Lipopolysaccharide-induced platinum accumulation in the cerebral cortex after cisplatin administration in mice: Involvement of free radicals

The relationship between the accumulation of platinum in the cerebral cortex following cisplatin administration and injury to the blood-brain barrier after lipopolysaccharide (LPS) treatment was investigated. The appearance of intravenously injected fluorescein in the brain was significantly increased 10–24 h after LPS treatment, the effect being dose-dependent. Platinum was detectable in the cerebral cortex of cisplatin-treated mice 24 h after LPS treatment, but not without LPS treatment. In mice pretreated with -tocopherol, LPS administration did not significantly augment fluorescein penetration into the brain, whereas pretreatment with either allopurinol or ascorbic acid did not modify the LPS-induced increase in fluorescein penetration. In contrast, platinum in the cerebral cortex after cisplatin administration was still detectable in the allopurinol-, ascorbic acid-, and -tocopherol-pretreated groups, and the levels of platinum in these groups were not significantly different from those in the group treated with LPS only. Administration of superoxide dismutase (SOD), but not of catalase, tended to inhibit the penetration of fluorescein. Both SOD and catalase significantly lowered platinum content in the cerebral cortex following cisplatin administration in mice treated with LPS. Thus, free radicals may injure the blood-brain barrier in mice challenged with LPS, and allow cisplatin to penetrate into the cerebral cortex, resulting in platinum accumulation.     

Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi‐institutional study

Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease‐specific survival (DSS) and disease‐free survival (DFS), and prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5‐year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5‐year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high‐grade chondrosarcoma, particularly for those with DDCS.     

Total syntheses of ent-hypocoprin A and ent-hypocoprin B

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular S_N2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B.     

Impact of Dietitian-Led Nutrition Therapy of Food Order on 5-Year Glycemic Control in Outpatients with Type 2 Diabetes at Primary Care Clinic: Retrospective Cohort Study

The aim of this retrospective cohort study was to evaluate the effect of 5-year follow-up of dietitian-led medical nutrition therapy (eating vegetables before carbohydrates) on glycemic control in outpatients with type 2 diabetes (T2DM) at a primary care clinic. A total of 138 patients with dietitian-led medical nutrition therapy (intervention group) and 104 patients without dietitian-led nutrition therapy (control group) were compared for glycemic control, serum lipid, blood pressure, and diabetic complications for 5 years. Each patient in the intervention group received dietary education focused on food order (eating vegetables before carbohydrates) by dietitians. A significant improvement in HbA1c after 5 years in the intervention group [8.5 ± 1.7% (69 mmol/mol) to 7.6 ± 1.1% (59 mmol/mol), p < 0.001] was observed, whereas no change was observed in the control group [7.9 ± 1.2% (62 mmol/mol) to 8.0 ± 1.2% (63 mmol/mol)]. Dietary intake of protein, fat, carbohydrates, cholesterol, and salt in the intervention group demonstrated significant reduction, while the intake of dietary fiber significantly increased after the dietary education. Simple dietary education of ‘eating vegetables before carbohydrates’ presented by dietitians achieved good glycemic control after a 5-year period in outpatients with T2DM at primary care clinic.     

Prognostic Factors in Endodontic Surgery Using an Endoscope: A 1 Year Retrospective Cohort Study

This retrospective study clarified the success rate of endoscopic endodontic surgeries and identified predictors accounting for successful surgeries. In this retrospective study, 242 patients (90 males, 152 females) who underwent endoscopic endodontic surgery at a single general hospital and were diagnosed through follow-up one year later were included. Risk factors were categorized into attributes, general health, anatomy, and surgery. Then, the correlation coefficient was calculated for the success or failure of endodontic surgery for each variable, the odds ratio was calculated for the upper variable, and factors related to the surgical prognosis factor were identified. The success rate of endodontic surgery was 95.3%, showing that it was a highly predictable treatment. The top three correlation coefficients were post, age, and perilesional sclerotic signs. Among them, the presence of posts was the highest, compared with the odds ratio, which was 9.592. This retrospective study revealed the success rate and risk factors accounting for endoscopic endodontic surgeries. Among the selected clinical variables, the presence of posts was the most decisive risk factor determining the success of endodontic surgeries.     

Clinical Characteristics Associated with the Development of Diabetic Ketoacidosis in Patients with Type 2 Diabetes

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated. Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated. Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p＜0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (＜65 years old) (p＜0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity. Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.