Mapping of odor-related neuronal activity using a fluorescent derivative of glucose

Activity labeling was applied to the olfactory systems of the terrestrial slug Limax valentianus using 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent derivative of glucose. 2-NBDG was incorporated into cultured Limax olfactory interneurons, and this was partially blocked by the presence of a high concentration of glucose in the medium, indicating that a part of the uptake of 2-NBDG is mediated by glucose transporters. Next, in order to map odor-related neuronal activity in the primary olfactory center, tentacular ganglion, we injected 2-NBDG into the body cavities of slugs and exposed them to odors or clean air (control). In the odor-stimulated animals, the cell mass region was strongly stained. The digit-like extensions and the neuropil region were also stained in some animals. The control animals showed no staining. The neurons in the cell mass are thought to be involved in generating oscillating activities in the tentacular ganglion, and their activation may imply modulation of oscillatory activity during odor processing. Our results show that 2-NBDG is useful for mapping neuronal activity in vivo.     

The biphasic response of hepatic arterial blood flow caused by vasoactive substances--an experimental study in dogs]

In ten male mongrel dogs, blood flow was measured in the common hepatic artery (CHA), portal vein (PV) and liver tissue before and after the injection of vasoactive substances: angiotensin II (1.0 micrograms/kg), prostaglandin F2 alpha (1.0 micrograms/kg) and vasopressin (0.1 Unit/kg), under observation of the systemic circulation. Each injection caused a biphasic response in CHA blood flow, an initial decrease followed by a marked increase, while PV blood flow decreased. Liver tissue blood flow was reduced just after injection, but soon returned to a normal level. The duration of action was the shortest with prostaglandin F2 alpha and the longest with vasopressin. In using vasoactive substances in pharmaco-angiography, it is important to consider the biphasic response in CHA blood flow as well as the duration of action of these substances.     

A case of Nasu-Hakola's disease with T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen]

A 30-year-old female received a head injury at the age of 22 years. Subsequently neurological and psychiatric symptoms, such as personality change, urinary incontinence, dementia and gait disturbance developed. On admission, her cognitive function was severely impaired. Brain CT disclosed cerebral atrophy, dilatation of the lateral ventricle and calcification of the basal ganglia. Pathologically membranous structures were recognized in bone marrow. On the basis of these clinical findings, a diagnosis of Nasu-Hakola's disease was made. In this case, a T2-weighted MRI finding of reduced signal intensity in the thalamus and putamen was characteristic. This finding may be related to intracranial calcification.     

Heterotopic ischemic pain attenuates somatosensory evoked potentials induced by electrical tooth stimulation: diffuse noxious inhibitory controls in the trigeminal nerve territory.

The purpose of this study was to determine whether the late component of somatosensory evoked potentials (SEP) induced by electrical tooth stimulation and pain intensity are inhibited by heterotopic ischemic stimulation. The tourniquet pressure with 50 mmHg greater than the individual's systolic pressure was applied to the left upper arm for 10 min as ischemic conditioning stimulation. The late component of SEP and visual analogue scale (VAS) were recorded at 4 times and both were significantly decreased when ischemic conditioning stimulation was applied. The maximum reductions in SEP amplitude and the VAS value were 26.1% and 21.2%, respectively, during ischemic conditioning stimulation. After-effect was observed 5 min after removal of the conditioning stimulation. The present study revealed that heterotopic ischemic stimulation attenuated the late component of SEP induced by electrical tooth stimulation, triggering diffuse noxious inhibitory controls (DNIC) and after-effects in the trigeminal nerve territory. It was also suggested that the DNIC effect differs, depending on the intensity, kind, and quality of the test and conditioning stimuli.     

Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study

A systematic analysis of both tumors and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. In this study we investigated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and in 51 tissue samples taken from sites of macroscopically uninvolved urothelium surrounding the tumors, using the fluorescence in situ hybridization method. Our data demonstrated a close genetic relationship between all examined tumors and normal-appearing mucosa. Numeric aberrations of chromosomes 1, 7, 9, and 17 were found to exhibit similar patterns in all analyzed specimens, although with different frequencies.     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

Pentoxifylline and intravenous gamma globulin combination therapy for acute Kawasaki disease

We compared the efficacy of oral administration of pentoxifylline (PTX) and intravenous infusions of gamma globulin (IVGG) combination therapy with that of IVGG in reducing the frequency of coronary-artery lesions (CAL) in children with Kawasaki disease (KD), in a randomized trial. All patients with KD received acetylsalicylic acid (30 mg/kg per day), until the 30th day, after the onset of fever, followed by daily acetylsalicylic acid at a dose of 3-5 mg/kg per day there-after, and intravenous IVGG, 200 mg/kg per day, for 5 consecutive days. In addition, patients randomly assigned to PTX and IVGG combination therapy groups received oral PTX at a dosage of 10 mg/kg per day (low-dose) or 20 mg/kg per day (high-dose), in three divided doses until the 30th day. Patients with KD were all free from CAL prior to treatment. We assessed the presence of CAL by two-dimensional echocardiography which was also done prior to treatment and then twice a week after hospital admission. We detected CAL in 3 of 18 patients (16.7%) in the IVGG therapy group, as compared with 2 of 18 patients (11.1%) in the low-dose PTX and IVGG combination therapy group. There were no significant differences between the two groups. In the next study, we detected CAL in 3 of 21 patients (14.3%) in the IVGG therapy group, as compared with none of 22 patients (0%) in the high-dose PTX and IVGG combination therapy group (² = 6.4, P < 0.02). No adverse side-effects were observed in 79 patients with KD.     

Trichloroethylene. I. Carcinogenicity of trichloroethylene.

Trichloroethylene (TCE) as an industrial pollutant may damage human health and can be considered as carcinogen. TCE has been detected in the environment and in various human organs, e.g., liver, kidney and brain etc. There are histological alterations such as depletion of glycogen and hydropic degeneration in the liver, however, other signs of TCE effects can be found in various organs as well. TCE and its metabolites, e.g., trichlorethanol, trichloro-acetic acid and epoxides were recently identified as strong mutagens in Ames mutagenicity test inducing frameshift and base-substitution mutations. TCE induced predominantly hepatocellular carcinoma after long term administration in mice. In these animals, kidneys and liver were supposed to be primary target organs with low epoxy-hydrolase activity. A high level of mitotic gene conversion (or gene rearrangement) was indicated by the metabolism of TCE after repeated administration. Purified TCE by was a weak mutagen in the presence of S9 microsomal fraction of rats and as a consequence, the carcinogenic activity was low in the kidney of rats. However, a dose related increase of Leydig cell tumors was found in male rats.     

Trichloroethylene. II. Mechanism of carcinogenicity of trichloroethylene.

The cancer inducing effect of trichloroethylene (TCE) was studied by various methods. DNA complexing activity and apoptosis inhibition were found to be the key elements of the carcinogenicity of TCE and its metabolites. The ability of TCE to interact with DNA was low, but its incorporation into the RNA and DNA of the brain, testis, pancreas, kidney, liver, lung and spleen, cannot be excluded. Exposure to TCE and its metabolites provides a selective growth advantage to spontaneously occurring mutations in some K- and H-ras oncogenes (as non specific results of secondary DNA or RNA damage). The amount of DNA-TCE adducts was higher in mouse hepatocytes than in rat hepatocytes. These differences may explain the species difference in carcinogenicity of TCE, which was dose dependent (due to metabolism) in mice but independent in rats. The blood level kinetics of TCE confirmed the faster metabolic rate in mice, including peroxisome proliferation and induction in hepatocytes. Dichloroacetic- and trichloroacetic acid were found to be hepatic carcinogens in mice, and the specificity depends on peroxisome proliferation induction. Possibly, TCE and related compounds down regulated apoptosis in mouse liver, and the reduced ability to remove initiated cells by apoptosis could be responsible for liver cancer induction by TCE.