Comparison of dapagliflozin and teneligliptin in nonalcoholic fatty liver disease patients without type 2 diabetes mellitus: a prospective randomized study

There are no reports regarding the efficacy of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and dipeptidyl peptidase 4 inhibitor (DPP4i) administrations in nonalcoholic fatty liver disease (NAFLD) patients without type 2 diabetes mellitus. The purpose of this study was to evaluate the efficacy of those drugs in such patients. NAFLD patients without type 2 diabetes mellitus were enrolled in this single center double-blind randomized prospective study, and allocated to receive either dapagliflozin (SGLT2i) or teneligliptin (DPP4i) for 12 weeks. Laboratory variables and body compositions were assessed at the baseline and end of treatment. The primary endpoint was alanine aminotransferase (ALT) reduction level at the end of treatment. Twenty-two eligible patients (dapagliflozin group, n = 12; teneligliptin group, n = 10) were analyzed. In both groups, the serum concentration of ALT was significantly decreased after treatment (p<0.05). Multiple regression analysis results showed that decreased body weight of patients with dapagliflozin administration was significantly related to changes in total body water and body fat mass. Administration of dapagliflozin or teneligliptin decreased the serum concentration of ALT in NAFLD patients without type 2 diabetes mellitus. With dapagliflozin, body weight decreased, which was related to changes in total body water and body fat mass (UMIN000027304).     

The Validity of Magnetic Resonance Imaging (MRI) in the Staging of Bladder Cancer: Comparison with Computed Tomography (CT) and Transurethral Ultrasonography (US)

The magnetic resonance imaging (MRI) of bladder cancer was accomplishedin 26 patients who had histologically proven transitional cellcarcinoma through transurethral resection. All 26 patients weresimultaneously studied by computed tomography (CT) and 21 werealso studied by transurethral ultrasonography (US) before surgeryor preoperative irradiation. The evaluations of the MRI andCT were carried out by the same radiologist and urologist postoperatively;the evaluation of the US was carried out by several urologistspreoperatively, and their results compared with the postoperativepathological findings. The staging accuracy for pT2 tumors andabove for each imaging modality was as follows. MRI: sensitivity83.3%, specificity 71.4%, accuracy 76.9%; CT: sensitivity 58.3%,specificity 42.8%, accuracy 50%; US: sensitivity 100%, specificity70%, accuracy 85.7%. The results of the staging with regardto extravesical extensions were as follows. MRI: sensitivity60%, specificity 85.7%, accuracy 80.8%; CT: sensitivity 60%,specificity 81%, accuracy 76.9%. On the other hand, the sensitivityof US was 25%, specificity 94.1% and accuracy was 81%. The higherthe pathological staging, the more the diagnostic accuracy waslikely to be increased with MRI and CT, but diminished for US.There were three case of pT1 tumors being over-diagnosed byUS, but two of them were accurately staged by MRI. The other11 cases, diagnosed as T2 or above by US, were only minimallyoverstaged or understaged by MRI. MRI seemed able to overcomethe disadvantage of US which tended to over-diagnose pT1 tumorsand which was not suitable for use in diagnosing infil-trativetumors correctly. CT seemed useless for local staging.     

Identification of Genes Associated with Dedifferentiation of Hepatocellular Carcinoma with Expression Profiling Analysis

To identify the genes associated with dedifferentiation of hepatocellular carcinoma (HCC), gene expression profiles of HCCs of well-and moderately differentiated grades were compared by means of oligonucleotide arrays. One tumor showed a nodule-in-nodule appearance (NIN), which is occasionally observed in the course of progression of HCC from well to less differentiated grade, when an inner, moderately differentiated tumor (MD) develops sequentially from the outer, well-differentiated tumor (WD). Seventy-six genes were identified to be up-regulated more than 3-fold and 33 genes were down-regulated in the inner nodule in NIN. By statistical analysis of the profiles from 10 individual additional liver tumors, 5 WDs and 5 MDs, we were able to identify 12 genes, LAMA3, PPIB, ADAR, PSMD4, NDUFS8, D9SVA, CCT3, GBAP, ARD1, RDBP, CSRP2 , and TLE1 , with significantly elevated expression, and 4 genes, CP, IL7R, CD48 , and PLGL , with decreased expression in MD. These selected genes were further validated using another 12 tumors, 5 WDs and 7 MDs, with semi-quantitative RT-PCR. We also applied neighborhood analysis to list the genes with high predictability values as most closely correlated with WD-MD distinction. Seven genes, ADAR, PSMD4, D9SVA, CCT3, GBAP, RDBP , and CSRP2 , whose expression was elevated and one gene, IL7R , whose expression was decreased, were included among the top 50 predictor genes. These genes are likely to be associated with dedifferentiation of HCC and their identification may help to elucidate the mechanism of liver cancer progression.     

Intrathecal ACNU — a new therapeutic approach against malignant leptomeningeal tumors

Summary Pharmacokinetics, toxicity and therapeutic efficacy of intrathecal ACNU, 3-((4-amino-2-methyl-5-pyrimidinyl)methyl)-1-(2-chloroethyl)-1-nitrosourea, were studied in rats to determine if it is a new and effective method for the treatment of malignant leptomeningeal tumors. Pharmacokinetics of intracisternally administered ACNU was studied by macroscopial autoradiography using ¹⁴C-labeled ACNU. It was demonstrated that intracisternally administered ACNU distributed in the subarachnoid space and subpial layer of the brain in high concentration and was rapidly eliminated into the systemic circulation. The diffusional transport of ACNU into the deeper part of the brain was limited. More than 3.0 mg/kg of intracisternal ACNU induced progressive loss of the weight of body in normal rats, and 80% of the rat given 6.0 mg/kg died. Increase of capillary permeability, neuronal loss and gliosis were observed in the marginal layer of the brain facing to the subarachnoid space in the rat given more than 3.0 mg/kg of ACNU. Systemic and local toxicity was not observed in the rat given less than 1.5 mg/kg. Therapeutic effect of intrathecal ACNU against leptomeningeal tumors was evaluated in the rat with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells. The median survival time of the rat treated with 1.5 mg/kg of intracisternal ACNU once on day 2 or on day 5 after tumor inoculation was significantly prolonged by 173%, and 214% at maximum, respectively, as compared with that of the untreated animal. These findings suggest that intrathecal ACNU may be of value for clinical trial against leptomeningeal tumors.     

Usefulness of helical computed tomography for diagnosis of cystic lesions of the pancreas

Using helical computed tomography (CT), we evaluated cystic pancreatic lesions in 11 patients and compared the imaging and the histopathologic findings. Helical CT allowed us to assess the tumor vasculature. Contrastenhanced images showed satisfactory details of the cysts, cyst walls, and intracystic structures. Helical CT is extremely useful for the evaluation of cystic pancreatic lesions.     

Involvement of Opioid Receptors in Shaking Behaviour Induced by Paraquat in Rats

Paraquat (30-70 mg/kg intraperitoneally) caused typical shaking behaviour in rats in a dose-dependent manner. Myoclonus also appeared after the shaking behaviour in several rats treated with the highest dose of paraquat. Morphine (5 mg/kg intraperitoneally, 30 min. before paraquat) significantly reduced the frequency of shaking behaviour. The alleviation by morphine disappeared when naloxone (1.5 mg/kg intraperitoneally 15 min. after morphine) was coadministered. Although there was no histological change in brain slices of paraquat-treated rats (70 mg/kg intraperitoneally), the fluorescein uptake into brain was increased by the treatment. Morphine prevented the increase of fluorescein uptake, but naloxone failed to antagonize this effect. On the other hand, intracerebroventricularly administered paraquat (25.7 μg/rat) caused tremor in all rats, but not shaking behaviour nor myoclonus. These findings suggest that paraquat administered systemically as well as centrally may be toxic to the brain. Although the actions of paraquat on the brain seem to be complicated, opioid receptors may play a role in the actions.     

Molecular design of biodegradable functional polymers, 2 Poly(carboxylic acid) containing xylopyranosediyl groups in the backbone

Polymer 2 , containing unreacted xylopyranosediyl groups in the backbone, was prepared from xylan by the conversion of vicinal hydroxyl groups to carboxylic groups using periodic acid/sodium chlorite. 2 was found to be biodegraded quickly by the activated sludge. Arthrobacter sp. KM810 and Flavobacterium sp. KM811 were isolated as 2 -degrading strains. It was found that these strains biodegraded all molecular-weight fractions of 2 . 2 shows a good calcium sequestration capacity which is comparable to that of poly(sodium acrylate).