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Intrathecal delivery of glial cell line-derived neurotrophic factor (GDNF) reverses mechanical allodynia after 5th lumbar (L5) spinal nerve ligation (SNL). However, the molecular mechanism behind this process is not fully understood. Following sciatic nerve injury, primary afferent neurons in the injured dorsal root ganglion (DRG) begin to express neuropeptide Y (NPY) that is absent in normal DRG. The aim of the current study was to determine the relationship of this de novo expression of NPY and the anti-allodynic effect of GDNF. Following L5 SNL, 73% of neurons began to express NPY mRNA in the ipsilateral L5 DRG and robust NPY-immunoreactive fibers appeared in the ipsilateral GN where the touch-sense mediating A-fiber primary afferents from the hindpaw terminate. Seven-daylong intrathecal infusion of GDNF at the L5 DRG level, starting on day three when mechanical allodynia had fully developed, reversed once-established these changes. The GN neurons normally expressed NPY Y1 receptor, but not Y2, Y4, or Y5 receptors, and L5 SNL did not change the expression pattern. Bolus intracisternal injection of BIBP3226, a Y1 receptor antagonist, dose-dependently reversed mechanical allodynia. We demonstrated that GDNF reversed once-established mechanical allodynia as well as NPY induction in the touch-sense processing pathway. NPY could facilitate touch-sense processing by Y1 receptor in the gracile nucleus after peripheral nerve injury. GDNF may exert anti-allodynic effects through mitigation of this NPY up-regulation. The effectiveness of delayed treatment further indicates the therapeutic potential of GDNF on neuropathic pain. [ABSTRACT FROM AUTHOR]

Tetrodotoxin-sensitive (TTX-s) spontaneous activity is recorded from the dorsal roots after peripheral nerve injury. Primary sensory neurons in the dorsal root ganglion (DRG) express multiple TTX-s voltage-gated sodium channel α-subunits (Navs). Since Nav1.3 increases, whereas all other Navs decrease, in the DRG neurons after peripheral nerve lesion, Nav1.3 is proposed to be critical for the generation of these spontaneous discharges and the contributions of other Navs have been ignored. Here, we re-evaluate the changes in expression of three other TTX-s Navs, Nav1.1, Nav1.6 and Nav1.7, in the injured 5th lumbar (L5) primary afferent components following L5 spinal nerve ligation (SNL) using in situ hybridization histochemistry and immunohistochemistry. While the overall signal intensities for these Nav mRNAs decreased, many injured DRG neurons still expressed these transcripts at clearly detectable levels. All these Nav proteins accumulated at the proximal stump of the ligated L5 spinal nerve. The immunostaining patterns of Nav1.6 and Nav1.7 associated with the nodes of Ranvier were maintained in the ipsilateral L5 dorsal root. Interestingly, putative proprioceptive neurons characterized by α3 Na + /K + ATPase-immunostaining specifically lacked Nav1.7 mRNA in naïve DRG but displayed de novo expression of this transcript following SNL. Nav1.7-immunoreactive fibers were significantly increased in the ipsilateral gracile nucleus where central axonal branches of the injured A-fiber afferents terminated. These data indicate that multiple TTX-s channel subunits could contribute to the generation and propagation of the spontaneous discharges in the injured primary afferents. Specifically, Nav1.7 may cause some functional changes in sensory processing in the gracile nucleus after peripheral nerve injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Revascularization with emergency stent placement in patients with acute middle cerebral artery occlusion is still controversial in Japan. METHODS: We placed balloon-expandable coronary bare stents in 3 patients in whom revascularization was not obtained after intravenous tissue plasminogen activator therapy (IV t-PA) for acute ischemic stroke (middle cerebral artery M1 occlusion). RESULTS: Patient 1 was an 87-year-old woman with left hemiplegia. Her National Institutes of Health Stroke Scale score (NIHSS) was 12, and her magnetic resonance imaging diffusion-weighted image Alberta Stroke Programme Early Computed Tomography Score (MRI DWI-ASPECTS) was 8. Adequate revascularization was not obtained with IV t-PA and adjunctive percutaneous transluminal angioplasty (PTA) for right M1 occlusion, and a stent was placed 368 minutes after onset. Her Thrombolysis in Myocardial Infarction Trial (TIMI) score was 2. After 90 days, her modified Rankin scale (mRS) score was 4. Patient 2 was a 65-year-old woman with left hemiplegia. Her NIHSS score was 16, and MRI DWI-ASPECTS was 9. A stent was placed 337 minutes after onset after IV t-PA and adjunctive PTA for right M1 occlusion. Her TIMI score was 3. After 90 days, her mRS score was 3. Patient 3 was a 61-year-old woman with left hemiplegia. Her NIHSS score was 18, and MRI DWI-ASPECTS score was 7. Arterial dissection was found after IV t-PA and adjunctive PTA for the right M1 occlusion, so a stent was placed 312 minutes after onset. Her TIMI score was 2. After 90 days, her mRS score was 0. CONCLUSIONS: Revascularization with emergency stent placement seems likely to be successful in patients with acute middle cerebral artery occlusion, but clinical symptoms do not always improve in some cases and care is needed in selecting patients for the procedure. [ABSTRACT FROM AUTHOR]

Therapeutic results with respect to lesion size were analyzed and compared in patients with hyperacute cerebral infarction with and without major artery lesions on magnetic resonance angiography (MRA) and in those who did and did not receive intravenous (IV) tissue plasminogen activator (t-PA). Of the patients with cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and September 2009, 127 patients with cerebral infarction in the anterior circulation region in whom head magnetic resonance imaging (diffusion-weighted imaging [DWI]) or MRA was performed (81 men and 46 women; mean age, 71 ± 11 years) were enrolled. Major artery lesions (+) were defined as internal carotid artery occlusion and middle cerebral artery (M1/M2 segment) occlusion and >=50% stenosis. Based on the presence or absence of major artery lesions and the size of DWI lesions, the subjects were divided into 3 groups: MRA-DWI mismatch (+) group [major artery lesion (+) and DWI-ASPECTS >=6], MRA-DWI mismatch (-) group [major artery lesion (+) and DWI-ASPECTS <6], and major artery lesion (-) group. IV t-PA was given to 21 of the 64 patients in the MRA-DWI mismatch (+) group, to 1 of the 24 patients in the MRA-DWI mismatch (-) group, and to 9 of the 39 patients in the major artery lesion (-) group. In the MRA-DWI mismatch (+) group (n = 64), the median National Institutes of Health Stroke Scale (NIHSS) score on admission was higher in t-PA-treated patients than in t-PA-untreated patients (15 vs 11). The modified Rankin scale (mRS) score at day 90 after onset was more favorable in t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) than in t-PA-untreated patients (0-2 in 12 patients [28%] and 3-6 in 31 patients [72%]). After adjusting for admission NIHSS score, there was a significant difference in outcome (mRS score) between t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) and t-PA-untreated patients (0-2 in 3 patients [9%] and 3-6 in 29 patients [91%]) (P = .002). In the MRA-DWI mismatch (-) group (n = 24), mRS scores at day 90 after onset were poor in both t-PA-treated (3-6 in 1 patient [100%]) and t-PA-untreated patients (0-2 in 1 patient [4%] and 3-6 in 22 patients [96%]). In the major artery lesion (-) group (n = 39), mRS scores at day 90 after onset were favorable in both t-PA-treated (0-2 in 9 patients [100%]) and t-PA-untreated patients (0-2 in 28 patients [93%] and 3-6 in 2 patients [7%]). When comparing major artery lesions in the MRA-DWI mismatch (+) group, outcomes were more favorable in patients with M1/M2 segment lesions who received t-PA than in those who did not receive t-PA. In the MRA-DWI mismatch (+) group, the prognosis was significantly better for t-PA-treated patients than for t-PA-untreated patients, suggesting that IV t-PA is indicated in patients with MRA-DWI mismatch.Copyright © 2012 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Abstract: By introducing design of experiment (DOE), we examined the effect of processing parameters, such as peening pressure, particle supply rate, peening time, and heating time, on the characteristics of modified layers. The surface of structural steel was modified by AIH-FPP with Cr shot particles at 900°C in an argon atmosphere. Results showed that the peening time strongly affected the levels of oxygen concentration at the treated surface; the longer the peening time, the higher the oxygen concentration. Heating time also affected the Cr concentration at the surface; the longer the heating time, the higher the Cr concentration. Corrosion tests were performed using a three-electrode electrochemical cell connected to a computer driven potentiostat. The specimens with Cr diffused layers showed higher corrosion resistance compared to other specimens. This is because of the existence of passive films on treated surfaces. [Copyright &y& Elsevier]

In recent years, patient selection for intravenous tissue plasminogen activator (t-PA) therapy based on clinical-diffusion mismatch (CDM) has been closely examined. We investigated the relationship between prognosis and CDM in patients with hyperacute cerebral infarction within 3 hours of onset and compared CDM with diffusion-perfusion mismatch (DPM). Of 122 patients with hyperacute cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and November 2008, 85 patients with cerebral infarction in the anterior circulation who underwent head magnetic resonance imaging diffusion-weighted imaging (DWI)/magnetic resonance angiography (MRA) (51 men and 34 women; average age, 74 ± 10 years) were enrolled. Seventeen of these patients underwent CT perfusion imaging. CDM-positive cases were those with a National Institute of Health Stroke Scale (NIHSS) score ≥ 8 and a DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥ 8; CDM-negative cases were those with an NIHSS score ≥ 8 and an ASPECTS-DWI < 8. The other patients were classified as belonging to the NIHSS score < 8 group. Of the 32 CDM-positive cases, 10 received t-PA infusion. These patients had markedly higher modified Rankin Scale scores 90 days after onset compared with the 22 patients who did not receive t-PA infusion. The 8 CDM-positive cases included 4 DPM-positive cases and 4 DPM-negative cases, and a discrepancy was confirmed between CDM and DPM. In all DPM-positive cases, MRA confirmed lesions in major intracranial arteries. CDM may enable more accurate prediction of outcomes in patients with hyperacute cerebral infarction. In addition, the combination of CDM findings and MRA findings (stenosis or occlusion in major intracranial arteries) may be an alternative to DPM for determining the indications for IV t-PA therapy in patients with hyperacute cerebral infarction. [ABSTRACT FROM AUTHOR]

Abstract: While the voltage-gated sodium channels (VGSCs) are the key molecules for neuronal activities, the precise distribution of them in spinal cord is not clear in previous studies. We examined the expression of mRNAs for α-subunits of VGSC (Navs) in adult rat spinal cord before and 7 days after L5 spinal nerve ligation (SPNL) or complete Freund''s adjuvant (CFA)-induced paw inflammation by in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, and immunohistochemistry. Nav1.1 and Nav1.6 mRNAs were present in all laminae, except for lamina II, including the spinothalamic tract neurons in lamina I identified by retrograde tracing of Fluoro-gold. Nav1.2 mRNA was predominantly observed in the superficial layers (laminae I, II), and Nav1.3 mRNA was more restricted to these layers. All these transcripts were expressed by the neurons characterized by immunostaining for neuron-specific nuclear protein. Nav1.7 mRNA was selectively expressed by a half of motoneurons in lamina IX. No signals for Nav1.8 or Nav1.9 mRNAs were detected. Immunohistochemistry for Nav1.1, Nav1.2, Nav1.6, and Nav1.7 proteins verified some of these neuronal distributions. L5 SPNL decreased Nav1.1 and Nav1.6 mRNAs, and increased Nav1.3 and Nav1.7 mRNAs in the axotomized spinal motoneurons, without any changes in other laminae of L4–6 spinal segments. Intradermal injection of CFA did not cause any transcriptional change. Our findings demonstrate that spinal neurons have different compositions of VGSCs according to their location in laminae. Pathophysiological changes of spinal neuronal activity may due to post-transcriptional changes of VGSCs. Comparison with our previous data concerning the subpopulation-specific distribution of Nav transcripts in primary afferent neurons provides potentially specific targets for local analgesics at the peripheral nerve and spinal levels. [Copyright &y& Elsevier]

Abstract: A new simple and accurate shell FE-based structural Hot Spot Stress (HSS) determination method for web-stiffened cruciform joints has been proposed. Local stress of welded joints in full-scale bulk carrier (BC)’s lower stool models subject to bending and pressure loadings are examined. HSSs determined by the proposed method are compared with those derived by Lotsberg’s method and the conventional 0.5t–1.5t extrapolation. As results, following are found: [(1)] The local stress of full-scale BC lower stool models with various stool angle and plate thickness can be calculated accurately solely from shell FE results by means of the proposed method. [(2)] HSSs of welded joints in full-scale BC lower stool models subject to bending and pressure loadings derived by the proposed method show good agreement with the target HSSs determined from fine solid models. This demonstrates the validity of the proposed method for actual ship structures under the real load. [(3)] The excessive safety allowance of HSS determined by the conventional 0.5t–1.5t extrapolation can be reduced substantially by adopting Lotsberg’s method or our proposal. The proposed HSS determination method gives more accurate estimates compared to Lotsberg’s method under the conditions chosen, and the application range of the proposed method is equal to or wider than Lotsberg’s method. [Copyright &y& Elsevier]

Abstract: We have previously found that tissue type and urokinase type plasminogen activators (tPA and uPA) are induced in dorsal root ganglia (DRG) neurons after peripheral axotomy and that tPA plays crucial roles in generating neuropathic pain. Here we examined whether the plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) mRNA, endogenous inhibitors of tPA and uPA, are induced in the DRG following sciatic nerve transection. L4 and L5 DRG sections were examined using in situ hybridization histochemistry. The results showed that both PAI-1 and PAI-2 mRNA were up-regulated in DRG neurons within 1 day, and peaked at 1–3 days, after injury. Reduction of these mRNA was observed from 7 days after injury. The precise expression patterns of PAI-1 and PAI-2 mRNA at 3 days after axotomy revealed that PAI-1 mRNA was observed in predominantly small neurons, while much of the PAI-2 mRNA was expressed in large neurons. Double-labeling analysis of these mRNAs with activated transcription factor 3, known as an injury marker, revealed that most PAI-1 and PAI-2 mRNAs was induced in injured neurons. Co-expression of PAI-1, 2 with tPA and uPA in DRG neurons suggests that these inhibitors may act in an autocrine manner to modulate extracellular proteolytic activity after nerve injury. [Copyright &y& Elsevier]

Background Although complete resection of colorectal cancer liver metastasis (CLM) is the only potentially curative treatment, surgery alone is not enough, as the recurrence rate after resection of CLM is high. Therefore, in clinical practice, adjuvant chemotherapy (AC) has been performed after resection of CLM. However, the evidence supporting the efficacy of AC after resection of CLM is not sufficient. Previous reports have noted that AC after resection of CLM is effective only in patients with a high risk of recurrence. The purpose of this study was to classify the risk of recurrence using systemic inflammatory markers, which have been reported to be associated with the clinical outcomes, and to evaluate the efficacy of AC according to the risk of recurrence. Methods We retrospectively reviewed the medical records of 119 patients with CLM who underwent potentially curative surgery. The C-reactive protein-to-albumin ratio (CAR) was calculated from the blood samples by dividing the serum C-reactive protein level by the serum albumin level. The optimal cut-off value of the CAR was determined according to the ROC curve analysis, and then the patients were classified into the high- or low-CAR group. We examined the relationship between the CAR and the relapse-free survival (RFS) after resection of CLM and evaluated the efficacy of AC according to the risk of recurrence. Results The cut-off value of the CAR was set at 0.0471 based on the ROC curve analysis. The RFS rates were significantly better in the low-CAR group than in the high-CAR group. The efficacy of AC after resection of CLM was not recognized in the low-CAR group (with a low risk of recurrence), whereas the RFS rates were significantly better for the patients who were treated with AC after resection of CLM in the high-CAR group (with a high risk of recurrence). Conclusions The preoperative CAR was found to be useful as prognostic markers in patients with CLM who were treated with potentially curative resection. Furthermore, it was suggested that AC after resection of CLM may be effective for preventing recurrence in patients with high inflammatory markers who have a high risk of recurrence. Legal entity responsible for the study Osaka City University. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Abstract: The possible involvement of fibroblast growth factor receptor (FGFR) activation in the dorsal root ganglion (DRG) was examined following peripheral nerve injury in the rat. Ligation of the sciatic nerve down-regulated FGFR2, -3 and -4 mRNA; however, the expression of FGFR1 mRNA showed no change. Activation of FGFR was examined by immunohistochemistry using an antibody of the phosphorylated form of FGFR1-4. Ligation of the sciatic nerve produced phosphorylation of FGFR in the L4 and 5 DRG ipsilateral to the injury, starting at 3 days after the lesion and persisting for more than 30 days. Substantial activation of FGFR was observed, mainly in unmyelinated small DRG neurons that co-expressed phosphorylated p38 mitogen-activated protein kinase (MAPK). Continuous intrathecal infusion of the FGFR1 inhibitor, 3-[3-(2-carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone, reduced p38 MAPK phosphorylation in the DRG and pain-related behaviors in the partial sciatic nerve model rat without affecting on the activation of spinal glia cells (microglia and astrocyte). In the injured small DRG neurons, activation of FGFR1 may contribute to the generation of neuropathic pain by activating p38 MAPK. [Copyright &y& Elsevier]

Abstract: Two cold-sensitive transient receptor potential (TRP) channels, TRPA1 and TRPM8, have been identified and considered interesting because of their possible roles in thermosensation, nociception and other functions. Recently, we have reported that the phosphorylation of extracellular signal-regulated protein kinase and p38 mitogen-activated protein kinase occurred in primary afferent neurons in response to noxious heat stimulation of the peripheral tissue, i.e. activity-dependent activation of extracellular signal-regulated protein kinase and p38 in dorsal root ganglion neurons. In the present study, we investigated the phosphorylation of extracellular signal-regulated protein kinase, p38, and c-Jun N-terminal kinase in the rat dorsal root ganglion by cold stimulation using immunohistochemistry. Cold stimuli (28-4 °C) were applied by immersion of the hind paw into a water bath (six times of 10 s stimulation and 10 s interval, total 2 min). Noxious cold stimulation induced phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38, but not phosphorylated-c-Jun N-terminal kinase, in small to medium diameter sensory neurons with a peak at 2 min after stimulation. We found that a cold stimulation at 4 °C showed a marked increase in the number of activated neurons. Furthermore, double staining for phosphorylated-extracellular signal-regulated protein kinase and phosphorylated-p38 showed no colocalization in the dorsal root ganglion neurons. We then performed double-labeling experiments for TRPA1 and TRPM8 mRNA and phosphorylation of mitogen-activated protein kinase. The majority of phosphorylated-extracellular signal-regulated protein kinase-positive neurons also expressed TRPM8 mRNA, whereas phosphorylated-p38 heavily colocalized with TRPA1 mRNA after noxious cold stimulation. Our data suggest that the noxious, but not innocuous, cold stimulation in vivo induced differential activation of extracellular signal-regulated protein kinase and p38 pathways in each subpopulation containing TRPA1 or TRPM8 in dorsal root ganglion. [Copyright &y& Elsevier]

Abstract: A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. L5 ventral rhizotomy and spinal nerve transection produced not only mechanical and heat hypersensitivity, but also an increase in brain-derived neurotrophic factor mRNA/protein in the L5 dorsal root ganglion at 7 days after surgery. In contrast, rats in the L5 dorsal rhizotomy and dorsal rhizotomy+ventral rhizotomy groups did not show both pain behaviors at 7 days after surgery, despite brain-derived neurotrophic factor upregulation in medium- and large-size neurons in the L5 dorsal root ganglion. On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury. [Copyright &y& Elsevier]

Inflammation of the primary afferent proximal to the dorsal root ganglion (DRG) and the DRG itself is known to produce radicular pain. Here, we examined pain-related behaviors and the activation of extracellular signal-regulated protein kinase (ERK) in the DRG after inflammation near the DRG somata. Inflammation of the L4/5 nerve roots and DRG induced by complete Freund''s adjuvant (CFA) produced mechanical allodynia on the ipsilateral hindpaw and induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase (trk) A-expressing small- and medium-size neurons. This CFA-induced increase in ERK phosphorylation was mediated through trk receptors, because intrathecal treatment with the tyrosine kinase inhibitor, K252a, reduced the activation of ERK. On the other hand, an increase in brain-derived neurotrophic factor (BDNF) mRNA/protein in the DRG concomitant with the ERK activation was also observed. Furthermore, we found that nerve growth factor (NGF) injection directly into the L4/5 nerve roots and DRG produced mechanical allodynia, and an increase in the phosphorylation of ERK and BDNF expression in the DRG, but the mitogen-activated protein kinase (MAPK) kinase1/2 inhibitor, U0126, inhibited the effects induced by NGF. Therefore, we suggest that after inflammation near the cell body, NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK-MAPK. The activation of MAPK in the primary afferents may be involved in the pathophysiological mechanisms of inflammation-induced radiculopathy and MAPK pathways in the primary afferents may be potential targets for pharmacological intervention for neuropathic pain produced by inflammation near the DRG somata. [Copyright &y& Elsevier]

Multiple voltage-gated sodium channels are the primary mediators of cell excitability. They are multimers that consist of the pore-forming α subunit and auxiliary β subunits. Although ion permeability and voltage sensing are primarily determined by the α subunit, β subunits are important modulators of sodium channel function. The purpose of this study was to assess the effect of axotomy on the expression of β subunits (β1, β2 and β3) and coexpression of Nav1.3 and β3 subunits in the dorsal root ganglion (DRG). We used sciatic nerve transection models or spared nerve injury (SNI) models in the rat. In reverse transcriptase–polymerase chain reaction analysis, there were no significant differences between contralateral and ipsilateral DRGs of β1 and β2 mRNA 3 days after axotomy. β3 mRNA expression in ipsilateral DRGs increased significantly compared with contralateral DRGs 3 days after axotomy. In in situ hybridization histochemistry, β1 mRNA was predominantly expressed in medium- to large-size neurons, whereas β2 mRNA was expressed in small- to large-size neurons. There were no significant differences in β1 and β2 mRNA between contralateral and ipsilateral DRGs 3 days after axotomy. In contrast, β3 mRNA was mainly expressed in small neurons and occasionally in medium- to large-size neurons, and β3 mRNA expression in small c-type neurons in ipsilateral DRGs was increased significantly compared with contralateral DRGs. We examined β3 mRNA expression with one of α subunits, Nav1.3-ir, in DRG neurons after axotomy using the double labeling method. We found a high percentage of coexpression in injured DRG neurons: 83.6±2.8% of neurons expressing β3 mRNA were labeled for Nav1.3-ir; 70.1±3.1% of Nav1.3-ir neurons expressed β3 mRNA. We also examined the expression of β3 mRNA in DRG neurons in the SNI model, a neuropathic pain model. We used activating transcription factor 3 to identify axotomized neurons, and found that β3 mRNA up-regulation occurred mainly in axotomized neurons in the neuropathic pain model. These data strongly suggest that β3 expression in injured DRG neurons following axotomy might be an important pathomechanism of post-nerve injury pain in primary sensory neurons. [Copyright &y& Elsevier]

To help understand planetary gamma-ray spectra, the energies and intensities of gamma rays produced by energetic particles interacting in thick targets were simulated experimentally and numerically. Using the accelerator at RIKEN, thick targets of iron, granite, and gabbro were exposed to 180 or 210 MeV proton beam, and characteristic gamma rays emitted from the targets were measured by Ge detectors. The experimental results were compared with the values calculated by Geant4. The relative intensities of gamma-ray lines from the iron target in the experiment were consistent with those in the calculation within the error of ∼5%. As for stone targets, strong inconsistencies were observed. Further improvement in the calculation code and cross section files, as well as experimental resemblance to space missions are indispensable for gamma-ray spectroscopy. [Copyright &y& Elsevier]

Increased left ventricular (LV) mass and abnormal geometry have a powerful prognostic value for cardiovascular morbidity and mortality including stroke. However, there have been no studies on the association between LV hypertrophy and preclinical brain damage in essential hypertensive patients. In the present study, we investigated the relation between LV hypertrophy and asymptomatic cerebrovascular damage identified by magnetic resonance imaging in 150 essential hypertensive patients, with an emphasis on LV geometry. Patients were divided into the following 4 groups according to their LV mass index and relative wall thickness; normal ventricular geometry (n = 50), concentric remodeling (n = 22), eccentric hypertrophy (n = 44), and concentric LV hypertrophy (n = 34). Lacunar lesions and leukoaraiosis were evaluated. The prevalence of lacunae was significantly higher in patients with LV remodeling than in patients with normal LV (chi-square 19.6, p = 0.0002). The number of lacunae was significantly higher in patients with LV hypertrophy than in patients with normal LV or concentric remodeling (F [3,146] = 8.03, p<0.0001). The severity of leukoaraiosis was also significantly greater in patients with LV hypertrophy than in patients with a normal left ventricle (chi-square 14.5, p = 0.02). Stepwise regression analysis confirmed that LV mass index and relative wall thickness, in addition to age and systolic blood pressure, were independent predictors for asymptomatic cerebrovascular damage, even in the absence of neurologic abnormalities. In hypertensive patients, LV hypertrophy, and especially concentric LV hypertrophy, provides important prognostic information on the presence of pre-clinical brain damage. [ABSTRACT FROM AUTHOR]