Risk factors for persistent positive anticardiolipin antibodies in women with recurrent pregnancy loss.

Antiphospholipid syndrome (APS) is an established cause of recurrent pregnancy loss (RPL). It is necessary to detect persistently positive antiphospholipid antibodies to diagnose APS. This study aimed to explore risk factors for persistent anticardiolipin (aCL) positivity. Women with a history of RPL or with a history of one or more intrauterine fetal deaths after 10 weeks underwent examinations to determine the causes of RPL, including antiphospholipid antibodies. If aCL-IgG or aCL-IgM antibodies were positive, retests were performed at least 12 weeks apart. Risk factors for persistent aCL antibody positivity were retrospectively investigated. The number and percentage of cases above the 99th percentile were 74/2399 (3.1%) for aCL-IgG, and 81/2399 (3.5%) for aCL-IgM. Of the initially tested cases, 2.3% (56/2399) for aCL-IgG and 2.0% (46/2289) for aCL-IgM were ultimately positive above the 99th percentile in retests. Retest values after 12 weeks were significantly lower than the initial values for both IgG and IgM immunoglobulin classes. Initial aCL antibody titers were significantly higher in the persistent-positive group than in the transient-positive group for both IgG and IgM immunoglobulin classes. The cut-off values for predicting persistent positivity of aCL-IgG antibodies and aCL-IgM antibodies were 15 U/mL (99.1 percentile) and 11 U/mL (99.2 percentile), respectively. The only risk factor for persistently positive aCL antibodies is a high antibody titer during the initial test. When the aCL antibody titer in the initial test exceeds the cut-off value, therapeutic strategies can be defined in subsequent pregnancies without waiting for 12 weeks.

Congenital venous anomalies associated with retrocaval ureter: evaluation using computed tomography.

BACKGROUND: Retrocaval ureter is a rare congenital anomaly resulting from anomalous development of inferior vena cava (IVC) and not from anomalous of the ureter. The anomaly always occurs on the right side due to regression of right supracardinal vein and persistence of right posterior cardinal vein. Retrocaval ureter tends to be associated with various vena cava anomalies because of the embryogenesis. We aimed to identify the prevalence of associated congenital venous anomalies (CVA) resulting from cardinal vein development in adults with retrocaval ureter using computed tomography (CT) images. MATERIALS AND METHODS: The study included 22 adults with retrocaval ureter. We evaluated CT findings and determined the incidence of associated CVA using thin slice data sets from CT scanner with 64 or more detectors. We compared the prevalence of CVA in the retrocaval ureter group (mean age: 57 ± 19 years) and in the control group of 6189 adults with normal ureter (mean age: 66 ± 14 years). RESULTS: In the retrocaval ureter group, 4 (18.2%) adults had CVA including double IVC, right double IVC, preisthmic IVC with horseshoe kidney, and preaortic iliac confluence. One of 2 adults with preaortic iliac confluence had right double right IVC. In the control group, 49 (0.79%) adults had CVA including 37 double IVC, 11 left IVC, and 1 IVC interruption azygos continuation. Fifteen horseshow kidneys were found. The prevalence of associated CVA in the retrocaval ureter group was higher than that in the control group (p < 0.001). CONCLUSIONS: Retrocaval ureter is frequently associated with CVA. Various CVA with retrocaval ureter could happen because of abnormal development of not only the right posterior or supra cardinal vein but also other cardinal veins.

Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Craniofacial penetration by a wooden stick.

INTRODUCTION: Penetrating craniofacial injuries caused by stick-like foreign bodies occur as a result of accidents particularly in children, and often lead to significant morbidity. CASE SUMMARY: We describe a 5-year-old boy who sustained facial trauma after falling on a wooden stick which penetrated his left cheek. At the initial visit, his vital and neurological signs were normal. However, the stick had penetrated the frontal lobe to a depth of 3cm via the orbital cavity and the anterior skull base. The stick was successfully removed while visualizing the anterior skull base in an endoscopic transethmoidal approach. A follow-up examination one year after the accident demonstrated normal visual acuity and ocular motility, with no diplopia, tearing or pain. DISCUSSION: Penetrating facial injuries caused by stick-like objects carry a significantly higher risk of serious neurological involvement. Even if penetrating facial injuries sometimes appear trivial, the external injury site is often insufficient to determine the position of the object within the head. Although the cheek is a rare entry site for intracranial injuries, the extent of damage should be assessed fully before attempting removal.

Phase Angle Is a Useful indicator for Muscle Function in Older Adults.

AIM: Phase angle (PhA) can be determined through bioelectrical impedance analysis and is a unique variable for skeletal muscle. The objective of this study was to evaluate the relationship between PhA and muscle mass/quality in older adults. In addition, we attempted to determine the cutoff value of PhA for poor muscle function. METHODS: Community-dwelling Japanese older men (n=285, 81.1±7.1 years) and women (n=724, 80.4±6.8 years) participated in this study and were classified into four groups based on the Asian Working Group for Sarcopenia (normal, presarcopenia, dynapenia, and sarcopenia). We measured PhA using bioelectrical impedance analysis, muscle quantity and quality indicators using ultrasonography, muscle strength, and physical performance and compared them in four groups. We also tried to determine the cutoff value of PhA for poor muscle function. RESULTS: We found a significant difference in PhA among the four groups in men (P<0.05), and the dynapenia (3.61±0.75°) and sarcopenia groups (3.40±0.74°) showed significantly lower values than the normal group (4.50±0.86°) (P<0.05), but not the presarcopenia group (4.12±0.85°). In women, a significant difference was also observed among the four groups (P<0.05), and the dynapenia (3.41±0.65°) and sarcopenia groups (3.31±0.66°) showed significantly lower measures than the normal group (4.14±0.71°) (P<0.05), but not the presarcopenia group (4.07±0.51°). The receiver-operating characteristic curve analysis indicated the best cutoff value of PhA (men: 4.05°, women: 3.55°) to discriminate sarcopenia and dynapenia from normal and presarcopenia. CONCLUSION: These findings suggest that PhA is a useful indicator for muscle function.

Plasma Amino Acid Concentrations Are Associated with Muscle Function in Older Japanese Women.

BACKGROUND: Although several previous studies have found benefits for amino acid supplementation in terms of muscle function, the role of plasma amino acid concentrations on sarcopenia are not well addressed yet. OBJECTIVE: The aim of this study was to compare the amino acid concentrations at each stage of sarcopenia (normal, pre-sarcopenia, dynapenia, and sarcopenia) in community-dwelling older Japanese adults. SETTING AND SUBJECTS: Community-dwelling older Japanese women (n=232, 79.4±7.0 years) participated in this study. MEASUREMENTS: We measured plasma amino acid concentrations, 5-m walking speed, grip strength, and skeletal muscle mass using a bioelectrical impedance data acquisition system and compared them among participants at each stage of sarcopenia. RESULTS: The proportions of normal, pre-sarcopenia, dynapenia, and sarcopenia patients were 40.5% (n=94), 12.1% (n=28), 26.3% (n=61), and 21.1% (n=49), respectively. Significant differences were observed for concentrations of leucine, branched-chain amino acid (BCAAs), and essential amino acid (EAAs) among the four groups (p<0.05), and the dynapenia and sarcopenia groups showed significantly lower concentrations of leucine than the normal group (p<0.05). CONCLUSIONS: This study indicated a positive relationship between plasma leucine, BCAA and EAA concentrations and muscle function. A longitudinal study is needed to determine the causal relationship between leucine/BCAA concentrations and muscle function.

Fibroblast growth factor 13 regulates glioma cell invasion and is important for bevacizumab-induced glioma invasion.

Glioblastoma has the poorest prognosis, and is characterized by excessive invasion and angiogenesis. To determine the invasive mechanisms, we previously used two glioma cell lines (J3T-1 and J3T-2) with different invasive phenotypes. The J3T-1 showed abundant angiogenesis and tumor cell invasion around neovasculature, while J3T-2 showed diffuse cell infiltration into surrounding healthy parenchyma. Microarray analyses were used to identify invasion-related genes in J3T-2 cells, and the expressed genes and their intracellular and intratumoral distribution patterns were evaluated in J3T-2 cell lines, human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens. To determine the role of the invasion-related genes, invasive activities were evaluated in vitro and in vivo. Fibroblast growth factor 13 (FGF13) was overexpressed in J3T-2 cells compared to J3T-1 cells, and in human glioma cell lines, human glioblastoma stem cells and human glioblastoma specimens, when compared to that of normal human astrocytes. Immunohistochemical staining and the RNA-seq (sequencing) data from the IVY Glioblastoma Atlas Project showed FGF13 expression in glioma cells in the invasive edges of tumor specimens. Also, the intracellular distribution was mainly in the cytoplasm of tumor cells and colocalized with tubulin. Overexpression of FGF13 stabilized tubulin dynamics in vitro and knockdown of FGF13 decreased glioma invasion both in vitro and in vivo and prolonged overall survival of several xenograft models. FGF13 was negatively regulated by hypoxic condition. Silencing of FGF13 also decreased in vivo bevacizumab-induced glioma invasion. In conclusion, FGF13 regulated glioma cell invasion and bevacizumab-induced glioma invasion, and could be a novel target for glioma treatment.

Pathogenic factors in Candida biofilm-related infectious diseases.

Candida albicans is a commonly found member of the human microflora and is a major human opportunistic fungal pathogen. A perturbation of the microbiome can lead to infectious diseases caused by various micro-organisms, including C. albicans. Moreover, the interactions between C. albicans and bacteria are considered to play critical roles in human health. The major biological feature of C. albicans, which impacts human health, resides in its ability to form biofilms. In particular, the extracellular matrix (ECM) of Candida biofilm plays a multifaceted role and therefore may be considered as a highly attractive target to combat biofilm-related infectious diseases. In addition, extracellular DNA (eDNA) also plays a crucial role in Candida biofilm formation and its structural integrity and induces the morphological transition from yeast to the hyphal growth form during C. albicans biofilm development. This review focuses on pathogenic factors such as eDNA in Candida biofilm formation and its ECM production and provides meaningful information for future studies to develop a novel strategy to battle infectious diseases elicited by Candida-formed biofilm.

An innovative masticatory efficiency test using odour intensity in the mouth as a target marker: a feasibility study.

A large number of studies have reported the findings for masticatory efficiency tests; however, some objective masticatory efficiency tests have a drawback, in that subjects are required to spit out the test material. This study examined the possibility of a masticatory efficiency test that evaluates the intensity of odours released when chewing an odour compound-containing material. A total of 20 volunteers were used in this study. The odour intensity in the breath after chewing a gum was measured by portable odour sensor device. The odour intensity after chewing the gum was measured over four chewing durations and at four intervals between spitting out and measurement of the odour intensity. The volume of stimulated saliva was measured by calculating the difference in the weight of the gauze before and after chewing to examine the effect of saliva flow. With an increase in chewing duration, odour intensity reduced. The odour intensity was the highest immediately after chewing. There was a positive correlation between odour intensity and gummy jelly-related masticatory efficiency test value (G-METV), which was significant for 10-s chewing. The regression equation was calculated from three objective variables of odour intensity and G-METV as dependent variable. Pearson's correlation coefficient between G-METV and the odour intensity-related masticatory efficiency value (O-METV) was 0·68. The coefficient of variation of O-METV was significantly lower than that of G-METV. These results suggest that the masticatory performance can be estimated by measuring the odour intensity immediately after chewing food containing odour compounds for 10 s.

Port-site transversus abdominis fascia closure reduced the incidence of incisional hernia following retroperitoneal laparoscopic nephrectomy.

PURPOSE: The incidence of incisional hernia after laparoscopic surgery is reportedly 0-5.2 %; there are only a few reports of that following retroperitoneal laparoscopic nephrectomy. We evaluated the incidence of and risk factors for incisional hernia after retroperitoneal laparoscopic nephrectomy, and the efficacy of our novel prophylaxis technique. METHODS: A total of 207 renal cell carcinoma patients who underwent laparoscopic nephrectomy at Chiba University Hospital were retrospectively enrolled in this study. We compared the incidences of incisional hernia following the transperitoneal vs. retroperitoneal approaches, and, among the latter group, the incidences with vs. without use of our prophylaxis method. Also among the retroperitoneal-approach group, we evaluated selected patient characteristics as potential hernia risk factors. RESULTS: The rate of incisional hernias was 14 (8.7 %) after 161 retroperitoneal laparoscopic nephrectomies and one (2.2 %) after 46 transperitoneal laparoscopic nephrectomies (P = 0.132). For those undergoing the retroperitoneal approach, 14 (11.3 %) hernias were identified in 124 non-prophylaxed patients and none in 37 prophylaxed patients. Transversus abdominis fascia closure was a statistically significant factor for reducing the incidence of incisional hernia after retroperitoneal laparoscopic nephrectomy (P = 0.0324): rectus abdominis muscle thickness ≤7 mm and perioperative blood loss >100 ml were statistically significant independent risk factors, by multivariate analysis. CONCLUSIONS: To prevent incisional hernia after retroperitoneal laparoscopic nephrectomy in the patients with risk factors, it is useful to close the transversus abdominis fascia at the port sites from inside the surgical cavity, through the open specimen-removal trocar port site, under direct observation.

Impact of Donor and Recipient Single Nucleotide Polymorphisms in Living Liver Donor Transplantation for Hepatitis C.

INTRODUCTION: Recently, several studies have shown that specific single nucleotide polymorphisms (SNPs) affect liver fibrosis progression in patients with hepatitis C virus (HCV) infection. In this study, we examined the impact of donor and recipient SNPs on the progression of fibrosis after liver transplantation for HCV infection. METHODS: This cohort study enrolled 43 patients with HCV infection who underwent liver transplantation at our hospital. We evaluated 5 genotypes (rs4374383, rs2629751, rs9380516, rs8099917, and rs738409) that have been reported to be significant predictors of fibrosis in HCV infection using a Taqman assay. RESULTS: Liver fibrosis (stage ≥ F1, New Inuyama classification) was detected at 1 year after liver transplantation in 30 cases (70%). The rs2629751 non-AA-genotype was found to be significantly associated with fibrosis progression at 1 year after liver transplantation (AA:GG or GA = 46%:88%, P < .05). The primary outcome was stage ≥F2 (portoportal septa) or liver-related mortality in 22 patients. The time to stage ≥F2 fibrosis or liver-related mortality was significantly different only in terms of the donor rs2629751 genotype (AA:GG or GA = 5.5 ± 0.6 years:3.6 ± 0.7 years, P = .025). CONCLUSIONS: The rs2629751 genotype may be an important predictor of posttransplant outcome in HCV-infected patients. This result might be useful in donor selection for liver transplantation in HCV-infected patients and may guide therapeutic decisions regarding early antiviral treatment.

Integrin antagonist augments the therapeutic effect of adenovirus-mediated REIC/Dkk-3 gene therapy for malignant glioma.

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) was identified as a gene whose expression is reduced in many human cancers. REIC/Dkk-3 expression is also downregulated in malignant glioma and regulates cell growth through caspase-dependent apoptosis. cRGD (EMD121974), an antagonist of integrins, has demonstrated preclinical efficacy against malignant glioma. In this study, we investigated the antiglioma effect of combination therapy using an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) and cRGD. Quantitative real-time reverse-transcription PCR revealed the reduction of REIC/Dkk-3 mRNA levels in malignant glioma cell lines. The reduction of REIC/Dkk-3 protein expression in malignant glioma cell lines was also confirmed with western blot analysis. After treatment with Ad-REIC and cRGD, the proliferative rate of malignant glioma cells was significantly reduced in a time-dependent manner. In vivo, there was a statistically significant increase in the survival of mice treated with Ad-REIC and cRGD combination therapy compared with Ad-REIC monotherapy. We identified an apoptotic effect following monotherapy with Ad-REIC. Moreover, cRGD augmented the antiglioma efficacy of Ad-REIC. These results may lead to a promising new approach for the treatment of malignant glioma.

A metagenetic approach for revealing community structure of marine planktonic copepods.

Marine planktonic copepods are an ecologically important group with high species richness and abundance. Here, we propose a new metagenetic approach for revealing the community structure of marine planktonic copepods using 454 pyrosequencing of nuclear large subunit ribosomal DNA. We determined an appropriate similarity threshold for clustering pyrosequencing data into molecular operational taxonomic units (MOTUs) using an artificial community containing 33 morphologically identified species. The 99% similarity threshold had high species-level resolution for MOTU clustering but overestimated species richness. The artificial community was appropriately clustered into MOTUs at 97% similarity, with little inflation in MOTU numbers and with relatively high species-level resolution. The number of sequence reads of each MOTU was correlated with dry weight of that taxon, suggesting that sequence reads could be used as a proxy for biomass. Next, we applied the method to field-collected samples, and the results corresponded reasonably well with morphological analysis of these communities. Numbers of MOTUs were well correlated with species richness at 97% similarity, and large numbers of sequence reads were generally observed in MOTUs derived from species with large biomass. Further, MOTUs were successfully classified into taxonomic groups at the family level at 97% similarity; similar patterns of species richness and biomass were revealed within families with metagenetic and morphological analyses. At the 99% similarity threshold, MOTUs with high proportions of sequence reads were identified as biomass-dominant species in each field-collected sample. The metagenetic approach reported here can be an effective tool for rapid and comprehensive assessment of copepod community structure.

Sleep disturbances and quality of life in patients after living donor liver transplantation.

BACKGROUND: Following improvements in patient and graft survival after liver transplantation (LT), the recipients' quality of life has become an important focus of patient care. Sleep is closely related to physical and mental health; however, sleep disturbances in LT patients have not yet been evaluated. METHODS: We assessed 59 LT patients (aged ≥18 years) between September 2011 and September 2012. The patients completed the restless legs syndrome (RLS), 36-item short-form health survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) questionnaires. In addition, laboratory data were obtained and neuropsychological tests (NPT) were performed during study entry. RESULTS: Thirty-eight patients (64%) were included in the poor sleep group (PSQI ≥6 or ESS ≥10). The SF-36 scores were lower in the poor sleep group than in the good sleep group. Eleven patients (18%) had RLS. An NPT score ≥3 indicated minimal hepatic encephalopathy (MHE3). The MHE3 group consisted of 22 patients (43%). The time after LT was shorter; serum albumin, branched chain amino acid/tyrosine molar ratio (BTR), and role limitations due to poor physical health were lower; and serum ammonia levels were higher in the MHE3 group than in the MHE0-2 group. When the poor sleep group was divided into subgroups (control, MHE, RLS, and unknown), MHE patients had high model for end-stage liver disease scores, high ammonia levels, and low BTR, whereas RLS patients showed a short time after LT. CONCLUSION: Sixty-four percent of recipients were classified as poor sleepers. SF-36 scores were lower for poor sleepers than good sleepers. RLS and MHE are major diseases that cause sleep disturbances in patients after LT.

Hydrogen negative ion production in a 14 GHz electron cyclotron resonance compact ion source with a cone-shaped magnetic filter.

The plasma electrode structure of a 14 GHz ECR ion source was modified to enlarge the plasma volume of low electron temperature region. The result shows that the extracted beam current reached about 0.6 mA/cm(2) with about 40 W microwave power. To investigate the correlation between the volume of the low electron temperature region and the H(-) current, a vacuum ultraviolet (VUV) spectrometer had been installed to observe light emission in the VUV wavelength range from the plasma. From the results of the negative ion beam current and that from VUV spectrometry, production rate of vibrationally excited hydrogen molecule seems to be enhanced by increasing the volume of low electron temperature region.

Effects of extracellular DNA from Candida albicans and pneumonia-related pathogens on Candida biofilm formation and hyphal transformation.

AIMS: The aim of this study was to investigate the effects of genomic DNA purified from Candida albicans and pneumonia-related pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, on in vitro biofilm formation and morphological change of 3 Candida species (C. albicans, C. glabrata, and C. tropicalis). METHODS AND RESULTS: Biofilm formation was evaluated by the crystal violet assay and colony-forming unit counts. Morphological characteristics of biofilms were evaluated by scanning electron microscopy and fluorescence microscopy. Addition of DNA at a low concentration (<1·0 µg ml(-1)) significantly increased biofilm mass of all three Candida species. In contrast, the addition of DNA at a high concentration (10 µg ml(-1)) decreased the biofilm mass. Interestingly, the formation of hyphae in a dense network of yeast cells was observed in C. albicans biofilms exposed to a low concentration of DNA (<1·0 µg ml(-1)). CONCLUSIONS: These findings demonstrated that extracellular DNA (eDNA) plays a crucial role in Candida biofilm formation and suggested that eDNA may induce the morphological transition from yeast to hyphal growth form during C. albicans biofilm development. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel therapy targeting eDNA may be applicable for Candida infection to decrease biofilm formation and hyphal formation.

Orbital masses: the usefulness of diffusion-weighted imaging in lesion categorization.

INTRODUCTION: Diffusion-weighted imaging (DWI) produces contrast among different kinds of tissues according to their diffusibility characteristics. The purpose of our study was to evaluate the role of DWI including measurement of apparent diffusion coefficient (ADC) values in recognizing benignancy or malignancy of orbital masses. METHODS: A total of 39 orbital masses were evaluated visually for signal characteristics on DWI and ADC maps. ADC values were calculated for each lesion. Visual signal characteristics were compared using the Fisher exact test. Receiver operating characteristic (ROC) analysis was carried out to determine sensitivity and specificity for distinguishing malignant from benign lesions using ADC values. The Mann-Whitney U test was applied to compare the ADC values between orbital lymphomas and idiopathic orbital inflammatory (IOI) lesions, and between optic nerve sheath meningiomas and gliomas. RESULTS: Visual assessment revealed no significant difference between benign and malignant lesions on DWI (p-value = 0.66). However, visual assessment of ADC maps revealed a statistically significant (p-value ≤ 0.0001) between benign and malignant lesions. ROC analysis showed a sensitivity of 83.33 % and a specificity of 85.71 % when using an optimal cut off ADC value of 0.84 × 10(-3) mm(2)/s for differentiating malignant from benign lesions. Significant differences in mean ADC values were observed between lymphomas and IOI lesions (p-value = 0.05), and between optic nerve sheath meningiomas and gliomas (p-value = 0.03). CONCLUSION: DWI is useful for differentiating malignant and benign orbital tumors if accompanied by visual assessment of ADC maps and ADC value calculations.

The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus.

Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic herpes simplex virus-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared with RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared with the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87ΔEGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than that of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared with RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents.

Reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy.

BACKGROUND: Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. AIM: To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. METHODS: Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. RESULTS: Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. CONCLUSIONS: The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.