[Daytime flexible application of Insulin degludec in patients with type 1 diabetes or type 2 diabetes]. / Tageszeitlich flexible Gabe von Insulin degludec bei Patienten mit Typ-1-Diabetes oderTyp-2-Diabetes.

BACKGROUND: Insulin degludec (IDeg) is a basal insulin with a stable, flat action profile and an even distribution of the blood glucose lowering effect over 24 hou rs. The terminal half-life of IDeg is about 25 hours, which reflects a mean prolongation by factor 2 compared to Insulin glargin (lGlar).This may enable for a more flexible daytime dosing versus up to now available basal insulins. METHOD: Two open, randomized, treat-to-target studies enrolled patients with type 1 diabetes (n =493) or type 2 diabetes (n = 687). Both phase 3 studies compared a daytime flexible dosing of IDeg (IDeg-flex) with IDeg at the evening meal (IDeg-evening) and IDler at a fixed daytime. In the IDeg-flex-group dosing intervals were predefined with variations between 8 and 40 hours. RESULTS: In patients with type 1 diabetes IDeg-flex proved to be non-inferior with respect to reduction of HbA1C (-0.40%) versus IDeg-evening (-0.41%) and IGlar (-0.58%) after 26 weeks. In addition, nocturnal hypoglycemic events were reduced by 40% (p < 0.01) with IDeg-flex versus IGlar. In patients with type 2 diabetes reduction of HbA1C with ID)eg-flex (-1.28%) was non-inferior to IDeg-evening (-1.07%) and IGlar (-1.26%), respectively, whereas rates for hypoglycemia were comparable. CONCLUSION: Patients with diabetes mellitus are enabled to dose a basal insulin flexibly when needed (minimum interval of 8 hours afterthe last injection is necessary). Impacts of this treatment option on quality of life and adherence and outcomes should be examined in observational trials.

[Daytime flexible application of Insulin degludec in patients with type 1 diabetes or type 2 diabetes]. / Tageszeitlich flexible Gabe von Insulin degludec bei Patienten mit Typ-1-Diabetes oderTyp-2-Diabetes.

BACKGROUND: Insulin degludec (IDeg) is a basal insulin with a stable, flat action profile and an even distribution of the blood glucose lowering effect over 24 hou rs. The terminal half-life of IDeg is about 25 hours, which reflects a mean prolongation by factor 2 compared to Insulin glargin (lGlar).This may enable for a more flexible daytime dosing versus up to now available basal insulins. METHOD: Two open, randomized, treat-to-target studies enrolled patients with type 1 diabetes (n =493) or type 2 diabetes (n = 687). Both phase 3 studies compared a daytime flexible dosing of IDeg (IDeg-flex) with IDeg at the evening meal (IDeg-evening) and IDler at a fixed daytime. In the IDeg-flex-group dosing intervals were predefined with variations between 8 and 40 hours. RESULTS: In patients with type 1 diabetes IDeg-flex proved to be non-inferior with respect to reduction of HbA1C (-0.40%) versus IDeg-evening (-0.41%) and IGlar (-0.58%) after 26 weeks. In addition, nocturnal hypoglycemic events were reduced by 40% (p < 0.01) with IDeg-flex versus IGlar. In patients with type 2 diabetes reduction of HbA1C with ID)eg-flex (-1.28%) was non-inferior to IDeg-evening (-1.07%) and IGlar (-1.26%), respectively, whereas rates for hypoglycemia were comparable. CONCLUSION: Patients with diabetes mellitus are enabled to dose a basal insulin flexibly when needed (minimum interval of 8 hours after the last injection is necessary). Impacts of this treatment option on quality of life and adherence and outcomes should be examined in observational trials.

Penicillin acylase from the hybrid strains Escherichia coli 5K(pHM12): enzyme formation and hydrolysis of beta-lactam antibiotics with whole cells.

Penicillin acylase formation by the hybrid strain Escherichia coli 5K(pHM12) was studied under different culture conditions and reached 200 to 250 mumol of 6-aminopenicillanic acid per min per g of bacteria (wet weight) for penicillin G. The Km of whole-cell acylase was determined with 9 to 11 mM for penicillin G at a pH optimum of 7.8 at 45 degrees C. A competitive product inhibition for phenylacetic acid of Ki = 130 mM was found. 6-Aminopenicillanic acid acts as a noncompetitive inhibitor, with a Ki of 131. The temperature optimum of the reaction lies at 54 degrees C. Penicillin G inhibits the reaction at Ki(S) = 1,565 to 1,570 mM. Whole-cell acylase reacts on a wide spectrum of penicillins and cephalosporins, but those substrates with a delta-aminoadipyl rest are not hydrolized. beta-Lactamase activity of less than 1% relative to the acylase activity was found at reaction temperatures between 28 and 45 degrees C. After a comparison of different methods for the estimation of beta-lactamase activity, we found that high-pressure liquid chromatography is to be preferred. During batch fermentation of E. coli 5K(pHM12), problems of plasmid stability in the host strain arose which were overcome by the addition of 4 mg of tetracycline per liter to the medium as a selective marker.