The Influence of Hyperactivity of the Hypothalamic-pituitary-adrenal Axis and Hyperglycemia on the 5-HT2A Receptor-mediated Wet-dog Shake Responses in Rats

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induces hyperglycemia and serotonin (5-HT)2A receptor supersensitivity. In the present study, to investigate the effect of hyperglycemia on the function of 5-HT2A receptors, we compared the 5-HT2A receptor-mediated wet-dog shake responses in rats treated with adrenocorticotropic hormone (ACTH), dexamethasone and streptozotocin. ACTH (100 &#956;g/rat per day, s.c.), dexamethasone (1 mg/kg per day, s.c.) and streptozotocin (60 mg/kg, i.p.) produced significant hyperglycemia at 14 days after the start of these treatments, and the hyperglycemia was most pronounced in the streptozotocin-treated rats. The wet-dog shake responses induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, were significantly enhanced at 14 days after repeated treatment with ACTH and dexamethasone. However, streptozotocin-induced diabetes had no effect on the wet-dog shake responses. The results of the present study suggest that hyperglycemia is not strongly associated with the enhanced susceptibility of 5-HT2A receptors under the condition of hyperactivity of the HPA axis.</p

Intra-Day Variation of Urinary Nuclear Matrix Protein 22

Nuclear Matrix Protein 22 (NMP22), a urinary tumor marker for urothelial cancers, is directly released into the urine from the nucleus after cell death, Accordingly, values of NMP22 do not requlre adjustment using other substances such as urinary creatinine. On the other hand, its values might vary according to urine concentration. This study investigated the intra-day variation in the urinary level of NMP22. NMP22 and urinary creatinine were measured in a 24-hour urine sample and 4 spot urine samples obtained from 20 inpatients (10 with bladder cancer, and 10 with non-urothelial cancer or benign tumors). The spot urine samples were collected at 6 a.m., 10 a.m., 2p.m. and 9 p.m. There were no significant differences in NMP22 values between the 24-hour and spot samples in all patients. Out of 10 bladder cancer patients, 6 had positive 24-hour samples. Among these 6 patients, only 3 had 4 positive spot samples (>12.O U/ml): one had 3 positive samples, and 2 had one positive sample. Among the controls, only one patient with renal cancer had a positive 24-hour sample. Only 3 controls, 2 With prostatic cancer and one with renal cancer, had a single positive spot sample. The highest margin between the maximum and minimum levels in the 4 spot samples was 237.8 U/ml in the bladder cancer patients and 16.6 U/ml in the controIs. When the ratios of NMP22 and urinary creatinine values for the 24-hour to spot samples were calculated in each patient, a significant correlation was observed between the ratios of NMP22 and urinary creatinine (r=0.575, p<0.001). The urinary level of NMP22 shows intra-day variation and might be affected by the extent of the concentration of urine samples. The measurement results must be judged with this in mind, especially when judging the results around the cut-off value

Adenovirus-mediated transfection of caspase-8 sensitizes hepatocellular carcinoma to TRAIL- and chemotherapeutic agent-induced cell death

AbstractCaspase-8 belongs to the cysteine protease family and is known to be activated at the initial step in the cascade of TRAIL-induced apoptosis. The activation of procaspase-8 can be blocked by a relatively large amount of c-FLIP, which renders resistance to death receptor-mediated apoptosis in many types of cancer cells. To ask if extrinsic over-expression of caspase-8 contributes to the induction of apoptosis, we introduced the caspase-8 gene into HCC cells using an adenoviral (Adv) vector (Adv-Casp8). We demonstrated that Adv-Casp8 increased expression of active forms of caspase-8 in MOI-dependent manner. A large amount of Adv-Casp8 (MOI of 50) induced apoptosis significantly in HCC cells and resulted in downregulation of c-FLIP (in SK-Hep1, HLE, and HepG2 cells), XIAP, survivin, and Bcl-xL (in HLE cells) and dynamic release of cytochrome c and Smac from the mitochondria into the cytosol. On the other hand, a small amount of Adv-Casp8 (MOI of 10) causes a slight but detectable increase in the level of apoptosis with only a small effect on anti-apoptotic proteins and mitochondrial activation. However, small amounts of Adv-Casp8 augmented TRAIL- or chemotherapeutic agent-induced cell death (with an MOI of 10 or 20, respectively). These results suggest both that exogenous over-expression of caspase-8 by Adv-Casp8 may be essential for induction of HCC cell death and that the combination of Adv-Casp8 and TRAIL or chemotherapeutic agents could provide a useful strategy for treatment of HCC

A novel CACNA1A nonsense variant in a patient presenting with paroxysmal exertion-induced dyskinesia

ArticleJOURNAL OF THE NEUROLOGICAL SCIENCES. 399:214-216 (2019)journal articl

Initial Experience of Robot-Assisted Adrenalectomy in Japan: What is the Optimal Selection of Robotic Forceps for Adrenalectomy?

Minimally invasive adrenalectomy is the preferred technique for managing adrenal tumors. Laparoscopic adrenalectomy is widely performed and covered by insurance in Japan, but robot-assisted adrenalectomy is not. To investigate the best forceps combinations for performing robot-assisted adrenalectomy safely, we performed robot-assisted adrenalectomy for two left and two right adrenal adenomas using different robotic forceps combinations (bipolar forceps, monopolar curved scissors, Vessel Sealer Extend, and SynchroSeal) for each case. Although we evaluated a small number of RAs, lower blood loss was observed in patients where the vessel sealing devices were used. The extent of dissection is small for adrenalectomy, and robotic bipolar vessel sealing tools may not be necessary, especially for the small adrenal tumors. However, considering the risk benefits, the combination of forceps with Vessel Sealer Extend (by the left arm) and monopolar curved scissors (by the right arm) will become one of the best forceps combinations for performing robot-assisted adrenalectomy safely

Photoprecursor approach as an effective means for preparing multilayer organic semiconducting thin films by solution processes

[プレスリリース]「重ね塗り」で有機薄膜太陽電池を高性能化～光を当てると固まる材料使い、有効性を実証～プラスチック上にも作製可能 （2014/11/19）The vertical composition profile of active layer has a major effect on the performance of organic photovoltaic devices (OPVs). While stepwise deposition of different materials is a conceptually straightforward method for controlled preparation of multi-component active layers, it is practically challenging for solution processes because of dissolution of the lower layer. Herein, we overcome this difficulty by employing the photoprecursor approach, in which a soluble photoprecursor is solution-deposited then photoconverted in situ to a poorly soluble organic semiconductor. This approach enables solution-processing of the p-i-n triple-layer architecture that has been suggested to be effective in obtaining efficient OPVs. We show that, when 2,6-dithienylanthracene and a fullerene derivative PC71BM are used as donor and acceptor, respectively, the best p-i-n OPV affords a higher photovoltaic efficiency than the corresponding p-n device by 24% and bulk-heterojunction device by 67%. The photoprecursor approach is also applied to preparation of three-component p-i-n films containing another donor 2,6-bis(59-(2-ethylhexyl)-(2,29-bithiophen)-5-yl)anthracene in the i-layer to provide a nearly doubled efficiency as compared to the original two-component p-i-n system. These results indicate that the present approach can serve as an effective means for controlled preparation of well-performing multi-component active layers in OPVs and relatedorganic electronic devices

Utility of the HYBRID Method Incorporating the Advantages of Both Extracorporeal and Intracorporeal Urinary Diversion in Robotic-Assisted Radical Cystectomy

Background: Robotic-assisted radical cystectomy (RARC) is a well-known standard procedure for muscle-invasive bladder cancer. However, it remains controversial whether extracorporeal urinary diversion (ECUD) or intracorporeal urinary diversion (ICUD) is superior in this technique. We have developed a HYBRID method that combines ECUD and ICUD to retain the advantages of each. The purpose of this study was to compare perioperative outcomes between HYBRID and ECUD in RARC and to evaluate the usefulness of the HYBRID method. Methods: We retrospectively analyzed the perioperative outcomes of 36 consecutive bladder cancer patients who underwent RARC with ileal conduit at our institution between March 2013 and December 2021. Propensity-score matching was used to align patient backgrounds between the HYBRID and ECUD groups. Results: After matching, 12 cases were selected for each group. There was no significant difference in patient demographics between the groups except for the rate of neoadjuvant chemotherapy. Mean console time was significantly longer in the HYBRID group due to intracorporeal manipulation; however, a relatively favorable trend of mean blood loss was observed in this group. There was no significant difference between the groups in terms of positive surgical margin, mean number of lymph node removed, or positive lymph node. The incidences of complications associated and non-associated with the urinary tract and grade ≥III complications at postoperative day (POD) 0–30 and 31–90 were similar between the groups. In the HYBRID group, no complications non-associated with the urinary tract or grade ≥III complications were observed at POD 31–90. Conclusion: The HYBRID method takes advantage of the benefits of both ICUD and ECUD and is a highly applicable technique that can be used in a variety of patient backgrounds

Bone marrow stroma cells are susceptible to prion infection.

Abnormal protease-resistant prion protein (PrP-res) is the only surrogate biochemical marker for prion diseases, and a sensitive technique to detect PrP-res in blood or tissues is urgently needed. Primary cultured bone marrow stromal cells (MSCs) expressed PrP and were capable of supporting stable human prion infection. Using a mouse-adapted BSE strain, we demonstrated that PrP-res can be detected in expanded MSCs. We then analyzed the bone marrow cells collected at autopsy from two individuals with sporadic Creutzfeldt-Jakob disease (CJD), and, in both cases, cultured MSCs were positive for PrP-res. These data would suggest that ex vivo MSC expansion accompanied by PrP-res analysis could be a helpful tool in the definitive diagnosis of prion disease at an earlier stage in the disease process than is currently possible, and with considerably less distress to the patient

The synergistic effects of omega-3 fatty acids against 5-fluorouracil-induced mucosal impairment in mice

Background: Anti-cancer pharmaceuticals frequently have adverse side effects on patients such as gastrointestinal involvement limiting their clinical applications. These effects may be controlled by nutritional interventions, however, there are few studies that have shown any mechanistic effects. In this study, we examined effects of diet enhanced with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 5-fluorouracil (5-FU)-induced intestinal impairment and immunity in mice. Methods: C57Bl6 mice were randomized to control diet, control diet + EPA, control + DHA, control + fish oil, or diet enchanced with DHA/EPA. After seven days of each respective diet, mice, excluding those in the sham group, were treated with 10 mg/kg/day 5-FU for 7 days. The effects of 5-FU-induced impairment in the small intestine were assessed using cytokine concentrations in serum and tissue, secretory immunoglobulin (Ig) A, diamine oxidase (DAO) activity, the length of the small intestine, and the expression of apoptosis signaling genes. Results: The EPA/DHA-enhanced diet resulted in the most beneficial, synergystic and protective effect against 5-FU induced weight loss. Protection against inflammation, impaired intestinal function, and immunity of the small intestine were also observed. Individually, a DHA-enriched diet demonstrated a protective effect against 5-FU damage with longer small intestine mucosal and crypt lengths, greater DAO activity, and higher IgA concentrations, whereas the EPA-enriched diet resulted in decreased inflammatory cytokine concentrations in both plasma and small intestine and expression of apoptosis target genes. Conclusions: In conclusion, a diet enhanced with EPA and DHA results in synergism protecting against the detrimental effects of 5-FU and limiting chemotherapy induced mucosal impairment

Awa (Tokushima) lactate-fermented tea as well as green tea enhance the effect of diet restriction on obesity in rats

Drinking tea is recommended for promoting health due to its bioactive nutrients, such as catechins and caffeine. In Tokushima area, we have a unique traditional tea, named Awa tea, which are fermented with Lactobacillus pentosus and Lactobacillus plantarum. The present study was designed to investigate anti-obesity effects of the Awa tea and compare with those of non-fermented green tea. Obese male Wistar rats (19 weeks of age) were given by low energy diets containing 3% of Awa and green tea extracts, respectively, or without any tea extracts (control), for 4 weeks. Awa tea contained smaller amount of catechins than green tea, although they contained similar amounts of polyphenols. This finding indicates that there are distinct kinds of polyphenols from catechins. The diets containing Awa and green tea extracts further decreased whole body weight, fat tissue mass and plasma leptin level, compared with control diet. In addition, their diets increased the daily amount of lipid excreted to feces and total 24-h-energy consumption, compared with the control group. However, there is no significant difference in these anti-obesity effects between Awa tea and green tea. Our results indicate that Awa lactate-fermented tea as well as green tea similarly enhance the effect of diet restriction on obesity, at least in part, through the increase in fat energy consumption and the decrease in fat absorption in rats