Influence of different positioning of a local pain catheter on postoperative pain after paramedian laparotomy-a blinded, randomized trial.

BACKGROUND: Continuous application of local anaesthetics reduces postoperative pain after different approaches for laparotomy. In this randomized, blinded trial, we investigated the effect of continuous application of local anaesthetics after paramedian laparotomy either with subfascial or subcutaneous catheter in addition to a standardized systemic analgesia. MATERIALS AND METHODS: Patients with stage III/IV melanoma and indication for radical iliac lymph node dissection (RILND) were randomized to a continuous application of a local anaesthetic through either a subfascial or subcutaneous catheter. Participants and those assessing the outcomes were blinded. The main outcome criterion was the pain level on the first postoperative morning while exercising measured with a visual analogue scale. Minor criteria were the pain measured by the area-under-curve until the third postoperative day, the patient's satisfaction with analgesic treatment, the analgesic requirement, the overall complications and the day of discharge. RESULTS: Fifty-two patients were evaluated. Pain therapy was sufficient in both groups during the postoperative course while resting and during mobilization. There were no significant differences regarding the main and minor outcome criteria. Doses of additional analgesics did not differ between groups. No adverse events or side effects were observed. CONCLUSION: For patients who undergo paramedian laparotomy, none of the investigated techniques is superior to the other at a median pain level under visual analogue scale (VAS) 30 mm on the first postoperative morning. TRIAL REGISTRATION NUMBER: DRKS00003632 (German Register of Clinical Trials).

Microbial Cell Factories for Diol Production.

Diols are compounds with two hydroxyl groups and have a wide range of appealing applications as chemicals and fuels. In particular, five low molecular diol compounds, namely 1,3-propanediol (1,3-PDO), 1,2-propanediol (1,2-PDO), 2,3-butanediol (2,3-BDO), 1,3-butanediol (1,3-BDO), and 1,4-butanediol (1,4-BDO), can be biotechnologically produced by direct microbial bioconversion of renewable materials. In this review, we summarize recent developments in the microbial production of diols, especially regarding the engineering of typical microbial strains as cell factory and the development of corresponding bioconversion processes.

Improved n-butanol production by a non-acetone producing Clostridium pasteurianum DSMZ 525 in mixed substrate fermentation.

The kinetics of growth, acid and solvent production in batch culture of Clostridium pasteurianum DSMZ 525 were examined in mixed or mono-substrate fermentations. In pH-uncontrolled batch cultures, the addition of butyric acid or glucose significantly enhanced n-butanol production and the ratio of butanol/1,3-propanediol. In pH-controlled batch culture at pH = 6, butyric acid addition had a negative effect on growth and did not lead to a higher n-butanol productivity. On the other hand, mixed substrate fermentation using glucose and glycerol enhanced the growth and acid production significantly. Glucose limitation in the mixed substrate fermentation led to the reduction or inhibition of the glycerol consumption by the growing bacteria. Therefore, for the optimal growth and n-butanol production by C. pasteurianum, a limitation of either substrate should be avoided. Under optimized batch conditions, n-butanol concentration and maximum productivity achieved were 21 g/L, and 0.96 g/L × h, respectively. In comparison, mixed substrate fermentation using biomass hydrolysate and glycerol gave a n-butanol concentration of 17 g/L with a maximum productivity of 1.1 g/L × h. In terms of productivity and final n-butanol concentration, the results demonstrated that C. pasteurianum DSMZ 525 is well suitable for n-butanol production from mixed substrates of biomass hydrolysate and glycerol and represents an alternative promising production strain.

Saving the world by teaching behavior analysis: a behavioral systems approach.

This article presents a behavioral systems approach to organizational design and applies that approach to the teaching of behavior analysis. This systems approach consists of three components: goal-directed systems design, behavioral systems engineering, and performance management. This systems approach is applied to the Education Board and Teaching Behavior Analysis Special Interest Group of the Association for Behavior Analysis, with a conclusion that we need to emphasize the recruitment of students and the placement and maintenance of alumni. This systems approach is also applied at the scale of the individual faculty member running a university-based training system and is seen to generate special approaches to textbook preparation, undergraduate research, colloquium and conference attendance, career counseling, preparation for graduate examinations, graduate training and graduate seminars, and classroom alternatives to the traditional lecture.

BPTI backbone variants and implications for inhibitory activity.

Structural variants of BPTI were synthesized en route an enzymatic-chemical semisynthesis. The P1-P2 amide bond of the inhibitor molecule, which, as donor, contributes a hydrogen bond towards trypsin in the enzyme-inhibitor complex, was replaced by either a ketomethylene function or an ester bond yielding molecules with inhibitory activity. The two backbone-mutated BPTI derivatives showed increased dissociation constants of their respective trypsin complexes, obviously due to the lack of a single hydrogen-bond interaction in the enzyme-inhibitor complex.

Chemical semisynthesis of aprotinin homologues and derivatives mutated in P' positions.

An extended concept for the replacement of amino acids in the P' region of aprotinin by chemical semisynthesis is presented. Either fragment condensation with dipeptides protected as tert-butyl ester or stepwise introduction of two single amino acid-tert-butyl esters into a partially esterified aprotinin derivative (with free Lys15-carboxyl group) lacking the amino acids Ala16 and Arg17 leads to aprotinin homologues and derivatives mutated in the P'1 and P'2 position. This method may complement the recently reported enzymatic synthesis by enabling access to aprotinin homologues and derivatives, which cannot be prepared enzymatically. The synthesis of [Ala17]BPTI and [seco-17/18]BPTI is described in detail.

Enzymatic semisynthesis of aprotinin homologues mutated in P' positions.

The replacement of amino acids in the P'1 and P'2 position of aprotinin, the bovine pancreatic trypsin inhibitor, is described. Using the "modified" inhibitor as starting material, with the hydrolyzed reactive-site peptide bond Lys15-Ala16, the residues P'1 (Ala16) and P'2 (Arg17) were split off by the action of aminopeptidase K. Incorporation of suitable dipeptides containing a basic residue (Lys or Arg) in the C-terminal position was carried out in a "one pot" reaction involving trypsin-catalyzed coupling. In this way, the native fragment Ala16-Arg17 was reintroduced and also replaced by Gly-Arg, Ala-Lys, and Leu-Arg yielding intact inhibitor molecules. The mechanism for incorporation of dipeptides was investigated by treating the aprotinin derivative with the Arg17-Ile18 peptide bond hydrolyzed with trypsin under proteosynthetic conditions. We established that only inhibitor molecules cleaved between Lys15 and Xaa16 are intermediates leading to the desired products. The inhibitory properties of the new aprotinin homologues were tested, and the significance of the P'1 residue for the inhibition of trypsin, kallikrein, and chymotrypsin was deduced.

Enzymatic fragment substitution as a tool in protein design.

An easy and rapid enzymatic method is described which allows replacement of P'-residues in bovine pancreatic trypsin inhibitor. Insertion of Xaa-Arg or Xaa-Lys into a BPTI fragment lacking P1' = Ala16 and P2' = Arg17 was carried out in a "one pot" reaction catalysed by trypsin in the presence of 80% 1,4 butanediol.