Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

BACKGROUND: There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. OBJECTIVE: To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. RESULTS: Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. CONCLUSION: Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Excessive daytime sleepiness and alcohol consumption among commercial drivers.

BACKGROUND: Commercial drivers suffering from excessive daytime sleepiness (EDS) have been identified as a major cause of road traffic accidents. Alcohol usage directly affects sleep, adversely affecting next-day alertness and performance. AIMS: To examine the relationship between alcohol consumption and EDS among commercial truck drivers in Japan and the implications of this on public health. METHODS: All participants in this cross-sectional study were commercial motor vehicle drivers from Tokyo and Niigata Prefecture. Participants completed a self-administered questionnaire with details of their age, body mass index, alcohol consumption, Epworth Sleepiness Scale (ESS) score and tobacco usage. Participants' oxygen desaturation index was determined by a pulse oximetry device that participants took home. RESULTS: A total of 1422 males registered with the Japan Trucking Association and aged 20-69 years participated. The multivariate-adjusted odds ratio (OR) of EDS among participants aged <43 years was 0.81 (95% confidence interval (CI) 0.47-1.40) for light drinkers, 0.93 (95% CI 0.51-1.70) for moderate drinkers and 0.61 (95% CI 0.21-1.79) for heavy drinkers, compared to non-drinkers. The multivariate-adjusted OR among participants aged ≥43 years was 1.42 (95% CI 0.59-3.45) for light drinkers, 1.53 (95% CI 0.63-3.75) for moderate drinkers and 3.37 (95% CI 1.14-9.96) for heavy drinkers (P for interaction = 0.05). CONCLUSION: We found that the association between ESS and alcohol intake was more evident among those aged ≥43 years, who reported higher levels of EDS with increased alcohol consumption.

Diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess.

OBJECTIVE: To assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess. METHODS: Mean platelet volume and other laboratory data were retrospectively investigated. RESULTS: Mean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively. CONCLUSION: Our results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis.

Association of salivary lactate dehydrogenase level with systemic inflammation in a Japanese population.

BACKGROUND AND OBJECTIVE: Salivary lactate dehydrogenase (LDH) was reported to be a useful parameter for the screening of periodontal disease. We performed a cross-sectional study to verify the usefulness of salivary LDH as a biomarker of periodontitis and to investigate the association of severity of periodontitis with systemic inflammation by measuring salivary LDH and serum high sensitive C-reactive protein (hs-CRP) levels in a community-based middle-aged and elderly population in Japan. MATERIAL AND METHODS: We recruited 644 men and 1171 women, aged 30-79 years, who participated in the Toon Health Study during 2011-15. Periodontal condition was assessed by full-mouth examination including mean value of probing depth, percentage of probing depth of ≥4 mm and ≥6 mm, and bleeding on probing. Saliva and blood serum samples were collected for measurement of salivary LDH level and hs-CRP, respectively. A linear trend across quartiles of salivary LDH was calculated using linear regression. Interaction of salivary LDH and overweight status (body mass index of ≥25 kg/m2 ) was tested using the cross-product term of log-transformed continuous salivary LDH and overweight status. RESULTS: Analysis of covariance adjusted for potential confounders revealed strong associations between salivary LDH level and the indicators of periodontal condition (P < .01) in both men and women. Sex- and age-adjusted mean values of hs-CRP according to salivary LDH quartiles were 0.40, 0.45, 0.45 and 0.50 mg/L (P for trend <.01). Although the association was attenuated after further adjustment for body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol intake, smoking status and physical activity. When stratified by overweight status, the association remained significant in overweight individuals (P = .03). The multivariable adjusted odds ratio of hs-CRP level of ≥1 mg/L for the highest vs lowest quartile of salivary LDH was 1.93 (95% CI, 1.01-3.69) in overweight individuals, but not significant in non-overweight individuals. CONCLUSION: Salivary LDH appears to be a promising biomarker for the mass screening of periodontitis in local community health settings. High salivary LDH levels, particularly in overweight individuals might contribute to prevention of cardiovascular disease, through measuring systemic inflammatory burdens as well as traditional cardiovascular risk factors.

Scalloped tongue is associated with nocturnal intermittent hypoxia among community-dwelling Japanese: the Toon Health Study.

Scalloped tongue is considered as a possible clinical finding of obstructive sleep apnoea (OSA). There are few evidence of the association between scalloped tongue and OSA. To examine the association between scalloped tongue and nocturnal intermittent hypoxia (NIH), a surrogate marker of OSA, among a general Japanese population. Study participants were 398 men and 732 women aged 30-79 years who participated in the Toon Health Study from 2011 to 2014. Scalloped tongue was classified into three categories: none, mild and moderate-to-severe. Moderate-to-severe NIH was defined as the 3% oxygen desaturation index of ≥15 events/h during sleep for one night with pulse oximetry. The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for moderate-to-severe NIH were calculated according to scalloped tongue categories using a logistic regression model. There were 69 (6·1%) moderate-to-severe NIH cases in this population. The multivariable-adjusted ORs (95% CIs) of moderate-to-severe NIH were 1·59 (0·85-2·95) for mild and 2·39 (1·10-5·17) for the moderate-to-severe scalloped tongue group compared with the group without scalloped tongues. When stratified by overweight status (BMI <25 or ≥25 kg m-2 ), the respective ORs (95% CIs) were 2·83 (1·06-7·55) and 4·74 (1·28-17·49) among overweight individuals, and 0·94 (0·40-2·70) and 1·52 (0·57-4·05) among non-overweight individuals. Scalloped tongue was associated with higher prevalence of moderate-to-severe NIH among the general Japanese population and this association was more evident in overweight individuals.

Longitudinal effects of disaster-related experiences on mental health among Fukushima nuclear plant workers: The Fukushima NEWS Project Study.

BACKGROUND: The Fukushima Nuclear Energy Workers' Support (NEWS) Project Study previously showed that experiences related to the Fukushima nuclear disaster on 11 March 2011 had a great impact on psychological states, including post-traumatic stress response (PTSR) and general psychological distress (GPD), among the Fukushima nuclear plant workers. To determine the causal relationship between disaster-related experiences and levels of psychological states, we conducted a 3-year longitudinal study from 2011 to 2014. METHOD: PTSR and GPD of the nuclear plant workers were assessed by annual questionnaires conducted from 2011 to 2014. The present study included a total of 1417 workers who provided an assessment at baseline (2011). A total of 4160 observations were used in the present analysis. The relationship between disaster-related experiences and psychological states over time was analysed using mixed-effects logistic regression models. RESULTS: A declining influence of disaster-related experiences on PTSR over time was found. However, the impact on PTSR remained significantly elevated even 3 years after the disaster in several categories of exposure including the experience of life-threatening danger, experiences of discrimination, the witnessing of plant explosion, the death of a colleague and home evacuation. The associations between GPD and disaster-related experiences showed similar effects. CONCLUSIONS: The effects of disaster-related experiences on psychological states among the nuclear plant workers reduced over time, but remained significantly high even 3 years after the event.

Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

The longitudinal mental health impact of Fukushima nuclear disaster exposures and public criticism among power plant workers: the Fukushima NEWS Project study.

BACKGROUND: The Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated. METHOD: A total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2-3 months (time 1) and 14-15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses. RESULTS: Higher GPD at time 2 was predicted by higher GPD at time 1 (ß = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (ß = 0.065, p = 0.025, adjusted R 2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (ß = 0.548, p < 0.001), higher age (ß = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (ß = 0.079, p = 0.003, adjusted R 2 = 0.36). CONCLUSIONS: Higher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.

Characteristics of nighttime reflux assessed using multichannel intraluminal impedance pH monitoring and a portable electroencephalograph.

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate-to-severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off-proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent-awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post-awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent-awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post-awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances.

Mechanisms of NLRP3 inflammasome activation and its role in NSAID-induced enteropathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce cytokines, including tumor necrosis factor-α and interleukins (ILs), in the small intestine via a Toll-like receptor 4 (TLR4)-dependent pathway, leading to intestinal ulceration. Activation of the inflammasome promotes pro-caspase-1 cleavage, leading to pro-IL-1ß maturation. We examined the role of NLRP3 inflammasome in NSAID-induced enteropathy. Small intestinal damage developed 3 h after indomethacin administration, accompanied by increases in IL-1ß and NLRP3 mRNA expression and mature caspase-1 and IL-1ß levels. In vivo blocking of IL-1ß using neutralizing antibodies attenuated indomethacin-induced damage, whereas exogenous IL-1ß aggravated it. NLRP3(-/-) and caspase-1(-/-) mice exhibited resistance to the damage with reduction of mature IL-1ß production. This resistance was abolished by exogenous IL-1ß. TLR4 deficiency prevented intestinal damage and inhibited upregulation of NLRP3 and IL-1ß mRNAs and maturation of pro-caspase-1 and pro-IL-1ß, whereas TLR4 activation by its agonists exerted opposite effects. Apyrase, an adenosine triphosphate (ATP) scavenger, or Brilliant Blue G, a purinergic P2X7 receptor antagonist, inhibited the damage as well as caspase-1 activation and IL-1ß processing, despite there being sufficient amounts of pro-IL-1ß and NLRP3. These results suggest that NLRP3 inflammasome-derived IL-1ß plays a crucial role in NSAID-induced enteropathy and that both TLR4- and P2X7-dependent pathways are required for NLRP3 inflammasome activation.

Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100ß protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing locally administered exogenous nerve growth factor is retained in gastric tissue and is taken up by endothelial, neural, muscle and epithelial cells. This is likely the basis for the therapeutic action of locally administered nerve growth factor and its stimulation of angiogenesis, tissue regeneration and gastric ulcer healing.

Enteric glial cells are associated with stress-induced colonic hyper-contraction in maternally separated rats.

BACKGROUND: Enteric glial cells (EGCs) play important roles in enteric integrity and regulation of gastrointestinal function. However, whether EGCs undergo pathophysiological changes in stress-associated gastrointestinal disorders is unknown. We investigated structural and functional alterations in colonic EGCs and their roles in colonic contraction in an irritable bowel syndrome (IBS) model. METHODS: As a chronic stress, male Wistar rats underwent 3-h maternal separation during postnatal days 2-14. As an acute stress, we used water-immersion stress (4 h) in adulthood (at 8 weeks). We quantitatively and morphologically evaluated enteric neurons and EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. Colonic contraction was analyzed with electrical field stimulation (EFS). KEY RESULTS: Glial fibrillary acidic protein (GFAP) expression and the number of total, cholinergic, and nitrergic neurons were unchanged in maternally separated rats with acute stress (combined stress: an IBS model) compared with controls. However, the density of GFAP-positive EGC processes that apparently overlapped with the neurons and the extent of bulbous swelling of terminals increased according to the stress intensity: control, acute stress, maternal separation, and combined stress. EFS-induced colonic contractions were significantly greater in the combined stress rats than in controls. Higher dose of fluorocitrate, a selective inhibitor of EGC metabolism, was required to inhibit both EFS-induced contraction and EGCs activation in the combined stress rats than in controls. CONCLUSIONS & INFERENCES: Colonic EGCs exhibited structural alterations according to the stress intensity. EGCs were associated with stress-induced colonic hyper-contraction in the combined stress rats, which may underlie the pathogenesis of IBS.

Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor-responsive oesophageal eosinophilia.

BACKGROUND: The features of proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) are similar to those of eosinophilic oesophagitis (EoE), but PPI-REE demonstrates symptomatic and histological responses to PPI therapy. Several studies have shown that basophils play a crucial role in the pathogenesis of allergic diseases. AIM: To identify and compare basophil infiltration in the oesophageal epithelium in patients with EoE, PPI-REE, gastroesophageal reflux disease (GERD) and normal oesophagus (controls). METHODS: Biopsy specimens from 43 patients, including 12 with EoE, 11 with PPI-REE, 10 with GERD and 10 normal oesophagus, were analysed. Immunohistochemistry was performed to quantify the number of basophils and mast cells in the oesophageal epithelium. Double immunofluorescence staining for thymic stromal lymphopoietin (TSLP) and basophils was performed. Patients with EoE were treated with swallowed fluticasone. RESULTS: There were no differences in clinical, endoscopic or histological features between patients with EoE and PPI-REE. There were more basophils and mast cells in patients with EoE and PPI-REE than in patients with GERD and control subjects. Basophil infiltration of the oesophageal epithelium in patients with EoE was higher than that in patients with PPI-REE (3.6 ± 2.8 per high power field vs. 1.2 ± 0.9 per high power field respectively; P = 0.02); however, there was no significant difference in mast cell infiltration between the two groups. TSLP was highly expressed in the oesophageal epithelium in areas infiltrated by basophils. Steroid therapy significantly decreased intraepithelial basophils in patients with EoE. CONCLUSION: Basophils may play an important role in the pathogenesis of eosinophilic oesophagitis.

Usefulness of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging to detect inner-ear abnormalities in patients with sudden sensorineural hearing loss.

OBJECTIVE: Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging has been used to detect alterations in the composition of inner-ear fluid. This study investigated the association between hearing level and the signal intensity of pre- and post-contrast three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging in patients with sudden-onset sensorineural hearing loss. METHOD: Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging was performed in 18 patients with sudden-onset sensorineural hearing loss: 12 patients with mild-to-moderate sensorineural hearing loss (baseline hearing levels of 60 dB or less) and 6 patients with severe-to-profound sensorineural hearing loss (baseline hearing levels of more than 60 dB). RESULTS: High-intensity signals in the inner ear were observed in two of the six patients (33 per cent) with severe-to-profound sensorineural hearing loss, but not in those with mild-to-moderate sensorineural hearing loss (mid-p test, p = 0.049). These signals were observed on magnetic resonance imaging scans 6 or 18 days after sensorineural hearing loss onset. CONCLUSION: The results indicate that three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging is not a useful tool for detecting inner-ear abnormalities in patients with mild sensorineural hearing loss.

Importance of platinum-free interval in second-line chemotherapy for advanced or recurrent endometrial cancer.

PURPOSE: To investigate the effectiveness of platinum-based combination chemotherapy as second-line chemotherapy for patients with advanced or recurrent endometrial cancer treated initially by platinum-based combination chemotherapy. MATERIALS AND METHODS: Subjects were patients who had received platinum-based combination chemotherapy as second-line chemotherapy: 56 patients with recurrent disease who had previously received postoperative adjuvant platinum-based combination chemotherapy (Category 1) and 21 patients who had received first-line chemotherapy but not adjuvant chemotherapy for advanced or recurrent disease (Category 2). Patients' records were searched for the response to second-line chemotherapy and survival, particularly in relation to the platinum-free interval (PFI). RESULTS: APFI over 12 months was a predictor of response (64.7%) and overall survival time (23 months) in Category 1 patients. A PFI of less than three months was a negative predictor of response (0%) and overall survival (nine months) in Category 2 patients. CONCLUSION: Platinum-based combination chemotherapy appears to be effective as second-line chemotherapy for endometrial cancer if the PFI is sufficiently long.

Adiponectin deficiency exacerbates age-related hearing impairment.

Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.

Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of locoregional MMC injection therapy in patients with refractory esophageal strictures after ESD for SEC.

Small intestinal injury caused by NSAIDs/aspirin: finding new from old.

Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans.

Twelve oxo-eicosatetraenoic acid induces fetal membrane release after delivery in cows.

Fetal fibroblast cell culture from cotyledons of bovine placenta and animal experiments close to term were used to elucidate afterbirth release and factors missing in the signal transduction mechanism for retained fetal membranes (RFM) after delivery. In cell culture the addition of arachidonic acid (Ara) to the medium caused rapid release to free floating cell in the culture dish, accompanied by matrix metalloproteinase (MMP) activation, being consistent with previous in vivo observations, where a relation between MMP and fetal membrane release had been shown. Ara-induced cell floating was not inhibited by the addition of cyclooxygenase (COX) inhibitor, and not induced by the addition of PGF2α or PGE2 to replace Ara, while 12-lipoxygenase (12-LOX) metabolite of Ara, 12-oxo-eicosatetraenoic acid (12-oxoETE), strongly induced cell floating. In the animal experiments, 12-oxoETE injection to delivery-induced cows (n = 6) using prostaglandin (PG) and dexamethazone resulted in rapid release of fetal membranes. In cows with natural calf delivery, a 12-oxoETE peak (11.7-16.8 ng/ml) was observed in maternal blood plasma prior to release of fetal membranes. This investigation thus gives new indications for that the mediator for fetal membrane release is 12-oxoETE and not PG.