The complexation properties of the two isomers of the cyclic polyether dicyclohexyl-18-crown-6 are examined in aqueous solution for a series of metal ions at various reaction temperatures. The results are discussed in terms of size relationships and salvation characteristics of both polyether and metal ions. ΔCp° values are determined from the temperature dependence of the ΔH° values. A discussion of the errors involved in the determination of ΔH° from the temperature dependence of log K values is also included. Comparisons are made between the results of this study and those of a similar study by H. K. Frensdorff, E. I. duPont de Nemours and Co., Wilmington, Delaware, in press. The complexation reactions of dicyclohexyl- and dibenzo-18-crown-6 and benzo-15-crown-5 with Na^+ and K^+ ions are reported in non-aqueous solvents and methanol-water mixtures. The results are discussed with reference to their application in model systems of ion transport. In general the stabilities of the polyether-cation complexes were found to increase with decreasing dielectric constant of the solvent medium. In the methanol-water mixtures large compensating ΔH° and ΔS° changes were observed above 70 weight percent methanol, while the log K values showed a nearly linear increase with increasing methanol concentration. Salvation of the polyethers and metal ions and complexation of ion pairs in non-aqueous solvents are discussed.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21719号 / 薬科博第110号 / 新制||薬科||12(附属図書館) / 京都大学大学院薬学研究科医薬創成情報科学専攻 / (主査)教授 土居 雅夫, 教授 竹島 浩, 教授 中山 和久 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.

No description available.

During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.

Membrane proteins play a vital role in cellular processes. In this thesis, we use KcsA, a prokaryotic potassium channel, as a model to investigate the gating mechanism of ion channels and the effect of anionic lipids on the channel activity using solid-state NMR spectroscopy. KcsA activity is known to be highly dependent on the presence of negatively charged lipids. Multiple crystal structures combined with biochemistry assays suggest that KcsA is co-purified with anionic lipids with phosphatidylglycerol headgroup. Here, we identified this specifically bound, isotopically labeled lipid in the protein 13C-13C correlation spectra. Our results reveal that the lipid cross peaks show stronger intensity when the channel is in the inactivated state compared to the activated state, which indicates a stronger protein-lipid interaction when KcsA is inactivated. In addition, our data shows that including anionic lipids into proteoliposomes leads to a weaker potassium ion affinity at the selectivity filter. Considering ion loss as a model of inactivation, our results suggest anionic lipids promote channel inactivation. However, the surface charge is not the only physical parameter that regulates channel gating or conformational preference. We found that the channel adapted to different conformations when reconstituted into liposome either made of DOPC or DOPE, two zwitterionic lipids. Also, we were able to stabilize the open-conformation of KcsA in 3:1 DOPE/DOPG liposome at pH 4.0 and acquired several multi-dimensional solid-state NMR experiments for site-specific resonance assignments. This is the first time that we obtain wild-type full-length KcsA structural information on the transient state. The structure is not only important for understanding channel gating, but can also serve as a homology model for investigating drug binding with more complicated potassium channels such as human voltage gated channel (hERG).

Brisket disease, an affliction of cattle, is important because of : (1) economic losses, (2) similarities to chronic mountain sickness in humans, and (3) the provision of experimental animals for cardiac research. In afflicted cattle, right cardiac ventricular hypertrophy and dilatation occur and are manifestations of attempted compensation for reduced alveolar oxygen by increasing pulmonary circulation. Geographic variations in occurrence of brisket disease in Utah indicate that hypoxia is not the sole causative factor. From the findings that afflicted cattle exhibit hypocalcemia and hyperkalemia, and the disease occurs most commonly in wet meadowland environments where potassium is high and calcium low in browse, a dual stress theory of cause was hypothesized; i.e., altitude-induced hypoxia plus ionic calcium-potassium imbalance. To test the hypothesis, 40 Hereford calves were randomized into four equal groups, two at 1,372 meters (normal) and two at 2,745 meters (hypoxic) elevation. At each elevation there were control (balanced) and treated (calcium-potassium) groups. For 16 weeks, treated calves received, by diet, one-fourth the calcium and 10 times the potassium requirements; also, repeated injections of dipotassium ethylenediaminetetraacetate, potassium chloride, and an aldosterone inhibitor to further induce hypocalcemia and hyperkalemia. Control groups at each elevation received a balanced diet and no injections. Since optimal myocardial function is dependent upon proper ion balance, and concentrations of calcium, potassium, sodium, phosphorus, magnesium, chloride, iron, zinc, and copper in blood, heart, liver, kidney, and bone are indices, these elements were quantitated. Calcium concentration in serum was reduced by 1.6 milligrams per 100 milliliters from an initial value of 9.4 milligrams per 100 milliliters, and an average increase of 1.8 milliequivalents per liter in potassium concentration in whole blood, from the initial concentration of 12. 4 milliequivalents per liter, occurred in treated calves . Elevation caused an increase of 1.7 milliequivalents per liter in potassium concentration in serum from the initial concentration of 6.2 milliequivalents per liter. Iron concentration in whole blood increased in response to hypoxia and decreased due to treatment. In the serum, sodium and copper decreased and chloride increased due to treatment. Compared to low elevation, significant tissue compositional changes in calves at high elevation were as follows: (l) calcium: kidney 12 percent higher, heart 9 percent lower: (2) sodium: liver 5 percent lower, kidney 3 percent higher: (2) phosphorus: kidney 2 percent higher. More profound changes occurred in cattle subjected to treatment: compared to controls, the tissue compositions in imbalanced cattle were as follows: (1) calcium: heart 10 percent and liver 13 percent lower, kidney 92 percent higher; (2) potassium: heart 13 percent higher, liver and kidney 6 percent lower; (3) sodium: heart 18 percent, liver 8 percent, and kidney 14 percent lower; (4) magnesium: heart 20 percent and liver 5 percent higher, kidney 11 percent lower; (5) phosphorus: heart 6 percent and kidney 21 percent higher, liver xvi 2 percent lower; (6) absolute dry matter: liver 5 percent and kidney 13 percent lower; (7) total ash: kidney 4 percent lower. In addition, iron, zinc, and copper were decreased in both cardiac and hepatic tissues of treated calves. Treatment influenced bone ash composition as follows: compared to controls, calcium decreased to 25.3 from 32.5 percent; phosphorus decreased to 16.5 from 19.0 percent; potassium increased to 0.16 from 0.08 percent; and zinc increased to 319 parts per million from 227 parts per million. High altitude was also influential. Compared to controls, phosphorus increased to 18.1 percent from 17.5 percent, potassium decreased to 0.112 from 0.129 percent, sodium to 1.09 from 1.17 percent, and magnesium to 0. 64 from 0.70 percent.

Three greenhouse experiments were conducted with three phenotypes of alfalfa (Medicago sativa L.) obtained from a potassium (K)-deficient field and with their diallel crosses grown on low K soil. The first experiment was conduc ted to study the partitioning and broad-sense heritability of K a nd sodium (Na) between leaves and stems of the three phenotypes which were deficient in K and exhibited normal (N), marginal chlorotic (M), and white spot chlorotic (W) leaflets. The second experiment was conducted to study the partitioning of K and Na in leaves, stems, and roots as influenced by 32 alfalfa crosses obtained from diallel crossing of the mother plants of the three phenotypes. The objectives of the third experiment were to study the effects and interactions of nine alfalfa crosses and three soil K and Na levels on transpiration, biomass, and elemental composition of alfalfa components. The three phenotypes showed no variations in their leaf and stem K concentrations but varied in their ability to partition Na between the leaves and stems. Phenotype M accumulated more Na compared to N and W phenotypes. The Na trait was highly heritable in the broad sense. The K and Na concentrations varied among the diallel crosses. Crosses with M as the maternal parent had high Na concentrations in leaves while stems and roots accumulated lesser amounts. In contrast, the remaining crosses had higher Na concentrations in roots and lower and least amounts in stems and leaves, respectively. Significant genetic variation among alfalfa crosses from a single cultivar was observed for transpiration, biomass production, plant water-use efficiency, elemental concentrations, and K utilization efficiency. Leaf and stem biomass and K concentrations in alfalfa components increased in response to increasing soil K levels. The Na concentrations in stems and roots fell in response to increasing soil K levels and increased in response to Na application. The K utilization efficiency of alfalfa increased with increase in soil Na levels, indicating partial Na substitution for K. The differences among alfalfa phenotypes and crosses from a single cultivar in their Na accumulation and translocation were thought to be governed by plant genetics rather than the direct effect of K availability.

Compliance with the strict dietary regimen for the dialysis patient can be very challenging. Many foods are limited from the diet of a renal patient because of the high potassium content. The physiological consequences of failure to follow a diet prescription can be fatal for the dialysis patient. In an effort to improve patient compliance with nutritional protocols, several potato cooking methods and centrifugation of tomato sauce were investigated for their effects in reducing potassium content. All methods with a 24-hour soak were found to be significant in reducing potassium content of potatoes (P<0.05). However, some of the methods in which the potatoes were not soaked were also found to be effective in reducing potassium content. Slice thickness and volume of cooking water used were found to be two important factors in determining potassium loss. The 4-mm sliced potatoes, which had a mean potassium value of 84 mg/100 g, lost more potassium than the 8-mm ·sliced potatoes with a mean potassium value of 182 mg/100 g (P<0.05). Furthermore, the potatoes cooked in 10 times the amount of water lost more potassium (124 mg/100 g) than those cooked in only 5 times the amount of water (148 mg/100 g) (P<0.05). Soaking in cold versus hot water, agitation of the soak water, or the addition of chemical chelators to the soak water were not shown to be any more effective in reducing the potassium content than the other methods. Sensory data indicated that participants did not have a strong taste preference for potatoes cooked by any one particular method (P<0.05). Centrifugation of tomato sauce, and retention of the solids were found to be effective methods for reducing the potassium content of tomato sauce. There was, however, a significant difference (P<0.05) in the participants' taste preference for the tomato sauce that was centrifuged one time versus the tomato sauce that had been centrifuged twice The results of this study are significant because they suggest that there are more effective, alternative methods for preparing potatoes and tomato sauce than those that are currently being used. This would suggest an increased likelihood for patient adherence to nutritional recommendations.

Chlorosis, the yellowing of plant leaves, results from reduced synthesis of chlorophyll. It is caused by a deficiency or an unbalance of essential nutrient elements. The amount and pattern of yellowing varies with the cause and severity of the disturbance. Chlorosis results in reduced vigor of the affected plants and a corresponding loss in quantity and quality of the product grown. In severe cases chlorosis may lead to the eventual death of the plant. Lime-induced chlorosis refers to a chlorosis occurring on high lime soils. It affects principally horticultural plants. The disease is found in about 23 percent of Utah orchards. Lime-induced chlorosis is characteristically accompanied by high potasseium in the affected leaves. The hypothesis had been offered that this high potassium is a cause of lime-induced chlorosis. The object of this study is to investigate the validity of this hypothesis.