Effects of sevoflurane exposure during late pregnancy on brain development of offspring mice.

BACKGROUND: Exposure to some anesthetic agents during the fetal period has been shown to induce neurodegeneration or learning deficits in animal models. Sevoflurane is one of the most prevalent general anesthetics; however, the influence of sevoflurane at a clinically relevant concentration on the developing fetal brain remains unknown. OBJECTIVE: We investigated whether a single sevoflurane exposure during the fetal period would affect neuronal development and learning/memory ability in mice. METHODS: Pregnant mice at gestational day 17 were anesthetized with 1.5% sevoflurane in 50% oxygen for 6 h. Mice in the control group were exposed in 50% oxygen without sevoflurane. Pups of some mice in both groups subsequently were delivered early by cesarean section and whole fetal brains were excised. The rest of the pups were delivered naturally at gestational day 20 and were maintained for 8 weeks. The mRNA expression levels of caspase-3, brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), and LIM kinase-1 (LIMK-1) were measured in fetal whole brain and 8-week-old hippocampus sections. Synaptophysin protein in adult hippocampus was assessed immunochemically. In addition, 8-week-old mice were subjected to the radial maze test. RESULTS: No significant difference between sevoflurane and control groups regarding mRNA expression levels of all targets was seen, nor was there an obvious change in synaptophysin protein expression. The results of the maze test revealed that the each-day performance ratios (the rate of errors) of the sevoflurane group were not altered as compared with the control group. CONCLUSIONS: These results suggest that the exposure during late pregnancy to a clinically relevant concentration of sevoflurane does not affect neuronal development and learning/memory ability of offspring mice.

T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model.

BACKGROUND: Sepsis is a potentially fatal syndrome mediated by an early [e.g., tumor necrosis factor-alpha (TNF-α)] and late [high mobility group box-1 (HMGB-1)] proinflammatory cytokine response to infection. Sepsis-induced acute kidney injury (AKI) is associated with a high mortality. C-Fos/activator protein-1 (AP-1) controls the transactivation of proinflammatory cytokines via AP-1 binding in the promoter region. T-5224 is a de novo small molecule inhibitor of c-Fos/AP-1 that controls gene expression of multiple proinflammatory cytokines. We investigated whether T-5224, a selective inhibitor of c-Fos/AP-1, improves survival in lethal lipopolysaccharide (LPS)-induced AKI by inhibiting early (TNF-α) and late (HMGB-1) proinflammatory cytokine response. METHODS: Mice were divided into four groups (control, LPS, LPS + T-5224, and T-5224 only). Control mice were administered polyvinylpyrrolidone (PVP) solution orally, immediately after intraperitoneal (i.p.) saline injection. LPS mice were administered PVP solution orally immediately after i.p. LPS (10 mg/kg) injection. LPS + T-5224 mice were administered T-5224 orally (300 mg/kg) immediately after i.p. LPS injection. T-5224 mice were administered T-5224 orally (300 mg/kg) after i.p. saline injection. Serum concentrations of TNF-α, HMBG-1, and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA). Serum blood urea nitrogen (BUN) and creatinine concentrations were commercially analyzed. Finally, histological examination was performed on the kidney. RESULTS: Treatment with T-5224 decreased serum TNF-α and HMGB-1 levels and increased survival after LPS injection. Furthermore, T-5224 treatment decreased serum BUN and creatinine concentrations but increased serum IL-10 concentration. LPS-induced pathological changes in kidney were attenuated by T-5224 treatment. CONCLUSIONS: These results suggest that T-5224, a selective inhibitor of c-Fos/AP-1, inhibits expression of early and late proinflammatory cytokines, protecting mice from LPS-induced lethality. T-5224 is a potential approach for decreasing lethality in sepsis-induced AKI.

D-ribose ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice.

Cisplatin is one of the most potent chemotherapeutic anticancer drugs, but it can produce side effects such as nephrotoxicity. Inflammatory cytokines, chemokines and adhesion molecules have important roles in the pathogenesis of cisplatin-induced nephrotoxicity. D-Ribose is a naturally occurring five-carbon monosaccharide that is found in all living cells, and has anti-inflammatory effects in renal ischemia/reperfusion injury. The purpose of this study was to determine the protective effects of D-ribose on cisplatin-induced nephrotoxicity. Forty-eight mice were randomly divided into four groups: control, cisplatin, cisplatin + ribose, and ribose. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without D-ribose (400 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). At 72 h after cisplatin injection, we measured serum and renal tumor necrosis factor (TNF)-α and renal monocyte chemoattractant protein (MCP)-1 concentrations by enzyme-linked immunosorbent assay; renal expression of intercellular adhesion molecule (ICAM)-1 mRNA by real-time polymerase chain reaction; serum blood urea nitrogen and creatinine; and histological changes. Cisplatin increased serum and renal TNF-α concentrations, renal MCP-1 concentration, and renal ICAM-1 mRNA expression. Treatment with D-ribose attenuated the increase in serum and renal TNF-α concentrations, renal MCP-1 concentration, and renal ICAM-1 mRNA expression. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis were attenuated by D-ribose treatment. This is believed to be the first time that protective effects of D-ribose on cisplatin-induced nephrotoxicity via inhibition of inflammatory reactions have been investigated. Thus, D-ribose may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.

Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice.

Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. Curcumin is an orange-yellow polyphenol present in curry spice and has anti-inflammatory and antioxidant effects. The purpose of this study was to determine the protective effects of curcumin on cisplatin-induced nephrotoxicity. Mice were randomly divided into four groups: control, cisplatin, cisplatin + curcumin and curcumin. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without curcumin treatment (100 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). Serum and renal tumor necrosis factor (TNF)-alpha and renal monocyte chemoattractant protein (MCP)-1 concentrations, intercellular adhesion molecule-1 (ICAM-1) mRNA expression in kidney, renal function and histological changes were determined 72 h after cisplatin injection. Serum TNF-alpha concentration in the cisplatin + curcumin group significantly decreased compared with that in the cisplatin group. Renal TNF-alpha and MCP-1 concentrations and ICAM-1 mRNA expression in kidney in the cisplatin + curcumin group also significantly decreased compared with those in the cisplatin group. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis scores were attenuated by curcumin treatment. These results indicate that curcumin acts to reduce cisplatin-induced nephrotoxicity through its anti-inflammatory effects. Thus, curcumin may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.

The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin-induced acute kidney injury in mice.

BACKGROUND: Sepsis has been identified as the most common cause of acute kidney injury (AKI) in intensive care units. Lipopolysaccharide (LPS) induces the production of several proinflammatory cytokines including tumor necrosis factor (TNF)-alpha, a major pathogenetic factor in septic AKI. c-Fos/activator protein (AP)-1 controls the expression of these cytokines by binding directly to AP-1 motifs in the cytokine promoter regions. T-5224 is a new drug developed by computer-aided drug design that selectively inhibits c-Fos/AP-1 binding to DNA. In this study, we tested whether T-5224 has a potential inhibitory effect against LPS-induced AKI, by suppressing the TNF-alpha inflammatory response and other downstream effectors. METHODS: To test this hypothesis, male C57BL/6 mice at 7 weeks old were divided into three groups (control, LPS and T-5224 groups). Mice in the control group received saline intraperitoneally and polyvinylpyrrolidone solution orally. Mice in the LPS group were injected intraperitoneally with a 6 mg/kg dose of LPS and were given polyvinylpyrrolidone solution immediately after LPS injection. In the T-5224 group, mice were administered T-5224 orally at a dose of 300 mg/kg immediately after LPS injection. Serum concentrations of TNF-alpha, interleukin (IL)-1beta, IL-6 and IL-10 were measured by ELISA. Moreover, the expression of intercellular adhesion molecule (ICAM)-1 mRNA in kidney was examined by quantitative real-time RT-PCR. Finally, we evaluated renal histological changes. RESULTS: LPS injection induced high serum levels of TNF-alpha, IL-1beta and IL-6. However, the administration of T-5224 inhibited the LPS-induced increase in these cytokine levels. The serum levels of IL-10 in the LPS group and T-5224 group were markedly elevated compared with the control group. T-5224 also inhibited LPS-induced ICAM-1 mRNA expression. Furthermore histological studies supported an anti-inflammatory role of T-5224. CONCLUSIONS: In endotoxin-induced AKI, T-5224 inhibited the production of TNF-alpha and other downstream effectors. In contrast, T-5224 did not inhibit IL-10, an anti-inflammatory cytokine. These data support that the use of T-5224 is a promising new treatment for septic kidney injury.

[Case of anaphylactic reaction caused by sugammadex].

A 17-year-old man was scheduled for ventriculo-peritoneal shunt under general anesthesia. Anesthesia was induced by propofol, rocuronium and pentazocine, and maintained with sevoflurane and nitrous oxide. The operation was finished in 1 hour and 4 minutes without trouble. After the operation, sugammadex was administered. After about 2 minutes, the redness and the wheal appeared in the body trunk, and SpO2 dropped to The appearance of rapid symptom immediately after administration of sugammadex indicated that anaphylactic reaction had occurred. We administered adrenaline. After the administration of adrenaline several times, cutaneous findings became improved and SpO2 was stabilized. We started continuous infusion of adrenaline, and the patient was moved to the intensive care unit (ICU). Twelve hours after entering the ICU, the patient was extubated. He showed no troubles thereafter, and left hospital. After introduction of sugammadex to clinical use, 7 cases of anaphylactic reaction to sugammadex were reported. We must know that anaphylactic reaction can be induced by sugammadex.

T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice.

The effect of T-5224, a selective inhibitor of c-Fos/activator protein (AP)-1, on lipopolysaccharide (LPS) induced liver injury was examined in mice. Administration of LPS (10 mg kg(-1), i.p.) markedly increased serum levels of tumor necrosis factor-alpha (TNFα), high mobility group box 1 (HMGB1), alanine aminotransferase/aspartate aminotransferase (ALT/AST), liver tissue levels of macrophage-inflammatory protein-1 alpha (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1), as well as hepatic necrosis and inflammation, leading to 67 % lethality. Administration of T-5224 (300 mg kg(-1), p.o.) after intraperitoneal injection of LPS imparted appreciable protection against acute elevations in serum levels of TNFα, HMGB1, ALT/AST as well as in liver tissue levels of MIP-1α and MCP-1, and reduced the lethality (27 %). These data indicate that T-5224 ameliorates liver injury and improves survival through decreasing production of proinflammatory cytokines and chemokines in endotoxemic mice.

Erythropoietin attenuates isoflurane-induced neurodegeneration and learning deficits in the developing mouse brain.

OBJECTIVES: To examine whether recombinant erythropoietin (rEPO) attenuates neurodegeneration and the learning disability induced by isoflurane with the postnatal day 7 (P7) mice. BACKGROUND: Some of general anesthetic agents induce neurodegeneration in developing brain. Several drugs, but not rEPO, were reported as candidates for the prevention of or treatment for neurodegeneration. METHOD AND MATERIALS: We divided P7 mice into three groups at random. One group (IE group) was exposed to 6-h isoflurane (1.0%) after 50,000 IU·kg(-1) rEPO administered subcutaneously. The second group (I) was exposed to isoflurane in the same manner as IE group except saline instead of rEPO. The third group (E) was exposed to air after rEPO administered. The mice were assigned to the radial arm maze on four consecutive days from P56 (day 1) to P59 (day 4). We divided the number of errors each day by that of day 1 to establish each-day performance ratio. After the test, neurodegenerative change in the hilus of dentate gyrus was assessed using Nissl staining. RESULTS: In radial maze test, the performance ratios of day 3 (mean ± sd) were 0.3 ± 0.2 (P < 0.05, vs I group), 0.8 ± 0.5, and 0.6 ± 0.2 in IE, I, and E groups, respectively, while those of day 4 were 0.3 ± 0.1 (P < 0.05), 0.8 ± 0.5, and 0.3 ± 0.2 (P < 0.05), respectively. The histopathological study revealed that in IE group the degenerative neuronal change was attenuated compared with I group. CONCLUSIONS: These results suggested that rEPO attenuated isoflurane-induced neurodegeneration.

[Controversy in the treatment of acid-base abnormalities].

Sodium bicarbonate has been standard therapy for the treatment of acidosis. In lactic acidosis and hypercapnic acidosis, however, there is no clinical data supporting its effectiveness. We reviewed the literature of the efficacy of sodium bicarbonate on lactic acidosis and hypercapnic acidosis. On both conditions, we have no solid evidence supporting its beneficial effect. Conversely, acidosis or hypercapnia might be protective in acute lung and systemic organ injury. Therefore, the unprepared use of bicarbonate might be harmful in terms of fluid and sodium overload and excess lactate concentrations. According to current literature, we cannot recommend sodium bicarbonate administration for patients with lactic acidosis and hypercapnic acidosis.

[Preanesthetic evaluation of pediatric patients].

Preoperative evaluation of pediatric patients undergoing anesthesia requires specific consideration. Upper respiratory infection and fever are common problems encountered in the otherwise healthy children who are scheduled for minor surgery. Considerations for the preanesthetic evaluation of the patients with asthma or ex-preterm infants are discussed. It is important to provide less stressful environment to patients and to fulfill patients' satisfaction. Fasting time should be minimum. If patients are extremely anxious and feel fear for separation from their parents, anxiolytic medication might be helpful. Parents present at induction may be another option for smooth induction of anesthesia. Children may have received vaccines. Surgery should be planned in accordance with the vaccination program. Several laboratory examinations can be omitted after careful physical examination and interview. Blood count, ECG, or chest X-ray seldom affect the preoperative preparation or anesthetic method for the patients who do not have any particular findings in physical examination. Such examination is not only unnecessary, but gives stress to those patients. In recent years, there have been some reports that anesthesia during infancy affect the development of the brain and causes learning disability or emotional complication. These findings are mainly based on the results of animal experiments and the effect of anesthetics on the developing brain has not been thoroughly confirmed yet in the clinical settings. We need to keep our eyes on the forthcoming research.

[Preoperative evaluation, management and outcome in the elderly patient].

Two principles should be kept in mind when performing preoperative evaluation of the elderly patient. First, we should suspect the disease processes commonly associated with aging. Second, we should assess the degree of functional reserve of specific, pertinent organ systems. Preoperative risk assessment is focused on detailed review from anamnesis and physical examination together with the assessment of functional status. Especially, it is important to examine the cardiovascular and respiratory functions in the elderly patient. Further, this also includes assessment of consumed drugs, physiological function, cognitive function, competency, availability of social support, and sign of depression. Surgical risk and outcome in the elderly patient depend primarily on four factors: age, the patient's physiological status and coexisting disease, whether the surgery is elective or urgent, and the type of procedures.

[Case report : Severe anaphylactic shock followed by positive skin-prick-test to multiple vasoconstrictors].

A 71-year-old woman was scheduled for revision of total hip replacement under general anesthesia. Twenty minutes before entering the operating room, slight urticaria was caused by drop infusion of cefotiam. It was stopped immediately and the patient entered the operating room without any symptoms. Anesthesia was induced and maintained with sevoflurane and remifentanil. After 3 hours, systolic arterial pressure (SAS) dropped to 80 mmHg. Injecting of ephedrine 8 mg was not effective, and we injected a total of 3 mg of methoxamine. Then SAS dropped to 50 mmHg. We injected epinephrine 0.2 mg twice and also started continuous infusion of norepinephrine. Severe skin rash indicated that anaphylactic reaction had occurred. About 20 minutes after starting norepinephrine, the SAS was stabilized. We decided to stop the operation, and the patient was moved to the intensive care unit (ICU). A few hours after entering the ICU, she was extubated and moved to the general ward next day. Skin-prick-tests performed 14 days later indicated that she was allergic to ephedrine, methoxamine, epinephrine, dopamine and a few more drugs.

Protective action of D-ribose against renal injury caused by ischemia and reperfusion in rats with transient hyperglycemia.

Hyperglycemia amplifies the inflammatory state after ischemia/reperfusion (I/R), and activated neutrophils have been implicated in the development of I/R-induced renal injuries. D-ribose is a naturally occurring monosaccharide found in all living cells. In this study, we examined whether D-ribose attenuates I/R-induced renal injury by reducing neutrophil activation in rats with transient hyperglycemia. Male Wistar rats were divided into sham (n = 24), control (n = 64), and D-ribose (n = 32) groups. Rats received intraperitoneal injection of glucose (3 g/kg) 30 min before induction of ischemia to induce transient hyperglycemia. Anesthetized rats underwent right nephrectomy and subsequent occlusion of the left renal artery and vein for 45 min. D-ribose (400 mg/kg) was intravenously administered 30 min before induction of ischemia. D-ribose significantly reduced the degree of the I/R-induced increases in renal concentrations of cytokine-induced neutrophil chemoattractant-1 (a chemotactic factor for the activation of neutrophils and chemotaxis to the site of injury) and myeloperoxidase (an indicator of neutrophils infiltration). D-ribose also reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the corticomedullary junction fields. These results indicate that D-ribose reduces the I/R-induced acute renal injury in rats with transient hyperglycemia, probably by reducing neutrophil activation. D-ribose might thus be useful for surgical procedures, such as renal transplant surgery, under hyperglycemia.

D-ribose attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.

The ischemia/reperfusion (I/R) represents a common pathological mechanism that causes renal injuries. A monosaccharide D-allose has been shown to inhibit neutrophil activation, which is involved in the I/R-induced organ injuries. We therefore examined the role of D-ribose in the I/R-induced renal injury using a rat model. D-ribose, a monosaccharide found in all living cells, serves as a key component of adenosine-5'-triphosphate and nicotinamide adenine dinucleotide. Male Wistar rats were divided into the sham, control and D-ribose groups. In the control and D-ribose groups, rats were subjected to 45 min of left renal ischemia, followed by 24 h of reperfusion, while the I/R procedure was not performed in the sham group. Rats were intravenously administered D-ribose (sham group and D-ribose group, 400 mg/kg) or saline (control group) 30 min before ischemia. Blood urea nitrogen (BUN), serum creatinine and urinary N-acetyl beta-D-glucosaminidase (NAG) were measured as indicators of glomerular function and proximal tubular function. We also measured cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase concentrations to assess neutrophil activation and infiltration, respectively. The tissue sections were scored to evaluate the tubular injury. In the control group, BUN, creatinine, NAG, CINC-1, myeloperoxidase, histological severity score, and number of infiltrating neutrophils were increased following I/R insult, as compared with the sham group. Such increases in biochemical markers, severity score, and infiltrating neutrophils were significantly inhibited in the D-ribose group. Thus, D-ribose ameliorates the I/R-induced renal injury probably by inhibiting neutrophil activation, and may be useful in attenuating the renal injury associated with renal ischemia.

Urinary trypsin inhibitor ameliorates renal tissue oxygenation after ischemic reperfusion in rats.

PURPOSE: In order to determine the mechanism of the protective effect of a urinary trypsin inhibitor (UTI) on renal ischemic reperfusion injury, we measured the tissue oxygen partial pressure pO2 in both the renal cortex and medulla in rats, using electron paramagnetic resonance (EPR) oximetry. METHODS: We allocated the rats to three groups: normal saline (NS) group, a UTI 50,000 U x kg(-1) (LD) group, and a UTI 150,000 U x kg(-1) (HD) group, with the normal saline and UTI being administered 30 min before ischemia. Renal ischemia was achieved by inflating the balloon of a vascular occluder that had been placed around the abdominal aorta just above the bifurcation of the renal artery. Cortical and medullary pO2 were measured every 10 min during ischemia (30 min) and reperfusion (60 min) by EPR oximetry; also, systemic cardiopulmonary parameters were measured. RESULTS: The pO2 in the cortex and medulla decreased to less than 2 mmHg during ischemia in all groups. At 60 min after reperfusion, the pO2 values in the NS group were not fully restored, whereas those in the LD and HD groups were completely restored to the pre-ischemic values. There were no significant differences between the HD and LD groups. There were no differences between any groups in cardiopulmonary parameters. CONCLUSION: Because UTI improved renal oxygenation after reperfusion without changing cardiopulmonary parameters, the pharmacological properties of UTI, such as its renal protection and anti-shock activity, may be explained in part, by this improvement in tissue oxygenation.

The effect of lung expansion and positive end-expiratory pressure on respiratory mechanics in anesthetized children.

BACKGROUND: Imaging studies have shown that general anesthesia in children results in atelectasis. Lung recruitment total lung capacity (TLC) maneuvers plus positive end-expiratory pressure (PEEP) are effective in preventing atelectasis. However, physiological changes in children during general anesthesia have not been elucidated. METHODS: In eight anesthetized and mechanically ventilated children (median age: 3.5 years; range: 2.3-6.5), we measured static respiratory system elastance (E(st)), flow resistance (R(int)), and elastance and resistance components resulting from tissue viscoelasticity (deltaE and deltaR, respectively) using the constant inflow, end-inspiratory occlusion method preceded by TLC maneuvers, both with zero PEEP (ZEEP) and PEEP (5 cm H2O) for comparison. RESULTS: With constant inspiratory flow V(I) and ZEEP, increases in end-inspiratory lung volume above relaxation volume (tidal volume, V(T)) from 8 to 20 mL x kg(-1) resulted in decreases in E(st) from 1.06 to 0.82 cm H2O x mL(-1) x kg, deltaE from 0.16 to 0.09, and R(int) from 0.13 to 0.11 cm H2O x mL(-1) x s x kg, whereas deltaR increased from 0.08 to 0.12 (P < 0.05). Similar relationships were found with PEEP. Increases in V(I) (8 to 26 mL x s(-1) x kg) with constant V(T) and ZEEP resulted in decreases in E(st) from 1.09 to 0.9 and deltaR from 0.17 to 0.06 (P < 0.01), whereas deltaE and R(int) did not change. There was a similar flow and volume dependence of elastance and resistance with PEEP. CONCLUSIONS: The observed steady decreases in E(st) with increasing V(T) (up to 16 mL/kg with PEEP) indicate marked reductions in end-expiratory relaxation volume (functional residual capacity) even with PEEP. Similarity in results with ZEEP and PEEP suggests that TLC-maneuvers and O2-N2 ventilation prevented airway closure throughout the study.

Inhibitory effect of d-allose on neutrophil activation after rat renal ischemia/reperfusion.

D-Allose is one of the rare sugars produced from D-psicose. We examined whether d-allose reduces the extent of rat renal ischemia/reperfusion (I/R) injury by suppressing the activation of neutrophils. The renal concentrations of cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase were significantly increased after renal I/R. These increases were significantly inhibited by D-allose administration. Furthermore, D-allose significantly inhibited the increase in the concentrations of blood urea nitrogen (BUN), creatinine, N-acetyl beta-D-glucosaminidase (NAG) and histopathologic changes after renal I/R. These findings strongly suggest that D-allose protects against I/R-induced renal injury by inhibiting the activation of neutrophils that play an important role in I/R-induced renal injury. These findings may have important implications in understanding the biologic functions of D-allose. D-Allose may prove useful in renal surgery and transplantation.

Urinary trypsin inhibitor reduces inflammatory response in kidney induced by lipopolysaccharide.

Human urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used in Japan as a drug for patients with acute inflammatory disorders such as septic shock and pancreatitis. Lipopolysaccharide (LPS) triggers the sepsis syndrome by activating monocytes to produce proinflammatory cytokines, including tumor necrosis factor alpha (TNFalpha), which potently stimulate the activation of neutrophils. The inhibitory mechanism of UTI on the systemic inflammatory response induced by the intraperitoneal injection of LPS in the kidney is unclear. This study was undertaken to examine the inhibitory effects of UTI on renal injury associated with the systemic inflammatory response induced by LPS stimulation, with emphasis on systemic TNFalpha and the activation of neutrophils in rat kidney. The systemic inflammatory response syndrome was induced by LPS treatment. Serum and renal TNFalpha, renal cytokine-induced neutrophil chemoattractant-1 (CINC-1) and myeloperoxidase (MPO) levels, as well as renal function after LPS stimulation, were evaluated. UTI (50,000 U/kg) inhibited LPS-induced increases in the serum and renal tissue levels of TNFalpha, as well as the renal tissue levels of CINC-1 and MPO after LPS stimulation. UTI (50,000 U/kg) also inhibited the production of serum TNFalpha associated with the systemic inflammatory response syndrome induced by LPS stimulation, thereby attenuating neutrophil infiltration into renal tissues and subsequent neutrophil-mediated renal injury. These findings may have important implications in understanding the biologic functions of UTI. UTI may prove useful in protecting against acute renal injury associated with a systemic inflammatory response.

[Reappraisal of perioperative fluid therapy in children].

Two recently recognized issues are reviewed ; one is a hospital acquired hyponatremia in children treated with intravenous hypotonic maintenance fluids and the other is the pros and cons of glucose addition to these fluids. Children in the perioperative period are at risk for nonosmotic secretion of ADH and stress-induced insulin resistance, which necessitate reducing the volume of maintenance fluid to half the previously recommended volume, and the concentration of additive glucose to approximately 2%. While isotonic fluids are recommended intraoperatively, controversies still exist on the constitution of maintenance fluids in the postoperative period, where the choice of an isotonic solution should be more pertinent to that of a hypotonic solution, but evidence is weak ; further investigations are needed to make a decision.