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Purinergic Signalling. 2018 Sep;14(3):245-258., 平成30年度

Local anesthetics are administered intraarticularly for pain control in orthopedic clinics and surgeries. Although previous studies have shown that local anesthetics can be toxic to chondrocytes, the underlying cellular mechanisms remain unclear. The present study investigates acute cellular responses associated with lidocaine-induced toxicity to articular chondrocytes. Rabbit articular chondrocytes were exposed to lidocaine and their morphological changes were monitored with live cell microscopy. The viability of chondrocytes was evaluated using a fluorescence based LIVE/DEAD assay. Acute treatment of chondrocytes with lidocaine (3-30 mM) induced spherical protrusions on the cell surface (so called "membrane blebbing") in a time- and concentration-dependent manner. The concentration-response relationship for the lidocaine effect was shifted leftward by elevating extracellular pH, as expected for the non-ionized lidocaine being involved in the bleb formation. ROCK (Rho-kinase) inhibitors Y-27632 and fasudil completely prevented the lidocaine-induced membrane blebbing, suggesting that ROCK activation is required for bleb formation. Caspase-3 levels were unchanged by 10 mM lidocaine (p = 0.325) and a caspase inhibitor z-VAD-fmk did not affect the lidocaine-induced blebbing (p = 0.964). GTP-RhoA levels were significantly increased (p

Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using (123)I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). "Depression-Dejection" and "Confusion" POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children with AN. This may be a state-related change, which could be used to monitor and guide the treatment of eating disorders.

The Child Behavior Checklist–Dysregulation Profile (CBCL-DP) refers to a pattern of elevated scores on the Attention Problems, Aggression, and Anxiety/Depression subscales of the Child Behavior Checklist. The aim of the present study was to investigate the potential role of GABA inhibitory neurons in children with attention deficit/hyperactivity disorder (AD/HD) and dysregulation assessed with a dimensional measure. Brain single photon emission computed tomography (SPECT) was performed in 35 children with AD/HD using 123I-iomazenil, which binds with high affinity to benzodiazepine receptors. Iomazenil binding activities were assessed with respect to the presence or absence of a threshold CBCL-DP (a score ≥210 for the sum of the three subscales Attention Problems, Aggression, and Anxiety/Depression). We then attempted to identify which CBCL-DP subscale explained the most variance with respect to SPECT data, using “age”, “sex”, and “history of maltreatment” as covariates. Significantly higher iomazenil binding activity was seen in the posterior cingulate cortex (PCC) of AD/HD children with a significant CBCL-DP. The Anxiety/Depression subscale on the CBCL had significant effects on higher iomazenil binding activity in the left superior frontal, middle frontal, and temporal regions, as well as in the PCC. The present brain SPECT findings suggest that GABAergic inhibitory neurons may play an important role in the neurobiology of the CBCL-DP, in children with ADHD.

Two-dimensional prospective acquisition correction (2D-PACE) is a human body motion-correction technique that uses the navigator echo sequence. Clinically, this respiratory-gated technique is used to improve the image quality of magnetic resonance cholangiopancreatography (MRCP). However respiratory motion artifact caused by a mismatch in respiratory rhythm has been experienced. The newly developed breath pacemaker was developed with the aim of providing the best match between the breath cycle and 2D-PACE trigger. The breath pacemaker is composed of two stimulators, an auto voice (AV) system and an auto light (AL) system. The two systems can be controlled separately or concurrently. Using the new breath pacemaker, improvement in MRCP image quality was evaluated in normal volunteers, and definite improvement was noted. Particularly good efficacy was obtained with concurrent control of the AV system and AL system. The results clearly demonstrated that the breath pacemaker can provide good synchronization of 2D-PACE and can lead to enhanced quality of MRCP images.

We report an unusual hepatoid adenocarcinoma in Barrett's esophagus with achalasia, which developed in a 44-year-old Japanese woman. The patient received an esophago-gastrectomy after diagnosis of the tumor and achalasia at the lower esophagus, 4 months before her death due to multiple metastatic tumors of the liver. The main granular tumor removed surgically was a hepatoid adenocarcinoma, mainly composed of clear cancer cells (alpha-1 antitrypsin, albumin and alpha-fetoprotein positive), with elements of choriocarcinoma and tubular adenocarcinoma. Non-neoplastic specialized columnar epithelium was present extensively near the oral side of the tumor edge in the esophagus, indicating Barrett's esophagus. This unusual tumor was therefore considered to have originated in Barrett's esophagus. The gastroesophageal reflux was presumed to have occurred for a long period, as there was a well-preserved fundic gland in the stomach and a history of frequent vomiting from the patient's youth, accounting for the appearance of achalasia.

Rotational three-dimensional digital subtraction angiography (3D-DSA) is very useful for interventional neuroradiology, especially in the endovascular therapy of cerebral aneurysms. However, pseudo-stenosis artifact on the vessel, which runs vertically to the rotational axis, was observed clinically. In this study, this artifact was confirmed in an experiment with 4.5-millimeter diameter vessel phantoms. The attenuation of the phantom at each degree of exposure (44 directions) was measured on the workstation (DSA pixel value). DSA pixel values were plotted from data of 10, 20, 30, 40, and 50 millimeter lengths, respectively. The saturated DSA pixel value of tangent projection on phantoms of 30 millimeters or more in length was observed. This phenomenon induces pseudo-stenosis artifact on 3D-DSA. The maximum reduction in the diameter of the phantom was 27.4% on the length of 50 millimeters. We confirmed that the two-dimensional data vertical to the rotational axis were inaccurate when a straight-coursed, long, segmented vessel was present. Under this special condition, vessels on 3D-DSA were displayed as smaller than their actual diameter.

To cast light on tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer or gastric cancer, 45 cases in gastroduodenostomy (Billroth I, 17 cases) and gastrojejunostomy (Billroth II, 28 cases) groups were compared for a series of parameters. Cancers in Billroth II were significantly more predominant in the anastomosis area and more frequently associated with Epstein-Barr virus infection. Active gastritis, accelerated epithelial cell turnover (as assessed by measurements of apoptosis and cell proliferation), DNA damage, and foveolar cell hyperplasia were all greater in anastomotic areas after Billroth II than in proximal areas after Billroth II or either area after Billroth I. K-ras mutations were rare, but Epstein-Barr virus infection in cancers was seen frequently in anastomosis cases. In conclusion, active gastritis, possibly induced by enterogastric reflux, is linked to tumorigenesis in anastomosis sites in Billroth II cases.

The clinical usefulness of three dimensional images was widely recognized. The three dimensional digital subtraction angiography (3D-DSA) well demonstrated anatomical structures of cerebral arteries with high special resolution. This 3D observation allowed high quality planning for aneurysmal coil packing and neck clipping. Because of the bony structure and curvy arterial anatomy in the skull base region, 3D-CTA and MRA was sometimes distureved the demonstration of the anatomical relationship adjacent to the aneurysm. However, 3D-DSA not only demonstrated arterial anatomy, but also analyzed of vascular structure, quantifiably. And it was useful in radiation dose reduction by reduction of DSA exposure number. We believe that 3D-DSA should provided useful information for planning of surgical and endovascular treatment in the field of cerebro-vascular disease.