Sominone improves memory impairments and increases axonal density in Alzheimer's disease model mice, 5XFAD

Previously we showed that steroidal sapogenin, sominone improved memory after a single i.p. injection into normal mice. However, it had not been reported that sominone could recover memory deficits in a severe Alzheimer's disease (AD) model animal. Therefore, we aimed to investigate that sominone improved memory impairments in the 5XFAD mouse, model for AD. In the current study, we used sominone that we had synthesized. 5XFAD mice were given 10 μmol/kg sominone intraperitoneally for 9 days. In addition to object recognition memory, axonal density, amyloid plaque number, and activated microglia in the brain were evaluated. Sominone treatment significantly improved object recognition memory compared with vehicle control treatment. Sominone treatment significantly enhanced axonal densities in the frontal cortex and parietal cortex but had no effects on amyloid plaque number and activated microglia. In cultured cortical neurons, the axonal length was significantly reduced by Aβ(1-42) treatment. However, that was markedly recovered 5 days after the treatment with 1 μM sominone. Neuronal loss was not observed in the cortex and hippocampus of 5XFAD mice at 6-8 months of age. These results suggest that memory deficits in AD may be improved by sominone independently of reducing amyloid plaques and neuroinflammation.     

Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: its association with DNA methylation alteration and patient outcome

PURPOSE: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. EXPERIMENTAL DESIGN: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau, and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). RESULTS: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n=34) and B (n=17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. CONCLUSIONS: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.     

Effect of vestibular nerve section on cytochrome oxidase activity in the vestibular ganglion cells of the squirrel monkey

Cytochrome oxidase (CO) activity of the vestibular ganglion cells of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. Under general anesthesia, right vestibular nerve section was performed on adult squirrel monkeys between the vestibular ganglion and brain stem. The left side was left intact and was used as a within-animal normal control. One squirrel monkey that did not undergo vestibular nerve section was also included in the normal group. Following a survival period of seven months, neurons in the vestibular ganglion of both sides were examined. In the normal control sides, a significant negative correlation between the size of the neuron and its optical density for CO stain was observed. Many neurons in the vestibular ganglion survived after vestibular nerve section, but their cell sizes and optical densities of CO stain decreased compared with those of the control side.     

Effect of probucol on the blood concentration of cyclosporin A in patients with nephrotic syndrome: a case study with a microemulsion formulation (Neoral)

Cyclosporin A(CyA) is used frequently in the treatment of steroid-resistant or recurrent cases with nephrotic syndrome. Recently, a new microemulsion formulation of CyA(Neoral) has been developed and used preferably because of a more stable bioavailability than an oily formulation(Sandimmun). Nephrotic syndrome accompanies hyperlipidemia, and probucol is used in cases showing inadequate effects or some adverse reactions under therapy with HMG-CoA reductase inhibitors. We reported previously that combined use of probucol caused a decrease in blood concentrations of CyA to about half of those without probucol. In the present study, we evaluated the influence of probucol on the blood concentrations of CyA in patients with nephrotic syndrome following Neoral. Coadministration of Neoral and probucol decreased the blood concentrations of CyA to approximately 75% of the levels before combined use. The change of blood CyA concentrations appeared to be smaller compared to those in cases with Sandimmun. Based on the present findings, we suggest that Neoral should be used preferentially instead of Sandimmun when the concomitant use of probucol is required, and that optimal dose adjustment of CyA is needed by frequent monitoring of CyA blood concentrations.     

Accuracy and repeatability of prostate volume measurements by transrectal ultrasound

We evaluated six alternative methods of prostate volume determination by transrectal ultrasound, three based on planimetry and three based on measurement of prostate diameters. Prostate volume measurements were made on an average of 6.5 occasions over a 3 y period on 41 patients with benign prostatic hyperplasia, using standard techniques. We defined the average of multiple planimetries as the prostate reference volume. Agreement with the reference volume and reproducibility at repeat testing was in the same range for single planimetry and volume determinations based on the formulas height (H) x width (W) x length (L) x pi/6 and W x W x H x pi/6, but was poorer using the formula W x W x W x pi/6. Using the average result of two successive planimetry measurements increased the reproducibility of planimetry, being statistically significantly better than for one single planimetry (P=0.024) or for the formula W x W x H x pi/6 (P=0.048). Our study suggests that the simple formula based methods of prostate volume determination provide results that are only marginally inferior to one single planimetry, but results are improved by performing two planimetry measurements.     

Vasculitic condition following instillation of epirubicin hydrochloride in an outpatient chemotherapy

The appearance of vasculitis is often observed following the use of epirubicin hydrochloride in outpatients. As it is important to continue to provide a safe treatment for outpatient with little or no side effects, the aim of this study was to reveal causes underlying the outbreak of vasculitis or the vasculitic state of patients who had undergone instillation of epirubicin hydrochloride as an adjuvant therapy following a breast cancer surgery. The study was conducted based on past investigation records. We extracted relevant factors such as age, previous illness, physical condition and dosage of epirubicin hydrochloride from past records which may all be connected to the outbreak of vasculitis. We administered one dose of epirubicin hydrochloride that was diluted into 50-100 ml of normal saline solution or 5% glucose and instilled over a period of 30 minutes. As a result of this instillation of epirubicin hydrochloride, 35 out of 45 cases displayed vasculitis. We did not observe any relationship among the aged (over 60), previous illness or physical condition (BMI over 25) and the appearance of vasculitis. When a dosage amount of more than 110 mg of epirubicin hydrochloride was administered, 23 out of 29 cases displayed vasculitis. From the past records, it was observed that the cause of vasculitis was dependent on the administrative method itself. As previous studies reported that vasculitis was low when epirubicin hydrochloride was retained in blood vessels for only a short time, our study, however, concentrated on how to administer epirubicin hydrochloride. Our results suggested that an adoption of a single dosage system may suppress the outbreak of vasculitis.     

Development of hepatocellular carcinoma following treatment with6-mercaptopurine for ulcerative colitis: investigation of chromosomal aberration by comparative genomic hybridization

In a 64-year-old man who had been treated with prednisolone (PSL) and 6-mercaptopurine (6MP) for a long period, for ulcerative colitis (UC), hepatocellular carcinoma (HCC) was detected incidentally. The UC was in remission with these medications. After he had been taking these medications for about 8 years, HCC was detected by computed tomography (CT), done for the evaluation of an other disease. Blood chemistry examination results were normal, except that the protein induced by vitamin K antagonist (PIVKA)-II level was 7940 AU/ml. We performed resection of liver segment V. With comparative genomic hybridization, chromosomal aberrations were recognized; these were gains of 1q, 3ptel-21, 8p12, and 22q11.23–22q13.1. Generally, HCC is associated with hepatitis virus infection in most cases, but in this patient, the HCC was not related to hepatitis C virus (HCV) or HBV. It is presumed that this case was related to the immunosuppressive therapy for UC and was associated with the gains of 1q, 3p, and 8p.     

Tissue adhesives for repairing inguinal hernia: a preliminary study

AIM: To investigate the efficacy of tissue adhesives for closing the orifice of the inguinal hernia sac (IHS) as an alternative method for treating inguinal hernia. METHODS: Five-week-old male Lewis rats (n=4) were used, because Lewis rats have a large patent IHS. The rats were divided into 9 groups (n=6 in each) according to the type of tissue adhesive used: G1, fibrin glue (Beriplast); G1b, Beriplast plus blood; G2, microfibrillar collagen hemostat (Avitene); G2b, Avitene plus blood; G3, fibrinogen-based sealant (TachoComb); G3b, TachoComb plus blood; G4, synthetic absorbable sealant (Advaseal); G5, bilateral single port laparoscopic injection of octylcyanoacrylate (Dermabond); and G6, sham operation (control group). In G1-G4, surgery was performed through a midline lower abdominal incision. In G5, a 5-mm laparoscope was inserted in the epigastrium, a fine catheter was passed through the side port of the laparoscope into the right HIS, and 0.2 mL Dermabond was injected. The left IHS was treated in the same way. All rats were sacrificed 3 months after treatment, and IHS patency was examined macroscopically. All rats in G5 and G6 were mated 50 days after treatment to check fertility. RESULTS: All rats survived until sacrifice. At sacrifice, all IHS were patent in G6. All IHS were also patent in G1-G4, but all IHS were closed at the internal ring in G5. In G5 there were no adhesions between the orifice of the closed sac and the small bowel in 5/6, and only minor adhesions in 1/6. G5 fertility (5/6: 83%) was the same as for the control group (G6). CONCLUSION: Our results suggest that laparoscopic injection of Db into the IHS is simple, safe, reliable, virtually scarless, and may be a reasonable alternative to standard open surgical inguinal hernia repair.