Quantitative Microdialysis: Analysis of Transients and Application to Pharmacokinetics in Brain

The behavior of a microdialysis probe in vivo is mathematically described. A diffusion-reaction model is developed that not only accounts for transport of substances through tissues and probe membranes but also accounts for transport across the microvasculature and metabolism. Time-dependent equations are presented both for the effluent microdialysate concentration and for concentration profiles about the probe. The analysis applies either to measuring the tissue pharmacokinetics of drugs administered systemically, or for sampling of endogenously produced substances from tissue. In addition, an expression is developed for the transient concentration about the probe when it is used as an infusion device. All mathematical expressions are found to be a sum of an algebraic and an integral term. Theoretical prediction of time-dependent probe behavior in brain has been compared with experimental data for acetaminophen administered at 15 mg/kg to rats by intravenous bolus. Plasma and whole striatal tissue samples were used to describe plasma kinetics and to estimate a capillary permeability-area product of 0.07 min-1. Theoretical prediction of transient effluent dialysate concentrations exhibited close agreement with experimental data over 60 min. Terminal decline of the dialysate effluent concentration was slightly overestimated but theoretical concentrations still lay within the 95% confidence interval of the experimental data at 112 min. Microvasculature transport and metabolism play major roles in determining microdialysate transient responses. Extraction fraction (recovery) has been shown to be a declining function in time for five probe operating conditions. High rates of metabolism and/or capillary transport affect the time required to approach steady-state extraction, shortening the time as the rates increase. Conversely, for substances characterized by low permeabilities and negligible metabolism, experimental situations exist that are predicted to have very slow approaches to microdialysis steady state.     

Selenium status of patients with Balkan endemic nephropathy

The selenium (Se) contents in common cereals in endemic and nonendemic areas in Serbia are very low. Plasma Se levels of both patients and healthy subjects, were also low, reflecting low Se intakes. Patients with Balkan endemic nephropathy (BEN) had significantly lower (p<0.05) plasma Se levels than healthy individuals, both from regions close to endemic areas, and from Belgrade. Mean plasma Se of BEN patients was slightly but insignificantly higher in samples taken immediately after dialysis than in those taken before, suggesting that very little of the Se present in plasma is dialyzable. Plasma SeGSH-Px activities before and after hemodialysis in both BEN and Nonendemic chronic renal failure (NCRF) patients were not significantly different, but BEN patients had lower enzyme activities than those with NCRF and healthy controls. In BEN patients, a significant correlation between plasma Se and SeGSH-Px activity was found. NCFR patients were with diagnoses: TBC of kidneys, chronic glomerulonephritis, chronic pyelonephritis, and polycystic kidneys.     

Oenanthe aquatica (L.)Poir.: Seed reproduction,population structure,habitat conditions and distribution in Czechoslovakia

The paper summarizes data concerning the biology and ecology ofOenanthe aquatica. The species is commonly distributed all over Czechoslovakia, from lowlands to the submontane belt, especially in fishpond and river basins.O. aquatica shows no special relationship to the chemical and physical soil properties, and is well adapted to habitats with a changing water level. The reproduction ofO. aquatica depends on emerging of the bottom. The most developed populations are formed by biennial plants and arise in the year following summer or autumn drainage.     

N-tosyl-L-phenylalanylchloromethane reacts with cysteine 81 in the molecule of elongation factor Tu from Escherichia coli

Elongation factor EF-Tu from Escherichia coli was labelled with N-[¹⁴C]tosyl-L-phenylalanylchloromethane, digested with trypsin and the peptides obtained separated by HPLC. The only radioactive peak recovered corresponded to tryptic peptide containing residues 75–98. Sequencing of the peptide by automated Edman degradation identified cysteine 81 as the site of N-tosyl-L-phenylalanylchloromethane modification. These results confirm the importance of this residue for the interaction with aminoacyl-tRNAs.     

COMPARATIVE KINETIC STUDIES OF NITRATE-LIMITED GROWTH AND NITRATE UPTAKE IN PHYTOPLANKTON IN CONTINUOUS CULTURE1

A comparative study of nitrate-limited growth and nitrate uptake was carried out in chemostat cultures of Ankistrodesmus falcatus (Corda) Ralfs., Asterionella formosa Hass., and Fragilaria crotonensis Kit. In each species growth rate (μ) was related to total cell nitrogen or cell quota (q) by the empirical Droop growth function. Nitrate uptake was a function of both external N concentration and q. The apparent maximum uptake rate (V_m') at a given μ was inversely related to q – q₀, where q₀ is the minimum quota. The apparent half-saturation constant for uptake, (K_m') appears to show a slight inverse trend with μ, although statistical analysis shows that this trend is inconclusive. When q approaches q₀, V_m' is several orders of magnitude greater than μq, the calculated steady-state uptake rate. As q increases, however, the difference between these two variables decreases sharply until q approaches q_m, the cell quota for nitrogen-rich cells. At this point the difference between μq and V_m' disappears. This behavior is explained by the feedback regulation of N uptake. The inverse relationship between V_m' and q – q₀ can be described by an empirical three-parameter equation.     

OPTIMUM N:P RATIOS AND COEXISTENCE OF PLANKTONIC ALGAE1

The optimum atomic ratio of N to P, the ratio at which one nutrient limitation changes over to the other, was determined in seven species of freshwater planktonic algae. The ratio varied over a wide range among species; the average for these species was 17. If the cellular nutrient ratios in marine species are comparable with those in freshwater organisms, Redfield's ratio of 15 is remarkably close to the average. Cellular N:P ratios varied over a 24-h period under a light:dark cycle. The variation of the optimum ratio between species and diel change in cellular N:P ratios within a species could play an important role in population dynamics by enhancing the probability of coexistence of species.     

Flow rates of components in digesta of pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum, and fed semipurified, hard wheat, and soft wheat diets.

Four pigs prepared with re-entrant cannulas in the proximal duodenum and terminal ileum were used to study flow rates of total digesta, insoluble dry matter, nitrogen, and amino acids entering and leaving the small intestine. The pigs received a semipurified diet, a hard wheat diet, or a soft wheat diet. These were approximately isonitrogenous. A higher rate of passage of digesta through the proximal duodenum and terminal ileum were measured in pigs receiving the hard wheat diet. Peak flow of digesta at the duodenum of all pigs occurred at 1 h post feeding. Peak flow of digesta at the ileum occurred at 9 h post feeding on the soft wheat diet, but somewhat earlier on the hard wheat and semipurified diet. More nitrogen and essential amino acids flowed in the solid fraction of duodenal digesta during the first 2 h post feeding for the wheat diets and 4 h post feeding for the semipurified diet. It was concluded that flow rate of most nutrients from the stomach and through the small intestine of pigs is modified by the composition and texture of the food ingested. It is postulated that efficiency of mixing of digesta with digestive secretions in the stomach is a major factor influencing rate of flow.     

Infection of the heart cockle, Clinocardium nuttallii, from Yaquina Bay,Oregon, with an endosymbiotic alga

Clinocardium nuttallii from Yaquina Bay, Oregon, were found to harbor an endosymbiotic alga. Some aspects of this relationship are presented. The areas of infection include the siphon, mantle, and occasionally the foot. C. nuttallii under 2 years old are not infected; the incidence and intensity of the infection increases in the older age groups. For all ages the incidence averages 35%. Pigment composition, morphology, and growth characteristics of the alga are similar to those found in the genus Chlorella. In situ, the algae form dense, sometimes massive colonies but do not appear to cause any host reaction or enfeeblement. The thick layers surrounding the algal cells in situ, the dense colonies, and the in vitro reaction to host extract suggest the alga is parasitic. However, the presence of chloroplasts, the location of the algal cells only in illuminated tissue, the seemingly unhampered reproduction in situ, and the eventual adaptation to mineral medium suggest the alga is a facultative parasite. Experimental infection was achieved by feeding mature uninfected cockles a diet of only symbiont cells. In vitro observations found the symbiont cells readily engulfed by host blood amoebocytes. It is believed that the animal acquires the infection through phagocytosis of the symbiont cells and subsequent diapedesis across epithelial barriers by host amoebocytic cells.