Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

Neoadjuvant therapy with intensity-modulated radiotherapy combined with S-1 for borderline-resectable pancreatic cancer.

AIM: We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). METHODS: BRPC patients were treated with IMRT (45 Gy/15fr) combined with two courses of S-1 (40 mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. RESULTS: Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29 vs. 20 months, p = 0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p < 0.001). CONCLUSION: NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

Appropriate Patient Status for Ra-223 Treatment in the Treatment Sequence for Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Radium (Ra)-223 is widely used for treating castration-resistant prostate cancer (CRPC) with bone metastasis based on evidence of increased survival and decreased skeletal-related events. However, the timing of Ra-223 use in the treatment sequence of CRPC remains controversial. Therefore, this study aimed to explore the appropriate patient status for Ra-223 use in the CRPC treatment sequence by examining patients treated with Ra-223 from the time of CRPC diagnosis until death. PATIENTS AND METHODS: The medical records of 67 CRPC patients with bone metastasis who were treated with Ra-223 at two institutes were retrospectively analysed. The impact of 13 factors from the time of CRPC diagnosis until death was analysed using univariate and multivariate Cox hazard ratio models to evaluate the appropriate patient status for Ra-223 treatment. RESULTS: The median survival time following CRPC diagnosis for all the patient groups was 3.82 years. Univariate analysis identified a higher-than-normal alkaline phosphatase (ALP) level, bone scan indexes ≥2, and prostate-specific antigen (PSA) doubling time <3 months before Ra-223 treatment as predominant adverse prognostic factors. Ra-223 therapy discontinuation was not a significant factor. The survival of CRPC patients with these factors was significantly worse than that of patients without these factors. In the multivariate analysis, a higher-than-normal ALP level at the start of treatment was identified as a poor prognostic factor for mortality. CONCLUSION: The appropriate patient status for Ra-223 use includes low bone metastasis burden and well-controlled PSA levels.

Evaluation of internal margins for prostate for step and shoot intensity-modulated radiation therapy and volumetric modulated arc therapy using different margin formulas.

PURPOSE: This feasibility study evaluated the intra-fractional prostate motion using an ultrasound image-guided system during step and shoot intensity-modulated radiation therapy (SS-IMRT) and volumetric modulated arc therapy (VMAT). Moreover, the internal margins (IMs) using different margin formulas were calculated. METHODS: Fourteen consecutive patients with prostate cancer who underwent SS-IMRT (n = 5) or VMAT (n = 9) between March 2019 and April 2020 were considered. The intra-fractional prostate motion was observed in the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions. The displacement of the prostate was defined as the displacement from the initial position at the scanning start time, which was evaluated using the mean ± standard deviation (SD). IMs were calculated using the van Herk and restricted maximum likelihood (REML) formulas for SS-IMRT and VMAT. RESULTS: For SS-IMRT, the maximum displacements of the prostate motion were 0.17 ± 0.18, 0.56 ± 0.86, and 0.18 ± 0.59 mm in the SI, AP, and LR directions, respectively. For VMAT, the maximum displacements of the prostate motion were 0.19 ± 0.64, 0.22 ± 0.35, and 0.14 ± 0.37 mm in the SI, AP, and LR directions, respectively. The IMs obtained for SS-IMRT and VMAT were within 2.3 mm and 1.2 mm using the van Herk formula and within 1.2 mm and 0.8 mm using the REML formula. CONCLUSIONS: This feasibility study confirmed that intra-fractional prostate motion was observed with SS-IMRT and VMAT using different margin formulas. The IMs should be determined according to each irradiation technique using the REML margin.

Risk Scoring System for Ra-223 Discontinuation and Its Effect on Prognosis: A Retrospective Study.

Background/Aim: Radium-223 therapy prolongs overall survival in castration-resistant prostate cancer (CRPC) patients with bone metastasis. Patients who are unable to complete six courses of radium-223 therapy reportedly have a poor prognosis. This study aimed to develop a risk score using the discontinuation factors of the above therapy modality. Patients and Methods: Seventy patients who received radium-223 therapy for metastatic CRPC at two Japanese Institutions were evaluated. Univariate and multivariate analyses were performed to identify the discontinuation factors and determine the risk scores. Results: The median survival time was 24.3 and 9.5 months in patients who did and did not complete the therapy, respectively. Multivariate analysis revealed haemoglobin and prostate-specific antigen as key factors. A risk score was developed using these factors, and patients were stratified into three groups. The discontinuation rate and survival after radium-223 therapy were significantly different. Conclusion: Our risk score may help evaluate the suitability of radium-223 in CRPC patients.

Impact of histology on patterns of failure and clinical outcomes in patients treated with definitive chemoradiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: Chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. Unlike metastatic disease, histological differences are usually not considered while planning chemoradiotherapy. This study aimed to compare clinical outcomes and relapse patterns between squamous cell carcinomas and adenocarcinomas, and investigated possible histology-specific approaches for chemoradiotherapy in locally advanced non-small cell lung cancer. METHODS: We retrospectively analyzed the outcomes and relapse patterns in patients who received definitive chemoradiotherapy for locally advanced non-small cell lung cancer in Katsura hospital between 2003 and 2012. RESULTS: A total of 68 and 33 patients with squamous cell carcinomas and adenocarcinomas, respectively, were enrolled. Patients with adenocarcinoma had less advanced T stages, and a larger proportion of female patients. Other factors were not different between the two groups. The median follow-up duration in all patients and survivors was 21.3 months and 91.4 months, respectively. Median survival and relapse-free survival were not significantly different between the two groups. In contrast, the failure patterns and incidences of distant failure were significantly different. Patients with squamous cell carcinomas had predominantly locoregional disease features and a shorter duration from relapse to death compared to patients with adenocarcinoma. CONCLUSION: Failure pattern was significantly different between the two histologies. Among relapsed patients, the prognosis was poorer in those with squamous cell carcinomas than those with adenocarcinomas. Further studies, to evaluate histology-specific approaches in chemoradiotherapy, are warranted.

National survey on total-body irradiation prior to reduced-intensity stem cell transplantation in Japan: The Japanese Radiation Oncology Study Group.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI-RIST). Different institutes adopt different approaches for the administration of TBI-RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI-RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI-RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI-RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI-RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI-RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI-RIST in Japan and can assist future efforts to standardize TBI-RIST treatment methods and to design a future multicenter collaborative research study.

National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG).

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010-2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source-surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Image findings of bisphosphonate related osteonecrosis of jaws comparing with osteoradionecrosis.

OBJECTIVES: The aim of this study was to evaluate image characteristics of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and compare these with osteoradionecrosis (ORN). METHODS: 34 patients with BRONJ and 16 patients with ORN were included in this study. We investigated the CT and dental panoramic radiograph (DPR) images for osteolysis, osteosclerosis, sequestration, periosteal reaction, pathological fracture and spread of soft tissue inflammation around the jaws. RESULTS: Osteolysis, osteosclerosis, sequestration and spread of soft tissue inflammation around the jaws were common radiological features in both BRONJ and ORN. Osteolysis and spreading of soft tissue inflammation around the jaws were predominant in ORN, and by contrast osteosclerosis was predominant in BRONJ. Periosteal reaction was established in 15 of the 34 BRONJ cases, but none in the ORN cases. Pathological fractures were observed in 6 of 16 ORN cases, but none in BRONJ cases. CT was better for detection than DPR for osteolysis, osteosclerosis, sequestration and periosteal reactions. CONCLUSIONS: Image findings of BRONJ were characterized as a severe sclerotic change combined with osteolysis, sequestration, periosteal reaction and spread of soft tissue inflammation around the jaws.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method.

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior-posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful.

Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity.

Macrophages play crucial roles in combatting infectious disease by promoting inflammation and phagocytosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that induces tissue inflammation by attracting and activating macrophages to produce inflammatory cytokines in chronic inflammation-associated diseases such as obesity-associated metabolic syndrome, atherosclerosis, and rheumatoid arthritis. Here, we asked whether and how ANGPTL2 activates macrophages in the innate immune response. ANGPTL2 was predominantly expressed in proinflammatory mouse bone marrow-derived differentiated macrophages (GM-BMMs) following GM-CSF treatment relative to anti-inflammatory cells (M-BMMs) established by M-CSF treatment. Expression of the proinflammatory markers IL-1ß, IL-12p35, and IL-12p40 significantly decreased in GM-BMMs from Angptl2-deficient compared with wild-type (WT) mice, suggestive of attenuated proinflammatory activity. We also report that ANGPTL2 inflammatory signaling is transduced through integrin α5ß1 rather than through paired immunoglobulin-like receptor B. Interestingly, Angptl2-deficient mice were more susceptible to infection with Salmonella enterica serovar Typhimurium than were WT mice. Moreover, nitric oxide (NO) production by Angptl2-deficient GM-BMMs was significantly lower than in WT GM-BMMs. Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection.

Positive Intraoperative Peritoneal Lavage Cytology is a Negative Prognostic Factor in Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Study.

OBJECTIVE: The aim of this study is to evaluate the prognostic significance of intraoperative peritoneal lavage cytology (PLC) in pancreatic invasive ductal adenocarcinoma. METHODS: Intraoperative PLC was evaluated in 162 patients with resectable pancreatic invasive ductal adenocarcinoma. The results were analyzed for correlations with clinicopathological parameters and/or prognoses. RESULTS: In the 162 cases of resectable pancreatic ductal adenocarcinoma, 18 (11%), 141 (87%), and 3 (2%) were positive, negative, and equivocal for intraoperative PLC, respectively. Intraoperative PLC positivity was associated with older patients (over 65 years), large tumor size (over 35 mm), tumor location in the body/tail of the pancreas, and distant metastasis. Univariate analysis showed that larger tumor sizes (≥35 mm, P = 0.001), lymph node metastases (P = 0.005), distant metastasis (P = 0.004), advanced stage (stage IIB or III, P = 0.006), advanced tumor histological grade (G3, P < 0.001), or positive intraoperative PLC (P = 0.002) are associated with a shorter survival. Multivariate analysis revealed that larger tumor sizes (≥35 mm, P = 0.026), lymph node metastasis (P = 0.021), advanced tumor histological grade (G3, P < 0.001), and positive intraoperative PLC (P = 0.002) were independent prognostic factors. CONCLUSION: Intraoperative PLC is an independent prognostic factor for resectable pancreatic invasive ductal adenocarcinoma.

Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head and neck intensity-modulated radiation therapy.

In this study, we assessed the differences in the dose distribution of a 4 MV photon beam among different calculation algorithms: the Acuros XB (AXB) algorithm, the analytic anisotropic algorithm (AAA), and the pencil beam convolution (PBC) algorithm (ver. 11.0.31), in phantoms and in clinical intensity-modulated radiation therapy (IMRT) plans. Homogeneous and heterogeneous, including middle-, low-, and high-density, phantoms were combined to assess the percentage depth dose and lateral dose profiles among AXB, AAA, and PBC. For the phantom containing the low-density area, AXB was in agreement with measurement within 0.5%, while the greatest differences between the AAA and PBC calculations and measurement were 2.7% and 3.6%, respectively. AXB showed agreement with measurement within 2.5% at the high-density area, while AAA and PBC overestimated the dose by more than 4.5% and 4.0%, respectively. Furthermore, 15 IMRT plans, calculated using AXB, for oropharyngeal, hypopharyngeal, and laryngeal carcinomas were analyzed. The dose prescription was 70 Gy to 50% of the planning target volume (PTV70). Subsequently, each plan was recalculated using AAA and PBC while maintaining the AXB-calculated monitor units, leaf motion, and beam arrangement. Additionally, nine hypopharyngeal and laryngeal cancer patients were analyzed in terms of PTV70 for cartilaginous structures (PTV(70_cartilage)). The doses covering 50% to PTV70 calculated by AAA and PBC were 2.1% ± 1.0% and 3.7% ± 0.8% significantly higher than those using AXB, respectively (p < 0.01). The increases in doses to PTV(70_cartilage) calculated by AAA and PBC relative to AXB were 3.9% and 5.3% on average, respectively, and were relatively greater than those in the entire PTV70. AXB was found to be in better agreement with measurement in phantoms in heterogeneous areas for the 4 MV photon beam. Considering AXB as the standard, AAA and PBC overestimated the IMRT dose for head and neck cancer. The dosimetric differences should not be ignored, particularly with cartilaginous structures in PTV.

ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.

Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

Changes in parotid gland morphology and function in patients treated with intensity-modulated radiotherapy for nasopharyngeal and oropharyngeal tumors.

OBJECTIVE: To evaluate the morphological changes of the parotid glands in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal and oropharyngeal tumors and the correlations with parotid function. METHODS: Ten patients with nasopharyngeal and oropharyngeal tumors treated with IMRT between May 2009 and January 2010 at Hokkaido University Hospital were included in this study. In the morphological assessment of the parotid glands, the sizes and computed tomography (CT) numbers of the bilateral parotid glands before and after IMRT with CT were calculated. For functional assessment of the parotid glands, we conducted the Saxon test and used a visual analog scale (VAS) for xerostomia evaluation. RESULTS: Reductions in saliva secretion were observed in the patients treated with IMRT for nasopharyngeal and oropharyngeal tumors, and there was a significant correlation between the reduction in saliva secretion and the VAS. The reductions in the parotid gland size and CT number were larger on the ipsilateral side than on the contralateral side. The reduction in saliva secretion was not significantly correlated with the reduction in parotid gland size, but was significantly correlated with the reduction in CT number. CONCLUSIONS: Morphological and functional changes of the parotid glands were observed after IMRT for nasopharyngeal and oropharyngeal tumors, and preservation of the contralateral parotid glands was only partly achieved. Among the morphological changes of the parotid glands, the CT number may be considered a predictor of parotid function after radiotherapy.

Changes in cardiovascular risk factors over a 24-year follow-up period: a Japanese pediatric cohort study.

This study examined changes in body mass index (BMI), fasting blood sugar (FBS), total cholesterol (TC) and HDL-cholesterol (HDL-C) levels over a 24-year follow-up period in a pediatric cohort. An appropriate starting age for intervention to prevent cardiovascular diseases is still unclear. The subjects were 655 children, aged 10-12. A follow-up survey was conducted when the subjects reached ages 13-15, 16-18, and 35-45, respectively, and height, weight, and blood tests including FBS, TC and HDL-C were examined. Forty (6%) of these subjects participated. BMI at ages 35-45 were significantly higher than those at ages 10-12 (p < 0.0001), 13-15 (p < 0.001), and 16-18 (p < 0.001). TC levels at ages 35-45 were significantly higher than at ages 10-12 (p < 0.0001), 13-15 (p < 0.0001), and 16-18 (p < 0.0001). BMI at the end of the follow-up (ages 35-45) had a significant correlation with BMI at ages 13-15 (R = 0.38, p = 0.041) and 16-18 (R = 0.41, p = 0.049). TC and HDL-C values at the end of the follow-up had a significant correlation with those at ages 10-12 (R = 0.55, p = 0.0004; R = 0.55, p = 0.016), 13-15 (R = 0.35, p = 0.045; R = 0.42, p = 0.015), and 16-18 (R = 0.47, p = 0.019; R = 0.44, p = 0.028). These results may suggest that intervention for children in Japan with cardiovascular risk factors should be initiated in the early years of life.

Brain glycogen supercompensation following exhaustive exercise.

Brain glycogen localized in astrocytes, a critical energy source for neurons, decreases during prolonged exhaustive exercise with hypoglycaemia. However, it is uncertain whether exhaustive exercise induces glycogen supercompensation in the brain as in skeletal muscle. To explore this question, we exercised adult male rats to exhaustion at moderate intensity (20 m min(-1)) by treadmill, and quantified glycogen levels in several brain loci and skeletal muscles using a high-power (10 kW) microwave irradiation method as a gold standard. Skeletal muscle glycogen was depleted by 82-90% with exhaustive exercise, and supercompensated by 43-46% at 24 h after exercise. Brain glycogen levels decreased by 50-64% with exhaustive exercise, and supercompensated by 29-63% (whole brain 46%, cortex 60%, hippocampus 33%, hypothalamus 29%, cerebellum 63% and brainstem 49%) at 6 h after exercise. The brain glycogen supercompensation rates after exercise positively correlated with their decrease rates during exercise. We also observed that cortical and hippocampal glycogen supercompensation were sustained until 24 h after exercise (long-lasting supercompensation), and their basal glycogen levels increased with 4 weeks of exercise training (60 min day(-1) at 20 m min(-1)). These results support the hypothesis that, like the effect in skeletal muscles, glycogen supercompensation also occurs in the brain following exhaustive exercise, and the extent of supercompensation is dependent on that of glycogen decrease during exercise across brain regions. However, supercompensation in the brain preceded that of skeletal muscles. Further, the long-lasting supercompensation of the cortex and hippocampus is probably a prerequisite for their training adaptation (increased basal levels), probably to meet the increased energy demands of the brain in exercising animals.

Degradation and destabilization of abnormal prion protein using alkaline detergents and proteases.

There is a limited number of reports regarding detergents and proteases inactivating, degrading, or destabilizing abnormal prion protein (PrPSc). In the present study, the effect of alkaline detergents and proteases on the breakdown of PrPSc in the absence of proteinase K (PK) (degradation) and the presence of PK (destabilization) was investigated. PrPSc from brain homogenate of terminally-diseased mice infected with the Chandler strain of scrapie was used as a substrate. A surfactant-free alkaline detergent (pH 11.9, 1% aqueous solution) with potassium hydroxide as the main ingredient and an alkaline detergent (pH 11.9, 1% aqueous solution) containing about 1% surfactant as well as two commercially available alkaline proteases had a destabilizing effect on PrPSc. All these detergents and proteases showed degradative effects on PrPSc under appropriate conditions. These results demonstrate the usefulness of alkaline detergents and proteases for the degradation or destabilization of PrPSc.

Complete atrioventricular block due to venous stent migration from innominate vein to right ventricle: a case report.

A 78-year-old man who had been treated with maintenance hemodialysis for chronic renal failure was admitted with severe edema in left arm for 1 month. Venous angiography showed a severe stenosis in left innominate vein, then, he underwent percutaneous balloon angioplasty and venous stenting (Wall Stent RP). His arm edema soon improved after angioplasty, however, he complained of general fatigue and bradycardia 2 days after the venous angioplasty. Electrocardiogram showed complete atrioventricular block with 35 wide QRS complexes per minute. His echocardiogram showed a pipe-shaped structure with multiple slit and acoustic shadow in right ventricle. His radiographical right ventriculogram revealed the migrated venous stent from innominate vein to right ventricle. We tried to perform percutaneous transvenous stent extraction using Goose-Neck snare catheter, however, the wall stent stuck in the right external iliac vein, and contrast media leaked to the outside of the vascular wall. Therefore, we implanted this stent in the iliac vein with optimal-sized balloon inflation, and succeeded in stopping bleeding. Complete atrioventricular block was recovered to sinus rhythm with left bundle branch block just after the removal of the venous stent from right ventricle, and no cardiovascular events occurred after the treatment.