[Treatment of postprandial discomfort syndrome in the elderly: a multi-centered prospective randomized controlled clinical study].

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

Dysfunction of Poly (ADP-Ribose) Glycohydrolase Induces a Synthetic Lethal Effect in Dual Specificity Phosphatase 22-Deficient Lung Cancer Cells.

Poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme responsible for catabolism of poly (ADP-ribose) (PAR), synthesized by PARP. PARG dysfunction sensitizes certain cancer cells to alkylating agents and cisplatin by perturbing the DNA damage response. The gene mutations that sensitize cancer cells to PARG dysfunction-induced death remain to be identified. Here, we performed a comprehensive analysis of synthetic lethal genes using inducible PARG knockdown cells and identified dual specificity phosphatase 22 (DUSP22) as a novel synthetic lethal gene related to PARG dysfunction. DUSP22 is considered a tumor suppressor and its mutation has been frequently reported in lung, colon, and other tumors. In the absence of DNA damage, dual depletion of PARG and DUSP22 in HeLa and lung cancer A549 cells reduced survival compared with single-knockdown counterparts. Dual depletion of PARG and DUSP22 increased the apoptotic sub-G1 fraction and upregulated PUMA in lung cancer A549, PC14, and SBC5 cells, and inhibited the PI3K/AKT/mTOR pathway in A549 cells, suggesting that dual depletion of PARG and DUSP22 induced apoptosis by upregulating PUMA and suppressing the PI3K/AKT/mTOR pathway. Consistently, the growth of tumors derived from double knockdown A549 cells was slower compared with those derived from control siRNA-transfected cells. Taken together, these results indicate that DUSP22 deficiency exerts a synthetic lethal effect when combined with PARG dysfunction, suggesting that DUSP22 dysfunction could be a useful biomarker for cancer therapy using PARG inhibitors. SIGNIFICANCE: This study identified DUSP22 as a novel synthetic lethal gene under the condition of PARG dysfunction and elucidated the mechanism of synthetic lethality in lung cancer cells.

Nutritional evaluation of two barley cultivars, without and with carbohydrase supplementation, for broilers: metabolisable energy and standardised amino acid digestibility.

1. Two experiments were conducted to assess the nitrogen-corrected apparent metabolisable energy (AMEn; Exp. 1; 288 Ross 308 male broilers at d 14; 36 cages with eight birds each) and coefficient of standardised ileal digestibility (CSID) of amino acids (AA; Exp. 2; 336 Ross 308 male broilers at d 21; 42 cages with eight birds each) of two barley cultivars for broilers in comparison to wheat, without or with a multi-component non-starch polysaccharide (NSP) degrading enzyme. A 3 × 2 factorial arrangement of treatments was used in both experiments with three types of grains (normal starch hulled barley [NSH], waxy starch hull-less barley [WSHL], and wheat) and two levels of enzyme supplementation (0 and 200 g/tonne of feed). Enzyme supplemented diets contained 406 and 128 of endo-1, 4-ß-xylanase and endo-1, 3 (4)-ß-glucanase units per kg of feed, respectively. 2. Analysis showed that the starch content was higher in NSH (610 g/kg) than in wheat (537 g/kg) and WSHL (554 g/kg), and the composition of starch differed markedly among the grain types. The ß-glucan content was considerably higher in WSHL (68.6 g/kg) compared to NSH (38.5 g/kg) and wheat (7.74 g/kg). The contribution of soluble fraction to the total non-starch polysaccharides was higher in WSHL (38.2%) compared to NSH and wheat (17.1% and 13.3%, respectively). 3. A significant (P < 0.01) interaction was observed between the grain type and enzyme supplementation for AMEn. The WSHL, with the highest content of ß-glucan, showed the greatest response to enzyme supplementation for AMEn. 4. Birds fed wheat- and WSHL-based diets had the highest and lowest CSID of nitrogen and most of AA, respectively, with NSH diets being intermediate. Regardless of grain type, enzyme supplementation increased (P < 0.05) the CSID of nitrogen. 5. These data suggest that ß-glucan content plays an important role in determining the digestibility of nutrients in barley for broilers, resulting in a better feeding value for NSH over WSHL. Supplementation of a multi-component NSP-degrading enzyme can improve the feeding value of barley in broiler diets by increasing the digestibility with the effect being more pronounced in WSHL barley.

The Consequences of Biofilm Dispersal on the Host.

Chronic infections are often associated with the presence of a biofilm, a community of microorganisms coexisting within a protective matrix of extracellular polymeric substance. Living within a biofilm can make resident microbes significantly more tolerant to antibiotics in comparison to planktonic, free-floating cells. Thus, agents that can degrade biofilms are being pursued for clinical applications. While biofilm degrading and dispersing agents may represent attractive adjunctive therapies for biofilm-associated chronic infections, very little is known about how the host responds to the sudden dispersal of biofilm cells. In this study, we found that large-scale, in vivo dispersal of motile biofilm bacteria by glycoside hydrolases caused lethal septicemia in the absence of antibiotic therapy in a mouse wound model. However, when administered prudently, biofilm degrading enzymes had the potential to potentiate the efficacy of antibiotics and help resolve biofilm-associated wound infections.

Occupational asthma in fruit salad processing.

BACKGROUND: Three subjects employed in the preparation of fruit for fruit salads reported work-related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase. Objectives To investigate the respiratory symptoms reported by these workers and determine their causes. METHODS: The three workers were investigated by a respiratory physician, including spirometry and serial peak flow measurements. Blood was taken for the measurement of IgE and IgG antibody responses against the enzyme solution. RESULTS: Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work-related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. All three improved immensely following withdrawal from the workplace environment. CONCLUSION: Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma.

Enzyme exposure and enzyme sensitisation in the baking industry.

OBJECTIVES: To assess the exposure to enzymes and prevalence of enzyme sensitisation in the baking industry. METHODS: A cross sectional study was conducted in four bakeries, one flour mill, and one crispbread factory. Sensitisation to enzymes, flours, and storage mites was examined by skin prick and radioallergosorbent (RAST) tests. 365 workers were tested. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of alpha-amylase in air was measured by a catalytic method. An immunochemical method was used for measuring cellulase and xylanase in air. RESULTS: Total measured dust concentrations were from 0.1 to 18 mg/m3, with highest values in dough making areas of bakeries. The alpha-amylase concentrations generally followed the total dust concentrations and reached the highest values < 6.6 micrograms/m3 in the same areas. Cellulase and xylanase varied with concentrations < 180 ng/m3 and < 40 ng/m3, respectively, in the flour mill and the crispbread factory. No cellulase, but concentrations of 1-200 ng/m3 xylanase, were found in the bakeries, probably indicating the natural xylanase activity of wheat. 12 workers (8%) in the bakeries, three (5%) in the flour mill, and four (3%) in the crispbread factory were skin prick positive to enzymes. The corresponding percentages of positive reactions to flours were 12%, 5%, and 8%. CONCLUSIONS: The study confirmed that industrial enzymes in baking used as additives in a powdered form pose a risk of sensitisation. The no effect air concentrations for industrial enzymes are not known. Based on present knowledge, however, lowering exposures and eliminating short and high peaks by technical measures would lower the risk of sensitisation. This would be most effectively accomplished by shifting to non-dusty products.

Reduction of the formation of dental plaque and gingivitis in humans by crude mutanase.

The effect of a Trichoderma harzianum enzyme preparation containing mutanase (alpha-1,3 glucan glucanohydrolase) on plaque accumulation and composition and on occurrence of gingivitis was assessed in 20 persons in a double-blind cross-over investigation. The enzyme preparation was administered in chewing gum. Two test periods of 1 week were preceded by scaling and cleansing of the teeth, oral hygiene instruction, and controlled hygiene for at least 3 weeks. Oral hygiene measures were discontinued during the test periods, while the persons chewed six pieces of chewing gum per day, one half using enzyme-containing gum, and the other half using placebo gum. The test periods were identical, only enzyme gum was used instead of placebo, or vice versa. Evaluations of plaque and gingivitis showed that less plaque had accumulated and less gingivitis developed during the enzyme than during the placebo period, but bacteriologic studies of interproximal plaque did not reveal differences that could explain the clinical findings. Treatment with the enzyme preparation caused some local side effects, but no primary skin irritation, delayed hypersensitivity, nor anti-enzyme IgE was detected in any of the persons.