High preoperative serum strontium levels increase the risk of acute kidney injury after cardiopulmonary bypass.

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiac surgeries. The incidence of AKI after cardiac surgeries using cardiopulmonary bypass (CPB-AKI) is high, emphasizing the need to determine strategies to prevent CPB-AKI. This study investigates the correlation between CPB-AKI and trace metal levels in clinical and animal studies. METHODS: Samples and clinical data were obtained from 74 patients from the Nagoya City University Hospital and Okazaki City Hospital. Blood samples were collected before, immediately after, and 2 h after CPB withdrawal. Trace metal levels were measured using inductively coupled plasma mass spectrometry. Sr or vehicle treatment was orally administered to the rats to determine if Sr was associated with CPB-AKI. After the treatment, ischemia-reperfusion (IR) injury was induced, and serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. RESULTS: In this clinical study, the incidence of CPB-AKI was found to be 28% (21/74). The body mass index and estimated glomerular filtration rate were significantly different in patients with AKI. The intensive care unit and hospital stay were longer in AKI patients than in non-AKI patients. The Na, Fe, and Sr levels were significantly higher in AKI patients before CPB. Also, Fe and Sr were higher immediately after CPB withdrawal, and Sr was higher 2 h after CPB withdrawal in AKI patients. Animal studies showed that Sr-treated rats had significantly increased SCr and BUN levels than vehicle-treated rats at 24 h post-IR injury. CONCLUSIONS: High preoperative serum Sr levels may be associated with CPB-AKI.

Efficacy of intravenous dexamethasone on postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid: a systematic review and meta-analysis.

PURPOSE: Intravenous dexamethasone is recommended in elective caesarean delivery to decrease postoperative pain. However, the efficacy of spinal anaesthesia with an intrathecal long-acting opioid such as morphine or diamorphine for caesarean delivery has not been systematically investigated. METHODS: We searched all randomized controlled trials (RCTs) of pregnant women undergoing caesarean delivery under spinal anaesthesia with an intrathecal morphine or diamorphine via MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov on May 18, 2022. Primary outcomes were time to first rescue analgesia, consumption of oral morphine equivalents, and incidence of drug-related adverse reactions. We evaluated the risk of bias for each outcome using the Risk of Bias 2. We conducted a meta-analysis using a random effects model. We evaluated the certainty of evidence with the GRADE approach. RESULTS: Five RCTs (455 patients) were included. The results of intravenous dexamethasone were as follows: time to first rescue analgesia (mean difference [MD] 0.99 h, 95% confidence interval [CI] - 0.86 to 2.84; very low certainty) and consumption of oral morphine equivalents (MD - 6.55 mg, 95% CI - 17.13 to 4.02; moderate certainty). No incidence of drug-related adverse reactions was reported (very low certainty). CONCLUSION: The evidence was very uncertain about the efficacy of intravenous dexamethasone on time to first rescue analgesia and the incidence of drug-related adverse reactions. Intravenous dexamethasone probably reduces the consumption of oral morphine equivalents. Anaesthesiologists might want to consider intravenous dexamethasone for postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid.

Comparison of disinfection effect between benzalkonium chloride and povidone iodine in nasotracheal intubation: a randomized trial.

BACKGROUND: Nasotracheal intubation can potentially result in microbial contamination from the upper respiratory tract to the lower respiratory tracts. However, an ideal nasotracheal disinfection method is yet to be determined. Therefore, we compared the disinfection effects between benzalkonium chloride and povidone iodine in nasotracheal intubation. METHODS: Overall, this study enrolled 53 patients aged 20-70 years who were classified into classes 1 and 2 as per American Society of Anesthesiologists-physical status and were scheduled to undergo general anesthesia with NTI. Patients who did not give consent (n = 2) and who has an allergy for BZK or PVI were excluded from the study. The patients were randomly divided into two groups on the basis of the disinfection method: BZK (n = 26, one patient was discontinued intervention) and PVI (n = 25). 50 patients were assessed finally. The subjects' nasal cavities were swabbed both before (A) and after disinfection (B), and the internal surface of the endotracheal tube was swabbed after extubation (C). The swabs were cultured on Brain heart infusion agar and Mannitol salt agar. The number of bacteria per swab was determined and the rates of change in bacterial count (B/A, C/B) were calculated. The growth inhibitory activity of the disinfectants on Staphylococcus aureus were also investigated in vitro. RESULTS: Although the initial disinfection effects (B/A) were inferior for benzalkonium chloride compared with those for povidone iodine, the effects were sustained for benzalkonium chloride (C/B). In the in vitro growth inhibitory assay against S. aureus, benzalkonium chloride showed higher inhibitory activity than povidone iodine. CONCLUSION: Although both disinfectants were inactivated or diffused/diluted over time, benzalkonium chloride maintained the threshold concentration and displayed antimicrobial effects longer than povidone iodine; therefore, benzalkonium chloride appeared to show a better sustained effect. Benzalkonium chloride can be used for creating a hygienic nasotracheal intubation environment with sustained sterilizing effects. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000029645 ). Registered 21 Oct 2017.

Pharmacokinetics of mycophenolic acid in children with clinically stable idiopathic nephrotic syndrome receiving cyclosporine.

BACKGROUND: The suitable dosage regime of mycophenolate mofetil (MMF) based on the pharmacokinetics of mycophenoric acid (MPA) for pediatric patients with idiopathic nephrotic syndrome (INS) is controversial. The pharmacokinetics of MPA is influenced by renal function, serum albumin concentration, and concomitant medications, especially calcineurin inhibitors. This study analyzed the pharmacokinetics of MPA in clinically stable children with INS receiving cyclosporine (CyA). METHODS: This retrospective study enrolled children with INS receiving MMF (Cellcept®) (30-40 mg/kg/day in two divided doses) combined with CyA (Neoral®) without relapse and renal dysfunction. Pharmacokinetic parameters, including the area under the concentration-time curve (AUC) calculated by the trapezoid method, were calculated from seven serial blood samples. RESULTS: Thirty-two patients (22 males) of median age 11.0 years were included; 32 pharmacokinetic studies were performed. The median MMF dose was 16.2 mg/kg/time or 470.4 mg/m2/time. The median AUC0-12 was 44.3 ng h/mL. AUC0-12 of all patients showed excellent correlations with C2 (r 2  = 0.6405, P < 0.0001), resulting in a regression formula of AUC0-12 = 21.971 + 2.6059 C2. Comparisons of dose/body weight-normalized AUC0-12 values among age groups showed a lower value in the youngest group (≤5 years). CONCLUSION: In children with clinically stable INS receiving CyA, C2 monitoring was the most useful single parameter for estimating MPA pharmacokinetics. Younger children required higher MMF doses.

Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol.

BACKGROUND: This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome. METHODS: Cyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high-dose steroid therapy. CsA was maintained at an area under the whole blood concentration-time curve up to 4 h after dose (AUC0-4 ) of 1500 and 2000 ng·h/mL in steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. Ninety-one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission. RESULTS: In the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid-sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped. CONCLUSIONS: Treatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS.

Pharmacokinetics of glycopeptide antibiotics in children.

Vancomycin (VAN) and teicoplanin (TEIC) are the glycopeptide antimicrobials commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection in pediatric patients. This study examined the relationship between the initial doses of glycopeptides and the trough serum concentrations of drugs in children, with the intent to determine their optimal dosing. Consecutive patients between 0 and 18 years of age, who between June 2003 and December 2010 were treated with VAN (n = 50) or TEIC (n = 187) for >48 h, were enrolled in this study. Patients were classified into three groups depending on the dose administered: lower than, equal to, or higher than the recommended dosage by each package insert. The patient's age, body weight, dose of antimicrobial administered during the first 24 h, median trough serum concentrations between 48 and 72 h after the onset of treatment, and serum creatinine concentrations before and 3 and 7 days after its administration were recorded. Median trough concentrations for VAN and TEIC in the three dosage groups were 8.0, 8.5, and 13.0 µg/ml, and 11.8, 13.0, and 17.7 µg/ml, respectively. The median serum creatinine concentrations did not rise significantly between baseline and 3 and 7 days after the onset of treatment in any treatment group. Therapeutic serum concentrations of VAN and TEIC to treat MRSA infections, 15-20 and ≥20 µg/ml, respectively, were rarely reached by the administration of standard doses of drugs for children.

3M microfoam™ surgical tape prevents nasal pressure injury associated with nasotracheal intubation: A randomized double-blind trial.

BACKGROUND: 3M microfoam™ surgical tape (3ST: 3M Japan Limited) is used for pressure wound control of medical equipment. It is cushioned and can be fitted to any body part. Here we investigated whether 3ST prevents nasal pressure injury associated with nasotracheal intubation (NTI). METHODS: We conducted a prospective, randomized double-blind study, enrolling 63 patients aged 20 to 70 years, who underwent general anesthesia with NTI. They were divided into 2 groups; those treated with 3ST (group S; n = 31) and control (group C; n = 31). After NTI and before securing the nasotracheal tube, a 35 × 25 mm 3ST was used to protect the nasal wing in group S, and the nasotracheal tube was fixed in place after NTI without protection in group C. The primary outcome was the presence or absence of nasal pressure injury after extubation. The Chi-Square test was used to assess the association between the 2 categorical variables. RESULTS: Nasal pressure injury was observed in 7 and 19 patients from groups S and C, respectively, representing a significant difference between the 2 groups (24.1% vs 67.8%, P = .001). Remarkably, none of the patients developed ulcers. CONCLUSION: 3ST prevents nasal pressure injury associated with NTI.

Comparison of Emergence Agitation Scale Scores and Creatine Kinase Levels After General Anesthesia in Children: A Prospective Cohort Study.

Introduction A simple indicator of muscle damage is creatine kinase (CK). Although CK elevation is informative for malignant hyperthermia, no study has examined the relationship between the anesthetically awake state and CK in children. We aimed to prospectively examine the relationship between the awakening state and CK on the day after surgery in children who have undergone anesthesia with volatile inhalation anesthetics. Methods The study included 119 patients aged 0-15 years and scheduled to undergo general anesthesia for cleft lip and palate-related surgery. Emergence agitation (EA) was assessed after completion of general anesthesia using the five-point EA scale, and patients were divided into the following five groups according to the EA score: EA1, EA2, EA3, EA4, and EA5. The primary outcome was ΔCK (comparison of CK values one week prior to surgery to CK values on the day after surgery) in each EA group. The secondary outcome was ΔCK when the EA score was divided into the following two groups: EA ≤2 (EA score of 1 or 2) and EA ≥3 (EA score of 3, 4, or 5). Results The median ΔCK values in the EA1 to EA5 groups were 3 (quartile -19~9), 5 (-32~88), 99.5 (-18~190.5), 121 (29~219.5), and 144 (41~340.5), respectively, indicating a statistically significant difference overall. Statistically significant differences were also observed between the EA1 and EA4 groups and between the EA2 and EA4 groups. The median ΔCK values in the EA ≤2 and EA ≥3 groups were 3 (quartile -27~85) and 108 (23.5~206.7), respectively, indicating a statistically significant difference. Conclusion The results of this study revealed that a higher EA score at the time of anesthesia awakening is associated with a larger ΔCK, indicating that a high CK level on the day after surgery is highly related to the state of the patient upon awakening.

Detailed characterization of Mirafiori lettuce virus-resistant transgenic lettuce.

Lettuce big-vein disease is caused by Mirafiori lettuce virus (MiLV), which is vectored by the soil-borne fungus Olpidium brassicae. A MiLV-resistant transgenic lettuce line was developed through introducing inverted repeats of the MiLV coat protein (CP) gene. Here, a detailed characterization study of this lettuce line was conducted by comparing it with the parental, non-transformed 'Kaiser' cultivar. There were no significant differences between transgenic and non-transgenic lettuce in terms of pollen fertility, pollen dispersal, seed production, seed dispersal, dormancy, germination, growth of seedlings under low or high temperature, chromatographic patterns of leaf extracts, or effects of lettuce on the growth of broccoli or soil microflora. A significant difference in pollen size was noted, but the difference was small. The length of the cotyledons of the transgenic lettuce was shorter than that of 'Kaiser,' but there were no differences in other morphological characteristics. Agrobacterium tumefaciens used for the production of transgenic lettuce was not detected in transgenic seeds. The transgenic T(3), T(4), and T(5) generations showed higher resistance to MiLV and big-vein symptoms expression than the resistant 'Pacific' cultivar, indicating that high resistance to lettuce big-vein disease is stably inherited. PCR analysis showed that segregation of the CP gene was nearly 3:1 in the T(1) and T(2) generations, and that the transgenic T(3) generation was homozygous for the CP gene. Segregation of the neomycin phosphotransferase II (npt II) gene was about 3:1 in the T(1) generation, but the full length npt II gene was not detected in the T(2) or T(3) generation. The segregation pattern of the CP and npt II genes in the T(1) generation showed the expected 9:3:3:1 ratio. These results suggest that the fragment including the CP gene and that including the npt II gene have been integrated into two unlinked loci, and that the T(1) plant selected in our study did not have the npt II gene. DNA sequences flanking T-DNA insertions in the T(2) generation were determined using inverse PCR, and showed that the right side of the T-DNA including the npt II gene had been truncated in the transgenic lettuce.

Determination of Lycopene Concentration in Fresh Tomatoes by Spectrophotometry: A Collaborative Study.

BACKGROUND: Lycopene has been the object of considerable research attention recently, and the effects of the intake of lycopene, or of tomato products, have been studied in various ways. In Japan, interest in the health-promoting function of food components has increased. OBJECTIVE: Developing a method to determine lycopene contents in tomato that meets the Japanese Agricultural Standard (JAS). METHOD: In the proposed JAS method, the test sample consists of fresh tomatoes; a hexane-acetone mixture is utilized as the extraction solvent. A collaborative study was conducted to evaluate the interlaboratory performance of the method. RESULTS: Ten laboratories participated and analyzed six test materials characterized by a lycopene content between 39 and 170 mg/kg as blind duplicates. After removing statistical outliers, RSDr ranged from 1.2 to 3.0% and RSDR ranged from 2.4 to 4.2%. The HorRat values were calculated and found to be in the 0.26-0.49 range. CONCLUSIONS: The method for determining the lycopene content in tomato was evaluated by means of a collaborative study, and the reproducibility of this method was found to be acceptable. HIGHLIGHTS: Intended for standardization in Japan, a method to determine lycopene content in tomato has been developed and shown to have acceptable precision in a collaborative study.

General Anesthetic Management of a Child With Horseshoe Lung and Left Lung Hypoplasia for Cheiloplasty: A Case Report.

Horseshoe lung is an extremely rare congenital malformation in which the right and left lungs are fused due to stenosis of the lung parenchyma. In anesthetic management, it is important to avoid hypoxemia and hypercapnia caused by a decline in lung capacity and functional residual capacity. A 3-year-old boy with horseshoe lung and left lung hypoplasia was scheduled to undergo cheiloplasty. Regarding respiratory management, to prevent hypoxemia and hypercapnia, we avoided intraoperative peripheral airway obstruction with positive end-expiratory pressure, set a long inspiratory phase time for sufficient alveolar expansion, and maintained sufficient gas exchange in lungs with low reserve capacity.

[6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions.

Reactive nitrogen species (RNS), such as nitric oxide (NO) and its derivatives, e.g. peroxynitrite (ONOO-), have been proposed as being able to influence signal transduction and cause DNA damage, contributing to carcinogenic processes. In this study, the effect of [6]-gingerol, a pungent phenolic compound present in ginger (Zingiber officinale Roscoe), on NO synthesis in lipopolysaccharide (LPS)-activated J774.1 macrophages was tested, and the protective ability of this compound against peroxynitrite-mediated oxidation and nitration reactions were evaluated. [6]-Gingerol exhibited dose-dependent inhibition of NO production and significant reduction of inducible NO synthase (iNOS) in LPS-stimulated J774.1 cells. Moreover, [6]-gingerol effectively suppressed peroxynitrite-induced oxidation of dichlorodihydrofluorescein, oxidative single strand breaks in supercoiled pTZ 18U plasmid DNA, and formation of 3-nitrotyrosine in bovine serum albumin (BSA) and J774.1 cells. Our results indicate that [6]-gingerol is a potent inhibitor of NO synthesis and also an effective protector against peroxynitrite-mediated damage.

Combination of lipids and emulsifiers enhances the absorption of orally administered quercetin in rats.

The effects of lipids, emulsifiers, and ethanol on the absorption of orally administered quercetin in rats were investigated for its efficient intestinal absorption. Rats were administered 150 micromol/kg quercetin in water supplemented with lipids and/or emulsifiers, or ethanol, and blood was collected from the tail for 6 h after administration. Co-administration of lipids such as lecithin and soybean oil or emulsifiers including sucrose fatty acid ester, polyglycerol fatty acid ester, and sodium taurocholate had no statistically significant effects on quercetin absorption, although these constituents rather increased the accumulation of conjugated forms of quercetin and those of isorhamnetin in rat plasma. However, the combination of lipids and emulsifiers enhanced the absorption of quercetin significantly. Thirty and fifty percent (v/v) of the ethanol in the vehicle raised the efficiency of quercetin absorption in a concentration-dependent manner. Quercetin absorption-enhancing effects of these constituents seemed to be affected by quercetin's solubility in respective vehicles used for the administration. Ethanol is not helpful for the effective absorption of quercetin, as a high concentration is required. In conclusion, a combination of lipids and emulsifiers is necessary for enhancing quercetin absorption.

Clinical significance of IgM and C1q deposition in the mesangium in pediatric idiopathic nephrotic syndrome.

BACKGROUND: In biopsy-proven idiopathic nephrotic syndrome (INS), immunoglobulin M (IgM) and C1q are occasionally deposited in the mesangium. In pediatric nephrology, the significance of mesangial IgM or C1q deposits is controversial, based on previous reports. The aim of this study was to explore the clinical significance of mesangial IgM and/or C1q deposits in pediatric INS patients, especially the initial responses to steroids and final outcomes. METHODS: We reviewed the clinical courses of 70 children with steroid-dependent or steroid-resistant INS who underwent a renal biopsy at our hospital from 1998 to 2010. There were 30 mesangial IgM immunofluorescence (IF)-positive (IgM+) children. The IgM+ group was compared with the IgM IF-negative (IgM-) group. In addition, we reviewed the clinical characteristics of 8 mesangial C1q IF-positive (C1q+) children. RESULTS: Of the 30 IgM+ children, 10 (33.3%) were steroid-dependent (IgM- group: 18/40, 45%) and 14 (46.7%) were steroid-resistant (IgM- group: 11/40, 27.5%; p<0.05). Although a high frequency of steroid-resistant INS was observed in the IgM+ group, the efficacy of cyclosporine (CyA) therapy was relatively good (all 14 steroid-resistant children obtained complete or partial remission). Moreover, all 8 C1q+ children obtained complete remission after CyA therapy, although they had a high frequency of steroid resistance (7/8, 87.5%), and 1 child was steroid-dependent. CONCLUSIONS: Our results indicate that, regardless of the histological pattern (minimal change disease, focal segmental glomerulosclerosis or diffuse mesangial hypercellularity), children with IgM+ and/or C1q+ INS have good responses to CyA. IgM+ and/or C1q+ may be markers of the initial disease severity of INS.

Mechanism of inhibition of peroxynitrite-induced oxidation and nitration by [6]-gingerol.

[6]-Gingerol potently inhibits peroxynitrite-induced oxidation and nitration reactions, but its mechanism of action is unclear. In order to discover the mechanism of inhibition, [6]-gingerol was reacted with peroxynitrite and the reaction mixture was analyzed using HPLC. The HPLC chromatogram showed one novel peak, indicative of the formation of a reaction product between [6]-gingerol and peroxynitrite. This compound was purified and identified as a symmetrical dimer of [6]-gingerol covalently linked at the aromatic ring. It has been assumed that this dimer is generated from a phenoxyl radical intermediate produced from [6]-gingerol via one-electron oxidation by peroxynitrite-derived radicals. We propose a mechanism in which [6]-gingerol scavenges peroxynitrite-derived radicals and consequently inhibits peroxynitrite-induced oxidation and nitration reactions.

Enhancing effect of lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats.

The effects of co-ingested lipids and emulsifiers on the accumulation of quercetin metabolites in blood plasma after the short-term ingestion of onion by rats were investigated. Plasma extracts of rats that had been fed onion-containing diets for one and two weeks were analyzed by HPLC with electrochemical detection after a treatment with sulfatase/beta-glucuronidase. Almost all of the quercetin metabolites in the plasma were sulfate/glucuronide conjugates of quercetin and isorhamnetin. More than 4.6% (w/w) of soybean oil in the diets significantly enhanced the accumulation of quercetin metabolites in the plasma. Fish oil and beef tallow increased this to an extent similar to that with soybean oil, and lecithin was more effective than the other three lipids. Two emulsifiers, sodium caseinate and sucrose fatty acid ester, also showed an enhancing effect on the accumulation of quercetin metabolites. These results indicate that co-ingested lipids and emulsifiers could enhance the bioavailability of quercetin glucosides in onion.