Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.

PURPOSE: The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK). MATERIALS AND METHODS: Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined. RESULTS: Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells. CONCLUSION: This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.

SARC-F Validation and SARC-F+EBM Derivation in Musculoskeletal Disease: The SPSS-OK Study.

OBJECTIVES: To validate the SARC-F questionnaire for sarcopenia screening in musculoskeletal disease setting, and to assess improvements in diagnostic accuracy by adding "EBM" (elderly and body mass index information) to the SARC-F. DESIGN: Diagnostic accuracy study. SETTING AND PARTICIPANTS: The center involved in this study was located in an urban area of Kobe City, Japan. People with musculoskeletal disease in the knee, hip, or spine who were scheduled for surgical treatment were included. MEASUREMENTS: Sarcopenia was evaluated using the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP2), which included bioimpedance, handgrip strength, and gait speed. Patients answered the SARC-F questionnaire and their body mass index was measured. SARC-F and "EBM" information were combined into an original score. The sensitivities, specificities, and areas under the receiver operating characteristic curve (AUC) were estimated and compared to identify sarcopenia. RESULTS: A total of 959 patients were included. Sarcopenia by AWGS criteria was identified in 36 (3.8%) patients. SARC-F had a sensitivity of 41.7% and specificity of 68.5%. SARC-F+EBM had a sensitivity of 77.8% and specificity of 69.6%, with substantial improvement in sensitivity (P<0.001). The AUCs for SARC-F and SARC-F+EBM were 0.557 (95% confidence interval [CI] 0.452-0.662) and 0.824 (95% CI 0.762-0.886), respectively (P<0.001). Similar results were obtained when EWGSOP2 criteria were used as the reference standard. CONCLUSION: The SARC-F alone is not adequate for finding cases in musculoskeletal disease settings. SARC-F+EBM significantly improved the sensitivity and overall diagnostic accuracy of the SARC-F for screening sarcopenia. SARC-F+EBM is potentially useful for screening sarcopenia in different ethnic and disease settings.

Appropriate management of high-flow priapism based on color Doppler ultrasonography findings in pediatric patients: four case reports and a review of the literature.

INTRODUCTION: High-flow priapism in children is a very rare condition, and there is no clear consensus on its management. High-flow priapism is associated with increased cavernosal blood flow and broadly divided into two groups based on the presence or absence of arteriocavernous fistula in the corpora cavernosa. OBJECTIVE: This study aimed to determine the appropriate management of high-flow priapism based on the existence of arteriocavernous fistula using penile color Doppler ultrasonography (CDU) findings in the pediatric population. STUDY DESIGN: The cases of four boys aged between 6 and 11 years with high-flow priapism treated between 2009 and 2017 are reported. Two boys had prior perineal trauma, one boy had blunt penile glans trauma, and one had no obvious cause for the condition. All boys initially underwent penile CDU and were treated conservatively or via selective arterial embolization depending upon the presence or absence of an arteriocavernous fistula. RESULTS: Penile CDU revealed an arteriocavernous fistula inside the corpus cavernosum penis in two of four boys and increased blood flow inside the corpus spongiosum in the remaining boys. The former two boys underwent selective arterial embolization and one boy underwent repeated embolization because of remaining arteriocavernous fistula feeding from the contralateral cavernosal artery, whereas the boys with no arteriocavernous fistula on CDU were managed conservatively. All boys were successfully treated within 1 month, and they had normal morning erection and no evidence of recurrent priapism at the follow-up. DISCUSSION: Unlike low-flow priapism, high-flow priapism is not a medical emergency. Therefore, conservative therapy is an appropriate initial treatment, although selective arterial embolization can be effective for high-flow priapism with arteriocavernous fistula, with a success rate of 97% and no reported complications to date. Penile CDU is an imaging technique that can detect focal areas of turbulent flow with sensitivity close to 100%. This study has several limitations including a small number of cases, limited follow-up duration, and possibility of spontaneous arteriocavernous fistula closure in cases treated by arterial embolization. CONCLUSION: Penile CDU could be a reliable tool to diagnose high-flow priapism and detect the presence or absence of arteriocavernous fistula. Although conservative therapy remains the first choice, selective arterial embolization may be an early treatment option when CDU reveals an arteriocavernous fistula.

Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts.

BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.

Extending coherence time of macro-scale diamond magnetometer by dynamical decoupling with coplanar waveguide resonator.

Ultimate sensitivity for quantum magnetometry using nitrogen-vacancy (NV) centers in a diamond is limited by a number of NV centers and coherence time. Microwave irradiation with a high and homogeneous power density for a large detection volume is necessary to achieve a highly sensitive magnetometer. Here, we demonstrate a microwave resonator to enhance the power density of the microwave field and an optical system with a detection volume of 1.4 × 10-3 mm3. The strong microwave field enables us to achieve 48 ns Rabi oscillation which is sufficiently faster than the phase relaxation time of NV centers. This system combined with a decoupling pulse sequence, XY16, extends the spin coherence time (T 2) up to 27 times longer than that with a spin echo method. Consequently, we obtained an AC magnetic field sensitivity of 10.8 pt/ Hz using the dynamical decoupling pulse sequence.

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia.

BACKGROUND: Previously, the mucosal histology in achalasia has only been investigated using superficial biopsy or surgically resected esophageal specimens in end-stage cases. We investigated the histology of the full-layer mucosa in early and advanced achalasia. METHODS: Endoscopy was performed for the pinstripe pattern (PSP) (an early achalasia indicator) and dilation and thickening of the mucosa (advanced achalasia indicators). A mucosal entry site for peroral endoscopic myotomy was created using cap-fitted endoscopic mucosal resection to access the full-layer mucosa and the submucosa. KEY RESULTS: Mucosal histology was compared between 32 patients with achalasia and 15 controls. Histological esophagitis with findings of inflammatory cell infiltration and dilated intercellular spaces was observed more in patients with achalasia than in controls (87.5% vs 13.3%, P<.001; 84.4% vs 46.7%, P=.049). Muscularis mucosae (MM) atrophy and epithelial wave were only observed in achalasia (40.6% vs 0%, P=.005; 28.1% vs 0%, P=.043). Fibrosis was more common in achalasia, but without statistical significance (31.3% vs 20.0%, P=.503). In achalasia with endoscopic dilation and thickening of the mucosa, MM atrophy was observed histologically, and in cases involving endoscopic PSP, the histological epithelial wave was observed. CONCLUSIONS & INFERENCES: Histological findings of esophagitis were observed endoscopically even in early achalasia. Pinstripe pattern corresponds to the epithelial wave observed histologically in achalasia, whereas endoscopic findings in advanced achalasia correspond to MM atrophy. Appropriate management is necessary during early achalasia to prevent progression to advanced achalasia with more severe histological changes.

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study.

The effect of endoscopic submucosal dissection (ESD) on esophageal motility remains unknown. Therefore, the aim of this study is to elucidate changes in esophageal motility after ESD along with the cause of dysphagia using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility. Twenty patients who underwent ESD for superficial esophageal carcinoma were enrolled in this study. Patients filled out a questionnaire about dysphagia and underwent HRM before and after ESD. Results before and after ESD were compared. Data were obtained from 19 patients. The number of patients who complained of dysphagia before and after ESD was 1/19 (5.3%) and 6/19 (31.6%), respectively (P = 0.131). Scores from the five-point Likert scale before and after ESD were 0.1 ± 0.5 and 1.0 ± 1.6, respectively (P = 0.043). The distal contractile integral (DCI) before and after ESD and the number of failed, weak, or fragmented contractions were not significantly different. However, in five patients with circumferential ESD, DCI was remarkably decreased and the frequency of fail, weak, or fragmented contractions increased. Univariate regression analysis showed a relatively strong inverse correlation of ΔDCI with the circumferential mucosal defect ratio {P < 0.01, standardized regression coefficient (r) = -0.65}, the number of stricture preventions (P < 0.01, r = -0.601), and the number of stricture resolutions (P < 0.01, r = -0.77). This HRM study showed that impairment of esophageal motility could be caused by ESD. The impairment of esophageal motility was conspicuous, especially in patients with circumferential ESD and subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Impaired esophageal motility after ESD might explain dysphagia.

Chromosomal anomalies and sperm retrieval outcomes of patients with non-obstructive azoospermia: a case series.

Some preoperative factors affecting the outcome of microdissection testicular sperm extraction (micro-TESE) have been previously evaluated. However, other than Klinefelter syndrome (KS), no other chromosomal anomalies have been discussed in the context of sperm retrieval outcomes. The objective of this study was to describe chromosomal anomalies and their relationship with sperm retrieval outcomes in patients with non-obstructive azoospermia (NOA). Of the 197 NOA patients whose clinical records were retrospectively reviewed, 144 (73.1%) had normal 46,XY karyotype, 40 (20.3%) had KS (47,XXY), and 13 (6.6%) had other chromosomal anomalies (autosomal in seven cases and sex-chromosomal anomalies in six). Of the seven patients with autosomal anomalies, two had the reportedly normal variant 46,XY,inv(9)(p12;q13). Testicular volume and serum hormone levels (luteinizing hormone, follicle-stimulating hormone, and total testosterone) of the patients with chromosomal anomalies other than KS were comparable to those of the patients with normal karyotype. The sperm retrieval rate of the patients with 46,XY karyotype, KS, or other chromosomal anomalies were 27.1%, 22.5%, and 15.4%, respectively, with no statistically significant difference. However, among the samples collected from the 13 patients with chromosomal anomalies other than KS, only those from the two patients with the normal variant 46,XY,inv(9)(p12;q13) contained spermatozoa. Among our series of NOA patients, the incidence of autosomal anomalies was higher than that generally noted among neonates, which suggests that not only sex-chromosomal anomalies but also autosomal anomalies may affect the development of NOA. Furthermore, our findings suggest that sperm retrieval outcome is more unfavorable in NOA patients with chromosomal anomalies than in NOA patients with 46,XY karyotype or KS, despite the use of micro-TESE.

Effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese azoospermic men with and without Klinefelter syndrome.

Obesity is reported to have adverse effects on semen quality and the endocrine system. In this study, we evaluated the effect of obesity on sperm retrieval outcome and reproductive hormone levels in Japanese men with non-obstructive azoospermia (NOA). This study is based on the clinical records of 217 men [172 with a 46,XY karyotype, 45 with Klinefelter syndrome (KS)] with NOA who underwent microdissection testicular sperm extraction at Nagoya City University Hospital between January 2004 and December 2014. Body mass index (BMI) and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone (TT) were measured in all patients. In a subset of patients, bioavailable testosterone (cBAT) also was calculated. Values were evaluated separately in patients with and without KS. Sperm retrieval rates (SRRs) in 46,XY men with a BMI <25 kg/m2 and ≥25 kg/m2 were 29.3% and 18.4%, respectively (p = 0.142), while SRRs in KS men with a BMI <25 kg/m2 and ≥25 kg/m2 were 25.0% and 35.3%, respectively (p = 0.460). TT level in men with a BMI ≥25 kg/m2 was lower than that in men with a BMI <25 kg/m2 , regardless of KS status. According to Pearson product-moment correlation coefficients, TT and cBAT levels tended to have negative correlations with BMI; however, statistical significance was observed only for TT level in 46,XY men (r = 0.340, p < 0.001). LH and FSH levels were negatively correlated with BMI in KS men (r = -0.466, p = 0.001 and r = -0.647, p < 0.001, respectively), but not in 46,XY men. These results suggest that obesity may be irrelevant to sperm retrieval outcome in patients with NOA. The negative correlations between gonadotropins and BMI in patients with KS suggest an underlying suppressive effect on gonadotropin excretion, which is distinctive in obese patients with KS.

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia.

BACKGROUND: Histopathology of muscularis externa in primary esophageal motility disorders has been characterized previously. We aimed to correlate the results of high-resolution manometry with those of histopathology. METHODS: During peroral endoscopic myotomy, peroral esophageal muscle biopsy was performed in patients with primary esophageal motility disorders. Immunohistochemical staining for c-kit was performed to assess the interstitial cells of Cajal (ICCs). Hematoxylin Eosin and Azan-Mallory staining were used to detect muscle atrophy, inflammation, and fibrosis, respectively. KEY RESULTS: Slides from 30 patients with the following motility disorders were analyzed: achalasia (type I: 14, type II: 5, type III: 3), one diffuse esophageal spasm (DES), two outflow obstruction (OO), four jackhammer esophagus (JE), and one nutcracker esophagus (NE). ICCs were preserved in high numbers in type III achalasia (n=9.4±1.2 cells/high power field [HPF]), compared to types I (n=3.7±0.3 cells/HPF) and II (n=3.5±1.0 cells/HPF). Moreover, severe fibrosis was only observed in type I achalasia and not in other types of achalasia, OO, or DES. Four of five patients with JE and NE had severe inflammation with eosinophilic infiltration of the esophageal muscle layer (73.8±50.3 eosinophils/HPF) with no epithelial eosinophils. One patient with JE showed a visceral myopathy pattern. CONCLUSIONS & INFERENCES: Compared to types I and II, type III achalasia showed preserved ICCs, with variable data regarding DES and OO. In disorders considered as primary esophageal motility disorders, a disease category exists, which shows eosinophilic infiltration in the esophageal muscle layer with no eosinophils in the epithelium.

Joint awareness after total knee arthroplasty is affected by pain and quadriceps strength.

INTRODUCTION: There is a growing interest in the use of patient-reported outcomes to provide a more patient-centered view on treatment. Forgetting the artificial joint can be regarded as the goal in joint arthroplasty. The goals of the study were to describe changes in joint awareness in the artificial joint after total knee arthroplasty (TKA), and to determine which factors among pain, knee range of motion (ROM), quadriceps strength, and functional ability affect joint awareness after TKA. HYPOTHESIS: Patients undergoing TKA demonstrate changes in joint awareness and joint awareness is associated with pain, knee ROM, quadriceps strength, and functional ability. PATIENTS AND METHODS: This prospective cohort study comprised 63 individuals undergoing TKA, evaluated at 1, 6, and 12 months postoperatively. Outcomes included joint awareness assessed using the Forgotten Joint Score (FJS), pain score, knee ROM, quadriceps strength, and functional ability. RESULTS: Fifty-eight individuals completed all postoperative assessments. All measures except for knee extension ROM improved from 1 to 6 months. However, there were no differences in any measures from 6 to 12 months. FJS was affected most greatly by pain at 1 month and by quadriceps strength at 6 and 12 months. DISCUSSION: Patients following TKA demonstrate improvements in joint awareness and function within 6 months after surgery, but reach a plateau from 6 to 12 months. Quadriceps strength could contribute to this plateau of joint awareness. LEVEL OF EVIDENCE: Prospective cohort study, IV.

Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.

BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

BACKGROUND: Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long-term outcomes. However, the short-term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in-hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF. METHODS: The Acute Decompensated Heart Failure Syndromes (ATTEND) study investigators enrolled 4107 patients hospitalised with AHF. Investigators evaluated the presence or absence of an S3 during routine physical examination. RESULTS: On admission to hospital, 1673 patients (41%) had an S3. Patients with an S3 had a higher heart rate, higher serum level of B-type natriuretic peptide and higher creatinine levels than patients without an S3. However, there were no significant differences of systolic blood pressure, serum sodium, haemoglobin, C-reactive protein and total bilirubin between the two groups. Multivariate analysis adjusted for various markers of disease severity revealed that only the presence of an S3 was independently associated with an increase of in-hospital all cause death [adjusted odds ratio (OR), 1.69; 95% confidence interval (CI), 1.19-2.41; p = 0.003] and cardiac death (adjusted OR, 1.66; 95% CI, 1.08-2.54; p = 0.020) among the congestive physical findings related to heart failure (S3, rales, jugular venous distension and peripheral oedema). CONCLUSIONS: Detecting an S3 on admission was independently associated with adverse in-hospital outcomes in patients with AHF. Our findings suggest that careful bedside assessment is clinically meaningful.

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects.

Preliminary study for the assessment of physical activity using a triaxial accelerometer with a gyro sensor on the upper limbs of subjects with paraplegia driving a wheelchair on a treadmill.

OBJECTIVE: This study aimed to examine whether, on the basis of the relationship between sensors attached on the upper limbs and energy expenditure (EE) at the time of wheelchair propulsion, there are differences in the measurement of EE depending on the sensor attachment site and whether addition of the angular velocity information to the acceleration value is advantageous. We also aimed to clarify the variables used to estimate EE as well as the estimated error. SETTING: Laboratory of the National Hospital Organization Murayama Medical Center, Japan. METHODS: Six male subjects with spinal cord injuries participated in the study. Each wore sensors at the wrist and the middle upper arm on both sides while driving a wheelchair on a treadmill at three levels: very, very light; very light; and fairly light. Triaxial acceleration, triaxial angular velocity and EE were measured during driving. We analyzed the correlation between EE and acceleration, angular velocity and synthesized values of acceleration and angular velocity at each location using regression, multiple regression and Bland-Altman analyses. RESULTS: The determination coefficients between EE and the acceleration, angular velocity and synthesized values of acceleration and angular velocity varied from 0.68 to 0.87 at each location. The mean difference between the measured and estimated EE varied from 0.0028 (s.d., 0.0027) kcal min(-1) kg(-1) on the right upper arm. CONCLUSION: These findings suggest that combining the synthesized values of angular velocity and acceleration of the motion sensors on the upper limbs might reflect EE during a wheelchair driving activity on a treadmill.

Clinical effect of hyperbaric oxygen therapy in adhesive postoperative small bowel obstruction.

BACKGROUND: Hyperbaric oxygen (HBO) therapy is a controversial treatment for adhesive postoperative small bowel obstruction, with only a few small studies reported. The aim of this study was to assess the clinical value of HBO therapy in the treatment of adhesive postoperative small bowel obstruction. METHODS: Between April 2006 and March 2012, all patients with adhesive postoperative small bowel obstruction were treated using either decompression therapy or HBO. Patients undergoing HBO therapy were treated once a day at a pressure of 2·0 atmospheres absolute and received 100 per cent oxygen. Patients showing no clinical and radiological improvement with HBO therapy were converted to decompression therapy by means of a long tube. Medical records were reviewed and outcomes analysed. RESULTS: A total of 305 patients were treated, of whom 142 underwent tube decompression therapy during the first 3 years and the remaining 163 had HBO therapy during the last 3 years. The median number of HBO treatments was 3 (range 1-7). A total of 143 patients (87·7 per cent) were treated successfully with HBO without long-tube decompression. HBO therapy was associated with earlier resumption of oral intake (mean 4·7 versus 6·5 days; P = 0·001) and a shorter hospital stay (mean 10·3 versus 14·1 days; P = 0·001). The rate of operation was 7·4 per cent in the HBO group and 14·8 per cent in group treated by decompression alone (P = 0·037). CONCLUSION: In this study, HBO therapy was safe for the treatment of adhesive postoperative small bowel obstruction. It reduced the need for surgery and time to recovery as well as the hospital stay.

Regulation of type 1 IP3 receptor expression by dopamine D2-like receptors via AP-1 and NFATc4 activation.

Type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs-1), together with ryanodine receptors, are major calcium channels to regulate intracellular Ca²âº concentration. Although our recent report demonstrates the essential involvement of IP3R-1 up-regulation induced by dopamine D1-like and D2-like receptor (D1 and D2R) stimulation in psychological dependence, exact regulatory mechanisms of IP3R-1 expression by D2Rs have not yet been clarified. Mouse cerebral cortical neurons were treated with inhibitor of Ca²âº-related signal transduction pathways coupling to D2Rs and used to analyze the mechanisms of IP3R-1 expression regulated by transcriptional factor. A selective D2R agonist, quinpirole, up-regulated IP3R-1 protein following its mRNA increase, which was significantly inhibited by gallein (a Gßγ modulator), U73122 (a phospholipase C inhibitor), BAPTA-AM (an intracellular calcium chelating reagent), W7 (a calmodulin inhibitor), KN-93 (a calmodulin-dependent protein kinases inhibitor), and FK506 (a calcineurin inhibitor). Immunocytochemical assessment showed that quinpirole increased expression of both cFos and phosphorylated-cJun in nucleus and enhanced translocation of NFATc4 complex to nucleus from cytoplasm. In addition, quinpirole directly recruited bindings between AP-1 and IP3R-1 promoter region and between NFATc4 and IP3R-1 promoter region. These results indicate that D2Rs enhance IP3R-1 gene transcription via increased bindings of AP-1 and NFATc4 to IP3R-1 promoter region after Gßγ activation.