Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers

OBJECTIVE: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19-34 years, followed for 8 h after each drug administration. METHODS: For i.v. administration the subjects received 4 micrograms dDAVP. For intestinal administration 500 micrograms dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml.min-1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. RESULTS: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml.min.kg-1. The mean bioavailability after duodenal administration of dDAVP+ aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor.     

Designing houses for energy conservation

Domestic demands account for about 40 per cent of total energy supplies in Sweden. This article reviews research by the Building Technology Division of the Swedish Royal Institute of Technology over many years into the thermal behaviour of houses. It highlights the importance of effective insulation and of solar heat gains in particular situations, entailing modifications to conventional design calculations.     

Radiation quality dependence of DNA damage induction

Analysis of DNA fragmentation and repair in relation to radiation quality may give important information about the role of break complexity and correlated double strand breaks (DSBs). DNA fragment analysis was performed by pulsed-field gel electrophoresis after exposure to different radiation qualities. Normal human fibroblasts were irradiated with boron ions (40, 80 and 160 keV.micron-1), nitrogen ions (80, 125, 175 and 225 keV.micron-1) and neon ions (225 and 300 keV.micron-1). The amount of DNA less than 1.1 Mbp decreased with increasing linear energy transfer (LET) for all three ions. When theoretical random distributions were subtracted from the experimental data for 225 keV.micron-1 nitrogen ions in all size intervals (5-5700 kbp), there was a significant non-random distribution of DSBs for sizes up to 1-3 Mbp. This non-random distribution of breaks, probably produced by intra-track correlated DSBs, may constitute a substantial portion of the high-LET induced DSBs.     

Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes

Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a receptor recognizing a natural islet beta cell antigen. In BDC2.5 animals, activated T cells were found only in the islets and the lymph nodes draining them, and there was a close temporal correlation between lymph node T cell activation and islet infiltration. When naive BDC2.5 T cells were transferred into nontransgenic recipients, proliferating cells were observed only in pancreatic lymph nodes, and this occurred significantly before insulitis was detectable. Surprisingly, proliferation was not seen in 10-day-old recipients. This age-dependent dichotomy was reproduced in a second transfer system based on an unrelated antigen artificially expressed on beta cells. We conclude that beta cell antigens are transported specifically to pancreatic lymph nodes, where they trigger reactive T cells to invade the islets. Systemic or extrapancreatic T cell priming, indicative of activation via molecular mimicry or superantigens, was not seen. Compromised presentation of beta cell antigens in the pancreatic lymph nodes of juvenile animals may be the root of a first "checkpoint" in diabetes progression.     

Female Crucian Carp, Carassius carassius, Lose Predator Avoidance Behavior when Getting Ready to Mate

In predator–prey interactions, the prey often have to compromise fitness-related behaviors such as feeding, courting, and territorial defense in order to avoid predators. In these trade-off situations, some behaviors have priority over others. These priorities are not rigid, and may be context-dependent; for instance, many animals show increased risk-taking during courtship behavior by paying less attention to potential predators. We investigated whether the fright reaction, a stereotypical avoidance response to olfactory cues from injured conspecifics, may be affected by reproductive status in a teleost fish, the crucian carp. We demonstrate that among individuals not responding to alarm substances with a fright reaction, the majority were ovulated or spermiated. In females, mean plasma concentrations of 17β-estradiol and testosterone, gonadal steroids known to decrease during the later stages of sexual maturation, were lower in the individuals not responding with a fright reaction compared to those responding. In males, there were no differences between responsive and non-responsive individuals in mean plasma levels of androgens (testosterone and 11-ketotestosterone) involved in spermatogenesis and male sexual behavior. As the fright reaction in crucian carp consists of behavior incompatible with spawning behavior, we hypothesize that this short-term suppression of the alarm response has evolved so that spawning can occur uninterrupted.     

Automated optimization of key WCDMA parameters

This paper validates the feasibility of automated optimization of key wideband code division multiple access (WCDMA) radio resource management parameters using control methods. The parameters are regularly adjusted in order to improve performance. The parameters examined in this study include the total cell transmission power target, the received total interference target, the downlink radio link power maximums, the handover windows and the pilot channel powers. The control was based on expert‐defined rules, which applied specific trade‐off policies and statistics of poor quality calls, blocking, packet queuing, power and interference levels and terminal measurements to qualify the parameter values. The approach was validated using a dynamic WCDMA system simulator with a deployment of macro and micro cells on a city region. Results on automated optimization of single parameters on cell level and results on simultaneous multi‐parameter optimization on cell‐cluster level are presented in this paper. The use of the automated parameter optimization methods was shown to result in a significant increase of capacity in comparison to the default parameter settings. Copyright © 2004 John Wiley & Sons, Ltd.     

Simulation of Carbon Diffusion in Steel Driven by a Temperature Gradient

The basis of thermomigration in multicomponent alloys is summarized, and the general equations are given and implemented in the DICTRA software. Experimental information from Okafor et al. is analyzed with the new simulations and it is concluded that steady-state conditions was not established during their experiment. A heat of transport Q_C ^* = - 44000  textJ/mol Q_{C}^{ * } = - 44000;{text{J/mol}} , almost four times larger than the value given by Okafor et al., was found to give a satisfactory representation of the experimental information.     

Interfacial antiwear and physicochemical properties of alkylborate-dithiophosphates

Boron compounds have become of interest in tribology because of their unique tribochemical and tribological properties. At the same time, dialkyldithiophosphates (DTPs) of transition metals have been extensively used as multifunctional additives in lubricants to control friction and reduce wear in mechanical systems. Because of the environmental pollution and health hazards of these compounds, ashless compounds with reduced amounts of sulfur and phosphorus are desirable. This work reports on the synthesis, characterization, and tribological properties of a new class of compounds, alkylborate-dithiophosphates. This class combines two high-iron-affinity surface active groups, borate and dialkyldithiophosphate, into a single molecule. The final products, viscous liquids, were characterized by FT-IR, multinuclear (1)H, (13)C, (31)P, and (11)B NMR spectroscopy and thermal analyses. Residues of one representative compound from this class, DPB-EDTP, after thermal analyses were additionally characterized by multinuclear (13)C, (31)P and (11)B MAS and (31)P CP/MAS NMR spectroscopy. Solid-state NMR data suggest that a dominant part of the solid residue of DPB-EDTP consists of borophosphates. Antiwear and friction properties of a mineral oil with these novel additives were evaluated in a four-ball tribometer in comparison with O,O'-di-n-butyl-dithiophosphato-zinc(II), Zn-BuDTP, as a reference lubricant additive. The surface morphology and the elemental composition of the tribofilms were characterized using scanning electron microscopy with energy-dispersive X-rays spectroscopy (SEM/EDS). The results show that alkylborate-dithiophosphates, with substantially reduced amounts of sulfur and phosphorus compared with Zn-BuDTP, have considerably better antiwear and friction performance.