Arachidonate-enriched triglyceride oil does not promote tumor development in a rat medium-term multi-organ carcinogenesis model

The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.5% or 5.0%. No statistically significant differences in incidences and multiplicities of hyperplastic and neoplastic lesions were showed in the large intestine in either sex. In the liver, kidney, and lung in both sexes, and the mammary gland and uterus in females, tumor promoting potential was not evident with ARA-oil treatment. ARA-oil did not affect the quantitative data for glutathione S-transferase placental form positive foci of the liver. Increased induction of hyperplastic or neoplastic lesions in the urinary bladder and thyroid in ARA-oil-treated groups was without dose dependence. In addition, a second experiment with ARA-oil only administration for 8-week revealed no effects on cellular proliferation in the urinary bladder or thyroid in either sex. These results indicate that ARA-oil has no tumor promoting potential in any organs or tissues initiated with the five carcinogens applied in the present study.     

Beta-hydroxybutyrate,a cerebral function improving agent,protects rat brain against ischemic damage caused by permanent and transient focal cerebral ischemia

In our previous study, beta-hydroxybutyrate (BHB) was found to prolong survival time and to inhibit cerebral edema by improving energy metabolism in the hypoxia, anoxia and global cerebral ischemia models. In this study, the cerebroprotective effect of BHB was examined in rats with permanent (p)-occlusion and transient (t)-occlusion of middle cerebral artery (MCA). BHB (30 mg x kg(-1) x h(-1) was continuously administered through the femoral vein. In rats with p-MCA occlusion, BHB significantly reduced infarct area at 24 h after the occlusion, but not at 72 h after the occlusion. In rats with 2-h t-MCA occlusion followed by 22-h reperfusion, BHB significantly reduced cerebral infarct area, edema formation, lipid peroxidation and neurological deficits. Moreover, in the t-MCA occlusion model, delayed administration of BHB started at 1 h after the initiation of the MCA occlusion also significantly reduced cerebral infarct area. Taking together the results obtained in our previous study into account, these results indicate that BHB decreased cerebral edema formation and infarct area by improving of the cerebral energy metabolism during ischemia and by inhibition of lipid peroxidation after reperfusion.     

A retrospective study of parotid gland tumors at a single institution

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.     

The Priority of Non-HDL-C Assessment to Predict New Lesions among Stable Angina Patients with Strong Statins

Aim: In this study, we aim to examine the clinical meaning of low-density lipoprotein cholesterol (LDL-C) ＜70 mg/dL as assessed by Friedewald equation [LDL-C (F)] and Martin method [LDL-C (M)] and non-high-density lipoprotein cholesterol (HDL-C) ＜100 mg/dL on the occurrence of new lesions among Japanese patients with stable angina who underwent percutaneous coronary intervention (PCI) and were prescribed with strong statins. Methods: Among the 537 consecutive stable angina patients who had underwent PCI and had been prescribed with strong statins, the association between the occurrence of new lesions with myocardial ischemia at the 9-month follow-up coronary angiography and ≤ 2 years after PCI and baseline characteristics were assessed. Results: New lesions appeared 9 months and ≤ 2 years after PCI in 31 and 90 patients, respectively. Multivariate logistic regression analysis revealed diabetes mellitus (DM) was significantly associated with the occurrence of new lesions ≤ 2 years after PCI [odds ratio (OR) 1.71, 95 % confidence interval (CI) 1.06–2.83,p=0.031], and only non-HDL-C ≥ 100 mg/dL was associated with the occurrence of new lesions both at 9 months and ≤ 2 years after PCI [OR 1.80, 95 % CI 1.10–3.00,p=0.021 and OR 1.85, 95 % CI 1.13–3.07,p=0.016]. Conclusions: Non-HDL-C ≥ 100 mg/dL was determined to be the independent risk factor for the occurrence of new lesions 9 months and ≤ 2 years after PCI among stable angina patients with strong statins. Residual risk after PCI should be considered by assessing not only DM but also non-HDL-C beyond the scope of LDL-C-lowering therapy with strong statins.     

Effect of providing risk information on undergoing cervical cancer screening: a randomized controlled trial

Background

In Japan, the cervical cancer screening rate is extremely low. Towards improving the cervical cancer screening rate, encouraging eligible people to make an informed choice, which is a decision-making process that relies on beliefs informed by adequate information about the possible benefits and risks of screening, has attracted increased attention in the public health domain. However, there is concern that providing information on possible risks of screening might prevent deter from participating.

Methods

In total, 1,912 women aged 20–39 years who had not participated in screening in the fiscal year were selected from a Japanese urban community setting. Participants were randomly divided into 3 groups. Group A received a printed reminder with information about the possible benefits of screening, group B received a printed reminder with information about possible benefits and risks, and group C received a printed reminder with simple information only (control group).

Results

Out of 1,912 participants, 169 (8.8%) participated in cervical cancer screening. In the intervention groups, 137 (10.9%) participated in cervical cancer screening, compared to only 32 (4.9%) of the control group (p < 0.001). In addition, logistic regression analysis revealed that there was no significant difference in screening rate between group A and group B (p = 0.372).

Conclusions

Providing information on the possible risks of screening may not prevent people from taking part in cervical cancer screening among a Japanese non-adherent population.     

Total arch replacement using frozen elephant trunk technique with Frozenix for distal aortic arch aneurysms

Open in a separate window OBJECTIVESTotal arch replacement (TAR) using an endovascular approach has been initially introduced as the frozen elephant trunk technique (FET). In our institute, TAR using the FET with Frozenix has been used as the first-line treatment for distal aortic arch aneurysms since 2014. This study aimed to evaluate the early and long-term outcomes and demonstrate the efficacy of this procedure.METHODSBetween 2014 and 2021, 121 consecutive patients were treated with TAR using the FET with Frozenix for distal aortic arch aneurysms. Early and long-term outcomes were retrospectively analysed.RESULTSThe 30-day mortality rate was 2.5% (3/121). Of postoperative complications, paraplegia due to spinal cord injury occurred in 2 (1.7%) patients, stroke in 12 (9.9%) and acute renal failure in 10 (8.3%). At follow-up, 23 secondary aortic interventions were required and 8 (6.6%) patients underwent intended secondary thoracic endovascular aortic repair for residual descending aortic aneurysm. Late and aortic-related deaths occurred in 16 (13.2%) and 4 (3.3%) patients, respectively. The overall long-term survival rates at 1, 3 and 5 years were 87.6%, 83.1% and 65.4%, respectively, while the rates of freedom from aortic-related death at 1, 3 and 5 years were 95.7%, 95.7% and 84.8%, respectively.CONCLUSIONSTAR using the FET with Frozenix for distal aortic arch aneurysms has acceptable early mortality and morbidity. Spinal cord injury and paraplegia occur less frequently than previously reported. The technique has satisfactory long-term survival and freedom from aortic-related death.     

Reorganization of brain activity for multiple internal models after short but intensive training

Internal models are neural mechanisms that can mimic the input-output properties of controlled objects. Our studies have shown that: 1) an internal model for a novel tool is acquired in the cerebellum (Imamizu et al., 2000); 2) internal models are modularly organized in the cerebellum (Imamizu et al., 2003); 3) their outputs are sent to the premotor regions after learning (Tamada et al., 1999); and 4) the prefrontal and parietal regions contribute to the blending of the outputs (Imamizu et al., 2004). Here, we investigated changes in global neural networks resulting from the acquisition of a new internal model. Human subjects manipulated three types of rotating joystick whose cursor appeared at a position rotated 60 degrees, 110 degrees, or 160 degrees around the screen's center. In a pre-test after long-term training (5 days) for the 60 degrees and 160 degrees joysticks, brain activation was scanned during manipulation of the three joysticks. The subjects were then trained for the 110 degrees for only 25 min. In a post-test, activation was scanned using the same method as the pre-test. Comparisons of the post-test to the pre-test revealed that the volume of activation decreased in most of the regions where activation for the three rotations was observed. However, there was an increase in volume at a marginally significant level (p < .08) only in the inferior-lateral cerebellum and only for the 110 degrees joystick. In the cerebral cortex, activation related to 110 degrees decreased in the prefrontal and parietal regions but increased in the premotor and supplementary motor area (SMA) regions. These results can be explained by a model in which outputs of the 60 degrees and 160 degrees internal models are blended by prefrontal and parietal regions to cope with the novel 110 degrees joystick before the 25-minute training; after the acquisition within the cerebellum of an internal model for the 110 degrees, output is directly sent to the premotor and SMA regions, and activation in these regions increases.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Expression of parathyroid hormone/parathyroid hormone-related peptide receptor 1 in normal and diseased bladder detrusor muscles: a clinico-pathological study

Background

To investigate the expression of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor 1 (PTH1R) in clinical specimens of normal and diseased bladders. PTHrP is a unique stretch-induced endogenous detrusor relaxant that functions via PTH1R. We hypothesized that suppression of this axis could be involved in the pathogenesis of bladder disease.

Methods

PTH1R expression in clinical samples was examined by immunohistochemistry. Normal kidney tissue from a patient with renal cancer and bladder specimens from patients undergoing ureteral reimplantation for vesicoureteral reflux or partial cystectomy for urachal cyst were examined as normal control organs. These were compared with 13 diseased bladder specimens from patients undergoing bladder augmentation. The augmentation patients ranged from 8 to 31 years old (median 15 years), including 9 males and 4 females. Seven patients had spinal disorders, 3 had posterior urethral valves and 3 non-neurogenic neurogenic bladders (Hinman syndrome).

Results

Renal tubules, detrusor muscle and blood vessels in normal control bladders stained positive for PTH1R. According to preoperative urodynamic studies of augmentation patients, the median percent bladder capacity compared with the age-standard was 43.6% (range 1.5–86.6%), median intravesical pressure at maximal capacity was 30 cmH₂O (range 10–107 cmH₂O), and median compliance was 3.93 ml/cmH₂O (range 0.05–30.3 ml/cmH₂O). Detrusor overactivity was observed in five cases (38.5%). All augmented bladders showed negative stainings in PTH1R expression in the detrusor tissue, but positive staining of blood vessels in majority of the cases.

Conclusions

Downregulation of PTH1R may be involved in the pathogenesis of human end-stage bladder disease requiring augmentation.     

Value of percutaneous transhepatic cholangioscopy (PTCS)

Since July 1975, percutaneous transhepatic biliary drainage (PTBD) has been performed in 533 cases, and since April 1977 we have developed percutaneous transhepatic cholangioscopy (PTCS) as a diagnostic and therapeutic endoscopical tool in 198 cases of malignant disease and 195 benign cases. After dilating the sinus tract of PTBD using a 15-Fr catheter about 2 weeks after PTBD, PTCS was carried out through the sinus tract. PTCS has diagnostic advantages: the lesion can be accurately diagnosed histologically and the extent of cancer in the biliary tract can be assessed by taking biopsy specimens before the operation. PTCS has been applied for cholangioscopic lithotripsy in 145 cases of gallstone disease. In 44 cases, the Nd-YAG laser and/or electrohydraulic shock wave has been used to break up the stones. The PTCS morbidity was 6% and mortality was 0.3%.