Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Chewing Maintains Hippocampus-Dependent Cognitive Function.

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

Loss of molars early in life develops behavioral lateralization and impairs hippocampus-dependent recognition memory.

BACKGROUND: Using senescence-accelerated mouse prone 8 (SAMP8), we examined whether reduced mastication from a young age affects hippocampal-dependent cognitive function. We anesthetized male SAMP8 mice at 8 weeks of age and extracted all maxillary molar teeth of half the animals. The other animals were treated similarly, except that molar teeth were not extracted. At 12 and 24 weeks of age, their general behavior and their ability to recognize novel objects were tested using the open-field test (OFT) and the object-recognition test (ORT), respectively. RESULTS: The body weight of molarless mice was reduced significantly compared to that of molar-intact mice after the extraction and did not recover to the weight of age-matched molar-intact mice throughout the experimental period. At 12 weeks of age, molarless mice showed significantly greater locomotor activity in the OFT than molar-intact mice. However, the ability of molarless mice to discriminate a novel object in the ORT was impaired compared to that of molar-intact mice. The ability of both molarless and molar-intact SAMP8 mice to recognize objects was impaired at 24 weeks of age. These results suggest that molarless SAMP8 mice develop a deficit of cognitive function earlier than molar-intact SAMP8 mice. Interestingly, both at 12 and 24 weeks of age, molarless mice showed a lateralized preference of object location in the encoding session of the ORT, in which two identical objects were presented. Their lateralized preference of object location was positively correlated with the rightward turning-direction preference, which reached statistical significance at 24 weeks of age. CONCLUSIONS: Loss of masticatory function in early life causes malnutrition and chronic stress and impairs the ability to recognize novel objects. Hyperactivation and lateralized rotational behavior are commonly observed with dysfunction of the dopaminergic system, therefore, reduced masticatory function may deplete the mesolimbic and mesocorticolimbic dopaminergic systems to impair the cognitive functions of selective attention and recognition memory in the prefrontal cortex and the hippocampus.

Effects of chewing on cognitive processing speed.

In recent years, chewing has been discussed as producing effects of maintaining and sustaining cognitive performance. We have reported that chewing may improve or recover the process of working memory; however, the mechanisms underlying these phenomena are still to be elucidated. We investigated the effect of chewing on aspects of attention and cognitive processing speed, testing the hypothesis that this effect induces higher cognitive performance. Seventeen healthy adults (20-34 years old) were studied during attention task with blood oxygenation level-dependent functional (fMRI) at 3.0 T MRI. The attentional network test (ANT) within a single task fMRI containing two cue conditions (no cue and center cue) and two target conditions (congruent and incongruent) was conducted to examine the efficiency of alerting and executive control. Participants were instructed to press a button with the right or left thumb according to the direction of a centrally presented arrow. Each participant underwent two back-to-back ANT sessions with or without chewing gum, odorless and tasteless to remove any effect other than chewing. Behavioral results showed that mean reaction time was significantly decreased during chewing condition, regardless of speed-accuracy trade-off, although there were no significant changes in behavioral effects (both alerting and conflict effects). On the other hand, fMRI analysis revealed higher activations in the anterior cingulate cortex and left frontal gyrus for the executive network and motor-related regions for both attentional networks during chewing condition. These results suggested that chewing induced an increase in the arousal level and alertness in addition to an effect on motor control and, as a consequence, these effects could lead to improvements in cognitive performance.

Occlusal Disharmony Transiently Impairs Learning and Memory in the Mouse by Increasing Dynorphin A Levels in the Amygdala.

Occlusal disharmony sometimes causes not only stiffness of neck but also psychiatric depression, suggesting that the condition of oral cavity may affect the central nervous system. Dynorphin A is an endogenous opioid peptide that specifically binds the κ-opioid receptor and has a protective role against stress. Dynorphinergic nervous system is intensely distributed in the amygdala and hippocampus that are coping areas with stress. As a model of malocclusion, we placed dental resin on the molars to increase the occlusal vertical dimension (bite-raise). After various survival times, we analyzed the amygdala and hippocampus by immunohistochemistry and immunosorbent assay (ELISA). Furthermore, the effects on learning and memory were assessed by Morris water maze test. In the amygdala, the levels of dynorphin A were increased on the 1st day after increasing the vertical dimension as indicated by immunohistochemical and ELISA assessments. The levels of dynorphin A returned to control levels on the 5th day. In the hippocampus, there were no noticeable changes in dynorphin A levels. The water maze test indicated that increasing the vertical dimension caused longer escape latency times on the 3rd day compared to those of sham-operated group. However, the bite-raised mice treated with a dynorphin antagonist, nor-binaltorphimine, showed similar escape latency times to the times of sham-operated group, even on the 3rd day. These results suggest that occlusal disharmony causes stress resulting in a transient increase of dynorphin A levels at least in the amygdala and that the increased dynorphin A levels transiently impair learning and memory.

Active coping with stress suppresses glucose metabolism in the rat hypothalamus.

We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

Activation of dorsolateral prefrontal cortex in a dual neuropsychological screening test: an fMRI approach.

BACKGROUND: The Kana Pick-out Test (KPT), which uses Kana or Japanese symbols that represent syllables, requires parallel processing of discrete (pick-out) and continuous (reading) dual tasks. As a dual task, the KPT is thought to test working memory and executive function, particularly in the prefrontal cortex (PFC), and is widely used in Japan as a clinical screen for dementia. Nevertheless, there has been little neurological investigation into PFC activity during this test. METHODS: We used functional magnetic resonance imaging (fMRI) to evaluate changes in the blood oxygenation level-dependent (BOLD) signal in young healthy adults during performance of a computerized KPT dual task (comprised of reading comprehension and picking out vowels) and compared it to its single task components (reading or vowel pick-out alone). RESULTS: Behavioral performance of the KPT degraded compared to its single task components. Performance of the KPT markedly increased BOLD signal intensity in the PFC, and also activated sensorimotor, parietal association, and visual cortex areas. In conjunction analyses, bilateral BOLD signal in the dorsolateral PFC (Brodmann's areas 45, 46) was present only in the KPT. CONCLUSIONS: Our results support the central bottleneck theory and suggest that the dorsolateral PFC is an important mediator of neural activity for both short-term storage and executive processes. Quantitative evaluation of the KPT with fMRI in healthy adults is the first step towards understanding the effects of aging or cognitive impairment on KPT performance.

Chewing reduces sympathetic nervous response to stress and prevents poststress arrhythmias in rats.

Reducing stress is important in preventing sudden death in patients with cardiovascular disease, as stressful events may cause autonomic imbalance and trigger fatal arrhythmias. Since chewing has been shown to inhibit stress-induced neuronal responses in the hypothalamus, we hypothesized that chewing could ameliorate stress-induced autonomic imbalance and prevent arrhythmias. To test this hypothesis, we analyzed changes in radiotelemetered electrocardiograms in rats that were allowed to chew a wooden stick during a 1-h period of immobilization stress. Chewing significantly reduced the occurrence of ventricular premature beats (VPBs) and complex ventricular ectopy after immobilization and prevented stress-induced prolongation of the QT interval of VPBs throughout the 10-h experimental period. It also prevented prolongation of the QRS complex and fluctuations in the QT interval in normal sinus rhythm beats preceding VPBs during both immobilization and in the poststress period. Fast Fourier transform-based spectral analysis of heart-rate variability further showed that chewing significantly inhibited the stress-induced increase in the power ratio of low-to-high frequency activity (LF/HF: a marker of sympathetic activity) during immobilization and in addition was associated with blunting of the stress-induced increase in plasma noradrenaline observed at the termination of immobilization. Similar suppressive effects on the occurrence of VPBs and the LF/HF were observed in rats that were administered the ß-adrenergic blocker propranolol before immobilization. These results indicate that chewing can ameliorate sympathetic hyperactivity during stress and prevent poststress arrhythmias and suggest that chewing may provide a nonpharmacological and cost-effective treatment option for patients with a high risk of stress-induced fatal arrhythmia.

Staging hepatic fibrosis: comparison of gadoxetate disodium-enhanced and diffusion-weighted MR imaging--preliminary observations.

PURPOSE: To evaluate the utility of hepatocyte-phase gadoxetate disodium-enhanced magnetic resonance (MR) imaging in staging hepatic fibrosis and to compare it with diffusion-weighted imaging. MATERIALS AND METHODS: This retrospective study had institutional review board approval, and the requirement for informed consent was waived. Gadoxetate disodium-enhanced and diffusion-weighted MR images obtained in 114 consecutive patients (70 men, 44 women; age range, 37-91 years) were evaluated. Liver-to-muscle signal intensity (SI) ratio on hepatocyte-phase images (SI(post)), contrast enhancement index calculated as SI(post) /SI(pre), where SI(pre) is liver-to-muscle SI ratio on nonenhanced images, and apparent diffusion coefficient (ADC) of the liver were measured. Necroinflammatory activity grades and hepatic fibrosis stages were histopathologically determined in 99 patients. Multiple regressions of SI(post), contrast enhancement index, ADC, serum albumin concentration, serum total bilirubin level, prothrombin time, and Child-Pugh score were examined to determine correlation with hepatic necroinflammatory activity grades and fibrosis stages. RESULTS: Among the MR, hematologic, and clinical parameters, contrast enhancement index was most strongly correlated with fibrosis stage (r = -0.79, P < .001). Multiple regression analysis showed that the contrast enhancement index, ADC, and prothrombin time were significantly correlated (r(2) = 0.66, P < .05) with fibrosis stage and that the contrast enhancement index and serum total bilirubin level were weakly correlated (r(2) = 0.24, P < .05) with the necroinflammatory activity grade. CONCLUSION: Gadoxetate disodium-enhanced MR imaging is more reliable for staging hepatic fibrosis than are diffusion-weighted MR imaging, hematologic, and clinical parameters.

CT of the pancreas: comparison of anatomic structure depiction, image quality, and radiation exposure between 320-detector volumetric images and 64-detector helical images.

PURPOSE: To prospectively compare 320-detector volumetric and 64-detector helical computed tomographic (CT) images of the pancreas for depiction of anatomic structures, image noise, and radiation exposure. MATERIALS AND METHODS: This study was approved by the institutional review board, and written informed consent was obtained. A total of 154 patients (85 men, 69 women; age range, 26-85 years; mean age, 67 years) who underwent biphasic (arterial and pancreatic phase) contrast material-enhanced CT performed with a 320-detector scanner were randomized into two groups: the 320-detector group and the 64-detector group. Biphasic transaxial multiplanar reformatted images and volume-rendered CT angiograms were obtained. CT numbers in the abdominal aorta, pancreas, and abdominal wall fat tissue; signal-to-noise ratio (SNR); and dose-length product (DLP) were compared. In addition, image quality and focal lesion depiction (n = 35) were qualitatively determined in the two groups. Unpaired t and Mann-Whitney tests were used for quantitative and qualitative assessment, respectively. RESULTS: No significant difference in CT numbers of the abdominal aorta and pancreas was noted between the two groups. Mean DLP was 43% lower in the 320-detector group (675.4 mGy·cm) than in the 64-detector group (1187.8 mGy·cm) (P < .001). SNR of the abdominal aorta, pancreas, and abdominal wall fat on biphasic images was significantly lower in the 320-detector group than in the 64-detector group (P < .001). Image quality was acceptable in both groups and was slightly better in the 64-detector group for pancreatic phase axial images (P = .02) and arterial phase multiplanar reformatted images (P < .01). No significant difference was found in the depiction of pancreatic parenchyma, main pancreatic duct, focal pancreatic lesions, splanchnic arteries, or most of the small splanchnic arterial branches. CONCLUSION: A 320-detector CT scan facilitates fast volumetric contrast-enhanced CT of the entire pancreas with acceptable image quality, even though SNR was significantly lower at 320-detector volumetric scanning.

Body size indexes for optimizing iodine dose for aortic and hepatic enhancement at multidetector CT: comparison of total body weight, lean body weight, and blood volume.

PURPOSE: To evaluate and compare total body weight (TBW), lean body weight (LBW), and estimated blood volume (BV) for the adjustment of the iodine dose required for contrast material-enhanced multidetector computed tomography (CT) of the aorta and liver. MATERIALS AND METHODS: Institutional review committee approval and written informed consent were obtained. One hundred twenty patients (54 men, 66 women; mean age, 64.1 years; range, 19-88 years) who underwent multidetector CT of the upper abdomen were randomized into three groups of 40 patients each: (a) TBW group (0.6 g of iodine per kilogram of TBW), (b) LBW group (0.821 g of iodine per kilogram of LBW), and (c) BV group (men, 8.6 g of iodine per liter of BV; women, 9.9 g of iodine per liter of BV). Change in CT number between unenhanced and contrast-enhanced images per gram of iodine and maximum hepatic enhancement (MHE) adjusted for iodine dose were examined for correlation with TBW, LBW, and BV by using linear regression analysis. RESULTS: In the portal venous phase, correlation coefficients for the correlation of change in CT number per gram of iodine with TBW for the aorta and liver were -0.71 and -0.79, respectively, in the TBW group; -0.80 and -0.86, respectively, in the LBW group; and -0.68 and -0.66, respectively, in the BV group. In the liver, they were marginally higher in the LBW group than in the BV group (P = .03). Adjusted MHE remained constant at 77.9 HU +/- 10.2 (standard deviation) in the LBW group with respect to TBW, but it increased in the TBW (r = 0.80, P < .001) and BV (r = 0.70, P < .001) groups as TBW increased. CONCLUSION: When LBW, rather than TBW or BV, is used, the iodine dose required to achieve consistent hepatic enhancement may be estimated more precisely and with reduced patient-to-patient variability.

The Galectin-1 level in serum as a novel marker for stress.

Galectin-1(Gal-1), a carbohydrate-binding protein with an affinity for beta-galactoside, is widely expressed in various normal and pathological tissues and it also plays an important role in regulating immune cell homeostasis and tumorigenesis. This study investigated the effects of restraint stress on serum Gal-1 by Western blot analyses and enzyme-linked immunosorbent assays. The Gal-1 levels of the restraint-stress group were significantly higher than those of the control group. However, this increase by stress was not obvious in adolescent rats. The pattern of these changes was similar to that of corticosterone. Furthermore, this Gal-1 increase in the serum was prevented by pre-treatment with a neurotoxin 6-hydroxydopamine (6-OHDA), which destroys the noradrenergic nerve terminals. However, a bilateral adrenalectomy (ADX) had no effect on the Gal-1 increase. These results suggest that Gal-1 is a candidate stress marker protein and that the stress-induced increase of Gal-1 in serum is regulated by the sympathetic nervous system under stress conditions.

Hepatic hemangioma and metastasis: differentiation with gadoxetate disodium-enhanced 3-T MRI.

OBJECTIVE: The purpose of this study was to evaluate the gadoxetate disodium-enhanced MRI findings of hepatic hemangioma and to investigate the diagnostic performance in differentiating hepatic hemangioma and metastasis. MATERIALS AND METHODS: Images of 32 hepatic hemangiomas in 25 patients and of 29 hepatic metastatic lesions in 20 patients were retrospectively reviewed. Two independent readers interpreted hepatobiliary phase images alone, dynamic extracellular phase images alone, and combined hepatobiliary and dynamic extracellular phase images. MRI findings and performance with respect to the differential diagnosis of hemangioma and metastasis were assessed. RESULTS: During the hepatic arterial phase, 11 of the 32 hemangiomas (34%) exhibited early total enhancement, and nine (28%) exhibited peripheral nodular enhancement. A bright dot sign or minimal peripheral enhancement during the late dynamic phase was observed for a small number of lesions (6% and 28%, respectively). Twenty-three of the 29 metastatic lesions (79%) exhibited ring enhancement during the hepatic arterial phase. Twenty-nine hemangiomas (91%) and all of the metastatic lesions exhibited homogeneous or heterogeneous hypointensity during the hepatobiliary phase. The sensitivity, specificity, and area under the receiver operating characteristic curve for the detection of hemangioma were 76%, 81%, and 0.87 for the hepatobiliary phase alone; 97%, 88%, and 0.97 for the dynamic extracellular phase alone; and 97%, 88%, and 0.98 for the combination. Five nodules smaller than 1 cm (four hemangiomas, one metastatic lesion) that exhibited no enhancement during the arterial phase and minimal enhancement during the late dynamic phase were not differentiated. CONCLUSION: Gadoxetate disodium-enhanced MRI was found useful for differentiating hepatic hemangiomas and metastatic lesions, especially during the dynamic extracellular phase. Only a limited number of lesions smaller than 1 cm in diameter, which exhibited minimal enhancement on late dynamic phase images, were difficult to diagnose.

Hypothermic and normothermic ischemia-reperfusion activate microglia differently in hippocampal formation.

Using immunohistochemical methods, we investigated microglial profiles under normothermic ischemia and hypothermic ischemia using an anti-ionized calcium-binding adapter molecule 1 (Iba-1) antibody. In the early stages of ischemia-reperfusion, Iba-1-immunoreactive microglial cells under normothermic ischemia were characterized by swollen somata with short and thick processes, while fine long-branched processes in greater numbers were seen emanating from microglial somata under hypothermic ischemia. In animals subjected to hypothermic ischemia, immunoreactive microglial areas in the hippocampal CA1 sector were significantly increased after 5 and 8 h of reperfusion when compared with those under normothermic ischemia. In the dentate gyrus, an increase in the microglial area under hypothermic ischemia was already evident at 2 h after reperfusion; this increased level was maintained up to 8 h. Considering the various neuroprotective roles of hypothermic ischemia, the characteristic features of microglia under hypothermic ischemia may be associated with the formation of a neuroprotective environment.

Bruxism affects stress responses in stressed rats.

It has been proposed that suppression of stress-related emotional responses leads to the simultaneous activation of both sympathetic and parasympathetic divisions of the autonomic nervous system (ANS) and that the expression of these emotional states has a protective effect against ulcerogenesis. In the present study, we investigated whether stress-induced bruxism activity (SBA) has a physiological effect of on the stress-induced changes of the stomach, thymus, and spleen as well as blood leukocytes, cortisol, and adrenaline. This study demonstrated that SBA attenuated the stress-induced ulcer genesis as well as degenerative changes of thymus and spleen. SBA also attenuated increases of adrenaline, cortisol, and neutrophils in the blood. In conclusion, expression of aggression through SBA during stress exposure attenuates both stress-induced ANS response, including gastric ulcer formation.

Preoperative T staging of urinary bladder cancer: does diffusion-weighted MRI have supplementary value?

OBJECTIVE: The objective of our study was to evaluate whether diffusion-weighted MRI has supplementary value in the preoperative T staging of urinary bladder cancer. MATERIALS AND METHODS: Nineteen consecutive patients (18 men and one woman; age range, 55-83 years; mean, 71 years) known to have or suspected of having urinary bladder cancer underwent MRI at our institution. Urinary bladder cancer was pathologically proven in 18 patients. The pathologic stages were T1 in 14 patients, T2 in two, T3 in one, and T4 in one. Three separate MR image sets were retrospectively reviewed by two independent radiologists: unenhanced T1-weighted images (TR/TE, 607/10) and T2-weighted images (TR(eff)/TE(eff), 4,415/100); unenhanced T1-weighted, T2-weighted, and gadolinium-enhanced images (TR/TE, 10/4.2); and unenhanced T1-weighted, T2-weighted, and diffusion-weighted images (TR(eff)/TE(eff), 2,191/69; b factor, 1,000 s/mm(2)). The radiologists, who were blinded to the pathology findings, assigned T stages and confidence levels for tumors of stage T2 or greater. We used pathologic stages documented in the official pathologic reports as the standard of reference. Observer performance was tested using Spearman's rank correlation, the McNemar test, and receiver operating characteristic (ROC) curve analysis. RESULTS: The correlation between the radiologic and pathologic stages was greater with the diffusion sequence (rho = 0.66) than with the unenhanced (0.62) or gadolinium-enhanced (0.62) sequence (p = 0.34). The sensitivity, specificity, accuracy, and area under the ROC curve for tumors of stage T2 or greater were 80%, 79%, 79%, and 0.71 for the unenhanced sequence; 80%, 79%, 79%, and 0.77 for the gadolinium sequence; and 40%, 93%, 79%, and 0.56 for the diffusion-weighted sequence, respectively (p > 0.05). CONCLUSION: Our results suggest that diffusion-weighted MRI might have high specificity for the detection of invasive urinary bladder tumors. Patients with suspected urinary bladder carcinomas may well be evaluated by MRI including diffusion-weighted imaging for better preoperative T staging.

Optimal acquisition delay for dynamic contrast-enhanced MRI of hypervascular hepatocellular carcinoma.

OBJECTIVE: The purpose of this study was to prospectively determine the optimal acquisition delay for imaging of hypervascular hepatocellular carcinoma with multiphasic dynamic contrast-enhanced MRI. SUBJECTS AND METHODS: One hundred twenty patients with chronic hepatic disease underwent three-phase dynamic contrast-enhanced MRI of the liver, which revealed 49 hypervascular hepatocellular carcinomas. Abdominal aortic contrast arrival time was determined with test bolus imaging. Patients were assigned to one of the following four groups according to acquisition delay determined from abdominal aortic contrast arrival time to the middle of the k-space for the early, late hepatic arterial, and portal venous phases: 0, 12, and 49 seconds (group 1); 3, 15, and 52 seconds (group 2); 6, 18, and 55 seconds (group 3); and 9, 21, and 58 seconds (group 4). Each phase of imaging took 12 seconds. Contrast enhancement in the abdominal aorta, portal vein, hepatic parenchyma, and hepatocellular carcinoma was evaluated. Peritumoral sinusoidal enhancement (i.e., coronal enhancement) also was assessed. RESULTS: Intense enhancement of hepatocellular carcinoma with little background parenchymal enhancement occurred at 9-12 seconds (p < 0.05) after arrival of contrast material in the abdominal aorta. Hepatocellular carcinoma-to-liver contrast began to decline at 15 seconds and decreased to less than zero at 49 seconds. The conspicuity of coronal enhancement was greater 21 seconds after contrast administration than in earlier phases. CONCLUSION: With the injection protocol used in this study, optimal acquisition delay-determined from abdominal aortic contrast arrival time to the middle of the k-space acquisition-for imaging of hypervascular hepatocellular carcinoma was 9-12, 21 or more, and 49 seconds for the early, late hepatic arterial, and portal venous phases.

Optimal scan delays for multiphasic renal multidetector row computed tomography performed with fixed injection duration of contrast medium.

OBJECTIVE: The purpose of our study was to prospectively determine optimal scan delays for multiphasic imaging of the kidney performed with multidetector row computed tomography (CT) and fixed injection duration of intravenous contrast medium. MATERIALS AND METHODS: One hundred ninety-eight patients underwent 3-phase CT of the kidney with 8-slice CT after receiving 2 mL/kg of an intravenous contrast medium of 300 mg I/mL for a fixed duration of 30 seconds. The patients were prospectively randomized into 4 groups according to different scan delays from the start of injection: group 1 (25, 45, 65 seconds), group 2 (30, 50, 70 seconds), group 3 (35, 55, 75 seconds), and group 4 (40, 60, 80 sec). Mean CT values (Hounsfield units [HU]) of the abdominal aorta, renal arteries, veins, cortexes, and medulla were measured. Increases in CT values from precontrast to postcontrast CT (deltaHU) and renal artery-to-vein and renal cortex-to-medulla differential contrasts (deltaHU) were assessed. Qualitative analysis was also performed. RESULTS: Abdominal aorta and renal artery enhancements peaked at 35 seconds (305 DeltaHU; 253 DeltaHU) after injection start, and renal veins peaked at 45 seconds (196 DeltaHU). Renal cortexes peaked at 40 seconds (197 DeltaHU), and renal medullae peaked at 75 seconds (152 DeltaHU). Renal artery-to-vein differential contrasts were high (95-137 deltaHU) at 25 to 30 seconds, and cortex-to-medulla contrasts were high (79-130 deltaHU) at 30 to 55 seconds and then decreased to less than 10 deltaHU at 75 seconds. Qualitative results were in good agreement with quantitative results. CONCLUSIONS: With a fixed 30-second injection, estimated optimal scan delays for multiphasic imaging the kidney were, from the start of injection, 25 to 30 seconds for renal arterial CT angiography, 35 to 45 seconds for the corticomedullary, and 75 seconds for the nephrographic phase.

Depolarization-induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway.

The present study examined the role of phospholipase D2 (PLD2) in the regulation of depolarization-induced neurite outgrowth and the expression of growth-associated protein-43 (GAP-43) and synapsin I in rat pheochromocytoma (PC12) cells. Depolarization of PC12 cells with 50 mmol/L KCl increased neurite outgrowth and elevated mRNA and protein expression of GAP-43 and synapsin I. These increases were suppressed by inhibition of Ca2+-calmodulin-dependent protein kinase II (CaMKII), PLD, or mitogen-activated protein kinase kinase (MEK). Knockdown of PLD2 by small interfering RNA (siRNA) suppressed the depolarization-induced neurite outgrowth, and the increase in GAP-43 and synapsin I expression. Depolarization evoked a Ca2+ rise that activated various signaling enzymes and the cAMP response element-binding protein (CREB). Silencing CaMKIIdelta by siRNA blocked KCl-induced phosphorylation of proline-rich protein tyrosine kinase 2 (Pyk2), Src kinase, and extracellular signal-regulated kinase (ERK). Inhibition of Src or MEK abolished phosphorylation of ERK and CREB. Furthermore, phosphorylation of Pyk2, ERK, and CREB was suppressed by the PLD inhibitor, 1-butanol and transfection of PLD2 siRNA, whereas it was enhanced by over-expression of wild-type PLD2. Depolarization-induced PLD2 activation was suppressed by CaMKII and Src inhibitors, but not by MEK or protein kinase A inhibitors. These results suggest that the signaling pathway of depolarization-induced PLD2 activation was downstream of CaMKIIdelta and Src, and upstream of Pyk2(Y881) and ERK/CREB, but independent of the protein kinase A. This is the first demonstration that PLD2 activation is involved in GAP-43 and synapsin I expression during depolarization-induced neuronal differentiation in PC12 cells.

Abdomen: angiography with 16-detector CT--comparison of image quality and radiation dose between studies with 0.625-mm and those with 1.25-mm collimation.

PURPOSE: To prospectively compare image quality and volume computed tomographic (CT) dose index (CTDI(vol)) of 16-detector CT angiograms of the abdomen acquired with 0.625-mm collimation with those of images acquired with 1.25-mm collimation. MATERIALS AND METHODS: This study had institutional review board approval, and informed consent was obtained from all patients. Dual-phase contrast material-enhanced CT was performed in 78 patients (48 men and 30 women; age, 34-91 years; mean age, 64.8 years) by using a 16-detector CT scanner. Patients were prospectively randomized into two equal-sized groups: those who underwent CT with 0.625-mm collimation and nonoverlapped reconstruction and those who underwent CT with 1.25-mm collimation and 50% overlapped reconstruction. Scan acquisition time was 7.5 seconds in both groups. CTDI(vol) was recorded. Arterial phase volume-rendered, arterial phase multiplanar reformatted, and portal venous phase multiplanar reformatted CT angiograms were generated. Qualitative assessment was performed for image quality and for depiction of splanchnic, intercostal, and lumbar arteries and veins. The unpaired t test was used for statistical comparison. RESULTS: On the arterial phase CT angiograms, there was no difference between the two collimation groups for the depiction of proximal splanchnic arteries, while the dorsal pancreatic, intercostal, and lumbar arteries and some peripheral splanchnic arterial branches were better delineated on CT scans obtained with 0.625-mm collimation than on scans obtained with 1.25-mm collimation (P < .05). Regarding the portal venous phase CT angiograms, no difference between the two groups was found in most veins, except the right adrenal vein (P = .003). Image quality was superior for 1.25-mm collimation (P < .001). CTDI(vol) values were positively correlated with patient body weight (r = 0.34, P < .001) but had no correlation with collimation size (P = .24). CONCLUSION: Scanning with 1.25-mm collimation seems adequate for a routine CT angiography examination of most arteries and veins at 16-detector CT, while scanning with 0.625-mm collimation facilitates improved delineation of fine vessels. CTDI(vol) values correlate positively with body weight but have no correlation with collimation size.