related cognitive impairment.

Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats.

The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6 h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.

Therapeutic experience with tramadol for opioid dependence in a patient with chronic low back pain: a case report.

BACKGROUND: Long-term opioid treatment for chronic non-cancer pain has become controversial, given the increasing prevalence of opioid dependence. However, there is little information on therapeutic strategies for this condition in Japanese patients. Here, we present a case of successful management of iatrogenic opioid dependence with tramadol in a patient with chronic low back pain. CASE PRESENTATION: A 68-year-old male suffering from intractable low back pain was referred to our pain clinic. He was previously treated in another hospital with transdermal fentanyl patches 6 mg/day and fentanyl sublingual tablets (100 µg as required) for this condition. On the basis of medical examination, including a review of the patient's medical history, physical examination, X-ray, and his family statement, we diagnosed him with iatrogenic opioid dependence due to inadequate fentanyl use. Then, we developed a treatment plan consisting in fentanyl detoxification with a weak opioid, tramadol. At first, the use of fentanyl sublingual tablets was interrupted after obtaining informed consent. Then, we reduced the dose of transdermal fentanyl 1 mg per 4-5 days replacing with oral sustained-release tramadol. The patient developed mild to moderate withdrawal symptoms during this period, which could be effectively managed by supportive treatments. The hospital psychiatry liaison team continuously provided the patient and his wife with information, counseling, and education regarding the treatment of opioid dependence. Throughout the detoxification process, his reported pain did not exacerbate, even slightly improved over time. The final prescription was sustained-release tramadol 300 mg/day without fentanyl, and his activities of daily living drastically improved. However, unfortunately, he died due to an aortic dissection of stent-graft edge 65 days after surgery. CONCLUSIONS: Our case highlighted that sustained-release tramadol could be effectively applied as a detoxification agent for iatrogenic opioid dependence in patients with chronic non-cancer pain.

Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats.

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels.

Electron-Transfer Properties of Phenyleneethynylene Linkers Bound to Gold via a Self-Assembled Monolayer of Molecular Tripod.

The three-point adsorption of tripod-shaped molecules enables the formation of robust self-assembled monolayers (SAMs) on solid surfaces, where the component molecules are fixed in a strictly upright orientation. In the present study, SAMs of a rigid molecular tripod consisting of an adamantane core and three CH2SH groups were employed to arrange ferrocene on a gold surface through oligo(p-phenyleneethynylene) linkers. Cyclic voltammetry of the monolayers demonstrated high surface coverage of ferrocene, yet the molecular interaction among adjacent ferrocene units was negligible. This was because of the extended intermolecular distance caused by the bulky tripod framework. The rates of electron transfer from the ferrocene to the gold surface through different linker lengths were determined by electrochemical measurements, from which the decay factor for oligo(p-phenyleneethynylene) wire was evaluated.

Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats.

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway.

Low-voltage SEM contrasts of steel surface studied by observations and electron trajectory simulations for GEMINI lens system.

Scanning electron microscopy (SEM) is a powerful tool for observing the surface of materials. Modern SEM systems have multiple detectors with different geometries. Consequently, the SEM image contrast depends on the instrument and experimental conditions even for the same sample. Understanding the SEM imaging mechanism is necessary to clarify SEM contrast. In this paper, low-voltage (LV)-SEM image contrast is investigated by comparing LV-SEM images and electron trajectory simulation results. Surface observations of oxides on a steel surface, positive charging contrast and topographic contrast in the image systematically changed with the working distance (WD). The electron trajectory simulation revealed the sharing of emitted electrons by the in-lens and Everhart-Thornley detectors, and systematic changes in the electron sharing caused by changes in WD. The image contrast was reasonably explained by the kinetic energy and take-off angle (acceptance plots) of the detected electrons derived by the electron trajectory simulations. This approach is essential to understanding the SEM image contrast obtained by SEM systems with multiple detectors. Thorough image simulations based on acceptance plots are required in future work.

Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats.

PURPOSE: The purpose of this study was to investigate the age-, time-, and brain region-dependent postoperative neuroinflammatory trajectory, and its association with neurocognitive outcomes in rats. METHODS: Adult and aged rats were randomly assigned to one of three groups: control, isoflurane anesthesia alone, and isoflurane anesthesia with abdominal surgery. On either postoperative day 2 (early phase) or 7 (late phase), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Freezing behavior was used as an index of fear memory. Following the cognitive testing, the levels of pro-inflammatory cytokines in several brain regions were measured using enzyme-linked immunosorbent assay (n = 8 in each group). RESULTS: In the early postoperative period, surgery under isoflurane anesthesia induced acute neuroinflammation along with related trace and context memory dysfunction. Such acute neuroinflammatory responses were comparably observed in both adult and aged animals, whereas the aged rats were more likely to exhibit behavioral changes. On the other hand, in the late postoperative period, neither neuroinflammation in all tested brain regions nor concomitant memory decline were found in adult animals. Significant neuroinflammation was detected only in the hippocampus of aged rats, which was associated with context, but not trace memory dysfunction. CONCLUSION: Our findings indicate that surgery-induced acute, transient, brain-wide neuroinflammation may be involved in the pathogenesis of the postoperative delirium-like cognitive deficits in rats. Furthermore, neuroinflammation may convert from acute to chronic in an age- and hippocampal-specific manner, likely resulting in the development of sustained cognitive dysfunction.

The role of hippocampal brain-derived neurotrophic factor in age-related differences in neuropathic pain behavior in rats.

AIMS: This study was aimed to explore the contribution of central brain-derived neurotrophic factor (BDNF) in the neuropathic pain pathogenesis using an aged rodent model. MAIN METHODS: Adult and aged rats were randomly assigned to either a sciatic nerve ligation (SNL) group or a control skin sham surgery group. Sensory behavioral testing were performed on the day before surgery and on the 3rd, 7th, 14th, and 21st days after surgery, followed by measurement of BDNF protein levels in different brain regions. In another experiment, the hippocampal BDNF gene expression after SNL surgery was assessed at different time-points. Furthermore, the analgesic effects of intranasal BDNF administration were tested in SNL animals. KEY FINDINGS: Our behavioral results demonstrated that the hyperalgesia-like behavior after painful nerve injury has a higher incidence in aged rats compared with in adult animals. In particular, the hippocampal BDNF levels were inversely correlated with the probability of hyperalgesia-type behavior, in both brain-region specific and age-dependent manner. Time-course analysis showed that the hippocampal levels of BDNF mRNA in aged and adult rats started to decrease 7 and 14 days after surgery, respectively. However, the decrease was more pronounced in aged animals. Moreover, the repeated intranasal BDNF treatment could restore the central BDNF signaling, counteracting the age-related exacerbation of hyperalgesic behavior. SIGNIFICANCE: Our findings imply that hippocampal BDNF may be related with the pathogenesis of elderly neuropathic pain. Pharmacological data further suggest that brain BDNF may be modifiable in aged neuropathic animals, and therefore, represent a promising target for intervention.

Effects of epigallocatechin-3-gallate on systemic inflammation-induced cognitive dysfunction in aged rats.

PURPOSE: In this study, we examined the effects of epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on sepsis-induced neurocognitive abnormity in aged rats. METHODS: Aged rats received an intraperitoneal (i.p.) injection of 5.0 mg/kg lipopolysaccharide (LPS) or saline. Animals were further divided into three groups: control, low-dose EGCG (4.0 mg/kg), and high-dose EGCG (20 mg/kg). EGCG was i.p. injected at the same time, 24 and 48 h after LPS administration. Survival rate was recorded for 1 week. All surviving animals were assessed for cognitive function using the novel object recognition test, followed by measurement of hippocampal cytokine levels. In an additional set of experiments, the liver function test was performed. Furthermore, the effects of EGCG on cytokine release from microglia isolated from young and aged rats were assessed. RESULTS: The survival rate in LPS-treated control rats was 77.8%, which was decreased to 72.2 and 33.3% in the low and high EGCG groups, respectively. In the surviving animals, the LPS-treated control rats exhibited impaired cognitive performance and increased pro-inflammatory cytokine levels compared with untreated animals. None of these neurocognitive alterations were affected by low or high EGCG treatment. Blood chemical analysis showed co-administration of EGCG with LPS resulted in a marked increase in both aspartate aminotransferase and alanine aminotransferase levels. In addition, EGCG inhibited LPS-induced cytokine release, whereas the suppressive ability of EGCG was lower in aged microglia compared with in young microglia. CONCLUSIONS: Our findings demonstrated that EGCG cannot prevent hippocampal neuroinflammation and related memory deficits in aged rats surviving sepsis.

The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats.

PURPOSE: Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model. METHODS: The surgical and sham-surgical animals were randomly divided into saline-treated control, 5.0 mg/kg LPS-treated, 10 µg/kg DEX-treated, and 5.0 mg/kg LPS + 10 µg/kg DEX-treated groups. In the surgical animals, a 1-cm-long plantar incision was made through the skin and fascia under isoflurane anesthesia. The sham-surgical rats were only anesthetized. All treatments were administered by a single intraperitoneal (i.p.) injection 60 min before surgery. Acute postoperative pain was assessed using the Rat Grimace Scale (RGS) one day before surgery (baseline) and at 2 h post incision. In another experiment, the involvement of the α2-adrenergic receptor was tested using atipamezole, an α2-adrenergic receptor antagonist. RESULTS: In the sham-surgical animals, the RGS did not increase at 2 h after sham surgery compared with the corresponding baseline values in all groups. In the surgical rats, however, the postoperative RGS value of the LPS group was significantly higher than the control group, indicating LPS-induced postoperative hyperalgesia. Administration of intraoperative DEX could prevent the development of such LPS-induced exacerbated post-incisional pain. In addition, the preventive effects of intraoperative DEX were inhibited by pretreatment with atipamezole. CONCLUSION: Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α2-adrenergic receptor signaling pathway.