Composition of the domestic water supply and the incidence of fractures and encephalopathy in patients on home dialysis.

Of the 202 patients undergoing home dialysis in the Trent region, 11 developed dialysis encephalopathy, 21 suffered spontaneous fractures, and 36 who had undergone dialysis for over four years had neither of these complications. Because the incidence of complications seemed to be unevenly distributed the water supplies were analysed. Water supplied to the homes of the patients with fractures or encephalopathy contained significantly less calcium and fluorine and significantly more aluminium and manganese than that piped to patients without these complications. The high aluminium concentrations in the bone of patients with encephalopathy was confirmed, but aluminium concentrations in the brains from three patients with encephalopathy were not increased. Patients who undergo dialysis in areas where water contains high aluminium concentrations should be supplied with deionisers.     

Aluminium sucrose biscuit fillings to control hyperphosphataemia in patients undergoing dialysis.

Aluminium hydroxide is used to prevent hyperphosphataemia in patients undergoing dialysis, but many standard preparations are unpalatable. In this study hydrated aluminium sucrose was suspended in synthetic cream and used as a biscuit filling. Six patients undergoing dialysis took part in five five-week study periods comparing different forms of treatment. No significant difference was found between serum phosphate concentrations measured during standard treatment and those measured during treatment with aluminium sucrose biscuits. There was no significant difference in serum phosphate concentrations when the patients were given placebo biscuits and when they received no treatment. Aluminium sucrose presented in this form was an adequate phosphate binder and was acceptable to the patients.     

Water purification and the incidence of fractures in patients receiving home haemodialysis supervised by a single centre: evidence for "safe" upper limit of aluminium in water.

Between 1968 and 1980 fractures occurred in 56 of 284 patients treated by home haemodialysis in the Sheffield area for longer than one year. Patients sustained four times as many fractures while using dialysate prepared with water containing more than 1.0 mumol aluminium per 1 (2.7 micrograms/100 ml) than while using water containing a smaller concentration. When aluminium was removed from water by deionisation the incidence of fractures diminished during the next year and no patient developed dialysis encephalopathy. These findings show that 1.0 mumol/l is a safe maximum concentration of aluminium in water for use in home haemodialysis. It can be detected by the colorimetric aluminium analyses used by many water authorities. When financial resources are limited it is expedient to reserve aluminium analyses by electrothermal atomic absorption for plasma from patients receiving regular haemodialysis. Ingestion of aluminium hydroxide contributes significantly to the increased plasma aluminium concentration of these patients.     

Presence of high concentrations of aluminum in neurons of a patient dying from a rapidly developing dementia

Ultrastructural observation of brain cells of a patient dead from senile dementia associated with myoclonies, has shown a number of intracytoplasmic dense structures. High concentration of Aluminium has been detected in these structures by electron probe X ray analysis. The clinical symptomatology, the evolution and the cell pathology observed in this patients are very similar to the classical features observed in dialysis encephalopathy the origin of which is an aluminium intoxication. In this patient, the possible origin of the intoxication is the absorption in the last 10 years of aluminium gels.     

Aluminium in Bone from Patients with Renal Failure

Some samples of bone from patients with renal failure contained more aluminium than others, and the concentration tended to be highest in patients who had been uraemic or on dialysis longest. The significance of the association of raised concentrations of aluminium in bone with renal failure is discussed.     

Brain Amino Acids Measured by Intracerebral Dialysis in Portacaval Shunted Rats

Changes in brain amino acid uptake and metabolism have been proposed as a possible etiological factor in hepatic encephalopathy. By use of a brain dialysis technique (a thin tube implanted in the brain of the living animal), the extracellular amino acid concentrations in the striatum of portacaval (PC)-shunted and sham-operated rats were measured. Leucine, phenylalanine, methionine, and glutamine were increased two- to sixfold in the PC-shunted rats, whilst no changes were seen for GABA, valine, glutamate, or isoleucine, confirming previous reports. Aspartate levels were 350% higher in the PC-shunted rats, and this rise, as well as that of phenylalanine, was significantly correlated with the lower motor activity observed in the PC-shunted rats, suggesting a possible importance of these amino acids in the etiology of hepatic encephalopathy. The amino acid concentrations measured in whole blood demonstrated the well-known pattern of low levels of branched-chain amino acids and increased concentrations of phenylalanine, glutamine, and histidine.     

Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.     

Plasma immunoreactive melanotrophic hormones in patients on maintenance haemodialysis.

Circulating levels of melanotrophic horomones and ACTH were determined in patients treated by maintenance dialysis for chronic renal failure. Plasma melanotrophic hormone levels were greatly increased in all patients studied (125-1100 ng/1 as compared with 12-36 ng/1 in normal adults) and were correlated with the duration of treatment. Skin pigmentation, especially in exposed areas, was notably increased, particularly in those patients with the highest plasma melanotrophic concentrations. Plasma ACTH levels were normal or only slightly raised and circulating corticosteroid concentrations, as determined by a fluorimetric method, all lay within the physiological range. The dissociation between ACTH and melanotrophic hormone levels in these patients may have been the result of a slower metabolic clearance of the latter.     

Differential effects of low pH and aluminium on the caudal neurosecretory system of the brook trout, Salvelinus fontinalis

Brook trout were subjected to soft water at pH 6·5, 5·5 or 5·0 without aluminium added, or to water at pH 5·5 with 200,300 or 500 μg Al I^-1 added. The response of the caudal neurosecretory system to low pH or aluminium was evaluated after one week by measuring the urotensin I and urotensin II concentrations in the urophysis by radioimmunoassay, and by morphometric analysis of the caudal neurosecretory cells. A positive correlation was found between urotensin I concentrations and acidity, and a negative correlation was found between urotensin II concentrations and total aluminium in the water. Morphometric indices (cell size and proportion of lobed nuclei in the caudal neurosecretory cells) suggested increased synthetic activity in the caudal neurosecretory cells of fish at pH 5·5 compared to pH 6·5.     

Gallium-67 as a Potential Marker for Aluminium Transport in Rat Brain: Implications for Alzheimer''s Disease

Evidence of a link between aluminium and Alzheimer's disease, parkinsonism-dementia of Guam, and dialysis encephalopathy raises questions regarding the role of this element in the pathogenesis of these conditions. Therefore, we have investigated the use of gallium-67 (67Ga) as a marker for brain uptake of aluminium. The binding of 67Ga to plasma proteins has been studied, and the blood-brain barrier permeability and autoradiographic distribution of this isotope in rat brain determined in vivo. The autoradiographic distribution of 125I-Fe-transferrin receptors in rat brain has also been determined in vitro. Results show that 67Ga was bound to plasma transferrin, entered the brain with a blood-brain barrier permeability of 2.48 x 10(-6) ml/min/g, and showed a marked regional distribution that was very similar to that of 125I-Fe-transferrin receptors. Our data suggest that the vulnerability of the hippocampus, amygdala, and cerebral cortex in conditions such as those mentioned above may be partly due to an increased uptake and deposition of aluminium in these regions by the iron transport system.     

The effect of serum albumin and the effect of cell concentration on the in vitro growth of mouse and rat lymphocytes.

The growth of mouse and rat T and B lymphocytes, activated by concanavalin A or lipopolysaccharide, is increased over growth in protein-free medium 5–20-fold by human or bovine serum albumin. The growth is dependent on the concentration of albumin. At a concentration of 2–4 mg/ml the growth rate is the same as in the presence of 10% fetal bovine serum. Of the other serum proteins (Cohn fractions) only human fraction VI supports growth somewhat while human fractions II–IV and bovine fraction VI do not support growth. The growth of mouse and rat lymphocytes is greatly suppressed if lymphocytes are cultured at high cell concentrations, and the growth-promoting ability of serum albumin cannot be detected under such conditions. The growth rate can be improved by daily adjustment of the pH, by daily refeeding, and by daily change of medium. The growth inhibitory activity can be removed largely by dialysis. It is concluded that the suppression of growth at high cell concentrations is caused by a combination of effects, i.e., a shift of pH, lack of nutrients, and accumulation of cellular metabolites.     

乡村地区生态系统服务权衡与协同关系——以湖州市为例

湖州是中国"美丽乡村"发源地,十多年来乡村面貌发生较大改变,从而对其生境维持、文化保护带来压力,定量评估湖州乡村的生态系统服务及相关关系对其可持续发展具有重要意义。基于Thornthwaite Memorial模型、Miami模型、InVEST模型、水量平衡法、Maxent模型等方法对该区域2010-2018年粮食供给、碳贮存、水源涵养、文化服务等四项生态系统服务进行时空演变分析,探究不同生态系统服务间的权衡与协同关系。结果表明：(1)在2010-2018年,湖州市乡村地区粮食供给在波动中下降,一级区以东、西部的平原耕地为主;碳贮存均值与总量年际变化极小,中、西部的高山林地碳储量最高;水源涵养均值呈现先增后减的小幅波动,空间分布特点与碳贮存相似;文化服务能力逐年增强,一级区向景点区域集聚并扩张。(2)在权衡与协同分析中,水源涵养与碳贮存、粮食供给之间以协同效应为主,文化服务与水源涵养、粮食供给、碳贮存之间以权衡效应为主,粮食供给与碳贮存之间由权衡效应向协同效应转变,各服务间相关关系总体逐渐增强且存在空间差异性。(3)热点区域识别研究显示,Ⅰ类热点区主要为提供粮食供给的耕地,占比多且略有增强;Ⅱ类热点区主要为提供碳贮存、水源涵养的林地,总体有所减少;Ⅲ类热点区主要为提供碳贮存、水源涵养,以及粮食供给或文化服务的林地和耕地,占比较多并不断扩大;Ⅳ类热点区、非热点区分别位于山地-平原过渡区、靠近城镇区域,均占比极少且变化小。研究结果以期为揭示乡村地区生态系统供给、调节、文化服务间的关系,优化乡村经济结构与发展模式,推进乡村的合理规划和可持续发展提供参考。     

Effect of aluminium hydroxide on serum ionised calcium,immunoreactive parathyroid hormone,and aluminium in chronic renal failure.

According to the Bricker-Slatopolsky theory, secretion of parathyroid hormone (PTH) is switched on in chronic renal failure by hypocalcaemia due to phosphate retention. In an attempt to reverse this process 20 patients in preterminal renal failure (plasma creatinine 569 +/- 195 mumol/l) were given aluminium hydroxide, 3.8 g daily. They were studied for four weeks and all measurements were made at the start and weekly, except measurements of serum aluminium concentration, which were made at the start and at the end of the fourth week. Mean serum phosphate fell from 1.89 to 1.47 mmol/l (5.9 to 4.6 mg/100), mean serum calcium rose from 2.07 to 2.24 mmol/l (8.3 to 9.0 mg/100 ml), and serum ionised calcium rose from 1.07 to 1.20 mmol/l (4.3 to 4.8 mg/100 ml), but serum immunoreactive PTH did not fall. Thirteen patients had initial serum immunoreactive PTH concentrations at or near to normal and 11 were taking beta-blockers but even in those with neither explanation, PTH concentrations did not fall. Serum aluminium concentrations rose from 0.4 to 1.02 mumol/l (10.9 to 27.4 microgram/l). Aluminium hydroxide corrects serum phosphate, total calcium, and ionised calcium at the price of a rise in serum aluminium concentration; in this study it did not affect serum immunoreactive PTH. The Bricker-Slatopolsky theory still needs verification in studies of patients with chronic renal failure.     

鄂尔多斯高原沙柳幼苗对模拟降水量变化的响应

鄂尔多斯高原是中国干旱、半干旱沙区典型沙地。随着未来全球变化,尤其降水变化进一步激烈,将给这里的陆地生态系统分布格局和生产力带来巨大影响,选择鄂尔多斯高原优势灌木沙柳为研究对象,人为控制４种供水量水平来探讨沙柳幼苗对模拟降水量变化的响应,结果表明,幼苗净光合速率、蒸腾速率、气孔导率和荧光效率随着供水的增加而增大,而供水对幼苗的水分利用效率影响不显著;不同供水量的沙柳幼苗树高、枝条数、叶数和叶面积生长动态存在明显差异,随着供水量的增加,沙柳幼苗树高、基径、枝条数、叶数、叶面积、生物量干重和冠根生物量干重比值均逐渐增大;供水显著增加了沙柳幼苗总分枝率、各级枝条数、枝条长度和叶面积。     

Dilution and acidification effects during the spring flood of four Swedish mountain brooks

The seasonal variation in water chemistry was followed during 1980 and 1981 in four mountain brooks in the southern part of Swedish Lapland. In the area investigated the soil is calcareous and the brook water is very well buffered during the major part of the year, with alkalinity varying between 0.4 and 1.0 milliequivalents per liter and with pH values about 7.5. These years the snow had a pH of approximately 5.2, which was considerably higher than has been reported from adjacent areas in the lower, coniferous region. During snowmelt the water discharge increased drastically, and although the net transport of bicarbonate increased, alkalinity showed low values due to dilution with meltwater. pH decreased, but not further than to 6.3–6.5, far from values reported in 1979 (pH less than 5), apparently due to the comparatively clean snow. A slight deficit in alkalinity, as compared to the nonmarine calcium and magnesium content, points to an acidification impact on the area. During maximum runoff some chemical variables, like aluminium, iron, nitrogen and phosphorus, behaved reversely to what might be expected during dilution and reached maxima in concentrations. It is concluded that the extreme runoff characteristics of high mountain areas make brook water more sensitive to acid precipitation than might be expected when regarding only the calcareous properties of soil and bedrock.     

Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children

Background

The 2009 A(H1N1) influenza virus has caused a large outbreak, and resulted in major complications of severe pneumonia and acute encephalopathy in the pediatric population in Japan.

Methods

This study examined six patients with acute encephalopathy, 34 patients with severe pneumonia, five patients with both pneumonia and encephalopathy, and 46 patients without severe complications. The concentrations of 27 cytokines were examined in the cerebrospinal fluid of patients with encephalopathy, and the levels of these cytokines, Cytochrome c, high-mobility group box 1 (HMGB1) were measured in the serum of all patients.

Results

Patients with severe pneumonia had higher serum concentrations of 16 cytokines, including Th1 cytokines, Th2 cytokines, chemokines, and growth factors, than patients with uncomplicated influenza. The distribution of 27 cytokines in the CSF did not parallel the serum levels in 11 patients with acute encephalopathy. HMGB1 concentrations in the serum were significantly higher in pneumonia patients with or without encephalopathy than in uncomplicated influenza patients, and were significantly associated with the upregulation of 10 cytokines.

Conclusions

Elevated levels of Th2 cytokines appear to be unique to influenza caused by 2009 H1N1 influenza virus and HMGB1 could play an important role in the pathogenesis of severe pneumonia. There appear to be different pathologic processes for encephalopathy and pneumonia.     

Flow-dependent concentration polarization of plasma proteins at the luminal surface of a semipermeable membrane

The effect of steady shear flow on concentration polarization of plasma proteins and lipoproteins at the luminal surface of a semipermeable vessel wall was studied experimentally using suspensions of these molecules in a cell culture medium and a semipermeable membrane dialysis tube which served as a model of an implanted vascular graft or an artery. The study was carried out by flowing a cell culture medium containing fetal calf serum or bovine plasma lipoproteins or bovine albumin through a 7.5 mm diameter, 60 mm-long dialysis tube in steady flow under a physiologic mean arterial perfusion pressure of 100 mmHg, and measuring the filtration velocity of water (cell culture medium) at the vessel wall which varied as a consequence of the change in concentration of plasma protein particles at the luminal surface of the semipermeable membrane dialysis tube. It was found that for perfusates containing plasma proteins and/or lipoproteins, filtration velocity of water was the lowest in the absence of flow, and it increased or decreased as the flow rate (hence wall shear rate) increased or decreased from a certain non-zero value, indicating that surface concentration of protein particles varied reversibly as a direct function of flow rate. It was also found that at particle concentrations equivalent to those found in a culture medium containing serum at 5% by volume, plasma lipoproteins which were much smaller in number and lower in concentration but larger in size than albumin, had a much larger effect on the filtration velocity of water than albumin. These findings were very much the same as those previously obtained with a cultured endothelial cell monolayer, strongly suggesting that the flow-dependent variation in filtration velocity of water at a vessel wall results from a physical phenomenon, that is, flow-dependent concentration polarization of low density lipoproteins at the luminal surface of the endothelial cell monolayer.     

Accumulation of large neutral amino acids in the brain of sparse-fur mice at hyperammonemic state

Sparse-fur mice which are deficient in ornithine transcarbamylase, the second-step enzyme in the urea cycle, were examined for hyperammonemia and its relationship with encephalopathy. We compared amino acid concentrations in the serum and brain of spf mice with those of control mice. Unlike hepatic encephalopathy we could not find marked amino acid changes in the serum of spf mice besides low levels of citrulline and arginine. But in the brain of spf mice, glutamine was increased strikingly during hyperammonemia, and a concomitant accumulation of large neutral amino acids such as tyrosine, phenylalanine, methionine, and histidine was observed. The accumulation of these large neutral amino acids in the brain was not influenced by 24-hr fasting which caused increases in branched chain amino acids in the serum. From these results, we conclude that the accumulation of the large neutral amino acid in the brain of hyperammonemic state is caused by uptake of ammonia in the brain and the subsequent accumulation of glutamine, but is not influenced by a decreased ratio of branched chain amino acids to aromatic amino acids in the serum.     

The Relationship Between Plasma and Brain Quinolinic Acid Levels and the Severity of Hepatic Encephalopathy in Animal Models of Fulminant Hepatic Failure

Abstract: Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three- to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations ∼10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic l -tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized blood-brain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor.     

Endogenous Benzodiazepine Receptor Ligands in Human and Animal Hepatic Encephalopathy

The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzo-diazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained approximately 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased approximately 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.