Computational Oral Absorption Simulation for Low‐Solubility Compounds

Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.     

Distribution of zinc fractions and their transformation in submerged rice soils

Distribution of different forms of Zn in 16 acid alluvial rice growing soils of West Bengal (India) and their transformation on submergence were studied. The results showed that more than 84% of total Zn occurred in the relatively inactive clay lattice-bound form while a smaller fractionviz. 1.1, 1.6, 11.1 and 2.0 per cent of the total occurred as water-soluble plus exchangeable, organic complexed, amorphous sesquioxide-bound and crystalline sesquioxide bound forms, respectively. All these four Zn forms showed significant negative correlations with soil pH (r=−0.48^**, −0.39^*, −0.61^** and −0.67^**, respectively), while the latter two Zn forms showed significant positive correlations with Fe₂O₃ (0.68^** and 0.88^***) and Al₂O₃ (0.89^*** and 0.75^***) content of the soils. The different Zn forms were found to have positive and significant correlations amongst each other, suggesting the existence of a dynamic equilibrium of these forms in soil. Submergence caused an increase in the amorphous sesquioxide-bound form of Zn and a decrease in each of the other three forms. The magnitude of such decreases in water-soluble plus exchangeable and crystalline sesquioxide-bound forms was found to be correlated negatively with initial pH values of the soils and positively with the increase in the amorphous sesquioxide-bound form, indicating their adsorption on the surface of the freshly formed hydrated oxides of Fe, which view was supported by the existence of significant positive correlation between the increase in the amorphous sesquioxide-bound form of Zn and that in AlCl₃-extractable iron. The existence of a positive correlation between the decrease in crystalline sesquioxide-bound Zn and that in Fe₂O₃ content in soil suggested that on waterlogging the soil Zn occluded in the cry talline sesquioxide was released as a result of reduction of Fe₂O₃.     

A comparative study of the soil zinc fractions determined by chemical methods and electro-ultrafiltration (EUF) and their relations to zinc nutrition in rice

Rice (IR 42) was grown on two soils differing in zinc status for 30 days with and without Zn under submerged conditions in pots. The fate of soil zinc was characterized by extraction of the soil successively with copper acetate and sodium hypochlorite and by EUF extraction. Most of the applied zinc was extracted by copper acetate and represented as complexed fraction. There exists a close and significnat relation between Cu(OAc)₂-extractable zinc and Zn extracted by EUF for 5 minutes at 50 volts (r=0.98). The EUF-extractable zinc and Cu(OAc)₂-extractable zinc were significantly correlated with the zinc content in the plant (r=0.82). The data from this investigation suggest the possibility of Zn fractionation with the EUF technique and the fractions obtained agree closely to those determined by chemical methods. The results obtained indicate that Zn in soil is held by weak organic bonding and that the extractions by Cu(OAc)₂ and/or EUF-5 minutes serve as a useful basis for extimating zinc availability in rice soils.     

Biochemical characterization of chromatin fractions isolated from induced and uninduced friend erythroleukemia cells

Summary Chromatin fractions from Friend erythroleukemia cells after induction of differentiation by dimethylsulfoxide (DMSO) were compared in their biochemical characteristics to fractions from uninduced cells. Fractions were prepared by extracting chromatin from nuclei after mild micrococcal nuclease treatment with increasing concentrations of NaCl according to Sanders [1]. This procedure has been found to release chromatin containing hyperacetylated histones preferentially [2]. The fractions obtained by this procedure were analysed in respect to the amount of chromatin released, the amount of histone H1, the degree of acetylation of histone H4, the presence of non-histone proteins and the concentration of transcribed and non-transcribed sequences. It was found that the fractions differ in the amount of histone H1 present, in several non-histone proteins and in the acetylation of histonie H4, regardless whether induced or uninduced cells were analysed. The distribution of transcribed sequences versus non-transcribed sequences among the fractions was the same, demonstrating that this fractionation procedure, although leading to fractions with biochemical differences, is not able to discriminate functional states of chromatin and that the biochemical characteristics of the fractions may be common to both, active as well as inactive states of chromatin.     

Studies on the submicrosomal fractions of bovine oligodendroglia: Lipid composition and glycolipid biosynthesis

Oligodendroglia were isolated from bovine brain, and a crude, microsomal fraction obtained from cell homogenates was subfractionated into myelin (MP), plasma membranes (PM), Golgi (GF), smooth (SER) and rough (RER) endoplasmic membranes using discontinuous-sucrose gradient centrifugation. The submicrosomal fractions were characterized by ultrastructural examination and analysis of the specific organelle markers. The myelin and plasma membrane rich fractions contained characteristically the highest amounts of the lipid with lower mole percentages of total phospholipids and phosphatidylcholine, and higher concentrations of phosphatidylethanolamine (+plasmalogens), cholesterol and galactolipids. Considerable amounts of the typical myelin galactolipids (galacto-cerebrosides, sulfatides and monogalactosyl diglycerides) were also found in the Golgi fraction (GF). The GF fraction had the greatest enrichment of glycolipid-forming galactosyltransferases, and the distribution of these enzymes correlated well with that of the Golgi marker enzymes. The results give evidence that intracellular Golgi apparatus of oligodendroglia is rich in the myelin-specific lipids, and suggest its involvement in the synthesis and processing of myelin lipids.     

Protein synthesis rates in rat brain regions and subcellular fractions during aging

In vivo protein synthesis rates in various brain regions (cerebral cortex, cerebellum, hippocampus, hypothalamus, and striatum) of 4-, 12-, and 24-month-old rats were examined after injection of a flooding dose of labeled valine. The incorporation of labeled valine into proteins of mitochondrial, microsomal, and cytosolic fractions from cerebral cortex and cerebellum was also measured. At all ages examined, the incorporation rate was 0.5% per hour in cerebral cortex, cerebellum, hippocampus, and hypothalamus and 0.4% per hour in striatum. Of the subcellular fractions examined, the microsomal proteins were synthesized at the highest rate, followed by cytosolic and mitochondrial proteins. The results obtained indicate that the average synthesis rate of proteins in the various brain regions and subcellular fractions examined is fairly constant and is not significantly altered in the 4 to 24-month period of life of rats.A preliminary report of these results was previously presented at: WFN-ESN Joint Meeting on: Cerebral Metabolism in Aging and Neurological Disorders, Baden, August 28–31, 1986.     

Supersaturation of soil solutions with respect to gypsum

The products of activities of calcium and sulphate were calculated for solutions of 75 glasshouse soils. The majority of these products was found to be higher than the solubility product of gypsum, thus indicating that these soil solutions were possibly supersaturated. In another investigation, soil solutions were examined to determine whether such high activity products could be really attributed to supersaturation. By means of ultracentrifuging of solutions of glasshouse soils, it could be established that the solutions were practically free of sulphate-bearing colloidal particles. Some solutions contained calcium-bearing colloidal particles, but the quantities of calcium contained in these particles were too small to substantially influence the calcium activity. Addition of gypsum crystals to soil solutions led to crystallization of so much calcium and sulphate that the products of the activities of calcium and sulphate dropped from values that can be listed as high to values approaching the solubility product of gypsum. The results obtained demonstrate the occurrence of supersaturation of soil solutions with respect to gypsum. It is further postulated that the presence of humic substances in the soil solution is responsible for this supersaturation. The possible occurrence of supersaturation with respect to gypsum in soils other than glasshouse soils is discussed.     

Relationships between EUF-N fractions,N uptake and quality of sugar beet in deep loess soils of Southern Lower Saxony

Summary In field experiments conducted in 1981 on deep loess soils a significant correlation was obtained between EUF-N content in the topsoil and N in sugar beet roots as well as in whole plants. A very close correlation was found to exist between EUF-N values in June 1981 and -amino N in sugar beet roots at harvest. Also other quality criteria such as the contents of sugar, K and Na in roots and yield parameters correlated with EUF-N contents in topsoils.The inorganic and organic EUF-N fractions changed during the vegetation period due to both N uptake by the crop and mineralization. Therefore it appears to be expedient to use both fractions when calculating N fertilizer requirements.The correlation between EUF-N (topsoil samples drawn in the year preceding sugar beet) and sugar yield increases obtained by N fertilization that was found in Austria¹² was confirmed in our experiments with soils from Southern Lower Saxony.     

Uridine Transport and Metabolism in the Central Nervous System

Myelin and myelin-containing (P3) fractions were prepared from human white matter by discontinuous sucrose gradient centrifugation. The myelin isolated from each of the fractions of different densities was morphologically and biochemically distinct. Light myelin fractions consisted of compact, multilamellar myelin, whereas the denser fractions consisted predominantly of loose myelin with fewer lamellae. The amounts of both basic protein and lipophilin (proteolipid protein) were reduced in the denser fractions. In contrast, the high-molecular-weight components were elevated in the dense fractions. The lipid composition was similar in all the fractions studied. Analysis of basic protein by gel electrophoresis at pH 10.6 revealed differences in basic protein microheterogeneity among the fractions. The light myelin fraction was enriched in the more positively charged basic protein components (components 1, 2, and 3), whereas these components were reduced in the denser fractions. Myelin in the dense fractions was enriched in the more modified forms of basic protein (components 6, 7, and 8). The pattern of microheterogeneity was different for basic protein isolated from myelins of a 2-year-old and an adult brain; the former showed fewer components and mainly the most cationic species. On the other hand, the pattern of microheterogeneity of basic protein isolated from the different density gradient fractions was similar for both ages.