Oral administration of ferulic acid or ethyl ferulate attenuates retinal damage in sodium iodate-induced retinal degeneration mice.

Epidemiological studies indicate that the daily intake of antioxidants from a traditional Asian diet reduces the risk of developing age-related macular degeneration. Many of the phytochemicals that are abundant in whole grains exhibit a wide variety of biological activity such as antioxidant, anti-inflammatory, and neuroprotective effects. Ferulic acid (FA) is a phenolic acid found in vegetables and grains that has therapeutic potential for diabetes mellitus, Alzheimer's disease, and other diseases. We investigated the retinal protective effect of FA in a sodium iodate (NaIO3)-induced model of retinal degeneration. In a human retinal pigment epithelial cell line, FA attenuated H2O2-induced injury and lipopolysaccharide- or 7-ketocholesterol-induced inflammation. In mice, the oral administration of FA or its analog, ethyl ferulate, attenuated the morphological and functional features of NaIO3-induced retinal degeneration according to optical coherence tomography and electroretinography. Our results demonstrate that the oral administration of FA provides protective effects to the retina, suggesting that the intake of FA as a daily supplement or daily healthy diet containing rich vegetables and whole grains may prevent age-related macular degeneration.

Effects of sugar-sweetened beverage intake on the development of type 2 diabetes mellitus in subjects with impaired glucose tolerance: the Mihama diabetes prevention study.

In Japan, the incidence of type 2 diabetes mellitus (T2DM) is increasing for several reasons, including increased consumption of sugar-sweetened beverages (SSBs). However, whether SSBs cause T2DM by excess of energy production resulting in obesity remains unclear. Therefore, the present study was designed to evaluate the effects of SSB intake on the development of T2DM in subjects with impaired glucose tolerance (IGT). Ninety-three subjects (30 males and 63 females) with IGT aged 40-69 y and residing in the Mihama district (southern Mie Prefecture, Japan) were included in the study. The mean observational period was 3.6 y. All subjects underwent the 75-g oral glucose tolerance test (OGTT) and completed a lifestyle questionnaire survey related to SSB intake. OGTT results and SSB intake were evaluated before and after the observational period. In addition, the correlation between SSB intake and development of T2DM was investigated. Of the 93 subjects, 20 (21.5%) developed T2DM (T2DM group) and demonstrated a significantly high SSB intake compared with the group that did not develop the disease (non-T2DM group). The odds ratio for the incidence of T2DM based on SSB intake was 3.26 (95% confidence interval, 1.17-9.06). The body mass index (BMI; kg/m(2)) and the homeostasis model assessment for insulin resistance (HOMA-R) values was significantly higher in the T2DM group than in the non-T2DM group, while the insulinogenic indices were significantly lower in the former than in the latter group. The sum of insulin secretion levels during OGTT was not significantly different between groups. SSB intake correlated with the predisposition for developing T2DM, possibly by influencing body weight, insulin resistance, and the ability of the pancreatic beta cells to effectively compensate for the insulin resistance.

[Attentional control and task-switching costs investigated by the group version of the Stroop tasks].

When individuals are required to frequently switch among a small set of simple tasks, immediately after switching tasks, the responses become substantially slower and usually more error-prone. This phenomenon is known as the "switching cost." Two main hypotheses have been proposed to explain switching cost: (1) Proactive interference and (2) Time for task-set reconfiguration. The present study examined the relationship between the attentional control load of switching tasks and the switching cost from the perspective of the time for task-set reconfiguration hypothesis, by using the group version of the Stroop tasks. Healthy participants (N = 216; mean age 19.9 years) participated in the study. Four switching conditions were used: (1) No-switch, (2) Selective input control switch, (3) S-R mapping switch, and (4) Translation process switch. The results indicated that there was no significant difference between the number of correct responses in conditions (1) and (3), whereas there was a significant reduction in the number of correct responses in condition (4) relative to (1) and (2). These findings suggest that the switch cost in Stroop and reverse Stroop tasks results from the time taken for attentional control, such as the selective input control switch and the translation process switch.

[Life-span development of stroop and reverse-Stroop interference measured using matching responses].

We have developed a group Stroop Color-Word Test that measures both Stroop and reverse-Stroop interference. In this test, the participants had to match a pertinent word with a color patch from among the choices printed on paper. The purpose of this study was to investigate the life-span development of Stroop and reverse-Stroop interference as measured by this test. A total of 1 945 participants (age 7-86 years old) completed this test. We found that Stroop interference was greatest among children, then decreased with age to adulthood, and finally increased among the older people. These results correspond with the findings of previous developmental studies conducted using verbal responses. The reverse-Stroop interference was found to be smallest among children, increased with age to adulthood, and then remained constant even among older adults. These results suggest that Stroop interference and reverse Stroop interference reflect different cognitive processes.

Clinical characteristics of healthcare-associated pneumonia in a public hospital in a metropolitan area of Japan.

Healthcare-associated pneumonia (HCAP) is a new category that is essential in the present aging society. Knowing the different characteristics and outcomes between patients with HCAP and community-acquired pneumonia (CAP) would help physicians manage and treat HCAP patients. Although HCAP is thought to be heterogeneous in regions, there are no reports from a metropolitan area in Japan. We retrospectively reviewed the clinical findings of all consecutive pneumonia patients who required hospitalized care in our hospital between April 2006 and March 2010. There were 184 (35.0%) patients with HCAP and 342 (65.0%) patients with CAP. Previous hospitalization within 90 days of the infection was the most common criterion for HCAP (63.0%). HCAP patients were significantly older than CAP patients (82.5 vs. 70.0 years, P < 0.001). The percentage of patients with poor functional status was higher in HCAP than CAP (64.0% vs. 26.6%, P < 0.001). Hospital mortality was significantly higher in HCAP patients than in CAP patients (15.8% vs. 5.0%, P < 0.001). Low levels of serum albumin (odds ratio, 0.126; 95% CI, 0.025-0.640; P = 0.012) and high scores in the ADROP (age, dehydration, respiratory failure, orientation, and blood pressure) system (odds ratio, 2.846; 95% CI, 1.449-5.587; P = 0.002) were the risk factors for HCAP mortality. In conclusion, patients with HCAP have different epidemiological characteristics compared with those with CAP in a metropolitan area of Japan. Outcomes and risk factors for mortality of patients with HCAP included poor nutritional status and high severity scores on the pneumonia severity scoring system.

[Pulmonary non-tuberculous mycobacteriosis (Mycobacterium intracellulare) with cavities developing in a non-small cell lung cancer patient during chemotherapy].

A 70-year-old man was admitted to our hospital for examination of an abnormal shadow found on a chest radiograph. Chest CT showed a nodular shadow in the left upper lobe S1+2. We diagnosed non-small cell lung cancer (squamous cell carcinoma) clinical stage T4N2M1. Chemotherapy consisting of carboplatin and weekly paclitaxel was begun. After the second course of chemotherapy, another nodular shadow with small cavities in the left lower lobe S6 was seen, and which then increased in size. Bronchial lavage revealed a diagnosis of non-tubercular mycobacteriosis (Mycobacterium intracellulare). Anti-NTM chemotherapy consisting of rifampicin, ethambutol and clarithromycin was started in addition to anticancer chemotherapy, without severe side effects. Although there are some reports of the co-occurrence of lung cancer and non-tuberculous mycobacteriosis, this apparently rare case involved the appearance of a solitary nodule with a cavity caused by pulmonary non-tuberculous mycobacteriosis during anticancer chemotherapy.

Outcome of endoscopic submucosal dissection for colorectal tumors accompanied by fibrosis.

OBJECTIVE: Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure. We aimed to retrospectively assess the relationship between the outcome of ESD for colorectal tumors and the degree of fibrosis. PATIENTS AND METHODS: We examined 203 consecutive patients with colorectal tumors larger than 20 mm in diameter who had undergone ESD at our hospital from November 2002 to June 2009. During ESD, the degree of submucosal fibrosis was classified into three types (F0-2). The relationship between the degree of fibrosis and the lesion characteristics and those between the outcome of ESD and the degree of fibrosis were analyzed. RESULTS: In the cases of granular laterally spreading tumors, the incidence of F2 fibrosis in nodular mixed-type tumors was significantly higher than that in homogenous-type tumors. An increase in the experience of the operators caused significant improvements in the rates of complete en bloc resection (p = 0.022) and perforation (p = 0.03) in the cases of lesions with F0-1 fibrosis. By contrast, operator experience did not cause any significant improvements in the rates of complete en bloc resection and perforation in the cases of lesions with F2 fibrosis. CONCLUSIONS: Experienced operators could safely perform complete en bloc resection in the cases of lesions with F0-1 fibrosis. However, in the cases of lesions with F2 fibrosis, the rate of complete en bloc resection was low and the perforation rate was high even when ESD was performed by an experienced operator.

[Detection of pleural plaques on chest X-ray film by chest physicians].

With increasing awareness about health damage due to asbestos exposure, the number of people presenting with non-occupational exposure has increased remarkably. Consequently, chest physicians in general hospitals must read the chest X-ray films of patients with asbestos exposure. Can non-specialized chest physicians, who may have little experience of occupational medicine, diagnose pleural plaques accurately? The study subjects were 44 consecutive patients who were admitted to our hospital, under the Japanese medical health check system for workers employed in dangerous work. Their chest X-ray films were checked by 4 chest physicians, who were independently informed that the patients had a high suspicion of asbestos exposure. The detection rate of chest Xray for pleural plaques was compared with computed tomography (CT) results as the gold standard. The sensitivity was 0.818 and the specificity was 0.393. The sensitivity of the presence of pleural plaques was lower in anterior and posterior sites, and on the pleura adjacent to the mediastinum, pericardium and vertebral (0.429, 0.348, 0.217), while specificity was lower on lateral sites (0.610). Chest physicians in general hospitals must be trained in the manifestation of asbestos-related diseases.

Algorithm-guided treatment versus treatment as usual for major depression.

AIMS: The remission rates for patients with major depressive disorder (MDD) during algorithm-guided treatment (AGT), which consisted of four treatment strategy steps were prospectively compared with treatment as usual (TAU). METHODS: The remission rates of patients with mild or moderate MDD during AGT (n = 83) were compared with TAU (n = 127). RESULTS: The remission rate in the AGT group (60.2%) was approximately 10% greater than that in the TAU group (49.7%). The median number of days to achieve remission in the AGT group (93 days) was half as long as that in the TAU group (191 days). The hazard ratio of remission was 1.5 (95% confidence interval: = 1.2-1.8). A higher rate of lithium augmentation in the AGT group (20.5%) compared to the TAU (4.7%) may have led to the greater remission rate. Most participants who did not achieve remission either during the initial or second treatment steps dropped out from AGT. CONCLUSIONS: AGT may be superior to TAU for patients with mild or moderate MDD, based on the remission rates achieved. The later treatment steps in the AGT, however, were rarely utilized because participants who did not receive any benefit dropped out early.

Preventive effect of sulfamethoxasole-trimethoprim on Pneumocystis jiroveci pneumonia in patients with interstitial pneumonia.

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) is a potentially fatal complication in interstitial pneumonia patients receiving glucocorticoid therapy. Prophylaxis of PCP during glucocorticoid therapy is an important issue in the treatment of interstitial pneumonia. OBJECTIVE: We evaluated the prophylactic effect of sulfamethoxasole-trimethoprim (TMP-SMX) in interstitial pneumonia patients receiving glucocorticoids. METHODS: We retrospectively analyzed 74 interstitial pneumonia patients who received glucocorticoid therapy. RESULTS: Seven of the 74 patients developed PCP. At the time of diagnosis of PCP, the mean duration of glucocorticoid therapy was 71 days and the mean daily dose of prednisolone was 37 mg. Among the 7 patients, the circulating CD4+ lymphocyte count was 370 /microl on average and it was over 200 /microl in 3 cases. The PCP patients showed a significant reduction of the lymphocyte count at 4 weeks after initiation of steroid therapy. None of the patients who received prophylactic TMP-SMX therapy developed PCP even if the CD4+ lymphocyte count was less than 200 /microl. CONCLUSION: Interstitial pneumonia patients receiving glucocorticoid therapy can benefit from TMP-SMX prophylaxis against PCP. Development of PCP cannot be ruled out in patients with a CD4+ lymphocyte count of greater than 200 /microl.

Airway inflammatory responses to oxidative stress induced by low-dose diesel exhaust particle exposure differ between mouse strains.

Low-dose diesel exhaust particle (DEP) exposure induces airway inflammation and exaggerates asthmatic responses in mice, but it is unclear whether strains differ in their susceptibility to adverse effects from low-dose DEP exposure. The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to low-dose DEP (100 microg/m(3)) exposure in terms of airway inflammatory response. The macrophage count in bronchoalveolar lavage (BAL) fluid soon after DE exposure began was significantly greater in C57BL/6 mice (P < .05) than that in BALB/c mice. The count did not increase significantly in BALB/c mice until later. Heme oxygenase-1 (HO-1) mRNA expression and protein production in lung tissues soon after exposure began were more marked in BALB/c mice than in C57BL/6 mice, but the reverse was true later on. The increases in interleukin (IL)-1beta and interferon (IFN)-gamma levels in BAL fluid after DE exposure were significant only in BALB/c mice; there were significantly increases in monocyte chemoattractant protein (MCP)-1, IL-12, IL-10, IL-4, and IL-13 in both strains, but these were more marked in C57BL/6 mice. These interstrain differences in airway inflammatory response after DE exposure were significantly attenuated by antioxidant N-acetylcysteine (NAC) treatment. Changes in airway hyperresponsiveness were independent of the airway inflammation induced by low-dose DEP. Thus, in BALB/c mice, innate immunity may play a central role in DE exposure response, whereas in C57BL/6 mice Th2-dominant responses play a central role. Low-dose DEP exposure induces airway inflammatory responses that differ among strains, and these differences may be caused by differences in sensitivity to oxidative stress.

Repeated exposure to low-dose diesel exhaust after allergen challenge exaggerates asthmatic responses in mice.

BACKGROUND: In conjunction with allergens, diesel exhaust particles act as an adjuvant to enhance IgE responses, inducing expression of cytokines/chemokines and adhesion molecules, and increasing airway hyper-responsiveness (AHR). As most studies were designed to expose animals to diesel exhaust throughout the periods of both sensitization and allergen challenge, it remains unclear whether diesel exhaust (DE) exposure exaggerates airway responses in asthmatic animals. OBJECTIVE: To study effects of exposure to low-dose DE on AHR and allergic airway inflammation in asthmatic mice. METHODS: BALB/c mice were sensitized by intraperitoneal injection of ovalbumin and challenged by intranasal administration with ovalbumin. They were exposed to low-dose DE for 7 h/day, 5 days/week, for up to 12 weeks. AHR to methacholine was evaluated by whole-body plethysmography as well as bronchoalveolar lavage cell analysis and cytokine gene expression in lungs. RESULTS: Repeated exposure of asthmatic mice to low-dose DE resulted in increased AHR and gene expression of several pro-asthmatic cytokines/chemokines, but these effects rapidly subsided with continued exposure to DE. CONCLUSION: Repeated exposure to low-dose DE after ovalbumin challenge exaggerates allergic responses in mice, but effects are not prolonged with continuous DE exposure.

[Idiopathic pulmonary fibrosis (IPF)].

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease that prognosis (INF) has not improved by available therapy. Recently, much attention has focused on the utility of the T-helper type 1 cytokine interferon (IFN)-gamma as a treatment for IPF. The rationale for its use has been based on observations of its properties as an inhibitor of fibroblast proliferation, collagen synthesis and deposition, and expression of profibrotic cytokines. The clinical trial is advanced aiming at the prognosis improvement of IPF patients. Small-scale controlled clinical study in 1999, IFN-gamma has improved the respiratory functions of IPF, which was resistant to steroid therapy. Be based on these results, phase III large-scale study mainly in North America, the lagged effect of respiratory function aggravation was expected in IPF, in which pulmonary functions are mildly or moderately deteriolated. But in progressive cases, interferon gamma-1b did not affect progression-free survival, pulmonary function, or the quality of life.

[Pneumocystis jiroveci pneumonia as a complication of glucocorticoid therapy for interstitial pneumonia].

We evaluated the clinical features of pneumocystis jiroveci pneumonia (PCP) as a complication of glucocorticoid therapy for interstitial pneumonia We analyzed 74 interstitial pneumonia patients receiving glucocorticoid therapy, of whom 7 patients developed PCP. At the time of PCP diagnosis, the average duration of the glucocorticoid therapy was 71 days and the average daily dose of predonisolone was 37 mg. Circulating CD4+ lymphocyte counts were 370/microl on the average and more than 200/microl in three cases. PCP cases showed less circulating lymphocyte counts four weeks after the initiation of the therapy. Any cases receiving sulfamethoxazole-trimethoprim (TMP-SMX) did not develop PCP. In conclusion, interstitial pneumonia patients, who are treated with glucocorticoid, are benefit from TMP-SMX as PCP prophylaxis, but CD4 + lymphocyte counts greater than 200/microl is no reason to denying PCP.

Tyrosine phosphorylation of a novel 100-kDa protein coupled to CD28 in resting human T cells is enhanced by a signal through TCR/CD3 complex.

For T cell activation, two signals are required, i.e., a T cell receptor (TCR)/CD3-mediated main signal and a CD28-mediated costimulatory signal. CD28 binds to its ligand (CD80 or CD86) and transduces the most important costimulatory signal. The cytoplasmic domain of the CD28 molecule, composed of 41 amino acids, does not contain any intrinsic enzyme activity. The cytoplasmic domain of CD28 is remarkably conserved among species and is associated with a number of signaling molecules that affect the main signal. We report here that a tyrosine phosphorylated 100-kDa protein (ppl00) was coupled to the CD28 cytoplasmic domain in Jurkat and human peripheral T cells. The pp100 was distinguished from other CD28 associated molecules such as Vav, STAT5, PI 3-kinase, Valosin-containing protein (VCP), Nucleolin, Gab2 (Grb2-associated binding protein 2), and STAT6. The tyrosine phosphorylation of pp100 coprecipitated with CD28 was enhanced by CD3 stimulation by the specific antibody, tyrosine phosphatase inhibitor and PKC activator. Tyrosine phosphorylation of pp100 was attenuated by the prior addition of PKC inhibitor. These findings indicate that pp100 is a novel tyrosine phosphorylated protein coupled to CD28 under continuous control of tyrosine phosphatases and might play a role in T cell activation augmented by a TCR/CD3-mediated main signal.