Agitation Effects and Kinetic Constants of Exoglucomannan Production by Antarctic Yeast Strain in a Stirred Tank Bioreactor

Exoglucomannan production by Antarctic yeast Sporobolomyces salmonicolor AL1 is studied at semi-tech scale in a 5 L stirred tank bioreactor and the bioreaction kinetics is quantified. The organism’s unconventional response to agitation is analyzed in terms of the agitation-induced mechanical stress. The yeast maximum production activity was observed at agitation rate 400 rpm and conserved or decreased at further increase in mixing intensity. Referring to the relationship of cell growth and aeration intensity, the various production activity, oxygen availability and cell growth are considered as a starting point to elucidate the possible reasons for the anomaly. At suspicion of shear detrimental effect on the yeast cells, the hydrodynamic stress acting on cell particles is determined and the microorganism morphology at low and high mixing intensity is examined. Biological stability is registered and the agitation effect is attributed to depressed metabolic activity at the evolving dissolved oxygen tension rather than to direct effect of hydrodynamics. A kinetic model is proposed. The specific growth rate (µ, h–1) and growth-associated (g EPS g–1 cells), and non-growth associated (g EPS g–1 cells h–1) production constants are determined and compared with reported estimates for similar reference EPS fermentations. The model and its parameters are determined in well-mixed cultures and could be upgraded further to account for mixing non-ideality and mass transfer in larger vessels

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Agitation Effects and Kinetic Constants of Exoglucomannan Production…

Exoglucomannan production by Antarctic yeast Sporobolomyces salmonicolor AL 1 is studied at semi-tech scale in a 5 L stirred tank bioreactor and the bioreaction kinetics is quantified. The organism&apos;s unconventional response to agitation is analyzed in terms of the agitation-induced mechanical stress. The yeast maximum production activity was observed at agitation rate 400 rpm and conserved or decreased at further increase in mixing intensity. Referring to the relationship of cell growth and aeration intensity, the various production activity, oxygen availability and cell growth are considered as a starting point to elucidate the possible reasons for the anomaly. At suspicion of shear detrimental effect on the yeast cells, the hydrodynamic stress acting on cell particles is determined and the microorganism morphology at low and high mixing intensity is examined. Biological stability is registered and the agitation effect is attributed to depressed metabolic activity at the evolving dissolved oxygen tension rather than to direct effect of hydrodynamics. A kinetic model is proposed. The specific growth rate (µ, h -1 ) and growth-associated (g EPS g -1 cells), and non-growth associated (g EPS g -1 cells h -1 ) production constants are determined and compared with reported estimates for similar reference EPS fermentations. The model and its parameters are determined in well-mixed cultures and could be upgraded further to account for mixing non-ideality and mass transfer in larger vessels