Pharmacokinetic and pharmacodynamic studies of subcutaneously administered recombinant human interleukin-3 following chemotherapy for non-Hodgkin's lymphoma

The pharmacokinetics and the pharmacodynamic profile of subcutaneously administered recombinant human non-glycosylated interleukin-3 (rhIL-3) was studied in lymphoma patients after standard CHOP chemotherapy. 30 patients received 0.5, 1.0, 5.0, 7.5 and 10 micrograms/kg (six patients at each dose level) of rhIL-3 for 14 d. Serum rhIL-3 samples were obtained regularly, during the treatment and serially over a 24 h period on the first (cycle day 2) and the last (cycle day 15) day of rhIL-3 treatment for pharmacokinetic evaluation. Following s.c. injection on cycle day 2. the maximum rhIL-3 serum concentration ranged from 289 pg/ml (0.5 micrograms/kg) to 4690 pg/ml (10 micrograms/kg). Both the maximum serum concentration (R = 0.90. P < 0.0001) and the area under the serum concentration-time curve (R = 0.95, P < 0.0001) were related to dose. The elimination half-life T1/2 beta was 160 min for 0.5 micrograms/kg and 134 min for 10 micrograms/kg, with no apparent dose relationship. The systemic clearance of 3.0-6.0 ml/min/kg was comparable at all dose levels. No significant difference was noted between pharmacokinetic parameters on the first day of rhIL-3 and the last day of treatment, and no accumulation of the drug was noted throughout the study. The pharmacokinetic parameters correlated poorly to the clinical response of the growth factor. where dose in micrograms/kg seemed to be the most important single factor.     

Diffusion-limited reactive wetting: effect of interfacial reaction behind the advancing triple line

Using the “dispensed drop” variant of the sessile drop technique, spreading kinetics of dilute Cu–Cr alloys on smooth vitreous carbon substrates are measured under helium microleak conditions. In this system, it is known that the drop spreading rate is controlled by diffusion of the reactive atom species (Cr) from the bulk liquid to the triple line, where wetting is induced by formation of an interfacial layer of chromium carbide. Microstructural characterization of rapidly cooled drops shows that growth of the interfacial reaction product layer continues behind the moving solid–liquid–vapor triple line. The spreading velocity is modeled by finite-difference numerical analysis of diffusion near the triple line in the presence of continued interfacial reaction, simplifying the growth rate as being constant and using realistic parameter values. We show that continued interfacial reaction explains the dependence of the triple line spreading rate on the instantaneous wetting angle that is observed in this system.     

Enantioselective proteins: selection, binding studies and molecular modeling of antibodies with affinity towards hydrophobic BINOL derivatives

In this paper, the initial steps towards the design of novel artificial metalloenzymes that exploit proteins as a second coordination sphere for traditional metal-ligand catalysis are described. Phage display was employed to select and study antibody fragments capable of recognizing hydrophobic BINOL derivatives designed to mimic BINAP, a widely used ligand in asymmetric metal-catalyzed reactions. The binding affinities of the selected antibodies towards a series of haptens were evaluated by using ELISA assays. A homology model of one of the most selective antibodies was constructed, and a computer-assisted ligand-docking study was carried out to elucidate the binding of the hapten. It was shown that, due to the hydrophobic nature of the haptens, a higher level of theoretical treatment was required to identify the correct binding modes. A small selection of the antibodies was found to discriminate between enantiomers and small structural modifications of the BINOL derivatives. The selectivities arise from hydrophobic interactions, and we propose that the identified set of antibodies provides a foundation for a novel route to artificial metalloenzymes.     

Influence of frozen storage on herbicide degradation capacity in surface and subsurface sandy soils

The degradation of MCPA and metribuzin was investigated in laboratory batch experiments using fresh and frozen-stored soil samples from the unsaturated zone of a sandy soil. Mineralization potentials measured in fresh and frozen-stored soils were similar, and mineralization kinetics in surface and subsurface soils could be fitted using the same kinetic models. MCPA mineralization data from all three horizons were best described with the exponential growth form of the three-half-order model. During the mineralization of MCPA, growth in MCPA-degrading microbial populations was confirmed by increases in the abundance of tfdA genes following MCPA exposure. In contrast to MCPA, metribuzin mineralization followed zero-order kinetics, and very little metribuzin was mineralized (<1%) in all three of the investigated soil horizons. In addition, metribuzin dissipation and metabolite formation were also measured in surface and subsurface soils using LC-MS/MS. Differences in metribuzin dissipation were observed in the A-horizon at the beginning of the experiment and resulted in substantially different 50% disappearance time, DT50, values for frozen-stored (36 days) and fresh (<15 days) soil samples. However, the % of metribuzin remaining in fresh and frozen-stored surface soils was comparable from day 37 and thereafter.     

Investigation of airflow patterns in a microclimate by particle image velocimetry (PIV)

Problems with mould growth in dwellings usually occur in bedrooms in the microclimate behind closets placed next to exterior walls with poor insulation. It is anticipated that the problems are caused by lack of airflow behind the furniture in combination with a colder surface temperature and a high moisture production. The lack of air circulation decreases the surface temperature, which can cause problems. A particle image velocimetry (PIV) investigation was performed of the airflow patterns in such a microclimate. This paper describes the experimental set-up and the results. The results indicate that the flow rates behind the furniture will increase with increased distance between the closet and the wall, and even higher airflow rates are seen when the furniture is elevated by legs.     

Polymorphism, microstructure and rheology of butter. Effects of cream heat treatment

The effect of cream heat treatment prior to butter manufacturing, fluctuating temperatures during storage and presence of fat globules vs. no fat globules was examined in laboratory scale produced butter. X-ray diffraction and differential scanning calorimetry was used to study crystallization behaviour and nuclear magnetic resonance to measure solid fat content and water droplet size distribution. Furthermore, the crystal structure was linked to the rheological properties and microstructure of the butter using confocal laser scanning microscopy. Butter produced from non-matured cream mainly formed α- and β'-crystals with minor traces of β-crystals. Maturing of the cream caused a transition from α- to β'- and β-form. The rheological behaviour of slow cooled butter deviated from the matured ones by having a lower elastic modulus, caused by a weaker crystal network. Presence of fat globules did not affect the rheological properties significantly.     

Effect of freezing temperature, thawing and cooking rate on water distribution in two pork qualities

The effects of freezing temperature (-20 versus -80°C) in combination with long-term freezer storage (-20°C) on water mobility and distribution in pork of two qualities (normal and high ultimate pH) were explored using low-field NMR T(2) relaxometry. A marked effect of freezing temperature on the characteristics of intra- and extramyofibrillar water (T(2) relaxation times) in the thawed pork was demonstrated, implying that the freezing temperature in combination with prolonged freezer storage affects the distribution and chemical-physical state of water in the thawed meat. Determination of technological properties (thawing and cooking loss) revealed that the observed T(2) variations related to water distribution and water properties, which were found to be consistent with the degree of structural damage assessed by light microscopy, also were reflected in the technological quality of the meat. Low freezing temperature in combination with prolonged freezer storage was associated with increased thawing and cooking loss. In addition, pH in the fresh meat had a pronounced effect on the distribution of myofibrillar water, as a more homogenous pore size distribution was evident in meat with high pH compared with normal pH. A clear effect of cooking rate on the T(2) relaxation characteristics in the cooked pork was also demonstrated, probably reflecting a cooking rate-induced effect on the myofibrillar structures. The effect of cooking rate on water distribution resulted in a significantly lower cooking loss upon a slow cooking rate (0.5°C/min from 25 to 65°C and 0.3°C/min from 65 to 80°C) compared with a fast cooking rate (1°C/min).     

Atrioventricular conduction during long-term follow-up of patients with sick sinus syndrome

BACKGROUND: It has been claimed that patients with sick sinus syndrome have an increased risk of developing AV block, but this has never been assessed prospectively. The aim of the present study was to evaluate in a prospective trial AV conduction during the long-term follow-up of patients with sick sinus syndrome. METHODS: Two hundred twenty-five consecutive patients with sick sinus syndrome and intact AV conduction were randomized to undergo single-chamber atrial pacing (110 patients) or single-chamber ventricular pacing (115 patients). Follow-up after 3 months and then yearly included measurement of the PQ interval and, in patients with atrial pacemakers, determination of the atrial stimulus-Q intervals at pacing rates of 100 and 120 bpm. The occurrence of AV block in the atrial group was recorded. During follow-up (mean, 5.5+/-2.4 years), there was no change in PQ interval in either group and no change in atrial stimulus-Q intervals or Wenckebach block point in the atrial group. Four of 110 patients in the atrial group developed grade 2 to 3 AV block that required upgrading of the pacemaker (0.6% per year). Two of these 4 patients had right bundle-branch block at pacemaker implantation. CONCLUSIONS: AV conduction, estimated as PQ interval and atrial stimulus-Q interval at atrial pacing rates of 100 and 120 bpm and the Wenckebach block point, remains stable during long-term follow-up. Thus, treatment with single-chamber atrial pacing is safe and can be recommended to patients with sick sinus syndrome without bundle-branch block.