Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis

Summary The relationship between the incidence of childhood-onset insulin-dependent diabetes mellitus and levels of nitrate in drinking water in the former Yorkshire Regional Health Authority was investigated by means of an ecological analysis. A population-based register contributed 1797 0–16-year-olds diagnosed with diabetes between 1978 and 1994. Nitrate data were based on 9330 samples of drinking water tested between 1990 and 1995 in 148 water supply zones, for which 1991 census small area statistics were taken on population density, ethnicity and socio-economic status. Diabetes incidence was positively associated with raised mean nitrate levels with a standardised incidence ratio of 115 in zones with greater than 14.85 mg · l^–1 (χ² = 26.81, 1 df, p < 0.001). Significant negative trends were found between standardised incidence ratios and proportion of non-whites in the population (χ² = 33.57, 1 df, p < 0.001), childhood population density (χ² = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (χ² = 33.89, 1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors, showed a significant increase in relative incidence rate ratio from a baseline of 1 at nitrate levels below 3.22 mg · l^–1 to 1.27 (95 % confidence interval 1.09,1.48) for mean nitrate levels above 14.85 mg · l^–1. An association between higher nitrate levels in domestic drinking water and incidence of childhood diabetes has been demonstrated. This was not explained by the ethnic composition of the population, population density or socioeconomic status. Nitrate in drinking water may be a precursor of chemicals which are toxic to the pancreas. [Diabetologia (1997) 40: 550–556] Received: 24 October 1996 and in revised form: 20 December 1996     

新型饮水对小鼠繁殖及抗氧化酶活性的影响

目的　探讨新型饮水对健康的影响及其保健作用。方法　将矿溶生态水、活化水、纯净水、矿泉水、碱性离子水等 5种新型饮水作为唯一水源分别喂饲亲代及子代小鼠 3个月 ,对照给予天然水。观察它们对小鼠体重、繁殖及抗氧化酶活性的影响。结果　与天然水比较 ,活化水、矿溶生态水促进亲代雄性小鼠体重增长 (P <0 0 5) ;矿溶生态水使子代小鼠、矿泉水和碱性离子水使子代雄性小鼠体重增长缓慢 (P <0 0 5) ;纯净水使新生仔鼠体重减轻 (P <0 0 5) ,活化水、矿溶生态水使小鼠窝产仔数增多 (P <0 0 5) ,5种水对小鼠受孕率、妊娠率、出生存活率无影响 ;矿溶生态水、活化水、纯净水、矿泉水使小鼠肝组织SOD活力升高 (P <0 0 5) ,碱性离子水使肝组织SOD活力降低 (P <0 0 5)。结论　 5种新型饮水对小鼠体重有影响 ,对受孕率、妊娠率、出生存活率无影响 ;矿溶生态水、活化水、纯净水、矿泉水有提高SOD活力作用     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

一项新的水质检验——可同化有机碳测定

可同化有机碳(AOC)是一项新的水质检测指标,通过它可以评估供水系统的水中是否有足够的营养物质可使微生物再生长。由于目前尚无可行的化学方法检测 AOC,因此主要是用各种生物方法加以检测。本文介绍用荧光假单胞菌 P—17菌株和螺菌属 NOX 菌株作为测试菌,通过定量观察其在水样中的生长,如从接种到生长至最大数量,以考察其利用水中营养物质的情况,进而推算出水中 AOC 的浓度。     

Differential effects of kindling and kindled seizures on place learning in the morris water maze

There is some controversy about the role of long-term potentiation (LTP) in spatial learning. The authors have found that triggering generalized kindled seizures with stimulation of the perforant path disrupts spatial learning in the Morris water maze but that kindling per se does not affect spatial learning. It is suggested that abnormal electrical activity induced by high-frequency stimulation of the perforant path may have been responsible for the disruption of spatial learning previously attributed to LTP saturation.     

Consequences of fluid absorption during transurethral resection of the prostate using distilled water or glycine 1.5 per cent

This prospective and randomized study compared the consequences of two irrigating fluids, distilled water and glycine for transurethral prostatectomy. Forty-nine consecutive unselected patients undergoing transurethral resection of the prostate with spinal anaesthesia were investigated. The irrigating fluid was either distilled water (group A, 24 patients) or glycine 1.5 per cent (group B, 25 patients). The absorption of irrigating fluid was measured, all surgical events and any clinical signs of TURP syndrome during and after surgery were recorded. Early signs of TURP syndrome were observed in one patient in group A and in four in group B without further consequence. From all the biological variables, only plasma protein concentration, haematocrit, free plasma haemoglobin and free bilirubin concentrations were found to have changed. Plasma protein concentration and haematocrit decreased significantly during and after surgery in the two groups. Free plasma haemoglobin increased significantly with time: a significantly higher concentration was observed in group A than group B. Free bilirubin concentration increased with time in the two groups and was statistically greater in group A. With the two irrigating fluids, we observed a significant amount of haemolysis and haemodilution without clinical consequences. A low irrigating fluid pressure, a short resection time, and the use of spinal anaesthesia seems to us to be essential. Close observation of patients following transurethral prostatectomy is needed but the choice of the irrigating fluid does not seem to be important. Cette étude prospective et randomisée a comparé les conséquences de deux liquides d’irrigation, l’eau distillée et le glycocolle au cours de la chirurgie prostatique par voie basse. Quarante-neuf patients consécutifs, non sélectionnés, bénéficiant d’une résection transuréthrale de prostate sous rachianesthésie, sont étudiés. Le liquide d’irrigation est soil l’eau distillée (groupe A, 24 patients), soit le glycocolle à 1.5 pour cent (groupe B, 25 patients). L’absorption des liquides d’irrigation, les incidents chirurgicaux et les signes cliniques du syndrome de réabsorption sont systématiquement notés. Des signes caractéristiques du syndrome de réabsorption sont observés dans un cas dans le groupe A et dans quatre cos dans le groupe B sans conséquence ultérieure. Seuls la protidémie, l’hématocrite, l’hémoglobine plasmatique libre et la bilirubine libre changent significativement. L’hémoglobine plasmatique libre augmente significativement dans les deux groupes, avec un taux plasmatique significativement plus élevé dans le groupe A. Avec les deux liquides d’irrigation, on observe une hémolyse et une hémodilution sans conséquence clinique. Un temps de résection court, un faible niveau de pression d’irrigation, l’utilisation de l’anesthésie rachidienne nous semblent trés importants. Une surveillance clinique et biologique attentive pendant et après la résection transuréthrale de prostate sont nécessaires; en revanche, le choix du liquide d’irrigation ne semble pas l’élément essentiel.     

Assessment of Skin Barrier Function Using Transepidermal Water Loss: Effect of Age

To probe age-related changes in skin barrier function, transepidermal water loss (TEWL) rates have been measured in young (19–42 years) and old (69–85 years) subjects. TEWL was determined at ventral forearm skin sites, which had been occluded for 24 hr with polypropylene chambers. Baseline TEWL rates (J , which showed no dependence on age, were measured for each subject before and after the experiment. Following removal of the occlusive chamber, TEWL was monitored continuously from t = 0.5 min until its return to the baseline (preocclusion) level, which was typically in the range of 2–7 g/m²/hr. Initial TEWL rates (mean ± SD) were found to differ significantly between young (28.6 ± 7.5 g/m²/hr; n = 26) and old (36.9 ± 10.5 g/m²/hr; n = 18) subjects (P < 0.01). Relaxation of TEWL to J was significantly slower in the aged cohort, such that the characteristic time for diffusion of water in the stratum corneum was estimated to be (mean ± SD) 176 ± 59 min for the young subjects, compared to 360 ± 76 min for the old (P < 0.001.). Thus, the initial TEWL value following removal of occlusion is significantly greater, and the excessive stratum corneum hydration produced by occlusion is dissipated more slowly, in old skin than in young. A hypothesis to explain the slower relaxation of perturbed TEWL in old skin is proposed.     

Determination of total body water by multifrequency bio-electric impedance: development of several models

Multifrequency bio-electronic impedance analysis (MF BIA) measurements are taken from a heterogeneous group of patients, varying in size between obese and slim. The measuring system uses four electrodes: two current and two potential electrodes. Three new models are developed to calculate total body water (TBW) from the BIA data, and the resulting TBW values are compared with TBW determined by D₂O dilution. The results demonstrate that the most simple model provides the best TBW values. For individual patients, TBW can be determined by means of bioimpedance measurement with an accuracy of 3 litres. In the most simple model (model 1), the body is electrically represented by a cylinder, and corrections are made for the amount of fat. This is an extension of the model used by Xitron. In the more advanced models (2 and 3), the body is represented by a cylinder for the trunk, and truncated cones represent the arms and legs. In model 2, ΔTBW amounts to 3 litres. It is shown that the resistance of the trunk is proportional to the square root of the length. In model 3, it is assumed that subcutaneous fat is a poor conductor if electric current. An equation is developed that describes the partition of subcutaneous fat, and the fat layer is then removed from the cones representing arms and legs and from the cylinder that models the trunk.     

Contraluminal transport of organic cations in the proximal tubule of the rat kidney

In order to study the quantitative structure/activity relationship of organic cation transport across the contraluminal side of the proximal renal tubule cell, the stopped-flow capillary microperfusion method was applied and the inhibitory potency (apparent K _i values) of different homologous series of substrates against N ¹-[³H]methylnicotinamide (NMeN⁺) transport was evaluated. Aniline and its ring- or N-substituted analogues as well as the aminonaphthalines do not interact with the contraluminal NMeN⁺ transporter except for the quaternary trimethylphenylammonium and pararosaniline, which bear a permanent positive charge, and for 1,8-bis-(dimethylamino)naphthaline, which forms an intramolecular hydrogen bond. If, however, one or more than one methylene group is interposed between the benzene ring and the amino group, the compounds interact with the contraluminal NMeN⁺ transporter in proportion to their hydrophobicity parameter, i.e. the octanol/water partition coefficient (log octanol). The catecholamines and other hydroxyl-substituted phenylethyl analogues also follow this rule. In addition, the N-heterocyclic pyridine, quinoline, isoquinoline and acridine analogues also interact with the contraluminal NMeN⁺ transporter, when their pK _a values are higher than 5.0, and, an inverse correlation between pK _a and log K _{i, NMeN} was observed. An exception to this rule are those hydroxy compounds of pyridine, quinoline and isoquinoline that show tautomerism. These compounds slightly inhibit NMeN⁺ transport despite low pK _a values. The quaternary nitrogen compounds of aniline and the N-heterocyclic analogues, as far as tested, all interact with the contraluminal NMeN⁺ transporter in relation to their hydrophobicity. The data indicate that the contraluminal NMeN⁺ transporter interacts with N-compounds according to their hydrophobicity and/or according to their basicity (affinity to protons). The reason for deviation of the aniline analogues and the OH-tautomeric heterocyclic N-compounds from this behaviour is discussed.