Trace elements in rock salt and their bioavailability estimated from solubility in acid

In this study, 18 partly commercially available samples of rock salt from Austria, Germany, Pakistan, Poland, Switzerland, and Ukraine were investigated with respect to their content of trace elements using instrumental neutron activation analysis. Elements detected were Al, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Eu, Fe, Hf, La, Mn, Na, Rb, Sb, Sc, Sm, Sr, Ta, Tb, Th, and Zn, some of them only in individual cases. An estimation of the bioavailability of these trace elements was performed by dissolving an equivalent of the sodium chloride samples in diluted hydrochloric acid (simulating stomach acid), filtering off the insoluble components, and analyzing the evaporated filtrate. It could be shown that in most cases bioactive trace elements like Fe can be found in rock salt in the form of almost insoluble compounds and are therefore not significantly bioavailable, whereas thorium, for example, was partly bioavailable in two cases. A significant contribution to the recommended daily intake of metal trace elements by using rock salt for nutrition can be excluded.     

Taurine and GABA release from mouse cerebral cortex slices: Effects of structural analogues and drugs

The effects of structural analogues, excitatory amino acids and certain drugs on spontaneous and potassium-stimulated exogenous taurine and GABA release were investigated in mouse cerebral cortex slices using a superfusion system. Spontaneous efflux of both amino acids was rather slow but could be enhanced by their uptake inhibitors. Taurine efflux was facilitated by exogenous taurine, hypotaurine, -alanine and GABA, whereas GABA, nipecotic acid and homotaurine effectively enhanced GABA release. The stimulatory potency of the analogues closely corresponded to their ability to inhibit taurine and GABA uptake, respectively, indicating that these efflux processes could be mediated by the carriers operating outwards. Glutamate induced GABA release, whereas taurine efflux was potentiated by aspartate, glutamate, cysteate, homocysteate and kainate. The centrally acting drugs, including GABA agonists and antagonists, as well as the proposed taurine antagonist TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide), had no marked effects on spontaneous taurine and GABA release. Potassium ions stimulated dosedependently both taurine and GABA release from the slices, the responses of taurine being strikingly slow but sustained. Exogenous GABA and nipecotic acid accelerated the potassium-stimulated GABA release, whereas picrotoxin and bicuculline were ineffective. The potassium-stimulated taurine release was unaltered or suppressed by exogenous taurine and analogues, differing in this respect from GABA release. The apparent magnitude of the depolarization-induced GABA release is thus influenced by the function of membrane transport sites, but the same conclusion cannot be drawn with regard to taurine. Haloperidol and imipramine were able to affect the evoked release of both taurine and GABA.     

Relative cytotoxicity of psychotropic drugs in cultured rat hepatocytes

The relative cytotoxic effects of ten psychotropic drugs were assessed in rat hepatocyte monolayer cultures. Clear concentration-related toxicity was seen in the narrow range of 10^–5M to S × 10^–5M. The four cytotoxicity endpoints chosen were: release of the cytosolic enzyme, lactate dehydrogenase, and impairment of biosynthesis and secretion of proteins, bile acids and glycerolipids. LDH leakage and inhibition of protein secretion into the culture medium proved to be the parameters which allowed the best differentiation between the test compounds. The inhibition of glycerolipid secretion was the most sensitive test in relation to concentration and time of exposure. Based on the effects of these endpoints, the following ranking of relative in vitro toxicity, using equimolar drug concentrations, could be established: clomipramine > imipramine = thioridazine > chlorpromazine > amitriptyline = fluperlapine > haloperidol > promazine > clozapine sulpiride. This ranking order of in vitro cytotoxicity correlated well with the potential of the drugs to impair liver function in man. Only clozapine had to be classified as a false negative. There was, however, no correlation between the cytotoxicity and the intracellular accumulation of the test drugs. Furthermore, the comparison of the data obtained with psychotropics with the data from five other amphiphilic cationic drugs was consistent with the widely accepted concept of a direct toxic interaction of the drugs with cytomembranes. This nonspecific toxicity of the membrane-active drugs was further corroborated by a positive correlation between their potential to induce LDH leakage in hepatocytes and their ability to induce hemolysis in red cells. In conclusion, the results obtained in our study strongly suggest that it is possible to assess the relative cytotoxicity of psychotropic drugs in rat hepatocyte cultures. It is proposed that this in vitro system provides a useful tool to evaluate new drugs at an early stage of their development, and to identify the most promising candidates within a class of structurally related compounds. In addition, it allows information to be obtained on possible mechanisms of cytotoxicity.Abbreviations AIB aminoisobutyric acid - AMT amitriptyline - BSA bovine serum albumin - CLP clomipramine - CLZ clozapine - CPZ chlorpromazine - FLU fluperlapine - HAL haloperidol - HC₅₀ dose causing 50% hemolysis - IMP imipramine - LDH lactate dehydrogenase - PZ promazine - SUL sulpiride - TCA trichloroacetic acid - TRZ thioridazine     

Metallothionein induction by nonsteroidal antiinflammatory drugs

In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA).     

Effect of High Doses of Dietary Vitamin E on the Concentrations of Vitamin E in Several Brain Regions, Plasma, Liver, and Adipose Tissue of Rats

The object of this study was to assess the influence of high levels of dietary vitamin E on vitamin E concentrations in specific areas of the brain. Four-week-old male rats were fed vitamin E-deficient, control, and high-vitamin E (1,000 IU/kg) diets for 4 months. Concentrations of alpha-tocopherol in serum, adipose tissue, liver, cerebrum, cerebellum, and striatum were determined by liquid chromatography with fluorescence detection. In the high-vitamin E group, alpha-tocopherol concentrations in cerebrum, cerebellum, and striatum increased uniformly to 1.4-fold of values in controls; serum, adipose tissue, and liver attained even higher concentrations: 2.2-, 2.2-, and 4.6-fold, respectively, of control values. As observed before, brain levels of alpha-tocopherol were somewhat resistant to vitamin E deficiency, in contrast to the peripheral tissues.     

Ecophysiology of Aufwuchs-eating cichlids in Lake Tanganyika: niche separation by trophic specialization

Synopsis The Aufwuchs-eating cichlids of Lake Tanganyika show clear trophic differences that are correlated to their morphology, physiology and foraging behaviour. The species are grouped into three categories of relative intestinal length according to their feeding habits. A correlation between the intestinal length and the diet could be demonstrated, ranging from around 2.5 for species ingesting more animal food, to 7.8 for detritivorous and microalgivorous species. The relative intestinal length of domesticTropheus moorii, raised in aquaria was significantly lower than that of wild individuals by a factor of 1.7, demonstrating a wide range of phenotypic adaptability. The activities of trypsin and amylase were at an equal level in four Aufwuchseating species, but the activity of laminarinase of a detritivorous-microalgivorous species (Petrochromis orthognathus) was 2.6 times higher than that of an algivorous species (Tropheus moorii). The laminarinase seems to be an excellent marker enzyme for detritivorous or microalgivorous feeding.     

The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat.

The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta-oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism.     

Indirect chiral separation and analyses in human biological fluids of the stereoisomers of a thienothiopyran-2-sulfonamide (TRUSOPT), a novel carbonic anhydrase inhibitor with two chiral centers in the molecule.

The indirect chiral separation of the four stereoisomers (1)-(4) of a novel carbonic anhydrase inhibitor with two chiral centers in the molecule is reported. The method is based on chemical derivatization of the secondary amino group of the inhibitor with chiral isocyanate, formation of diastereomeric urea derivatives, each with three chiral centers in the molecule, and their separation under nonchiral HPLC conditions. The attempts to separate racemic mixture (1) + (2) from its diastereomeric counterpart (3) + (4) under nonchiral conditions, and to separate enantiomers (1) and (2) directly on a chiral stationary phase (CSP) are also reported. The indirect method was utilized for the assessment of an in vivo inversion of configuration at either one or both chiral centers of the molecule of (1). Analyses of selected whole blood and urine samples from human subjects after multiple bilateral topical ocular dosing with (1) did not reveal the presence of any of the three possible stereoisomers (2)-(4) of (1) indicating that the inversion of configuration at neither one nor two chiral centers of (1) occurs in vivo.     

The utilization of nitrogen from insect capture by different growth forms of Drosera from Southwest Australia

Summary Plants of Drosera species, neighbouring noncarnivorous plants, and arthropods on or near each Drosera sp. were collected at 11 contrasting habitat locations in SW Australia. At three of the sites clones of the rare glandless mutant form of D. erythrorhiza were collected alongside fully glandular counterparts. The ¹⁵N value (¹⁵N/¹⁴N natural isotope composition) of insect-free leaf and stem fractions was measured, and the data then used to estimate proportional dependence on insect N (%N_dI) for the respective species and growth forms of Drosera. The data indicated lower %N_dI values for rosette than for self-supporting erect or for climbing vine species. The latter two groups showed an average %N_dI value close to 50%. The %N_dI increased with length and biomass of climbing but not erect forms of Drosera. ¹⁵N values of stems were positively correlated with corresponding values for leaves of Drosera. Leaf material was on average significantly more ¹⁵N enriched than stems, possibly due to delayed transport of recent insect-derived N, or to discrimination against ¹⁵N in transfer from leaf to the rest of the plant. The comparison of ¹⁵N values of insects and arthropod prey, glandless and glandular plants of D. erythrorhiza indicated %N_dI values of 14.3, 12.2 and 32.2 at the respective sites, while matching comparisons based on ¹⁵N of insect, reference plants and glandular plants proved less definitive, with only one site recording a positive %N_dI (value of 10.4%) despite evidence at all sites of feeding on insects by the glandular plants. The use of the ¹⁵N technique for studying nutrition of carnivorous species and the ecological significance of insect feeding of different growth forms of Drosera growing in a large range of habitats is discussed.     

Are prealbumin plasma levels linked to amino acid supply from peripheral tissues in liver cirrhosis?

Summary Prealbumin plasma level is considered a good index of liver function in liver cirrhosis. However, plasma protein levels depend not only on liver function, but also on amino acid supply which is consequent to nutritional status.In 12 cirrhotics we measured prealbumin plasma levels and the lower limb venous-artero difference of amino acid plasma levels in blood samples taken from femoral vein and femoral artery in post-absorptive conditions considered as a direct index of protein release from peripheral tissues and an indirect index of protein nutritional status.In arterial and in venous plasma amino acid sum was 1.86±0.40 (mean + sd) and 2.00 ± 0.04 mMol/l respectively.Prealbumin plasma levels were found directly correlated with the venousartero difference of amino acid plasma levels (r = 0.57p < 0.05) and of glutamate + glutamine levels (r = 0.73p < 0.007).In conclusions, these data suggest that prealbumin plasma levels are linked to amino acid supply from peripheral tissues in cirrhotics.