Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer.

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

Osteoglycin, a novel coordinator of bone and glucose homeostasis.

OBJECTIVE: The skeleton, which is strongly controlled by endocrine factors, has recently been shown to also play an active endocrine role itself, specifically influencing energy metabolism. However, much less is known about this role. Therefore, we sought to identify novel endocrine factors involved in the regulation of both bone mass and whole-body glucose homeostasis. METHODS: We used transcriptomic and proteomic analysis of Y1 receptor deficient osteoblasts combined with the generation of a novel osteoglycin deficient mouse model and performed comprehensive in vivo phenotype profiling, combined with osteoglycin administration in wildtype mice and human studies. RESULTS: Here we identify a novel role for osteoglycin, a secreted proteoglycan, in coordinating bone accretion with changes in energy balance. Using an osteoglycin knockout mouse model, we show that at a whole body level, osteoglycin acts to suppress bone formation and modulate whole body energy supplies by altering glucose uptake through changes in insulin secretion and sensitivity, as well as by altering food intake through central signaling. Examining humans following gastric surgery as a model of negative energy balance, we show that osteoglycin is associated with BMI and lean mass as well as changes in weight, BMI, and glucose levels. CONCLUSIONS: Thus, we identify osteoglycin as a novel factor involved in the regulation of energy homeostasis and identify a role for it in facilitating the matching of bone acquisition to alterations in energy status.

Characterization of the transcriptional regulation of the tarIJKL locus involved in ribitol-containing wall teichoic acid biosynthesis in Lactobacillus plantarum.

Lactobacillus plantarum strains produce either glycerol (Gro)- or ribitol (Rbo)-backbone wall teichoic acid (WTA) (Gro-WTA and Rbo-WTA, respectively). The strain WCFS1 has been shown to be able to activate the tarIJKL locus involved in Rbo-WTA synthesis when the tagD1F1F2 locus for Gro-WTA synthesis was mutated, resulting in switching of the native Gro-WTA into Rbo-WTA. Here, we identify a regulator involved in the WTA backbone alditol switching and activation of the tarIJKL locus. Promoter reporter assays of the tarI promoter (Ptar) demonstrated its activity in the Rbo-WTA-producing mutant derivative (ΔtagF1-2) but not in the parental strain WCFS1. An electrophoresis mobility shift assay using a Ptar nucleotide fragment showed that this fragment bound to Ptar-binding protein(s) in a cell-free extract of WCFS1. Three proteins were subsequently isolated using Ptar bound to magnetic beads. These proteins were isolated efficiently from the lysate of WCFS1 but not from the lysate of its ΔtagF1-2 derivative, and were identified as redox-sensitive transcription regulator (Lp_0725), catabolite control protein A (Lp_2256) and TetR family transcriptional regulator (Lp_1153). The role of these proteins in Ptar regulation was investigated by knockout mutagenesis, showing that the Δlp_1153 mutant expressed the tarI gene at a significantly higher level, supporting its role as a repressor of the tarIJKL locus. Notably, the Δlp_1153 mutation also led to reduced expression of the tagF1 gene. These results show that Lp_1153 is a regulatory factor that plays a role in WTA alditol switching in Lb. plantarum WCFS1 and we propose to rename this gene/protein wasR/WasR, for WTA alditol switch regulator.

Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.

Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats.

This study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced testicular toxicity and oxidative damage in rats. GM (100 mg kg(-1) ) was injected intraperitoneally (i.p.) to rats for 6 days. MT (15 mg kg(-1) ) was administered i.p. to rats for 6 days at 1 hr after the GM treatment. GM caused a decrease in prostate and seminal vesicle weights, sperm count and sperm motility. Histopathological examination showed various morphological alterations in the testis, characterised by degeneration of spermatogonia/spermatocytes, decrease in the number of early spermatogenic cells and vacuolisation. In addition, an increased malondialdehyde concentration and decreased glutathione content and glutathione reductase, catalase and glutathione-S-transferase activities were found in the testis. In contrast, MT treatment significantly attenuated the testicular toxicity of GM, including decreased reproductive organ weights, sperm count, and sperm motility and increased histopathological alterations. MT also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the level of the antioxidant glutathione and the activities of antioxidant enzymes in the testis. These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity.

Chewing ability, nutritional status and quality of life.

In the literature, most researchers evaluate individuals' nutritional status and chewing ability by types of foods chosen or blood test. However, most of previous researches enrolled small sample size and the results might be influenced by personal preference of foods as well as the individuals' response to invasive examination. In this study, researchers assessed individuals' nutritional status and chewing ability with non-invasive test and excluded the personal preference of foods. This study had two aims: first, to explore associations between chewing ability, edentulous or dentulous, self-perceived oral health and individuals' nutritional status and quality of life; second, to assess whether the association proposed by Locker's model is valid. This study used the database of Phase I 'Publicly-funded Denture Installation Plan for the Elderly' of Kaohsiung City Government. Nine hundred and fifty-four subjects aged 65 years and older completed the questionnaires for data analysis. The research results supported and verified the theoretical model proposed by Locker. Individual's chewing ability associated significantly with his/her nutritional status and quality of life. The results demonstrated that better chewing ability of the elderly leads to better nutritional status and quality of life. The appropriateness of the indicators and measurements of individual's chewing ability and nutritional status used in this study has been evaluated and presented. These indicators and measurements are suggested to be generally used for clinical or research application on future-related issues. Consequently, the maintenance or improvement in the chewing ability of the elderly is extremely beneficial to healthy ageing.

Apoptotic cell death in rat epididymis following epichlorohydrin treatment.

Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility. This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment. Rats were administrated with a single oral dose of ECH (50 mg/kg). ECH-induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay. The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively. The Western blot analysis demonstrated no significant changes in proapoptotic Bcl-2-associated X (Bax) and anti-apoptotic Bcl-2 expression during the time course of the study. However, phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and phospho-c-Jun amino-terminal kinase (p-JNK) expression increased at 8-24 h. Caspase-3 and caspase-8 activities also increased at 8-48 h and 12-48 h, respectively, in the same manner as p-p38 MAPK and p-JNK expression. These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway.

NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.

AIMS: Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. METHODS: To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. RESULTS: PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. CONCLUSIONS: These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis.

Melatonin attenuates doxorubicin-induced testicular toxicity in rats.

This study investigated the protective effects of melatonin (MLT) against doxorubicin (DXR)-induced testicular toxicity and oxidative stress in rats. DXR was given as a single intraperitoneal dose of 10 mg kg(-1) body weight to male rats at 1 h after MLT treatment on day 6 of the study. MLT at 15 mg kg(-1) body weight was administered daily by gavage for 5 days before DXR treatment followed by an additional dose for 5 days. Sperm analysis, histopathological examination and biochemical methods were used for this investigation. DXR caused a decrease in the weight of seminal vesicles, epididymal sperm count and motility and an increase in the incidence of histopathological changes of the testis. In addition, an increased malondialdehyde (MDA) concentration and decreased glutathione content, glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase activities were observed. On the contrary, MLT treatment significantly ameliorated DXR-induced testicular toxicity in rats. Moreover, MDA concentration and GR, GST and SOD activities were not affected when MLT was administered in conjunction with DXR. These results indicate that MLT had a protective effect against DXR-induced testicular toxicity and that the protective effects of MLT may be due to both the inhibition of lipid peroxidation and increased antioxidant activity.

Individuals' perception of oral health and its impact on the health-related quality of life.

This research divides oral health status into two parts: clinical disease and patients' subjective perceptions, and then discusses what impact these two items have on the health-related quality of life. A total of 1600 elderly persons, over 65 years old, were sampled as the research target. The overall response rate was 71.62%. SF-36 was used to measure the health-related quality of life, Oral Health Impact Profile (OHIP) was used to measure individuals' subjective perception of their oral health status, and the number of natural teeth was considered as the clinical issue. There are 12 items which affect quality of life in the physical aspect, namely: OHIP score; age; gender; weekly frequency of social activities and interactions; financial status; physician visits per month on a regular basis; hospitalization during the last 6 months; arthritis, rheumatism, cardiovascular disease or diabetes; abnormal IADL patients; and the satisfaction level of current lifestyle. Factors affecting quality of life (i.e. mental aspects), are few, including: OHIP score, gender, education level, weekly frequency of social activities and interactions and satisfaction level of current lifestyle. The results indicate that individuals' subjective perceptions of their oral health status had a greater impact, than did the clinical issue, on their health-related quality of life. The outcomes and findings derived from this research may provide alternative perspectives for professionals, so that they may be more careful concerning individuals' subjective perceptions.

Seasonal variations in growth rate of phytoplankton in Hakata Bay, Japan.

Recently, water pollution with high concentrations of organic matter has occurred frequently in Hakata Bay. It is said that a high level of primary production provides much organic matter and affects water quality of the bay, and it is proved by the appearance of phytoplankton throughout the year. In this study, we simulated variations of phytoplankton population with a box-type model using monthly data in a long-term measurement and we analyzed the final growth rate changes of phytoplanktons that explain the conditions for its appearance. Consequently, we found that the final growth rate varies with pattern of half-year periodicity and water temperature and/or ambient nutrient controls the final growth rate to be low every January and July.

Study on generation of oxygen-depleted water based on stochastically changing solar radiation intensity.

To examine the generation probability of oxygen-depleted sea water in Hakata Bay, possible 20 time-series of different hourly-solar-radiation intensities were generated stochastically, and a numerical simulation on dissolved oxygen was carried out for each time series. The results of the model calibration followed the seasonal variation of observed water quality well, and generated cumulative-frequency-distribution curves of daily solar radiation agreed well with the observed ones. The simulation results indicated that the exchange of sea water would have a great influence on the DO concentration, and that the concentration could change more than 1 mg/L in a day. This prediction method seems to be an effective way to examine a solution to minimize fishery damages when DO is depleted.

Pathogenic role of endothelin 1 in hemodynamic dysfunction in experimental acute pulmonary thromboembolism.

The plasma endothelin-1 (ET-1) level is elevated in patients with acute pulmonary thromboembolism (APE). Whether ET-1 is a pathogenic mediator or a simple marker of APE is not known. We investigated the role of ET-1 in hemodynamic dysfunction in APE through evaluating the effects of ET(A) receptor antagonist in an experimental APE model. We also examined ET-1 expression in embolized lungs. In a canine autologous blood clot pulmonary embolism model, ET(A) receptor antagonist ZD2574 (10 mg/kg, intravenous; ZD2574 group; n = 6) or vehicle (control group; n = 5) was administered. Hemodynamic and gas exchange parameters and plasma levels of ET-1 were serially measured. Prepro-ET-1 mRNA expression and the distribution of ET-1 peptide in lung tissues were also examined. With ZD2574 pulmonary arterial pressure and pulmonary vascular resistance significantly decreased, and were lower compared with the control group. The decrease in cardiac output was also less in the ZD2574 group. Plasma ET-1 levels increased after embolization. Prepro-ET-1 mRNA expression increased in embolized lungs and ET-1 peptide expression also increased in embolized lungs, particularly in the muscular pulmonary arteries, compared with normal lungs. These findings suggest that ET-1 partially contributes to hemodynamic derangements of APE, and that ET(A) receptor antagonists might constitute a useful therapeutic tool for APE.

A prospective correlation of Laurén's histological classification of stomach cancer with clinicopathological findings including DNA flow cytometry.

Between November 1990 and December 1992, 217 patients with stomach cancer were enrolled in a prospective study evaluating the prognostic value of DNA flow cytometry. Laurén's histological type was evaluated in 216 cases, of which 102 (47%) were of the diffuse type, 74 (34%) were of the intestinal type, and 40 (19%) were mixed type tumors. Laurén's histological type showed a significant correlation with age (p = 0.028), sex (p = 0.004), tumor size (p = 0.002), T stage (p = 0.006), overall TNM stage (p = 0.008), histological grade (p < 0.001), and tumor ploidy (p < 0.001). Intestinal type stomach cancer showed a significantly higher proportion of aneuploidy [diffuse vs. intestinal type; 41/102 (40%) vs. 52/74 (70%)]. After a median follow-up of 66.1 months (range, 29.6-78.1), 110 of 216 patients (51%) survived. Patients with intestinal type stomach cancer had a significantly better survival than did those with diffuse type stomach cancer (64% vs. 42% of patients surviving, p = 0.020). Our study suggests that there are biological differences between the two subtypes of Laurén's classification of stomach cancer in addition to the morphological differences. Laurén's classification should remain valid in future studies investigating the pathogenetic and clinical aspects of stomach cancer.

Characteristics of primary production in a eutrophicated bay.

The primary production of phytoplanktons provides organic matter in high concentration in eutrophicated Hakata bay in Japan, even during the winter season in spite of low water temperature. Phytoplanktons may have the biological capabilities to maintain activities of photosynthesis under unfavorable conditions, and these capabilities affect water quality in the bays. In this study, characteristics of primary production were analyzed with a simple box-type ecosystem model. We introduced a concept of efficiency for absorption of sunlight energy to our simulation model of water quality to explain rather high growth rates of phytoplanktons in low sunlight intensity. Through simulation with a box model, we found that the efficiency of primary production in winter is higher than that in summer. It was suggested that the organic pollution comes from dissolved organic carbon (DOC) throughout the year and that the DOC is originated from the primary production of phytoplanktons in biological response of the seasonal change of ambient conditions.

Clinical Features of Neuroendocrine Lung Cancer.

PURPOSE: This study was performed to investigate the clinical features of neuroendocrine lung cancer. MATERIALS AND METHODS: We performed a retrospective review of the histopathology and clinical information of 21 patients diagnosed as having neuroendocrine lung cancer between 1995 and 1999. RESULTS: Nineteen cases were male and 2 were female. The median age was 64 years (range: 45~80). Pathologic classification were atypical carcinoid (AC) in 2 cases, large cell neuroendocrine carcinoma (LCNEC) in 7 cases, and intermediate cell neuroendocrine carcinoma (ICNC) in 12 cases. Nine patients received tumor resection as first line therapy; adjuvant chemotherapy was given to 3 patients. Concurrent chemoradiotherapy was given to 1 patient. Six patients received palliative chemotherapy. The chemotherapy regimen included etoposide cisplatin in 5 cases and vinorelbine+cisplatin in 1 case. The median survival times were 11, 16 and 59 weeks for AC, LCNEC and ICNC, respectively. The estimated 2-year survival rates were AC 0%, LCNEC 22% and ICNC 31%. CONCLUSION: Surgery may have a positive effect on survival in patients with early stage cansers. Further investigation is required to improve survival in cases of advanced stage cancer.

Gene expression profile and identification of differentially expressed transcripts during human intrathymic T-cell development by cDNA sequencing analysis.

The development of immature thymocytes to mature T-lymphocytes is a central process for establishing a functional immune system. The gene regulatory events involved in this process are of outstanding interest in understanding the generation of the T-cell repertoire as well as the differentiation of lineage-specific cells, such as CD4(+) helper T-cells or CD8(+) cytotoxic T-lymphocytes. While some essential genes involved in lineage decision and thymocyte differentiation have been already identified, the exact regulatory mechanisms and differential gene expressions are still unknown. The present study was performed to analyze the gene expression profile during T-cell development, in particular, during the differentiation of immature thymocytes into CD4(+) mature T-cells by analyses of expressed sequence tags (ESTs), and to elucidate novel human genes involved in this process. Based on distinct developmental stages, three PCR-based cDNA libraries from immature CD3(-),4(-),8(-) triple-negative, CD4(+),8(+) double-positive, and mature CD4(+),8(-) single-positive thymocytes were constructed. A total of 1477 randomly selected clones were analyzed by automated single-pass sequencing, and the assembly of ESTs resulted in 1027 different species of contig sequences. Among them, 392 contig sequences were matched to known genes, and several novel transcripts were discovered. The matched clones were classified into seven categories according to their functional aspects, and the gene expression profiles of the three thymocyte subsets were compared. The information obtained in current study will serve as a valuable resource for elucidating the molecular mechanism of intrathymic T-cell development.

The prevalence and influence of significant psychiatric abnormalities in men undergoing comprehensive management of organic erectile dysfunction.

Psychiatric factors are etiologically important in a proportion of patients with erectile dysfunction. We determined the prevalence of psychopathology and the impact it has on current erectile dysfunction (ED) assessment and management. A group of 120 consecutive men with ED presenting to the Human Sexuality Clinic for the first time was prospectively investigated. All patients participated in a standardized evaluative protocol, including history, physical exam, assessment by a psychiatrist (using DSM-IV criteria), selective hormonal screen, and diagnostic intracavernosal injection. Follow-up appointments were to discuss diagnostic findings and, eventually, treatment choices. The prevalence of significant psychiatric pathology, excluding interview stress, was 33%. Only 16 of 40 cases were recognized and highlighted in the initial assessments by urological staff. There was no significant difference in the modalities of treatment choices between patients with psychiatric problems and those without. 10% of the patients had multiple organic risk factors, normal ICI, and significant psychiatric pathology. Psychopathology or emotional factors play a significant role in the etiology of ED and they are difficult to identify in a non-directed assessment. Even in the face of significant vascular risk factors, psychological abnormalities may be the primary etiology. Treating the 'phallodynamically challenged' individual without adequately addressing the possible presence of psychopathology, will account for treatment failures and have the potential for leaving untreated serious emotional problems.

Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia.

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.

Immature gastric teratoma in an infant: a case report.

Gastric teratomas are extremely rare neoplasms and almost exclusively benign. They occur predominantly in males and generally present as a palpable abdominal mass. To our knowledge, only one adult case has been described in the Korean literature. We report a case in which an immature gastric teratoma in a 3-month-old boy was revealed by CT and US.