Prethrombin-1 as a Drug Substance Promoting Hemostasis with Reduced Risk of Thrombosis.

INTRODUCTION: Prethrombin-1 is a Gla-domain lacking enzymatically inactive split product that results from the cleavage of fragment 1 from prothrombin by thrombin in a feedback reaction. METHODS: A prethrombin-1 preparation derived from human plasma was tested for its hemostatic and thrombogenic properties. Animal models of nail clipping (for rabbits) and tail clipping (for mice) were developed to measure blood loss in FVIII-inhibitor or rivaroxaban anticoagulated rabbits and mice, respectively. A modified Wessler test was used in rabbits to assess the thrombogenic potential by Wessler score and clot weight. Studies were performed in groups of three to six for prethrombin-1 dose escalation and comparison with prothrombin, Beriplex®, FEIBA®, and saline as a control. Data were analyzed using t-statistics or the Mann Whitney U test as applicable. RESULTS: Prethrombin-1 has excellent hemostatic properties in anticoagulated mouse and rabbit bleeding models. Wessler tests suggest that in contrast to activated and nonactivated prothrombin complexes, prethrombin-1 has negligible thrombogenic potential. CONCLUSION: The thrombin zymogen prethrombin-1 promotes hemostasis with reduced risk of thrombosis. Prethrombin-1 may have potential to become a life-saving treatment for patients who bleed or are at risk of bleeding.

Fermented and extruded wheat bran in piglet diets: impact on performance, intestinal morphology, microbial metabolites in chyme and blood lipid radicals.

The aim of the present study was to evaluate the influence of native, fermented and extruded wheat bran on the performance and intestinal morphology of piglets. Additionally, short-chain fatty acids (SCFA), biogenic amines, ammonia, lactic acid, pH as well as E. coli and lactic acid bacterial counts were analysed in digesta samples from three gut sections. Furthermore, the antioxidant potential in blood samples was evaluated based on the lipid radicals formed. For this purpose, 48 newly weaned piglets (28 d old) were allocated to one of the four different dietary treatment groups: no wheat bran (Control), native wheat bran, fermented wheat bran as well as extruded wheat bran. Wheat bran variants were included at 150 g/kg into the diets. All diets were mixed to reach the calculated isonitrogenic nutrient contents. Gut tissue and digesta samples were collected from the proximal jejunum, the terminal ileum and the colon ascendens, blood samples directly at slaughter. Although none of the dietary interventions had an impact on performance parameters, the amount of goblet cells in the ileum was increased upon feeding native and extruded wheat bran, compared to fermented bran (p < 0.05). The E. coli counts in colonic chyme were significantly lower (p < 0.05) in the Control group compared to the groups fed with wheat bran. The concentration of SCFA showed differences for minor compounds (p < 0.05), while linear contrast analyses revealed a reduced concentration of total SCFA in the colon following the feeding of modified wheat bran compared to native wheat bran. This may suggest that several compounds are more easily digested already in the ileum, resulting in a reduced nutrient flow into the large intestine and therefore less unexploited digesta is available as substrate for the microorganisms there. Fermentation also resulted in a significant decrease of methylamine in the colon (p < 0.05), while other biogenic amines in the ileum and colon showed no statistically significant differences. The formation of lipid radicals was decreased (p < 0.05) after feeding native wheat bran compared to the Control group. These results suggest that fermentation and extrusion of wheat bran exert some different impact regarding their physiological mode of action.

Comparison of homo- and heterofermentative lactic acid bacteria for implementation of fermented wheat bran in bread.

Despite its potential health benefits, the integration of wheat bran into the food sector is difficult due to several adverse technological and sensory properties such as bitterness and grittiness. Sourdough fermentation is a promising strategy to improve the sensory quality of bran without inducing severe changes to the bran matrix. Therefore, identification of species/strains with potential for industrial sourdough fermentations is important. We compared the effects of different representatives of species of lactic acid bacteria (LAB) on wheat bran. Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus brevis, Lactobacillus sanfranciscensis and Fructobacillus fructosus produced highly individual fermentation patterns as judged from carbohydrate consumption and organic acid production. Interestingly, fructose was released during all bran fermentations and possibly influenced the fermentation profiles of obligately heterofermentative species to varying degrees. Except for the reduction of ferulic acid by L. plantarum and L. pentosus, analyses of phenolic compounds and alkylresorcinols suggested that only minor changes thereof were induced by the LAB metabolism. Sensory analysis of breads baked with fermented bran did not reveal significant differences regarding perceived bitterness and aftertaste. We conclude that in addition to more traditionally used sourdough species such as L. sanfranciscensis and L. brevis, also facultatively heterofermentative species such as L. plantarum and L. pentosus possess potential for industrial wheat bran fermentations and should be considered in further investigations.

Wheat bran biorefinery--a detailed investigation on hydrothermal and enzymatic treatment.

Due to the enormous quantities arising in the milling industry and its specific properties, wheat bran can be considered as a feedstock for future biorefineries. In the present work, a detailed investigation was carried out on the hydrothermal (140-200°C) and enzymatic treatment of wheat bran. After hydrothermal pretreatment and a subsequent enzymatic hydrolysis a glucose yield of 65% and 90% was achieved, respectively. Interestingly, the hemicelluloses could be disintegrated to monomers only to approx. 50%. About 70% of the proteins were dissolved, however, practically no free amino acids were obtained under given conditions. Severe treatment conditions induce elevated losses of some amino acids. Minerals could be extracted almost completely. To disintegrate fat into glycerol and fatty acids severe process conditions were necessary. The formation of undesired by-products such as furfural or hydroxymethylfurfural starts at approx. 180°C.