Isolation and Structure Determination of New Pyrones from Dictyostelium spp. Cellular Slime Molds Coincubated with Pseudomonas spp.

Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, we revealed the structural diversity of secondary metabolites. Cellular slime molds grow by feeding on bacteria, such as Klebsiella aerogenes and Escherichia coli, without using medium components. Although changing the feeding bacteria is expected to affect dramatically the secondary metabolite production, the effect of the feeding bacteria on the production of secondary metabolites is not known. Herein, we report the isolation and structure elucidation of clavapyrone (1) from Dictyostelium clavatum, intermedipyrone (2) from D. magnum, and magnumiol (3) from D. intermedium. These compounds are not obtained from usual cultural conditions with Klebsiella aerogenes but obtained from coincubated conditions with Pseudomonas spp. The results demonstrate the diversity of the secondary metabolites of cellular slime molds and suggest that widening the range of feeding bacteria for cellular slime molds would increase their application potential in drug discovery.

A case of Legionella pneumonia after robot-assisted radical prostatectomy.

Introduction: Postoperative Legionella pneumonia is very rare. Case presentation: A 71-year-old male patient with prostate cancer (cT2bN0M0) underwent a robotic-assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable. Conclusion: When bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

Older versus younger patients in robot-assisted radical cystectomy with intracorporeal ileal conduit comparing safety and clinical outcomes.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted radical cystectomy using an intracorporeal ileal conduit in older compared to younger patients. METHODS: We retrospectively analyzed 122 patients who underwent robot-assisted radical cystectomy with an intracorporeal ileal conduit at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2012 and 2022. Patients were categorized into two groups: older (age ≥ 75 years; n = 53) and younger (age < 75 years; n = 69). Perioperative outcomes, complications, recurrence-free survival, cancer-specific survival, and overall survival were compared between the cohorts. RESULTS: The groups had no significant differences in perioperative outcomes, such as estimated blood loss, operative time, and blood transfusion rate. However, hospital stay was longer in the older patients than in the younger group (19 vs. 16 days; p < 0.001). The 30-day minor and major complication rates were 33.3% and 13.0%, respectively, for the younger group and 50.9% and 9.4% for the older group (p = 0.11). Urinary tract infection and bowel ileus were the most common complications in both groups. No significant differences were observed in recurrence-free survival, cancer-specific survival, and overall survival between the groups (p = 0.58, p = 0.75, and p = 0.78), and subgroup analysis in ≥cT3 revealed the older group tended to have poorer cancer-specific survival and overall survival (p = 0.07 and p = 0.01). Multivariate analysis indicated that older age was not associated with high-grade complications and cancer-specific survival. CONCLUSIONS: Robot-assisted radical cystectomy with an intracorporeal ileal conduit is a safe and effective treatment option for older patients.

Robot-assisted retroperitoneal lymph node dissection: Initial experience in Japan.

For patients with testicular tumors who need the surgical management, open retroperitoneal lymph node dissection (O-RPLND) is considered the gold standard treatment. However, recently, robot-assisted RPLND (R-RPLND) has gained popularity as a minimally invasive therapy alternative to O-RPLND and laparoscopic RPLND. Here, we report the case of a 32-year-old man presenting with a left testicular teratoma with several enlarged left para-aortic lymph nodes. After the orchiectomy, the patient underwent R-RPLND with an operation time of 279 min, console time of 189 min, bleeding volume of 59 mL, and no significant complications, resulting in a successful outcome. To the best of our knowledge, this is the first reported case of R-RPLND in Japan. Based on our experience, R-RPLND may provide safe and effective outcomes; however, further research is required before the widespread implementation of this technique.

The Role of Lymph Node Dissection in Patients With Muscle-Invasive Bladder Cancer Who Underwent Radical Cystectomy Following Neoadjuvant Chemotherapy.

BACKGROUND: The interaction between lymph node dissection (LND) during radical cystectomy (RC) and neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the role of LND in patients undergoing RC after NAC. PATIENTS AND METHODS: We retrospectively analyzed 259 patients with muscle-invasive bladder cancer (MIBC) who underwent RC following NAC at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2010 and 2022. Baseline characteristics, pathological outcomes, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between propensity score (PS)-matched cohorts. RESULTS: PS matching analysis resulted in 94 matched pairs from the adequate (standard or extended template) and inadequate (limited template or unilateral- or no-LND) LND groups. The median number of dissected nodes was significantly higher in the adequate LND group than in the inadequate LND group (19 vs. 5, P < .001). Similarly, a higher pathological node-positive rate (ypN+) was observed in the adequate group than in the inadequate group (18.1% vs. 7.4%, P = .03). The adequate LND group identified more ypN+ with ≤ ypT1 cases than the inadequate group (4 vs. 1). There were no statistically significant differences between the adequate and inadequate groups in RFS (P = .94), CSS (P = .54), and OS (P = .65). Subgroup analysis also showed comparable survival rates, even in patients with ≥ pT3 or cN+ disease. ypN+ was an independent predictor of OS in the Cox regression analysis, while adequate LND and the number of lymph nodes removed (≥10 or ≥15) were not associated with survival. CONCLUSIONS: Although adequate LND did not show a significant therapeutic effect in RC after NAC, adequate LND may have an important diagnostic role in detecting ypN+, which is a robust predictor, and is a useful biomarker to perform appropriate adjuvant immunotherapy especially in ≤ ypT1 cases.

Comparing pentafecta outcomes between nerve sparing and non nerve sparing robot-assisted radical prostatectomy in a propensity score-matched study.

Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levels > 0.2 ng/mL after RARP; 90-day Clavien-Dindo complications ≤ 3a; and a negative surgical pathologic margin. The median follow-up period was 61.3 months (IQR 6-159 months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51-6.9), p < 0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31-6.37, p < 0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14-13.36, p < 0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (p < 0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice.

Total Cell-Free DNA as a Noninvasive Biomarker of a Delayed Graft Function After Kidney Transplantation From Donors After Cardiac Death.

BACKGROUND: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. STUDY DESIGN AND METHOD: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. RESULTS: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05). CONCLUSION: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

Robot-assisted radical nephrectomy with inferior vena cava thrombectomy: a case report.

Background: Recently, robot-assisted surgery has been widely used to treat several urological cancers. Robot-assisted radical nephrectomy (RARN) was approved by the health insurance system in April 2022; however, RARN with inferior vena cava tumor thrombectomy (IVCTT) is still challenging. Also, its safety and feasibility have not yet been established owing to lack of literature, especially in Japan. Case Description: We performed RARN with IVCTT in four patients between April 2022 and March 2023 at Fujita Health University Hospital. To reduce the risk of tumor embolism and major hemorrhage, an "IVC-first, kidney-last" robotic technique was developed. The safety and feasibility of RARN with IVCTT were evaluated by assessing the perioperative outcomes. Three women and one man were enrolled in this study. The median age was 72 years, and the tumor was on the right side in all cases. According to the Mayo Clinic thrombus classification, two patients were classified as level I, and the others were classified as level II. The two patients at level I did not undergo presurgical treatments, whereas the others at level II underwent presurgical treatments, which were combinations of tyrosine kinase inhibitors and immune-checkpoint inhibitors. The median operation and console times were 341 and 247 min, respectively. The median bleeding volume was 577 mL, and no complications beyond grade III of the Clavien-Dindo classification were observed. The median length of postoperative hospital stay was 10 days. Conclusions: Although the sample size was relatively small, we demonstrated the safety and feasibility of RARN with IVCTT in the Japanese population.

Versatile live-attenuated SARS-CoV-2 vaccine platform applicable to variants induces protective immunity.

Live-attenuated vaccines are generally highly effective. Here, we aimed to develop one against SARS-CoV-2, based on the identification of three types of temperature-sensitive (TS) strains with mutations in nonstructural proteins (nsp), impaired proliferation at 37°C-39°C, and the capacity to induce protective immunity in Syrian hamsters. To develop a live-attenuated vaccine, we generated a virus that combined all these TS-associated mutations (rTS-all), which showed a robust TS phenotype in vitro and high attenuation in vivo. The vaccine induced an effective cross-reactive immune response and protected hamsters against homologous or heterologous viral challenges. Importantly, rTS-all rarely reverted to the wild-type phenotype. By combining these mutations with an Omicron spike protein to construct a recombinant virus, protection against the Omicron strain was obtained. We show that immediate and effective live-attenuated vaccine candidates against SARS-CoV-2 variants may be developed using rTS-all as a backbone to incorporate the spike protein of the variants.

Robotic surgery for pelvic organ prolapse with complete bladder eversion.

Introduction: Pelvic organ prolapse with complete bladder eversion is extremely rare. Case presentation: An 82-year-old woman was diagnosed with uterine prolapse 3 years ago and underwent occasional urethral catheter placement for difficulty in micturition. She presented with vulvar bleeding and prolapsed uterus from the vagina. Pelvic examination revealed uterine prolapse and a 65 × 65-mm red mass ventrally with urinary outflow. Contrast medium leakage from the vulvar mass and guidewire observed on antegrade pyeloureterography indicated pelvic organ prolapse with complete bladder eversion. Manual reduction of the everted bladder, robotic sacrocolpopexy, and bladder neck reconstruction was performed. However, eversion recurred 10 months postoperatively. Subsequently, robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed. There was no recurrence postoperatively. Conclusion: Robotic Burch colposuspension, cystopexy to the rectus fascia, bladder neck reconstruction, colpoclesis, and cystostomy were performed for complete bladder eversion.

Functional Outcomes after Selective Clamping in Robot-Assisted Partial Nephrectomy.

This study aimed to assess the risks and benefits of selective clamping in robot-assisted partial nephrectomy (RAPN). We retrospectively analyzed 372 patients who had undergone RAPN at our hospital between July 2010 and March 2021. After propensity score matching between the full and selective clamping groups, perioperative outcomes and postoperative preservation ratio of the estimated glomerular filtration rate (eGFR) were compared at 6 and 12 months of follow-up. After propensity score matching, we evaluated 47 patients from each group. While no significant differences were observed in surgical time, warm ischemia time, or incidence rates of all grades of complications between the two cohorts, the estimated blood loss (EBL) was significantly lower in the full clamping group than in the selective clamping group (30 vs. 60, p = 0.046). However, no significant intergroup differences were observed in the postoperative preservation ratio of eGFR at 6 or 12 months of follow-up (full clamping 94.0% vs. selective clamping 92.7%, p = 0.509, and full clamping 92.0% vs. selective clamping 91.6%, p = 0.476, respectively). Selective clamping resulted in higher EBL rates than did full clamping in RAPN. However, selective clamping provided no renal functional advantage over full clamping in our propensity-score-matched cohort.

Alanine-Serine-Cysteine Transporter 2 Inhibition Suppresses Prostate Cancer Cell Growth In Vitro.

Alanine-serine-cysteine transporter 2 (ASCT2) has been associated with increased levels of metabolism in various malignant tumors. However, its biological significance in the proliferation of prostate cancer (PCa) cells remains under investigation. We used the cBioPortal database to assess the effect of ASCT2 expression on the oncological outcomes of 108 PCa patients. To evaluate the function of ASCT2 in castration-sensitive PCa (CSPC) and castration-resistant PCa (CRPC), LNCaP cells and the ARV7-positive PCa cell line, 22Rv1, were assessed using cell proliferation assays and Western blot analyses. The ASCT2 expression level was associated with biochemical recurrence-free survival after prostatectomy in patients with a Gleason score ≥ 7. In vitro experiments indicated that the growth of LNCaP cells after combination therapy of ASCT2 siRNA and enzalutamide treatment was significantly reduced, compared to that following treatment with enzalutamide alone or ASCT2 siRNA transfection alone (p < 0.01, 0.01, respectively). After ASCT2 inhibition by siRNA transfection, the growth of 22Rv1 cells was significantly suppressed as compared with negative control siRNA via downregulation of ARV7 both in fetal bovine serum and androgen-deprivation conditions (p < 0.01, 0.01, respectively). We demonstrated that ASCT2 inhibition significantly reduced the proliferation rates of both CSPC and CRPC cells in vitro.

Nutritional Assessment of Hospital Meals by Food-Recording Applications.

Mobile food records are currently used to determine the nutrition of healthy subjects. To determine the accuracy of such records, we evaluated the nutritional composition of a test meal (noodles and fruit juice) and a hospital meal (Japanese set meal) using two types of mobile food records. Eighteen healthy subjects (2 males and 16 females) were enrolled. Using these diets and validated nutrient-composition information, we evaluated the accuracy of the dietary assessments made by two dietary-record applications, Asken® and Calomeal®, over 5 days. For the test meal, the values provided by the two applications were close to the actual values. In contrast, for the hospital meal, the values provided by the two applications were approximately 1.5 times higher than the actual values. A linear-mixed-model analysis showed that the total energy, carbohydrate, and salt contents were significantly overestimated in the hospital meal. Protein also tended to be overestimated, while the fat content was not significantly overestimated. Furthermore, the total energy and fat contents increased significantly over time. No association with age was observed. A comparison of the coefficients of variation (CVs) for each nutrient in the hospital meal indicated that the fat levels were significantly higher than those in the test meal. In conclusion, the accuracy of mobile food records depends on the type of meal. Our data will provide lessons for the use of meal-recording applications in special cases, such as hospital food.

Novel Intraoperative Navigation Using Ultra-High-Resolution CT in Robot-Assisted Partial Nephrectomy.

To assess the perioperative and short-term functional outcomes of robot-assisted partial nephrectomy (RAPN) with intraoperative navigation using an ultra-high-resolution computed tomography (UHR-CT) scanner, we retrospectively analyzed 323 patients who underwent RAPN using an UHR-CT or area-detector CT (ADCT). Perioperative outcomes and the postoperative preservation ratio of estimated glomerular filtration rate (eGFR) were compared. After the propensity score matching, we evaluated 99 patients in each group. Although the median warm ischemia time (WIT) was less than 25 min in both groups, it was significantly shorter in the UHR-CT group than in the ADCT group (15 min vs. 17 min, p = 0.032). Moreover, the estimated blood loss (EBL) was significantly lower in the UHR-CT group than in the ADCT group (33 mL vs. 50 mL, p = 0.028). However, there were no significant intergroup differences in the postoperative preservation ratio of eGFR at 3 or 6 months of follow-up (ADCT 91.8% vs. UHR-CT 93.5%, p = 0.195; and ADCT 91.7% vs. UHR-CT 94.0%, p = 0.160, respectively). Although no differences in short-term renal function were observed in intraoperative navigation for RAPN in this propensity score-matched cohort, this study is the first to demonstrate that UHR-CT resulted in a shorter WIT and lower EBL than ADCT.

Perioperative and long-term functional outcomes of robot-assisted versus open partial nephrectomy: A single-center retrospective study of a Japanese cohort.

Objective: This study aimed to compare the perioperative and long-term functional outcomes between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) in Japanese patients. Methods: We retrospectively analyzed 242 patients who underwent either RAPN or OPN between 2007 and 2017 at our hospital. Propensity score matching was carried out between the two groups at a ratio of 1:1. Perioperative outcomes and postoperative estimated glomerular filtration rates (eGFR) were compared at one and three years of follow-up. Results: After propensity score matching, we evaluated 39 patients from each group. The ischemia duration of the RAPN group was significantly shorter than that of the OPN group (18 vs. 24, p < 0.001). Moreover, the estimated blood loss (EBL) was significantly lower in the RAPN group than in the OPN group (50 vs. 174, p < 0.001). However, there were no significant differences in the postoperative eGFR between the two groups at one or three years of follow-up (OPN 54.8 vs. RAPN 61.2, p = 0.109, and OPN 54.8 vs. RAPN 55.5, p = 0.262, respectively). Conclusion: RAPN resulted in shorter ischemia durations and lower rates of EBL than did OPN; however, no differences in long-term renal function were observed between RAPN and OPN in our propensity-score matched Japanese cohort.

Risk factors for postoperative ileus after robot-assisted radical cystectomy with intracorporeal urinary diversion.

OBJECTIVES: To evaluate the risk factors for postoperative ileus in patients who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion. METHODS: We retrospectively analyzed 78 patients with bladder cancer who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion at Fujita Health University between 2011 and 2021. Baseline characteristics and perioperative outcomes were compared between the cohorts with and without ileus. Logistic regression analysis was used to identify the risk factors for postoperative ileus. RESULTS: Out of the 78 patients included in this study, 20 (25.6%) developed postoperative ileus. The ileus cohort was associated with a significantly lower Geriatric-8 score (P = 0.003) and a higher rate of previous abdominal/pelvic surgery (P = 0.04) compared with those of the nonileus cohort. Significantly longer intestinal tract reconstruction time, hospital stay, time to mobilization, fluid intake, solid intake, flatus, and stool were observed in the ileus cohort. According to the results of the logistic regression analysis, the Geriatric-8 sum (P = 0.009), time to mobilization (P = 0.03), and time to fluid intake (P = 0.004) were independent predictors of postoperative ileus. In the model predicting postoperative ileus, the area under the receiver operating characteristic curve was 0.716, and the cutoff value of the Geriatric-8 sum was 13. CONCLUSIONS: Early mobilization and fluid intake and low Geriatric-8 scores were significant risk factors for postoperative ileus. Preoperative Geriatric-8 evaluation is a useful tool for predicting postoperative ileus. Comprehensive enhanced recovery after surgery, including key components, may help bowel recovery and prevent subsequent ileus.

Genotype-phenotype correlation of renal lesions in the tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by loss-of-function mutations in either of two tumor suppressor genes, TSC1 and TSC2. These mutations lead to the growth of benign tumors and hamartomas in many organs, including those of the central nervous system, the skin, and the kidneys. To investigate the genotype-phenotype correlation, we performed sequence analysis of the TSC1/2 genes using next-generation sequencing. We classified 30 patients with TSC whose pathogenic variants were identified into two groups: those with mutations producing premature termination codons (PTCs) and those with missense mutations. Then, we compared the phenotypes between the two groups. Patients with a PTC were significantly more likely to manifest the major symptoms of the diagnostic criteria than those without a PTC (P = 0.035). The frequencies of subependymal nodules (P = 0.026), cortical tubers (P = 0.026), and renal cysts (P = 0.026) were significantly higher in PTC-containing variants than in cases without a PTC. When the analyses were limited to renal angiomyolipoma (AML) cases with TSC2 mutations, there was no difference in tumor size between cases with and without a PTC. However, the cases with a PTC showed a trend toward disease onset at a younger age and multiple tumors, and bilateral disease was observed in their AML lesions. TSC patients with PTC-producing mutations might potentially manifest more severe TSC phenotypes than those with missense mutations. A larger-scale study with appropriate samples deserves further investigation.

Predictors of Secondary Bladder Cancer in Patients with Prostate Cancer Treated with Brachytherapy: A Single-institution Study of a Japanese Cohort.

PURPOSE: The incidence of secondary bladder cancer after treatment for localized prostate cancer (PCa) remains unclear. In this study, PCa cases treated with brachytherapy (BT) were evaluated to assess the incidence of a second malignancy of bladder cancer in a Japanese cohort. MATERIALS AND METHODS: Overall, 969 patients treated with BT at our hospital between July 2006 and January 2019 were included in the study cohort. The incidence and predictors of secondary bladder cancer were also assessed. RESULTS: The incidence of secondary bladder cancer was 1.5% (n = 14). Of the seven factors (age, pretreatment PSA, Gleason score, cTNM stage, prostate volume, total activity, and combined external beam), prostate volume and total activity showed significant differences between the cohorts with and without secondary bladder cancer (P = .03 and P = .001, respectively). Upon comparison of the seven parameters for the 969 patients treated with BT, we found that only the total activity factor was affected by the incidence of secondary bladder cancer in the multivariate analysis (P = .007). CONCLUSION: The incidence of secondary bladder cancer was evaluated after BT for PCa. Total activity was associated with the incidence of secondary bladder cancer in Japanese patients who received BT.

Urinary and Plasma Antioxidants in Behavioral Symptoms of Individuals With Autism Spectrum Disorder.

The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.