Application and Efficacy of Vitamin E-Bonded Polysulfone Membrane in Acute Blood Purification Therapy.

INTRODUCTION: Acute blood purification therapy (BPT) has been evaluated in the context of intensive care for serious conditions related to systemic inflammation, but its mechanism and efficacy are not fully understood. OBJECTIVE: This study examined the feasibility of using vitamin E-bonded polysulfone membranes (VEPS) for BPT in a LPS-induced rat model of systemic inflammation. METHODS: To evaluate the efficacy of BPT with a VEPS membrane, polysulfone (PS) membranes conventionally used in intensive care were bonded with the antioxidant vitamin E and used in a rat model of lipopolysaccharide (LPS)-induced systemic inflammation. BPT using a PS membrane (PS group) or a VEPS membrane (VEPS group) was performed 6 h after administration of LPS. Extracorporeal circulation was established in normal rats as a control (sham group). Survival rates, histology of lung specimens, and levels of myeloperoxidase (MPO) and high mobility group box-1 (HMGB-1) were examined in each group. RESULTS: Survival rates at 24 h after LPS administration were 100% in the VEPS group and 50% in the PS group. Pulmonary architecture was largely maintained and the level of infiltration of inflammatory cells remained moderate in the VEPS group. Levels of active MPO before and after BPT were significantly higher in the PS and VEPS groups than in the sham group, with no significant differences between the PS and VEPS groups. HMGB-1 levels were significantly elevated after BPT in the PS group. CONCLUSIONS: This study demonstrated that use of the VEPS membrane for BPT increased survival rate and reduced lung injury in a rat model of systemic inflammatory response syndrome (SIRS), suggesting the possible use of VEPS membranes in the treatment of serious conditions related to systemic inflammation.

Real-time monitoring of vitamin C levels in trauma patients by electron-spin resonance spectrometry.

BACKGROUND: In critically ill patients, healthy vitamin C levels are important to avoid an imbalance in reactive oxygen species. To achieve this, oxidative stress levels in emergency patients need to be accurately measured in real-time. However, normally, reactive oxygen/nitrogen species are short-lived, rendering measurement difficult; moreover, measurement of relatively stable antioxidants and other oxidative stress markers in real-time is challenging. Therefore, we used electron-spin resonance spectrometry (ESR) to assess vitamin C levels, clarify their relationship with patients' severity, and establish more effective vitamin C therapy in critically ill patients. METHODS: We studied 103 severely ill emergency patients and 15 healthy volunteers. Vitamin C radical (VCR/dimethyl sulfoxide [DMSO]) values were analyzed in arterial blood samples by ESR at admission and once daily thereafter during the acute recovery phase. Severity scores were calculated. The relationship between these scores and VCR/DMSO values and chronological changes in VCR/DMSO values were analyzed. RESULTS: Serum VCR/DMSO values were significantly lower in critically ill patients than in healthy volunteers (0.264 ± 0.014 vs. 0.935 ± 0.052, p < 0.05), particularly in the severe trauma group and the cardiopulmonary arrest/post-cardiac arrest syndrome group. VCR/DMSO values and various severity scores did not correlate at admission; however, they correlated with SOFA scores from days 2-6. VCR/DMSO values remained low from the first measurement day through Day 6 of illness. CONCLUSIONS: Vitamin C levels were low at admission, remained low with conventional nutritional support, and did not correlate with the initial patient's severity; however, they correlated with patients' severity after admission. Some patients had normal vitamin C levels. Therefore, vitamin C levels should be measured in real-time and supplemented if they are below normal levels. TRIAL REGISTRATION: Retrospectively registered.

The dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals.

This study aimed to illustrate the dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals in vitro. We have demonstrated that amide-type local anesthetics selectively and directly scavenge some free radicals. Three kinds of free radicals were eliminated by all the four local anesthetics examined. Mepivacaine, lidocaine, bupivacaine, and dibucaine scavenged hydroxyl radicals in dose-dependent manners. Ascorbyl free radicals were also scavenged in dose-dependent manners, and lastly singlet oxygen was scavenged in dose-dependent manners. Three other free radicals were not scavenged by all of the four local anesthetics; tert-butoxyl radical was scavenged by all the anesthetics examined but dibucaine, nitric oxide by mepivacaine but not by the other three, and tyrosyl radical by mepivacaine and lidocaine but not by the other two. Some free radicals (superoxide anion, tert-butyl peroxyl radical, DPPH) were not scavenged by any of the four local anesthetics. The local anesthetics were also shown to inhibit lipid peroxidation by TBARS assay. These results suggest that local anesthetics have antioxidant properties through their free radical scavenging activities.

Comparison of three obturator nerve block techniques for injectate spread into the obturator canal: a randomized controlled trial.

PURPOSE: The obturator nerve branches into the obturator canal; therefore, local anesthetic spread into the obturator canal predicts the success of the obturator nerve block (ONB). We compared three ONB techniques for the spread of local anesthetic mixed with contrast medium into the obturator canal. METHODS: We performed the ONB using the classical pubic approach (PA), inguinal approach (IA), or ultrasound-guided methodologic approach (UMA) in 143 patients undergoing transurethral resection of bladder tumors. The obturator nerve course and branching patterns of the UMA group were examined using ultrasound imaging. After injecting a local anesthetic mixed with a contrast medium, we evaluated its spread into the obturator canal using fluoroscopic imaging. P < 0.05 indicated statistical significance. RESULTS: Success rate of obturator canal enhancement was the greatest in the UMA group (84%; P < 0.001); the PA (42.6%; 20/47 patients) and IA (47.8%; 22/46 patients) groups did not differ significantly (P = 1.000). Both branches of the obturator nerve passed above the superior margin of the external obturator muscle (EOM), and the obturator canal was enhanced in 13 of 50 (26%) patients in the UMA group. The posterior branch of the obturator nerve passed between the superior and main fasciculi of the EOM in 37 of 50 patients (74%) in the UMA group; the obturator canal was enhanced in 29 of these 37 patients (78%). CONCLUSION: Local anesthetic spread into the obturator canal using the UMA was superior to that using the PA and IA. Both branches of the obturator nerve could be blocked using the UMA.

Dose-dependent scavenging activity of the ultra-short-acting ß1-blocker landiolol against specific free radicals.

Landiolol, a highly cardioselective ultra-short-acting ß1-blocker, prevents perioperative atrial fibrillation associated with systemic inflammation and oxidative stress. We evaluated the direct scavenging activity of landiolol against multiple free radical species. Nine free radical species (hydroxyl, superoxide anion, ascorbyl, tert-butyl peroxyl, tert-butoxyl, singlet oxygen, 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and tyrosyl radicals) were directly quantified using an X-band ESR spectrometer with the spin-trapping method. IC50 and reaction rate constants were estimated from the dose-response curve for each free radical. Landiolol scavenged six of the free radical species examined: hydroxyl radical (IC50 = 0.76 mM, k landiolol = 1.4 × 10|10 M|-1 s|-1, p<0.001), superoxide anion (58 mM, 2.1 M|-1 s|-1, p = 0.044), tert-butoxyl radical (4.3 mM, k landiolol/k CYPMPO = 0.77, p<0.001), ascorbyl free radical (0.31 mM, p<0.001), singlet oxygen (0.69 mM, k landiolol/k 4-OH |TEMP = 2.9, p<0.001), and nitric oxide (15 mM, 1.7 × 10 M|-1 s|-1, p<0.001). This study is the first to report that landiolol dose-dependently scavenges multiple free radical species with different reaction rate constants. These results indicate the potential clinical application of landiolol as an antioxidative and anti-inflammatory agent in addition to its present clinical use as an anti-arrhythmic agent.

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (k fv for fluvastatin, and k pv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with k fv and k pv of 4.82 M-1s-1 and 49.0 M-1s-1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both k fv and k pv were >109 M-1s-1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative k fv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with k fv and k pv of 68.6 M-1s-1 and 701 M-1s-1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.

Lateral deviation of four types of epidural catheters from the lumbar epidural space into the intervertebral foramen.

BACKGROUND: During epidural anesthesia, the catheter tip occasionally deviates from the epidural space into the intervertebral foramen, resulting in inadequate anesthesia. METHODS: During postoperative plain radiography, iohexol was injected via the epidural catheter to determine its position and to observe the spread of the material. After exclusion of seven patients with catheters that migrated into the subcutaneous area and 25 patients with no evidence of the contrast medium, 415 patients were evaluated. We retrospectively compared patients to determine whether the incidence of deviation into the intervertebral foramen differed between four types of epidural catheters. We also investigated the load applied to the catheter tip using a Shimadzu Autograph AG-X-500 N-111 universal testing machine. RESULTS: Deviation of the epidural catheter into the intervertebral foramen was observed in eight and 33 patients in the Hakko and Perifix Soft tip catheter groups, respectively. The incidence of deviation was higher in the Perifix Soft tip catheter group, and lower in the FlexTip Plus and Perifix FX catheter groups. A rapid increase was observed in the force exerted on the tips of the Hakko and Perifix Soft tip catheters, while the force transmitted to the tips of the FlexTip Plus and Perifix FX catheters gradually increased and then reached a plateau at a low level. CONCLUSIONS: The incidence of deviation was significantly lower with spiral-type catheters than with other types of catheters. This might be attributable to the gradual transmission of a lower level of force to the tip in spiral-type catheters.

Sonographic diagnosis and evaluation in patients with superficial radial arteries.

BACKGROUND: The superficial radial artery (SRA) is a rare congenital anomaly in the forearm. However, it can be detected incidentally via trauma, intraoperative findings, angiography, or ultrasonography. In addition, intra-arterial infusion of intravenous medications and difficulties in radial artery catheterization may occur in cases of the SRA. METHODS: Between December 2016 and July 2020, anomalous branches of radial arteries were found incidentally in nine patients at the preoperative visit and identified during ultrasound-guided radial artery puncture in 21 patients when radial artery catheterization using the palpation method proved difficult. Ultrasound examinations were performed for diagnosis and evaluation of these 30 patients. RESULTS: All anomalous branches of the radial artery were SRAs; 11 (37%), 13 (43%), 6 (20%) were present on the right side, on the left side, and bilaterally, respectively. All SRAs ran close to the cephalic vein. The vascular diameters of the radial arteries were the smallest in the radial artery distal to the SRA bifurcation (followed by in the SRA) and the largest in the radial artery proximal to the bifurcation (p < .001). In two cases, color Doppler study revealed that both the blood flow and color Doppler signal of the SRA disappeared with compression of the radial artery proximal to the SRA bifurcation. CONCLUSIONS: Because the SRA runs very close to the cephalic vein, a tourniquet applied to the arm may easily lead to intravenous catheter misplacement into the SRA. In addition, the small radial artery distal to the SRA bifurcation causes difficulty in radial artery catheterization. Furthermore, SRA cases may have falsely normal Allen's test results. Therefore, the authors recommend that the SRA must be identified before vascular puncture for safe vascular catheterization in the forearm.

General anesthesia with remimazolam for emergency cesarean section in a patient with acute infective endocarditis: a case report.

BACKGROUND: The anesthetic management of pregnant women with acute heart failure remains challenging with regard to maintaining the hemodynamic status of the mother and baby. The likelihood of decreased blood pressure is lower with remimazolam than with propofol. However, there is no report of general anesthesia with remimazolam for cesarean section. CASE PRESENTATION: The patient was a 34-year-old pregnant woman who was diagnosed with acute heart failure associated with infective endocarditis. We performed cesarean section under general anesthesia using remimazolam, with percutaneous cardiopulmonary support on standby. The mother's mean blood pressure was maintained above 65 mmHg during the surgery, without catecholamines or vasopressors. The infant's Apgar scores were 4 at 1 min and 7 at 5 min. CONCLUSION: Cesarean section was successfully performed under general anesthesia with remimazolam in a pregnant patient with acute heart failure. Further studies are needed to clarify the association between remimazolam and neonatal hypotension.

Human atrial natriuretic peptide attenuates renal ischemia-reperfusion injury.

BACKGROUND: Acute kidney injury (AKI) is common in the intensive care unit, and one of its primary causes is renal ischemia-reperfusion (I/R) injury. Human atrial natriuretic peptide (hANP) exerts various pharmacologic effects, including renal protection. In the present study, we evaluated the renal protective effect of hANP in a rat model of renal I/R. MATERIALS AND METHODS: Male Wistar rats were divided into three groups that received the following treatments: induction of renal I/R (I/R group); continuous intravenous injection of hANP followed 30 min later by induction of renal I/R (hANP+I/R group); and sham treatment (control group). Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion or sham treatment. To evaluate the renal protective effects if hANP, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and serum biomarkers of oxidative stress were evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with hANP to assess its antioxidant effects. RESULTS: Serum BUN and Cre levels were elevated in the I/R group; however, these increases were significantly inhibited in the hANP + I/R group. Similarly, kidney tissue damage observed in the I/R group was attenuated in the hANP + I/R group. In vitro, AMA-stimulated cells treated with hANP showed reduced reactive oxygen species activity compared to cells treated with AMA alone. CONCLUSIONS: Our findings indicate that hANP may be effective in the treatment of various types of I/R injuries.

EPCK1, a vitamin C and E analogue, reduces endotoxin-induced systemic inflammation in mice.

BACKGROUND: Phosphate ester of vitamin C and vitamin E (EPCK1), a strong antioxidant, is a water- and lipid-soluble phosphate ester of vitamin C and vitamin E. In the current study, we tested whether EPCK1 inhibits oxidative stress and prevents systemic inflammation. MATERIALS AND METHODS: Mice were randomly divided into a negative control group, a lipopolysaccharide (LPS)-induced sepsis group, and a group treated with an intraperitoneal infusion of EPCK1 (10 mg/kg) prior to or following LPS administration. In addition, RAW 264.7 cells were treated with LPS in the presence or absence of EPCK1. We examined levels of high mobility group box 1 (HMGB1) protein and inducible nitric oxide synthase (iNOS) in both in vivo and in vitro experiments, and liver histopathology in the in vivo experiment. RESULTS: Liver histopathology significantly improved in the EPCK1 group compared with the LPS group. Although LPS administration increased HMGB1 and nitric oxide (NO) secretion, EPCK1 decreased the secretion of these mediators in vitro and in vivo. CONCLUSIONS: Our findings suggest that EPCK1 may inhibit inflammation and potentially function as a novel anti-inflammatory therapeutic agent.

Danaparoid sodium attenuates the effects of heat stress.

BACKGROUND: Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke. MATERIALS AND METHODS: Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples. RESULTS: In rats pretreated with DA, induction of cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation. CONCLUSION: Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.

Catecholamine-resistant shock and hypoglycemic coma after cardiotomy in a patient with unexpected isolated ACTH deficiency.

Isolated adrenocorticotropic hormone (ACTH) deficiency is an extremely rare disease in which ACTH-producing cells of the pituitary gland are selectively damaged. The resulting decline in ACTH production and secretion results in chronic secondary adrenocortical insufficiency. The patient in this case did not present with adrenal insufficiency symptoms prior to surgery. However, after cardiotomy under extracorporeal circulation, the patient lapsed into a catecholamine-resistant shock and hypoglycemic coma. Acute adrenal insufficiency was strongly suspected, and the patient was diagnosed with isolated ACTH deficiency after careful examination. Because the demand for cortisol increases after highly invasive surgeries, cortisol supplementation therapy is essential for patients with complications from isolated ACTH deficiency. There is a high risk of a lethal outcome when surgery is carried out without a diagnosis, as in this case. Therefore, cortisol must be supplemented without delay when acute adrenal insufficiency is suspected during the perioperative period.

An electron spin resonance study for real-time detection of ascorbyl free radicals after addition of dimethyl sulfoxide in murine hippocampus or plasma during kainic acid-induced seizures.

Electron spin resonance (ESR)-silent ascorbate solutions generate a detectable, likely concentration-dependent signal of ascorbyl free radicals (AFR) immediately upon addition of a molar excess of dimethyl sulfoxide (DMSO). We aimed to perform quantitative ESR analysis of AFR in real time after addition of DMSO (AFR/DMSO) to evaluate ascorbate concentrations in fresh hippocampus or plasma following systemic administration of kainate in mice. Use of a special tissue-type quartz cell allowed immediate detection of AFR/DMSO ESR spectra in fresh tissues from mice. AFR/DMSO content was increased significantly in fresh hippocampus or plasma obtained during kainate-induced seizures of mice, reaching maximum levels at 90 min after intraperitoneal administration of 50 mg/kg kainic acid. This suggests that oxidative injury of the hippocampus resulted from the accumulation of large amounts of ascorbic acid in the brain after kainic acid administration. AFR/DMSO content measured on an ESR spectrometer can be used for real-time evaluation of ascorbate content in fresh tissue. Due to the simplicity, good performance, low cost and real-time monitoring of ascorbate, this method may be applied to clinical research and treatment in the future.

High-dose antithrombin III prevents heat stroke by attenuating systemic inflammation in rats.

OBJECTIVE: Systemic inflammatory mediators, including the high mobility group box 1 (HMGB1) protein, play important roles in the development of various inflammatory conditions. Although anticoagulants, such as antithrombin III (AT III), inhibit inflammation resulting from various causes, their anti-inflammatory mechanism of action is not well understood. Nevertheless, as heat stroke is a severe inflammatory response disease, we hypothesized that AT III would inhibit inflammation and prevent heat stress-induced acute heat stroke. METHODS: Male Wistar rats received a bolus injection of saline or 250 U of AT III per kg of body weight into the tail vein, followed by heat stress (exposure to 42 degrees C for 30 min). Levels of cytokines (interleukin-1 beta, interleukin-6, and TNF-alpha), NOx, and HMGB1 were measured in serum and tissue at regular intervals for 6 h after the heat stress induction. RESULTS: Levels of cytokines, NOx, and HMGB1 in serum decreased over time in AT III-treated rats. AT III pretreatment also reduced NOx levels during heat stress-induced inflammation. As a result, AT III pretreatment improved survival in a rat model of heat stress-induced acute inflammation. CONCLUSIONS: Our data suggest that AT III pretreatment inhibited the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced acute inflammation.

Human atrial natriuretic peptide ameliorates LPS-induced acute lung injury in rats.

Acute lung injury, a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. However, recent studies have demonstrated that the multifunctional human atrial natriuretic peptide (hANP) exerts anti-inflammatory effects. Therefore, we tested the hypothesis that hANP could prevent lipopolysaccharide (LPS)-induced acute lung injury in a rodent model. Rats received an LPS injection and continuous intravenous infusion (CIV) of hANP or saline solution. We evaluated the anti-inflammatory effects of hANP by histological examination and determination of serum cytokine levels and lung myeloperoxidase (MPO) activity. Histological examination revealed marked reductions in interstitial congestion, edema, inflammation, and hemorrhage in lung tissue harvested 12 h after hANP treatment compared with tissue from rats that received saline treatment after LPS. LPS injection induced elevated cytokine (IL-1beta and IL-6) secretion and lung MPO activity, which was also attenuated by hANP treatment. Taken together, these data demonstrate that hANP exerts an anti-inflammatory effect and may have potential as a therapeutic agent to treat systemic inflammatory diseases.

The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.

BACKGROUND: Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results. METHODS: Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI. RESULTS: We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond. CONCLUSIONS: Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.

Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury.

PURPOSE: Renal ischemia-reperfusion (I/R), an important cause of acute kidney injury, is unavoidable during various types of operations, including renal transplantation, surgical revascularization of the renal artery, partial nephrectomy, and treatment of suprarenal aortic aneurysms. Exacerbation of I/R injury is mediated by reactive oxygen species (ROS). A recent study has shown that hydrogen has antioxidant properties. In this study, we tested the hypothesis that a hydrogen-rich saline solution (HRSS) attenuates renal I/R injury in a rodent model. METHODS: Rats were treated with an intravenous injection of HRSS or control saline solution followed by renal I/R. After 24 h of treatment, we performed a histological examination and transmission electron microscopy, and measured serum levels of 8-OHdG. RESULTS: Histological analysis revealed a marked reduction of interstitial congestion, edema, inflammation, and hemorrhage in renal tissue harvested 24 h after HRSS treatment compared to saline administration. Renal I/R injury, which led to altered mitochondrial morphology, was also inhibited by HRSS. Furthermore, serum 8-OHdG levels were significantly lower in rats treated with HRSS and subjected to renal I/R. CONCLUSIONS: These protective effects were likely due to the antioxidant properties of HRSS. These results suggest that HRSS is a potential therapeutic candidate for treating various I/R diseases.

Heat shock protein 72 protects insulin-secreting beta cells from lipopolysaccharide-induced endoplasmic reticulum stress.

PURPOSE: Hyperthermia-induced activation of stress response proteins allows cells to withstand metabolic insults. In this study we set out to determine whether insulin secretion by pancreatic beta cells was affected by the acute inflammatory response, systemic inflammation-induced hyperglycaemia, and whole-body hyperthermia. Given that systemic-inflammation induces ER stress, we further examined whether hyperthermia can attenuate the extent of LPS-induced ER stress. MATERIALS AND METHODS: Rats were randomised and divided into three treatment groups. Control rats received a 0.9% NaCl solution. Rats in the lipopolysaccharide (LPS) group received 7.5 mg of LPS/kg. Rats in the whole-body hyperthermia (WBH) + LPS group were exposed to 42 degrees C for 15 min, followed by injection with 7.5 mg of LPS/kg after 48 h. Glucose-potentiated insulin release and extent of ER stress were measured in beta cells. RESULTS: LPS inhibited glucose-induced insulin release from islet cells and induced the expression of Bip/GRP78, XBP-1, and CHOP transcripts. The inhibition of glucose-induced insulin release and induction of ER stress proteins by LPS was attenuated by WBH. CONCLUSIONS: Our findings suggest that LPS-induced systemic inflammation decreased insulin release due to the effects of ER stress proteins on insulin secretion. Furthermore, the induction of ER stress proteins was prevented by pretreating rats with WBH. This may suggest that inhibiting the induction of ER stress proteins through WBH can restore insulin release in various disease states.