Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses.

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

Effects of early experience with low-quality roughage on feed intake, digestibility and metabolism in lambs.

The objective of this study was to compare the feed intake, digestibility and metabolism in lambs fed low-quality roughage with those of lambs fed normal roughage from an early stage of their life. The study consisted of two treatments [low-quality roughage group (LR) and control group (C)] over three time periods (P1, P2 and P3; 2 months each). Four lambs (4 months old) were allocated to each treatment. In P1 and P2, LR was fed sudangrass hay (CP: 5.1% DM; NDF: 70.4% DM), whereas C was fed timothy hay (CP: 8.4% DM; NDF: 60.3% DM). In P3, all lambs were fed sudangrass hay. Although the feed intake was significantly greater (p < 0.05) in C in P1, there were no differences between the groups in P2. The digestibility, serum glucose (GLU), urea nitrogen (SUN) and insulin-like growth factor 1 (IGF-1) did not differ between the groups in P1 and P2. The average nitrogen retention, triiodothyronine (T3) and thyroxine (T4) were significantly higher in C (p < 0.05) during P1 and P2. No interaction was observed between the treatment and periods. In P3, the feed intake was greater in C (p < 0.05), whereas digestibility and nitrogen retention tended to be greater in LR. The body weight did not differ between the treatments. T4 and T3 were numerically lower in LR, while the SUN was greater in LR (p < 0.05). These results suggest that the early experience with low-quality roughage may have improved feed digestibility and nitrogen metabolism in lambs after 4 months of rearing. Furthermore, the experienced lambs became more efficient at utilizing the low-quality roughage. The lower thyroid hormone concentrations observed in LR suggest an adaptive change occurred in experienced lambs that to a lower basal metabolic rate.

Brain structural changes as vulnerability factors and acquired signs of post-earthquake stress.

Many survivors of severe disasters, even those without posttraumatic stress disorder (PTSD), need psychological support. To understand the pathogenesis of PTSD symptoms and prevent the development of PTSD, the critical issue is to distinguish neurological abnormalities as vulnerability factors from acquired signs of PTSD symptoms in the early stage of adaptation to the trauma in the normal population. The neurological underpinnings of PTSD have been well characterized, but the causal relationships with the traumatic event are still unclear. We examined 42 non-PTSD subjects to find brain morphometric changes related to the severity of PTSD symptoms in a longitudinal magnetic resonance imaging study extending through the Great East Japan Earthquake. We found that regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex (OFC) through the earthquake were negatively associated with PTSD symptoms. Our results indicate that subjects with smaller GMV in the ACC before the earthquake, and subjects with decreased GMV in the OFC through the earthquake were likely to have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our results indicate that these processing are related to vulnerability for PTSD symptoms. In addition, decreased OFC volume was induced by failing to extinct conditioned fear soon after the traumatic event. These findings provide a better understanding of posttraumatic responses in early stage of adaptation to the trauma and may contribute to the development of effective methods to prevent PTSD.

A rapid HPLC with evaporative light scattering method for quantification of forskolin in multi-herbal weight-loss solid oral dosage forms.

A rapid reverse-phase HPLC method with evaporative light scattering detection (ELSD) was developed for the determination of forskolin in weight loss multi-herbals products. The analysis was performed by water-acetonitrile gradient elution at a temperature of 40 degrees C and a flow rate of 1.0 mL/min. The evaporator tube temperature of ELSD was set at 35 degrees C, and with the nebulizing gas flow-rate (pressure) of 3.0 bar. The method was validated for linearity, accuracy, precision and limits of detection (LOD) and quantification (LOQ). Good linear relationships were obtained with correlation coefficients exceeding 0.9995. The average recovery of forskolin ranged from 99.4% to 100.4% with RSDs below 3%. The percent relative standard deviations (%RSD) of intra- and inter-day precision varied by less than 2.1%. LOD and LOQ were 0.95 microg/ml and 3.21 microg/ml, respectively. The validated ELSD method permits a shorter determination time without compromising accuracy and demonstrates that it can be used for quantification of forskolin incorporated in multi-herbal solid oral dosage forms.

Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells.

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

Significance of arterial ketone body ratio measurement in human liver transplantation.

Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation.

Short-term changes in blood ketone body ratio in the phase immediately after liver transplantation.

Arterial blood ketone body ratio was measured after orthotopic liver transplantation in piglets. Ketone body ratio immediately decreased at the beginning of the anhepatic phase and was rapidly restored to the normal levels within 30 min after the revascularization of the allograft. Serum lactate and pyruvate levels increased in anhepatic phase and gradually decreased after revascularization. Changes in the lactate and pyruvate levels were always preceded by changes in ketone body ratio. In the case of transplantation after 12-hr-preservation of the allograft, ketone body ratio failed to maintain normal levels after transplantation, resulting in a high mortality. It is suggested that the elevation of decreased ketone body ratio is prerequisite for the normalization of the deranged metabolic state after liver transplantation, and that ketone body ratio provides an accurate means to assess the initial metabolic function of the allograft.

Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy.

Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradation and inactivation of 5-fluorouracil (5-FU). The amount of its expression in a tumor is thought to be a factor determining the response of the tumor to 5-FU therapy. We compared DPD activity and DPD mRNA expression in resected tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAC) and surgery and a group of 24 patients with advanced gastric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. In the surgery alone group, DPD activity decreased significantly as the tumor stage advanced. This change was not observed in the NAC plus surgery group. Neither tumor depth (T factor) nor lymph node metastasis was found to correlate with DPD activity. Patients who responded to preoperative chemotherapy had lower DPD mRNA levels. Based on these results, we anticipate that measurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.

A prolongation of hepatic vascular exclusion by in situ hypothermic perfusion in dogs.

In situ hypothermic hepatic perfusion was performed in dogs to explore whether the time limit of hepatic vascular exclusion could be prolonged. During hepatic vascular exclusion, hepatic hypothermic perfusion was performed via portal vein using various perfusates under active bypass from the portal vein and infrahepatic inferior vena cava area to the superior vena cava system. Dogs receiving hepatic hypothermic perfusion for 1 hour died when given Ringer's solution but survived more than 7 days when given Euro-Collins' and University of Wisconsin solutions. Although dogs tolerated 2 hours of hepatic hypothermic perfusion when give University of Wisconsin solution, all dogs died by 2 hours of hepatic hypothermic perfusion when given Euro-Collins' solution. The hepatic energy charge and arterial ketone body ratio of dogs that died were significantly lower than for those that survived. This suggests that the regimen of hepatic hypothermic perfusion with University of Wisconsin solution is able to maintain the energy metabolism of the liver under hepatic vascular exclusion for prolonged periods, hence, its possible clinical application.

Percutaneous intrapelvic pressure registration in patients with ureterointestinal urinary diversion.

Intrapelvic pressure registration using percutaneous needle renal pelvic puncture in 4 patients with intestinal loop diversion was done to determine whether or not there is loop-ureteral reflux under physiologic condition in loop diversion without any urinary tract obstruction. There was no pressure elevation related to reflux on pressure recording. We concluded that loop-ureteral reflux in intestinal loop diversion does not occur without obstruction.

Fluoride and iron concentrations in the enameloid of lower teleostean fish.

Our quantitative elemental analyses with the electron microprobe indicated that the fluoride and iron concentrations in the enameloid of bony fish are related to the phylogeny of fish. The enameloid of some bony fish with high F also contained high Fe. In order to clarify the phylogenetic significance of such a peculiar dual deposition of F and Fe into developing enameloid, quantitative electron microprobe analyses of these elements were made on the teeth of taxonomically lower teleosts. There were significantly different trends of F and Fe concentrations in the enameloid among various forms of lower teleosts. In the Osteoglossiformes, the enameloid of the osteoglossid species contained very low levels of F and Fe, whereas in the single representative of the Mormyroidei, the F was very low but Fe was very high. In the Elopomorpha, the enameloid of the elopiform species contained a medium level of F and high Fe, and that of the anguilliform high levels of F and Fe. In the Salmoiformes, the salmonid species had medium F and high Fe, and in a species of the Esocidae, high F and high Fe levels were found. The stomiiform fish exhibited levels of medium and high F and high Fe. The results of the present study and our previous investigations made on archaic non-teleostean and various teleostean fish indicate that the mechanisms of F and Fe concentrations into developing enameloid are independent of each other, and that the mechanisms of Fe concentration appeared earlier and disappeared later than, or concurrently with, that of the F concentration, in the course of fish evolution.

Iron in the enameloid of perciform fish.

It is known that a high concentration of iron is deposited in the enameloid of some teleostean fish. Previously, Suga et al. (1989) pointed out that the iron concentration in the enameloid is related to the phylogeny of fish rather than to the feeding habits, according to the results of quantitative iron analyses on the teeth of marine teleost fish of the Tetraodontiformes. In the present study, in order for the previous idea to be verified, quantitative iron analysis was made with an electron microprobe on the enameloid of fish belonging to the Perciformes, which is the largest group of teleostean fish in the world and consists of both marine and freshwater species. The enameloid of all the fish examined (57 species) contained high iron concentrations ranging from 0.2% to 10.2% at the surface or middle layer, whereas that of an advanced suborder, Tetraodontoidei, of the Tetraodontiformes was very low in iron, at a level which could not be discriminated from the background value of the emission intensity. The distribution pattern of iron in the enameloid was classified into at least two types, namely, type A, in which a high iron concentration was observed mainly in the surface layer, and type B, in which iron was deposited throughout the entire layer, although there were differences in concentration. There were some differences in the concentration and distribution of iron in the enameloid for the families; for example, those of the Scaridae had a type A distribution, with about 0.2% iron only at the surface layer, whereas those of the Cichlidae, Centrarchidae, and Acanthuridae, which showed a type B distribution, contained iron ranging from 2.9% to 10.5% at the surface or middle layer of enameloid. Such differences seemed to be associated with the difference in timing of the commencement of the iron deposition into the developing enameloid, which is probably related to the phylogeny of fish. There was no evidence to support the idea that the iron concentration in the enameloid is associated with the feeding habits of fish, as proposed by previous investigators.

Iron concentration in teeth of Tetra-odontiform fishes and its phylogenetic significance.

It is known that iron is deposited in the enameloid of some teleost fishes, although its biological significance has not been clarified. In the present investigation, a quantitative analysis of iron in the enameloid of fishes of a primitive suborder, the Balistoidei, and an advanced suborder, the Tetra-odontoidei, of the Tetra-odontiformes of marine teleosts was performed by means of the electron microprobe. The results indicated that the enameloid of Balistoidei contained from 0.4-13.5% iron at its surface layer, whereas that of Tetra-odontoidei was very low in iron, which could not be discriminated from the background value of the emission intensity. The enameloid of three perciform species belonging to the Acanthuridae--from which the Tetra-odontiformes are considered to have been derived--also contained high iron (2.7-3.9%) throughout its entire layer. The iron concentration in the enameloid seemed to be related to the phylogeny of fishes rather than to their environmental water and feeding habits, and it is believed that the mechanisms of iron concentration into the developing enameloid have been lost during evolution from the Achanthuridae to the Tetra-odontoidei. Since a similar phenomenon has been previously observed with respect to the fluoride concentration in the enameloid of the same fishes (Suga et al., 1981a), it is speculated that the concentrations of iron and fluoride, which have originally no chemical correlation, have some special biological significance, although the timing and distribution pattern of their deposition are completely different.

Changes in coenzyme Q level in mitochondria of cirrhotic rat liver.

In the cirrhotic rat liver induced by carbon tetrachloride and phenobarbitone, the concentrations of mitochondrial Coenzyme Q were measured in comparison with other respiratory components. The concentration of cytochrome a(+a3) and Coenzyme Q significantly increased in the cirrhotic liver, without any changes in the ratio of Coenzyme Q to cytochrome a(+a3). It is suggested that such increase of Coenzyme Q plays an important role as one of the adaptive responses to compensate for the prolonged metabolic overload on the mitochondrial respiratory assembly. Also, from the findings that the concentrations of cytochrome a(+a3) in the mitochondria of cirrhotic liver increase concomitant with the severity of cirrhosis, it is suggested that the rise of Coenzyme Q levels may be one of the indicators for the decreased functional reserve capacity in liver cirrhosis.

Changes in acetoacetate/beta-hydroxybutyrate ratio in arterial blood following hepatic artery embolization in man.

Acetoacetate/beta-hydroxybutyrate ratio in the hepatic venous blood was compared to the ratios in arterial blood and peripheral venous blood in hypoxic state following right hepatic artery embolization in 5 patients with liver cancer. Ketone body ratios in right hepatic venous blood were positively correlated with those in arterial blood (r = 0.960, p less than 0.001), but not with those in peripheral venous blood. The free NAD+/NADH ratio of the liver mitochondria, which is reflected by the ketone body ration in hepatic venous blood, can be evaluated by the ketone body ratio in the arterial blood.

Short-term changes in blood ketone body ratios in the phase immediately after hepatic artery embolization: their clinical significance.

Changes in arterial and hepatic venous blood ketone bodies were investigated following transcatheter hepatic artery embolization (THAE) in patients with hepatocellular carcinoma. Acetoacetate/ beta-hydroxybutyrate ratio (ketone body ratio) in arterial blood was positively correlated with those of hepatic venous blood (r = 0.960, p less than 0.001), which reflects the mitochondrial redox potential in the embolized lobe. Nine cirrhotic patients were classified into three groups according to the changes in arterial blood ketone body ratio following THAE: Type A without decrease to below 0.7; Type B with a transient decrease to below 0.7, followed by its restoration within 5 hours; and Type C with decrease to below 0.7 without recovery within 5 hours. There were no serious complications in Type A and B patients. By contrast, severe sepsis and hepatic failure developed in Type C patients, possibly due to the extended embolization of both lobes. It is suggested that THAE can be successfully performed even in severely cirrhotic patients, as long as the embolized area is restricted to one lobe. In addition, changes in arterial blood ketone body ratios can give early information about the likely consequences of the THAE procedure just performed.

The influence of hemodilution in normal and cirrhotic rats in relation to hepatic energy metabolism.

The effects of acute hemodilution on hepatic energy status were compared between carbon-tetrachloride-induced cirrhotic rats and normal rats, using arterial blood ketone body ratio and hepatic energy charge as indices. Arterial blood was withdrawn and replaced with rat plasma in hemodiluted rats and with whole blood in sham-diluted control rats. In normal rats, arterial blood ketone body ratio and energy charge level at 6 hours after hemodilution decreased when the hematocrit value was less than 15%. In contrast, the values decreased at an even higher hematocrit level in cirrhotic rats. It was suggested from these results that the hemodilution procedure exerts a more profound hypoxic effect at a milder hemodilution on a cirrhotic liver than on a normal liver.