SWI by 7T MR Imaging for the Microscopic Imaging Diagnosis of Astrocytic and Oligodendroglial Tumors.

BACKGROUND AND PURPOSE: Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. MATERIALS AND METHODS: 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. RESULTS: Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. CONCLUSIONS: Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.

The relationship between bite force and oral sensation during biting in molars.

BACKGROUND: In prosthodontic treatment, the occlusal form should be designed such that bite force is applied at the position that has higher load-bearing capacity and is comfortable for the patient. The purpose of this study was to clarify the differences in bite force and occlusal sensation with different loading positions on the occlusal surface. METHODS: Twelve healthy subjects were recruited for this study. Bite force and occlusal sensation were measured at five loading points on the upper and lower left first molars. Occlusal sensation was evaluated using a Visual Analogue Scale (VAS). RESULTS: Bite forces on the lingual side of the upper first molar and the buccal side of the lower first molar were significantly higher and VAS scores were significantly lower, i.e. the subjects felt less discomfort during biting on the buccal side of the upper first molar and the lingual side of the lower first molar compared to the other side of each molar. CONCLUSIONS: Loading on the occlusal surfaces of the functional cusps of the upper and lower first molars produces more load-bearing capacity and is more comfortable than loading on the non-functional cusps.

Acute hyperglycaemia prevents the protective effect of pre-infarction angina on microvascular function after primary angioplasty for acute myocardial infarction.

BACKGROUND: Acute hyperglycaemia has been associated with impaired microvascular function after acute myocardial infarction (AMI), whereas pre-infarction angina (PIA) occurring shortly before the onset of AMI has been shown to reduce microvascular injury after reperfusion. OBJECTIVE: To examine whether acute hyperglycaemia prevents the protective effect of PIA on microvascular function after AMI. METHODS: We studied 205 patients with a first anterior wall AMI who underwent primary angioplasty within 12 hours of onset. Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire. Severe microvascular injury was defined as the presence of systolic flow reversal and diastolic deceleration time <600 ms. Echocardiographic wall motion was analysed before revascularisation and 4 weeks later. RESULTS: Acute hyperglycaemia, defined as a blood glucose level of >or=198 mg/dl on admission, was found in 67 (33%) patients. In patients without acute hyperglycaemia, PIA was associated with a lower incidence of systolic flow reversal, a longer diastolic deceleration time and a higher coronary flow reserve. However, in patients with acute hyperglycaemia there was no significant difference in these same parameters between patients with and without PIA. In the presence of acute hyperglycaemia PIA did not improve the change in wall motion score. In a multivariate model, the absence of PIA was an independent determinant of severe microvascular injury in patients without acute hyperglycaemia (odds ratio 6.28, p = 0.001), but not in patients with acute hyperglycaemia. CONCLUSION: The protective effect of PIA on microvascular function was attenuated in patients with acute hyperglycaemia, resulting in unfavourable functional recovery.

Genotoxicity studies on green tea catechin.

The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.

Antifungal activity of DNA-lipid complexes and DNA-lipid films against Candida species.

In this study amphiphilic lipids, DNA-lipid complexes, and DNA-lipid films were prepared, and their antifungal activity against Candida species was examined. The amphiphilic lipids were synthesized from a reaction of glycine or L-alanine with n-alkyl alcohol in the presence of p-toluene sulfonic acid. DNA-lipid complexes, which were prepared by the simple mixing of DNA and amphiphilic lipids, were insoluble in water. Self-standing, water-insoluble DNA-lipid films were prepared by casting the DNA-lipid complexes from a chloroform/ethanol solution. The antifungal activities of the lipids and DNA-lipid complexes against the Candida species were evaluated by minimum inhibitory concentrations (MICs); those of DNA-lipid films were evaluated by the disk diffusion method. The seven kinds of lipids, DNA-lipid complexes, and DNA-lipid films showed antifungal activity, and no differences were seen in the antifungal activities between glycine and L-alanine derivatives. The lipids, DNA-lipid complexes, and DNA-lipid films, which have shorter alkyl chain length in lipids, showed antifungal activity against all Candida species. However, the effect of antifungal activity against Candida species decreased with increased alkyl chain length in lipids. In this study, it was found that lipids, DNA-lipid complexes, and films with a decyl or dodecyl group exhibit more favorable antifungal activity.

Genotoxicity studies on dietary diacylglycerol (DAG) oil.

Dietary diacylglycerol (DAG) oil is an edible oil enriched in DAG (more than 80%). A recent investigation indicated that DAG oil or its components may have beneficial effects on the prevention and management of obesity. We evaluated the genotoxic potential of DAG oil using standard genotoxicity tests. Bacterial reverse mutation assay (Ames test), the chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), and a bone marrow micronucleus assay in ICR CD mice were employed in the present study. In addition we have tested the possibility that genotoxic substances may be formed during cooking, heated DAG oil (HDG) was prepared by batch frying potato slices in the oil at 180 degrees C for 8 h/day for three consecutive days. Therefore, genotoxicity tests were also performed on HDG. Results obtained did not show any genotoxic effect on either unheated DAG oil (UDG) or HDG. We conclude that there are no safety concerns on the genotoxicity of DAG oil under the conditions for normal use.

Relation between the TIMI frame count and the degree of microvascular injury after primary coronary angioplasty in patients with acute anterior myocardial infarction.

OBJECTIVE: To investigate the relation between thrombolysis in myocardial infarction (TIMI) frame count (TFC) and coronary blood flow velocity (CBFV) parameters reflecting the degree of microvascular injury in patients with acute myocardial infarction. RESULTS: TFC and CBFV were measured after primary coronary angioplasty in 103 consecutive patients with their first anterior wall acute myocardial infarction. TFC correlated inversely with the averaged peak velocity (r = -0.43, p < 0.0001). However, TFC did not correlate significantly with diastolic deceleration time and with the averaged systolic peak velocity (r = -0.16, p = 0.22, and r = -0.23, p = 0.16, respectively). The patients were divided into two groups according to presence (35 patients) or absence (68 patients) of systolic flow reversal. There was no significant difference in TFC between the two groups (29 (16) v 25 (13), p = 0.20). CONCLUSIONS: These findings suggest that the TFC reflects epicardial CBFV. However, it is not accurate enough to assess the degree of microvascular injury after primary coronary angioplasty.

Cardiac rescue of an infant with fulminant myocarditis using extracorporeal membrane oxygenation.

A 7-month-old boy presented with fulminant myocarditis. He was in cardiac shock and cardiac dysfunction progressed despite aggressive support. Extracorporeal membrane oxygenation (ECMO) was applied for 8 days and he recovered with mild dilated cardiomyopathy.

Properties of Ca(2+)-dependent K+ channels of human gingival fibroblasts.

Cells in the oral cavity are normally exposed to different temperatures. Ion transport systems are influenced by temperature in other tissues: In particular, changes in intracellular K+ ion can affect cell growth and synthesis of macromolecules. The purpose of this investigation was to identify K+ channels in human gingival fibroblast cells and analyze the effect of temperature on their K+ conduction properties. Ca(2+)-dependent K+ channels with a large conductance (125 pS in symmetrical K(+)-rich solutions) were identified in human gingival fibroblasts and studied by the patch-clamp technique. The open probability of the channels varied with membrane potential between +40 and -100 mV. When the bath temperature was decreased from 40 to 4 degrees C, channel conductance was reduced, but the mean open time of the channels was increased. The activation energies for the conductance and the reciprocal of the mean open time were estimated to be 9.1 and 22.9 kJ/mol, respectively. These values are lower than those reported for these and other types of channels in cells from other tissues. The open probability of the channels was nearly constant in the temperature range studied. These results suggest that the properties of Ca(2+)-dependent K+ channels of gingival fibroblasts remain relatively unchanged when the cells are exposed to a wide range of temperatures.

Effect of alpha-tocopherol on high energy phosphate metabolite levels in rat heart by 31P-NMR using a Langendorff perfusion technique.

To examine the action of alpha-tocopherol on high energy phosphate compounds, a 31P-NMR technique was applied to perfused Langendorff rat hearts. Rats were treated with tocopherol acetate (25 mg/kg body wt i.p.) for 7 consecutive days. On the 7th day, the rat hearts were isolated for the Langendorff experiment. After 30 min of global ischemia the NMR signals of creatine phosphate and ATP in myocardium disappeared, and then recovered slightly in the reperfusion following ischemia. However, in the tocopherol-treated rat hearts, the restoration of high energy phosphate compounds occurred quickly after the beginning of reperfusion, although there was no significant difference in the destruction of high energy phosphate compounds during the ischemia. The alpha-tocopherol level in the myocardium was severely depleted by ischemia-reperfusion. In the alpha-tocopherol-treated animals, the alpha-tocopherol level in myocardium was still significantly higher than the control level at the end of 30 min of global ischemia. The heart mitochondrial respiratory function was simultaneously protected against ischemia-reperfusion injury. The role of alpha-tocopherol was discussed as a radical scavenger and membrane stabilizer against oxygen stress.

Hydroxyl radical generation and membrane fluidity of erythrocytes treated with lipopolysaccharide.

The effect of lipopolysaccharide (LPS) and/or bile acids on rat erythrocyte membranes was studied in vitro. Addition of LPS isolated from E. coli (J5 mutant) into the erythrocyte resulted in the decrease of membrane fluidity as determined by spin labelling using electron paramagnetic resonance (EPR). This was accompanied by membrane fragility. It was found that hydroxyl radicals were generated from erythrocytes treated with LPS by using DMPO spin trapping. However, pretreatment of erythrocytes with taurine-conjugated bile acids was found to modify the membrane response induced by LPS. Taurocholic acid (TCA) and tauroursodeoxycholic acid (TUDCA) prevented the decrease of membrane fluidity induced by LPS, and, as a result, the membrane integrity was maintained although no significant changes were observed in the amount of hydroxyl radicals produced by LPS addition. However, taurochenodeoxycholic acid (TCDCA) exhibited little beneficial effect on the dynamic properties and the function of the erythrocyte membranes, although the hydroxyl radical declined markedly in the erythrocytes. Therefore, it is suggested that TCA and TUDCA have a protective effect against LPS-induced membrane fragility by modulating membrane fluidity.

Fatal encephalitis/encephalopathy in primary human herpesvirus-6 infection.

An encephalitic illness with a fatal outcome occurred in a 9 month old girl with virologically confirmed exanthem subitum. Human herpes-virus-6 (HHV-6) DNA was found in the cerebrospinal fluid at the acute stage of the disease by the polymerase chain reaction, but the virus antigen was not detected in her brain tissue. This suggests that HHV-6-induced encephalitis/encephalopathy may be due to a non-infectious process.

Effect of vitamin E on cytotoxicity, DNA single strand breaks, chromosomal aberrations, and mutation in Chinese hamster V-79 cells exposed to ultraviolet-B light.

The effect of pretreatment with vitamin E on cytotoxicity, DNA single strand breaks, and chromosomal aberrations as well as on mutation induced by ultraviolet-B light (UV-B) was investigated in Chinese hamster V-79 cells. Cellular pretreatment with non-toxic levels of 25 microM alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure resulted in a 10-fold increase in cellular levels of alpha-tocopherol. Using a colony-forming assay, this pretreatment decreased the cytotoxicity of UV-B light. However, alkaline elution assays demonstrated that pretreatment with vitamin E did not affect the number of DNA single strand breaks caused by UV-B light. In addition, UV-B exposure produced a dose-dependent induction of chromosomal aberrations and mutations at the HGPRT locus, and neither of these actions of UV-B was influenced by pretreatment with the vitamin. These results suggest that vitamin E protects cells from UV-B-induced cytotoxicity, possibly through its ability to scavenge free radicals. The results also suggest that the extent of genotoxicity induced by UV-B light may not correlate directly with the cytotoxic action of this wavelength region in sunlight.

Identification of free and esterified hydroxyoctadecadienoates (HODEs) and linoleate-hydroxylating pathway in the epidermis of hairless mice.

Epidermal homogenates of hairless mice contained a large amount of lipid material showing a single peak on reverse phase (RP)-high pressure liquid chromatography (HPLC) with a maximum absorbance of 234 nm, which was different in retention time from arachidonate metabolites such as 12-HETE, 15-HETE and 5-HETE. The production of this material was dependent on exogenous linoleate concentration, protein concentration and buffer pH. This material was identified to be a mixture of 13-HODE and 9-HODE on the basis of UV absorbance spectra, retention times on RP-HPLC, straight phase (SP)-HPLC, gas chromatography-mass spectrometry (GC/MS) and mass spectra obtained. As assessed by SP-HPLC after saponification, these two HODEs were found to exist primarily in esterified forms in the skin. Neither substance was produced following heat denaturation of the homogenate. These results indicate that 13- and 9-HODEs are produced from linoleate enzymatically at physiologically relevant levels in the epidermis of hairless mice. Thus, it is possible that these two materials may play some important role in pathophysiology of the skin.

Hydroxyl radical generation from heart mitochondria damaged by ischemia.

The hydroxyl radicals are known to be a biologically active oxygen species. A remarkable enhancement of hydroxyl radical generation was observed in the mitochondria obtained from ischemic myocardium. The hydroxyl radicals are the primary reactive species leading to cellular damages, such as membrane damages, DNA damages, enzyme inactivation, protein denaturation and so forth. The origin of the hydroxyl radicals appeared in mitochondria was discussed.

Mechanism of lipid radical formation following exposure of epidermal homogenate to ultraviolet light.

It has been suggested that oxygen free radicals are important mediators of lipid peroxidation in the epidermis exposed to ultraviolet (UV) light. However, it is not clear whether it is the superoxide anion radical (O2-.) or the hydroxyl radical (.OH) that plays the major role in producing the lipid radicals (L.) following UV exposure. In this study, we used electron spin resonance (ESR) technique with the spin trap (5,5-dimethyl-1-pyrroline-N-oxide [DMPO]) to determine which active oxygen species is involved in the UV-induced lipid radical formation (DMPO-L.: aN = 15.5 G, aH = 22.7 G). In the presence of superoxide dismutase or the metal-chelating agent, the DMPO-spin adduct spectrum of lipid radicals was reduced remarkably. The lipid radicals were formed by the hydroxyl radical generation system, not the superoxide anion generation system. The hydroxyl radical was found to be the direct active oxygen species that can generate lipid radicals as a result of .OH-mediated hydrogen atom abstraction. Superoxide anion radical stimulated the generation of hydroxyl radical via the iron-catalyzed reaction.

Generation of leukotrienes and hydroxyeicosatetraenoic acids in peritoneal macrophages of tumor-bearing mice.

To examine the potential role of lipoxygenase products in the pathophysiology observed after experimental tumor implantation, we examined the generation of leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) in peritoneal macrophages. C57BL/6 mice were given subcutaneous inoculations of B16 melanoma cells, and peritoneal macrophages were isolated various days after the inoculation. Macrophages were incubated for 1 h at 37 degrees C in serum-free RPM11640 containing 10 microM calcium ionophore A23187, 10 microM exogenous arachidonic acid (AA), 5 mM cysteine hydrochloride and 1 mM reduced glutathione. LTs and HETEs were separately extracted, passed through Sep-Pak cartridges, then identified and quantitated with a HPLC system using UV absorbance. The B16 melanoma-cell-treated/untreated macrophages were found to produce substantial amounts of 15-HETE, 12-HETE and 5-HETE and LTC4 by enzymatic mechanisms. Thus, when determined under various conditions, the production of HETEs was dependent on substrate-concentration, incubation-time and cell-number. The production of LTC4 was dependent on incubation-time and cell number but not substrate-concentration, indicating utilization of endogenous AA stores. Of these products, 12-HETE and LTC4 showed a significant increase on the fourth day after the tumor cell inoculation and returned to the control level by the 11th day after the same treatment. These results suggest that in vivo tumor cell implantation may induce a transient increase of 12-HETE and LTC4 production in macrophages.

Prevention of 4-pentenoic acid-induced liver injury in rats by 16,16-dimethyl PGE2.

16,16-Dimethyl PGE2 (dmPGE2) is known to protect against cellular damage in various tissues. Histological and biochemical approaches were used to examine the effect of this prostaglandin on hepatocellular damage in an experimental Reye's syndrome model produced in rats by 4-pentenoic acid. Chronic intraperitoneal administration of 4-pentenoic acid induced an accumulation of fatty droplets throughout the hepatic lobules along with mitochondrial abnormalities including swelling, disappearance of christae, and heterogeneity of matrix. These abnormalities were more intense in the marginal zone and successively decreased nearer to the central vein. Such hepatic abnormalities were markedly reduced by the combined administration of dmPGE2 with 4-pentenoic acid. Biochemical examination confirmed that dmPGE2 was able to inhibit the accumulation of hepatic triglyceride seen after the treatment with 4-pentenoic acid alone. These results indicated that dmPGE2 can prevent characteristic hepatocellular damage in this experimental Reye's syndrome model, suggesting that the involvement of prostaglandins should be taken into account in discussing the etiology and management of this syndrome.

Riboflavin deficiency caused by treatment with adriamycin.

The present study was undertaken to determine whether administration of adriamycin causes the depletion of riboflavin content. Rats received intraperitoneal injections of adriamycin (4 mg per kg body weight) for 6 consecutive days. Urinary riboflavin excretion began to increase after 2 days of treatment with adriamycin. Erythrocyte FAD levels decreased gradually and plasma lipid peroxide contents increased markedly at the 6th day. The activity coefficient of erythrocyte glutathione reductase showed a significant increase before the decrease of flavin content and the elevation of lipid peroxide level. Therefore, the value of this coefficient obtained from erythrocyte appears to be a reliable index of riboflavin deficiency, particularly during the early stage.

Non-dimer DNA damage in Chinese hamster V-79 cells exposed to ultraviolet-B light.

To understand and characterize non-dimer DNA damage and cytotoxicity induced by ultraviolet-B light (UV-B, 290-320 nm), an alkaline elution technique for analysis of DNA damage was used on Chinese hamster V-79 cells. Ultraviolet-B exposure produced a dose-dependent induction of DNA single strand breaks and DNA-protein crosslinks; however, there was an absence of DNA-DNA interstrand crosslinks. Neither of these types of DNA damage were repaired within a a 24 h incubation of the cells following a single UV-B exposure; rather the damage increased. Using a colony forming assay, we found that UV-B exposure resulted in an increase of cytotoxicity in a dose-dependent fashion. In addition, UV-B exposure inhibited DNA and RNA synthesis. The role of non-dimer DNA damage in the cytotoxicity induced by UV-B is discussed.